Laparoscopic treatment for adult inguinal hernia with cryptorchidism: A case report.
Cryptorchidism or undescended testis is the most common disorder of male children, which is often diagnosed and treated during childhood. Adult patients with cryptorchidism are uncommon. Herein we report the case of adult inguinal hernia with cryptorchidism successfully treated by laparoscopic surgery simultaneously. We report a case of 68 year-old-man who was admitted to our hospital with a complaint of bulge and pain in the right groin area from 2 weeks before. CT or MRI revealed a right inguinal hernia and an undescended testis in the right inguinal canal. He was diagnosed with right inguinal hernia accompanied by cryptorchidism. Laparoscopic transabdominal preperitoneal repair (TAPP) and orchiectomy were performed simultaneously. Postoperative period was uneventful and he was discharged home on the 1st postoperative day. Pathological examination of the specimen was reported as atrophic testis with no malignancy. There has been no recurrence during a follow-up. To our Knowledge, the case report of adult inguinal hernia with cryptorchidism treated by laparoscopic surgery is rare. All cases recommended the feasibility of laparoscopic surgery. Adult inguinal hernia with cryptorchidism is a rare condition. TAPP and simultaneous laparoscopic orchiectomy for inguinal hernia with cryptorchidism were safe and feasible. It could be the first surgical option for the treatment of such adult patients.


Positive Mental Health Scale (PMHS) in Parents of Children with Cancer: A Psychometric Evaluation Using Item Response Theory.
Mental health is currently a public health issue worldwide. However, evidence is lacking regarding the validity of the instruments used to measure and assess positive mental health in specific populations. The objective of this study was to evaluate the psychometric properties of the PMHS using IRT. A cross-sectional retrospective study with non-probabilistic convenience sampling was conducted with 623 parents of children undergoing cancer treatment at the National Institute of Health in Mexico City. The participants responded to a battery of tests, including a sociodemographic questionnaire, the PMHS, Measurement Scale of Resilience, Beck Depression Inventory, Inventory of Quality of Life, Beck Anxiety Inventory, an interview regarding caregiver burden, and the World Health Organization Well-Being Index. PMHS responses were analyzed using Samejima's graded response model. The PMHS findings indicated that the IRT-based graded response model validated the single latent trait model. The scale scores were independent of depression, anxiety, well-being, caregiver burden, quality of life, and resilience. The PMHS scores were associated with low subjective well-being. The PMHS findings reveal that from an IRT-based perspective, this scale is unidimensional and is a valid, reliable, and culturally relevant instrument for assessing positive mental health in parents of children with chronic diseases.


Optimal timing of coronary artery bypass after acute myocardial infarction: a review of California discharge data.
The optimal timing for coronary artery bypass grafting after acute myocardial infarction is not well established. The California Discharge Database facilitates the study of this issue by providing data from a large patient cohort free of institutional bias. We examine the timing of coronary artery bypass grafting after acute myocardial infarction on short-term outcomes. We reviewed California Discharge Data to identify 40,159 patients who were hospitalized for acute myocardial infarction (day 0) and underwent subsequent coronary artery bypass grafting. Patients were stratified by the timing of coronary artery bypass grafting to "early" (days 0-2) and "late" groups (day 3 or later). The primary outcome variable was all-cause hospital mortality. Multiple logistic and linear regression and propensity analyses assessed the risk of adverse events, controlling for factors associated with preoperative clinical acuity, including the Charlson Comorbidity Index, shock, mechanical ventilation, and the use of intra-aortic balloon counterpulsation. Of 9476 patients identified, 4676 (49%) were in the early coronary artery bypass grafting group and 4800 (51%) were in the late coronary artery bypass grafting group. A total of 444 patients (4.7%) died during hospitalization, with a peak mortality rate of 8.2% among patients undergoing coronary artery bypass grafting on day 0, declining to a nadir of 3.0% among patients undergoing coronary artery bypass grafting on day 3. The mean time to coronary artery bypass grafting was 3.2 days. Patients undergoing early coronary artery bypass grafting experienced a higher mortality rate than those undergoing late coronary artery bypass grafting (5.6% vs 3.8%, P < .001). Early coronary artery bypass grafting was an independent predictor of mortality after controlling for clinical acuity and on propensity analysis (odds ratio 1.43, P = .003). Patients undergoing coronary artery bypass grafting within 2 days of hospitalization for acute myocardial infarction experienced higher mortality rates than those undergoing coronary artery bypass grafting 3 or more days after acute myocardial infarction, independently of clinical acuity. This suggests that coronary artery bypass grafting may best be deferred for 3 or more days after admission for acute myocardial infarction in nonurgent cases.


[The comparative characteristics of the immunomodulating properties of protein A from Staphylococcus aureus of different origins].
The immunomodulating properties of highly purified staphylococcal protein A and its analog obtained by gene engineering techniques have been compared with those of commercial preparations. The comparison has shown that the differences observed in this investigation may be explained by the presence of admixtures of staphylococcal nature in commercial preparations. The preparations of highly purified staphylococcal and recombinant protein A stimulate humoral immune response and the processes of phagocytosis and do not show mitogenic activity with respect to T cells. The conclusion on the identity of the immunomodulating activity of the preparations of natural and recombinant protein A has been made.


Effects of metal (Ag, Cd, Cr, Cu, Zn) exposures on some enzymatic and non-enzymatic indicators in the liver of Oreochromis niloticus.
Freshwater fish Oreochromis niloticus exposed to 0.05 microg/mL of Cu, Cd, Zn, Ag and Cr for up to 30 days. Only Ag, which exceeded environmentally realistic concentrations by a factor of >100 caused fish mortality within this period. Metals increased aspartate transaminase (AST) activity, while they decreased alanine transaminase (ALT) activity, except Cr exposure. Concentrations of free -SH group decreased whereas protein concentrations did not alter following metal exposures. Detectable metal accumulation occurred in the liver of Cd, Cu and Zn exposed fish. This study emphasized that both enzymatic and non-enzymatic mechanisms may be useful in understanding the degree of metal toxicity in fish liver.


Antagonism towards endogenous adenosine and inhibition of cGI-PDE in the cardiac effects of amrinone, milrinone and related analogues.
1. The effect of amrinone, milrinone and of three milrinone analogues was tested on spontaneous chronotropic and inotropic activity of guinea-pig isolated atria, on the activity of cGMP-inhibited phosphodiesterase (cGI-PDE) from guinea-pig heart and on specific binding of N6-cyclohexyl[3H]adenosine ([3H]CHA) to Ri adenosine receptors in guinea-pig atria. 2. The Ki-values towards [3H]CHA binding to Ri receptors were linearly related to the EC50S for the increase in force of contraction but not to the EC50S for the increase in frequency of the atria. The Ki values towards cGI-PDE were linearly related to the EC50S for the positive chronotropic effect.


Delivery of vanillin by poly(lactic-acid) nanoparticles: Development, characterization and in vitro evaluation of antioxidant activity.
Poly(lactic acid) (PLA) nanoparticles containing vanillin were prepared using an emulsion-solvent evaporation technique and were characterized and assessed for their in vitro antioxidant potential. Physicochemical properties of the nanoparticles were characterized by size, polydispersity index, zeta potential, encapsulation efficiency and stability. Solid state and thermal properties were assessed using X-ray diffraction and differential scanning calorimetry, while in vitro drug release profile was also evaluated. Results showed PLA nanoparticles having a characteristic amorphous structure, sizes in the range of 240 nm with high homogeneity in size distribution, zeta potential of -22 mV and vanillin encapsulation efficiency of 41%. In vitro release study showed a slow and sustained release of vanillin governed by diffusion. Nanoparticles were stable over a period of three months. Antioxidant ability of the vanillin-loaded PLA nanoparticles in scavenging the radical 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) was inferior to free vanillin and due to its prolonged release showed a profile that was both time and concentration dependent, while free vanillin showed concentration-dependent activity. The study concluded that PLA nanoparticles are potential carriers for vanillin delivery.


Influence of pore size on tensile strength, permeability and porosity of hyaluronan-collagen scaffolds.
Recent investigations have shown the importance of scaffold pore size on the realisation of tissue engineered cartilage which promotes cell adhesion, proliferation and differentiation. The objective of this study was to investigate the influence of pore size on the mechanical properties, the permeability and the porosity of hyaluronan-collagen scaffolds. Hyaluronan-collagen scaffolds with three different mean pore sizes (302.5, 402.5 and 525 microm) have been produced according to a standardised protocol. The maximum stress at rupture, the Young's Moduli, permeability and porosity of the scaffolds were investigated. The permeability was determined both empirically and mathematically. Increased pore sizes indicated a larger stress at rupture as well as increased Young's Moduli. Porosity and permeability were raised by increasing pore sizes. The mathematically calculated permeability showed the same trend. The results indicate a higher mechanical stability for scaffolds with larger pores. The experimental and mathematical experiments both show increased permeability and fluid mobility for larger pores in scaffolds. Morphological changes resulting from the alteration of pore size led to non-correlation between the calculated and the experimental permeability.


Development of a carbamate-conjugated catechol ligand and its application to Cs extraction from contaminated soil by using supercritical CO2.
Extraction of radioactive Cs from contaminated soil is a crucial aspect of remediation after nuclear accidents. For this purpose, we have developed a new type of ligand, carbamate-conjugated catechol, to assist in metal extraction by using supercritical CO2 (SCCO2). The synthesis process for this ligand is relatively simple, and the carbamate-conjugated catechol ligand dissolves well in SCCO2. The measured ligand distribution coefficient increased according to a power law with an exponent of 1.7 as the ligand concentration increased, indicating that approximately two ligand molecules are needed to extract one Cs ion. The roles of additives (ligand, co-ligand, and water) were limited when they were used separately, but the combination of these additives was important. We tested 27 combinations of these three additives for extracting Cs from artificially contaminated sea sand. A quantitative analysis indicated that the ligand had the strongest influence on Cs extraction, followed by water, and the co-ligand. The carbamate-conjugated catechol ligand was then used for Cs extraction from artificially contaminated real soil. Three types of soil were prepared: coarse soil (particle size = 0.5-1 mm), medium soil (particle size = 0.2-0.5 mm), and fine soil (particle size < 0.2 mm). The Cs fractions extracted from the coarse, medium, and fine soils were measured to be 95%, 91% and 70% of the Cs fraction extracted from sea sand, respectively, which indicates the existence of a surface area effect. Additionally, we suspect that Cs undergoes chemical interaction on the surface of real soil.


HIV-Related Skin Disease in the Era of Antiretroviral Therapy: Recognition and Management.
Antiretroviral therapy (ART) has revolutionized the treatment and prognosis of people living with HIV (PLHIV). With increased survival and improved overall health, PLHIV are experiencing dermatologic issues both specific to HIV and common to the general population. In this new era of ART, it is crucial for dermatologists to have a strong understanding of the broad range of cutaneous disease and treatment options in this unique population. In this review, we outline the most common skin diseases in PLHIV, including HIV-associated malignancies, inflammatory conditions, and infections, and focus on the role of ART in altering epidemiology, clinical features, diagnosis, and treatment of cutaneous conditions.


The prevention of experimentally induced necrotic enteritis in chickens by avoparcin.
Four groups of about seventy 2-week-old broiler chickens were challenged with a Clostridium perfringens Type A isolate. Inclusion of avoparcin at 20 ppm in feed prevented necrotic enteritis in one group, but 10 ppm was only marginally effective. Bacitracin at 110 ppm also prevented the disease. Necrotic enteritis was successfully reproduced in untreated control birds.


Comparison and evaluation of empirical zone settling velocity parameters based on sludge volume index using a unified settling characteristics database.
Over the past few decades classic and contemporary research on the process of secondary clarification in activated sludge plants has illuminated several aspects of the solids-flux theory which actually require a closer examination. Inter alia the most challenging and controversial part in the field has been the development of reliable models for the settling properties of the activated sludge in the settler. Numerous studies have been performed aiming at the evolvement of reliable mathematical formulas that would satisfactorily describe this behaviour, but no universally accepted solution seems to exist to date. That is mostly because different experimental conditions, sludge types and instrumentation have been employed, thus complicating the process of reaching a conclusive result. In order to bring theoretical and practical developments of secondary settling tank design and simulation closer together, a number of related tasks are addressed in this study by the use of an integrated and unified settling characteristics database. Several drawbacks and advantages of the methodologies published hitherto are examined on a universal basis and under the same assumptions in order to reveal artifacts that complicate the procedure of settling velocity estimation. It is suggested that universally accepted solutions may be feasible especially for design purposes. For simulation analysis real-time data of settling velocity should be tested rather than values derived from laboratory experiments which are shown to produce different results depending on the applied approach. In conclusion, an integrated database is proposed as a means for a more robust and universally accepted design procedure.


Fluorometric detection of adenine in target DNA by exciplex formation with fluorescent 8-arylethynylated deoxyguanosine.
We demonstrated an intriguing method to discriminate adenine by incident appearance of an intense new emission via exciplex formation in hybridization of target DNA with newly designed fluorescent 8-arylethynylated deoxyguanosine derivatives. We described the synthesis of such highly electron donating fluorescent guanosine derivatives and their incorporation into DNA oligomers which may be used for the structural study and the fluorometric analysis of nucleic acids.


Sofosbuvir plus ribavirin in treatment-naïve patients with chronic hepatitis C virus genotype 1 or 3 infection in India.
Until 2014, pegylated interferon plus ribavirin was the recommended standard of care for the treatment of chronic hepatitis C virus (HCV) infection in India. This open-label phase 3b study, conducted across 14 sites in India between 31 March 2014 and 30 November 2015, evaluated the efficacy and safety of sofosbuvir plus ribavirin therapy among treatment-naïve patients with chronic genotype 1 or 3 HCV infection. A total of 117 patients with genotype 1 or 3 HCV infection were randomized 1:1 to receive sofosbuvir 400 mg and weight-based ribavirin (1000 or 1200 mg) daily for 16 or 24 weeks. Among those with genotype 1 infection, the primary efficacy endpoint of sustained virologic response at 12 weeks post-treatment (SVR12) was reported in 90% (95% confidence intervals [CI], 73-98) and 96% (95% CI, 82-100) of patients following 16 and 24 weeks of treatment, respectively. For patients with genotype 3 infection, SVR12 rates were 100% (95% CI, 88-100) and 93% (95% CI, 78-99) after 16 and 24 weeks of therapy, respectively. Adverse events, most of which were mild or moderate in severity, occurred in 69% and 57% of patients receiving 16 and 24 weeks of treatment, respectively. The most common treatment-emergent adverse events were asthenia, headache and cough. Only one patient in the 24-week group discontinued treatment with sofosbuvir during this study. Overall, sofosbuvir plus ribavirin therapy achieved SVR12 rates ≥90% and was well tolerated among treatment-naïve patients with chronic genotype 1 or 3 HCV infection in India.


ZNF322A-mediated protein phosphorylation induces autophagosome formation through modulation of IRS1-AKT glucose uptake and HSP-elicited UPR in lung cancer.
ZNF322A is an oncogenic transcription factor that belongs to the Cys2His2-type zinc-finger protein family. Accumulating evidence suggests that ZNF322A may contribute to the tumorigenesis of lung cancer, however, the ZNF322A-mediated downstream signaling pathways remain unknown. To uncover ZNF322A-mediated functional network, we applied phosphopeptide enrichment and isobaric labeling strategies with mass spectrometry-based proteomics using A549 lung cancer cells, and analyzed the differentially expressed proteins of phosphoproteomic and proteomic profiles to determine ZNF322A-modulated pathways. ZNF322A highlighted a previously unidentified insulin signaling, heat stress, and signal attenuation at the post-translational level. Consistently, protein-phosphoprotein-kinase interaction network analysis revealed phosphorylation of IRS1 and HSP27 were altered upon ZNF322A-silenced lung cancer cells. Thus, we further investigated the molecular regulation of ZNF322A, and found the inhibitory transcriptional regulation of ZNF322A on PIM3, which was able to phosphorylate IRS1 at serine1101 in order to manipulate glucose uptake via the PI3K/AKT/mTOR signaling pathway. Moreover, ZNF322A also affects the unfolded protein response by phosphorylation of HSP27S82 and eIF2aS51, and triggers autophagosome formation in lung cancer cells. These findings not only give new information about the molecular regulation of the cellular proteins through ZNF322A at the post-translational level, but also provides a resource for the study of lung cancer therapy.


Antibodies with specificities to preselected protein regions evoked by free synthetic peptides representing protein antigenic sites or other surface locations: demonstration with myoglobin.
Previous studies have resulted in the determination of the entire structure of myoglobin. The present work was carried out to investigate the antigenicity of the synthetic antigenic sites and other surface peptides of Mb in their free form (i.e. without coupling to a carrier). Site 1 (peptide 15-22), site 2 (peptide 56-62), site 3 (peptide 94-100), site 4 (peptide 113-120), site 5 (peptide 145-151) and two surface peptides, peptide 1-6 and peptide 121-127, were injected in complete Freund's adjuvant into Balb/c mice. Radioimmune antibody binding studies showed that immunization with each of these peptides, in their free form, resulted in the formation of antibodies that bound specifically to Mb and to the immunizing peptide. The advantage and significance of these findings are discussed.


Allele-specific Expression Reveals Multiple Paths to Highland Adaptation in Maize.
Maize is a staple food of smallholder farmers living in highland regions up to 4,000 m above sea level worldwide. Mexican and South American highlands are two major highland maize growing regions, and population genetic data suggest the maize's adaptation to these regions occurred largely independently, providing a case study for convergent evolution. To better understand the mechanistic basis of highland adaptation, we crossed maize landraces from 108 highland and lowland sites of Mexico and South America with the inbred line B73 to produce F1 hybrids and grew them in both highland and lowland sites in Mexico. We identified thousands of genes with divergent expression between highland and lowland populations. Hundreds of these genes show patterns of convergent evolution between Mexico and South America. To dissect the genetic architecture of the divergent gene expression, we developed a novel allele-specific expression analysis pipeline to detect genes with divergent functional cis-regulatory variation between highland and lowland populations. We identified hundreds of genes with divergent cis-regulation between highland and lowland landrace alleles, with 20 in common between regions, further suggesting convergence in the genes underlying highland adaptation. Further analyses suggest multiple mechanisms contribute to this convergence in gene regulation. Although the vast majority of evolutionary changes associated with highland adaptation were region specific, our findings highlight an important role for convergence at the gene expression and gene regulation levels as well.


Carbon, oxygen and hydrogen isotope abundances inStylites reflect its unique physiology.
Natural abundances of oxygen-18, carbon-14, carbon-13 and deuterium were measured inStylites andicola, a terrestrial vascular plant lacking stomates, and two terrestrial plant species having stomates that grew nearby. No substantial differences in oxygen-18 and carbon-13 abundances were observed among the three species. The deuterium concentration inStylites was much higher than in the other species, confirming a previous report of CAM inStylites. Stylites was depleted in carbon-14 relative to the present day atmosphere, consistent with the proposal that it fixes CO2 derived from decomposing peat.


Analysis of the effect of Tenebrio Molitor rennet on the flavor formation of Cheddar cheese during ripening based on gas chromatography-ion mobility spectrometry (GC-IMS).
This study aimed to evaluate the potential application of Tenebrio Molitor rennet (TMR) in Cheddar cheese production, and to use gas chromatography-ion mobility spectrometry (GC-IMS) to monitor flavor compounds and fingerprints of cheese during ripening. The results indicated that Cheddar cheese prepared from TMR (TF) has fat content significantly lower than that of commercial rennet (CF) (p < 0.05). However, the results of the sensory evaluation showed that there were no statistically significant differences between the two kinds of cheese (p > 0.05). Both cheeses were rich in free amino acids and free fatty acids. Compared to the CF cheese, gamma-aminobutyric acid and Ornithine contents of the TF cheese reached 187 and 749 mg/kg, respectively, during 120 days of ripening. Moreover, GC-IMS provided information on the characteristics of 40 flavor substances (monomers and dimers) in the TF cheese during ripening. Only 30 flavor substances were identified in the CF cheese. The fingerprint of the two kinds of cheese during ripening can be established by GC-IMS and principal component analysis based on the identified flavor compounds. Therefore, TMR has potential application in Cheddar cheese production. GC-IMS might be applied for the quick, accurate and comprehensive monitoring of cheese flavor during ripening.


Angiotensin II induces podocyte metabolic reprogramming from glycolysis to glycerol-3-phosphate biosynthesis.
Recent studies have reported that Angiotensin II (Ang II) contributes to podocyte injury by interfering with metabolism. Glycolysis is essential for podocytes and glycolysis abnormality is associated with glomerular injury in chronic kidney disease (CKD). Glycerol-3-phosphate (G-3-P) biosynthesis is a shunt pathway of glycolysis, in which cytosolic glycerol-3-phosphate dehydrogenase 1 (GPD1) catalyzes dihydroxyacetone phosphate (DHAP) to generate G-3-P in the presence of the NADH. G-3-P is not only a substrate in glycerophospholipids and glyceride synthesis but also can be oxidated by mitochondrial glycerol-3-phosphate dehydrogenase (GPD2) to regenerate DHAP in mitochondria. Since G-3-P biosynthesis links to glycolysis, mitochondrial metabolism and lipid synthesis, we speculate G-3-P biosynthesis abnormality is probably involved in podocyte injury. In this study, we demonstrated that Ang II upregulated GPD1 expression and increased G-3-P and glycerophospholipid syntheses in podocytes. GPD1 knockdown protected podocytes from Ang II-induced lipid accumulation and mitochondrial dysfunction. GPD1 overexpression exacerbated Ang II-induced podocyte injury. In addition, we proved that lipid accumulation and mitochondrial dysfunction were correlated with G-3-P content in podocytes. These results suggest that Ang II upregulates GPD1 and promotes G-3-P biosynthesis in podocytes, which promote lipid accumulation and mitochondrial dysfunction in podocytes.


Osteoradionecrosis of sphenoid and temporal bones in a patient with maxillary sinus carcinoma: a case report.
A case of radionecrosis of sphenoid and temporal bones is reported. The patient received a combination of surgery, radiotherapy, and chemotherapy for his left maxillary sinus carcinoma. After the combined therapy, necrosis accompanying inflammation developed in the maxillary and temporal regions. Excision of the necrotic tissues was done, and the left ascending ramus of the mandible was resected because of persistent tumor mass at the left infratemporal fossa. Although the excision wound of the maxilla healed by epithelialization, an area of nonvital bone remained exposed in the temporal region, where progressive osteonecrosis with infection led to breakdown of the skin. The necrotic bones of the zygomatic arch and the sphenotemporal sutural region became visible through the skin defect, and computerized tomography scan revealed bone necrosis involving the inferolateral area and the base of the skull. Excision of the necrotic bone and reconstruction with sternocleidomastoid myocutaneous flap were performed.


Changes in the aortic and pulmonary diameters in a fetus with hypoplastic left heart syndrome.
We diagnosed hypoplastic left heart syndrome in a 26-week-old fetus using fetal echocardiography. Color Doppler ultrasonography was helpful for evaluating the structural abnormalities. The diameters of the aorta and the pulmonary artery were measured periodically from 26 to 38 weeks of gestation. Aortic diameter was below the normal range throughout gestation. The diameter of the pulmonary artery was normal at 26 weeks of gestation but gradually dilated and was abnormally dilated after the 36th week of gestation. Here we discuss the cause of enlarged pulmonary artery in fetal hypoplastic left heart syndrome.


Milestones for the Final Mile: Interspecialty Distinctions in Primary Palliative Care Skills Training.
Primary palliative care (PPC) skills are useful in a wide variety of medical and surgical specialties, and the expectations of PPC skill training are unknown across graduate medical education. We characterized the variation and quality of PPC skills in residency outcomes-based Accreditation Council for Graduate Medical Education (ACGME) milestones. We performed a content analysis with structured implicit review of 2015 ACGME milestone documents from 14 medical and surgical specialties chosen for their exposure to clinical situations requiring PPC. For each specialty milestone document, we characterized the variation and quality of PPC skills in residency outcomes-based ACGME milestones. We identified 959 occurrences of 29 palliative search terms within 14 specialty milestone documents. Within these milestone documents, implicit review characterized 104 milestones with direct saliency to PPC skills and 196 milestones with indirect saliency. Initial interrater agreement of the saliency rating among the primary reviewers was 89%. Specialty milestone documents varied widely in their incorporation of PPC skills within milestone documents. PPC milestones were most commonly found in milestone documents for Anesthesiology, Pediatrics, Urology, and Physical Medicine and Rehabilitation. PPC-relevant milestones were most commonly found in the Interpersonal and Communication Skills core competency with 108 (36%) relevant milestones classified under this core competency. Future revisions of specialty-specific ACGME milestone documents should focus on currently underrepresented, but important PPC skills.


Formulation, characterization and antimicrobial properties of black cumin essential oil nanoemulsions stabilized by OSA starch.
Preparation of oil-in-water nanoemulsions has emerged as a subject of interest for the encapsulation of lipophilic functional ingredients to increase their stability and activity. In this study, black cumin essential oil nanoemulsions (BCO-NE) using different ratios of essential oil with canola and flax seed oils (ripening inhibitors) were formulated and stabilized with octenyl succinic anhydride (OSA) modified waxy maize starch. The nanoemulsions exhibited monomodal size distributions with mean droplet diameter below 200 nm and zeta potential above -30, indicating a strong electrostatic repulsion between the dispersed oil droplets. Further, during storage (4 weeks at 25 °C ± 2) emulsions showed shear thinning phenomena and stability towards coalescence. Antimicrobial properties of nanoemulsions were determined by minimum inhibitory concentration and time-kill method against two Gram-positive bacterial (GPB) strains (Bacillus cereus and Listeria monocytogenes). Negatively charged BCO-NE showed prolonged bactericidal activities as compared to pure BCO due to better stability, controlled release and self-assembly with GPB cell membrane followed by destruction of cellular constituents. Our results suggest the application of BCO-NE may be exploited in aqueous food systems for extending the shelf life and other functional properties.


A randomized, controlled, double-blind, crossover trial of triheptanoin in alternating hemiplegia of childhood.
Based on the hypothesis of a brain energy deficit, we investigated the safety and efficacy of triheptanoin on paroxysmal episodes in patients with alternating hemiplegia of childhood due to ATP1A3 mutations. We conducted a randomized, double-blind, placebo-controlled crossover study of triheptanoin, at a target dose corresponding to 30% of daily calorie intake, in ten patients with alternating hemiplegia of childhood due to ATP1A3 mutations. Each treatment period consisted of a 12-week fixed-dose phase, separated by a 4-week washout period. The primary outcome was the total number of paroxysmal events. Secondary outcomes included the number of paroxysmal motor-epileptic events; a composite score taking into account the number, severity and duration of paroxysmal events; interictal neurological manifestations; the clinical global impression-improvement scale (CGI-I); and safety parameters. The paired non-parametric Wilcoxon test was used to analyze treatment effects. In an intention-to-treat analysis, triheptanoin failed to reduce the total number of paroxysmal events (p = 0.646), including motor-epileptic events (p = 0.585), or the composite score (p = 0.059). CGI-I score did not differ between triheptanoin and placebo periods. Triheptanoin was well tolerated. Triheptanoin does not prevent paroxysmal events in Alternating hemiplegia of childhood. We show the feasibility of a randomized placebo-controlled trial in this setting. The study has been registered with clinicaltrials.gov ( NCT002408354 ) the 03/24/2015.


Cytokine and chemokine mRNA expressing cells in muscle tissues of experimental autoimmune myasthenia gravis.
In-situ hybridization with labeled oligonucleotide probes was applied to explore cytokine and chemokine mRNA expression in sections of striated muscle, the target organ in experimental autoimmune myasthenia gravis (EAMG), induced in Lewis rats by immunization with acetylcholine receptor (AChR) and complete Freund's adjuvant (CFA). A transient burst of TNF-alpha, IL-1beta and IL-6 mRNA expressing cells was detected during the early phase of EAMG. This cytokine pattern was related to muscular infiltration of macrophages. Levels of IL-4, IL-10, IFN-gamma, cytolysin and TGF-beta mRNA expressing cells were low and observed mainly during the early phase of EAMG. C-C chemokine RANTES, MCP, MIP-1alpha and MIP-2 mRNA expressing cells were not detected over the course of EAMG. The low and transient expression of cytokines in EAMG muscle tissues suggests that the immune effector responses are unlikely operated by infiltrating cells in muscle. Muscular infiltrations in EAMG are unlikely due to local accumulation of C-C chemokines.


Improving awareness, accountability, and access through health coaching: qualitative study of patients' perspectives.
To assess patients' experiences with and perceptions of health coaching as part of their ongoing care. A qualitative research design using semistructured interviews that were recorded and transcribed verbatim.Setting Ottawa, Ont. Eleven patients (> 18 years of age) enrolled in a health coaching pilot program who were at risk of or diagnosed with type 2 diabetes. Patients' perspectives were assessed with semistructured interviews. Interviews were conducted with 11 patients at the end of the pilot program, using a stratified sampling approach to ensure maximum variation. All patients found the overall experience with the health coaching program to be positive. Patients believed the health coaching program was effective in increasing awareness of how diabetes affected their bodies and health, in building accountability for their health-related actions, and in improving access to care and other health resources. Patients perceive one-on-one health coaching as an acceptable intervention in their ongoing care. Patients enrolled in the health coaching pilot program believed that there was an improvement in access to care, health literacy, and accountability,all factors considered to be precursors to behavioural change.


Migraine incidence in 5 years: a population-based prospective longitudinal study in Turkey.
The incidence of migraine has been investigated only in a few studies worldwide and it is not known in our country. We, therefore, aimed to estimate the migraine incidence in a previously accomplished population-based prevalence study sample of 5323 individuals in the year 2008. The former Turkish headache prevalence study has been completed as a nationwide, randomized, home-based study of face-to-face examination by physicians trained for headache diagnosis by using ICHD criteria. Five years after this study an optimized survey including 50 questions was performed to estimate the migraine incidence in migraine-free individuals in the previous study, with a 56.4 % responder rate. Two validation studies for this survey were performed prior and after the study each in 100 subjects by comparing the gold standard of expert diagnosis of headache, showing high rate of reliability (Crohnbach alpha: 0.911 and 0.706, respectively). Migraine incidence was estimated as 2.38 % (2.98 % in women and 1.93 % in men) per year in 2563 migraine-free individuals; if the population at risk is defined as the group without any headaches, the migraine incidence decreased to 1.99 %. The chronic migraine (CM) incidence [without medication overuse (MOH)] was 0.066 % and that of MOH was 0.259 %. We found a significant burden of the disease on the occupational functionality as well as on social and family life, even in the early years of the migraine. The family history of headaches especially in the fathers could be useful to predict new cases of migraine, besides the well-known risk factor, diagnosis of depression, whereas income and education did not seem to relate to migraine onset. Our study with a large population-based nation-wide sample, using ICHD-II criteria, with structured headache interviews as well as blinded re-validation of the questionnaire diagnoses showed a 2.38 % incidence rate of migraine in Turkey, higher than most of the other previous reports; a finding which could be related to genetic factors and also to the methodological differences in the study designs. Moreover the incidence of CM was found to be 0.066 %.


Histochemical changes of carbohydrate and protein contents in the digestive gland cells of the land snail Monacha cartusiana following starvation.
The present study was designed to investigate histochemically the detection of carbohydrate and protein in the normally feeding snails and after 15 and 30 days of starvation. Generally, abundant carbohydrate and protein materials were detected in the component cells of the digestive gland of normally feeding snails. The results of this investigation revealed a pronounced decline of carbohydrates in the digestive gland cells of Monacha cartusiana snails after starvation. Severe decline in carbohydrate content was observed especially after 30 days of starvation. Moreover, protein inclusions have exhibited a week stainability in the digestive gland cells of these snails as a consequence of starvation.


[Renovascular hypertension secondary to Takayasu arteritis].
Secondary arterial hypertension (HT) is an increase in blood pressure due to a recognisable cause. It is estimated that the prevalence of people with HT is around 5%-15%. The search for secondary HT in all hypertensive patients is neither feasible nor cost-effective. However, there are a series of signs that force us to discount its diagnosis such as newly diagnosed hypertension before the age of 40, acute worsening of hypertension, resistant hypertension, the presence of extensive organ injury or clinical-analytical alterations, etc. It is important to diagnosis these patients since treatments can be curative, especially in young people. We present the case of a 46-year-old man with hypertensive emergency and subarachnoid haemorrhage due to aneurysmal rupture. The study of secondary causes was diagnostic for renal artery stenosis due to Takayasu arteritis in the scarring stage.


Effects of octreotide therapy in progressive head and neck paragangliomas: case series.
Octreotide, a somatostatin analog, may be beneficial in the treatment of head and neck paragangliomas (HNPGLs). We conducted a nonblinded, prospective intervention study. During 1 year, patients received a monthly intramuscular injection of 30 mg octreotide. Pretreatment and posttreatment tumor volumes were assessed by MRI, urinary catecholamine secretion was measured, and HNPGL-related signs and symptoms were recorded. In 1 of 4 included patients with HNPGL, a stabilization of tumor growth was observed after octreotide therapy. In 1 patient, octreotide therapy was discontinued before the end of the study because of potential side effects. No improvements in HNPGL-related signs and symptoms were observed. In 1 of 4 patients, HNPGL tumor growth velocity was reduced after octreotide therapy. Research assessing the effects of somatostatin analogues targeting different somatostatin receptor subtypes or combined with other therapies may offer new possibilities for the treatment of HNPGLs.


Ductal carcinoma in situ arising from fibroadenoma; a rare case with review of literature.
ibroadenoma (FA) is a common benign breast mass representing a group of hyperplastic breast lobules due to the deviation of normal development. This study aims to present a rare case of ductal carcinoma in situ (DCIS) associated with fibroadenoma. A 49-year-old married female presents with a right breast mass for five years. Core needle biopsy diagnosed the specimen as cellular complex fibroadenoma. A breast-lumpectomy and the histopathological examination of the surgical specimen confirmed ductal carcinoma in-situ. Malignant changes within fibroadenomas typically happen at an older age, with the age of detection in the fifth decade. Complex fibroadenomas are more related to malignant transformation. Old age and strong family history are risk factors for malignant transformation of fibroadenomas. Fibroadenomas are common benign tumors. They can rarely be associated with DCIS. Therefore, the risk of malignancy should always be kept in mind.


New species of Euschistus (Euschistus) from Jamaica, Euschistus (Mitripus) and Ladeaschistus from southern South America (Hemiptera: Heteroptera: Pentatomidae: Pentatominae).
Three new species of the Carpocorini are described: Euschistus (Euschistus) baranowskii Eger & Bianchi sp. nov. from Jamaica, Euschistus (Mitripus) saramagoi Bianchi, Cioato & Grazia sp. nov. from Brazil, and Ladeaschistus borgesi Bianchi, Cioato & Grazia sp. nov. from Argentina, Bolivia and Brazil. Comparative illustrations of external and internal genitalia of the species are provided.


Variational principle for limit cycles of the Rayleigh-van der Pol equation.
We show that the amplitude of the limit cycle of Rayleigh's equation can be obtained from a variational principle. We use this principle to reobtain the asymptotic values for the period and amplitude of the Rayleigh and van der Pol equations. Limit cycles of general Liénard systems can also be derived from a variational principle.


Uncovering transformation products of four organic contaminants of concern by photodegradation experiments and analysis of real samples from a local river.
In this study, photodegradation experiments simulating the exposure conditions of sunlight on the commonly detected in surface and wastewater contaminants atorvastatin (ATV), bezafibrate (BEZ), oxybenzone (OXZ), and tris(2-butoxyethyl)phosphate (TBEP) were conducted as the fate of these compounds and their transformation products (TPs) was followed. Then a nontargeted analysis was carried out on an urban river to confirm the environmental occurrence of the TPs after which the ECOSAR software was used to generate predicted effect levels of toxicity of the detected TPs on aquatic organisms. Five TPs of ATV were tentatively identified including two stable ones at the end of the experiment: ATV_TP557a and ATV_TP575, that were the product of hydroxylation. Complete degradation of OXZ was observed in the experiment with no significant TP identified. BEZ remained stable and largely undegraded at the end of the exposure. Five TPs of TBEP were found including four that were stable at the end of the experiment: TBEP_TP413, TBEP_TP415, TBEP_TP429, and TBEP_TP343. In the nontargeted analysis, ATV_TP557b, a positional isomer of ATV_TP557a, ATV_TP575 and the 5 TPs of TBEP were tentatively identified. The predicted concentration for effect levels were lower for ATV_TP557b compared to ATV indicating the TP is potentially more toxic than the parent compound. All the TPs of TBEP showed lower predicted toxicity toward aquatic organisms than their parent compound. These results highlight the importance of conducting complete workflows from laboratory experiments, followed by nontargeted analysis to confirm environmental occurrence to end with predicted toxicity to better communicate concern of the newfound TPs to monitoring programs.


Efficacy and hypnotic effects of melatonin in shift-work nurses: double-blind, placebo-controlled crossover trial.
Night work is associated with disturbed sleep and wakefulness, particularly in relation to the night shift. Circadian rhythm sleep disorders are characterized by complaints of insomnia and excessive daytime sleepiness that are primarily due to alterations in the internal circadian timing system or a misalignment between the timing of sleep and the 24-h social and physical environment. We evaluated the effect of oral intake of 5 mg melatonin taken 30 minutes before night time sleep on insomnia parameters as well as subjective sleep onset latency, number of awakenings, and duration of sleep. A double-blind, randomized, placebo-controlled crossover study with periods of 1 night and washouts of 4 days comparing melatonin with placebo tablets was conducted. We tried to improve night-time sleep during recovery from night work. Participants were 86 shift-worker nurses aged 24 to 46 years. Each participant completed a questionnaire immediately after awakening. Sleep onset latency was significantly reduced while subjects were taking melatonin as compared with both placebo and baseline. There was no evidence that melatonin altered total sleep time (as compared with baseline total sleep time). No adverse effects of melatonin were noted during the treatment period. Melatonin may be an effective treatment for shift workers with difficulty falling asleep.


Effects of strobilurin containing fungicides on the deoxynivalenol content in winter wheat.
The effects of the strobilurin fungicides Juwel, Juwel Top and Amistar on the deoxynivalenol contamination of winter wheat was studied in field experiments. In general, the application of strobilurins during stem elongation and inflorescence emergence of wheat resulted in increased deoxynivalenol contents in kernels as compared with the untreated control. This stimulating effect can be reversed by a following azole fungicide applied within a time period of one week during the stages of flowering.


Property improvement of biodegradable citric acid-crosslinked rice starch films by calcium oxide.
Due to several important limitations for packaging applications of starch film such as strength and hydrophilicity, rice starch (Oryza sativa) film was crosslinked with citric acid and modified by different contents of calcium oxide. FTIR spectra showed the evidence of crosslinking by citric acid and the presence of calcium oxide in the modified rice starch films. After the crosslinking, the decrease of degree of crystallinity and swelling including the increase of film smoothness and strain at maximum load were observed. The application of both citric acid and calcium oxide caused greater decrease of swelling, moisture uptake as well as higher stiffness and antibacterial activity than those of the use of only the citric acid. The highest stiffness and antibacterial activity were found for the crosslinked film added by 5 wt% calcium oxide. Moreover, the effect of calcium oxide contents on morphological, thermal and biodegradable properties of the crosslinked films was also investigated.


The associations between US state and local social spending, income inequality, and individual all-cause and cause-specific mortality: The National Longitudinal Mortality Study.
To investigate government state and local spending on public goods and income inequality as predictors of the risks of dying. Data on 431,637 adults aged 30-74 and 375,354 adults aged 20-44 in the 48 contiguous US states were used from the National Longitudinal Mortality Study to estimate the impacts of state and local spending and income inequality on individual risks of all-cause and cause-specific mortality for leading causes of death in younger and middle-aged adults and older adults. To reduce bias, models incorporated state fixed effects and instrumental variables. Each additional $250 per capita per year spent on welfare predicted a 3-percentage point (-0.031, 95% CI: -0.059, -0.0027) lower probability of dying from any cause. Each additional $250 per capita spent on welfare and education predicted 1.6-percentage point (-0.016, 95% CI: -0.031, -0.0011) and 0.8-percentage point (-0.008, 95% CI: -0.0156, -0.00024) lower probabilities of dying from coronary heart disease (CHD), respectively. No associations were found for colon cancer or chronic obstructive pulmonary disease; for diabetes, external injury, and suicide, estimates were inverse but modest in magnitude. A 0.1 higher Gini coefficient (higher income inequality) predicted 1-percentage point (0.010, 95% CI: 0.0026, 0.0180) and 0.2-percentage point (0.002, 95% CI: 0.001, 0.002) higher probabilities of dying from CHD and suicide, respectively. Empirical linkages were identified between state-level spending on welfare and education and lower individual risks of dying, particularly from CHD and all causes combined. State-level income inequality predicted higher risks of dying from CHD and suicide.


Phosphonormalizer: an R package for normalization of MS-based label-free phosphoproteomics.
Global centering-based normalization is a commonly used normalization approach in mass spectrometry-based label-free proteomics. It scales the peptide abundances to have the same median intensities, based on an assumption that the majority of abundances remain the same across the samples. However, especially in phosphoproteomics, this assumption can introduce bias, as the samples are enriched during sample preparation which can mask the underlying biological changes. To address this possible bias, phosphopeptides quantified in both enriched and non-enriched samples can be used to calculate factors that mitigate the bias. We present an R package phosphonormalizer for normalizing enriched samples in label-free mass spectrometry-based phosphoproteomics. The phosphonormalizer package is freely available under GPL ( > =2) license from Bioconductor (https://bioconductor.org/packages/phosphonormalizer). firstname.lastname@example.com or email@example.com. Supplementary data are available at Bioinformatics online.


Lab-made 3D-printed accessories for spectroscopy and spectroelectrochemistry: a proof of concept to investigate dynamic interfacial and surface phenomena.
3D printing is presented as an auspicious additive manufacturing technique for diverse interesting applications coupling electrochemistry and spectroscopy techniques, proposing as utilities: a general-purpose module for specular spectroscopy and spectroelectrochemical (SEC) cells for in situ UV-VIS and Raman measures capable of acting in flux or a stationary regime. As a proof of concept, UV-VIS absorption and middle-infrared spectra of an azo dye thin film were collected with the specular module showing characteristic bands according to the literature data. SEC investigations related to the Prussian Blue (PB) film growth on the platinum electrode surface were also investigated. By applying appropriate potentials, the PB film growth was accompanied by a proportional increase in the absorption signal at 700 nm in the UV-VIS region. This signal was related to the intervalence charge transfer from the Fe(II)-C to Fe(III)-N. Moreover, the Raman SEC experiment presented scattering intensity at 2092 and 2156 cm-1, related to the (CN) mode associated with the Fe(II) and Fe(III) cations, which was observed during the thin film growth. In addition, the conversion to the Berlin Green (BG) and Prussian White (PB) forms was monitored while applying the suitable potential and in situ spectroscopic observations of structural changes during the redox processes were also detected as described in the literature. Thus, it is possible to state that the accessories successfully validated in situ spectroelectrochemical dynamic investigations unlocking many other applications in this research field.


A new synthetic toll-like receptor 1/2 ligand is an efficient adjuvant for peptide vaccination in a human volunteer.
We previously showed that the bacterial lipopeptide Pam3Cys-Ser-Ser, meanwhile established as a toll-like receptor (TLR) 1/2 ligand, acts as a strong adjuvant for the induction of virus specific CD8+ T cells in mice, when covalently coupled to a synthetic peptide. We now designed a new water-soluble synthetic Pam3Cys-derivative, named XS15 and characterized it in vitro by a TLR2 NF-κB luciferase reporter assay. Further, the capacity of XS15 to activate immune cells and stimulate peptide-specific CD8+ T and NK cells by 6-sulfo LacNAc+ monocytes was assessed by flow cytometry as well as cytokine induction using immunoassays. The induction of a functional immune response after vaccination of a volunteer with viral peptides was assessed by ELISpot assay and flow cytometry in peripheral blood cells and infiltrating cells at the vaccination site, as well as by immunohistochemistry and imaging. XS15 induced strong ex vivo CD8+ and TH1 CD4+ responses in a human volunteer upon a single injection of XS15 mixed to uncoupled peptides in a water-in-oil emulsion (Montanide™ ISA51 VG). A granuloma formed locally at the injection site containing highly activated functional CD4+ and CD8+ effector memory T cells. The total number of vaccine peptide-specific functional T cells was experimentally assessed and estimated to be 3.0 × 105 in the granuloma and 20.5 × 106 in peripheral blood. Thus, in one volunteer we show a granuloma forming by peptides combined with an efficient adjuvant in a water-in-oil-emulsion, inducing antigen specific T cells detectable in circulation and at the vaccination site, after one single vaccination only. The ex vivo T cell responses in peripheral blood were detectable for more than one year and could be strongly boosted by a second vaccination. Hence, XS15 is a promising adjuvant candidate for peptide vaccination, in particular for tumor peptide vaccines in a personalized setting.


Synergistic stabilization of oil in water emulsion with chitin particles and tannic acid.
The aim of the present study was to explore the effect of CP and TA on stability of oil in water emulsion stabilized by the two components, so as to fabricate the most efficient chitin based emulsifying agents. It was found that there was synergistic effect for CP and TA in stabilizing emulsion, specifically, the complex of chitin particles (CP) (3 g/L) with tannic acid (TA) (2 g/L) produced the most physically and oxidatively stable oil-in-water emulsion compared with other groups in this study. This is because CP-TA (3/5) complex had the lowest zeta potential, the lowest the oil water interfacial tension, the highest viscosity and the highest content of TA with excellent antioxidant activity. Furthermore, this is because there was intense interaction between CP and TA in CP-TA complex from results of FTIR, XRD and ITC, which then result in the formation of large CP-TA particles.


Enzymatic production of L-tryptophan from DL-serine and indole by a coupled reaction of tryptophan synthase and amino acid racemase.
Enzymatic production of L-tryptophan from DL-serine and indole by a coupled reaction of tryptophan synthase and amino acid racemase was studied. The tryptophan synthase (EC 126.96.36.199) of Escherichia coli catalyzed beta-substitution reaction of L-serine into L-tryptophan and the amino acid racemase (EC 188.8.131.52) of Pseudomonas putida catalyzed the racemization of D-serine simultaneously in one reactor. Under optimal conditions established for L-tryptophan production, a large-scale production of L-tryptophan was carried out in a 200-liter reactor using intact cells of E. coli and P. putida. After 24 h of incubation with intermittent indole feeding, 110 g liter-1 of L-tryptophan was formed in molar yields of 91 and 100% for added DL-serine and indole, respectively. Continuous production of L-tryptophan was also carried out using immobilized cells of E. coli and P. putida. The maximum concentration of L-tryptophan formed was 5.2 g liter-1 (99% molar yield for indole), and the concentration decreased to 4.2 g liter-1 after continuous operation for 20 days.


Patient information in the light of quality assurance.
The relationship between patients and doctors has markedly changed over the last century. While until the turn of the 19th/20th century the patient was considered an object upon whom the doctor had the right to exert his art, the patient was then thought to have an integrity which the doctor could only legally injure with the consent of the patient. This was reflected in many court rulings, e.g. in Germany in 1894, requesting a doctor to inform the patient about therapy before performing surgery or even before giving medication, but also before performing invasive diagnostic procedures. The intensity of information required by law/court to be given to the patient varies also over time. Details of the implications to today's medical treatments are discussed.


Mechanistic insights into the effect of poly ferric sulfate on anaerobic digestion of waste activated sludge.
Poly ferric sulfate (PFS), one of the typical inorganic flocculants widely used in wastewater management and waste activated sludge (WAS) dewatering, could be accumulated in WAS and inevitably entered in anaerobic digestion system at high levels. However, knowledge about its impact on methane production is virtually absent. This study therefore aims to fill this gap and provide insights into the mechanisms involved through both batch and long-term tests using either real WAS or synthetic wastewaters as the digestion substrates. Experimental results showed that the maximum methane potential and production rate of WAS was respectively retarded by 39.0% and 66.4%, whereas the lag phase was extended by 237.0% at PFS of 40 g per kg of total solids. Mechanism explorations exhibited that PFS induced the physical enmeshment and disrupted the enzyme activity involved in anaerobic digestion, resulting in an inhibitory state of the bioprocess of hydrolysis, acidogenesis, and methanogenesis. Furthermore, PFS's inhibition to hydrogenotrophic methanogenesis was much severer than that to acetotrophic methanogenesis, which could be supported by the elevated abundances of Methanosaeta sp and the dropped abundances of Methanobacterium sp in PFS-present digester, and probably due to the severe mass transfer resistance of hydrogen between the syntrophic bacteria and methanogens, as well as the higher hydrogen appetency of PFS-induced sulfate reducing bacteria. Among the derivatives of PFS, "multinucleate and multichain-hydroxyl polymers" and sulfate were unveiled to be the major contributors to the decreased methane potential, while the "multinucleate and multichain-hydroxyl polymers" were identified to be the chief buster to the slowed methane-producing rate and the extended lag time.


Inner ear pressure evaluation using wideband tympanometry in children with Large Vestibular Aqueduct Syndrome (LVAS): A pilot study.
To investigate middle ear function in children with Large Vestibular Aqueduct Syndrome (LVAS) to explore the feasibility of measuring inner ear pressure using Wideband tympanometry (WBT). 13 young children with LVAS were recruited. WBT and other audiological measurements i.e., Auditory Steady State Response (ASSR), Auditory Brain Stem Response (ABR), and Distorted Product Otoacoustic Emissions (DPOAE) were performed. Absorbance under ambient and peak pressure were compared with normative data, and analyzed using a one sample t-test. Average absorbance in children with LVAS was significantly lower than normative data under ambient pressure at 1000, 1189, 1296, 2000 Hz and 4000 Hz. Absorbance under peak pressure was also significantly lower at 707, 794, 917, 1000, 1189, 1297, 1498 and 2000 Hz. However, absorbance was higher than standard values above 4000 Hz under ambient and peak pressure. It was also higher under ambient pressure at frequencies below 500 Hz. The special characteristics of middle ear function found in children with Large Vestibular Aqueduct Syndrome (LVAS) indicate that WBT offers a sensitive and non-invasive method to evaluate inner ear pressure indirectly.


How much polysomnography is enough?
Sleep studies combined with the analysis of autonomic functions are, in several cases, necessary in order to make an accurate diagnosis. Polysomnograms require minimal technical equipment, the absence of which may cause the data obtained to be unreliable.


Euglycemic diabetic ketoacidosis in a patient with type 2 diabetes mellitus 3 days after initiating sodium-glucose cotransporter 2 inhibitor while on an extremely low carbohydrate diet: A case report.
This paper presents a case with type 2 diabetes mellitus on a very-low-carbohydrate diet who developed euglycemic diabetic ketoacidosis (EDKA) 3 days after starting sodium-glucose cotransporter 2 inhibitors (SGLT2i). When initiating SGLT2i, healthcare providers should confirm the implementation of a low-carbohydrate diet and provide intensive guidance to prevent EDKA.


[Effect of potable mineral waters with various chemical compositions on reparative processes of the mucosa of the gastroduodenal area].
Examinations covered patients recovering after gastroduodenal ulcer exacerbation treated with oral mineral waters of different chemical composition. Drinking mineral water was found to stimulate trophic processes in gastroduodenal mucosa, more pronounced for waters of complex chemical composition, e. g. Moscow calcium-magnesium-sodium sulfate water.


Exercise-induced muscle uptake of technetium-99m MDP.
Intense muscle localization of Tc-99m MDP to upper extremity musculature was noted three days following weight lifting exercises. This phenomenon is due to an unknown mechanism although several causative factors have been suggested.


Life Expectancies With Depression by Age of Migration and Gender Among Older Mexican Americans.
Prior studies examining depression among older Mexican Americans suggest both women and immigrants are at higher risk of depressive symptomatology than males and U.S.-born Mexican Americans. We use data from the Hispanic Established Populations for the Epidemiologic Study of the Elderly to examine whether life expectancy with depression and without depression varies by nativity, age of migration, and gender. Sullivan-based life tables were used to estimate depression life expectancies among Mexican Americans aged 65 years and older residing in the Southwestern United States. Depression is based on the 20-item Center for Epidemiological Studies Depression scale (CES-D). The CES-D is a continuous scale (0-60) with higher values indicating worse mental health. We dichotomize depression as a score of 16 or greater. Immigrant women, particularly those who migrated in late-life (after age 50) are at a significant disadvantage in the number of years after age 65 lived with depression and the ratio of years spent without depression relative to U.S.-born women. Among men, only late-life immigrants were disadvantaged in the number of years spent with depression. Early- and mid-life immigrant males did not differ from U.S.-born males. Our results highlight the heterogeneity among older Mexican Americans in life expectancies with depression. These findings illustrate the importance of considering age of migration as a high-risk factor for depression among Mexican-origin immigrants. Including this risk factor as a part of depression screening is a key step for timely interventions in preventing disability and comorbidities associated with untreated depression.


Gaining supervision skills in pre-registration nursing through peer teaching: An evaluative survey.
It is now a requirement that all qualified nurses act as practice supervisors and support student nurses' education in practice, hence preparing third-year students for this role is a priority. This study evaluates students' experiences of peer teaching in clinical skills setting from the perspective of these students taking up the supervisory role once they graduate. An evaluative survey was utilised to explore and understand student nurse participation in peer teaching. Seventeen students took part in a questionnaire containing closed and open questions. This research suggests that students who engaged in peer teaching gained confidence in their own skills, through the revision of their own skills and knowledge. It also triggered reflection upon continuous professional development and inspired students to consider a future career in teaching. Peer teaching provides an opportunity to reinforce the students' knowledge, clinical and communication skills. It helps prepare them for the role of practice supervisor upon qualifying by building confidence and enhancing their teaching skills.


A Novel Self-Assembling Al-based Composite Powder with High Hydrogen Generation Efficiency.
In this study, a novel self-assembling hydrogen generation powder comprised of 80Al-10Bi-10Sn wt.% was prepared using the gas atomization method and then collected in an air environment. The morphological and hydrolysis properties of the powders were investigated. The results indicated that the powders formed unique core/shell microstructures with cracked surfaces and (Bi, Sn)-rich phases distributed on the Al grain boundaries. The powders exhibited good oxidation resistance and reacted violently with distilled water at temperatures as low as 0 °C. Furthermore, at 30 °C, the powders exhibited a hydrogen conversion yield of 91.30% within 16 minutes. The hydrogen produced by this powder could be directly used in proton exchange membrane fuel cells. The mechanisms of the hydrolysis reactions were also analyzed.


Evaluating a skills centre: the acquisition of psychomotor skills in nursing--a review of the literature.
In 1994, as a result of both programme evaluations which identified students' fears and apprehensions about their practical ability, and a review of the literature on skill acquisition, experiential skills teaching was resumed within the faculty. Having invested considerable finance into the reconstruction of a skills centre to teach skills, it is now imperative that its use be formally evaluated. Part of the evaluative process includes a review of the empirical literature on the acquisition of psychomotor skills in nursing. This paper summarizes this review.


Case study of a commercial sheep flock under extensive mountain grazing: Pasture derived lipid compounds in milk and cheese.
Terpenoid, fat-soluble antioxidant and fatty acid (FA) composition of pasture as well as those of milk and cheese from a commercial sheep flock managed under extensive mountain grazing in the east region of the Cantabrian mountain (Northern Spain) was investigated. The grazing period lasted for 2 months and ewes were at late lactation stage. Plants, feces, bulk milk and cheese samples were collected on two sampling dates. The abundance of the dominating botanical families in the mountain pasture prevailed in the sheep diet of the commercial flock. Major terpenoids and tocols in the pasture appeared as major ones in milk and cheese, whereas C18 unsaturated FAs in milk and cheese were derived from the intake of C18 polyunsaturated FAs which were prevalent in the pasture. No carotene was detected in the dairy samples but retinol (free or esterified), derived from the intake of β-carotene present in pasture plants, was found in milk and cheese.


Person perception and autonomic nervous system response: the costs and benefits of possessing a high social status.
This research was designed to investigate the relationship between sympathetic and parasympathetic autonomic nervous system (ANS) responses to the perception of social targets varying in social status. Participants varying in subjective financial status were presented with faces assigned with either a low, average, or high financial status. Electrocardiographic and impedance cardiography signals were recorded and measures of sympathetic (pre-ejection period; PEP) and parasympathetic (high frequency heart rate variability; HF HRV) cardiac control were derived. These measures associated with the presentation of each face condition were examined in relation to the subjective status of the perceivers. Participants with high subjective financial status showed reduced sympathetic activity when viewing low- and medium-status targets as compared to high-status targets, and lower parasympathetic response when viewing high- and medium-status targets relative to low-status targets.


Chondroitin sulfate characterized by the E-disaccharide unit is a potent inhibitor of herpes simplex virus infectivity and provides the virus binding sites on gro2C cells.
Although cell surface chondroitin sulfate (CS) is regarded as an auxiliary receptor for binding of herpes simplex virus to cells, and purified CS chain types A, B, and C are known to interfere poorly or not at all with the virus infection of cells, we have found that CS type E (CS-E), derived from squid cartilage, exhibited potent antiviral activity. The IC(50) values ranged from 0.06 to 0.2 mug/ml and substantially exceeded the antiviral potency of heparin, the known inhibitor of virus binding to cells. Furthermore, in mutant gro2C cells that express CS but not heparan sulfate, CS-E showed unusually high anti-herpes virus activity with IC(50) values of <1 ng/ml. Enzymatic degradation of CS-E with chondroitinase ABC abolished its antiviral activity. CS-E inhibited the binding to cells of the purified virus attachment protein gC. A direct interaction of gC with immobilized CS-E and inhibition of this binding by CS-E oligosaccharide fragments greater than octasaccharide were demonstrated. Likewise, the gro2C-specific CS chains interfered with the binding of viral gC to these cells and were found to contain a considerable proportion (13%) of the E-disaccharide unit, suggesting that this unit is an essential component of the CS receptor for herpes simplex virus on gro2C cells and that the antiviral activity of CS-E was due to interference with the binding of viral gC to a CS-E-like receptor on the cell surface. Knowledge of the determinants of antiviral properties of CS-E will help in the development of inhibitors of herpes simplex virus infections in humans.


Rapamycin increases fetal hemoglobin and ameliorates the nociception phenotype in sickle cell mice.
Fetal hemoglobin-inducing therapies are disease-modifying and ameliorate the pain phenotype in sickle cell disease (SCD). Rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, increases HbF in erythroid precursor cells in vitro. We hypothesized that rapamycin would increase HbF levels and improve nociception phenotype in SCD mice. We used sine-wave electrical stimulation to examine nocifensive phenotype and evaluate myelinated [2000Hz (Aβ-fiber) and 250Hz (Aδ-fiber)] and unmyelinated (5Hz C-fibers)] sensory fiber function. Rapamycin significantly increased γ-globin mRNA and HbF levels [+2.3% (0.7, 3.9), mean increase (95% confidence interval, CI), p=0.006]. In homozygous (sickling) mice, long- (16 weeks), but not short-term (6 weeks), rapamycin treatment increased 2000Hz and 250Hz current thresholds in a pattern that varied according to sex. In male, but not female mice, rapamycin (compared with vehicle) was associated with increases in 2000Hz [21Units (7, 35), mean difference (95% CI), p=0.009 for sex∗treatment interaction] and 250Hz [9Units (1, 16), p=0.01] current thresholds. In rapamycin-treated homozygotes, HbF levels directly correlated with myelinated [2000Hz(Aβ-fiber, r=0.58, p=0.01) and 250Hz(Aδ-fiber, r=0.6, p=0.01)] but not unmyelinated sensory fiber current thresholds. These findings suggest that in SCD mice, rapamycin increases HbF and modulates current thresholds of myelinated fibers. Therefore, mTOR signaling might be implicated in the pathobiology of SCD.


Point prevalence and risk factors of hospital acquired infections in a cluster of university-affiliated hospitals in Shiraz, Iran.
Hospital-acquired infections (HAIs) are critical and mostly preventable complications that occur in hospitalized patients and lead to major health and economic burdens. Most of the information on HAI risk factors and the recommended preventive measures is based on data acquired from only a few countries. The aim of this point prevalence HAI study conducted in Shiraz, Iran, was to study the local epidemiology of HAIs and the major risk factors for acquiring HAIs in a Middle-Eastern region. The study employed four identical point prevalence surveys in eight university hospitals, each consisting of 60-700 beds. The study was conducted during all four season of 2008-2009. All of the patients admitted for ≥48h were studied, although the patients admitted to emergency wards were excluded. A standardized data collection form that included name, age, gender, presence or absence of HAI, administration of any antibiotics, insertion of a central line, use of an endotracheal tube, mechanical ventilation, and use of an urinary catheter was completed for each patient. The HAI definitions used in this study were based on the US National Nosocomial Infection Surveillance (NNIS) guidelines. Data from 3450 patients were prospectively collected and analyzed. The overall HAI prevalence was 9.4%. The most common HAIs were blood stream infections (2.5%), surgical site infections (2.4%), urinary tract infections (1.4%), and pneumonia (1.3%). A logistic regression analysis showed that the odds ratio OR for males rather than females acquiring infections was 1.56 (95% confidence interval [CI] 1.21-2.02). Other HAI risk factors included using a central intravascular catheter, adjusted OR of 3.86 (95% CI 2.38-6.26), and using an urinary catheter, adjusted OR of 3.06 (95% CI 2.19-4.28). Being admitted to an ICU was not an independent HAI risk factor. For all HAIs, the OR of acquiring infection was 3.24 (95% CI 2.34-4.47) in the patients with hospital stays longer than eight days. A high discrepancy between HAIs and antibiotic use was observed. Antibiotics were administered to 71% of the patients, but only 9.4% of the patients also had at least one documented infection. This point prevalence study showed that HAIs are frequent in Shiraz university hospitals, and that the proportion of patients receiving antibiotics is high. The results imply that more primary prevention efforts are necessary to address HAIs associated with using indwelling devices and to prevent surgical site infections.


Estimating historical changes in physical activity levels.
To compare activity levels between a simulated "historical" lifestyle and a "modern" lifestyle to try to validate earlier estimates of secular changes in activity. Triaxial accelerometers (TRACMORs) were used to measure activity levels in a "historical" group of seven male actors who were paid to live like early Australian settlers at a theme park north of Sydney (eg, minimising the use of modern technology) for a week. Results were compared with those from a group of seven "modern" sedentary office workers. Activity levels were up to 2.3 times greater in the historical group than the modern group. Calculations based on body weight and energy expenditure suggest the difference is the equivalent of walking up to 16 km per day more in the past than today. These findings accord with two previous estimates of changes in daily activity levels over time and suggest that recent public health guidelines for increasing physical activity may be inadequate.


Outcome of Muscle-Invasive Urothelial Bladder Cancer After Radical Cystectomy.
We aimed at clarification of reasons for recurrence of urothelial carcinoma after radical cystectomy in a retrospective study that included 189 patients. Presence of lymphovascular invasion even in node-negative cases, high tumor grade, and high nodal stage appeared to be independent predictors for recurrence. This raises the necessity for postoperative multimodality treatment to improve disease-free survival. Radical cystectomy remains the gold standard for local control of muscle-invasive bladder cancer. Despite that, a significant proportion of patients develop disease recurrence. Several predictors for recurrence have been described and the implication of such factors on development of recurrence will help in modification of treatment strategies to improve the prognosis of bladder cancer patients. This is a retrospective study carried on patients with muscle-invasive urothelial carcinoma who underwent radical cystectomy at the National Cancer Institute in 3 years; January 2007 to December 2009, and analyzed for the development of recurrence and potential risk factors. The 3-year disease-free survival (DFS) rate was 56%. Seventy patients (37%) developed disease recurrence during the follow-up period. Of these recurrences, 17 patients (24.3%) developed local and/or regional recurrences, 45 patients (64.3%) developed distant metastasis, and 8 patients (11.4%) developed local and/or regional and distant recurrences. In univariate analysis, lymph node metastasis (P < .001), lymphovascular invasion (LVI) (P < .001), high grade (P = .005), and advanced tumor stage (P = .002) were significantly associated with development of recurrence. In multivariate analysis, lymph node metastasis, LVI, and high grade were significantly associated with tumor recurrence and poor DFS. Lymph node metastasis, LVI, and high tumor grade were independent prognostic factors that affected tumor recurrence and DFS. LVI status should be reported in radical cystectomy specimens to help in risk assessment of patients especially in node-negative cases.


Hepatitis types A, B, and non A--non B in childhood.
199 children with acute hepatitis hospitalized between 1968 and 1978 were tested for serological markers of hepatitis A and B infection. In 24 out of 28 HBsAg-positive patients, hepatitis B infection was diagnosed because of the disappearance of the antigen during convalescence. The histories of the 171 HBsAg-negative children suggested acute hepatitis A infection in 69% of the patients. This diagnosis could be confirmed in 110 of the 116 tested cases (95%) by a more than fourfold increase in the anti-HAV titer or by detection of anti-HAV of the IgM class. In the 55 HBsAg-negative patients without epidemiological clues as to the type of hepatitis, 40 children exhibited anti-HAV which could be related to acute A infection in 21 out of 22 tested cases. At least 11 patients had to be classified as having nonn A--non B infection. The results indicate that a combination of evaluation of the patient's history and selected serological tests will permit a fast preliminary diagnosis. This is important in the clinical management of patients and protection of contacts with immunoglobulin.


The changes in the T-lymphocyte subsets in a population of Turkish children with puberty gingivitis.
The aim of the study was to investigate the number of CD4 and CD8 T lymphocytes, analyse subjects with gingivitis and those without, and determine the role of T lymphocytes in the pathobiology of puberty gingivitis. Fifty individuals with and without puberty gingivitis were recruited for this study. The CD4(+) and CD8(+) T-lymphocyte counts were determined using flow cytometry on the biopsy samples, and the CD4(+)/CD8(+) ratio was calculated. At the same time, periodontal index scores were recorded to assess the periodontal status. Acquired data were analysed statistically using a paired t-test to compare laboratory values obtained before and after the treatment in individuals with puberty gingivitis and disease-free individuals. In addition, Pearson's correlation analysis was performed to investigate the relation between laboratory values and clinical measurements. The CD4(+)/CD8 ratio in gingival tissues obtained from test group was significantly higher (P < 0.05) than that found in the gingival tissue obtained from control group. We found that the CD4(+) and CD8(+) lymphocyte counts continued to increase significantly (P < 0.001) and the CD4(+)/CD8(+) ratio continued to drop significantly (P < 0.05) after treatment in test group. T lymphocytes could play a significant role in the pathobiology of puberty gingivitis.


Ventricular outputs, central blood flow distribution and flow pattern through the aortic isthmus of fetuses with simple transposition of the great arteries.
Our objective was to determine the impact of simple transposition of the great arteries (TGA) on fetal left ventricular (LV) and right ventricular (RV) performances and central circulatory dynamics including the aortic isthmus. Ventricular stroke volumes were calculated as the product of the cross-sectional area of the corresponding semi-lunar valve and the flow velocity integral through these valves. Volume flow in ductus arteriosus (QDA ) was evaluated using the same technique. Flow through the lungs (QLUNGS ) was calculated by subtracting net QDA from flow in main pulmonary artery [net QDA = QDA minus retrograde ductus arteriosus (DA) diastolic flow]. Relative performance of each ventricle expressed as percentage of combined cardiac output was also indirectly assessed by the aortic isthmus systolic index (ISI) (nadir of incisura/peak systolic of the Doppler waveforms in the isthmus); the relation between ISI and QLUNGS was investigated. Fifty-one fetuses with TGA were compared with 74 normal controls matched for gestational age. TGA fetuses had higher QLV at T2 (58.6 ± 9.4% vs. 43.4 ± 5.0%, p < 0.001) and T3 (53.7 ± 8.9% vs. 43.9 ± 5.7%, p < 0.001). QLUNGS was higher in fetuses with TGA, in the second (50.4 ± 16.3% vs. 39.0 ± 16.8%, p = 0.007) and third trimesters of gestation (52.8 ± 22.0% vs. 37.1 ± 16.3%, p = 0.005). No difference was found between ISI values from normal and TGA groups. A significant inverse correlation was observed between ISI and QLUNGS (r = -0.55, p = 0.006). Central distribution of combined cardiac output of fetuses with simple TGA is characterized by a greater QLUNGS leading to a dominant LV. In prenatal TGA, changes in QLUNGS could be monitored by measuring ISI. The clinical importance of this last observation deserves further investigations.


Follicular T Helper Cell Signatures in Primary Biliary Cholangitis and Primary Sclerosing Cholangitis.
Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are the most common cholestatic liver diseases. While PBC is generally accepted to be an autoimmune disorder characterized by pathognomonic autoantibodies against mitochondrial antigens, the pathogenesis of PSC is less precisely defined; however, some degree of altered immunity toward autoantigens has been suggested. Follicular T helper (Tfh) cells, a distinct clusters of differentiation (CD)4 T-cell subset specialized in facilitating antibody responses, have been shown to contribute to humoral autoimmunity in various disorders; yet, there is only limited information on possible alterations of Tfh cells in the context of cholestatic liver diseases. Thus, we addressed this important question by analyzing the frequency, activation status, and function of Tfh cells and frequencies of regulatory follicular T helper (Tfr) cells in well-defined cohorts of patients with PBC and patients with PSC. Interestingly, we observed a significant increase in circulating chemokine (C-X-C motif) receptor 5 (CXCR5)+programmed death 1 (PD-1) +CD4+ Tfh cells in patients with PBC but not in those with PSC. Although the frequency of potentially pathogenic chemokine (C-C motif) receptor 7 (CCR7)lowCXCR5+PD-1+CD4+ Tfh cells was increased in both disorders compared to healthy donors, the increase was significantly more pronounced in PBC. Furthermore, in patients with PBC, Tfh cells displayed stronger expression of the activation markers OX40 and inducible costimulator of T cells, correlated with anti-anti-mitochondrial antibody M2 and immunoglobulin M titers, and were most significantly increased in patients with cirrhosis. Tfr cell numbers were similarly increased; however, Tfh/Tfr ratios were unaltered in PSC and PBC. These alterations did not correlate with increased secretion of the Tfh signature cytokine interleukin-21 in sorted CD4 T cells. Conclusion: Significant alterations occur in the Tfh cell compartment in cholestatic liver diseases, suggesting that Tfh cells influence the pathogenesis of PBC and to a lesser extend PSC.


Effects of Docosahexaenoic Acid and Its Peroxidation Product on Amyloid-β Peptide-Stimulated Microglia.
Growing evidence suggests that docosahexaenoic acid (DHA) exerts neuroprotective effects, although the mechanism(s) underlying these beneficial effects are not fully understood. Here we demonstrate that DHA, but not arachidonic acid (ARA), suppressed oligomeric amyloid-β peptide (oAβ)-induced reactive oxygen species (ROS) production in primary mouse microglia and immortalized mouse microglia (BV2). Similarly, DHA but not ARA suppressed oAβ-induced increases in phosphorylated cytosolic phospholipase A2 (p-cPLA2), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-α (TNF-α) in BV2 cells. LC-MS/MS assay indicated the ability for DHA to cause an increase in 4-hydroxyhexenal (4-HHE) and suppress oAβ-induced increase in 4-hydroxynonenal (4-HNE). Although oAβ did not alter the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, exogenous DHA, ARA as well as low concentrations of 4-HHE and 4-HNE upregulated this pathway and increased production of heme oxygenase-1 (HO-1) in microglial cells. These results suggest that DHA modulates ARA metabolism in oAβ-stimulated microglia through suppressing oxidative and inflammatory pathways and upregulating the antioxidative stress pathway involving Nrf2/HO-1. Understanding the mechanism(s) underlying the beneficial effects of DHA on microglia should shed light into nutraceutical therapy for the prevention and treatment of Alzheimer's disease (AD).


Characterizations and hepatoprotective effect of polysaccharides from Mori Fructus in rats with alcoholic-induced liver injury.
Crude polysaccharides of Mori Fructus (MFPs) were found to have anti-inflammatory antioxidant, and immuno-enhancing activities. However, the structure of the polysaccharides was ambiguous and its holistic hepatic protection evaluation was defective. This study was conducted to illustrate the characterization of MFPs, and evaluate its hepatoprotective activities. The results found that MFPs contained 67.93±1.18% carbohydrates, 31.03±0.54% uronic acid, and little protein and sulfate. The average molecular weight was ranging from 112.2kDa to 181.9kDa. Monosaccharide component analysis indicated that MFPs was mainly composed of glucose, galacturonic acid, rhamnose and galactose. Both the acute and subacute alcoholic-induced liver injury animal models were adopted to evaluate the MFPs's hepatoprotective activity. After administration of MFPs, both serological indexes (aspartate aminotransferase and alanine aminotransferase) and hepatic indicators (glutathione, superoxide dismutase, glutathione peroxidase and malondialdehyde) were improved by comparing with the non-MFPs group. The hepatic histopathology results also showed a prominent lipid degeneration and microvesicular steatosis attenuation in the MFPs groups. These outstanding hepatic protecting activities of MFPs might be related to its activation of ethanol dehydrogenase, elimination of free radicals and/or inhibition of lipid peroxidation capacities. MFPs could be important active substances for preventing and remedying liver injury.


Understanding Hyperporphyrin Spectra: TDDFT Calculations on Diprotonated Tetrakis(p-aminophenyl)porphyrin.
A detailed TDDFT study (with all-electron STO-TZ2P basis sets and the COSMO solvation model) has been carried out on the effect of diprotonation on the UV-vis-NIR spectra of free-base tetraphenylporphyrin and tetrakis(p-aminophenyl)porphyrin. The diprotonated forms have been modeled as their bis-formate complexes, i.e., as so-called porphyrin diacids. The dramatic redshift of the Q-band of the TAPP diacid has been explained in terms of an elevated "a2u" HOMO and lowered LUMOs, both reflecting infusion of aminophenyl character into the otherwise classic Gouterman-type frontier MOs. The exercise has also yielded valuable information on the performance of different exchange-correlation functionals. Thus, the hybrid B3LYP functional was found to yield a substantially better description of key spectral features, especially the diprotonation-induced redshifts, than the pure OLYP functional. Use of the range-separated CAMY-B3LYP functional, on the other hand, did not result in improvements relative to B3LYP.


Relationship of neonatal cerebral blood flow velocity asymmetry with early motor, cognitive and language development in term infants.
The objective of this study was to examine the relationships of Doppler cerebral blood flow velocity (CBFV) asymmetry measures with developmental outcomes in term infants. Doppler CBFV parameters (peak systolic velocity [PSV] and mean velocity [MV]) of the bilateral middle cerebral arteries of 52 healthy term infants were prospectively examined on postnatal days 1-5, and then their motor, cognitive and language development was evaluated with the Bayley Scales of Infant and Toddler Development, Third Edition, at 6, 12, 18 and 24 months of age. The left CBFV asymmetry measure (PSV or MV) was calculated by subtracting the right-side value from the left-side value. Left CBFV asymmetry measures were significantly positively related to motor scores at 6 (r = 0.3-0.32, p < 0.05) and 12 (r = 0.35, p < 0.05) months of age, but were not related to cognitive or language outcome. Thus, the leftward hemodynamic status of the middle cerebral arteries, as measured by cranial Doppler ultrasound in the neonatal period, predicts early motor outcome in term infants.


True, true, and unrelated: tubal patency, tubal architecture, and tubal function.
"To understand the actual world as it is, not as we should wish it to be, is the beginning of wisdom." - Bertrand Russell.


Protein inhibitor of activated STAT1 (PIAS1) inhibits IRF8 activation of Epstein-Barr virus lytic gene expression.
Epstein-Barr virus (EBV), a major human oncogenic pathogen, establishes life-long persistent infections. In latently infected B lymphocytes, the virus persists as an episome in the nucleus. Periodic reactivation of latent virus is controlled by both viral and cellular factors. Our recent studies showed that interferon regulatory factor 8 (IRF8) is required for EBV lytic reactivation while protein inhibitor of activated STAT1 (PIAS1) functions as an EBV restriction factor to block viral reactivation. Here, we show that IRF8 directly binds to the EBV genome and regulates EBV lytic gene expression together with PU.1 and EBV transactivator RTA. Furthermore, our study reveals that PIAS1 antagonizes IRF8/PU.1-mediated lytic gene activation through binding to and inhibiting IRF8. Together, our study establishes IRF8 as a transcriptional activator in promoting EBV reactivation and defines PIAS1 as an inhibitor of IRF8 to limit lytic gene expression.


Evaluating gender differences in prognosis following SPECT myocardial perfusion imaging among patients with diabetes and known or suspected coronary disease in the modern era.
Previous data suggested that diabetic women were at greater risk for future cardiac events than diabetic men. Increasing awareness of coronary artery disease (CAD) in women and advances in the management of CAD may have changed this paradigm. To investigate gender differences in prognosis among patients with diabetes who were clinically referred for single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI). Patients with diabetes undergoing SPECT-MPI from 1996 to 2006 were followed for 5 years or until cardiac death or non-fatal myocardial infarction. Clinical characteristics and nuclear parameters were compared with χ (2) and t tests. Multivariable Cox regression controlled for baseline differences and tested the impact of gender on survival. A total of 4,628 SPECT-MPI patients with diabetes (50% women, mean age 63 ± 12 years) were analyzed. There were 380 events, with rates higher in men (10% vs 7%, P < .001). Patients of either gender with abnormal scans had higher event rates than patients with normal scans. There were fewer cardiac events in diabetic females with no known CAD and normal scans compared to similar males (P = .044). However, diabetic males and females with known CAD had similar event rates for all degrees of perfusion abnormalities. Only age, history of heart failure, nuclear perfusion defect, and LVEF predicted survival; gender did not. LVEF ≤ 50% had the strongest association with cardiac events (hazard ratio = 2.518, 95% confidence interval, 1.922-3.298). Cardiovascular outcomes among patients with diabetes, regardless of a history of CAD, were similar in women and men. The size and severity of stress-induced perfusion abnormalities predicted outcomes equally in both genders.


Glucocorticoids inhibit the transcriptional response of the uncoupling protein-1 gene to adrenergic stimulation in a brown adipose cell line.
Glucocorticoids may inhibit brown adipose tissue (BAT) thermogenesis acting at a central level as well as reducing the responses of the tissue to adrenergic stimulation in vivo. This latter effect is not well understood. We investigated whether or not glucocorticoids directly reduce the expression of the key molecule for BAT thermogenesis, uncoupling protein-1 (UCP1), and if so, to what extent and by what mechanisms. We used HIB-1B brown adipose cells obtained from a hibernoma. The response of UCP1 mRNA to adrenergic stimulation in these cells is qualitatively and quantitatively similar to that seen in vivo. Dexamethasone and other glucocorticoids, given simultaneously with NE, nearly abolish the ensuing UCP1 mRNA accumulation. This effect was negated by the glucocorticoid receptor antagonist RU-486. Significant inhibition is seen within the physiological range of concentrations, with ID(50)s for dexamethasone and corticosterone of 1 and 75 nM, respectively. Within the time span of the experiments, glucocorticoids did not reduce the strength of the NE signal nor did they necessitate ongoing protein synthesis or reduce the stability of mature UCP1 mRNA, but they significantly inhibited the stimulation of transcription by NE in a run-on in vitro transcription assay. These observations indicate that glucocorticoids are powerful inhibitors of the UCP1 gene response to adrenergic stimulation acting at transcriptional level, and provide further evidence for a global inhibitory effect of glucocorticoids on BAT thermogenesis.


Affinity capillary electrophoresis and isothermal titration calorimetry for the determination of fatty acid binding with beta-cyclodextrin.
Affinity capillary electrophoresis (ACE) and isothermal titration calorimetry (ITC) were used to investigate the binding interaction between several fatty acids (FAs) and beta-cyclodextrin (beta-CD). Within each method, steps taken to obtain accurate binding constants are discussed. The stoichiometry of interaction was revealed to be 1:1 regardless of FA chain length. The binding constants obtained using ACE were: octanoate, 6.4x10(2); 2-octenoate, 4.7x10(2); decanoate, 3.7x10(3); 9-decenoate, 1.8x10(3) and dodecanote, 1.4x10(4). The binding constants obtained from ITC were of the same order of magnitude, but were consistently greater than those from ACE. Thermodynamic data obtained using ITC are used to explain the observed trends in binding strength.


Is season a prognostic factor in breast cancer?
Some studies have indicated an inverse relationship between cancer risk and sunlight exposure. Others have reported that the prognosis of some cancers such as prostate, colon, ovarian and non melanoma skin cancer, were affected by the season in which the cancer was diagnosed. In our study, we evaluated whether season is prognostic in Turkish patients with breast cancer. A total of 517 patients from Kayseri Training and Research Hospital were analysed retrospectively. Patients were divided into 4 groups according to season of cancer diagnosis: winter, spring, summer and autumn. The prognostic factors for disease free survival and overall survival were investigated. No significant differences were found among groups regarding prognostic factors overall. Only estrogen receptor status and lymphovascular invasion were independent prognostic factors (p=0.001 and p=0.001 respectively). We found significantly differences for mean disease free survival among groups (p=0.019). Winter group had better mean DFS while summer group had worse DFS. Mean overall survival was similar in the four groups (p=0.637). The season is not an independent predictive factor. However, due to interaction with other factors, we think that the season of cancer diagnosis is important for cancer prognosis.


Gene expression profiles in peripheral lymphocytes by arsenic exposure and skin lesion status in a Bangladeshi population.
Millions of individuals worldwide are chronically exposed to arsenic through their drinking water. In this study, the effect of arsenic exposure and arsenical skin lesion status on genome-wide gene expression patterns was evaluated using RNA from peripheral blood lymphocytes of individuals selected from the Health Effects of Arsenic Longitudinal Study. Affymetrix HG-U133A GeneChip (Affymetrix, Santa Clara, CA) arrays were used to measure the expression of approximately 22,000 transcripts. Our primary statistical analysis involved identifying differentially expressed genes between participants with and without arsenical skin lesions based on the significance analysis of microarrays statistic with an a priori defined 1% false discovery rate to minimize false positives. To better characterize differential expression, we also conducted Gene Ontology and pathway comparisons in addition to the gene-specific analyses. Four-hundred sixty-eight genes were differentially expressed between these two groups, from which 312 differentially expressed genes were identified by restricting the analysis to female never-smokers. We also explored possible differential gene expression by arsenic exposure levels among individuals without manifest arsenical skin lesions; however, no differentially expressed genes could be identified from this comparison. Our findings show that microarray-based gene expression analysis is a powerful method to characterize the molecular profile of arsenic exposure and arsenic-induced diseases. Genes identified from this analysis may provide insights into the underlying processes of arsenic-induced disease and represent potential targets for chemoprevention studies to reduce arsenic-induced skin cancer in this population.