Capillary high-performance liquid chromatography/electrospray ion trap time-of-flight mass spectrometry using a novel nanoflow gradient generator.
A type of high-performance liquid chromatography (HPLC) based on a novel nanoflow gradient generator (Asymptotic-Trace-10-Port-Valve (AT10PV) nanoGR generator) was developed and coupled with an electrospray ion trap time-of-flight mass spectrometer (ESI-IT-TOF MS). Stability of the nanoflow GR HPLC system was tested at flow rates of 20 and 50 nL/min by using a nanoflow meter. Average flow rates in a 2-h run were 51.2 nL/min with RSD 0.7% and 21.0 nL/min with RSD 1.8%. Repeatability of analysis of the nanoHPLC/ESI-IT-TOF MS system was also tested by injecting 1.0 microL of trypsin digested bovine serum albumin (BSA) (100 fmol) into a monolithic silica-ODS column (30 microm i.d., 150 mm in length) through a packed silica-ODS trapping column (particle size 5 microm, 150 microm i.d., 10 mm in length). At a flow rate of 50 nL/min, the result demonstrated a reasonably good repeatability of peak retention times (RSD: 0.32-1.1%) and base-ion peak areas (RSD: 4.4-6.6%).


Heparanase and Chemotherapy Synergize to Drive Macrophage Activation and Enhance Tumor Growth.
The emerging role of heparanase in tumor initiation, growth, metastasis, and chemoresistance is well recognized, encouraging the development of heparanase inhibitors as anticancer drugs. Unlike the function of heparanase in cancer cells, little attention has been given to heparanase contributed by cells composing the tumor microenvironment. Here, we focused on the cross-talk between macrophages, chemotherapy, and heparanase and the combined effect on tumor progression. Macrophages were markedly activated by chemotherapeutics paclitaxel and cisplatin, evidenced by increased expression of proinflammatory cytokines, supporting recent studies indicating that chemotherapy may promote rather than suppress tumor regrowth and spread. Strikingly, cytokine induction by chemotherapy was not observed in macrophages isolated from heparanase-knockout mice, suggesting macrophage activation by chemotherapy is heparanase dependent. paclitaxel-treated macrophages enhanced the growth of Lewis lung carcinoma tumors that was attenuated by a CXCR2 inhibitor. Mechanistically, paclitaxel and cisplatin activated methylation of histone H3 on lysine 4 (H3K4) in wild-type but not in heparanase-knockout macrophages. Furthermore, the H3K4 presenter WDR5 functioned as a molecular determinant that mediated cytokine induction by paclitaxel. This epigenetic, heparanase-dependent host-response mechanism adds a new perspective to the tumor-promoting functions of chemotherapy, and offers new treatment modalities to optimize chemotherapeutics. SIGNIFICANCE: Chemotherapy-treated macrophages are activated to produce proinflammatory cytokines, which are blunted in the absence of heparanase.


Uncommon and fatal case of cystoisosporiasis in a non HIV-immunosuppressed patient from a non-endemic country.
Cystoisospora belli (previously known as Isospora belli) is a tropical coccidian parasite sometimes leading to severe diarrhea in immunocompromised patients. Here we describe a fatal case of cystoisosporiasis in a non HIV-immunocompromised 71-year-old female with no recent travel history. Infection was either latent or potentially caused by the consumption of contaminated imported food from Asia. Diagnosis was made by microscopical detection of numerous C. belli oocysts in stools without specific staining. Treatment with TMP-SMZ slightly improved diarrhea within 3days, but dehydration subsequently led to acute decompensated heart failure and a fatal evolution. This report illustrates the possibility of severe cystoisosporiasis in non HIV-immunocompromised patients in a non-endemic country and highlights the risk of transmission through imported contaminated food consumption.


Is Myofascial Release Therapy Cost-Effective When Compared With Manual Therapy to Treat Workers' Mechanical Neck Pains?
The aim of this study was to do a cost-benefit analysis of myofascial release therapy (MRT) compared to manual therapy (MT) for treating occupational mechanical neck pain. Variables regarding the outcomes of the intervention were intensity of neck pain, cervical disability, quality of life, craniovertebral angle, and ranges of cervical motion. Costs were assessed based on a social perspective using diary costs. Between-groups differences in average cost, cost-effectiveness, and cost-utility ratios were assessed using bootstrap parametric techniques. The economic cost-benefit evaluation was with regard to an experimental parallel group study design. There were 59 participants. Myofascial released therapy showed significant improvement over MT for cervical mobility (side bending, rotation, and craniovertebral angle). The total cost of MRT was approximately 20% less (-$519.81; 95% confidence interval, -$1193.67 to $100.31) than that of MT, although this was not statistically significant. Cost-effectiveness and cost-utility ratios showed that MRT could be associated with lower economic costs. With probabilities of 93.9% and 95.8%, MRT seems to be cost-effective for treating mechanical neck pain without the need to add any additional cost to obtain a better clinical benefit. Consequently, we believe it could be included in the clinical practice guidelines of different Spanish health care institutions.


Absence of reuptake of serotonin influences susceptibility to clinical autoimmune disease and neuroantigen-specific interferon-gamma production in mouse EAE.
Serotonin (5-hydroxytryptamine, 5-HT) is one of the most extensively studied neurotransmitters of the central nervous system. It also has been identified in constituents of the immune system. Therefore serotonin has been suggested to serve as a mediator of bidirectional interactions between the nervous system and the immune system. We investigated this interaction in experimental autoimmune encephalomyelitis (EAE), a well-defined animal model of autoimmune disease of the central nervous system (CNS) mimicking features of the human disease multiple sclerosis. EAE was induced by immunization with the autoantigens myelin basic protein (MBP) or the immunodominant peptide of myelin oligodendrocyte glycoprotein (MOG) spanning amino acids 35-55 (MOGp 35-55). We studied EAE in knockout (KO) mice lacking the 5-HT transporter (5-HTT) on a C57.BL/6 background, in comparison with wild-type C57.BL/6 animals. After immunization with MOGp 35-55, or with rat MBP, the disease courses of the 5-HTT knockout mice were attenuated as compared to wildtype control mice. This difference was more pronounced in female animals. To dissect potential immune mechanisms underlying this phenomenon, histological studies of the CNS and cytokine measurements in mononuclear cells from the spleens of 5-HTT KO mice and wild-type controls were performed. We found a reduction of the inflammatory infiltrate in the CNS and of the neuroantigen-specific production of IFN-gamma in splenocytes, again accompanied by a gender difference. These findings suggest a potential role of extracellular 5-HT homeostasis in the fine-tuning of neuroantigen-specific immune responses.


[Importance of prostaglandins for the in vitro adhesiveness and in vivo margination of neutrophilic granulocytes].
The (patho-)physiological role of prostaglandins and thromboxanes on granulocyte function remains controversial. In a combined in vitro and in vivo study, we analyzed the influence of these arachidonic acid metabolites on granulocyte adhesion and margination. A dichotomous dose-dependent effect on epinephrine-induced granulocyte demargination parallels the paradoxical effect of low (0.5 g)- and high (4 g)-dose aspirin on bleeding time. These observations suggest that prostacyclin acts as a modulator for low-affinity adhesion and margination of granulocytes. With respect to the induction of high-affinity adhesion, which is reflected in a state of hypermargination in vivo and accompanied by potentially cytotoxic cell activation, prostaglandins in general and prostacyclin in particular are without effect when such activation is induced, either by endotoxin, by formylated chemotactic peptide, or by activated complement.


The relationship between ankle dorsiflexion range of motion, frontal plane projection angle, and patellofemoral pain syndrome.
Ankle range of motion abnormalities have been often linked with alteration in knee kinematics leading to the development of patellofemoral pain syndrome (PFPS). Literature exploring the relationship between ankle dorsiflexion range of motion (DF ROM) and knee kinematics during functional tasks is scanty. This study aims to assess the relation between ankle DF ROM and frontal plane projection angle (FPPA), one of the knee kinematic variables, in individuals with and without PFPS during a step-down test. This is a case-control study in which seventy PFPS patients and other 70 asymptomatic control subjects had their ankle DF ROM measured using an inclinometer with the knee flexed and extended. Their FPPA angles were measured using Kinovea software while doing the step-down test. When the two groups were compared, ankle DF ROM measured with the knee flexed was higher in the control group (33.15 ± 4.96) than in the PFPS group (30.20 ± 6.93) (p = 0.03). In both the PFPS group and the control group, the correlation between FPPA and ankle DF ROM with the knee flexed was statistically insignificant (p = 0.075 and 0.323 respectively). Decreased ankle DF ROM can be one of the contributing factors to the development of PFPS in the context of greater dynamic knee valgus.


Naphthoquinone-based Hydrazone Hybrids: Synthesis and Potent Activity Against Cancer Cell Lines.
Natural naphthoquinones have shown diversified biological activities including antibacterial, antifungal, antimalarial, and cytotoxic activities. However, they are also compounds with acute cytotoxicity, immunotoxicity, carcinogenesis, and cardio- and hepatotoxicity, and the modification at their redox center is an interesting strategy to overcome such harmful activity. In this study, four novel semisynthetic hydrazones, derived from the isomers α- and β- lapachones (α and β, respectively) and coupled with the drugs hydralazine (HDZ) and isoniazid (ACIL), were prepared, evaluated by electrochemical methods and assayed for anticancer activity. The semisynthetic hydrazones were obtained and had their molecular structures established by NMR, IR, and MS. Anticancer activity was evaluated by cell viability determined by reduction of 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide (MTT). The electrochemical studies, mainly cyclic voltammetry, were performed, in aprotic and protic media. The study showed that the compounds 2, 3, and 4 were active against at least one of the cancer cell lines evaluated, compounds 3 and 4 being the most cytotoxic. Toward HL-60 cells, compound 3 was 20x more active than β-lapachone, and 3x more cytotoxic than doxorubicin. Furthermore, 3 showed an SI value of 39.62 for HL-60 cells. Compound 4 was active against all cancer cells tested, with IC50 values in the range 2.90-12.40 μM. Electrochemical studies revealed a profile typical of self-protonation and reductive cleavage, dependent on the supporting electrolyte. These results therefore indicate that compounds 3 and 4 are strong candidates as prototypes of new antineoplastic drugs.


Site specific mineral composition and microstructure of human supra-gingival dental calculus.
Dental calculus has been implicated in the aetiology of several periodontal conditions. Its prevention and removal are therefore desirable clinical goals. While it is known that calculus is very variable in chemical composition, crystallinity and crystallite size little is known about site specific variability within a dentition and between individuals. With this in mind, a study was undertaken to investigate the comparative site specific nature and composition of human dental supra-gingival dental calculus obtained from 66 male patients visiting for their dental check-up using fluorescent X-ray spectroscopy, X-ray diffractometry and Fourier transform infrared spectroscopy. The supra-gingival dental calculus formed on the lingual surfaces of lower anterior teeth and the buccal surfaces of upper molar teeth were classified into four types based on calcium phosphate phases present. There was significant difference in composition of the crystal phase types between lower and upper teeth (p<0.01). There was no significant difference in crystal size between dental calculus on anterior or molar teeth of all samples. The degree of crystallinity of dental calculus formed on the upper molar teeth was higher than that formed on the lower anterior teeth (p<0.01). The CO(3)(2-) contents in dental calculus formed on the lower anterior teeth were higher than on upper molar teeth (p<0.05) which might explain the difference in crystallinity. Magnesium and Si contents and Ca:P ratio on the other hand showed no significant difference between lower and upper teeth. It was concluded that the crystal phases, crystallinity and CO(3)(2-) contents of human dental supra-gingival dental calculus is related to its location in the mouth.


Ehlers-Danlos syndrome type VIIB. Deletion of 18 amino acids comprising the N-telopeptide region of a pro-alpha 2(I) chain.
A patient with Ehlers-Danlos syndrome Type VIIB was found to have an interstitial deletion of 18 amino acids in approximately half of the pro-alpha 2(I) chains of Type I procollagen. Analysis of pepsin-solubilized tissue and fibroblast collagen revealed an abnormal additional chain, alpha 2(I)', which migrated in sodium dodecyl sulfate-5% polyacrylamide gel electrophoresis between the normal alpha 1(I) and alpha 2(I) chains. The apparent ratio of normal alpha 1(I):mutant alpha 2(I)':normal alpha 2(I) was 4:1:1. Procollagen studies and enzyme digestion studies of native mutant collagen suggested defective removal of the amino propeptide. Sieve chromatography of CNBr peptides from purified alpha 2(I)' chains revealed the absence of the normal amino telopeptide fragment CB 1 and the appearance of a larger new peptide of approximately 60 residues (CB X). Compositional and sequencing studies of this peptide identified normal amino propeptide sequences. However, the most carboxyl-terminal tryptic peptide of CB X differed substantially in composition and sequence from the expected and was found to have an interstitial deletion of 18 amino acids corresponding to the N-telopeptide of the pro-alpha 2(I) chain. This deletion removes the normal sites of cleavage of the N-proteinase and also removes a critical cross-linking lysine residue. The 18 amino acids deleted correspond exactly to the residues encoded by exon 6 of the pro-alpha 2(I) collagen gene (COL 1 A2), and, therefore, the protein defect may be due to a genomic deletion, or alternatively, an RNA splicing defect.


Anti-inflammatory and anti-pathogenic potential of Lacticaseibacillus rhamnosus IDCC 3201 isolated from feces of breast-fed infants.
We investigated the anti-inflammatory and anti-pathogenic activities of Lacticaseibacillus rhamnosus IDCC 3201 isolated from the feces of breast-fed infants. Cell viability, nitric oxide (NO) production, and expression of inflammatory markers by L. rhamnosus IDCC 3201 were quantitatively analyzed in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. The antibacterial and antifungal activities of L. rhamnosus IDCC 3201 against various pathogens were also investigated. Treatment of LPS-induced macrophages with cell-free supernatant of L. rhamnosus IDCC 3201 significantly decreased the expression levels of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). Nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) levels also significantly decreased in LPS-induced macrophages. Phenotypically, the treatment of L. rhamnosus IDCC 3201 reduced the production of nitric oxide (NO) in LPS-induced macrophages. Furthermore, L. rhamnosus IDCC 3201 was proven to have potent inhibitory activities against various pathogens responsible for inflammatory responses in the gastrointestinal tract (i.e., Bacillus cereus, Enterococcus faecalis, Staphylococcus aureus, and Salmonella Typhimurium), respiratory system (i.e., Streptococcus pneumoniae), and vagina (i.e., Candida albicans). L. rhamnosus IDCC 3201 has anti-inflammatory activity in terms of decreased expression of cytokines, inflammation-inducible enzymes in LPS-induced macrophages, and anti-pathogenic activity.


Early-life exposure to Chinese famine and stroke risk in mid- to late life: the mediating roles of cognitive function and depression.
Limited research has examined the role that famine exposure plays in adulthood stroke risk. We aim to explore the causal implications of early exposure to the Great Chinese Famine on stroke risk and determine whether these associations were mediated by cognitive function, and depression. We sampled 12,681 individuals aged 45 years and older from the China Health and Retirement Longitudinal Study (CHARLS) and divided them into fetally exposed, childhood-exposed, adolescence/adulthood-exposed and unexposed groups. Stroke was defined by self- or proxy-reported physician diagnosis. Based on a counterfactual framework, marginal structural models were used to estimate the natural direct effect and the natural indirect effects through cognitive function and depression for causal inference. We found that early-life exposure to Chinese famine was directly related to increased stroke risk in mid- to late life. Cognitive function and depression accounted for a greater part of the effect for childhood famine exposure, mediating 36.35% (95%CI: 14.19, 96.19%) of the overall association between famine exposure and incident stroke, than for the fetal, adolescence/adulthood famine exposure groups. However, the natural indirect effect through depression was not significant in the fetally exposed group. The results were robust in the sensitivity analysis of model specification and unobserved confounding. Our findings are consistent with the latency, pathway, and accumulation models, supporting the life-course theory. Early stages of life exposed to the Chinese Famine were associated with higher risk of stroke in mid- to late life. Enhanced cognitive and depression interventions may reduce stroke risk in middle-aged and older Chinese adults who exposure to famine in early life.


Rejection sensitivity and depressive symptoms: Longitudinal actor-partner effects in adolescent romantic relationships.
The present study utilizes the actor-partner interdependence model to examine the longitudinal relationship between rejection sensitivity and one's own and one's partner's depressive symptoms. The sample included adolescent romantic couples from the U.S. (N = 198 adolescents; 50% girls; 90.2% Caucasian) whose rejection sensitivity at Time 1 and depressive symptoms approximately one year later (Time 2) were assessed. Additionally, aggressive behaviors and maintenance behaviors that commonly associated with rejection sensitivity (e.g., self-silencing) are explored as mediators. Results indicate that boyfriends' rejection sensitivity at Time 1 predicted girlfriends' depressive symptoms at Time 2. Additionally, girls' rejection sensitivity predicted their own and their boyfriends' self-silencing. Developmental and clinical implications are discussed.


[High fetal irradiation: about one pregnant woman receiving infradiaphragmatic radiotherapy for Hodgkin lymphoma].
We report the case of a 19-year-old young woman for whom was discovered a pregnancy at the end of the irradiation for a Hodgkin lymphoma (stage IV bone Bb), initially treated by chemotherapy. The radiotherapy delivered 36 Gy in infra-diaphragmatic volumes (lombo-aortic, spleen, L5), beginning in a pregnant patient for less than 4 amenorrhea weeks. The calculated received fetal dose (literature data, measurement with software TPS, measurement on phantom) is high: it's between 2.8 and 5 Gy. With a current follow-up of 4 years since the radiotherapy's end, the patient is in complete remission and her child presents with a normal development for the age, in spite of the infradiaphragmatic irradiation.


Antenatal three-dimensional sonographic features of fetal biliary atresia.
We present antenatal three-dimensional (3D) sonographic features of fetal biliary atresia. A 38-year-old pregnant Japanese woman was referred to our ultrasound clinic because of a fetal intra-abdominal cyst at 19 weeks of gestation. Conventional two-dimensional (2D) sonography and 3D sonography with an inversion mode showed a round cyst with a tiny dip in the subhepatic area. At 34 weeks, conventional 2D sonography and 3D sonography with inversion and transparent X-ray modes clearly revealed a round to oval cyst connected with the gallbladder via the cystic duct. A diagnosis of choledochal cyst (type I) was suggested antenatally. However, the final diagnosis made by employing operative cholangiography during surgery was biliary atresia (type I cyst) at 25 days of life. To the best of our knowledge, this is the first report of biliary atresia employing antenatal 3D sonography with inversion and transparent X-ray modes.


Morphology of open bite.
The purpose of this work was to define and illustrate the skeletal morphology of open-bite patients against the background of sagittal jaw relationships on the basis of lateral cephalograms. Lateral cephalograms of 197 untreated adults were analyzed in dental imaging software (Onyx Ceph 3™; Image Instruments, Chemnitz, Germany). Four groups were formed based on vertical (Index scores) and sagittal (individualized ANB values) parameters. Ninety-nine patients were defined as the control group due to their neutral sagittal and vertical relationships. The remaining patients were found by their vertical relationships to represent open-bite cases and were divided by their sagittal relationships into three study groups: neutral (Class I, n = 34), distal (Class II, n = 26), and mesial (Class III, n = 38). A geometric morphometric approach was used to analyze the x,y-coordinates of 28 skeletal landmarks on each cephalogram. Relative size was captured based on centroid size (CS). The shape-determining factors in the groups were compared by permutation testing after Procrustes transformation, and intergroup differences were visualized in the form of thin-plate splines. While size (CS) was significantly increased in the Class III group, the other two groups were not different from the control group. After Procrustes transformation, characteristic and invariably significant (p < 0.001) differences in shape were detected. Neutral (Class I) open bite involved compression in the mandibular ramus and the upper anterior facial third, including vertical expansion in the lower molar and anterior nasal spine areas. Mesial (Class III) open bite was associated with pronounced vertical and sagittal size reductions in the upper posterior segments and reduced lengths of the mandibular ramus. Distal (Class II) open bite involved expansion in the pterygoid area and compression in the mandibular ramus. Open bite is not a homogeneous group. Our geometric techniques of morphometric analysis revealed typical patterns, thus, confirming the differences observed by traditional morphometry. True skeletal overdevelopment appears to be present only in open-bite cases having a mesial jaw relationship. All open-bite groups have in common that the mandibular ramus is compressed, but marked differences are seen in terms of vertical development of the maxilla. This differentiated view of open-bite cases should be taken into consideration during individual etiology assessment and treatment planning.


Polymorphisms of myelin-associated glycoprotein gene are associated with schizophrenia in the Chinese Han population.
Results of gene expression microarray and quantitative PCR studies have suggested abnormalities in the expression of myelin-related genes including myelin-associated glycoprotein (MAG) in schizophrenic patients. Research provides strong evidence for oligodendrocyte dysfunction in schizophrenics. In order to further assess the role of MAG in schizophrenia, we examined four single nucleotide polymorphisms (SNPs), namely rs2301600, rs3746248, rs720309 and rs720308, of this gene in Chinese schizophrenic patients (n=470) and healthy controls (n=470). The distribution of rs720309 T/A genotypes showed a strong association with schizophrenia (chi(2)=14.58, d.f.=2, P=0.0008). A haplotype constructed of rs720309-rs720308 also revealed a significant association with schizophrenia (chi(2)=11.914, d.f.=3, P=0.0084). Our findings of a significant associations between schizophrenia and the MAG gene suggest that this gene may be involved in susceptibility to schizophrenia in the Chinese Han population.


Predicting early recurrence of hepatocellular carcinoma with texture analysis of preoperative MRI: a radiomics study.
To investigate the feasibility of using texture analysis in preoperative magnetic resonance imaging (MRI) to predict early recurrence (ER) in hepatocellular carcinoma (HCC) post-curative surgery. Institutional review board was obtained. A retrospective review of all patients who underwent hepatectomy between 1 January 2007 and 31 December 2015 was performed. Inclusion criteria included preoperative MRI, tumour size ≥1 cm, new cases of HCC. Exclusion criteria included loss to follow-up, ruptured HCCs, movement artefacts, and previous hepatectomy or interval adjuvant therapy. Patients were divided into ER and late or no recurrence (LNR) groups. ER was defined as new foci of HCC within 730 days of curative surgery. Radiomics feature extraction was performed on T2, diffusion-weighted imaging (DWI), T1 arterial, and T1 portovenous acquisitions on MATLAB (Mathworks, Matick, MA, USA). The MaZda software was used to analyse 290 texture parameters and PRTools was used for feature selection. Fifty patients (43 male, mean age 67 years) were divided into ER (n=20) and LNR (n=30) groups. Serum alpha-fetoprotein level (p=0.026), serum ɣ-glutamyltranspeptidase (p=0.014), Child-Pugh score (p=0.02) and the presence of vascular invasion (gross and/or microvascular, p=0.025) were found to be statistically significant different between the two groups. Parameters S(4,0)SumVarnc, S(0,3)SumOfSqs, and S(1,1)DifVarnc of the equilibrium phase were most accurate, achieving 84%, 82%, and 78% accuracy, respectively. Texture analysis of preoperative MRI has the potential to predict ER of HCC with up to 84% accuracy using an appropriate, single texture analysis parameter. Future studies are needed to validate these findings.


Effectiveness of preventive and corrective surgical intervention on hip disorders in severe cerebral palsy: a systematic review.
This review presents an overview of the effectiveness of preventive and corrective surgical interventions to treat hip displacement in patients with severe cerebral palsy (CP). A systematic literature search was applied to identify studies concerning surgical procedures in hip(sub)luxations in severe CP (GMFCS IV and V). A qualitative analysis and a best evidence synthesis were performed for soft tissue surgery and osteotomies. The literature search identified 15 studies, all of which were observational. Five studies involved soft tissue surgery and 10 involved osteotomies. Only one study involving soft tissue surgery was of sufficient quality. Nine of the 10 studies involving osteotomies were of sufficient quality, including a total of 189 patients. The mean MP (migration percentage) at follow-up ranged from 6 to 29%. No relationship could be established between the effect of the surgical procedure and the patients' age or the duration of follow-up. The percentage of patients reporting pain decreased from 81% preoperatively to 5% at follow-up. Twenty-five percent had complications such as osteoarthritis, ulcers or fractures. There is insufficient evidence for the effectiveness of soft tissue surgery to stabilize the hip, due to insufficient quality of the retrospective observational studies. This review shows indicative findings (provided by consistent, statistically significant findings on outcome and/or process measures in at least two Observational Studies with sufficient quality) for an effect of bony surgery in stabilizing the hip. Timing of the procedure remains an issue. Multicenter trials could shed further light on this complicated subject.


Prophylactic doses of low-molecular weight heparin as periprocedural bridging therapy in mechanical heart valve patients.
Mechanical heart valve (MHV) patients undergoing invasive procedures necessitating an interruption of their lifelong anticoagulant therapy, often require bridging with low-molecular weight heparin (LMWH) or unfractionated heparin. The aim of this study was to assess whether bridging MHV patients with prophylactic doses of LMWH undergoing invasive, elective procedures is a safe and effective method. This observational cohort study included all MHV patients on vitamin K anticoagulant therapy in Malmö, registered and monitored via AuriculA (the Swedish national quality registry for atrial fibrillation and anticoagulation), between 1/1/2008 and 31/12/2011. Inclusion criteria were periprocedural bridging therapies conducted via AuriculA. Primary endpoints were mortality, thromboembolic (TE) events or major bleedings (MBE) within 30 days of bridging. During the study period, 210 patients had undergone 434 bridging therapies managed via AuriculA; 203 due to subtherapeutic INR-values were excluded. The remaining 231 periprocedural bridging therapies were included. All were bridged with prophylactic doses of LMWH. When comparing patients with aortic and/or mitral valve replacements undergoing low- or high-risk interventions, only number of days bridged for a low-risk intervention differed significantly. Patients with a mitral or mitral and aortic valve replacement were bridged for a longer period (p=0.023). No TE events, 1 death (0.4%) and 3 MBEs (1.3%) occurred related to periprocedural bridging. Our study shows a low rate of MBEs, deaths and no TE events when bridging MHV patients undergoing invasive, elective procedures with prophylactic doses of LMWH.


Memory-dictated dynamics of single-atom Pt on CeO2 for CO oxidation.
Single atoms of platinum group metals on CeO2 represent a potential approach to lower precious metal requirements for automobile exhaust treatment catalysts. Here we show the dynamic evolution of two types of single-atom Pt (Pt1) on CeO2, i.e., adsorbed Pt1 in Pt/CeO2 and square planar Pt1 in PtATCeO2, fabricated at 500 °C and by atom-trapping method at 800 °C, respectively. Adsorbed Pt1 in Pt/CeO2 is mobile with the in situ formation of few-atom Pt clusters during CO oxidation, contributing to high reactivity with near-zero reaction order in CO. In contrast, square planar Pt1 in PtATCeO2 is strongly anchored to the support during CO oxidation leading to relatively low reactivity with a positive reaction order in CO. Reduction of both Pt/CeO2 and PtATCeO2 in CO transforms Pt1 to Pt nanoparticles. However, both catalysts retain the memory of their initial Pt1 state after reoxidative treatments, which illustrates the importance of the initial single-atom structure in practical applications.


Effect of over-the-counter drugs on the unborn child: what is known and how should this influence prescribing?
The developing organism is unique in its responsiveness to drugs. The predictability of therapeutic effectiveness and safety of drugs in pregnancy using the adult as a model for pharmacokinetics and pharmacodynamics can result in grave consequences in the fetus. There exists a general misconception that since over-the-counter (OTC) drugs are readily available, these pharmaceutical agents can be viewed as safe to use by adults. Ingestion of OTC preparations during pregnancy results in placental transfer and accumulation of these drugs in the fetus. As the fetus lacks the ability to handle pharmaceutical agents, since renal function, metabolic pathways, etc. are not fully developed, drug exposure in utero may produce deleterious effects in the fetus but not the mother. Clinicians are aware of drug-induced effects on the fetus and have dramatically reduced the use of prescription drugs during pregnancy. However, the use of self-medication (OTC) has significantly increased during pregnancy through extensive, effective advertising by the pharmaceutical industry and lack of sufficient data indicating an OTC effect on the fetus. However, the consequences of OTC drug use need to be established, since these compounds continue to be used extensively, especially during pregnancy.


Evaluation of CT angiography obstruction score and pulmonary perfusion defect score using the third-generation dual-source CT for pulmonary embolism.
To investigate the application value of computed tomography (CT) angiography (CTA) obstruction score and pulmonary perfusion defect score on the third-generation dual-source CT for pulmonary embolism and the changes of the right ventricular function. The clinical data of 52 patients with pulmonary embolism (PE) confirmed using the third-generation dual-source dual-energy CTPA were analysed retrospectively. These patients were divided into the severe group and non-severe group according to their clinical manifestations. The results of CTPA and dual-energy pulmonary perfusion imaging (DEPI) were recorded by two radiologists for index computation. The ratio of the maximum short-axis diameter of the right ventricle (RV) to that of the left ventricle (LV) was also recorded. The correlation analysis between RV/LV and the mean values of CTA obstruction score and perfusion defect score was performed. Correlation analysis and agreement analysis were performed on the data measured by two radiologists, CTA obstruction score, and pulmonary perfusion defect score. CTA obstruction score and perfusion defect score measured by the two radiologists had good correlation and agreement. CTA obstruction score, perfusion defect score, and RV/LV were significantly lower in the non-severe group than in the severe PE group. RV/LV had a significant positive correlation with CTA obstruction score and perfusion defect score (p<0.05). The third-generation dual-source dual-energy CT plays a positive role in assessing PE severity and RV function and can provide additional information for the clinical management and treatment of PE patients.


Hyperhomocysteinemia in pregnant rats: effects on arterial pressure, kidneys and fetal growth.
This study aimed to test the hypothesis that hyperhomocysteinemia plays a role in the development of pathological changes similar to human preeclampsia in pregnant rats. Arterial pressure and 24-h urinary excretion of proteins and electrolytes were measured during pre-pregnancy, pregnancy and postpartum periods in control (n = 12) and methionine-treated (2.0 g/kg/day, n = 11) Sprague-Dawley rats. Rats were then sacrificed at the end of this protocol and renal histological examination was performed. In another protocol, control (n = 6) and methionine-treated (n = 6) rats were anaesthetized at day 20 of gestation and pregnancy outcome was assessed. Hemodynamic and renal excretory differences between groups were analyzed using ANOVA and differences in renal histology and gestation outcome using t-test. Serum homocysteine in the methionine group (24.0+/-2.0 micromol/L) was significantly higher compared with controls (8.5+/-0.5 micromol/L). Systolic pressure, urinary protein excretion and renal histological changes were not significantly different between the two groups. However, fetal weights were significantly smaller and percent of dead fetuses were 15% higher in methionine-treated compared with control rats. Hyperhomocysteinemia is unlikely to cause maternal hypertension, proteinuria or renal damage in pregnant rats. However, hyperhomocysteinemia may restrict fetal growth and increase fetal mortality.


Rapamycin recruits SIRT2 for FKBP12 deacetylation during mTOR activity modulation in innate immunity.
The mammalian target of rapamycin (mTOR) is a serine-threonine kinase involved in cellular innate immunity, metabolism, and senescence. FK506-binding protein 12 (FKBP12) inhibits mTOR kinase activity via direct association. The FKBP12-mTOR association can be strengthened by the immunosuppressant rapamycin, but the underlying mechanism remains elusive. We show here that the FKBP12-mTOR association is tightly regulated by an acetylation-deacetylation cycle. FKBP12 is acetylated on the lysine cluster (K45/K48/K53) by CREB-binding protein (CBP) in mammalian cells in response to nutrient treatment. Acetyl-FKBP12 associates with CBP acetylated Rheb. Rapamycin recruits SIRT2 with a high affinity for FKBP12 association and deacetylation. SIRT2-deacetylated FKBP12 then switches its association from Rheb to mTOR. Nutrient-activated mTOR phosphorylates IRF3S386 for the antiviral response. In contrast, rapamycin strengthening FKBP12-mTOR association blocks mTOR antiviral activity by recruiting SIRT2 to deacetylate FKBP12. Hence, on/off mTOR activity in response to environmental nutrients relies on FKBP12 acetylation and deacetylation status in mammalian cells.


An audit of treatment withdrawal in one hundred patients on a general ICU.
The audit found that 72.6% of patients who died had treatment withdrawn. Three organ failures were most often present in patients when treatment was withdrawn. Withdrawal of treatment did not mean the cessation of care. Variation in involvement was demonstrated with different consultants.


Telomere shortening as a stress-related biomarker in children exposed to maternal chronic stress in utero measured 7 years after the Great East Japan Earthquake.
Seven years after the Great East Japan Earthquake, we investigated telomeres as a potential biomarker of maternal chronic stress in children according to the timing of exposure to the disaster. The subjects were children aged 5-9 years living in Rikuzentakata, Japan. Relative telomere length (rTL) was measured with PCR in saliva samples. The partial regression coefficient of the rTL was significantly shorter in the group of children conceived after the disaster than in the children who were in utero on the day of the disaster. Telomere length should be investigated as a biomarker for assessing disaster-related trauma in future studies.


PCB153 reduces apoptosis in primary cultures of murine pituitary cells through the activation of NF-κB mediated by PI3K/Akt.
Polychlorinated biphenyls (PCBs) are persistent pollutants involved in human tumorigenesis. PCB153 is a ubiquitous non-dioxin-like PCB with proliferative and anti-apoptotic effects. To explore the impact of PCB153 in the survival of pituitary cells, we exposed murine pituitary primary cells to PCB153 10 μM for 24 h. Apoptosis was assessed by RT-qPCR, Western-blot, immunoprecipitation, caspase activity, and immunofluorescence. We found that PCB153 decreased pituitary apoptosis through both the extrinsic and intrinsic pathways. PCB153 reduced the level of the pro-apoptotic protein p38-MAPK. Otherwise, PCB153 activated PI3K/Akt and Erk1/2 pathways and enhanced the expression and nuclear translocation of NF-κB. Cotreatments with specific inhibitors revealed that only PI3K/Akt changed the caspase-3 expression and NF-κB activation induced by PCB153. Also, PCB153 decreased the expression of the pro-apoptotic and pro-senescent cyclins p53 and p21. In summary, exposure to PCB153 leads to a downregulation of apoptosis in the pituitary driven by a PI3K/Akt-mediated activation of NF-κB.


Psychometric evaluation of the power of food scale in a diverse college sample: Measurement invariance across gender, ethnicity, and weight status.
The Power of Food Scale (PFS) is an instrument designed to examine individual differences in the drive to eat for pleasure (as opposed to in response to physiological hunger) and the effect of living in an obesogenic environment. Previous research supports the validity and reliability of the PFS, however, it had yet to be validated in an ethnically diverse college sample. The purpose of the current study was to test the factor structure and measurement invariance of the PFS across gender, ethnicity, and weight status. A sample of 432 college students completed the PFS (males=113, females = 319; non-Hispanic white=181, Hispanic=251; non-overweight=302, overweight=130). Confirmatory factor analysis was used to test a second-order, 3-factor (food available, food present, food tasted) structure of the PFS in each group separately (males, females, Hispanic, non-Hispanic white, non-overweight, and overweight) and tests of measurement invariance were conducted to test the equivalency of the measure across gender, ethnicity, and weight status. Results supported the measure's original factor structure (second-order, 3-factor model) and indicated that the measure is equivalent across each of these groups, respectively. Although the small, unbalanced groups may impact the stability of the findings, the results nonetheless suggest that the PFS is a psychometrically valid measure in a diverse college sample, and that mean comparisons on this measure are meaningful across gender, ethnicity, and weight status. Given the measurement invariance of the PFS, there is support for use of the PFS among diverse college students in future work.


A Case Report and Literature Review of the Role of Dupilumab in the Management of Lichen Planus: Cause or Treatment?
Lichen planus (LP) is a chronic inflammatory skin condition characterized by the six Ps (ie. purple, planar, polygonal, pruritic, plaques, and papules) often causing physical, emotional, and psychological stress for the person affected. Drug-induced LP has been described after the administration of drugs like antihypertensives, non-steroidal anti-inflammatory drugs (NSAIDs), and biologics like adalimumab and etanercept. Currently, there is a dearth of studies discussing the association between LP and dupilumab. Here, we present the case of a young adult female who developed LP 24 months after treatment with dupilumab for severe atopic dermatitis. We also conducted a review of the literature discussing the association between LP and dupilumab.


Reaction mechanism of chloramphenicol with hydroxyl radicals for advanced oxidation processes using DFT calculations.
The structure properties of chloramphenicol (CAP), including bond information and the Fukui function for the atoms in the main chain, were investigated computationally by density functional theory (DFT). The result shows that the chiral carbons in CAP offer the most active positions for chemical reactions, which is in good agreement with the experiment. The detailed degradation mechanism for CAP with hydroxyl radicals in advanced oxidation processes is further studied at the SMD/M06-2X/6-311 + G(d,p) level of theory. The main reaction methods, including the addition-elimination reaction, hydrogen abstract reaction, hydroxyl radical addition, and bond-breaking processes, are calculated. The results show that the nitro-elimination reaction is the most likely reaction in the first step of the degradation of CAP, and the latter two processes are more likely to be hydrogen abstract reactions. The details for the transition states, intermediate radicals, and free energy surfaces for all proposed reactions are given, which makes up for a lack of experimental knowledge.


HbA1C as a marker of retrograde glycaemic control in diabetes patient with co-existed beta-thalassaemia: A case report and a literature review.
The HbA1C marker used in assessing diabetes control quality is not sufficient in diabetes patients with thalassaemia. A male diabetic patient with thalassaemia was hospitalized due to distal neuropathic pain, right toe trophic ulcer, unacceptable five-point glycaemic profile and recommended HbA1C value. After simultaneously initiated insulin therapy and management of ulcer by hyperbaric oxygen, the patient showed improved glycaemic control and ulcer healing, which led to the patient's discharge. In thalassaemia and haemoglobinopathies, due to discrepancies in the five-point glycaemic profile and HbA1C values, it is necessary to measure HbA1C with a different method or to determine HbA1C and fructosamine simultaneously.


Characterizing car-following behaviors of human drivers when following automated vehicles using the real-world dataset.
As the market penetration rate of automated vehicles (AVs) increases, there will be a transition period when the traffic stream is composed of both AVs and human-driven vehicles (MVs) in the near future. However, the interactions between MVs and AVs, especially whether MVs will behave differently when following AVs compared to following MVs, have not been fully understood. Previous studies in this field mainly conducted traffic/numerical simulations or field experiments to investigate human drivers' behavior changes, but these approaches all have critical drawbacks such as simplified driving environments and limited sample sizes. To fill in the knowledge gap, this study uses the high-resolution (10 Hz) Waymo Open Dataset to reveal differences in car-following behaviors between MV-following-AV and MV-following-MV cases. Driving volatility measures, time headways and time-to-collision (TTC) are adopted to quantify and compare MV-following-AV and MV-following-MV interactions. The principal component analysis (PCA) is applied on the high-dimensional feature space, followed by the hierarchical clustering on the dimension-reduced feature set to categorize MV driving styles when following AVs. The comparison results indicate that MV-following-AV events have lower driving volatility in terms of velocity and acceleration/deceleration, smaller time headways and higher TTC values. Furthermore, the clustering results reveal that human drivers when following AVs exhibit four different car-following styles: high-velocity-non-aggressive, high-velocity-aggressive, low-velocity-non-aggressive, and low-velocity-aggressive. These findings highlight the vital importance of taking into account the heterogeneity of MV-following-AV behaviors when designing mixed traffic control algorithms and can be beneficial for AV fleet operators to improve their algorithms.


Expansion of Gamma-Butyrolactone Signaling Molecule Biosynthesis to Phosphotriester Natural Products.
Bacterial hormones, such as the iconic gamma-butyrolactone A-factor, are essential signaling molecules that regulate diverse physiological processes, including specialized metabolism. These low molecular weight compounds are common in Streptomyces species and display species-specific structural differences. Recently, unusual gamma-butyrolactone natural products called salinipostins were isolated from the marine actinomycete genus Salinispora based on their antimalarial properties. As the salinipostins possess a rare phosphotriester motif of unknown biosynthetic origin, we set out to explore its construction by the widely conserved 9-gene spt operon in Salinispora species. We show through a series of in vivo and in vitro studies that the spt gene cluster dually encodes the salinipostins and newly identified natural A-factor-like gamma-butyrolactones (Sal-GBLs). Remarkably, homologous biosynthetic gene clusters are widely distributed among many actinomycete genera, including Streptomyces, suggesting the significance of this operon in bacteria.


Reply to the 'Comment on "Elucidation of charge-transfer SERS selection rules by considering the excited state properties and the role of electrode potential"' by M. Mohammadpour, M. H. Khodabandeh, L. Visscher and Z. Jamshidi, Phys. Chem. Chem. Phys., 2017, 19, 7833.
We appreciate Aranda's comments on our recent work entitled ''Elucidation of charge-transfer SERS selection rules by considering the excited state properties and the role of electrode potential''. We would also like to thank the editor of Physical Chemistry Chemical Physics for giving us an opportunity to specify more details of our work in this reply. An important part of our article concerns the role of the electrode potential in charge-transfer SERS spectra and we would like to first address the questions that Aranda et al. posed about our labeling.


Repetitive activity and Hopf bifurcation under point-stimulation for a simple FitzHugh-Naguma nerve conduction model.
In response to point-stimulation with a constant current, a neuron may propagate a repetitive train of action potentials along its axon. For maintained repetitive activity, the current strength I must be, typically, neither too small nor too large. For I outside some range, time independent steady behavior is observed following a transient phase just after the current is applied. We present analytical results for a piecewise linear FitzHugh-Nagumo model for a point-stimulated (non-space-clamped) nerve which are consistent with this qualitative experimental picture. For each value of I there is a unique, spatially nonuniform, steady state solution. We show that this solution is stable except for an interval (I*, I(*)) of I values. Stability for I too small or too large corresponds to experiments with sub-threshold I or the excessive I which leads to 'nerve block'. For I = I*, I(*) we find Hopf bifurcation of spatially nonuniform, time periodic solutions. We conclude that (I*, I(*)) lies interior to the range of I values for repetitive activity. The values of I* and I(*) and their dependence on the model parameters are determined. Qualitative differences between results for the point-stimulated configuration and the space-clamped case are discussed.


The role of psychosocial, behavioural and emotional factors on self-reported major injuries in Brazilian adolescents: a case-control study.
The objective of this research was to investigate the sociodemographic, psychosocial, behavioural and emotional risk factors associated with self-reported major injuries. A case-control study, nested in a two-stage survey, was carried out in two cities of the Distrito Federal, Brazil. Cases were defined as subjects who reported an event resulting in injury or physical harm to the person, about which a hospital was visited or a doctor consulted (major injury), during the period of 6 months preceding the interview. Controls (n=640) were matched to cases (n=231) based on sex and neighbourhood. Information on determinants of injuries was collected by self-completed questionnaires and included sociodemographic, psychosocial, behavioural and emotional variables. Data analysis used conditional logistic regression models. Controlling for social support and pro-social behaviour, adolescents reporting "abnormal" behaviour and emotional problems had more than three times the chance of reporting a major injury compared to "normal" status adolescents (OR=3.65, 95%CI=1.83-7.32). The findings of this study suggest that preventive strategies, while addressing the broader community and environmental risk factors for injuries, need to address the behavioural and emotional factors associated with these injuries.


Concept analysis of maternal-infant attachment during the weaning process.
At the time that the mother and baby transit from breastfeeding to weaning, maternal-fetal attachment becomes a crucial basis for maintaining their emotional relationship. Conceptualization is needed to better understand the phenomenon of maternal-infant attachment during the weaning process. The purpose of this paper is to explore and identify the essence of the term maternal-infant attachment during weaning and to arrive at an operational definition of the concept. Concept analysis following Walker and Avant. The attributes of maternal-infant attachment during the weaning process include (1) consistent and properly timed, (2) dynamic transactional interaction, and (3) secured adjustment. Maternal-infant attachment during the weaning process is brought by maternal sensitivity, closeness and proximity seeking, gentle and positive weaning, and breastfeeding experiences, which later turn into favorable emotion regulation, maturity, self-efficacy, secured bond, less intrusive interaction, resilience, and child's behavioral and development. This concept analysis provides new insight into maternal-infant attachment during the weaning process that guides the nursing practice. Also, the findings can help develop or improve the models, theories, and instruments collected for maintaining maternal-fetal attachment during the weaning process.


An amicronucleate mutant of Tetrahymena thermophila.
A stable amicronucleate strain of Tetrahymena thermophila was isolated following nitrosoguanidine mutagenesis. The mutant has the same growth rate and viability as the micronucleate parent strain, and has no micronucleus detectable by chromatin-specific staining in vegetative growth or during conjugation. The mutant pairs with normal efficiency with cells of complementary mating type. Matings of the mutant with aneuploid strains which lose their micronucleus during meiosis produced cell pairs yielding one viable and one inviable cell. The mutant receives a micronucleus from a normal mating partner, but this micronucleus is lost by the mutant cells within two hundred generations.


Single nucleotide polymorphism of toll-like receptor 4 (TLR4) is associated with juvenile spondyloarthritis in Croatian population.
Single nucleotide polymorphisms (SNP) of toll-like and NOD-like receptors have been associated with altered receptor activity and modified production of proinflammatory cytokines leading to a number of diseases. Our aim was to determine whether SNP of TLR2 (Arg753Gln), TLR4 (Asp299Gly, Thr399Ile), and NLRP3 (Q705K) influence susceptibility to juvenile spondyloarthrtis (jSpA) and juvenile idiopathic arthritis (JIA). After the DNA extraction, 26 patients with jSpA, 11 with oligoarticular, polyarticular, or systemic JIA, and 40 healthy controls were genotyped for Arg753Gln, Asp299Gly, Thr399Ile, and Q705K SNP using real-time PCR-SNP analysis. Statistically significant difference in genotype frequency for Thr399Ile SNP of TLR4 was observed in the jSpA (χ2 = 6.705, p = 0.035) and not in the JIA group (χ2 = 3005, p = 0.223). Regarding Asp299Gly SNP, no significant difference in genotype frequency was found; however, allele frequency was significant in both jSpA and JIA patients. No significant difference in genotype or allele frequency was observed for Arg735Gln and Q705K SNP. The399Ile polymorphism of TLR4 may be responsible for altered immune response to microbial infection in variant carriers and represent a mechanism of triggering overproduction of proinflammatory cytokines and long-term inflammation in jSpA. SNP of TLR2, NLRP3, and TLR4 (Asp299Gly) were not associated with jSpA or JIA.


Retinoblastoma regression following intra-arterial chemotherapy to the contralateral eye.
Intra-arterial chemotherapy (IAC) has assumed a major role in the management of retinoblastoma. This targeted therapy involves the delivery of chemotherapy directly into the ophthalmic artery, minimizing systemic absorption. We report a case of retinoblastoma regression in the untreated eye following IAC to the contralateral eye.


Neuronal degeneration and microglial reaction in the fetal and postnatal rat brain after transient maternal hypoxia.
This study examined the neuropathological changes in different areas of the brain of fetal and postnatal rats after transient maternal hypoxia. At different time intervals following hypoxia, reactive microglia as determined immunohistochemically with the antibody OX-42 that recognizes complement type three (CR3) receptors, responded vigorously to the hypoxic stress. Microglial activation was particularly evident in the cingulate cortex and the corpus callosum between 3 h and 14 days after hypoxia. Massive cell degeneration as determined ultrastructurally and significant neuronal loss as evaluated by cell counts were observed in the cingulate cortex at 1 and 3 days after hypoxic insults; thereafter, however, the neuronal density was restored to normal levels. Present results suggest that the cingulate cortex is most vulnerable to the hypoxic injury probably due to a redistribution of cerebral blood flow and/or metabolic changes. Besides being involved in the phagocytosis of cellular debris, it is suggested that the reactive microglial cells may have both neurotoxic and neurotrophic functions.


Molecular cloning and sequence of the concatemer junction from vaccinia virus replicative DNA. Viral nuclease cleavage sites in cruciform structures.
The concatemer junction from replicative forms of vaccinia virus DNA was cloned into plasmid vectors and shown to be a precise duplex copy of the viral terminal hairpin structure, with each strand corresponding to one of the alternative sequence isomers. The plasmids were relaxed circles with extruded cruciforms representing two copies of the vaccinia telomere hairpin structure. Head-to-head dimers containing two copies of the vaccinia virus concatemer junction were observed to contain only one set of stem-loop structures per molecule, suggesting that the initial formation of a small cruciform, and not branch migration, was the rate-limiting step in cruciform formation. The plasmids containing the concatemer junction were converted into nicked circular, linear and cross-linked linear molecules by a nuclease isolated from vaccinia virions. The region-specific cleavage near the border of the hairpin loop and the formation of DNA cross-links in some of the molecules is consistent with the nuclease acting as a nicking-closing enzyme that participates in the resolution of mature termini from replicative concatemer intermediates.


Genomic mapping by fingerprinting random clones: a mathematical analysis.
Results from physical mapping projects have recently been reported for the genomes of Escherichia coli, Saccharomyces cerevisiae, and Caenorhabditis elegans, and similar projects are currently being planned for other organisms. In such projects, the physical map is assembled by first "fingerprinting" a large number of clones chosen at random from a recombinant library and then inferring overlaps between clones with sufficiently similar fingerprints. Although the basic approach is the same, there are many possible choices for the fingerprint used to characterize the clones and the rules for declaring overlap. In this paper, we derive simple formulas showing how the progress of a physical mapping project is affected by the nature of the fingerprinting scheme. Using these formulas, we discuss the analytic considerations involved in selecting an appropriate fingerprinting scheme for a particular project.


Serum prolactin in patients with liver disease in comparison with healthy adults: A preliminary cross-sectional study.
Studies from the west have shown raised prolactin levels in patients with liver disease. Considering the lacunae on Indian context, we conducted the present study with an objective to assess the prolactin levels in patients with cirrhosis and viral hepatitis with or without features of encephalopathy. The data presented here are the results of the preliminary analysis. The present study was a prospective, cohort study among patients diagnosed as either viral hepatitis or cirrhosis liver. A cohort of normal healthy adults was selected based on history and laboratory investigations (complete blood count, liver and renal function tests). Serum prolactin was measured for all the study participants, and Kruskal-Wallis H-test with post-hoc Dunn's test was used to analyze the significance of the differences in the levels between various groups. Tests of diagnostic accuracy were used to assess the prediction capability of serum prolactin with a cut-off level of 50 ng/ml. A total of 70 patients (10 - normal healthy; 25 - acute viral hepatitis; 35 - cirrhosis liver) were recruited in the present study with the median (range) age in years of 56 (34-68) and male: female ratio of 2:1. A statistically significant (P < 0.05) increase in the serum prolactin was observed in patients with cirrhosis with or without encephalopathy. But, among the patients with viral hepatitis, a significant elevation was observed only in patients with encephalopathy. Additionally, a statistically significant association was observed between serum prolactin levels with serum bilirubin (ρ =0.67, P = 0.04) and aspartate aminotransferase (ρ =0.72, P = 0.05). A cut-off value of 50 ng/ml of serum prolactin was found to predict the mortality. A total of 4/12 (33.3%) with prolactin value of <50 ng/ml died while 11/23 (47.8%) died with values >50 ng/ml (P < 0.05). Similarly, in patients with viral hepatitis with encephalopathy features, 1/4 (25%) with prolactin value of <50 ng/ml died while among those without any such features (n = 21), 9 (42.9%) died (P < 0.05). Serum prolactin has a significant association with patients with liver disease and predicts mortality.


Custom DNA-binding proteins come of age: polydactyl zinc-finger proteins.
Artificial transcription factors based on modified zinc-finger DNA-binding domains have been shown to activate or repress the transcription of endogenous genes in multiple organisms. Advances in both the construction of novel zinc-finger proteins and our understanding of the characteristics of a productive regulatory site have fueled these achievements.


Enhanced hydrogen bonding via epoxide-functionalization restricts mobility in poly(ethylenimine) for CO2 capture.
Free energy sampling, deep potential molecular dynamics, and characterizations provide insights into the impact of epoxide-functionalization on the hydrogen bonding and mobility of poly(ethylenimine), a promising CO2 sorbent. These findings rationalize the anti-degradation effects of epoxide functionalization and open up new avenues for designing more durable CO2 sorbents.


Developmental changes in duodenal calcium transport in female rats related to ovarian hormone status and growth rate.
Duodenal active calcium (Ca) transport is known to decrease with age in male rats. The present studies were undertaken to extend this observation to female rats, and to determine whether alterations in active Ca transport are related to sexual maturation in the female. Everted duodenal sacs from intact and ovariectomized (ovx) rats were used to measure duodenal active Ca transport. Female rats were raised from weaning, and Ca transport was measured at 2-week intervals until 12 weeks of age. Transport rates were found to be the highest from 4 to 6 weeks of age, and then to decline over the next 4-6 weeks. However, if females were ovx as weanlings, the age-related decline in Ca transport failed to occur. Ovariectomy of immature females also prevented the slowing of growth rate which normally accompanies sexual maturation in female rats. We therefore repeated the experiment, pair-feeding the ovx animal to intact controls to maintain normal growth rates. When growth was normalized in this manner, the Ca transport rate in ovx animals declined with age at the same rate as in intact animals. Since ovx of sexually mature rats has been reported to increase growth rate, we studied the relationship between duodenal Ca transport and growth rate in females ovx at 12 weeks of age and pair-fed to age-matched intact females. After 5 weeks, ovx was found to have resulted in an increase in both weight and duodenal active Ca transport relative to the intact animals. Ovariectomy did not alter circulating levels of 1,25-dihydroxyvitamin D.(ABSTRACT TRUNCATED AT 250 WORDS)


Increased rectal wall stiffness after prostate radiotherapy: relation with fecal urgency.
Late anorectal toxicity is a frequent adverse event of external beam radiotherapy (EBRT) for prostate cancer. The pathophysiology of anorectal toxicity remains unknown, but we speculate that rectal distensibility is impaired due to fibrosis. Our goal was to determine whether EBRT induces changes of rectal distensibility as measured by an electronic barostat and to explore whether anorectal complaints are related to specific changes of anorectal function. Thirty-two men, irradiated for localized prostate carcinoma, underwent barostat measurements, anorectal manometry, and completed a questionnaire prior to and 1 year after radiotherapy. The primary outcome measure was rectal distensibility in response to stepwise isobaric distensions. In addition, we assessed sensory thresholds, anal pressures, and anorectal complaints. External beam radiotherapy reduced maximal rectal capacity (227 ± 14 mL vs 277 ± 15 mL; P < 0.001), area under the pressure-volume curve (3212 ± 352 mL mmHg vs 3969 ± 413 mL mmHg; P < 0.005), and rectal compliance (15.7 ± 1.2 mL mmHg(-1) vs 17.6 ± 0.9 mL mmHg(-1) ; P = 0.12). Sensory pressure thresholds did not significantly change. Sixteen of the 32 patients (50%) had one or more anorectal complaints. Patients with urgency (n = 10) had a more reduced anal squeeze and maximum pressure (decrease 29 ± 11 mmHg vs 1 ± 7 mmHg; P < 0.05 and 31 ± 12 mmHg vs 2 ± 8 mmHg; P < 0.05 respectively) compared with patients without complaints, indicating a deteriorated external anal sphincter function. Irradiation for prostate cancer leads to reduced rectal distensibility. In patients with urgency symptoms, anal sphincter function was also impaired.


Analysis of cyclic nucleotide phosphodiesterase by isoelectric focusing coupled to a specific activity stain.
The procedure described allowed a convenient analysis of cyclic nucleotide phosphodiesterase. The different phosphodiesterase forms present in a crude cytosolic preparation from rat heart were separated by isoelectric focusing on a polyacrylamide gel plate. Phosphodiesterase activity bands were rendered evident by a specific staining method. They were then characterized by means of their substrate specificity and their sensitivity to selective phosphodiesterase inhibitors. The correspondence between the stain bands and the previously described activity peaks, obtained by a preparative technique and detected by radioisotopic enzyme assay, was also investigated.


Laparoscopic fundoplication in treating refractory gastroesophageal reflux-related chronic cough: A meta-analysis.
Gastroesophageal reflux-related chronic cough (GERC), is one common type of chronic cough. Drug treatment is effective for some GERC patients. But, there is refractory GERC (rGERC). For rGERC, fundoplication may be the only effective method. However, there were very few studies about laparoscopic fundoplication in treating rGERC, and the cure rate of fundoplication in treating rGERC was unknown. So there is a question, what is the cure rate of fundoplication in treating rGERC? To solve this question, we performed this meta-analysis. The PRISMA strategy and Cochrane collaboration method were used for this study. Our study was registered with PROSPERO (ID: CRD42021251072). We searched PubMed, Medline, Web of Science, and the Cochrane databases from 1990 to December 2022. The meta-analysis was performed with Review Manager 5.4 and Stata 14. After selection and exclusion, 8 articles out of 672 were included. The meta-analysis showed the cure rate of laparoscopic fundoplication in treating rGERC was 62% (95% confidence interval: 53-71%), with no deaths in 503 patients. There was no significant heterogeneity or bias in the meta-analysis. In terms of safety, laparoscopic fundoplication is quite reliable offered by skilled surgeons. In terms of cure rate, laparoscopic fundoplication could completely heal two-thirds of rGERC patients; however, there are still some patients who can not be completely cured by fundoplication.


FcgammaRIIa polymorphism and clinical response to rituximab in non-Hodgkin lymphoma patients.
Rituximab is a chimeric monoclonal antibody that specifically targets the CD20 surface marker expressed in neoplastic B-lymphoid cells. Combined with chemotherapy or alone, in maintenance/consolidation, it is used for the treatment of non-Hodgkin lymphoma (NHL). The role of a polymorphism in a specific Fc gamma receptor gene, FcgammaRIIa, in the clinical outcome of patients with NHL was investigated in this study. We characterized DNA samples from 64 non-Hodgkin lymphoma patients treated with rituximab using a polymerase chain reaction-restriction fragment length polymorphism method. The FcgammaRIIa HH genotype was significantly correlated with complete response to rituximab compared to the R allele (P=0.028). In terms of overall or event-free survival, no difference was found according to FcgammaRIIa alleles. We hypothesize that the HH genotype increases the affinity of the FcgammaRIIa receptor, not only for naturally occurring IgG2, but also to ameliorate connection with chimeric IgG1 rituximab, contributing to a genetic individual profile of great interest in clinical onco-hematology.


Sesquiterpenes from Echinacea purpurea and their anti-inflammatory activities.
Six unreported sesquiterpenes, purpureaterpenes A‒F, together with six known sesquiterpenes, were isolated and identified from the aerial part of Echinacea purpurea. Their chemical structures were established by detailed analyses of 1D and 2D NMR data. The relative configurations were assigned on the basis of their NOESY spectra and the calculated 13C NMR spectra. Their absolute configurations were determined by X-ray crystallographic analyses and optical rotation calculations. All the isolated compounds were tested for their anti-inflammatory effects against NO production in LPS-induced RAW246.7 macrophages. Among these compounds, purpureaterpene E was the most active (IC50 value 13.27 μM), even better than the positive control, minocycline (IC50 value 34.81 μM). Further investigation found that purpureaterpene E might exert anti-inflammatory property via the NF-κB signaling pathway.


Establishment of a patient-derived orthotopic osteosarcoma mouse model.
Osteosarcoma (OS) is the most common pediatric primary malignant bone tumor. As the prognosis for patients following standard treatment did not improve for almost three decades, functional preclinical models that closely reflect important clinical cancer characteristics are urgently needed to develop and evaluate new treatment strategies. The objective of this study was to establish an orthotopic xenotransplanted mouse model using patient-derived tumor tissue. Fresh tumor tissue from an adolescent female patient with osteosarcoma after relapse was surgically xenografted into the right tibia of 6 immunodeficient BALB/c Nu/Nu mice as well as cultured into medium. Tumor growth was serially assessed by palpation and with magnetic resonance imaging (MRI). In parallel, a primary cell line of the same tumor was established. Histology and high-resolution array-based comparative genomic hybridization (aCGH) were used to investigate both phenotypic and genotypic characteristics of different passages of human xenografts and the cell line compared to the tissue of origin. A primary OS cell line and a primary patient-derived orthotopic xenotranplanted mouse model were established. MRI analyses and histopathology demonstrated an identical architecture in the primary tumor and in the xenografts. Array-CGH analyses of the cell line and all xenografts showed highly comparable patterns of genomic progression. So far, three further primary patient-derived orthotopic xenotranplanted mouse models could be established. We report the first orthotopic OS mouse model generated by transplantation of tumor fragments directly harvested from the patient. This model represents the morphologic and genomic identity of the primary tumor and provides a preclinical platform to evaluate new treatment strategies in OS.


Clastogenic activity of sodium fluoride in great ape cells.
Conflicting evidence has been reported concerning the mutagenicity of sodium fluoride (NaF), especially clastogenicity at concentrations of more than 1 mM. NaF is known to induce chromosome aberrations at these concentrations in human cells, but not in most rodent cells. We considered that such species-specific difference in chromosomal sensitivity would be derived from the phylogenetic distance between rodents and man. To clarify the role of interspecies differences, we investigated the chromosomal sensitivity to NaF in cell lines from various primates, which diverged into many species, including rodent-like prosimians and human-like great apes. The results showed that the clastogenicity of NaF was limited to human and great ape cells.


Piezos thrive under pressure: mechanically activated ion channels in health and disease.
Cellular mechanotransduction, the process of translating mechanical forces into biological signals, is crucial for a wide range of physiological processes. A role for ion channels in sensing mechanical forces has been proposed for decades, but their identity in mammals remained largely elusive until the discovery of Piezos. Recent research on Piezos has underscored their importance in somatosensation (touch perception, proprioception and pulmonary respiration), red blood cell volume regulation, vascular physiology and various human genetic disorders.


[Monostotic fibrous dysplasia of the temporal bone: description of a case and review of the literature].
Only a few cases of fibrous dysplasia of the temporal bone (monostotic form) have been described in the literature. The recent observation of a 15-year-old child presenting this pathology led the authors to review the literature available and to analyze the most common aspects of this disease. The clinical and radiological aspects, the differential diagnosis, histopathological features and therapeutical approaches are discussed.


Giant bladder diverticulum in Ehlers-Danlos syndrome type I causing outflow obstruction.
We describe a 16-year-old patient with Ehlers-Danlos syndrome (EDS) type I and recurrent urinary retention caused by giant bladder diverticulum and review the literature on this association.


Identification of AFB1-interacting proteins and interactions between RPSA and AFB1.
A method using immobilized affinity chromatography (IAC) was developed to screen for aflatoxin B1 (AFB1)-binding proteins. AFB1 and bovine serum albumin (BSA) coupled protein (BSA-AFB1) was prepared using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride. The resulting coupled compound was immobilized onto PVDF transfer membranes, which were then incubated with total protein from mouse liver. AFB1-binding proteins were eluted, after non-specific washing, by specific elution, and the eluted proteins were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Two candidate AFB1-binding proteins were identified by liquid chromatography-tandem mass spectrometry as the 40S ribosomal protein SA (RPSA) and a putative uncharacterized protein. RPSA and AFB1 interactions were further analyzed by ELISA in vitro and laser confocal immunofluorescence analysis in vivo. The results from ELISA and immunofluorescence showed that RPSA efficiently bound AFB1 in vitro and in vivo. This study's conclusion laid the foundation for further exploration of the role of AFB1-binding proteins in AFB1 toxicology towards hepatocytes and the entry pathway of AFB1 into hepatocytes.


Hypothesis: smoking decreases breast feeding duration by suppressing prolactin secretion.
A number of studies, including new data summarized here, conclude that breast feeding duration is lower in smoking mothers. Although some have suggested that this merely reflects poor health motivation in those prone to smoke, several lines of evidence support the view that chronic smoking does indeed compromise breast feeding by suppressing prolactin secretion and thereby lowering breast milk volume. Moreover, a recent clinical trial shows that an effective smoking cessation program can boost breast feeding duration in smokers. An analysis of pertinent rodents studies suggests that chronic nicotine administration boosts dopaminergic activity in the tuberoinfundibular tract which functions to inhibit prolactin release; this increase in dopaminergic activity, in turn, may reflect a nicotine-mediated suppression of hypothalamic opioid activity.


The role of mallard ducks (Anas platyrhynchos) in distribution and germination of seeds of the submerged hydrophyteNajas marina L.
The effect of passage ofNajas marina L. seeds through the digestive system of the common mallard duck (Anas platyrhynchos) on their germinability was investigated. Most of the seeds (∼70%), which were consumed by the birds were digested. However, germination of the remaining seeds was remarkably improved. Germination of seeds whose seed coats were mechanically cracked was also higher than that of the controls and equalled the germination percentage of the mallard-treated seeds. Seeds ofNajas are retained in the diegestive tracts of mallards for over 10 hours. Thus, as mallards are strong flyers, the seeds ofNajas may be distributed over long distances.


In vitro hyperdiploidy in dermal fibroblasts: evidence for genetic predisposition in aerodigestive tract cancer.
A numerical alteration in chromosome complement in human dermal fibroblast cultures, hyperdiploidy with a normal occurrence of tetraploidy (IVH) has been reported (Danes 1984) to be associated with some heritable single tumors including squamous carcinoma of the nasopharynx (Danes 1986). The incidence of IVH was compared in cultures derived from 65 patients with squamous carcinoma in different regions of the aerodigestive tract (ADT) and 32 clinically normal subjects without a family cancer history by 2 different assays, metaphase assay (MA) and flow cytometry (FCM). By MA, none of the 32 normals showed IVH. Of the 65 ADT patients studied, 35 had IVH and 30 did not. By FCM, there were significant differences in the FCM DNA index (p values less than 0.001) of IVH- (all normals and 30 ADT patients) and IVH+ ADT patients. The per cent of cells with a DI of 2 and greater than 1 could be used to distinguish all IVH- from the IVH+ subjects and were thus considered to be the parameters of choice in assaying IVH by FCM. None of the subjects studied showed increased in vitro tetraploidy (IVT) which has been associated with some heritable colon cancer syndromes. Irrespective of family cancer history, approximately half (35/65) of the ADT patients had IVH which has been shown to be associated with the in vivo expression of certain heritable tumors. The average age of squamous carcinoma diagnosis was earlier (mean 50 yrs) for the IVH+ group than for the IVH- ADT group (mean 72 yrs).


Combined use of Doppler and conventional ultrasound for the diagnosis of vascular and other lesions in the head and neck.
Twenty-three patients with swellings of the head and neck were prospectively investigated by Doppler ultrasound and ultrasound imaging to determine the type and vascularity of the lesions and thereby aid pre-operative diagnosis. Four vascular lesions were correctly identified while vascularity was not found in patients with lipoma, cysts, abscess, or muscular hypertrophy. Increased vascularity was found in or near some tumours and lymphangiomas, but by careful comparison of findings these lesions were not confused with true vascular lesions. The value of the investigations was demonstrated by a change in the treatment in 6 of the cases in this series.


Saliency computation via whitened frequency band selection.
Many saliency computational models have been proposed to simulate bottom-up visual attention mechanism of human visual system. However, most of them only deal with certain kinds of images or aim at specific applications. In fact, human beings have the ability to correctly select attentive focuses of objects with arbitrary sizes within any scenes. This paper proposes a new bottom-up computational model from the perspective of frequency domain based on the biological discovery of non-Classical Receptive Field (nCRF) in the retina. A saliency map can be obtained according to the idea of Extended Classical Receptive Field. The model is composed of three major steps: firstly decompose the input image into several feature maps representing different frequency bands that cover the whole frequency domain by utilizing Gabor wavelet. Secondly, whiten the feature maps to highlight the embedded saliency information. Thirdly, select some optimal maps, simulating the response of receptive field especially nCRF, to generate the saliency map. Experimental results show that the proposed algorithm is able to work with stable effect and outstanding performance in a variety of situations as human beings do and is adaptive to both psychological patterns and natural images. Beyond that, biological plausibility of nCRF and Gabor wavelet transform make this approach reliable.


Periprosthetic aseptic osteolysis in total ankle replacement: cause and management.
Osteolysis is the loss of bone secondary to a pathologic process and remains the most common cause of failure of total ankle replacement. Friction at the bearing surface results in the generation of abraded wear debris of polyethylene. These activate a biologic cascade that may result in significant bone loss and subsequent loss of fixation of the prosthesis. Revision surgery must address this loss of bone and may be achieved through either bone grafting or use of appropriate revision prosthesis components.


Partitioning of perfluorooctanesulfonate and perfluorohexanesulfonate in the aquatic environment after an accidental release of aqueous film forming foam at Schiphol Amsterdam Airport.
In summer 2008, an accidental release of aqueous film forming foam (AFFF) took place at Schiphol Amsterdam Airport (The Netherlands). After the release, water, fish, and sediment samples were collected and analyzed for perfluoroalkyl sulfonates (PFSAs). In situ perfluorooctane sulfonate (PFOS) sediment-water distribution factor (KD ) values, bioaccumulation factor (BAF) values, and biota-sediment accumulation factor (BSAF) values showed a remarkable agreement among reference and impacted sites, 10 wk after the incident as well as after 3 yr.


The Parental Stress Scale revisited: Rasch-based construct validity for Danish parents of children 2-18 years old with and without behavioral problems.
Experiencing parental stress is common among parents of children of all ages and is elevated in families characterized by stressors such as poverty, mental health problems, and developmental problems. The Parental Stress Scale (PSS) is a short measure for the assessment of perceived stress resulting from being a parent. This study examines the construct validity and psychometric properties of the Danish PSS using Rasch and graphical loglinear Rasch models in a sample of parents of 2-18-year-old children with and without known behavior problems. We emphasized analyses of differential item functioning, to ascertain whether the scale yields unbiased scores for subgroups of parents. The 18-item PSS did not fit the Rasch model or a graphical loglinear Rasch model. After dichotomizing item responses and eliminating items 2 and 11, we found the PSS to consist of two distinct subscales measuring parental stress and lack of parental satisfaction. For the total sample, the Parental Stress subscale fit a very complex graphical loglinear Rasch model with differential item functioning relative to parental education and whether children had behavior problems or not. The Lack of Parental Satisfaction subscale fit a simple graphical loglinear Rasch model with differential item functioning only relative to subsample. When dividing into subsamples of parents of children with and without behavior problems, the Parental Stress subscale fit a simple graphical loglinear Rasch model, though still with differential item functioning, while the Lack of Parental Satisfaction subscale fit the Rasch model in each subsample of parents. Both subscales performed best for parents of children with behavior problems. The PSS should be used in a 16-item version and scored as two subscales. The PSS appears better suited for use among parents of children with behavior problems than within a sample without any known difficulties.


[Effect of prostaglandin F2alpha on several morphofunctional characteristics of mouse embryos during the pre-implantation period of development].
Prostaglandin F2alpha in vivo and in vitro effects were studied in mouse embryos at different developmental stages. Inhibiting effect of this factor on cell reproduction (cleavage) was demonstrated, and in vivo experiments the process of the embryo release from the zona pellucida was also investigated. The studies were carried out in a large statistically significant material with an adequate mathematical processing of the data obtained. The critical point of the greatest sensitivity in the embryo to prostaglandin F2alpha effect was determined--the morula stage (16 cells).


Structure and membrane remodeling activity of ESCRT-III helical polymers.
The endosomal sorting complexes required for transport (ESCRT) proteins mediate fundamental membrane remodeling events that require stabilizing negative membrane curvature. These include endosomal intralumenal vesicle formation, HIV budding, nuclear envelope closure, and cytokinetic abscission. ESCRT-III subunits perform key roles in these processes by changing conformation and polymerizing into membrane-remodeling filaments. Here, we report the 4 angstrom resolution cryogenic electron microscopy reconstruction of a one-start, double-stranded helical copolymer composed of two different human ESCRT-III subunits, charged multivesicular body protein 1B (CHMP1B) and increased sodium tolerance 1 (IST1). The inner strand comprises "open" CHMP1B subunits that interlock in an elaborate domain-swapped architecture and is encircled by an outer strand of "closed" IST1 subunits. Unlike other ESCRT-III proteins, CHMP1B and IST1 polymers form external coats on positively curved membranes in vitro and in vivo. Our analysis suggests how common ESCRT-III filament architectures could stabilize different degrees and directions of membrane curvature.


Effect of nutrition and environmental factors on the endoparasitic fungus Esteya vermicola, a biocontrol agent against pine wilt disease.
The nematophagous fungus Esteya vermicola has tremendous potential for biological control. This species exhibits strong infectious activity against pinewood nematodes, whereas the study on the effect of nutrition and environmental factors is still of paucity. Carbon (C), nitrogen (N), pH value, temperature, and water activity have great impact on the fungal growth, sporulation, and germination. In nutrition study, the greatest number of conidia (2.36 × 10(9) per colony) was obtained at the C:N ratio of 100:1 with a carbon concentration 32 g l(-1). In addition, the germination rate and radial growth of E. vermicola were used to evaluate the effects of environmental conditions and they were optimized as following: pH 5.5, 26 °C and water activity of 0.98. Our results also confirmed that variation of environmental factors has a detrimental influence on the efficacy of active conidia and growth of fungus. Moreover, under above optimal condition, the biocontrol efficacy was significantly improved in regard to the increase of adhesive and mortality rate, which highlight the study on the application of E. vermicola as pine wilt disease biocontrol agent.


A membrane-bound form of protein disulfide isomerase (PDI) and the hepatic uptake of organic anions.
Protein disulfide isomerase (PDI) was considered to be involved in the hepatic uptake of certain organic anions because the protein is photoaffinity labeled by photolabile derivatives of the bile acid taurocholate. Several lines of evidences including photoaffinity labeling experiments indicated a close relationship between the uptake of bile acids and the organic anion bumetanide. The possible involvement of PDI in hepatic transport processes of these organic anions was tested with polyclonal antibodies raised against a PDI-beta-galactosidase fusion protein. Western blot analysis and immunofluorescence of intact hepatocytes showed that protein disulfide isomerase is located in sinusoidal rat liver plasma membranes. This protein is immunologically identical with microsomal PDI prepared from bovine liver. The plasma membrane form of PDI is, however, not labeled by photoactivated bumetanide as revealed by two-dimensional gel electrophoresis. These results indicate that, although a membrane-bound form of the PDI is present in the sinusoidal plasma membrane of rat hepatocytes, this protein is not involved in the hepatocellular uptake of the organic anion bumetanide.


Detection of estrogen receptor messenger ribonucleic acid in human oocytes and cumulus-oocyte complexes using reverse transcriptase-polymerase chain reaction.
To examine the expression of estrogen receptor (ER) messenger ribonucleic acid in the human ovary. To detect ER gene transcripts in human oocytes; and to study the possible autocrine effect of estrogen (E) in granulosa/cumulus cells. Human ovaries from benign gynecological surgeries as well as the oocytes, cumulus-oocyte complexes, and granulosa/cumulus cells from the in vitro fertilization program were used to detect ER gene transcripts using the highly sensitive reverse transcriptase-polymerase chain reaction technique. Molecular biology laboratory. The ER gene is expressed in human ovary. Estrogen receptor transcripts were detected in human cumulus-oocyte complexes and oocytes but not in granulosa/cumulus cells. These results suggest a lack of receptor-mediated autocrine effect of E during folliculogenesis and that E, secreted by granulosa/cumulus cells, may exert a paracrine effect to influence oocyte maturation and fertilization competence directly.


Hospital-acquired Clostridioides difficile infections in Alberta: The validity of laboratory-identified event surveillance versus clinical infection surveillance.
Clostridioides difficile infection (CDI) is one of the most common health care-associated infections. This study assessed the validity of a laboratory-based surveillance method as compared with a traditional, clinical surveillance method to identify hospital-acquired CDIs. Retrospective analysis of positive C difficile laboratory records between April 2015 and March 2017 were compared with a clinical dataset of positive inpatient C difficile cases for all acute care facilities in Alberta, Canada. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated using STATA/IC 13.0. The laboratory surveillance method had a sensitivity of 96.6% (95% confidence interval [CI], 95.7%-97.3%) and a specificity of 65.7% (95% CI, 63.6%-67.8%); positive predictive value and negative predictive value were 74.3% (95% CI, 73.2%-75.5%) and 94.9% (95% CI, 93.7%-95.9%), respectively. To date, the breadth of research on alternate CDI surveillance systems has focused on the use of International Statistical Classification of Diseases and Related Health Problems 9th and 10th Revision coding mechanisms. Our results expand on the published literature, as a laboratory approach may provide more timely information, with a smaller amount of misclassified cases. Using a laboratory surveillance method to capture hospital-acquired CDI cases is highly sensitive but not overly specific. Changes to improve the specificity of this method are provided.


Sipa1l3/SPAR3 is targeted to postsynaptic specializations and interacts with the Fezzin ProSAPiP1/Lzts3.
Rap GTPase-activating proteins (RapGAPs) are essential for synaptic function as they tightly regulate synaptic Rap signaling. Among the most abundant synaptic RapGAPs in brain are the Spine-associated RapGAPs (SPARs) Sipa1l1/SPAR and Sipa1l2/SPAR2, whereas nothing has been reported on Sipa1l3/SPAR3. In this study, we show that Sipa1l3/SPAR3 is conserved across species, has a distinct expression pattern in the developing rat brain and is localized at excitatory postsynapses. We further demonstrate that the Sipa1l3/SPAR3 C-terminus is required for postsynaptic targeting and represents an interaction module for Fezzins such as ProSAPiP1/Lzts3, a binding partner of the postsynaptic scaffold protein Shank3. Taken together, our data imply that Sipa1l3/SPAR3 is a hitherto unknown synaptic RapGAP, which is targeted to postsynaptic specializations and interacts with Fezzins. Spine-associated RapGAPs (SPARs) are essential modulators of synaptic signaling. Our study is the first to characterize the SPAR family member Sipa1l3/SPAR3 in neuronal tissue. We show that Sipa1l3/SPAR3 is conserved across species, has a distinct expression pattern in brain and is localized to excitatory postsynapses via its C-terminus, which represents an interaction module for other postsynaptic proteins including the Fezzin ProSAPiP1/Lzts3.


Repression of enzymes of the pentose phosphate pathway by glucose in fission yeast.
We examine here the effect of carbon sources on the synthesis of the shunt pathway enzymes in the fission yeast Schizosaccharomyces pombe growing on a mixture of ethanol and glycerol. Delta-gluconolactone induces practically every one of these enzymes. Glucose in contrast tends to attenuate the synthesis of the majority of them. RNA analysis confirms that their induction and repression reflect changes in the levels of their transcripts.


Identification of an alkaline lipase capable of better enrichment of EPA than DHA due to fatty acids selectivity and regioselectivity.
The whole genome of Streptomyces violascens (=ATCC 27968) was sequenced and the cloning and expression of OUC-Lipase 6 were conducted in Bacillus subtilis WB800. The recombinant enzyme belongs to the lipolytic enzymes family V. OUC-Lipase 6 showed optimal activity at 30 °C and pH 9.0, and retained 90.2% of its activity in an alkaline buffer (pH 8.0, 30 °C and 96 h). OUC-Lipase 6 showed good stability under medium temperature conditions (residual activity of 68.8%, pH 8.0, 45 °C and 96 h). OUC-Lipase 6 could selectively hydrolyze fatty acids on the glyceride backbone, thus improving the contents of DHA and EPA in codfish oil. OUC-Lipase 6 also showed regioselectivity, resulting in a better enrichment efficiency for EPA than DHA. After hydrolyzing for 36 h via OUC-Lipase 6, the contents of EPA and DHA were improved to 3.24-fold and 1.98-fold, respectively.


Calculation of surface enthalpy of solids from an ab initio electronegativity based model: case of ice.
A very simple route to calculation of the surface energy of solids is proposed because this value is very difficult to determine experimentally. The first step is the calculation of the attractive part of the electrostatic energy of crystals. The partial charges used in this calculation are obtained by using electronegativity equalization and scales of electronegativity and hardness deduced from physical characteristics of the atom. The lattice energies of the infinite crystal and of semi-infinite layers are then compared. The difference is related to the energy of cohesion and then to the surface energy. Very good results are obtained with ice, if one compares with the surface energy of liquid water, which is generally considered a good approximation of the surface energy of ice.


18 F-FDG PET and PET/CT as a diagnostic method for Ewing sarcoma: A systematic review and meta-analysis.
The aim of this study was to evaluate the diagnostic accuracy of 18 -fluorodeoxyglucose-positron emission tomography (18 F-FDG PET) and PET/computed tomography (PET/CT) in imaging primary and metastatic lesions in Ewing sarcoma (ES). PubMed, Cochrane, Scopus, and Web of Science were searched for relevant studies. Data concerning 18 F-FDG PET/CT diagnostic accuracy were extracted and then analyzed using Open Meta-analyst software. Reported diagnostic accuracy outcomes included sensitivity, specificity, negative likelihood ratio (NLR), positive likelihood ratio (PLR), and diagnostic odds ratio. Thirty-one studies with a total of 735 patients were included in this meta-analysis. The sensitivity and specificity of 18 F-FDG PET/CT were: 92.6% and 74.1% for total ES lesions, 96.7% and 68.3% for ES primary lesions, 76.1% and 92.4% for lung metastasis, 83.9% and 93.2% for bone metastasis, and 89.9% and 92.6% for ES recurrence, respectively. 18 F-FDG PET/CT is sensitive and accurate in diagnosing, staging, and detecting the recurrence of ES compared with non-PET imaging. It has high accuracy for diagnosing recurrence of ES in bone metastases; however, CT remains a superior diagnostic method for detecting lung metastasis.


Outdoor mm-wave 5G/6G transmission with adaptive analog beamforming and IFoF fronthaul.
Adaptive analog beamforming is a key technology to enable spatial control of millimeter-wave wireless signals radiated from phased array antennas (PAAs) which is essential to maximize the capacity of future mobile networks and to ensure efficient usage of scarce spectrum. Intermediate frequency-over-fiber (IFoF), on the other hand, is a promising technology for the millimeter-wave (mm-wave) mobile fronthaul due to its low complexity, high optical spectral efficiency, and low latency. The combination of IFoF and PAA is key to implement mm-wave mobile communications in a scalable, centralized, efficient, and reliable manner. This work presents, for the first time to the best of the authors' knowledge, an extensive outdoor measurement campaign where an experimental IFoF mm-wave wireless setup is evaluated by using PAAs with adaptive beamforming on the transmitter and receiver sides. The configuration of the experimental setup is according to 5G standards, transmitting signals wirelessly at 27 GHz central frequency in the n258 band. The employed PAAs are composed of 8-by-8 patch antenna arrays, allowing beam steering in the azimuth and elevation angles. Furthermore, different end-user locations, antenna configurations, and wireless scenarios are tested in the outdoor experiment, showing excellent EVM performance and achieving 64-QAM transmission over up to 165.5 m at up to 1.88 Gbit/s. The experimental results enable optimization of the experimental setup for different scenarios and prove the system's reliability in different wireless conditions. In addition, the results of this work prove the viability and potential of IFoF combined with PAA to be part of the future 5G/6G structure.