FlowCal: A User-Friendly, Open Source Software Tool for Automatically Converting Flow Cytometry Data from Arbitrary to Calibrated Units.
Flow cytometry is widely used to measure gene expression and other molecular biological processes with single cell resolution via fluorescent probes. Flow cytometers output data in arbitrary units (a.u.) that vary with the probe, instrument, and settings. Arbitrary units can be converted to the calibrated unit molecules of equivalent fluorophore (MEF) using commercially available calibration particles. However, there is no convenient, nonproprietary tool available to perform this calibration. Consequently, most researchers report data in a.u., limiting interpretation. Here, we report a software tool named FlowCal to overcome current limitations. FlowCal can be run using an intuitive Microsoft Excel interface, or customizable Python scripts. The software accepts Flow Cytometry Standard (FCS) files as inputs and is compatible with different calibration particles, fluorescent probes, and cell types. Additionally, FlowCal automatically gates data, calculates common statistics, and produces publication quality plots. We validate FlowCal by calibrating a.u. measurements of E. coli expressing superfolder GFP (sfGFP) collected at 10 different detector sensitivity (gain) settings to a single MEF value. Additionally, we reduce day-to-day variability in replicate E. coli sfGFP expression measurements due to instrument drift by 33%, and calibrate S. cerevisiae Venus expression data to MEF units. Finally, we demonstrate a simple method for using FlowCal to calibrate fluorescence units across different cytometers. FlowCal should ease the quantitative analysis of flow cytometry data within and across laboratories and facilitate the adoption of standard fluorescence units in synthetic biology and beyond.


Revisiting preeclampsia: a metabolic disorder of the placenta.
Preeclampsia (PE) is a leading cause of maternal and neonatal mortality and morbidity worldwide, impacting the long-term health of both mother and offspring. PE has long been characterized by deficient trophoblast invasion into the uterus and consequent placental hypoperfusion, yet the upstream causative factors and effective interventional targets for PE remain unknown. Alterations in the metabolism of preeclamptic placentas are thought to result from placental ischemia, while disturbances of the metabolism and of metabolites in PE pathogenesis are largely ignored. In fact, as one of the largest fetal organs at birth, the placenta consumes a considerable amount of glucose and fatty acid. Increasing evidence suggests glucose and fatty acid exist as energy substrates and regulate placental development through bioactive derivates. Moreover, recent findings have revealed that the placental metabolism adapts readily to environmental changes, altering its response to nutrients and endocrine signals; this adaptability optimizes pregnancy outcomes by diversifying available carbon sources for energy production, hormone synthesis, angiogenesis, immune activation, and tolerance, and fetoplacental growth. These observations raise the possibility that carbohydrate and lipid metabolism abnormalities play a role in both the etiology and clinical progression of PE, sparking a renewed interest in the interrelationship between PE and metabolic dysregulation. This review will focus on key metabolic substrates and regulatory molecules in the placenta and aim to provide novel insights with respect to the metabolism's role in modulating placental development and functions. Further investigations from this perspective are poised to decipher the etiology of PE and suggest potential therapies.


Malaria during Pregnancy.
One hundred and twenty-five million women in malaria-endemic areas become pregnant each year (see Dellicour et al. PLoS Med7: e1000221 [2010]) and require protection from infection to avoid disease and death for themselves and their offspring. Chloroquine prophylaxis was once a safe approach to prevention but has been abandoned because of drug-resistant parasites, and intermittent presumptive treatment with sulfadoxine-pyrimethamine, which is currently used to protect pregnant women throughout Africa, is rapidly losing its benefits for the same reason. No other drugs have yet been shown to be safe, tolerable, and effective as prevention for pregnant women, although monthly dihydroartemisinin-piperaquine has shown promise for reducing poor pregnancy outcomes. Insecticide-treated nets provide some benefits, such as reducing placental malaria and low birth weight. However, this leaves a heavy burden of maternal, fetal, and infant morbidity and mortality that could be avoided. Women naturally acquire resistance to Plasmodium falciparum over successive pregnancies as they acquire antibodies against parasitized red cells that bind chondroitin sulfate A in the placenta, suggesting that a vaccine is feasible. Pregnant women are an important reservoir of parasites in the community, and women of reproductive age must be included in any elimination effort, but several features of malaria during pregnancy will require special consideration during the implementation of elimination programs.


Impact of Therapy in Patients with Hematologic Malignancies on Seroconversion Rates After SARS-CoV-2 Vaccination.
The leading professional organizations in the field of hematology have recommended severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) vaccination for all patients with hematologic malignancies notwithstanding efficacy concerns. Here we report a systematic literature review regarding the antibody response to SARS-CoV-2 vaccination in patients with hematologic malignancies and its key determinants. We conducted a systematic search of original articles evaluating the seroconversion rates with SARS-CoV-2 vaccines in hematological malignancies from the PubMed database published between April 1, 2021 and December 4, 2021. Calculated risk differences (RD) and 95% confidence intervals (CI) to compare seroconversion rates between patients with hematologic malignancies versus healthy control subjects used the Review Manager software, version 5.3. In our meta-analysis, we included 26 studies with control arms. After the first dose of vaccination, patients with hematologic malignancies had significantly lower seroconversion rates than controls (33.3% vs 74.9%; RD: -0.48%, 95% CI: -0.60%, -0.36%, P < .001). The seroconversion rates increased after the second dose, although a significant difference remained between these 2 groups (65.3% vs 97.8%; RD: -0.35%, 95% CI: -0.42%, -0.28%, P < .001). This difference in seroconversion rates was particularly pronounced for Chronic Lymphocytic Leukemia (CLL) patients (RD: -0.46%, 95% CI: -0.56, -0.37, P < .001), and for patients with B-lineage leukemia/lymphoma treated with anti-CD20 antibodies (RD: -0.70%, 95% CI: -0.88%, -0.51%, P < .001) or Bruton Tyrosine Kinase Inhibitors (BTKi; RD: -0.63%, 95% CI: -0.85%, -0.41%, P < .001). The RD was lower for patients under remission (RD: -0.10%, 95% CI: -0.18%, -0.02%, P = .01). The seroconversion rates following SARS-CoV-2 vaccination in patients with hematologic malignancies, especially in CLL patients and patients treated with anti-CD20 antibodies or BTKi, were significantly lower than the seroconversion rates in healthy control subjects. Effective strategies capable of improving vaccine efficacy in these vulnerable patient populations are urgently needed.


The specific binding of thrombin to human polymorphonuclear leucocytes.
Thrombin is a chemotaxin for polymorphonuclear leucocytes. In this paper the binding kinetics of 125I-labelled thrombin to purified polymorphonuclear leucocytes is characterized. At 4 degrees C, the 125I-labelled thrombin bound to the cells with a half-time of about 3 min. About 0.77 of the bound tracer dissociated upon addition of a surplus of unlabelled thrombin or hirudin. Each cell possessed about 50 receptors with a Kd of 18 pmol/l and about 6000 receptors with a Kd of 31 nmol/l. Although the binding affinity at 37 degrees C was 7-10-fold lower than that measured at 4 degrees C, it may be high enough to constitute the molecular basis for the reported thrombin-induced chemotaxis.


[Benefits and adverse effects of post-operative radiation therapy after radical cystectomy for patients with advanced bladder cancer].
The benefits and adverse effects of post-operative irradiation for advanced bladder cancer patients were investigated. Ten patients with pT3b, pT4 or pN+ bladder cancer who underwent radical cystectomy at Yamanashi Medical University hospital during 7 years and 3 months from October 1983 to December 1991 received adjuvant chemotherapy and radiotherapy (Group 1). During the same period, six patients with recurrent tumor after radical cystectomy were treated by radiotherapy (Group II). Stages of the primary tumors were pT2 in 1, pT3a in 2, pT3b in 6 and pT4 in 7 cases. In addition, 10 of 16 patients (63%) had positive nodes. During the follow up period, seven patients died of cancer, and one died of other cause. As a result eight patients (5 in Group I, 3 in Group II) are alive. The cumulative 5-year survival rate is 50%. However, nine of the 16 patients (56%) suffered from the small bowel obstruction as an adverse effect of irradiation. Six patients required resection of the small bowel or bypass surgery. Radiation after radical cystectomy seemed to be effective for the local control of the tumor, but the adverse effect to the digestive system was very severe and common.


A lighting approach for clinical photographs of the face.
This article describes an alternative approach of lighting setup for taking clinical photographs of the face. The lighting techniques presented in this article will help the clinician obtain good-quality clinical photographs.


Bacteriochlorophyll Synthesis and the Ultrastructure of Wild Type and Mutant Strains of Rhodopseudomonas spheroides.
The ultrastructure of sectioned cells of mutant and wild type Rhodopseudomonas spheroides has been examined by electron microscopy. The characteristic vesicles associated with the presence of bacteriochlorophyll were found in wild type cells grown with low aeration. These were also found in mutant TA-R which forms bacteriochlorophyll under high aeration. None of the mutants with blocks in bacteriochlorophyll synthesis contained intracytoplasmic membrane. These included mutant 8-17 which accumulates bacteriochlorophyllide but fails at the phytolation step. We conclude that the intact bacteriochlorophyll molecule, or some particular membrane protein associated with it, is needed for the development of the characteristic intracytoplasmic membrane system in R. spheroides.


Oral misoprostol administration for labor induction.
Using oral agents for induction of labor would reduce the need for repeated vaginal examinations; this is more acceptable to women and could reduce infection rates. A systematic review was conducted of 41 randomized trials comparing oral misoprostol to other induction agents. Oral misoprostol is effective at achieving vaginal delivery, and may have benefits over both vaginal and intracervical dinoprostone. Although it does not achieve vaginal delivery as quickly as vaginal misoprostol, the rates of hyperstimulation are lower when using comparable doses. As the primary consideration should be safety rather than speed, an oral regimen using a maximum of 50 mcg 4 hourly is recommended.


Preservation of aquatic food using edible films and coatings containing essential oils: a review.
Edible films and coatings have recently received growing attention in the food packaging sector due to their protective ability from the external environment and biodegradability characteristic. Generally, any layer of biomaterial incorporated into food to prolong its shelf-life and that can be consumed along with the food with or without further peeling is defined as an edible film or coating. These biodegradable films improve mechanical properties, moisture and gas barriers, microbial protection, sensory perception, and the shelf-life of food products. In particular, films obtained from polysaccharides are characterized by better gas barrier properties, whereas proteins are known for their excellent mechanical properties. However, both polysaccharides and proteins show poor water barrier properties in films which can be improved by incorporating lipids as well as combining one or more hydrocolloids (proteins and polysaccharides). Moreover, essential oils (EOs) consist mainly of volatile components obtained from plants, which can be added to the film to improve antimicrobial and antioxidant properties. On the other hand, fishery products are highly perishable due to the combined action of chemical reaction, lipid oxidation, endogenous enzymes, and microbial growth. Cold storage and freezing with or without vacuum packaging are often used to preserve fishery products, but they do not always completely preserve quality. Therefore, this review aims to summarize the components and chemistry of edible films and coatings, and their application to aquatic food for quality preservation. Moreover, deterioration of aquatic food and how these films and coatings can improve antimicrobial, antioxidant, physical, and sensory properties are also discussed.


The Physical Effect of Exergames in Healthy Elderly-A Systematic Review.
Exergames have been suggested as an innovative approach to enhance physical activity in the elderly. The objective of this review was to determine the effectiveness of exergames on validated quantitative physical outcomes in healthy elderly individuals. We used Centre for Review and Disseminations guidance to conduct systematic reviews. Four electronic databases were searched. We included randomized controlled trials (RCTs), the study participants were healthy elderly individuals, and the intervention of interest was exergaming. The title and abstract screening of the 1861 citations identified 36 studies as potentially eligible for this review, and an additional nine were identified from reference lists. The full text screening identified seven studies with a total of 311 participants, all reporting RCTs with low-to-moderate methodological quality. Six of the seven studies found a positive effect of exergaming on the health of the elderly. However, the variation of intervention approaches and outcome data collected limited the extent to which studies could be compared. This review demonstrates how exergames have a potential to improve physical health in the elderly. However, there is a need for additional and better-designed studies that assess the effectiveness and long-term adherence of exergames designed specifically for the elderly.


Effects of dynavision training as a preparatory intervention status postcerebrovascular accident: a case report.
ABSTRACT Objective. This is a case study of a 67-year-old woman, status post right hemispheric ischemic lesion cerebrovascular accident (CVA), and her use of Dynavision training as a preparatory intervention to determine its influence on her performance skills and perceived occupational performance. Method. The participant engaged in 6 weeks of Dynavision intervention, 3 days per week. The participant was evaluated using a broad battery of assessments at pretest and posttest. Outcome measures included the Action Research Arm Test (ARAT), Canadian Occupational Performance Measure (COPM), and goniometric active range of motion (AROM) measurements for the upper extremity. Standing activity tolerance during engagement in occupations also was assessed. A qualitative interview was employed to ascertain the participant's perceptions of how Dynavision training influenced her performance in activities of daily living (ADL) and instrumental activities of daily living (IADL). Results. Improvements in performance skills, perceived occupational performance, and perceived satisfaction with engagement in occupation were noted. The participant demonstrated improved AROM, functional activity tolerance, and greater awareness of the neglected side. Qualitative interviews revealed that the participant's satisfaction and confidence with ADL and IADL tasks improved at the time of posttest. Conclusion. Data suggest positive effects of Dynavision intervention when used with an individual status post-CVA.


Case of an atypical pituitary abscess.
A pituitary abscess is a rare intrasellar infection. Correct identification can be challenging preoperatively given its non-specific symptoms and imaging findings. We report a case of a young woman presenting with secondary amenorrhea, visual field deficits and a 2.6 cm pituitary lesion diagnosed to be a craniopharyngioma. A concomitant unexpected pituitary abscess was diagnosed intraoperatively without associated meningeal symptoms.


Treatment of radiation-induced proctitis with sucralfate enemas.
To report a case of radiation-induced proctitis treated with sucralfate enemas. A 77-year-old white woman was transferred from an acute care institution to our inpatient rehabilitation unit with impaired mobility and reduced activities of daily living. Her condition was secondary to myopathy and peripheral neuropathy associated with postradiation chemotherapy and metastatic ovarian carcinoma. During her stay, she developed hematochezia and pain secondary to a diagnosis of radiation-induced proctitis. Her hemoglobin had reached a nadir of 7.3 g/dL. The patient received blood transfusions and was started on 10% w/v sucralfate retention enemas 2 g/20 mL daily for 12 consecutive days. She was symptom-free at discharge, with a stable hemoglobin of approximately 10 g/dL. Proctitis is a common adverse effect of radiotherapy to the lower abdomen and pelvic area. Sucralfate is an aluminum complex that acts as a local cytoprotective agent against ulceration of the gastrointestinal mucosal lining. Rectal administration of sucralfate, as described in our patient and reported in published case studies, may provide an alternative therapy for patients with radiation-induced proctitis. Sucralfate suspension enemas provide a viable treatment option in patients who are intolerant of, refractory to, or not candidates for standard therapy for radiation-induced proctitis.


Heme deficiency interferes with the Ras-mitogen-activated protein kinase signaling pathway and expression of a subset of neuronal genes.
Defective heme synthesis in mammals has been suspected of causing neuropathy associated with porphyrias and lead poisoning. To determine the molecular action of heme in neuronal cells, we examined the effect of the inhibition of heme synthesis on nerve growth factor (NGF) signaling in PC12 cells. We found that the inhibition of heme synthesis by succinyl acetone interferes with NGF-induced neurite outgrowth in PC12 cells. Furthermore, we show that heme deficiency obliterates the activation of the signaling intermediates of the Ras-mitogen-activated protein kinase signaling pathway and its downstream target, the transcription activator cyclic AMP response element-binding protein. Strikingly, microarray expression analysis shows that the inhibition of heme synthesis selectively diminishes the induction of expression of a subset of neuron-specific genes by NGF, such as Ras and neurofilament proteins, whereas NGF induces the expression of several major classes of neuronal genes that encode regulatory and structural proteins at three days after induction. Our data provide insights into how heme deficiency interferes with NGF signaling and abrogates programs of neuronal gene expression, thus ultimately causing defective neuronal functions.


Coenzyme Q10 Modulates Apoptotic Effects of Chronic Administration of Methadone on NMRI Mouse Hippocampus.
Methadone is one of the widely used drug substances prescribed in treatment of opioid dependence and pain management; however, several studies have shown its neurotoxic effects on individuals and animal models. The purpose of this study was to assess neuroprotective effects of Coenzyme Q10 (CoQ10) on neurotoxicity induced by methadone in hippocampus of adult NMRI male mice. In this experimental study, 48 adult NMRI male mice were randomly divided into 4 groups (n=12 in each) including Methadone, Methadone with sesame oil, Methadone with CoQ10 and saline. The injections of methadone, saline and sesame oil were performed intraperitoneally for 20 days. 24 hours after last injection, half of the animals in each group (n=6) were randomly assessed for evaluating of spatial memory by radial maze. Following behavioral study, animals were sacrificed, and their brains were removed to evaluate pyknotic cells through histological assessment. The remaining were used to study the expression of Arc, Bax, Bcl-2 and Bdnf genes. Results of the present study showed that daily administration of methadone increased the number of pyknotic neurons in the CA1 hippocampus and altered the expression of Bax, Bdnf, Arc and Bcl-2. However, it did not alter spatial memory comparing to saline group. CoQ10 treatment significantly reduced the number of pyknotic cells and expression of Bax, Bdnf, Arc when compared to the vehicle group treated by sesame oil. However, the expression of Bcl-2 significantly increased as a result of CoQ10 treatment. CoQ10 reduced the neuronal damage caused by methadone in the hippocampus CA1.


Epoxidized Jatropha Oil as a Sustainable Plasticizer to Poly(lactic Acid).
A renewable resource, epoxidized jatropha oil (EJO), was used as a green plasticizer and added to poly(lactic acid) (PLA). EJO was compounded into PLA at different contents. The addition of 3 wt % EJO to the PLA demonstrates significant improvement in flexibility, which leads to a percentage increase of about 7000% in elongation at break. This tensile result was confirmed by surface morphology analysis with clear proof of plastic deformation in EJO-plasticized PLA. EJO imparts a good heat stabilization effect. Thermal stability of PLA was enhanced upon addition of EJO, which is due to their good interaction and plasticizer dispersion within the PLA matrix. This EJO-plasticized PLA has wide applications in various industries, such as packaging of food and non-food products.


The incidence of symptomatic malrotation post gastroschisis repair.
Gastroschisis is known to be associated with abnormal bowel rotation. Currently, the broadly accepted practice is not to perform Ladd's procedure routinely at the time of closure of gastroschisis defects. However the incidence of symptomatic malrotation and volvulus post gastroschisis repair is unknown; this incidence is important in view of the current practice of bedside gastroschisis closure. This study examined the incidence of symptomatic malrotation and volvulus following gastroschisis repair. Patients who had undergone gastroschisis repair between 1999 and 2009 in any of 2 tertiary centers were identified using the Hospital Inpatient Enquiry system. The medical records were reviewed to obtain demographic data and postoperative outcomes. Patients were contacted for follow-up. 128 patients were identified with a median postoperative follow-up of 4 years (range: 6 weeks to 12 years). Upper gastrointestinal (GI) contrast studies were performed in 30 patients (23.4%), 21 (16.4%) of whom showed evidence of malrotation. Malrotation was documented during the primary repair in 12 patients (9.4%); however Ladd's procedure was performed primarily in only 3 patients. 7 patients underwent Ladd's procedure in a second laparotomy for mechanical obstruction secondary to causes not related to malrotation and volvulus. A total of 29 patients (22.7%) had either operative or radiological evidence of malrotation. None of these patients developed volvulus after being followed for a median period of 4 years. Bedside gastroschisis closure without concomitant Ladd's procedure is a safe practice. None of the patients with documented malrotation developed volvulus post gastroschisis repair.


Simvastatin induces a central hypotensive effect via Ras-mediated signalling to cause eNOS up-regulation.
Clinical studies indicate that statins have a BP-lowering effect in hypercholesterolemic individuals with hypertension. Specifically, statins modulate BP through the up-regulation of endothelial NOS (eNOS) activation in the brain. However, the signalling mechanisms through which statins enhance eNOS activation remain unclear. Therefore, we examined the possible signalling pathways involved in statin-mediated BP regulation in the nucleus tractus solitarii (NTS). To investigate the involvement of Ras and other signalling pathways in simvastatin-induced effects on BP, BP and renal sympathetic nerve activity (RSNA) were determined in spontaneously hypertensive rats (SHRs) before and after i.c.v. administration of simvastatin in the absence and presence of a Ras-specific inhibitor (farnesyl thiosalicylic acid, FTS), a geranylgeranyltransferase inhibitor (GGTI-2133), a PI3K inhibitor (LY294002) or a MAPK-ERK kinase (MEK) inhibitor (PD98059). FTS significantly attenuated the decrease in BP and increased NO evoked by simvastatin and reversed the decrease in basal RSNA induced by simvastatin. Immunoblotting and pharmacological studies showed that inhibition of Ras activity by FTS significantly abolished simvastatin-induced phosphorylation of ERK1/2, ribosomal protein S6 kinase (RSK), Akt and decreased eNOS phosphorylation. Likewise, administration of Akt and ERK1/2 signalling inhibitors, LY294002 and PD98059, attenuated the reduction in BP evoked by simvastatin. Furthermore, i.c.v. simvastatin decreased Rac1 activation and the number of ROS-positive cells in the NTS. Simvastatin modulates central BP control in the NTS of SHRs by increasing Ras-mediated activation of the PI3K-Akt and ERK1/2-RSK signalling pathways, which then up-regulates eNOS activation.


The World Health Organization African region laboratory accreditation process: improving the quality of laboratory systems in the African region.
Few developing countries have established laboratory quality standards that are affordable and easy to implement and monitor. To address this challenge, the World Health Organization Regional Office for Africa (WHO AFRO) established a stepwise approach, using a 0- to 5-star scale, to the recognition of evolving fulfillment of the ISO 15189 standard rather than pass-fail grading. Laboratories that fail to achieve an assessment score of at least 55% will not be awarded a star ranking. Laboratories that achieve 95% or more will receive a 5-star rating. This stepwise approach acknowledges to laboratories where they stand, supports them with a series of evaluations to use to demonstrate improvement, and recognizes and rewards their progress. WHO AFRO's accreditation process is not intended to replace established ISO 15189 accreditation schemes, but rather to provide an interim pathway to the realization of international laboratory standards. Laboratories that demonstrate outstanding performance in the WHO-AFRO process will be strongly encouraged to enroll in an established ISO 15189 accreditation scheme. We believe that the WHO-AFRO approach for laboratory accreditation is affordable, sustainable, effective, and scalable.


1D and 2D assembly structures by imidazole···chloride hydrogen bonds of iron(II) complexes [Fe(II)(HL(n-Pr))3]Cl·Y (HL(n-Pr) = 2-methylimidazol-4-yl-methylideneamino-n-propyl; Y = AsF6, BF4) and their spin states.
Two Fe(II) complexes fac-[Fe(II)(HL(n-Pr))(3)]Cl·Y (Y = AsF(6) (1) and BF(4) (2)) were synthesized, where HL(n-Pr) is 2-methylimidazole-4-yl-methylideneamino-n-propyl. Each complex-cation has the same octahedral N(6) geometry coordinated by three bidentate ligands and assumes facial-isomerism, fac-[Fe(II)(HL(n-Pr))(3)](2+) with Δ- and Λ-enantiomorphs. Three imidazole groups per Δ- or Λ-fac-[Fe(II)(HL(n-Pr))(3)](2+) are hydrogen-bonded to three Cl(-) ions or, from the viewpoint of the Cl(-) ion, one Cl(-) ion is hydrogen-bonded to three neighbouring fac-[Fe(II)(HL(n-Pr))(3)](2+) cations. The 3 : 3 NH···Cl(-) hydrogen bonds between Δ- or Λ-fac-[Fe(II)(HL(n-Pr))(3)](2+) and Cl(-) generate two kinds of assembly structures. The directions of the 3 : 3 NH···Cl(-) hydrogen bonds and hence the resulting assembly structures are determined by the size of the anion Y, though Y is not involved into the network structure and just accommodated in the cavity. Compound 1 has a 1D ladder structure giving a larger cavity, in which the Δ- and Λ-fac-[Fe(II)(HL(n-Pr))(3)](2+) enantiomorphs are bridged by two NH···Cl(-) hydrogen bonds. Compound 2 has a 2D network structure with a net unit of a cyclic trimer of {fac-[Fe(II)(HL(n-Pr))(3)](2+)···Cl(-)}(3) giving a smaller cavity, in which Δ- or Λ-fac-[Fe(II)(HL(n-Pr))(3)](2+) species with the same chirality are linked by NH···Cl(-) hydrogen bonds to give a homochiral 2D network structure. Magnetic susceptibility and Mössbauer spectral measurements demonstrated that compound 1 showed an abrupt one-step spin crossover with 4.0 K thermal hysteresis of T(c↓) = 125.5 K and T(c↑) = 129.5 K and compound 2 showed no spin transition and stayed in the high-spin state over the 5-300 K temperature range.


Exclusion of TACSTD2 in an Iranian GDLD pedigree.
To perform a mutation screen of TACSTD2 in an Iranian Gelatinous Drop-like Corneal Dystrophy (GDLD) pedigree. In addition to the coding region of TACSTD2, for the first time the promoter, the entire 5'-noncoding region, and the entire 3'-untranslated region of the gene were sequenced from an affected member of the pedigree. Phenotypic features of affected individuals were assessed. The proband carried six sequence variations in TACSTD2. One of the variations was homozygous and caused a synonymous codon change. The remaining five were heterozygous variations in the 3'-untranslated region. None of the variations were assessed to be associated with GDLD. Fibroblastic scars were evident in in corneal histology sections of two affected members of the pedigree. It is concluded that GDLD in the pedigree is probably not caused by mutations in TACSTD2, supporting evidence for the existence of at least one other locus for GDLD. Phenotypic features of the Iranian patients, including the existence of fibroblastic scars in the corneas, were similar to those of a previously reported GDLD patient without TACSTD2 mutations. This suggests the disease in these individuals may be due to mutations in the same gene.


Modulation of gut microbiota in rats fed high-fat diets by processing whole-grain barley to barley malt.
The gut microbiota is linked with human health, and by manipulating its composition, health conditions might be improved. The aim of this study was to investigate whether two barley products, whole-grain barley and barley malt, caused differentiation of the cecal microbiota in rats fed high-fat diets and whether there were correlations with the short-chain fatty acids formed. Male Wistar rats were given barley or malt (7-8 dietary fiber/100 g) for 4 weeks. Cellulose was used as a control, and the cecal microbiota was analyzed with next-generation sequencing of 16S rDNA. The barley group had higher abundances of Verrucomicrobia and Actinobacteria and lower abundances of Firmicutes and Deferribacteres than the control group; the alpha diversity was also lower. At the genus level, the barley group had higher abundances of Akkermansia, Ruminococcus, Blautia, and Bilophila. Turicibacter and Roseburia were more abundant in the malt group, and Parabacteroides, Dorea and rc4-4 were enriched in the control group. Most genera correlated with acetic and propionic acids, but Roseburia and Turicibacter instead correlated with butyric acid. Succinic acid correlated with Clostridium and Akkermansia. Bioprocessing is a potential method to modulate the gut microbiota for enhanced effects on human health.


Work of breathing using high-flow nasal cannula in preterm infants.
To compare the work of breathing (WOB) in premature neonates supported with high-flow nasal cannula (HFNC) and nasal continuous positive airway pressure (NCPAP). Eighteen preterm neonates <2.0 kg on HFNC or NCPAP support were studied in a random order. A ventilator was used to deliver 6 cm H2O of NCPAP with nasal prongs. High-flow nasal cannula delivered with Vapotherm (VAPO) at 3, 4 and 5 l/min was used. Tidal ventilation was obtained using respiratory inductance plethysmography calibrated with face-mask pneumotachography. An esophageal balloon estimated pleural pressure from which changes in end distending pressure were calculated. Inspiratory, elastic and resistive WOB and respiratory parameters were calculated. No differences were found in the WOB for all settings. Changes in end distending pressure did not vary significantly over all device settings except VAPO at 5 l/min. In these preterm infants with mild respiratory illness, HFNC provided support comparable to NCPAP.


Self-limiting fall armyworm: a new approach in development for sustainable crop protection and resistance management.
The fall armyworm, Spodoptera frugiperda, is a significant and widespread pest of maize, sorghum, rice, and other economically important crops. Successful management of this caterpillar pest has historically relied upon application of synthetic insecticides and through cultivation of genetically engineered crops expressing insecticidal proteins (Bt crops). Fall armyworm has, however, developed resistance to both synthetic insecticides and Bt crops, which risks undermining the benefits delivered by these important crop protection tools. Previous modelling and empirical studies have demonstrated that releases of insecticide- or Bt-susceptible insects genetically modified to express conditional female mortality can both dilute insecticide resistance and suppress pest populations. Here, we describe the first germline transformation of the fall armyworm and the development of a genetically engineered male-selecting self-limiting strain, OX5382G, which exhibits complete female mortality in the absence of an additive in the larval diet. Laboratory experiments showed that males of this strain are competitive against wild-type males for copulations with wild-type females, and that the OX5382G self-limiting transgene declines rapidly to extinction in closed populations following the cessation of OX5382G male releases. Population models simulating the release of OX5382G males in tandem with Bt crops and non-Bt 'refuge' crops show that OX5382G releases can suppress fall armyworm populations and delay the spread of resistance to insecticidal proteins. This article describes the development of self-limiting fall armyworm designed to control this pest by suppressing pest populations, and population models that demonstrate its potential as a highly effective method of managing resistance to Bt crops in pest fall armyworm populations. Our results provide early promise for a potentially valuable future addition to integrated pest management strategies for fall armyworm and other pests for which resistance to existing crop protection measures results in damage to crops and impedes sustainable agriculture.


Comparison of intra-coronary cell transplantation after myocardial infarction: Autologous skeletal myoblasts versus bone marrow mesenchymal stem cells.
Cell transplantation promises restoration of cardiac function after myocardial infarction (MI). Comparison of intracoronary cell transplantation with skeletal myoblasts (SMs) versus bone marrow mesenchymal stem cells (BM-MSCs) was carried out in rabbits with MI induced by ligation of the left anterior descending artery. The infarction-affected artery was injected with SMs, BM-MSCs or cell-free medium (control) 24 h post-infarction (n = 15 per group). At baseline, there were no differences in cardiac parameters between the groups. At 4 weeks post-transplantation, left ventricular ejection fraction significantly improved and left ventricular end-diastolic diameter was significantly decreased in the cell-treated groups compared with pre-transplantation and the control group. Engrafted cells were found in all of the cell-treated rabbits. The cell-treated animals had significantly higher numbers of neovessels compared with the control. No significant difference was seen between the SM and BM-MSC groups. In conclusion, intra-coronary transplantation of SMs and BM-MSCs induced neoangiogenesis with comparable enhancements of cardiac performance and reduced cardiac remodelling in a rabbit MI model.


Hyperglycemia- and hyperinsulinemia-induced alteration of adiponectin receptor expression and adiponectin effects in L6 myoblasts.
Adiponectin has been shown to regulate glucose and fatty acid uptake and metabolism in skeletal muscle. Here we investigated the role of the recently cloned adiponectin receptor (AdipoR) isoforms in mediating effects of both globular (gAd) and full-length (fAd) adiponectin, and their regulation by hyperglycemia (25 mM, 20 h) and hyperinsulinemia (100 nM, 20 h). We used L6 rat skeletal muscle cells, which were found to express both AdipoR1 and AdipoR2 mRNA in a ratio of over 6:1 respectively. Hyperglycemia and hyperinsulinemia both decreased AdipoR1 receptor expression by approximately 50%, while the latter induced an increase of approximately threefold in AdipoR2 expression. The ability of gAd to increase GLUT4 myc translocation, glucose uptake, fatty acid uptake and oxidation, as well as AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, was decreased by both hyperglycemia and hyperinsulinemia. Interestingly, hyperinsulinemia induced the ability of fAd to elicit fatty acid uptake and enhanced fatty acid oxidation in response to fAd. In summary, our results suggest that both hyperglycemia and hyperinsulinemia cause gAd resistance in rat skeletal muscle cells. However, hyperinsulinemia induces a switch toward increased fAd sensitivity in these cells.


Ultraviolet light depletes surface markers of Langerhans cells.
This report defines the influence of ultraviolet light (UV) on Langerhans cells (LC). Human volunteers and hairless mice (Swiss ha/ha) were exposed to various single and/or cumulative doses of either UV-A, UV-B, or UV-A plus small amounts of UV-B (UV-A (+B)). 24 hr after the last irradiation, morphology of the entire epidermis was evaluated by both light and electron microscopy while LC, in addition, were tested for expression of specific histochemical (ATPase) and functional immunological markers (Ia antigens). In both men and mice, cumulative doses of either 80-120 J/cm2 UV-A (+B) or 1-2 X 100 J/cm2 UV-A resulted in a dramatic reduction of cells exhibiting ATPase and Ia-reactivity. In the UV-B spectrum, single doses of 60-80 mJ/cm2 produced a virtually complete elimination of LC membrane markers. By contrast, pemphigus antigens of keratinocytes were unaffected by these energy doses. Electron microscopy revealed cellular damage of some LC after UV-doses which produce a virtually complete abolition of LC membrane markers. At certain dose ranges (15-30 mJ/cm2 UV-B and 1 x 40 to 2 x 100 J/cm2 UV-A) LC were the only epidermal cells to display morphological damage at the ultrastructural level whereas higher doses affected all epidermal cells. The finding that LC surface markers and to a lesser extent the cells themselves are particularly susceptible to UV irradiation has important implications in view of previous findings that LC are potent stimulators of antigen-specific and allogeneic T cell activation. UV-induced alteration of LC plasma membrane integrity may represent a tool to manipulate adverse immune reactions involving the epidermis.


Spectroscopic and computational evidence for SO2 ionization on 128 K ice surface.
The experimental part of this study focuses on FTIR spectroscopy of SO(2) adsorbate on the surface of ice nanoparticles at 128 K, in the 0.5-1 monolayer coverage range. In addition to the infrared spectroscopic features due to molecular SO(2), a structured band is observed at approximately 1030 cm(-1). A similar band was observed in past spectroscopic studies of SO(2) aqueous solutions, and assigned to anionic products of SO(2) ionization. Ab initio normal mode analysis of HSO(3)(-) yielded intense SO stretch bands in the vicinity of the observed "ionic" feature. The relative intensities of the molecular and the anionic bands indicate that 0.3 approximately 0.5 of the adsorbate is ionized. These results are consistent with the previously published data on isotopic exchange in SO(2)-covered ice nanoparticles (Devlin and Buch, J. Chem. Phys., 2007, 127, 091101) which pointed towards substantial SO(2) ionization at low temperatures. Density functional theory modeling of molecular and ionized adsorbate on a crystal ice slab suggests that anion solvation by molecular SO(2) adsorbate facilitates the SO(2) ionization process at the ice surface.


Response accuracy of hazard identification in migrant farm workers.
This study assessed potential biases introduced by using maternal proxies for reporting work hazards, illness symptoms, and acute agricultural injuries in studies of migrant farmworker families. A convenience sample of 79 mother/spouse and mother/oldest child pairs was obtained from a two-year cohort study of migrant farmworker families from Starr County, Texas. Pairs completed an interviewer-administered survey including 27 close-ended items describing work history, illness symptoms, and acute injuries during the 2001 migration season. Data analysis included prevalence, sensitivity, and specificity measures. Maternal proxy reports of subjective symptoms of a spouse or child were approximately 50% lower than spouse or child self-reports. Sensitivity and specificity of mothers' responses regarding hazard items were higher for spouses than for children. For items measuring illness symptoms, sensitivity of mothers' responses for spouses and oldest child pairs was generally less than 30%; however, specificity was generally above 90%. For acute agricultural injury, the mother/spouse sensitivity was 75%, the mother/child 40%, and specificities were 100% and 97%, respectively. Sensitivity and specificity for mother/ spouse pairs was generally higher than mother/child pairs for work hazards, illness symptoms and acute injuries. While mothers may be acceptable proxies for spouses in this population, efforts should be made to collect data directly from adolescent children in studies of agricultural injuries.


Physicians helping the underserved: the Reach Out program.
In the current health care environment of competition and market forces, concern has arisen that the classic principle of serving disadvantaged persons may not be fulfilled due to pressures from managed care. Reach Out, a $12 million national program of the Robert Wood Johnson Foundation, was developed to recruit leaders from among practicing physicians to organize projects to care for the uninsured and underserved. Physician volunteerism was a key component of all projects. Thirty-nine Reach Out projects were implemented and carried out across the United States, with average funding per project of $300000 distributed over a period of 4 years. Seven model types emerged, the most common of which, the free clinic and the referral network, accounted for two thirds of the total. At the program's conclusion, 199584 patients were enrolled and 11252 physicians recruited. Project execution was more complex than initially supposed, and major progress commonly was not evident until the third or fourth year, but at least two thirds of the projects are likely to continue with local support. With strong physician leadership and a funded administrative core, organized community efforts can develop and sustain an effective program. Programs such as Reach Out cannot solve the national problem of access to health care, but they can make a small but important impact on the number of uninsured and underserved persons without access to health care.


Cytochemical and cytofluorometric evidence for guard cell photosystems.
Evidence for photosynthetic linear electron transport in guard cells was obtained with two sensitive methods of high spacial resolution. Light-dependent diaminobenzidine oxidation (an indicator of PSI) and DCMU-sensitive, light-dependent thiocarbamyl nitroblue tetrazolium reduction (an indicator of PSII) were observed in guard cell plastids of Hordeum vulgare L. cv Himalaya using electron microscopic cytochemical procedures. DCMU-sensitive Chl a fluorescence induction (an indicator of PSII) was detected in individual guard cell pairs of Vicia faba L. cv Longpod using an ultramicrofluorometer. At least for these species, we conclude these results are proof for the presence of PSII in guard cell chloroplasts, which until now has been somewhat controversial.


Suppression of Surface Oxygen on Nanocarbon Film Electrodes for Maintaining Electrode Activity.
We investigated sputtered nanocarbon films with respect to the effect of suppressing surface oxygen on their electrochemical properties. The nanocarbon film consisted of nanocrystallites with mixed sp2 and sp3 bonds formed by unbalanced magnetron sputtering. Ultraviolet/ozone (UV/O3) irradiation and electrochemical pretreatment (ECP) were conducted to change the surface oxygen concentration of nanocarbon film. X-ray photoelectron spectroscopy (XPS) measurements revealed that nanocarbon films with different amounts of surface oxygen could be prepared. In addition, we observed no significant increase of the surface roughness (Ra) at the angstrom level after treatments, owing to a stable structure containing 40% of sp3 bonds. The electrode characteristics, including the potential window and electrochemical properties for some redox species, such as Ru(NH3)63+/2+, were investigated. Some electrochemical measurements of zinc ions (Zn2+) and hydrogen peroxide (H2O2) showed that the electrochemical reaction was improved by suppressing the surface oxygen. These results clearly indicated that the low surface oxygen concentration plays an important role in these electrochemical reactions.


Perceptual "vowel spaces" of cochlear implant users: implications for the study of auditory adaptation to spectral shift.
Cochlear implant (CI) users differ in their ability to perceive and recognize speech sounds. Two possible reasons for such individual differences may lie in their ability to discriminate formant frequencies or to adapt to the spectrally shifted information presented by cochlear implants, a basalward shift related to the implant's depth of insertion in the cochlea. In the present study, we examined these two alternatives using a method-of-adjustment (MOA) procedure with 330 synthetic vowel stimuli varying in F1 and F2 that were arranged in a two-dimensional grid. Subjects were asked to label the synthetic stimuli that matched ten monophthongal vowels in visually presented words. Subjects then provided goodness ratings for the stimuli they had chosen. The subjects' responses to all ten vowels were used to construct individual perceptual "vowel spaces." If CI users fail to adapt completely to the basalward spectral shift, then the formant frequencies of their vowel categories should be shifted lower in both F1 and F2. However, with one exception, no systematic shifts were observed in the vowel spaces of CI users. Instead, the vowel spaces differed from one another in the relative size of their vowel categories. The results suggest that differences in formant frequency discrimination may account for the individual differences in vowel perception observed in cochlear implant users.


Effects of a health care provider intervention in reduction of sexual risk and related outcomes in economically marginal communities in Mumbai, India.
The present study assessed the effectiveness of a brief narrative intervention implemented by trained biomedical and Ayurveda, Yoga, Unani, Siddha, Homeopathy (AYUSH) providers from three low-income communities in Mumbai, India. A quasi-experimental research design compared attitudinal and behavioural changes among a cohort of 554 patients presenting gupt rog ('secret sexual illnesses') to biomedical and AYUSH providers who were trained in the narrative intervention model (NIM; referred to as 'narrative prevention counseling' in the intervention manual) with those providing standard care (untrained in NIM). Data were analysed using multivariate and longitudinal statistical models. Patients who received treatment for gupt rog from trained providers reported receiving a significantly higher number of services than those receiving services from untrained providers (mean 8.9 vs 7.6 services, respectively; P<0.001). In addition, a higher number of patients seeing the trained providers no longer had gupt rog problems than those seeing untrained providers (42% vs 25%, respectively; P<0.001). Patient-reported sex with a partner who was not the wife decreased significantly from baseline to follow-up for the entire sample but was significantly greater among patients receiving treatment from trained AYUSH providers (from 27% at baseline to 2% at follow up) compared with untrained providers (from 18% at baseline to 5% at follow up; P<0.001). The results support the effectiveness of brief narrative intervention in primary care settings for reducing sexual risk and associated vulnerabilities among married men.


Nucleotide sequence of the lipase gene lip2 from the antarctic psychrotroph Moraxella TA144 and site-specific mutagenesis of the conserved serine and histidine residues.
The lip2 gene from the antarctic psychotroph Moraxella TA144 was sequenced. The primary structure of the Lip2 preprotein deduced from the nucleotide sequence is composed of 433 amino acids with a predicted Mr of 47,222. This enzyme contains a Ser-centered consensus sequence and a conserved His-Gly dipeptide found in most lipase amino-terminal domains. These sequences are involved in the lipase active site conformation since substitution of the conserved Ser or His residues by Ala and Gln, respectively, results in the loss of both lipase and esterase activities. Structural factors that would allow proper enzyme flexibility at low temperatures are discussed. It is suggested that only subtle changes in the primary structure of these psychrotrophic enzymes can account for their ability to catalyze lipolysis at temperatures close to 0 degrees C.


Quantifying stent-induced damage in coronary arteries by investigating mechanical and structural alterations.
Vascular damage develops with diverging severity during and after percutaneous coronary intervention with stent placement and is the prevailing stimulus for in-stent restenosis. Previous work has failed to link mechanical data obtained in a realistic in vivo or in vitro environment with data collected during imaging processes. We investigated whether specimens of porcine right coronary arteries soften when indented with a stent strut shaped structure, and if the softening results from damage mechanisms inside the fibrillar collagen structure. To simulate the multiaxial loading scenario of a stented coronary artery, we developed the testing device 'LAESIO' that can measure differences in the stress-stretch behavior of the arterial wall before and after the indentation of a strut-like stamp. The testing protocol was optimized according to preliminary experiments, more specifically equilibrium and relaxation tests. After chemical fixation of the specimens and subsequent tissue clearing, we performed three-dimensional surface and second-harmonic generation scans on the deformed specimens. We analyzed and correlated the mechanical response with structural parameters of high-affected tissue located next to the stamp indentation and low-affected tissue beyond the injured area. The results reveal that damage mechanisms, like tissue compression as well as softening, fiber dispersion, and the lesion extent, are direction-dependent, and the severity of them is linked to the strut orientation, indentation pressure, and position. The findings highlight the need for further investigations by applying the proposed methods to human coronary arteries. Additional data and insights might help to incorporate the observed damage mechanisms into material models for finite element analyses to perform more accurate simulations of stent-implantations.


Is mutated serine hydroxymethyltransferase (SHMT) involved in the etiology of neural tube defects?
Neural tube defects (NTD) arise in the first weeks of pregnancy due to a combination of environmental and genetic factors. In mothers of children with NTD elevated homocysteine (Hcy) levels and decreased plasma folate levels were observed, which suggests a defect in the folate-dependent Hcy metabolism. Therefore, mutations in genes coding for enzymes of this metabolism could be involved in NTD. Serine hydroxymethyltransferase (SHMT) catalyzes the reversible reaction of serine and tetrahydrofolate (THF) to glycine and 5,10-methylene THF. Two different isoforms of SHMT are known, one is present in the cytosol (cSHMT) and the other in the mitochondrion (mSHMT). Theoretically, mutated SHMT could lead to elevated Hcy levels and to an altered distribution of the different folate derivatives and might therefore become a risk factor for NTD. This study concerns the molecular genetic analysis of genes coding for both isoforms of the SHMT enzyme by single-stranded conformation polymorphism analysis. Several mutations as well as polymorphisms were found in both genes. The relevance of two variations, the 1420 C>T mutation of the cytosolic isoform and the 4-bp deletion of the mitochondrial isoform (delTCTT 1721-1724), to NTD risk was tested in a study group, which consisted of 109 NTD patients, 120 mothers of children with NTD, and 420 controls. Neither of the two polymorphisms led to an increased risk of NTD. In mothers with the 1420 CC genotype, significant increased Hcy levels are present. Also, significantly decreased red blood cell folate and plasma folate levels were present in individuals with the 1420 CC genotype. Probably, the 1420 C>T polymorphism causes a shift in distribution of the different folate derivatives. The 4-bp deletion of the mSHMT gene did not lead to altered Hcy or folate levels. So far, the results of this study provide no direct evidence for a role of defective SHMT functioning in NTD. Still, the influence of the 1420 C>T polymorphism of the cSHMT gene on the folate-related risk of NTD needs further investigation.


Congenital abnormalities among children with cerebral palsy: More evidence for prenatal antecedents.
To investigate the association between cerebral palsy (CP) and congenital abnormalities among children with very low, low, and normal birth weight. A population-based, case-control study among the cohort of 155,636 live births delivered between 1983 and 1985 in 4 California counties. Children with moderate or severe congenital CP (n = 192) diagnosed by age 3 were identified from 2 California State service agencies, and 551 control children were randomly sampled from birth certificate files. Information on congenital abnormalities diagnosed by the age of 1 year was obtained from the California Birth Defects Monitoring Program registry. Odds ratios (OR) and 95% CIs were calculated to estimate risk for CP associated with congenital abnormalities. Among singletons, congenital abnormalities were present in 33 (19.2%) children with CP and 21 (4.3%) control children (OR = 5.2, 95% CI 2.8-9.7). For each birth weight group, the percent of children with congenital abnormalities among children with CP exceeded that among control children. Structural abnormalities of the central nervous system were more common among children with CP (OR = 16.2, 95% CI 5.8-49.3) than control children. In contrast, the percent of children with non-central nervous system abnormalities only was similar between case patients and control subjects. These findings provide further evidence that factors operating in the prenatal period contribute significantly to the etiology of CP.


Tip-Selective Growth of Silver on Gold Nanostars for Surface-Enhanced Raman Scattering.
Nanogaps as "hot spots" with highly localized surface plasmon can generate ultrastrong electromagnetic fields. Superior to the exterior nanogaps obtained via aggregation and self-assembly, interior nanogaps within Au and Ag nanostructures give stable and reproducible surface-enhanced Raman scattering (SERS) signals. However, the synthesis of nanostructures with interior hot spots is still challenging because of the lack of high-yield strategies and clear design principles. Herein, gold-silver nanoclusters (Au-Ag NCs) with multiple interior hot spots were fabricated as SERS platforms via selective growth of Ag nanoparticles on the tips of Au nanostars (Au NSs). Furthermore, the interior gap sizes of Au-Ag NCs can be facilely tuned by changing the amount of AgNO3 used. Upon 785 nm excitation, single Au-Ag NC350 exhibits 43-fold larger SERS enhancement factor and the optimal signal reproducibility relative to single Au NS. The SERS enhancement factors and signal reproducibility of Au-Ag NCs increase with the decrease of gap sizes. Collectively, the Au-Ag NCs could serve as a flexible, reproducible, and active platform for SERS investigation.


Ellagic acid and intestinal microflora metabolite urolithin A: A review on its sources, metabolic distribution, health benefits, and biotransformation.
Foods rich in ellagic tannins are first hydrolyzed into ellagic acid in the stomach and small intestine, and then converted into urolithins with high bioavailability by the intestinal flora. Urolithin has beneficially biological effects, it can induce adipocyte browning, improve cholesterol metabolism, inhibit graft tumor growth, relieve inflammation, and downregulate neuronal amyloid protein formation via the β3-AR/PKA/p38MAPK, ERK/AMPKα/SREBP1, PI3K/AKT/mTOR signaling pathways, and TLR4, AHR receptors. But differences have been reported in urolithin production capacity among different individuals. Thus, it is of great significance to explore the biological functions of urolithin, screen the strains responsible for biotransformation of urolithin, and explore the corresponding functional genes. Tannin acyl hydrolase can hydrolyze tannins into ellagic acid, and the genera Gordonibacter and Ellagibacter can metabolize ellagic acid into urolithins. Therefore, application of "single bacterium", "single bacterium + enzyme", and "microflora" can achieve biotransformation of urolithin A. In this review, the source and metabolic pathway of ellagic tannins, and the mechanisms of the biological function of a metabolite, urolithin A, are discussed. The current strategies of biotransformation to obtain urolithin A are expounded to provide ideas for further studies on the relationship between urolithin and human health.


Equilibrium and transient thermodynamics: A unified dissipaton-space approach.
This work presents a unified dissipaton-equation-of-motion (DEOM) theory and its evaluations on the Helmholtz free energy change due to the isotherm mixing of two isolated subsystems. One is a local impurity, and the other is a nonlocal Gaussian bath. DEOM constitutes a fundamental theory for such open quantum mixtures. To complete the theory, we also construct the imaginary-time DEOM formalism via an analytical continuation of dissipaton algebra, which would be limited to equilibrium thermodynamics. On the other hand, the real-time DEOM deals with both equilibrium structural and nonequilibrium dynamic properties. Its combination with the thermodynamic integral formalism would be a viable and accurate means to both equilibrium and transient thermodynamics. As illustrations, we report the numerical results on a spin-boson system, with elaborations on the underlying anharmonic features, the thermodynamic entropy vs the von Neumann entropy, and an indication of "solvent-cage" formation. Beside the required asymptotic equilibrium properties, the proposed transient thermodynamics also supports the basic spontaneity criterion.


Glomerular inflammation in pregnant rats after infusion of low dose endotoxin. An immunohistological study in experimental pre-eclampsia.
Increased endotoxin sensitivity during pregnancy occurs in many animals, including rats. The mechanism of this phenomenon is not understood. In the present study it was investigated whether this increased sensitivity is reflected by an altered inflammatory pattern. Inflammatory cell influx, the O2(-)-producing potential of these cells, and expression of adhesion molecules was studied in the glomeruli of pregnant and cyclic rats at various intervals after low dose endotoxin infusion. Kidney sections were stained for monocytes and adhesion molecules (ICAM-1, VCAM-1, LFA-1, and VLA-4) using monoclonals, while potentially O2(-)-producing neutrophils (ie, activated neutrophils) were quantified using immunohistochemical methods. The results show early glomerular influx of activated neutrophils, maximally 4 hours after endotoxin. Both absolute neutrophil counts and relative numbers of activated neutrophils were significantly increased in pregnant versus cyclic rats. In contrast to cyclic rats, showing transient monocyte influx, in pregnant endotoxin-treated rats monocyte influx reaches a maximum at t = 168 hours. These cell kinetics were paralleled by expression of the various adhesion molecules. It was concluded that pregnancy profoundly influences not only the inflammation kinetics after endotoxin, but also the violence of the reaction, reflected by activated neutrophils. This altered glomerular inflammatory pattern may help to explain why low dose endotoxin infusion induces pre-eclamptic-like symptoms (such as an intraglomerular prothrombotic microenvironment and proteinuria) exclusively in the pregnant rat.


Use of antibodies against the P36 protein of Mycoplasma hyopneumoniae for the identification of M. hyopneumoniae strains.
Mycoplasma hyopneumoniae, the principal aetiological agent of porcine enzootic pneumonia, synthesizes a 36 kDa protein (P36) which is an early and strong immunogenic factor in experimentally and naturally infected swine. Polyclonal antibodies were made against the recombinant P36 protein in rabbits and used for the identification of M. hyopneumoniae by the immunoblot technique. The proteins from the M. hyopneumoniae reference strains and from 13 M. hyopneumoniae field strains isolated from naturally infected pigs in Switzerland, Hungary, France and Canada were analysed by the immunoblot technique using anti-P36 antibodies. All 13 field strains and the three reference J strains of M. hyopneumoniae, received from different collections and laboratories, exhibited a strong reaction with a protein of 36 kDa indicating that the P36 protein is a common M. hyopneumoniae antigen. None of the different porcine Mycoplasma species including M. flocculare, M. hyorhinis, M. hyosynoviae, A. axanthum, A. laidlawii and A. granularum showed any reaction on the immunoblot with the anti-P36 antibodies. In addition, we have found no reaction with anti-P36 antibodies using 47 different Mycoplasma or Acholeplasma species isolated from human, mice, rat, poultry, ruminant, dog and cat. In conclusion we have shown that P36 is a protein that is a common antigen of M. hyopneumoniae strains and is not found in other Mycoplasma or Acholeplasma species tested. Because of its high specificity, P36 protein, or antibodies made against this protein can be used for the identification of M. hyopneumoniae strains.


The role of nucleus accumbens dopamine in motivated behavior: a unifying interpretation with special reference to reward-seeking.
Studies addressing behavioral functions of dopamine (DA) in the nucleus accumbens septi (NAS) are reviewed. A role of NAS DA in reward has long been suggested. However, some investigators have questioned the role of NAS DA in rewarding effects because of its role in aversive contexts. As findings supporting the role of NAS DA in mediating aversively motivated behaviors accumulate, it is necessary to accommodate such data for understanding the role of NAS DA in behavior. The aim of the present paper is to provide a unifying interpretation that can account for the functions of NAS DA in a variety of behavioral contexts: (1) its role in appetitive behavioral arousal, (2) its role as a facilitator as well as an inducer of reward processes, and (3) its presently undefined role in aversive contexts. The present analysis suggests that NAS DA plays an important role in sensorimotor integrations that facilitate flexible approach responses. Flexible approach responses are contrasted with fixed instrumental approach responses (habits), which may involve the nigro-striatal DA system more than the meso-accumbens DA system. Functional properties of NAS DA transmission are considered in two stages: unconditioned behavioral invigoration effects and incentive learning effects. (1) When organisms are presented with salient stimuli (e.g., novel stimuli and incentive stimuli), NAS DA is released and invigorates flexible approach responses (invigoration effects). (2) When proximal exteroceptive receptors are stimulated by unconditioned stimuli, NAS DA is released and enables stimulus representations to acquire incentive properties within specific environmental context. It is important to make a distinction that NAS DA is a critical component for the conditional formation of incentive representations but not the retrieval of incentive stimuli or behavioral expressions based on over-learned incentive responses (i.e., habits). Nor is NAS DA essential for the cognitive perception of environmental stimuli. Therefore, even without normal NAS DA transmission, the habit response system still allows animals to perform instrumental responses given that the tasks take place in fixed environment. Such a role of NAS DA as an incentive-property constructor is not limited to appetitive contexts but also aversive contexts. This dual action of NAS DA in invigoration and incentive learning may explain the rewarding effects of NAS DA as well as other effects of NAS DA in a variety of contexts including avoidance and unconditioned/conditioned increases in open-field locomotor activity. Particularly, the present hypothesis offers the following interpretation for the finding that both conditioned and unconditioned aversive stimuli stimulate DA release in the NAS: NAS DA invigorates approach responses toward 'safety'. Moreover, NAS DA modulates incentive properties of the environment so that organisms emit approach responses toward 'safety' (i.e., avoidance responses) when animals later encounter similar environmental contexts. There may be no obligatory relationship between NAS DA release and positive subjective effects, even though these systems probably interact with other brain systems which can mediate such effects. The present conceptual framework may be valuable in understanding the dynamic interplay of NAS DA neurochemistry and behavior, both normal and pathophysiological.


Peroxidase-like Active Nanomedicine with Dual Glutathione Depletion Property to Restore Oxaliplatin Chemosensitivity and Promote Programmed Cell Death.
The nanocatalytic activity of nanozymes provides a vision for tumor treatment. However, the glutathione (GSH)-related antioxidant defense system (ADS) formed on the basis of excessive GSH in the tumor microenvironment limits its catalytic activity. Here, dendritic mesoporous silica nanoparticles (DMSNs) were employed as nanocarrier; ultrasmall Fe3O4 nanoparticles, Mn2+ ions, and glutaminase inhibitor Telaglenastat (CB-839) were subsequently integrated into large mesopores of DMSNs, forming DMSN/Fe3O4-Mn@CB-839 (DFMC) nanomedicine. This nanomedicine exhibits peroxidase mimicking activities under acidic conditions, which catalyzes the decomposition of hydrogen peroxide (H2O2) into hydroxyl radical (•OH). This also promotes the formation of lipid peroxides, which is required for ferroptosis. Furthermore, this nanomedicine can effectively deplete the existing GSH, thereby enhancing reactive oxygen species (ROS)-mediated tumor catalytic therapy. Moreover, the introduced CB-839 blocks the endogenous synthesis of GSH, further enhancing GSH depletion performance, which reduces the excretion of oxaliplatin (GSH-related resistance) from tumor cells, thereby restoring the chemical sensitivity of oxaliplatin. The dual GSH depletion property significantly weakens the GSH-related ADS and restores the chemical sensitivity of oxaliplatin, leading to the high DFMC-induced apoptosis and ferroptosis of tumor cells. Our developed nanomedicine based on integrated nanotechnology and clinical drug may aid the development of tumor treatment.


Voltage-dependent inward currents of interstitial cells of Cajal from murine colon and small intestine.
Electrical slow waves in gastrointestinal (GI) muscles are generated by pacemaker cells, known as interstitial cells of Cajal (ICC). The pacemaker conductance is regulated by periodic release of Ca2+ from inositol 1,4,5-trisphosphate (IP(3)) receptor-operated stores, but little is known about how slow waves are actively propagated. We investigated voltage-dependent Ca2+ currents in cultured ICC from the murine colon and small intestine. ICC, identified by kit immunohistochemistry, were spontaneously active under current clamp and generated transient inward (pacemaker) currents under voltage clamp. Depolarization activated inward currents due to entry of Ca2+. Nicardipine (1 microM) blocked only half of the voltage-dependent inward current. After nicardipine, there was a shift in the potential at which peak current was obtained (-15 mV), and negative shifts in the voltage dependence of activation and inactivation of the remaining voltage-dependent inward current. The current that was resistant to dihydropyridine (I(VDDR)) displayed kinetics, ion selectivity and pharmacology that differed from dihydropyridine-sensitive Ca2+ currents. I(VDDR) was increased by elevating extracellular Ca2+ from 2 to 10 mM, and this caused a +30 mV shift in reversal potential. I(VDDR) was blocked by Ni2+ (100 microM) or mebefradil (1 microM) but was not affected by blockers of N-, P- or Q-type Ca2+ channels. Equimolar replacement of Ca2+ with Ba2+ reduced I(VDDR) without effects on inactivation kinetics. BayK8644 had significantly less effect on I(VDDR) than on I(VDIC). In summary, two components of inward Ca2+ current were resolved in ICC of murine small intestine and colon. Since slow waves persist in the presence of dihydropyridines, the dyhydropyridine-resistant component of inward current may contribute to slow wave propagation.


[Compliance Control Strategy in the Practical Randomized Controlled Trial Study of Electroacupuncture Combined with Behavior Control for Overweight and Simple Obesity].
Electroacupuncture (EA) has been extensively used in clinical treatment of obesity. The effectiveness relies not only on the correct diagnosis and rational treatment, but also on the voluntary cooperation of patients, that is the satisfactory compliance. The patient compliance refers to his/her submissiveness and executive ability to medical advice, which is the indispensable factor for the clinical efficacy. The strength of it depends on the patient himself/herself, and moreover is improved through some therapeutic strategies. Based on the emphasis of individual treatment in the real world, the practical randomized controlled trial (RCT) study pays attention to patient's compliance at the beginning of trial design. In this paper, in terms of the influential factors and control strategies, the compliance of simple obesity patient in the practical RCT study was summarized systematically.


Intradermal nodular fasciitis: a rare lesion analyzed in a series of 24 cases.
Nodular fasciitis, a benign myofibroblastic proliferation that usually occurs in the subcutaneous tissues of the upper extremities, trunk, as well as head and neck of young adults, is not widely recognized to arise primarily within the dermis. Here, we examined the clinicopathologic and immunohistochemical features of a series of 24 cases of intradermal nodular fasciitis retrieved from consult files. Clinical follow-up was obtained from medical records and referring physicians. Fourteen patients were females and 10 were males, with age ranging from 8 to 77 years (mean 27.5 y and median 22.5 y). Most patients presented with a rapidly growing painless solitary mass. Grossly, the lesions were solid, nodular, rubbery, or firm (mean size 1.96 cm and median 1.3 cm). Nine cases (37.5%) arose on limbs, 9 cases (37.5%) on the trunk, and 6 (25%) on the head and neck. All tumors were situated primarily in the dermis and were well circumscribed but unencapsulated. One case showed ill-defined margins. The epidermis was ulcerated in 11 cases. All tumors were composed of cytologically bland, uniform plump spindle cells with elongated, tapering nuclei, vesicular chromatin, small nucleoli, and palely eosinophilic cytoplasm, with no significant cytologic atypia or pleomorphism. These cells were arranged in short-intersecting bundles within a focally microcystic myxoid stroma, containing extravasated red blood cells and scattered lymphocytes. Mitoses ranged from 1 to 6 per 10 high-power fields (mean 2.5). All cases examined were diffusely positive for smooth muscle actin. Only one tumor "recurred" locally. No lesion metastasized. In summary, intradermal nodular fasciitis occurs most commonly on the limbs and trunk of young adults, shows morphologic features similar to nodular fasciitis at conventional sites and should not be confused with sarcoma.


Coumarin- and Carboxyl-Functionalized Supramolecular Polybenzoxazines Form Miscible Blends with Polyvinylpyrrolidone.
In this study, we synthesized a novel multifunctional benzoxazine monomer (Coumarin-COOH BZ), possessing both coumarin and COOH groups, through the reaction of 4-methyl-7-hydroxycoumarin, 4-aminobenzoic acid, and paraformaldehyde in 1,4-dioxane, with the structure confirmed using ¹H and 13C nuclear magnetic resonance and Fourier transform infrared (FTIR) spectroscopy. Differential scanning calorimetry (DSC), FTIR spectroscopy, and thermogravimetric analysis were then employed to monitor the thermal curing behavior of Coumarin-COOH BZ and its blends with poly(N-vinyl-2-pyrrolidone) (PVP), both before and after photodimerization of the coumarin moieties. DSC revealed a single glass transition temperature for each Coumarin-COOH BZ/PVP blend composition; a large positive deviation based on the Kwei equation suggested that strong hydrogen bonding existed between the Coumarin-COOH BZ and PVP segments, confirmed through FTIR spectroscopic analyses. The thermal properties improved (i.e., increased glass transition and thermal degradation temperatures) as a result of the increased crosslinking density after photodimerization under UV exposure.


Immunogenic and nondividing mafosfamide-treated L 1210 cells--comparison of lines resistant and nonresistant to cyclophosphamide.
Cyclophosphamide/mafosfamide-resistant L 1210 cell line [L 1210(Cy)R] was established from a sensitive parental line. The L 1210(Cy)R line was resistant to cyclophosphamide at the dose of 100 mg/kg. Cells of L 1210(Cy)R line were more immunogenic for semisyngeneic CD2F1, mice as compared with parental line. They grew slower in immunocompetent mice compared to immunosuppressed mice. It has been shown that L 1210(Cy)R cells treated with mafosfamide at high concentration not only retained immunogenicity but were even more immunogenic than parental L 1210 cells. In conclusion, it was possible to produce immunogenic, nondividing leukemia cells even when cells were resistant to the cytostatic used for cell modification.


Effect of basal and pulsatile LH release on FSH-stimulated follicle growth in ewes chronically treated with gonadotrophin-releasing hormone agonist.
Ewes chronically treated with gonadotrophin-releasing hormone (GnRH) agonist were used to investigate the importance of the peripheral concentration of LH in FSH-stimulated follicular development. Twenty-four Welsh Mountain ewes were treated with two agonist implants containing 3.3 mg buserelin. During week 6 of treatment all the ewes were given a 72-h continuous infusion of ovine FSH alone (3 micrograms/h) or FSH with large (7.5 micrograms)- or small (2.5 micrograms) amplitude pulses of ovine LH delivered at 4-hourly intervals. The importance of baseline LH throughout the FSH infusion was evaluated in six animals which were treated with a specific antiserum against bovine LH (LH-AS) 15-20 h before the start of FSH treatment. In the absence of LH-AS, infusion of FSH alone or with large or small pulses of LH stimulated the development of a normal number of small follicles (less than or equal to 2.5 mm in diameter) and large follicles (greater than 2.5 mm in diameter). These follicles had normal diameter and steroid secretion compared with control ewes on day 8 of the luteal phase. In contrast, the animals pretreated with LH-AS developed no follicles greater than 2.0 mm in diameter but the number of small follicles per ewe was significantly (P less than 0.05) increased. These results support the hypothesis that FSH in the absence of pulsatile LH release stimulates preovulatory follicular development in ewes treated with GnRH agonist. The follicular response to LH pulses of different amplitude is dependent on both the stage of development of the follicle and the peripheral concentration of FSH.(ABSTRACT TRUNCATED AT 250 WORDS)


Free energy landscapes of encounter complexes in protein-protein association.
We report the computer generation of a high-density map of the thermodynamic properties of the diffusion-accessible encounter conformations of four receptor-ligand protein pairs, and use it to study the electrostatic and desolvation components of the free energy of association. Encounter complex conformations are generated by sampling the translational/rotational space of the ligand around the receptor, both at 5-A and zero surface-to-surface separations. We find that partial desolvation is always an important effect, and it becomes dominant for complexes in which one of the reactants is neutral or weakly charged. The interaction provides a slowly varying attractive force over a small but significant region of the molecular surface. In complexes with no strong charge complementarity this region surrounds the binding site, and the orientation of the ligand in the encounter conformation with the lowest desolvation free energy is similar to the one observed in the fully formed complex. Complexes with strong opposite charges exhibit two types of behavior. In the first group, represented by barnase/barstar, electrostatics exerts strong orientational steering toward the binding site, and desolvation provides some added adhesion within the local region of low electrostatic energy. In the second group, represented by the complex of kallikrein and pancreatic trypsin inhibitor, the overall stability results from the rather nonspecific electrostatic attraction, whereas the affinity toward the binding region is determined by desolvation interactions.


Hemodynamic effects of chronic tetrandrine and propranolol administration on portal hypertensive rats.
The purpose of this study was to investigate the therapeutic effects of tetrandrine and propranolol, alone or in combination, on portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation in Sprague-Dawley rats. Animals were allocated into one of the four groups: vehicle group (0.1 N.HCl, 0.7 ml/day), tetrandrine group (50 mg/kg/ day), propranolol group (30 mg/kg/day), and tetrandrine (50 mg/kg/day) plus propranolol (30 mg/kg/day) group. Drug or vehicle was administered by gavage for consecutive 9 days. After 9 days of treatment, the portal venous pressure and mean arterial pressure in each treatment group were significantly lower than those in the vehicle group. The cardiac index was not changed by tetrandrine alone, but reduced in the two groups receiving propranolol alone or in combination. Total peripheral resistance was significantly decreased in the tetrandrine group and significantly increased in the tetrandrine plus propranolol group as compared with the vehicle group. Our results suggested that tetrandrine or propranolol alone induced portal hypotensive effects, with propranolol achieving better antihyperdynamic effects in terms of cardiac index, and in combination propranolol effects predominated over those of tetrandrine.


Carbon-Nanosheet Based Large-Area Electrochemical Capacitor that is Flexible, Foldable, Twistable, and Stretchable.
With the growing demand for wearable electronics, developing new compatible energy systems is a prominent topic of research. Energy systems mounted on wearable electronics should exhibit high cost efficiency, mechanical robustness, and high electrochemical activity. Herein, all-carbon-based large-area nanocomposites for freely deformable electrochemical capacitors are suggested to address these requirements. The three-dimensionally integrated, self-supported nanocomposites consist of activated carbons (ACs) distributed in direct spinning-derived carbon nanotube (DS-CNT) sheets without any additives, including conducting agents or binders. Owing to synergetic effects of the highly porous AC particles, high electron transport kinetics of CNTs, and facile ion accessibility resulting from acid treatment, the nanocomposites show a greatly improved specific capacitance of 128 F g-1 , compared to that of pristine ACs (62 F g-1 ), based on the total mass of the electrodes. The exceptional mechanical stability of the nanocomposites, which are attached on prestretched elastomer substrates, is confirmed; only a ≈15% increase in the electrical resistance is observed under a tensile strain of 100%, and the initial resistance is fully recovered after releasing. Finally, the outstanding durability and electrochemical performance of the deformable all-carbon-based symmetric capacitors under various mechanical deformations of bending, folding, twisting, and stretching are successfully demonstrated.


Effects of caregiver communication on the outcomes of requests in spouses with dementia of the Alzheimer type.
Three clinical and three matched nonclinical couples were studied for the effectiveness of their discourse in eliciting outcomes to requests made. Caregivers in the clinical couples were less likely to achieve successful outcomes than dominant communicators in the nonclinical couples. In studying the context for the requests, differences could not be attributed to the degree of concreteness of reference that was used by caregivers of spouses with Dementia of the Alzheimer type. More abstract and less abstract references were equally likely to be responded to by two of the three clinical couples. Differences in the styles of communication by the caregivers contributed to outcomes and reflected a self-reported degree of strain or comfort in the couples' relationships. Suggested is a method of study of outcomes that could be used in clinical assessment and intervention for nonresponsiveness and noncompliance with dementia patients.


Plant systemic induced responses mediate interactions between root parasitic nematodes and aboveground herbivorous insects.
Insects and nematodes are the most diverse and abundant groups of multicellular animals feeding on plants on either side of the soil-air interface. Several herbivore-induced responses are systemic, and hence can influence the preference and performance of organisms in other plant organs. Recent studies show that plants mediate interactions between belowground plant parasitic nematodes (PPNs) and aboveground herbivorous insects. Based on the knowledge of plant responses to pathogens, we review the emerging insights on plant systemic responses against root-feeding nematodes and shoot-feeding insects. We discuss the potential mechanisms of plant-mediated indirect interactions between both groups of organisms and point to gaps in our knowledge. Root-feeding nematodes can positively or negatively affect shoot herbivorous insects, and vice versa. The outcomes of the interactions between these spatially separated herbivore communities appear to be influenced by the feeding strategy of the nematodes and the insects, as well as by host plant susceptibility to both herbivores. The potential mechanisms for these interactions include systemic induced plant defense, interference with the translocation and dynamics of locally induced secondary metabolites, and reallocation of plant nutritional reserves. During evolution, PPNs as well as herbivorous insects have acquired effectors that modify plant defense responses and resource allocation patterns to their advantage. However, it is also known that plants under herbivore attack change the allocation of their resources, e.g., for compensatory growth responses, which may affect the performance of other organisms feeding on the plant. Studying the chemical and molecular basis of these interactions will reveal the molecular mechanisms that are involved. Moreover, it will lead to a better understanding of the ecological relevance of aboveground-belowground interactions, as well as support the development of sustainable pest management technologies.


Dissociation energetics of the phenol(+)⋯Ar(2) cluster ion: The role of π→H isomerization.
The dissociation energetics in the phenol(+)⋯Ar(2)(2π) cluster ion have been investigated using photoionization efficiency and mass analyzed threshold ionization spectroscopy. The appearance energies for the loss of one and two Ar atoms are determined as ∼210 and ∼1115 cm(-1), respectively. The difference between the appearance energy for the first Ar ligand in phenol(+)⋯Ar(2)(2π) and the dissociation energy of the phenol(+)⋯Ar(π) dimer (535cm(-1)) is explained by the isomerization of one π-bound Ar ligand to the OH binding site (H-bond) upon ionization. The energy difference between phenol(+)⋯Ar(2)(2π) and phenol(+)⋯Ar(2)(H/π) could also be estimated to be around 325cm(-1), which corresponds roughly to the difference of the binding energy of a π-bound and H-bound Ar ligands. The binding energy of the H-bound Ar atom in phenol(+)⋯Ar(2)(H/π) is derived to be ∼905cm(-1).


Direct observation of thiolate displacement reactions on Au(111): the role of physisorbed disulfides.
Line-of-sight mass spectroscopy (LOSMS) has been used to study the displacement reaction of ( radical3x radical3)R30 degrees methylthiolate on Au(111) by butylthiolate. The reaction was carried out at room temperature and constant saturation coverage, by exposing the methylthiolate-covered surface to dibutyl disulfide gas. The adsorbed methylthiolate was desorbed as dimethyl disulfide and the cross product methylbutyl disulfide, both identified by LOSMS. This shows that reaction occurs between adsorbed thiolates of different chain length at room temperature, while the kinetics indicate that a rapid equilibrium is established between immobile, chemisorbed thiolates, and highly mobile, physisorbed disulfides.


Proliferative effect and osteoinductive potential of extracellular matrix coated on cell culture plates.
Different cell/tissue derived extracellular matrix (ECM) display subtle differences that might provide important cues for proliferation and differentiation of cells in vitro or in vivo. However, the bioactivities of different ECMs in vitro were not fully understood. In this study, osteoblasts-derived and fibroblast-derived ECM-coated cell culture dishes were prepared respectively by culturing osteoblastic MC3T3-E1 cells and rat fibroblast then decellularizing the cultures. We investigated the bioactivities of the two different ECMs coated on cell culture plates using cellular, biochemical and molecular method. The proliferative activity of the bone marrow-derived mesenchymal stem cells (BMSCs) cultured on osteoblast-ECM was lower than for BMSCs grown on fibroblast-ECM. Compared with the BMSCs cultured on fibroblast-derived ECM, the cells grown on osteoblastic ECM showed enhanced alkaline phosphatase (ALP) activity, higher BMP-2 and osteopontin protein levels, increased secreted calcium content, and higher levels of runt-related transcriptional factor 2 (Runx 2) and osteocalcin (OCN) mRNA. Knockdown of BMP-2 or FGF-2 with shRNA transfection hardly effected osteoblastic differentiation or proliferation of MC3T3-E1 seeded on osteoblast-ECM or fibroblast-ECM. Therefore, the osteoblastic ECM had better osteoinductive potential and lower proliferative effect than fibroblastic ECM, and the two ECM presented enough bioactivity, knockdown of growth factors had no significant effect on differentiation and proliferation of re-seeded cells.


Effect of some acetylcholinesterase reactivators on human platelet aggregation in vitro.
Acetylcholinesterase (AChE) reactivators are employed for the prophylaxis and treatment of intoxications with organophosphorus AChE inhibitors, including nerve agents and pesticides. For the recovery of inhibited enzyme, derivatives from the group of pyridinium or bispyridinium aldoximes (called oximes) are used. Adverse effects of these substances are not well elucidated, because of their narrow and one-shot usage. Owing to this fact, the study evaluated the influence of some currently applied oximes on human platelet aggregation in vitro. The antiplatelet activity of pralidoxime, obidoxime, HI-6, methoxime and HLö 7 was assayed in human platelet rich plasma (2.5 x 10(8) platelets.ml(-1)) at a concentration of 1.35 mM. Arachidonic acid (AA), adenosine diphosphate (ADP), collagen (COL) and thrombin (TR) were used as agonists of platelet aggregation. All tested substances, except pralidoxime and methoxime, caused a significant inhibition of the aggregation process induced by AA, ADP and COL. Of the oximes assayed, none was found to influence TR triggered aggregation. Since reduced platelet aggregation can play an important role as an adverse effect in reactivator administration, further evaluation is needed for the estimation of the real impact of active oximes to the aggregation process in humans.


The CRP/FNR family protein Bcam1349 is a c-di-GMP effector that regulates biofilm formation in the respiratory pathogen Burkholderia cenocepacia.
Burkholderia cenocepacia is an opportunistic respiratory pathogen that can cause severe infections in immune-compromised individuals and is associated with poor prognosis for patients suffering from cystic fibrosis. The second messenger cyclic diguanosine monophosphate (c-di-GMP) has been shown to control a wide range of functions in bacteria, but little is known about these regulatory mechanisms in B. cenocepacia. Here we investigated the role that c-di-GMP plays in the regulation of biofilm formation and virulence in B. cenocepacia. Elevated intracellular levels of c-di-GMP promoted wrinkly colony, pellicle and biofilm formation in B. cenocepacia. A screen for transposon mutants unable to respond to elevated levels of c-di-GMP led to the identification of the mutant bcam1349 that did not display increased biofilm and pellicle formation with excessive c-di-GMP levels, and displayed a biofilm defect with physiological c-di-GMP levels. The bcam1349 gene is predicted to encode a transcriptional regulator of the CRP/FNR superfamily. Analyses of purified Bcam1349 protein and truncations demonstrated that it binds c-di-GMP in vitro. The Bcam1349 protein was shown to regulate the production of a number of components, including cellulose and fimbriae. It was demonstrated that the Bcam1349 protein binds to the promoter region of the cellulose synthase genes, and that this binding is enhanced by the presence of c-di-GMP. The bcam1349 mutant showed reduced virulence in a Galleria mellonella wax moth larvae infection model. Taken together, these findings suggest that the Bcam1349 protein is a transcriptional regulator that binds c-di-GMP and regulates biofilm formation and virulence in B. cenocepacia in response to the level of c-di-GMP.


Malignant peripheral nerve sheath tumor with primitive neuroepithelial differentiation in an adult: a case report.
Primitive neuroepithelial differentiation in malignant peripheral nerve sheath tumors (MPNSTs) has been reported in children but is extremely rare in adults. The authors report the case of a 70-year-old woman who presented with swelling of the right leg of 1-month duration. Fine-needle aspiration cytology was suggestive of a benign peripheral nerve sheath tumor. Histopathological examination of the excised mass revealed a MPNST with spindle-cell areas and a few round-cell areas with rosettes. The spindle cells showed positive immunoreactivity for S-100 protein and vimentin and negativity for desmin, confirming their nerve sheath origin. The round cells were immunoreactive for synaptophysin and chromogranin, indicating primitive neuroepithelial differentiation. These cells did not stain for CD99, which is consistently expressed by the cells of primitive neuroectodermal tumors (PNETs) of bone and soft tissue but not by central nervous system (CNS) PNETs or medulloblastomas. In this case, the PNET-like focus resembled a CNS-PNET.


Biosynthesis of gold nanoparticles using fungus Trichoderma sp. WL-Go and their catalysis in degradation of aromatic pollutants.
An efficient green method of gold nanoparticles (AuNPs) biosynthesis was achieved by cell-free extracts of fungus Trichoderma sp. WL-Go. Based on UV-Vis spectra, AuNPs biosynthesised by cell-free extracts with 90 mg/l protein exhibited a characteristic absorption band at 556 nm and was stable for 7 days. Transmission electron microscopy images revealed that the as-synthesised AuNPs were spherical and pseudo-spherical, and the average size was calculated to be 9.8 nm with a size range of 1-24 nm. The AuNPs illustrated their good catalytic activities for reduction of nitro-aromatics (2-nitrophenol, 3-nitrophenol, 4-nitrophenol, 2-nitroaniline, 3-nitroaniline) with catalytic rate constants of 7.4 × 10-3 s-1, 10.3 × 10-3 s-1, 4.9 × 10-3 s-1, 5.8 × 10-3 s-1, 15.0 × 10-3 s-1, respectively. Meanwhile, the AuNPs also showed excellent catalytic performance in decolourisation of azo dyes with decolourisation efficiency from 82.2 to 97.5%. This study provided a green gentle method for AuNPs synthesis as well as exhibiting efficient catalytic capability for degradation of aromatic pollutants.


Educational disparities in home smoking bans among households with underage children in the United States: can tobacco control policies help to narrow the gap?
The prevalence of home smoking bans in the United States has increased overtime, but educational disparities have persisted. Little research has explored potential associations between tobacco control policies and disparities by socioeconomic status in home smoking bans. We examined educational disparities in home smoking bans in the United States from 1995 to 2007 and investigated the association between these disparities and statewide tobacco control policies, including cigarette taxes, smoke-free air laws, and media campaigns. We used data from the 1995-1996, 1998-1999, 2001-2002, and 2006-2007 Current Population Survey's Tobacco Use Supplement surveys (TUS-CPS) and data on state-level tobacco control policies. Disparities by level of education were calculated, and logistic regressions were estimated to explore the association between statewide tobacco control policies and educational disparities in the adoption of complete home smoking bans. Between 1995 and 2007, average absolute educational disparities in complete home smoking bans between those with and without a college degree were 8.5 percentage points (pp) and 17.1 pp among nonsmoker and smoker households, respectively. The adjusted odds ratio for education increased among nonsmoker households over time (p < .01) but remained stable among households with smokers. Households with less than college were generally more responsive to antitobacco policies. Antitobacco media campaigns at the state level were associated with reduced disparities by education among households with smokers (p < .05). More vigorous tobacco control policies at the state level may help promote the adoption of home smoking bans and reduce educational disparities in these protective behaviors.


Evaluating psychosocial functioning in dental patients.
In order to make a reliable diagnosis and offer appropriate treatment, it is important that the dentist is aware of the role played by psychosocial factors in the origin and persistence of dental problems and has the ability to recognise their importance in the patient's overall presentation. This paper is an attempt to improve dentist's awareness of psychosocial issues and recognition of possible psychological problems in general dental practice. It focuses on directions for the gathering of information on patients through careful assessment prior to dental examination, covering patients biological or physical history and present symptoms, their social background, their psychological history and mental functioning, and the observation of their behaviour and mood. It is argued that interpreting these types of information will enable the dentist to be better prepared for any pitfalls that may arise in the course of treatment.


Permanent magnet electron beam ion source/trap systems with bakeable magnets for improved operation conditions.
The magnetic system of a Dresden electron beam ion source (EBIS) generating the necessary magnetic field with a new type of permanent magnet made of high energy density NdFeB-type material operable at temperatures above 100 °C has been investigated and tested. The employment of such kind of magnets provides simplified operation without the time-consuming installation and de-installation procedures of the magnets for the necessary baking of the ion source after commissioning and maintenance work. Furthermore, with the use of a new magnetization technique the geometrical filling factor of the magnetic Dresden EBIS design could be increased to a filling factor of 100% leading to an axial magnetic field strength of approximately 0.5 T exceeding the old design by 20%. Simulations using the finite element method software Field Precision and their results compared with measurements are presented as well. It could be shown that several baking cycles at temperatures higher than 100 °C did not change the magnetic properties of the setup.