SPECT-CT in routine clinical practice: increase in patient radiation dose compared with SPECT alone.
To assess the patient radiation dose during routine clinical single-photon emission computed tomography-computed tomography (SPECT-CT) and measure the increase as compared with SPECT alone. Data pertaining to 357 consecutive patients who had undergone radioisotope imaging along with SPECT-CT of a selected volume were retrospectively evaluated. Dose of the injected radiopharmaceutical (MBq) was noted, and the effective dose (mSv) was calculated as per International Commission on Radiological Protection (ICRP) guidelines. The volume-weighted computed tomography dose index (CTDIvol) and dose length product of the CT were also assessed using standard phantoms. The effective dose (mSv) due to CT was calculated as the product of dose length product and a conversion factor depending on the region of investigation, using ICRP guidelines. The dose due to CT was compared among different investigations. The increase in effective dose was calculated as CT dose expressed as a percentage of radiopharmaceutical dose. The per-patient CT effective dose for different studies varied between 0.06 and 11.9 mSv. The mean CT effective dose was lowest for 99mTc-ethylene cysteine dimer brain SPECT-CT (0.9 ± 0.7) and highest for 99mTc-methylene diphosphonate bone SPECT-CT (4.2 ± 2.8). The increase in radiation dose (SPECT-CT vs. SPECT) varied widely (2.3-666.4% for 99mTc-tracers and 0.02-96.2% for 131I-tracers). However, the effective dose of CT in SPECT-CT was less than the values reported for conventional CT examinations of the same regions. Addition of CT to nuclear medicine imaging in the form of SPECT-CT increases the radiation dose to the patient, with the effective dose due to CT exceeding the effective dose of RP in many instances. Hence, appropriate utilization and optimization of the protocols of SPECT-CT is needed to maximize benefit to patients.


Changes in tight junctional resistance of the cervical epithelium are associated with modulation of content and phosphorylation of occludin 65-kilodalton and 50-kilodalton forms.
Treatment of human cervical epithelial CaSki cells with ATP or with the diacylglyceride sn-1,2-dioctanoyl diglyceride (diC8) induced a staurosporine-sensitive transient increase, followed by a late decrease, in tight-junctional resistance (R(TJ)). CaSki cells express two immunoreactive forms of occludin, 65 and 50 kDa. Treatments with ATP and diC8 decreased the density of the 65-kDa form and increased the density of the 50-kDa form. ATP also decreased threonine phosphorylation of the 65-kDa form and increased threonine phosphorylation of the 50-kDa form and tyrosine phosphorylation of the 65- and 50-kDa forms. Staurosporine decreased acutely threonine and tyrosine phosphorylation of the two isoforms and in cells pretreated with staurosporine ATP increased acutely the density of the 65-kDa form and threonine phosphorylation of the 65-kDa form. Treatment with N-acetyl-leucinyl-leucinyl-norleucinal increased the densities of the 65- and 50-kDa forms. Pretreatment with N-acetyl-leucinyl-leucinyl-norleucinal attenuated the late decreases in R(TJ) induced by ATP and diC8 and the decrease in the 65-kDa and increase in the 50-kDa forms induced by ATP. Correlation analyses showed that high levels of R(TJ) correlated with the 65-kDa form, whereas low levels of R(TJ) correlated negatively with the 65-kDa form and positively with the 50-kDa form. The results suggest that in CaSki cells 1) occludin determines gating of the tight junctions, 2) changes in occludin phosphorylation status and composition regulate the R(TJ), 3) protein kinase-C-mediated, threonine dephosphorylation of the 65-kDa occludin form increases the resistance of assembled tight junctions, 4) the early stage of tight junction disassembly involves calpain-mediated breakdown of occludin 65-kDa form to the 50-kDa form, and 5) increased levels of the 50-kDa form interfere with occludin gating of the tight junctions.


Dermal nerve sheath myxoma. A light and electron microscopic, histochemical and immunohistochemical study.
Two cases of dermal nerve sheath myxoma have been examined by light and electron microscopy, and by immunohistochemical and histochemical methods. The nomenclature of this tumor has been debated, and the histogenesis unsettled. Light microscopically, the lobulated myxoid tumors were generally composed of spindle-shaped and stellate tumor cells in an abundant matrix of mucosubstances. Ultrastructural features indicated an origin from the peripheral nerve sheath; among the pertinent findings were a single or duplicated external lamina investing the cells, desmosome-like junctions, cytoplasmic microfilaments and myelin figures, and interdigitating cytoplasmic processes. S-100 protein was demonstrated by means of the immunoperoxidase technique within both tumors, further supporting this origin. The histochemical analysis of the mucosubstance showed the presence of sulphated glucosaminoglycans. The name dermal nerve sheath myxoma, suggested by Harkin and Reed, is recommended.


The role of non-chromosomal histones in the host defense system.
Histone H1 is located at the inter-nucleosome and more correctly at both ends of the double-stranded DNA that protrude from the nucleosome unit. It has long been recognized to be localized only inside the nuclei as a constituent for packaging nucleosome into chromatin. Thus, it could be hardly believed that detatched or solubilized histone H1 plays the role of a host defense molecule. Given the old reports on histone-like basic proteins that show bacteriostatic functions, I herein chose some recent related articles and tried review them. Recent advances in research on the cell death mechanism makes it possible to understand that programmed cell death, (i.e. apoptosis) could serve as a good source of soluble histones. Some forms of them are highly probable to be bacteriostatic.


IMP-6 Carbapenemase-Producing Enterobacteriaceae Bacteremia Successfully Treated with Amikacin-Meropenem in Two Patients.
Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) are becoming increasingly common worldwide. Although CPE infections can be fatal, few reports in the literature have described effective and successful treatments for infectious diseases caused by several types of IMP CPE, and, to our knowledge, no reports have described the successful treatment of IMP-6 CPE infections. We describe two patients who developed bacteremia caused by IMP-6 CPE after surgery for cancer who were successfully treated with amikacin plus high-dose prolonged-infusion meropenem. Both patients were treated over a 2-week period using amikacin 15 mg/kg at various intervals based on therapeutic drug monitoring and meropenem 2000 mg infused over 3 hours every 12 hours. The dosages of amikacin and meropenem were determined based on the creatinine clearance of each patient. Both patients were cured of their bacteremia and did not experience any antibiotic-related adverse effects. Based on the outcomes of these patients, it appears that amikacin plus high-dose prolonged-infusion meropenem may be safe and effective for the treatment of bacteremia caused by IMP-6 CPE.


[Hemosorption in serotherapy (serosorption) in experimental acute diphtheric toxemia with the use of affinity sorbents].
In modeling acute diphtheric toxemia in guinea pigs, the authors propose to perform hemosorption using selective sorbents under continuous introduction of antitoxic immune sera into extracorporeal contour in front of sorption column. Combination of hemosorption with serotherapy in the same time interval may be denoted as serosorption. As specific sorbents, affine preparations imasorb A-700 and Imasorb G-700 were used. They selectively eliminate from the blood flow CIC produced by diphtheric toxin (anatoxin) and antitoxic rabbit and horse antibodies. Changes in the titers of the diphtheric toxin (anatoxin) and CIC in blood evidence for efficiency of selective sorbents were confirmed by immunohistochemical analysis of the preparations' granules after hemoperfusion.


How sensitive may cytochemical methods detect alterations of the glycocalyx?
This review reports on the relationship of light and electron microscopic cytochemical staining and chemo-affinity labelling to the conformational state of the human erythrocyte glycocalyx glycophorin. According to a recent suggestion, primary glycophorin conformation is associated with binding to the lipid bilayer of this glycoprotein's N-terminal segment. Pretreatment of cells prior to fixation may cause this segment of detach from the lipid lamella and to acquire a less orientation. Alterations of the glycocalyx were sensitively demonstrated by topo-optical staining and by the labelling of unmasked binding sites.


Fig extract drying: The relationship between the main operating parameters of a pilot-scale spray dryer and product specifications.
This study aims to optimize extraction and drying conditions of fig syrup. Drying was done in a pilot scale two-fluid nozzle spray dryer. A total of 27 experiments were conducted with varying inlet air temperatures, air flow rates, and also a maltodextrin (MD)- low methoxyl pectin (LMP) ratios. While feed rate, feed temperature, and compressed air flow rate of the atomizer were kept constant. The results of differential scanning calorimetry revealed that high levels of glucose and fructose in the extract resulted in a low glass transition temperature of fig syrup. By an increase in the inlet air temperature, the powder bulk density decreased. However, the MD:LMP ratio and the air flow rate were not significantly effective (p < 0/05) in changing the bulk density. SEM micrographs of spray-dried particles and particle size distribution analysis showed that particles were largely in a range of 5 to 50 μm. The best powders were obtained at an inlet air temperature of 170°C.


Microwave photonic injection locking frequency divider based on a tunable optoelectronic oscillator.
We present a novel broadband divide-by-2 microwave photonic injection locking frequency divider (ILFD) based on a dual-loop optoelectronic oscillator (OEO). In the proposed scheme, a tunable microwave photonic filter is used to replace the traditional electrical filter, which makes sure a large tuning range of the ILFD. The microwave photonic ILFD whose center frequency tracks the tunable frequency of the free-running OEO, links up with every single locking range together. Thus the frequency range is only determined by the tunable OEO. In the experiment, a wide operating frequency range from 4.51 GHz to 34.88 GHz is realized. Furthermore, a divide-by-3 ILFD is experimentally demonstrated with the help of a frequency mixer.


Central release of nitric oxide mediates antinociception induced by aerobic exercise.
Nitric oxide (NO) is a soluble gas that participates in important functions of the central nervous system, such as cognitive function, maintenance of synaptic plasticity for the control of sleep, appetite, body temperature, neurosecretion, and antinociception. Furthermore, during exercise large amounts of NO are released that contribute to maintaining body homeostasis. Besides NO production, physical exercise has been shown to induce antinociception. Thus, the present study aimed to investigate the central involvement of NO in exercise-induced antinociception. In both mechanical and thermal nociceptive tests, central [intrathecal (it) and intracerebroventricular (icv)] pretreatment with inhibitors of the NO/cGMP/KATP pathway (L-NOArg, ODQ, and glybenclamide) prevented the antinociceptive effect induced by aerobic exercise (AE). Furthermore, pretreatment (it, icv) with specific NO synthase inhibitors (L-NIO, aminoguanidine, and L-NPA) also prevented this effect. Supporting the hypothesis of the central involvement of NO in exercise-induced antinociception, nitrite levels in the cerebrospinal fluid increased immediately after AE. Therefore, the present study suggests that, during exercise, the NO released centrally induced antinociception.


Masking the Pathogen: Evolutionary Strategies of Fungi and Their Bacterial Counterparts.
Pathogens reduce immune recognition of their cell surfaces using a variety of inert structural polysaccharides. For example, capsular polysaccharides play critical roles in microbial survival strategies. Capsules are widely distributed among bacterial species, but relatively rare in eukaryotic microorganisms, where they have evolved considerable complexity in structure and regulation and are exemplified by that of the HIV/AIDS-related fungus Cryptococcus neoformans. Endemic fungi that affect normal hosts such as Histoplasma capsulatum and Blastomyces dermatitidis have also evolved protective polysaccharide coverings in the form of immunologically inert α-(1,3)-glucan polysaccharides to protect their more immunogenic β-(1,3)-glucan-containing cell walls. In this review we provide a comparative update on bacterial and fungal capsular structures and immunogenic properties as well as the polysaccharide masking strategies of endemic fungal pathogens.


Expression of keratinocyte growth factor and its receptor in adaptive changes of ileorectal pouch mucosa.
Total proctocolectomy with formation of an ileo-anal pouch is a well-established surgical procedure for patients with ulcerative colitis (UC) or familiar adenomatous polyposis (FAP). The pouch mucosa undergoes adaptive changes, with inflammation of the ileal reservoir being the most common complication. The aetiology is unknown. The keratinocyte growth factor (KGF) has not only been shown to promote intestinal wound healing and re-epithelialization but also to have some immunomodulatory properties. This study was designed to investigate a putative involvement of KGF in observed histomorphological changes in the pouch mucosa. Multiple biopsies were obtained from age-matched and sex-matched patients. Biopsies were stained with H&E and scored for inflammation and morphological changes. mRNA expression levels of KGF and KGF-receptor (KGFR) were determined using competitive RT-PCR, protein expression and phosphorylation was analyzed by Western blotting. KGF and KGFR were localized in tissue samples by immunohistochemistry. Expression of KGF and KGFR was significantly increased in inflamed and adapting mucosa. Patterns of expression did not significantly differ in pouch mucosa from UC or FAP patients. Protein expression correlated with the mRNA results and KGFR was shown to be activated in adapting pouch mucosa. KGF was detected on subepithelial cells, mainly on fibroblasts, whereas expression of KGFR was restricted to epithelial cells. Expression of KGF and KGFR is significantly increased in the pouch mucosa, suggesting an involvement of this growth factor in tissue repair and adaptive changes. Topical application of KGF might alleviate the inflammatory and promote the adaptive process in the ileo-anal pouch mucosa.


Cell subset (CS) parameter to record the identities of individual cells in flow cytometric data.
The Flow Cytometry Standard (FCS) for cytometric data (Dean et al.: Cytometry 11:323-332, 1990) provides for appending an ANALYSIS section to a data file, but it does not explicitly provide for recording the identities of individual cells. We propose an extension to the FCS definition in order to record the identity of each individual cell in list mode data. In order to do so, one first defines the subpopulations of cells to be identified and one than assigns a number to each defined population. For example, in an analysis in which peripheral blood mononuclear cells are labeled with antibodies to CD3, CD4, and CD8, the "negative" lymphocytes that are labeled with none of the antibodies could be identified as population 1, the CD3-CD4-CD8+ lymphocytes as population 2, etc. As the measured values from each cell are analyzed, the number that identifies the population to which that cell belongs is assigned as the value of an additional parameter. Since this procedure merely adds a new parameter, the only necessary extension to the FCS specification is that a particular name is recognized for this parameter. We propose that CS (abbreviation for cell subset) be recognized as the name and that CS be used as the value for the $PnN (parameter name) keyword in the FCS file TEXT. The CS values that are created can be used to aid in data analysis and can be permanently recorded in a conventional FCS file. A data file that is saved with CS values includes an explicit and integral record of the complete analysis, regardless of the complexity of the analysis.(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of Preoperative Severity on Postoperative Improvement Among Patients With Myeloradiculopathy Following Anterior Cervical Discectomy and Fusion.
Retrospective cohort. The aim was to determine how neck pain and disability improve following anterior cervical discectomy and fusion among patients with myeloradiculopathy. Neck pain and disability have traditionally been assessed using the neck disability index (NDI) and visual analog scale (VAS). Few studies have investigated how neck pain/disability improve differently among patients with symptoms of both myelopathy and radiculopathy. Patients were identified through retrospective review of a prospective surgical database from 2013 to 2020. Patient-reported outcome measures (PROMs) collected included VAS neck and arm, NDI, 12-Item Short Form physical composite score (SF-12 PCS), Patient-Reported Outcomes Measurement Information System physical function (PROMIS PF), and Patient Health Questionnaire 9 (PHQ-9). PROMs were collected preoperatively and up to 1-year postoperatively. Patients were categorized by preoperative symptom severity: high VAS arm (>7); high NDI (>55); high VAS arm and NDI; and moderate symptoms. Linear and logistic regression evaluated the impact of preoperative symptom severity on PROM scores and achievement of minimum clinically important difference (MCID), respectively. A total of 187 patients were included, 98 with neither high VAS arm nor NDI (moderate group), 14 with high NDI, 46 with high VAS arm, and 29 with high NDI and VAS arm. Postoperatively, greater symptom severity was a significant predictor of VAS neck (all timepoints; P ≤0.002, all), VAS arm (6 weeks; P =0.007), NDI (6 weeks to 6 months; P <0.001, all), SF-12 PCS (6 months; P =0.004), P ROMIS PF (6 weeks; P =0.007), and PHQ-9 (6 weeks to 6 months; P <0.001, all). Mean postoperative improvement was different among the four severity groups for VAS arm, NDI, and VAS neck (except for 1-year) ( P ≤0.002, all). Overall MCID achievement rates were significantly greater among higher symptom severity groups across VAS arm and NDI ( P ≤0.003, both). PROM improvement and MCID achievement for NDI, VAS neck, and VAS arm differed based on symptom severity.


Efficacy and mechanisms of alpha-solasonine-and alpha-solamargine-induced cytolysis on two strains of Trypanosoma cruzi.
Two genetically diverse strains of Trypanosoma cruzi were tested in vitro for susceptibility to the solanum-derived triglycoside alkaloids solasonine and solamargine. Cytolytic assays were performed on epimastigotes (EMs) and bloodstream form trypomastigotes (BSFs) lifecycle stages by using serial dilutions of each alkaloid. Each alkaloid effectively lysed both lifecycle stages, although solasonine routinely required higher concentrations to induce similar results. EMs demonstrated greater resistance to cytolysis than BSFs at equal concentrations of either alkaloid. No significant resistance could be correlated to parasite strain. The reported synergistic cytolytic effects observed upon compounding solasonine and solamargine together were also tested. We failed to identify any cytolytic synergism in cultures of EMs or BSFs. The role of rhamnose-binding proteins (RBPs) in mediating cytolysis was investigated through competitive inhibition experiments. The addition of exogenous L: -rhamnose to the media failed to reduce parasite attrition independent of the parasite lifecycle stage. Based on these results, we suggest the mechanisms involved in cytolysis of T. cruzi by solasonine and solamargine are largely independent of rhamnose receptor-specific interactions. We propose that attrition likely involves less-specific carbohydrate interactions, which lead to the formation and intercalation of sterol complexes into the parasite plasma membrane.


Public-private collaboration in clinical research during pregnancy, lactation, and childhood: joint position statement of the Early Nutrition Academy and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
This position statement summarises a view of academia regarding standards for clinical research in collaboration with commercial enterprises, focussing on trials in pregnant women, breast-feeding women, and children. It is based on a review of the available literature and an expert workshop cosponsored by the Early Nutrition Academy and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Clinical research collaborations between academic investigators and commercial enterprises are encouraged by universities, public funding agencies, and governmental organisations. One reason is a pressing need to obtain evidence on the effects, safety, and benefits of drugs and other commercial products and services. The credibility and value of results obtained through public-private research collaborations have, however, been questioned because many examples of inappropriate research practice have become known. Clinical research in pregnant and breast-feeding women, and in infants and children, raises sensitive scientific, ethical, and societal questions and requires the application of particularly high standards. Here we provide recommendations for the conduct of public-private research collaborations in these populations. In the interest of all stakeholders, these recommendations should contribute to more reliable, credible, and acceptable results of commercially sponsored trials and to reducing the existing credibility gap.


4-Pyridyl carbonyl compounds as thrips lures: effectiveness for Western flower thrips in y-tube bioassays.
In a search for chemical lures to manage the cosmopolitan crop pest western flower thrips (WFT), Frankliniella occidentalis, a Y-tube olfactometer was used to screen 20 compounds, including 18 4-pyridyl compounds. Comparison of Y-tube results for New Zealand flower thrips (NZFT), Thrips obscuratus, with field trapping data for ethyl nicotinate and ethyl isonicotinate, suggested that the minimum attractive dose (MAD) of an odor compound, where significantly ( p < 0.05) more than 50% of thrips walked up the odor-laden arm, provided a measure for selecting compounds to evaluate for potential lure efficacy in the field. Eighteen synthetic 4-pyridyl compounds were tested on female WFT in a Y-tube olfactometer and four 4-pyridyl carbonyl compounds had MADs lower than the known WFT attractants p-anisaldehyde (MAD 10 (-3) microL) and ethyl nicotinate (10 (-2) microL): methyl isonicotinate (10 (-6) microL), ethyl-2-chloropyridine-4-carboxylate (10 (-6) microL), ethyl isonicotinate (10 (-4) microL) and methyl 4-pyridyl ketone (10 (-5) microL). The suitability of MAD for selecting compounds for further evaluation of practical lure efficacy is discussed. Comparisons of activities within homologous series of esters and ketones showed that attractant activity decreased with chain length. 4-Formyl pyridine was an attractant at a dose of 10 (-5) microL, but was repellent at higher doses (10 (-2)-10 degrees microL).


Associations of Cardiometabolic Multimorbidity With All-Cause and Coronary Heart Disease Mortality Among Black Adults in the Jackson Heart Study.
A combination of diabetes, coronary heart disease (CHD), and stroke has multiplicative all-cause mortality risk compared with any individual morbidity in White populations, but there is a lack of studies in Black populations in the US. To examine the association of cardiometabolic multimorbidity (diabetes, stroke, and CHD) individually and collectively with all-cause and CHD mortality. This cohort study included Black adults in the Jackson Heart Study followed over a median of 15 years. Baseline examinations were performed between 2000 and 2004, with follow-up on all-cause and CHD mortality through May 31, 2018. Participants were categorized into mutually exclusive groups at baseline: (1) free of cardiometabolic morbidity, (2) diabetes, (3) CHD, (4) stroke, (5) diabetes and stroke, (6) CHD and stroke, (7) diabetes and CHD, and (8) diabetes, stroke, and CHD. Data were analyzed from 2019 to 2021. Cardiometabolic disease alone or in combination. The main outcomes were all-cause mortality and CHD mortality. Cox models estimated hazard ratios (HRs) with 95% CIs adjusted for sociodemographic and cardiovascular risk factors. Among 5064 participants (mean [SD] age, 55.4 [12.8] years; 3200 [63%] women) in the Jackson Heart Study, 897 (18%) had diabetes, 192 (4%) had CHD, and 104 (2%) had a history of stroke. Among participants with cardiometabolic morbidities, the crude all-cause mortality rates were lowest for diabetes alone (24.4 deaths per 1000 person-years) and highest for diabetes, CHD, and stroke combined (84.1 deaths per 1000 person-years). For people with only 1 cardiometabolic morbidity, risk for all-cause mortality was highest for people with stroke (HR, 1.74; 95% CI, 1.24-2.42), followed by CHD (HR, 1.59 (95% CI, 1.22-2.08) and diabetes (HR, 1.50; 95% CI, 1.22-1.85), compared with no cardiometabolic morbidities. There were also increased risks of mortality with combinations of diabetes and stroke (HR, 1.71; 95% CI, 1.09-2.68), CHD and stroke (HR, 2.23; 95% CI, 1.35-3.69), and diabetes and CHD (HR, 2.28; 95% CI, 1.65-3.15). The combination of diabetes, stroke, and CHD was associated with the highest all-cause mortality (HR, 3.68; 95% CI, 1.96-6.93). Findings were similar for CHD mortality, but with a larger magnitude of association (eg, diabetes, stroke, and CHD: HR, 13.52; 95% CI, 3.38-54.12). In this cohort study, an increasing number of cardiometabolic multimorbidities was associated with a multiplicative increase in risk of all-cause mortality among Black adults, with a greater magnitude of association for CHD mortality.


[Orthogonal test analysis of compressive strength of porous hydroxylapatite prepared by gel-casting process].
Porous hydroxylapatite (HA) has excellent osseous inductive ability. It has been prepared by gel-casting process, which is feasible and can make complex ceramic material. According to the result of orthogonal test based on the compressive strength, the order and the level of the factors, including monomer HA, initiator MBAM, catalyst APS and water, were dealt with. The effects of drying and sintering technique on the properties of porous hydroxylapatite were also researched. The results showed that the order of every factor in the gel-casting process is as follows, AM-APS, MBAM, H2O. Based on the determined level of each factor, the suitable slurry constituents and drying and sintering technologies were selected, and the porous hydroxylapatite with compressive strength of 6-7 MPa was produced.


Masculinity beliefs predict psychosocial functioning in African American prostate cancer survivors.
Research examining psychosocial functioning in African American prostate cancer survivors has been limited, in spite of documented higher mortality from prostate cancer and worse long-term physical and emotional outcomes from prostate cancer treatment reported by this group of survivors. In addition, the role of masculinity in psychosocial adjustment among prostate cancer survivors is not well understood. In this study, 59 African American prostate cancer survivors completed a questionnaire assessing masculinity beliefs related to self-reliance, emotional control, and dominance, as well as measures of psychosocial functioning (i.e., symptom distress, negative mood, and functional and social well-being). Results of regression analyses indicated that masculinity beliefs predicted negative mood, functional well-being, and social well-being, controlling for age, income, and medical comorbidities. The findings reported here, although preliminary, suggest that masculinity beliefs could be important therapeutic targets for improving the efficacy of cognitive-behavioral interventions for men adjusting to prostate cancer survivorship.


Agrobacterium-Mediated Genetic Transformation of Embryogenic Callus in a Liriodendron Hybrid (L. Chinense × L. Tulipifera).
A highly efficient genetic transformation system of Liriodendron hybrid embryogenic calli through Agrobacterium-mediated genetic transformation was established and optimized. The Agrobacterium tumefaciens strain EHA105, harboring the plasmid pBI121, which contained the ß-glucuronidase (GUS) gene and neomycin phosphotransferase II (npt II) gene under the control of the CaMV35S promoter, was used for transformation. Embryogenic calli were used as the starting explant to study several factors affecting the Agrobacterium-mediated genetic transformation of the Liriodendron hybrid, including the effects of various media, selection by different Geneticin (G418) concentrations, pre-culture period, Agrobacterium optical density, infection duration, co-cultivation period, and delayed selection. Transformed embryogenic calli were obtained through selection on medium containing 90 mg L-1 G418. Plant regeneration was achieved and selected via somatic embryogenesis on medium containing 15 mg L-1 G418. The optimal conditions included a pre-culture time of 2 days, a co-culture time of 3 days, an optimal infection time of 10 min, and a delayed selection time of 7 days. These conditions, combined with an OD600 value of 0.6, remarkably enhanced the transformation rate. The results of GUS chemical tissue staining, polymerase chain reaction (PCR), and southern blot analysis demonstrated that the GUS gene was successfully expressed and integrated into the Liriodendron hybrid genome. A transformation efficiency of 60.7% was achieved for the regenerated callus clumps. Transgenic plantlets were obtained in 5 months, and the PCR analysis showed that 97.5% of plants from the tested G418-resistant lines were PCR positive. The study of the Liriodendron hybrid reported here will facilitate the insertion of functional genes into the Liriodendron hybrid via Agrobacterium-mediated transformation.


[Emergency CAT in stroke-why?].
A stroke is considered to be a neurological emergency, and it is recommended that an immediate CAT scan should be done in all patients. However, its usefulness may be controversial in the early stages. To show the diagnostic usefulness of early CAT scans following strokes. We made a retrospective study of a random sample of the requests for cranial CAT scans in suspected cerebrovascular disease between October 1998 and April 2000. We analyzed the diagnostic and therapeutic variations before and after CAT scans (pre CAT and post CAT moments). We selected 210 cases. Average age: 72 10.4 (57% males). There was no difference in CAT findings (normal or vascular) related to the day it was done. Pre CAT diagnosis: non specific, 39.3%; intracranial haemorrhage (ICH), 17%. Post CAT diagnosis: the commonest was thrombotic infarct (23.7%), followed by non vascular , 20%. Pre CAT treatment: no treatment 47.9%; antiaggregant 30.4%; low molecular weight heparin 7.4%. Post CAT treatment: no treatment 17%, 21.7% of the patients with ICH received antiaggregants or anticoagulants prior to cranial CAT. Hemiplegia was more often associated with a vascular CAT scan whilst isolated dysarthria was with a normal CAT scan. Nineteen patients died and all of these had vascular CAT scans. The patients with vascular CAT scans were more often admitted to hospital. The findings of cranial CAT scans during the acute stage of strokes are unpredictable. Early CAT scans in stroke patients permits improved diagnosis and treatment of patients, avoids serious errors of treatment and affects the outcome.


Guided versus self-guided internet delivered cognitive behavioural therapy for diagnosed anxiety and related disorders: a preliminary meta-analysis.
Guided and self-guided internet-delivered cognitive-behavioural therapy (ICBT) has been demonstrated to be efficacious in the treatment of anxiety and related disorders (ARDs). The aim of the current study was to examine the efficacy of guided and self-guided ICBT for adults diagnosed with ARDs using a meta-analytic synthesis of randomised controlled trials directly comparing the two treatment approaches. Eleven studies (n = 1414) were included. There was a small, but significantly pooled between-group effect size at post-treatment (g = 0.16; 95% CI: 0.03-0.28) favouring guided ICBT. At follow-up, the between-group effect size was small and non-significant (g = 0.13; 95% CI: -0.04-0.30). Gender distribution moderated outcome at post-treatment (higher proportions of females resulted in a smaller between-group effect size). Type of support provided in the guided-treatment arm moderated treatment outcome at follow-up (those receiving synchronous support had a larger between-group effect size). Amount of guidance in the guided-treatment arm moderated effect sizes at post-treatment and follow-up (more guidance leading to larger between-group effect sizes). Automated reminders, disorder type, and treatment length did not moderate outcomes. The results suggest that guided and self-guided ICBT interventions result in similar outcomes, however guided interventions may be marginally more effective in the short term.


Models for wave propagation in two-dimensional random composites: A comparative study.
This paper provides a set of benchmark results on existing theoretical models for wave propagation in two-dimensional composite materials. This comparative study is motivated to investigate the reason why results from an accurate ultrasonic measurement often significantly contradict theoretical predictions. Eight different models are evaluated with their numerically calculated effective wave speeds and coherent attenuations. For computational simplicity, the problem of horizontal shear wave propagation in an elastic matrix containing parallel circular cylinders is considered. Numerical calculations are conducted for different composites in wide ranges of material properties, volume concentration, and frequency. Some of the numerical results are compared with experimental data. Judgments are made based on fundamental theoretical and physical criteria as well as relative agreements in the numerical results, and then possible causes of failures are discussed. The effect of microstructure, potentially as a major source of the observed disagreements between models, is also discussed.


Atypical chest pain syndrome in patients with breast implants.
Eleven patients, aged 36 to 55 years, with silicone breast implants had episodes of severe chest pain similar to heart attacks 6 weeks to 7 years after breast implantation; one patient had a severe attack 1 month after explantation. The chest pain, which was not related to physical exertion, lasted from 15 minutes to 4 days, and descriptions of it varied from a "pressing" type of pain to "stabbing" pain with radiation to the shoulders, left arm, and jaw. The associated symptoms were diaphoresis, nausea, vomiting, dyspnea, and palpitations. All of the patients had a normal electrocardiogram (ECG) with the exception of one, whose ECG showed nonspecific ST changes. Ten had cardiac evaluations, all of which yielded normal results. All had implant removal, and five were found to have at least one ruptured implant. Nine had an implant capsule biopsy; all had chronic inflammatory rinds, and five had free silicone in tissue whether or not the implants were ruptured. All eight who had a pectoralis major muscle biopsy had abnormal results: (neurogenic atrophy [six], fasciitis [three], myositis [one], chronic inflammation [one], free silicone [one], and neuroma [one]). We concluded that silicone breast implants may cause an atypical chest pain syndrome, probably due to local inflammatory reactions and neuroma formation.


Antiproliferative and apoptotic effects of the natural alkaline water (Zamzam) in breast cancer cell line MCF-7.
Zamzam water (ZW) is a natural alkaline water that contains several minerals that may represent a powerful tool for cancer therapy. In this research, in vitro antiproliferative and apoptotic effects of ZW were investigated in the human breast cancer cell line MCF-7. This study was conducted between January 2015 and February 2016. The effects of ZW on the morphology and the cell viability of human breast cancer cell line MCF-7 were determined. The cell death type and cell cycle changes were investigated using flow cytometry. Finally, reactive oxygen species (ROS) were also measured by fluorometric technique. MCF-7 cells treated with either ZW with adjusted pH at 7.2 or unadjusted pH at 8 showed reduced cell viability of cancerous cells. The cell death occurred through the apoptosis pathway under both treatment conditions. The treated MCF-7 cells were arrested in the G2/M phase and decreased in the G1 phase. Only the unadjusted pH ZW sample demonstrated an increase in the production of both cytoplasmic and mitochondrial ROS in MCF-7 cells. All the results in the present study indicated, for the first time, that ZW might have anticancer and apoptotic effects on breast cancer cell line.


Microbiome Tools for Forensic Science.
Microbes are present at every crime scene and have been used as physical evidence for over a century. Advances in DNA sequencing and computational approaches have led to recent breakthroughs in the use of microbiome approaches for forensic science, particularly in the areas of estimating postmortem intervals (PMIs), locating clandestine graves, and obtaining soil and skin trace evidence. Low-cost, high-throughput technologies allow us to accumulate molecular data quickly and to apply sophisticated machine-learning algorithms, building generalizable predictive models that will be useful in the criminal justice system. In particular, integrating microbiome and metabolomic data has excellent potential to advance microbial forensics.


Ru(II)-catalyzed C-H bond activation for the synthesis of substituted isoquinolinium salts from benzaldehydes, amines, and alkynes.
An efficient method for the synthesis of substituted isoquinolinium salts from benzaldehydes, amines, and alkynes via ruthenium-catalyzed C-H bond activation and annulation in one pot is described.


Survival of childhood cancer patients in Italy, 1978-1989. ITACARE Working Group.
In the framework of the ITACARE project, a cooperative investigation conducted on the data from the Italian population-based cancer registries, survival of patients with childhood malignant neoplasms was studied. The study included 1,768 cases diagnosed at age 0-14 plus 29 osteosarcoma cases diagnosed at age 15-19. Cases were collected over the period 1978-1989, or more limited periods for some participating registries. A total of 1,138 cases were from the Childhood Cancer Registry of Piedmont and 659 from the registries operating in the provinces of Varese, Parma, Modena, Forli and Ravenna, Florence, Latina, Ragusa and in the cities of Genova and Torino (the last contributed only for bone neoplasm diagnosed at age 15-19). Overall 5-year survival was 54% for malignancies diagnosed in 1978-1981, 60% for the period 1982-1985; and 69% for the period 1986-1989. The range among registries of 5-year survival for cases diagnosed in 1986-1989 was 55-78%. Most diagnostic categories presented an improved prognosis for the cases diagnosed more recently. For cases diagnosed in 1986-1989, 5-year survival was: 74% for acute lymphatic leukaemia, 40% for acute non-lymphatic leukaemia, 65% for central nervous system neoplasms (76% for astrocytoma, 75% for ependymoma and 85% for medulloblastoma), 66% for osteosarcoma, 55% for Ewing's sarcoma, 87% for Hodgkin's disease, 64% for non-Hodgkin's lymphoma, 74% for rhabdomyosarcoma, 64% for neuroblastoma, 78% for nephroblastoma and 100% for retinoblastoma. Italian survival was similar to that observed in other population-based surveys in the UK and USA.


Assessing in vivo the impact of gene context on transcription through DNA supercoiling.
Gene context can have significant impact on gene expression but is currently not integrated in quantitative models of gene regulation despite known biophysical principles and quantitative in vitro measurements. Conceptually, the simplest gene context consists of a single gene framed by two topological barriers, known as the twin transcriptional-loop model, which illustrates the interplay between transcription and DNA supercoiling. In vivo, DNA supercoiling is additionally modulated by topoisomerases, whose modus operandi remains to be quantified. Here, we bridge the gap between theory and in vivo properties by realizing in Escherichia coli the twin transcriptional-loop model and by measuring how gene expression varies with promoters and distances to the topological barriers. We find that gene expression depends on the distance to the upstream barrier but not to the downstream barrier, with a promoter-dependent intensity. We rationalize these findings with a first-principle biophysical model of DNA transcription. Our results are explained if TopoI and gyrase both act specifically, respectively upstream and downstream of the gene, with antagonistic effects of TopoI, which can repress initiation while facilitating elongation. Altogether, our work sets the foundations for a systematic and quantitative description of the impact of gene context on gene regulation.


Sebacinoids within rhizospheric fungal communities associated with subsistence farming in the Congo Basin: a needle in each haystack.
The unique ecosystem of the Congolese rainforest has only scarcely been explored for its plant-fungal interactions. Here, we characterized the root fungal communities of field-grown maize and of Panicum from adjacent borders in the Congo Basin and assessed parameters that could shape them. The soil properties indicated that comparable poor soil conditions prevailed in fields and borders, illustrating the low input character of local subsistence farming. The rhizosphere fungal communities, dominated by ascomycetous members, were structured by plant species, slash-and-burn practices and soil P, pH and C/N ratio. Examining fungi with potential plant growth-promoting abilities, the glomeromycotan communities appeared to be affected by the same parameters, whereas the inconspicuous symbionts of the order Sebacinales seemed less susceptible to environmental and anthropogenic factors. Notwithstanding the low abundances at which they were detected, sebacinoids occurred in 87% of the field samples, implying that they represent a consistent taxon within indigenous fungal populations across smallholder farm sites. Pending further insight into their ecosystem functionality, these data suggest that Sebacinales are robust root inhabitants that might be relevant for on-farm inoculum development within sustainable soil fertility management in the Sub-Saharan region.


Dental radiography: an overview for the radiologic technologist.
The methods and techniques involved in dental radiography are presented to familiarize the radiologic technologist with this practice. Additionally, the uses and pathologies commonly encountered in dental radiography are discussed. Although dental radiography is seldom performed by many radiographers, the techniques and methods used may be of interest and use to the radiographer.


Acoustic correlates of Burmese voiced and voiceless sonorants.
Voiceless sonorant consonants are typologically rare segments, appearing in only a few of the world's languages, including Burmese. In this study, Burmese sonorants and their adjacent vowels are investigated in an attempt to (1) determine what acoustic correlates distinguish voiced and voiceless sonorants and (2) determine whether there are multiple realizations of voiceless sonorants and, if so, establish what acoustic correlates distinguish them. In order to pursue these questions, a production study was carried out and target words were analyzed, demonstrating that Burmese voiceless sonorants have a spread glottis period resulting in turbulent airflow 78 % of the time. Findings from linear mixed-effects models showed that voiced and voiceless sonorants are significantly different in terms of duration of the sonorant, F0 of the sonorant, and strength of excitation measured over the following vowel. A linear discriminant analysis was able to predict voicing category with 86.7 % accuracy, with the duration of the spread glottis period being the best indicator of voicelessness, followed by the cues that were significant in the linear mixed-effects models. In cases when the spread glottis period is absent from voiceless sonorants, the sonorant only has correlates that are associated with voicelessness (such as F0 and strength of excitation) but not correlates that are associated with the spread glottis gesture (such as duration and harmonics-to-noise ratio). These results have implications both for our understanding of the acoustics of Burmese sonorants and for our understanding of voiceless sonorants more generally.


A review of toxoplasmosis in wild birds.
Toxoplasma gondii affects most species of warm-blooded animals, including birds. There is considerable confusion regarding the identity of T. gondii-like parasites and the diagnosis of toxoplasmosis in wild birds. In this review, T. gondii-like infections in different species of wild birds are reviewed with particular reference to prevalences, clinical signs, pathology, diagnosis, and treatment. Although subclinical T. gondii infections are prevalent in many avian species, toxoplasmosis can be clinically severe in pigeons and canaries. Blindness associated with T. gondii in canaries is reviewed in detail.


Equilibrium dynamics of European pre-industrial populations: the evidence of carrying capacity in human agricultural societies.
Human populations tend to grow steadily, because of the ability of people to make innovations, and thus overcome and extend the limits imposed by natural resources. It is therefore questionable whether traditional concepts of population ecology, including environmental carrying capacity, can be applied to human societies. The existence of carrying capacity cannot be simply inferred from population time-series, but it can be indicated by the tendency of populations to return to a previous state after a disturbance. So far only indirect evidence at a coarse-grained scale has indicated the historical existence of human carrying capacity. We analysed unique historical population data on 88 settlements before and after the Thirty Years War (1618-1648), one the longest and most destructive conflicts in European history, which reduced the population of Central Europe by 30-50%. The recovery rate of individual settlements after the war was positively correlated with the extent of the disturbance, so that the population size of the settlements after a period of regeneration was similar to the pre-war situation, indicating an equilibrium population size (i.e. carrying capacity). The carrying capacity of individual settlements was positively determined mostly by the fertility of the soil and the area of the cadastre, and negatively by the number of other settlements in the surroundings. Pre-industrial human population sizes were thus probably controlled by negative density dependence mediated by soil fertility, which could not increase due to limited agricultural technologies.


Emotions' impact on viewing behavior under natural conditions.
Human overt attention under natural conditions is guided by stimulus features as well as by higher cognitive components, such as task and emotional context. In contrast to the considerable progress regarding the former, insight into the interaction of emotions and attention is limited. Here we investigate the influence of the current emotional context on viewing behavior under natural conditions.In two eye-tracking studies participants freely viewed complex scenes embedded in sequences of emotion-laden images. The latter primes constituted specific emotional contexts for neutral target images.Viewing behavior toward target images embedded into sets of primes was affected by the current emotional context, revealing the intensity of the emotional context as a significant moderator. The primes themselves were not scanned in different ways when presented within a block (Study 1), but when presented individually, negative primes were more actively scanned than positive primes (Study 2). These divergent results suggest an interaction between emotional priming and further context factors. Additionally, in most cases primes were scanned more actively than target images. Interestingly, the mere presence of emotion-laden stimuli in a set of images of different categories slowed down viewing activity overall, but the known effect of image category was not affected. Finally, viewing behavior remained largely constant on single images as well as across the targets' post-prime positions (Study 2).We conclude that the emotional context significantly influences the exploration of complex scenes and the emotional context has to be considered in predictions of eye-movement patterns.


Enzyme-linked immunosorbent assay for detection of red clover necrotic mosaic virus in the host plants.
Detection of three isolates of red clover necrotic mosaic virus (RCNMV) representing A, B, and C serotypes was experimentally proved in 18 host plant species by enzyme-linked immunosorbent assay (ELISA). In all plant species tested, the homologous serotype reactions showed high selectivity. Individual virus serotypes could be reliably detected in the extracts of infected plants only with the homologous IgG fraction. Group specific detection of RCNMV without serotype determination was possible using the mixture of IgG directed to all virus serotypes occurring in the region of investigation. Intensity of positive reaction of optimally diluted IgG with the extracts from infected plants differed markedly from that of negative reaction and from the reaction background. The latter depended on the quality of serum used for the IgG preparation. For detection of small amounts of RCNMV, virus infectivity test on indicator plants was more sensitive than ELISA.


Deep Learning for Drug-Induced Liver Injury.
Drug-induced liver injury (DILI) has been the single most frequent cause of safety-related drug marketing withdrawals for the past 50 years. Recently, deep learning (DL) has been successfully applied in many fields due to its exceptional and automatic learning ability. In this study, DILI prediction models were developed using DL architectures, and the best model trained on 475 drugs predicted an external validation set of 198 drugs with an accuracy of 86.9%, sensitivity of 82.5%, specificity of 92.9%, and area under the curve of 0.955, which is better than the performance of previously described DILI prediction models. Furthermore, with deep analysis, we also identified important molecular features that are related to DILI. Such DL models could improve the prediction of DILI risk in humans. The DL DILI prediction models are freely available at http://www.repharma.cn/DILIserver/DILI_home.php.


Three in One: The Versatility of Hydrogen Bonding Interaction in Halide Salts with Hydroxy-Functionalized Pyridinium Cations.
The paradigm of supramolecular chemistry relies on the delicate balance of noncovalent forces. Here we present a systematic approach for controlling the structural versatility of halide salts by the nature of hydrogen bonding interactions. We synthesized halide salts with hydroxy-functionalized pyridinium cations [HOCn Py]+ (n=2, 3, 4) and chloride, bromide and iodide anions, which are typically used as precursor material for synthesizing ionic liquids by anion metathesis reaction. The X-ray structures of these omnium halides show two types of hydrogen bonding: 'intra-ionic' H-bonds, wherein the anion interacts with the hydroxy group and the positively charged ring at the same cation, and 'inter-ionic' H-bonds, wherein the anion also interacts with the hydroxy group and the ring system but of different cations. We show that hydrogen bonding is controllable by the length of the hydroxyalkyl chain and the interaction strength of the anion. Some molten halide salts exhibit a third type of hydrogen bonding. IR spectra reveal elusive H-bonds between the OH groups of cations, showing interaction between ions of like charge. They are formed despite the repulsive interaction between the like-charged ions and compete with the favored cation-anion H-bonds. All types of H-bonding are analyzed by quantum chemical methods and the natural bond orbital approach, emphasizing the importance of charge transfer in these interactions. For simple omnium salts, we evidenced three distinct types of hydrogen bonds: Three in one!


Origin and countermeasure for common skin flap complications after radical operation for breast cancer.
To discuss the various factors which cause the common skin flap complications after radical operation for breast cancer. Two hundred sixteen patients with T1-3N0-1M0 breast cancer underwent radical surgery at The Cancer Hospital of Xingtai City, China during 1995-2003. Patey mastectomy was performed in majority of patients. Skin flaps were dissected using scalpel after injecting adrenaline containing saline into subcutaneous tissue. Diathermy was used only to stop bleeding vessels. A subset of patients who developed abnormal vascularity of skin flaps, seroma collection and flap necrosis was analyzed. Pressure garment and suction drains were used routinely. Flap necrosis < 3cm(2) was allowed to heal with secondary intention whereas larger defects were skin grafted. In 56 patients, flap associated complications were noted. Abnormal vascularity, flap necrosis and seroma collection were absorbed in 34 (15.7%), 13 (6%) and 9 (4.2%) patients, respectively. Eight patients (3.7%) required skin grafting. All patients were discharged with full recovery. To minimize the skin flap complications after radical surgery for breast cancer, lesser use of cautery, injection of adrenaline containing solution into subcutaneous tissue, routine use of suction drains and application of pressure garment may be recommended.


Mitotic neuroblasts in the 9-day-old and 11-month-old rodent hippocampus.
Ultrastructural identification of mitotic neuronal precursors beneath the basal hippocampal granule cell layer was made using electron micrographs of [3H]thymidine-labeled cells. Ultrathin sections were obtained by a method that allows serial thin sectioning of reembedded sections previously prepared for light microscopic radioautography. The electron microscopic observations reported in this study reveal: (1) that a steady rate of granule cell neurogenesis occurs during the first year of a rodent's life; (2) that newly formed granule neurons in the dentate gyrus of the newborn mouse and adult rat are a result of neuroblast division; and (3) two distinct classes of mitotic cells can be identified during the peak period of postnatal neurogenesis--those with synapses on their cell bodies and processes and those with no synapses or processes.


Phenotyping of Passiflora edulis, P. setacea, and their hybrids by a multivariate approach.
Morphological characterization is the most accessible and used method to quantify the genetic diversity of the available germplasm. The multivariate statistical method is highly important for this purpose. This study aimed to characterize parents and hybrids of Passiflora according to morphoagronomic descriptors and estimate the genetic divergence between them based on the joint analysis of qualitative and quantitative variables using the Ward-modified location model (MLM) procedure. One hundred and thirty-eight individuals were assessed (10 P. edulis, 10 P. setacea, and 118 interspecific hybrids) using 23 quantitative and 12 qualitative descriptors. The values for the quantitative descriptors were measured and subjected to multivariate statistics using the Ward-MLM strategy. Large genetic variability was detected by the morphoagronomic data in the 138 genotypes that were evaluated, and the hybrids presented higher variability than the parents. Pseudo-F and pseudo-t2 criteria showed that the optimal number of groups was three. Group I was composed of 118 hybrid genotypes; group II was composed of the 10 P. setacea genotypes, and group III was composed of the 10 P. edulis genotypes. The longest distance was found between groups II and III (474.96). The shortest distance was detected between groups I and II (198.78), which indicates that the segregating population is genetically closer to P. setacea than to P. edulis. The Ward-MLM procedure is a useful tool to detect genetic diversity and group accessions using both qualitative and quantitative variables.


Provider group type and Tdap coverage in pregnancy.
The Advisory Committee on Immunization Practices (ACIP) has focused on maternal Tdap immunization as an important means to protect neonates from pertussis infections. There is little published data on provider and/or clinic characteristics as predictors of maternal Tdap uptake. This study examined differences in maternal Tdap coverage in women delivering at a single academic institution, but cared for prenatally in different clinical settings, in 2013, 2014, and 2015. Additionally, the accuracy and utilization of Vermont's immunization information system (IIS) was assessed. This was a retrospective, multiple time-point cross-sectional analysis of annual maternal Tdap coverage in women delivering at a single academic institution in the 3 years following a fundamental change in national maternal Tdap vaccination guidelines. Tdap administration was examined across different obstetric groups using chart review and data from the state's IIS. All obstetric care groups except the resident-staffed clinic significantly increased maternal Tdap coverage in 2014, compared to 2013 coverage, with no further increase in 2015. In contrast, there was no increase in maternal Tdap coverage in 2014 in the resident-staffed clinics, but then a statistically significant increase in 2015. Overall Tdap coverage in 2014 was 80.4%, with variation in Tdap coverage between clinics types. In the subset of women who were cared for by the University-based groups, there was significant variation in Tdap coverage between clinics, despite racial homogeneity, which persisted after adjustment for maternal age and insurance type. The state's IIS was found to be highly accurate, using individual chart review as the "gold standard." While we demonstrated high maternal Tdap coverage in women delivering at our institution, differences in clinic type and provider training appeared to impact immunization rates, as well as how quickly evolving national recommendations were adopted. Additionally, the fidelity of the state's IIS data was verified.


Dysmenorrhea in industrial workers.
In two Norwegian industrial companies 234 women of menstruating age were examined by the industrial nurse with regard to menstrual complaints. Every second woman experienced pain, 23% had consulted a doctor previously, about 30% had to stay in bed, and about 30% had been absent from work recently due to dysmenorrhea. Although pain was prevalent in all age groups, there were age-specific differences in other complaints, such as headache and depression, which were more frequent among the older women. In a selected group of 32 women with severe complaints, the history and gynecological examination indicated secondary dysmenorrhea in only a few cases. Hormonal assays and endometrial biopsy indicated anovulatory cycles in 4 out of 12 women, in spite of dysmenorrhea.


Rapid Construction of Fe-Co-Ni Composition-Phase Map by Combinatorial Materials Chip Approach.
One hundred nanometer thick Fe-Co-Ni material chips were prepared and isothermally annealed at 500, 600, and 700 °C, respectively. Pixel-by-pixel composition and structural mapping was performed by microbeam X-ray at synchrotron light source. Diffraction images were recorded at a rate of 1 pattern/s. The XRD patterns were automatically processed, phase-identified, and categorized by hierarchical clustering algorithm to construct the composition-phase map. The resulting maps are consistent with corresponding isothermal sections reported in the ASM Alloy Phase Diagram Database, verifying the effectiveness of the present approach in phase diagram construction.


Improving access to medicines and beyond: the national volume-based procurement policy in China.
Since 2019, the Chinese central government has taken significant steps to centralize national purchasing power and has implemented a pooled procurement system. In this paper, we provide an in-depth analysis of China's National Volume-Based Procurement (NVBP) policy, which represents a unique approach to pooled procurement within the pharmaceutical sector. The primary objectives of the NVBP are to reduce drug prices, enhance access to affordable medications, and improve the overall functioning of the pharmaceutical industry in China. Our analysis delves into the key features of the NVBP, including its centralized procurement system, volume-based procurement approach, and the guaranteed procurement volumes allocated to winning bidders. We also address the challenges and implications associated with the NVBP, such as its impact on the pharmaceutical industry, the sustainability of price reductions, and the importance of striking a balance between price reduction and industry sustainability. Through a comparative analysis, we shed light on the distinct characteristics of China's approach to pooled procurement and its potential ramifications for healthcare policies and practices. By examining the NVBP within the broader context of China's evolving healthcare landscape, we aim to contribute to a deeper understanding of the implications and effectiveness of this unique policy initiative.


HER2 amplification in recurrent breast cancer following breast-conserving therapy correlates with distant metastasis and poor survival.
The authors analyzed the HER2 status in early-stage nonrecurrent and recurrent breast cancer groups following breast-conserving treatment. Retrospective analyses of a group of 36 invasive early breast cancer (IBC) patients who developed a local recurrence as a first event and of a random control group of 69 IBC patients were made. HER2 status was assessed by the HercepTest and fluorescence in situ hybridization. The Kaplan-Meier proportional log-rank test was used to study the impact of the biological factors on the metastasis-free interval (MFI) and the overall survival (OS). The Cox proportional hazards model, using stepwise selection was performed to identify the independent predictors of poor outcome. The median time of follow-up was 156 months (range: 22-230) for the nonrecurrent group of patients and 119 months (range: 36-228) for the recurrent group. No significant differences between either group were observed in terms of either patient or tumor characteristics, or of HER2 expression. However, a higher proportion of HER2 amplified cases were found in the recurrent group, in contrast to a higher proportion of hormonal receptor positive cases in the nonrecurrent group. After univariate and multivariate analyses, HER2 amplification was found to be an independent predictive factor for distant metastasis (HR = 10.75; p = 0.00008) and for survival (HR = 4.22; p = 0.004). In conclusion, HER2 amplification constitutes an independent poor prognostic factor for the MFI and OS in patients with recurrent breast cancer. The clinical implications are discussed.


Mapping genes for resistance to stripe rust in spring wheat landrace PI 480035.
Stripe rust caused by Puccinia striiformis Westend. f. sp. tritici Erikks. is an economically important disease of wheat (Triticum aestivum L.). Hexaploid spring wheat landrace PI 480035 was highly resistant to stripe rust in the field in Washington during 2011 and 2012. The objective of this research was to identify quantitative trait loci (QTL) for stripe rust resistance in PI 480035. A spring wheat, "Avocet Susceptible" (AvS), was crossed with PI 480035 to develop a biparental population of 110 recombinant inbred lines (RIL). The population was evaluated in the field in 2013 and 2014 and seedling reactions were examined against three races (PSTv-14, PSTv-37, and PSTv-40) of the pathogen under controlled conditions. The population was genotyped with genotyping-by-sequencing and microsatellite markers across the whole wheat genome. A major QTL, QYr.wrsggl1-1BS was identified on chromosome 1B. The closest flanking markers were Xgwm273, Xgwm11, and Xbarc187 1.01 cM distal to QYr.wrsggl1-1BS, Xcfd59 0.59 cM proximal and XA365 3.19 cM proximal to QYr.wrsggl1-1BS. Another QTL, QYr.wrsggl1-3B, was identified on 3B, which was significant only for PSTv-40 and was not significant in the field, indicating it confers a race-specific resistance. Comparison with markers associated with previously reported Yr genes on 1B (Yr64, Yr65, and YrH52) indicated that QYr.wrsggl1-1BS is potentially a novel stripe rust resistance gene that can be incorporated into modern breeding materials, along with other all-stage and adult-plant resistance genes to develop cultivars that can provide durable resistance.


Conformational states of the cell-penetrating peptide penetratin when interacting with phospholipid vesicles: effects of surface charge and peptide concentration.
The most commonly studied of the cell-penetrating peptides (CPP) is "penetratin" (pAntp), which functions as a carrier (vector), even for large hydrophilic (cargo) molecules. pAntp originates from the third helix of the Antennapedia homeodomain protein. The peptide is known to interact with negatively charged phospholipid vesicles, which leads to induction of secondary structure. In the present study, circular dichroism (CD) spectroscopy has been used to characterize the different secondary structures induced upon interaction with small unilamellar vesicles (SUVs) from mixtures of zwitterionic 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) and negatively charged 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG). The interaction was monitored using an electron paramagnetic resonance (EPR) spin probe attached to the peptide, and the intrinsic fluorophore (tryptophan). We measured the secondary structure as a function of surface charge density, total lipid-to-peptide (L/P) molar ratio, and salt concentration, for completely bound peptide. With vesicles from POPG/POPC in a molar ratio below 30:70, at a high L/P, the peptide adopts a mainly helical conformation. Increasing the charge density, at the same L/P, promotes a higher degree of beta-structure. At a fixed charge density, reducing the L/P also results in an alpha-->beta structure conversion. Hence, low membrane surface charge density and low pAntp concentration both favor a mainly helical conformation, while high charge density and pAntp concentration promote a dominating beta-structure. We conclude that pAntp, when residing at the surface of a membrane, is chameleon-like in terms of its induced structure.


Adverse histological features in malignant colorectal polyps: a contemporary series of 239 cases.
Screening colonoscopy has led to more colorectal carcinomas presenting at an early stage potentially curable by endoscopic resection. In this study, we examined the clinical and histological features of a contemporary series of malignant colorectal polyps (MCPs) with subsequent surgical resection. We conducted a retrospective study on a consecutive series of MCPs from 239 patients, predominantly males (57.7%) with a median age of 66 years, and assessed histological parameters associated with residual disease on the surgical specimens. Median MCP size was 18.6 mm, with 23.1% polyps measuring ≤10 mm. From the 140 surgical resection specimens, residual disease was identified in 20 cases, including 12 cases with metastatic lymph nodes and/or 9 cases with residual carcinoma in the large bowel wall. Histological parameters associated with nodal metastases were greater width and greater depth of the invasive component (p=0.001 and 0.006, respectively), poor differentiation (p=0.003) and a cribriform pattern (p=0.01). The risk of nodal metastases was 23.3% if two or three of these features were identified, while it was 0% and 4.5% if none or one was present, respectively. A positive margin was not associated with nodal metastasis and might be adequately treated by local endoscopic resection. Surgical resection should be recommended if ≥2 of these adverse histological features are present and may be warranted if one feature is present. A positive margin may require additional local resection but not necessarily surgery if no other adverse factors are present.


Podophyllotoxin and Rutin Modulates Ionizing Radiation-Induced Oxidative Stress and Apoptotic Cell Death in Mice Bone Marrow and Spleen.
The present study is aimed to investigate the radioprotective efficacy of G-003M (combination of podophyllotoxin and rutin) against gamma radiation-induced oxidative stress and subsequent cell death in mice bone marrow and spleen. Prophylactic administration of G-003M (-1 h) rendered more than 85% survival in mice exposed to 9 Gy (lethal dose) with dose reduction factor of 1.26. G-003M pretreated mice demonstrated significantly reduced level of reactive oxygen species, membrane lipid peroxidation, and retained glutathione level. In the same group, we obtained increased expression of master redox regulator, nuclear factor erythroid-derived like-2 factor (Nrf-2), and its downstream targets (heme oxygenase-1, Nqo-1, glutathione S-transferase, and thioredoxin reductase-1). In addition, G-003M preadministration has also shown a significant reduction in Keap-1 level (Nrf-2 inhibitor). Radiation-induced lethality was significantly amended in combination-treated (G-003M) mice as demonstrated by reduced 8-OHdG, annexin V FITC+ cells, and restored mitochondrial membrane potential. Expression of antiapoptotic protein Bcl-2 and Bcl-xL was restored in G-003M pretreated group. However, proapoptotic proteins (Puma, Bax, Bak, Caspase-3, and Caspase-7) were significantly declined in this group. Further analysis of immune cells revealed G-003M-mediated restoration of CD3 and CD19 receptor, which was found decreased to significant level following irradiation. Similarly, Gr-1, a marker of granulocytes, was also retained by G-003M administration prior to radiation. Modulatory potential of this formulation (G-003M) can be exploited as a safe and effective countermeasure against radiation-induced lymphohemopoietic injury.


Use of in-field bioreactors demonstrate groundwater filtration influences planktonic bacterial community assembly, but not biofilm composition.
Using in-field bioreactors, we investigated the influence of exogenous microorganisms in groundwater planktonic and biofilm microbial communities as part of the Integrated Field Research Challenge (IFRC). After an acclimation period with source groundwater, bioreactors received either filtered (0.22 μM filter) or unfiltered well groundwater in triplicate and communities were tracked routinely for 23 days after filtration was initiated. To address geochemical influences, the planktonic phase was assayed periodically for protein, organic acids, physico-/geochemical measurements and bacterial community (via 16S rRNA gene sequencing), while biofilms (i.e. microbial growth on sediment coupons) were targeted for bacterial community composition at the completion of the experiment (23 d). Based on Bray-Curtis distance, planktonic bacterial community composition varied temporally and between treatments (filtered, unfiltered bioreactors). Notably, filtration led to an increase in the dominant genus, Zoogloea relative abundance over time within the planktonic community, while remaining relatively constant when unfiltered. At day 23, biofilm communities were more taxonomically and phylogenetically diverse and substantially different from planktonic bacterial communities; however, the biofilm bacterial communities were similar regardless of filtration. These results suggest that although planktonic communities were sensitive to groundwater filtration, bacterial biofilm communities were stable and resistant to filtration. Bioreactors are useful tools in addressing questions pertaining to microbial community assembly and succession. These data provide a first step in understanding how an extrinsic factor, such as a groundwater inoculation and flux of microbial colonizers, impact how microbial communities assemble in environmental systems.


RADON AND PROGENY SOURCED DOSE ASSESSMENT OF SPA EMPLOYEES IN BALNEOLOGICAL SITES.
This study was conducted in the scope of IAEA project with the name 'Establishing a Systematic Radioactivity Survey and Total Effective Dose Assessment in Natural Balneological Sites' (TUR/9/018), at the Health Physics department of Sarayköy Nuclear Research and Training Center (SANAEM). The aim of this study is estimation of radon and progeny sourced effective dose for the people who are working at the spa facilities by measuring radon activity concentration (RAC) at the ambient air of indoor spa pools and dressing rooms. As it is known, the source of the radon gas is the radium content of the earth crust. Therefore, thermal waters coming from ground may contain dissolved radon and the radon can diffuse water to air. So the ambient air of spa pools can contain serious RAC that depends on a lot of parameters. In this regard, RAC measurements were executed at the 70 spa facilities in Turkey. The measurements were done with both active and passive methods at ambient air of spa pools and dressing rooms. Thus, active measurements were carried out by using the Alphaguard(®) with diffusion mode during half an hour, and passive measurements were carried out by using the humidity resistive CR-39 radon detectors during 2 months. Results show that RAC values at ambient air of spa pools varies between 13 Bq m(-3) and 10 kBq m(-3) Because long-term measurements are more reliable, if it is available, for dose calculations passive radon measurements (with CR-39 detectors) at ambient air of spa pools and dressing rooms were used, otherwise active measurement results were used. With the measurement by the conversion coefficients of ICRP 65 and occupational data of the employees has got from questionary forms, effective dose values were calculated. According to the calculations, spa employees are exposed to annual average dose between 0.05 and 29 mSv because of radon and progeny.


[A novel capsule-style manometric system and its application on non-invasive measurement of pancolonic pressure].
Pan-colonic motility was studied under normal conditions with a novel capsule-style system. A single use telemetry capsule embedded with one pressure sensor was ingested by subjects. It is capable of transmitting colonic pressure wirelessly greater than 130 h. Time of capsule entering segmental colon was determined by ultrasonic detection for tracing the batteries in capsule. The ultrasonic electrodes were mounted on the surface of subjects' ileocecum, navel as well as the junction of left colon and rectosigmoid colon in sequence. They were identified by abdominal X-rays with radiopaque markers. The confirming X-rays showed all telemetry capsules were detected successfully when passing through the key points in colon. A total of 613 h of colorectal recording was obtained from 20 healthy subjects. When compared with the parameters in the time of waking, the number of contractions and the area under contractions were significantly (P<0.05) decreased during sleep (21 +/- 5 vs 15 +/- 4 h(-1); 463 +/- 54 vs 342 +/- 45 mmHg x s x min(-1)). The colonic motility exhibited significant regional variation in the circadian behavior, as well as in its response to waking and meal. The clinical study proved the reliability and non-invasiveness of the system. It may represent a useful tool for the study on physiology and pathology of colonic motor disorders.


ASL expression in ALDH1A1+ neurons in the substantia nigra metabolically contributes to neurodegenerative phenotype.
Argininosuccinate lyase (ASL) is essential for the NO-dependent regulation of tyrosine hydroxylase (TH) and thus for catecholamine production. Using a conditional mouse model with loss of ASL in catecholamine neurons, we demonstrate that ASL is expressed in dopaminergic neurons in the substantia nigra pars compacta, including the ALDH1A1 + subpopulation that is pivotal for the pathogenesis of Parkinson disease (PD). Neuronal loss of ASL results in catecholamine deficiency, in accumulation and formation of tyrosine aggregates, in elevation of α-synuclein, and phenotypically in motor and cognitive deficits. NO supplementation rescues the formation of aggregates as well as the motor deficiencies. Our data point to a potential metabolic link between accumulations of tyrosine and seeding of pathological aggregates in neurons as initiators for the pathological processes involved in neurodegeneration. Hence, interventions in tyrosine metabolism via regulation of NO levels may be therapeutic beneficial for the treatment of catecholamine-related neurodegenerative disorders.


Who breastfeeds in New Brunswick, when and why?
We studied infant feeding in a representative sample of primiparous mothers of six-month-old infants in New Brunswick in 1982-83. At birth, 56% of infants were breastfed, decreasing to 31% at three months and 16% at six months; fewer were breastfed, and this for shorter periods of time, among the French population, those of lower socio-economic status or younger mothers. Most of the mothers who did not breastfeed did not attend prenatal classes and almost half had decided before their pregnancy to breastfeed or not. Most mothers breastfed because they felt their milk was better. Bottlefeeding mothers were mainly motivated by its convenience.


Measuring carer quality of life in Duchenne muscular dystrophy: a systematic review of the reliability and validity of self-report instruments using COSMIN.
Duchenne muscular dystrophy is a rare, progressive, life-limiting genetic neuromuscular condition that significantly impacts the quality of life of informal caregivers. Carer quality of life is measured using heterogeneous self-report scales, yet their suitability for Duchenne remains unclear. This review aimed to identify and evaluate the reliability and validity of quality of life instruments in Duchenne carers. Systematic searches were conducted in Embase, MEDLINE, CINAHL, PsycINFO, Cochrane Library and Google Scholar. Full research articles reporting data on multiple-item self-report quality of life instruments in informal Duchenne carers were included. Extracted evidence was qualitatively synthesised and evaluated, including risk of bias, against the Consensus-based Standards for the selection of health Measurement Instruments. Duchenne carer collaborators (N = 17) helped rate the instruments' content validity. Thirty-one articles featuring thirty-two quality of life instruments were included. Content validity was rated as "inconsistent" based on very low quality evidence. For Duchenne carer collaborators, the best instrument was PedsQL Family Impact Module. Only one instrument had evidence for structural validity (rated "unsatisfactory") and measurement invariance (rated "satisfactory"). Instruments received "satisfactory" ratings for internal consistency and mixed ratings for construct validity and responsiveness. There was no evidence for reliability, measurement error, or criterion validity. Instruments used to measure Duchenne carer quality of life have limited and often inconsistent supportive psychometric evidence. Further work must investigate instruments' measurement properties in Duchenne carers and/or the development of new tools. In the interim, we recommend considering the PedsQL Family Impact Module based on Duchenne carer ratings.


Dyslipidemic drugs in metabolic syndrome.
Metabolic syndrome predisposes to diabetes and atherosclerotic vascular disease. Statins reduce cardiovascular events, so all metabolic syndrome patients should be evaluated for dyslipidemia. Many patients fail to achieve lipid goals with statin monotherapy. Co-administration of ezetimibe (EZE) and atorvastatin (ATV) may enable more patients to achievelow-density lipoproteincholesterol (LDL-C) goal while avoiding risks of high-dose statin monotherapy. The present study compares rosuvastatin (Rsv) with a combination of (Atv) and (Eze). Metabolic syndrome patients, 30-70 years with LDL-C ≥130 mg/dl and a 10-year CHD risk score of 10% were randomized to double-blind treatment with (Rsv) 5 mg (n = 67) or (Atv) 10 mg+(Eze) 10 mg (n = 68) for 12 weeks. LDL-C reduced significantly; (32.3% and 30.3%, P < 0.001) in (Atv)+(Eze) and (Rsv), respectively, but there was no significant difference between two arms. More patients achieved LDL-C goal of ≤100 mg/dl with (Atv)+(Eze) compared to (Rsv) (65% vs. 58%, P < 0.05). Triglycerides (TG) were reduced more with (Atv)+(Eze) compared to (Rsv) (28.1% and 21.4%, P < 0.001). Greater increase in high-density lipoprotein cholesterol (HDL-C) was observed with (Atv)+(Eze). Both treatments were well tolerated. This study shows that the combination of (Atv)+(Eze) has more efficacy and comparable safety to that of (Rsv).


Presynaptic opioid delta-receptors in the rabbit mesenteric artery.
Excitatory junction potentials (e.j.p.s) evoked by nerve stimulation were recorded from muscle cells of the rabbit isolated mesenteric artery. At 0.03 Hz the e.j.p. amplitudes were stable. When a train of fifteen pulses was applied at 0.25 Hz or at higher frequencies (0.5, 1 and 2 Hz), e.j.p.s showed an initial facilitation followed by depression. [Met5]enkephalin 0.1 and 1 mumol/l, [D-Ala2,D-Leu5]enkephalin 0.1 and 1, but not 0.01 mumol/l, and [D-Pen2, L-Pen5]enkephalin 3 mumol/l all depressed the e.j.p.s evoked by trains of fifteen pulses at 1 Hz. When more than one concentration was used ([Met5]enkephalin, [D-Ala2,D-Leu5]enkephalin), the inhibition was concentration dependent. It was always greater for the first few e.j.p.s than for the later ones in a train. [Met5]enkephalin 1 mumol/l reduced the first e.j.p. at 1 Hz and the e.j.p.s evoked by 0.03 Hz to a similar extent. The inhibitory effect of [Met5]enkephalin 1 mumol/l on e.j.p.s persisted in the presence of yohimbine 0.3 mumol/l. Naloxone 1 mumol/l did not interfere with the effect of [Met5]enkephalin 1 mumol/l. Naloxone 10 mumol/l depressed some e.j.p.s and prevented the inhibition by [Met5]enkephalin 1 mumol/l. Neither ICI 154129 10 mumol/l nor ICI 174864 0.3 mumol/l had any effect of their own and both compounds antagonized the action of [Met5]enkephalin 1 mumol/l. Normorphine 10 mumol/l, fentanyl 1 mumol/l, ethylketocyclazocine 0.1 mumol/l, and dynorphin A(1-13) 1 mumol/l were all ineffective. Ethylketocyclazocine 1 mumol/l did not change the e.j.p.s either, but antagonized [Met5]enkephalin 1 mumol/l. [Met5]enkephalin 1 mumol/l failed to influence both the resting membrane potential of the muscle cells and the depolarizing effect of noradrenaline 3 and 30 mumol/l. We suggest that the axon terminals of post-ganglionic sympathetic neurones in the rabbit mesenteric artery possess opioid delta-, but not mu- or kappa-receptors. The activation of presynaptic delta-receptors inhibits the release of the neuroeffector transmitter. There is no evidence for any effect of co-released endogenous opioid peptides under our experimental conditions.


Peptide hormone modulation of a neuronally modulated motor circuit.
Rhythmically active motor circuits are influenced by neuronally released and circulating hormone modulators, but there are few systems in which the influence of a peptide hormone modulator on a neuronally modulated motor circuit has been determined. We performed such an analysis in the isolated crab stomatogastric nervous system by assessing the influence of the hormone crustacean cardioactive peptide (CCAP) on the gastric mill (chewing) rhythm elicited by identified modulatory projection neurons. The gastric mill circuit is located in the stomatogastric ganglion. In situ, this ganglion is located within the ophthalmic artery and thus is in the path of circulating hormones such as CCAP. Focally-applied CCAP directly excited some gastric mill neurons, including the gastric mill central pattern generator neurons LG and Int1, but it did not elicit a sustained gastric mill rhythm. At concentrations as low as 10(-10) M, however, CCAP did influence gastric mill rhythms elicited by coactivating the projection neurons MCN1 and CPN2 and by selectively stimulating MCN1. In both cases, CCAP slowed this rhythm by selectively prolonging the protraction phase, although its influence on the MCN1-elicited rhythm was limited to those with relatively brief cycle periods. Interestingly, CCAP also reduced the threshold MCN1 firing frequency for activating the gastric mill rhythm. Last, the gastric mill neurons that exhibited altered activity during these CCAP-influenced rhythms did not correspond completely to the set of CCAP-responsive neurons. These results highlight the ability of hormonal modulation to enhance the flexibility provided by the neuronal modulation of rhythmically active motor circuits.


Cytarabine Induced Acute Cerebellar Syndrome during Hyper-CVAD Treatment for B-Cell Acute Lymphoblastic Leukemia.
Acute cerebellar syndrome can be caused by high doses of cytarabine, but it has not been described in patients with acute lymphoblastic leukemia (ALL) who received hyper-CVAD chemotherapy. Herein, we report two cases with histories of positive Philadelphia chromosome B-cell ALL who developed acute cerebellar syndrome after the exposure to relatively low doses of cytarabine in the second cycle of hyper-CVAD regimen. The cerebellar symptoms were attenuated by cytarabine discontinuation and administration of steroids. This case report provides detailed discussions on the treatments, the potential role of methotrexate in cytarabine-induced cerebellar syndrome, and the importance of carefully monitoring renal function during hyper-CVAD treatment.


Photo-induced in situ crosslinking of polymer brushes with dimethyl maleimide moieties for dynamically stimulating stem cell differentiation.
We designed photo-crosslinkable polymer brushes with dimethylmaleimide moieties, in order to demonstrate dynamic stimulation of cell differentiation in mesenchymal stem cells (MSCs). The polymer brushes were synthesized by surface-initiated reversible addition fragmentation chain transfer polymerization using dimethylmaleimide ethyl methacrylate and methyl methacrylate on a chain transfer agent-immobilized glass surface. The polymer brushes were crosslinked by photodimerization of the dimethylmaleimide moieties within polymer chains with stem cells present on the surface. In order to evaluate the effects of in situ photo-induced crosslinking of the polymer brushes on gene expression of stem cells, human bone marrow MSCs were cultured under static and dynamic culture conditions for 7 days. Expression of the osteocalcin (Ocn) gene in MSCs was used as an indicator of osteoblast differentiation under dynamic culture conditions. Structural conversion from non-crosslinked polymer brushes to crosslinked polymer brushes increased the expression of Ocn by 1.4-fold in the presence of adhered cells, compared with non-crosslinked polymer brushes under static culture conditions. These results suggest that MSCs recognized surface conversion from non-crosslinked to crosslinked structures, which resulted in altered differentiation lineages. Therefore, photo-crosslinkable surfaces with dimethyl maleimide moieties are potential novel materials for dynamically stimulating MSC differentiation.


Volume-activated chloride currents in interstitial cells of Cajal.
Interstitial cells of Cajal (ICC) undergo marked morphological changes on contraction of the musculature, making it essential to understand properties of mechanosensitive ion channels. The whole cell patch-clamp technique was used to identify and to characterize volume-activated Cl- currents in ICC cultured through the explant technique. Hypotonic solutions (approximately 210 mosM) activated an outwardly rectifying current, which reversed near the equilibrium potential for Cl-. Time-dependent inactivation occurred only at pulse potentials of +80 mV, with a time constant of 478 +/- 182 ms. The degree of outward rectification was calculated using a rectification index, the ratio between the slope conductances of +65 and -55 mV, which was 13.9 +/- 1.5 at 76 mM initial extracellular Cl- concentration. The sequence of relative anion permeability of the outwardly rectifying Cl- channel was I- > Cl- > aspartate-. The chloride channel blockers, DIDS and 5-nitro-2-(3-phenlypropl-amino)benzoic acid, caused a voltage-dependent block of the outwardly rectifying Cl- current, inhibition occurring primarily at depolarized potentials. On exposure to hypotonic solution, the slope conductance significantly increased at the resting membrane potential (-70 mV) from 1.2 +/- 0.2 to 2.0 +/- 0.4 nS and at the slow-wave plateau potential (-35 mV) from 2.1 +/- 0.3 to 5.0 +/- 1.0 nS. The current was constitutively active in ICC and contributed to the resting membrane potential and excitability at the slow-wave plateau. In conclusion, swelling or volume change will depolarize ICC through activation of outwardly rectifying chloride channels, thereby increasing cell excitability.


Assessing transneuronal dysfunction utilizing manganese-enhanced MRI (MEMRI).
In this study we utilized manganese-enhanced MRI (MEMRI) to evaluate the in vivo transneuronal efficiency of manganese ion (Mn(2+)) movement as a means to assess overall changes in neuronal function. We designated this extension the manganese transfer index (MTI) value. To evaluate the MTI value as an index of transneuronal physiology we examined both pharmacological agents and different mouse models of neuronal dysfunction. We found that treatment with isoflurane, which attenuates synaptic vesicle release, or memantine, which attenuates postsynaptic uptake of Ca(2+) as well as Mn(2+), resulted in a decrease in the MTI value. Furthermore, we evaluated if changes in the MTI value can be detected in three knockout mice with altered brain function accompanied either with or without neurodegeneration. Our data demonstrate that the MTI values either decreased or increased in response to different functional as well as anatomical changes. These results demonstrate the potential utility of the MTI value as an in vivo index for the detection of changes in neuronal function in animal models of human disease.


In vitro and in vivo characteristics of frozen/thawed neonatal pig split-skin strips: a novel biologically active dressing for areas of severe, acute or chronic skin loss.
The recurrent shortage of human skin autografts or allografts used to close extensive wounds has rekindled the search for feasible alternatives. In the past, adult pig skin was a popular biological dressing, yet doubts regarding its benefits have induced most people to abandon its use. Here we investigated the aptness of neonatal pig split-skin (NPSS) strips to be used as a novel kind of temporary dressing for areas of skin loss. NPSS strips are able to be prepared in bulk amounts, stored at -80 degrees C for up to six months, and recovered by swift thawing at 45 degrees C with no change in histological structure. When set into organ cultures in vitro for up to three weeks, these frozen/thawed NPSS strips exhibited both a skin-typical energy-linked metabolism (i.e., a predominant consumption of L-glutamine instead of glucose), and an enduring ability to secrete cytokines/chemokines such as IL-1alpha, IL-6, GM-CSF, and TNF-alpha; all features alike in quantitative terms to those exhibited by freshly prepared NPSS strips directly set into culture. Moreover, once applied as temporary dressings onto deep burn wounds in vivo, frozen/thawed NPSS strips produced, for at least seven days, porcine IL-1alpha, IL-6, GM-CSF, TNF-alpha, and TGF-beta; the cytokines/chemokines importantly involved in wound healing. Hence, frozen/thawed NPSS strips not only are capable of closing extensive areas of skin loss, but even release several cytokines/chemokines beneficial to tissue regeneration and repair.


B cell activating factor (BAFF) and a proliferation inducing ligand (APRIL) mediate CD40-independent help by memory CD4 T cells.
Donor-reactive memory T cells undermine organ transplant survival and are poorly controlled by immunosuppression or costimulatory blockade. Memory CD4 T cells provide CD40-independent help for the generation of donor-reactive effector CD8 T cells and alloantibodies (alloAbs) that rapidly mediate allograft rejection. The goal of this study was to investigate the role of B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) in alloresponses driven by memory CD4 T cells. The short-term neutralization of BAFF alone or BAFF plus APRIL synergized with anti-CD154 mAb to prolong heart allograft survival in recipients containing donor-reactive memory CD4 T cells. The prolongation was associated with reduction in antidonor alloAb responses and with inhibited reactivation and helper functions of memory CD4 T cells. Additional depletion of CD8 T cells did not enhance the prolonged allograft survival suggesting that donor-reactive alloAbs mediate late graft rejection in these recipients. This is the first report that targeting the BAFF cytokine network inhibits both humoral and cellular immune responses induced by memory CD4 T cells. Our results suggest that reagents neutralizing BAFF and APRIL may be used to enhance the efficacy of CD40/CD154 costimulatory blockade and improve allograft survival in T cell-sensitized recipients.


Long-term efficacy of vasodilating β-blocker in patients with acute myocardial infarction: nationwide multicenter prospective registry.
Long-term benefit of vasodilating β-blockers is unknown. This study aimed to investigate the long-term benefit of vasodilating β-blockers over conventional β-blockers in patients with acute myocardial infarction (AMI). Using nationwide prospective multicenter Korean Acute Myocardial Infarction Registry data, we analyzed 3-year clinical outcomes of 7,269 patients with AMI who received percutaneous coronary intervention (PCI) and β-blocker therapy. Patients were classified according to treatment strategy (vasodilating β-blockers vs. conventional β-blockers). The primary endpoint was a composite of cardiac death, myocardial infarction (MI), and hospitalization for heart failure (HF) at 3 years. Secondary outcomes were each component of the primary outcome. Propensity score matching was performed to adjust for differences of baseline characteristics. In 3,079 pairs (6,158 patients) of propensity score-matched patients, the primary outcome occurred significantly less in the vasodilating β-blockers group compared with the conventional β-blockers group (7.6% vs. 9.8%, p = 0.003). Among the secondary outcomes, cardiac death occurred significantly less in the vasodilating β-blockers group than in the conventional group (3.5% vs. 4.8%, p = 0.015). The incidence rates of MI (2.4% vs. 3.0%, p = 0.160) or hospitalization for HF (2.6% vs. 3.2%, p = 0.192) were not significantly different between the two groups. Vasodilating β-blocker therapy was associated with better clinical outcomes compared with conventional β-blocker therapy in AMI patients undergoing PCI during 3 years follow-up. Vasodilating β-blockers could be recommended preferentially for these patients.


Coordination of Cu(2+)and Ni(2+) with the histone model peptide of H2B N-terminal tail (1-31 residues): A spectroscopic study.
The interaction of Cu(2+) and Ni(2+) with the N-terminal tail of histone H2B, the 31 amino acid peptide H2B(1-31) (Ac-PEPAKSAPAPKKG(13)SKKAVTKAQKKD(25)GKKRKR-NH(2)), studied by various spectroscopic techniques (UV/Vis, CD, EPR and NMR) are described. The results showed the formation of Cu(2+)-H2B(1-31) complexes above pH 7.3 most probably through the beta-carboxylate group of D25. With the increase of the pH, a mixture of 3 N and 4 N species presenting {2N(-), CO, epsilonNH(2)} and {2N(-), OH(2), epsilonNH(2)}{epsilonNH(2)} coordination modes, respectively is formed, while at highly basic solutions the binding of an additional amide donor is suggested. NMR spectroscopy supported by CD spectroscopy indicated that Ni(2+) coordination takes place most likely through Q22-K23-K24-D25 peptide fragment. Direct coordination to Ni(2+), in a {4N(-)} coordination mode, with a severe conformation change in all residues from G13 to G26 was observed. Cu(2+) and Ni(2+) binding to the N-terminal tail of H2B causes a severe conformational change that might interfere with histone post-translational modifications, possibly leading to epigenetic changes.


Seasonal differences in the parameters of luteinizing hormone release to exogenous gonadotropin releasing hormone in prepubertal Holstein heifers in Sapporo.
Stress due to summer heat has adverse effects on reproduction in Holstein dairy cattle. Summer suppression of reproduction of Holsteins can pose an important economic problem, even in Hokkaido prefecture located in the northern region of Japan. Hokkaido is one of the most important dairy farming areas of Japan. This study is an attempt to clarify the seasonal differences in the parameters of luteinizing hormone (LH) response to exogenous gonadotropin releasing hormone (GnRH) in Sapporo, Hokkaido, Japan. A total of 12 prepubertal heifers received an injection with GnRH analogue intramuscularly in either May (n=4, May group), July (n=4, July group), or November (n=4, November group), and serial blood samples were collected to analyze the parameters of the LH response curve after GnRH injection. The parameters were as follows: the basal LH concentration, peak LH concentration, duration from the time of GnRH injection to the time of the peak LH concentration, and area under the LH response curve (AUC). There were no significant differences in the basal and peak LH concentrations or the AUC among the three groups. The July group reached the LH peak significantly (P<0.05) faster than the May group, but there was no significant difference with the November group. Therefore, the results of the present study do not demonstrate an effect of summer heat on the LH response to the exogenous GnRH in Holstein heifers.