Action of PBAN and related peptides on pheromone biosynthesis in isolated pheromone glands of the redbanded leafroller moth, Argyrotaenia velutinana.
Isolated pheromone glands from the redbanded leafroller moth, Argyrotaenia velutinana, were utilized to demonstrate the action of pheromone biosynthesis activating neuropeptide (PBAN) and bursa pheromonotropic peptide plus several other related peptides on pheromone biosynthesis. All peptides belonging to the PBAN family and the bursa peptide stimulated pheromone biosynthesis as measured by pheromone titer and incorporation of radiolabeled acetate. These peptides required the presence of extracellular Ca2+ for expression of full activity and several inorganic Ca2+ channel blockers inhibited the stimulation of pheromone biosynthesis. The Ca2+ ionophore A23187 alone stimulated pheromone biosynthesis as did a cAMP analogue. Stimulation by the cAMP analogue in the absence of extracellular Ca2+ was observed. Maximum pheromone titers were observed in 16 hr gland incubations; however, 2-6 hr incubations were required if pheromone biosynthesis was measured by incorporation of radiolabeled acetate. Radiolabeled glucose incorporation was not increased in the presence of PBAN. These results are discussed in the context of how the pheromone biosynthetic pathway is stimulated by these peptides.


Direct observation of epoxy resin blocks for renal biopsy by low-vacuum scanning electron microscopy.
To improve the resolution of low-vacuum scanning electron microscopy (LVSEM), the epoxy resin block for the transmission electron microscopy (TEM) was observed directly with LVSEM. After observing ultrathin sections from renal biopsies of IgA nephropathy, membranous nephropathy, lupus nephritis, diabetic nephropathy (DM), thin basement membrane disease (TBMD), Alport's syndrome, Fabry's disease, and renal amyloidosis, the epoxy resin blocks of the same sites were observed by LVSEM and compared. The LVSEM image of the epoxy resin block corresponds to the negative of the TEM image, and when the gradation is reversed, the LVSEM image was comparable to the TEM image. At a low magnification of 100 ×, the entire specimen, including the glomerulus, was obtained. LVSEM at 5000 × magnification was sufficient to identify paramesangial deposits in IgA nephropathy and subepithelial electron-dense deposits (EDD) and spikes in membranous nephropathy. Glomerular basement membrane thickening in DM and thinning in TBMD could be sufficiently diagnosed with LVSEM at 6000 ×. Accumulation of ceramide in Fabry's disease was easily identified, but amyloid fibril could not be identified by LVSEM. LVSEM of renal biopsy epoxy resin blocks can replace TEM up to moderate magnification.


Fall Armyworm, spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), female moths respond to herbivore-induced corn volatiles.
In response to herbivore attack, plants release herbivore-induced plant volatiles (HIPVs) that represent important chemical cues for herbivore natural enemies. Additionally, HIPVs have been shown to mediate other ecological interactions with herbivores. Differently from natural enemies that are generally attracted to HIPVs, herbivores can be either attracted or repelled depending on several biological and ecological parameters. Our study aimed to assess the olfactory response of fall armyworm-mated female moths toward odors released by mechanically and herbivore-induced corn at different time intervals. Results showed that female moths strongly respond to corn volatiles, although fresh damaged corn odors (0-1 h) are not recognized by moths. Moreover, females preferred volatiles released by undamaged plant over herbivore-induced plants at 5-6 h. This preference for undamaged plants may reflect an adaptive strategy of moths to avoid competitors and natural enemies for their offspring. We discussed our results based on knowledge about corn volatile release pattern and raise possible explanations for fall armyworm moth behavior.


Chlamydia pneumoniae infection and hyperlipidaemia-induced expression of P50 and c-Fos in the heart of C57BL6J mice.
The objective of this study was to investigate infection by Chlamydia pneumoniae (C. pneumoniae) and the combined effects of an atherogenic diet on the expression of AP-1 or the subunit of AP-1 (c-Fos) and NF-kappaB or the subunit of NF-kappaB (P50) in myocardial cells of C57BL/6J mice. Thirty-six 8-week-old female C57BL/6J mice were divided into three groups: A, B and C (twelve mice in each group). Mice in group A were fed an atherogenic diet (consisting of 15% fat and 2.5% cholesterol). Those in group B and C (as blank control) were fed a regular diet. The mice in group B were infected with C. pneumoniae. Fourteen weeks later, the expression of P50 (subunit of NF-kappaB) and c-Fos (subunit of AP-1) in the heart was determined by indirect immunofluorescence in the myocardial cells. Binding activity of NF-kappaB and AP-1 in the heart was determined by electrophoretic mobility shift assay (EMSA). The expression of NF-kappaB and AP-1 in the myocardial cells was upregulated in group A and B, compared with group C (P < 0.05). There was no significant difference between group A and B. The inflammatory process was already initiated in the myocardial cells in C57BL/6J mice at the early stage of C. pneumoniae infection and hyperlipidaemia. The expression of NF-kappaB and AP-1 was upregulated in mice infected by C. pneumoniae or fed an atherogenic diet. C. pneumoniae or hyperlipidaemia may involve the pathogenesis and progression of ischaemic cardiomyopathy.


Prostaglandin profiles in nervous tissue and blood vessels of the brain of various animals.
The endogenous formation of prostaglandin (PG) D2, E2, F2 alpha, and 6-keto-PGF1 alpha was determined in homogenates of mouse, rat, and rabbit brain, and of rat cerebral blood vessels, using gas chromatography mass spectrometry. In all species tested, 6-keto-PGF1 alpha could be identified in the brain homogenates, but was a minor component in relation to other PGs. In contrast 6-keto-PGF1 alpha was the most abundant PG in the blood vessels, being present in about 40-fold higher levels than in the brain tissue. PGD2 was the most abundant PG in rat and mouse brains, but was below detection limits in the analyzed blood vessels. These studies indicating differential metabolism of PG endoperoxides in nervous and vascular tissue, provide a biochemical basis for further studies on the role of the PGs in brain circulation and neuronal activity.


The functional dlt operon of Clostridium butyricum controls the D-alanylation of cell wall components and influences cell septation and vancomycin-induced lysis.
Clostridium butyricum is a Gram-positive bacterium involved in the development of necrotizing enterocolitis (NEC) in preterm infants. To colonize the digestive tract, components of the cell wall of C. butyricum must interact with the intestinal mucosa. The D-alanylation of cell wall components such as teichoic acids results in a net positive charge on the cell wall, which is important for many functions of Gram-positive bacteria. Notably, D-alanylation mediates resistance to antimicrobial peptides and antibiotics. Here, we show that the dlt operon of C. butyricum encodes the enzymes responsible for the D-alanylation of cell wall components and influences the surface properties of the cell wall. We show that the D-alanylation of cell wall components controls the septation of C. butyricum, which is an essential mechanism during vegetative growth. Furthermore, we find that D-alanylation is involved in the resistance of C. butyricum to some cationic antimicrobial peptides (CAMPs) and lysozyme. Finally, we show that the D-alanylation of cell wall components influences vancomycin-induced lysis.


Comparison of sex steroid measurements in men by immunoassay versus mass spectroscopy and relationships with cortical and trabecular volumetric bone mineral density.
In men, measurement of serum testosterone and estradiol levels with immunoassays correlated with mass spectroscopic measurements, and correlations of sex steroids with volumetric bone mineral density were similar. While immunoassays have been used extensively for measurement of serum testosterone (T) and estradiol (E(2)) levels, there is concern about their specificity, particularly at low E(2) levels as present in men. We compared T and E(2) measured by mass spectroscopy to levels measured by immunoassay in men (n = 313, age 22 to 91 years) and related these to volumetric bone mineral density (vBMD) at various skeletal sites. Serum T and non-SHBG bound (or bioavailable) T levels by immunoassay correlated well with the corresponding mass spectroscopy measurements (R = 0.90 and 0.95, respectively, P < 0.001); the correlations for serum E(2) measured using the two techniques were less robust (R = 0.63 for total E(2) and 0.84 for bioavailable E(2), P < 0.001). Overall relationships between serum bioavailable T and E(2) levels with vBMD at various skeletal sites were similar for the immunoassay and mass spectroscopic measures. Although E(2) levels with immunoassay correlate less well with the mass spectroscopic measurements than do the T measurements in men, our findings indicate that the fundamental relationships observed previously between vBMD and the sex steroids by immunoassay are also present with the mass spectroscopic measurements.


Remyelination in PNS and CNS: current and upcoming cellular and molecular strategies to treat disabling neuropathies.
Myelin is a lipid-rich nerve cover that consists of glial cell's plasmalemma layers and accelerates signal conduction. Axon-myelin contact is a source for many developmental and regenerative signals of myelination. Intra- or extracellular factors including both enhancers and inhibitors are other factors affecting the myelination process. Myelin damages are observed in several congenital and hereditary diseases, physicochemical conditions, infections, or traumatic insults, and remyelination is known as an intrinsic response to injuries. Here we discuss some molecular events and conditions involved in de- and remyelination and compare the phenomena of remyelination in CNS and PNS. We have explained applying some of these molecular events in myelin restoration. Finally, the current and upcoming treatment strategies for myelin restoration are explained in three groups of immunotherapy, endogenous regeneration enhancement, and cell therapy to give a better insight for finding the more effective rehabilitation strategies considering the underlying molecular events of a lesion formation and its current condition.


An investigation into the robustness of a double-ended wideband impedance-based fault location technique.
The double-ended impedance-based fault location technique (DEFLT) uses the wideband frequency content of the transient generated by the fault to determine the impedance from the point of measurement to the fault. This paper evaluates and develops the DEFLT experimentally for a Shipboard Power System (SPS) to determine its robustness to source impedance, the presence of interconnected loads ("tapped" loads) and tapped lines. Results demonstrate that the estimated impedance (and therefore distance to the fault) is influenced by the presence of tapped loads when the source impedance is large, or when the tapped load is comparable to the rated load of the system. Therefore, a scheme is proposed that compensates for any tapped load without requiring any additional measurements. Using the proposed scheme, the maximum error is significantly reduced from 92 to 13%. Simulation and experimental results show that a high accuracy for the estimated fault location can be achieved.


Fluid Therapy in Patients Undergoing Abdominal Surgery: A Bumpy Road Towards Individualized Management.
Prudent intraoperative fluid replacement therapy, inotropes, and vasoactive drugs should be guided by adequate hemodynamic monitoring. The study aimed to evaluate the single-centre practice on intraoperative fluid therapy in abdominal surgery (AS). The evaluation, based on a review of medical files, included 235 patients (103 men), aged 60 ± 15 years who underwent AS between September and November 2017. Fluid therapy was analyzed in terms of quality and quantity. There were 124 high-risk patients according to the American Society of Anaesthesiologists Classification (ASA Class 3+) and 89 high-risk procedures performed. The median duration of procedures was 175 (IQR 106-284) min. Eleven patients died post-operatively. The median fluids volume was 10.4 mL/kg/h of anaesthesia, including 9.1 mL/kg/h of crystalloids and 2.7 mL/kg/h of synthetic colloids. Patients undergoing longer than the median procedures received significantly fewer fluids than those who underwent shorter procedures. The volume of fluids in the longer procedures depended on the procedural risk classification and was significantly greater in high-risk patients undergoing high-risk surgery. Patients who died received significantly more fluids than survivors. In all patients, a non-invasive blood pressure monitoring was used and only six patients had therapy guided by metabolic equilibrium. The fluid therapy used was liberal but complied with the recommendations regarding the type of fluid and risk-adjusted dosing. Hemodynamic monitoring was suboptimal and requires modifications. In conclusion, the optimization of intraoperative fluid therapy requires a balanced and standardized approach consistent with treatment procedures.


Electrochemical study of ferrocenemethanol-modified layered double hydroxides composite matrix: application to glucose amperometric biosensor.
A novel amperometric glucose sensor based on co-immobilization of ferrocenemethanol (MeOHFc) and glucose oxidase (GOD) in the layered double hydroxides (LDHs) was described. MeOHFc immobilized in LDHs played effectively the role of an electron shuttle and allowed the detection of glucose at 0.25 V (versus SCE), with dramatically reduced interference from easily oxidizable constituents. The sensor (LDHs/MeOHFc/GOD) exhibited a relatively fast response (response time was about 5s), low detection limit (3 microM), and high sensitivity (ca. 60 mA M(-1)cm(-2)) with a linear range of 6.7 x 10(-6) to 3.86 x 10(-4)M of glucose. Apparent Michaelis-Menten constant was calculated to be 2.25 mM.


Chemical derivatization for enhancing sensitivity during LC/ESI-MS/MS quantification of steroids in biological samples: a review.
Sensitive and specific methods for the detection, characterization and quantification of endogenous steroids in body fluids or tissues are necessary for the diagnosis, pathological analysis and treatment of many diseases. Recently, liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) has been widely used for these purposes due to its specificity and versatility. However, the ESI efficiency and fragmentation behavior of some steroids are poor, which lead to a low sensitivity. Chemical derivatization is one of the most effective methods to improve the detection characteristics of steroids in ESI-MS/MS. Based on this background, this article reviews the recent advances in chemical derivatization for the trace quantification of steroids in biological samples by LC/ESI-MS/MS. The derivatization in ESI-MS/MS is based on tagging a proton-affinitive or permanently charged moiety on the target steroid. Introduction/formation of a fragmentable moiety suitable for the selected reaction monitoring by the derivatization also enhances the sensitivity. The stable isotope-coded derivatization procedures for the steroid analysis are also described.


Cross-sectional survey of sleep, fatigue and mental health in veterinary anaesthesia personnel.
To evaluate the sleep quality, prevalence of fatigue and depressive symptoms in veterinary anaesthesia personnel. Anonymous online voluntary survey. Sleep quality, fatigue, depressive symptoms and self-perceived burnout were scored using the Pittsburgh Sleep Quality Index (PSQI), Fatigue Severity Scale (FSS), Patient Health Questionnaire-9 (PHQ-9) and single-item burnout measure, respectively. Demographic data and questions about work-related fatigue, out-of-hours duty, transport and rest periods were included. PSQI, FSS and PHQ-9 scores were compared using Spearman rank correlation tests. Responses from 393 participants were obtained from an estimated population of 1374 including diplomates of the American and European Colleges of Veterinary An(a)esthesia and Analgesia (43.9%), residency-trained veterinarians (15.6%), residents-in-training (13.8%) and veterinary technicians and nurses (12.0%), from 32 countries. Most were employed in clinical university teaching hospitals (54.2%) or clinical private practice (41.5%). PSQI scores > 5 were reported by 71.2% of respondents, with 52.4% reporting insufficient sleep to meet their job demands. Many showed high or borderline fatigue (56.4%), and 74.7% reported mistakes due to work-related fatigue. Major depressive symptoms (PHQ-9 score ≥ 10) were found in 42.7%, with 19.2% reporting they had thought about suicide or self-harm in the previous 2 weeks. Over half (54.8%) met the criteria for burnout and more veterinary nurses and technicians suffered from burnout than other roles, with 79.6% of this group affected (p < 0.001). Scores for PSQI and FSS [r (388) = 0.40, p < 0.001]; PSQI and PHQ-9 [r (389) = 0.23, p < 0.001]; and FSS and PHQ-9 [r (387) = 0.24, p < 0.001] were all positively correlated. This survey demonstrates a high prevalence of poor sleep, fatigue, depressive symptoms and burnout in veterinary anaesthesia personnel, and more should be done to improve the health of those in the profession.


Mineralized calcium carbonate/xanthan gum microspheres for lysozyme adsorption.
Calcium carbonate/xanthan gum (Ca2CO3/XG) microspheres were prepared using biomimetic mineralization method for lysozyme (Ly) adsorption. The morphology of Ca2CO3/XG microspheres was characterized by field emission scanning electron microscope (FE-SEM). The Ly adsorption behavior was verified by Fourier transform infrared (FTIR) and in situ fluorescence microscope images. The effects of pHs on lysozyme adsorption were investigated as well. It was revealed that CaCO3/XG microspheres could immobilize lysozyme efficiently via electrostatic interactions with adsorption rate and adsorption quantity of 58.55 ± 0.56% and 18.7 ± 1.2 μg/mg as the pH was 7.0. Comparatively, the values markedly improved to 80.97 ± 0.15% and 24.3 ± 0.1 μg/mg respectively as the pH was 9.0 (p < 0.05). Additionally, UV and fluorescence spectrum showed that Ly maintained its original secondary structure during the adsorption/desorption process. The study therefore demonstrated that CaCO3/XG microspheres can be used as a practical and efficient support for Ly adsorption and desorption.


Recent updates of carbapenem antibiotics.
Carbapenems are among the most commonly used and the most efficient antibiotics since they are relatively resistant to hydrolysis by most β-lactamases, they target penicillin-binding proteins, and generally have broad-spectrum antibacterial effect. In this review, we described the initial discovery and development of carbapenems, chemical characteristics, in vitro/in vivo activities, resistance studies, and clinical investigations for traditional carbapenem antibiotics in the market; imipenem-cilastatin, meropenem, ertapenem, doripenem, biapenem, panipenem/betamipron in addition to newer carbapenems such as razupenem, tebipenem, tomopenem, and sanfetrinem. We focused on the literature published from 2010 to 2016.


Integrating patient values and preferences in healthcare: a systematic review of qualitative evidence.
To identify and thematically analyse how healthcare professionals (HCPs) integrate patient values and preferences ('values integration') in primary care for adults with non-communicable diseases (NCDs). Systematic review and meta-aggregation methods were used for extraction, synthesis and analysis of qualitative evidence. Relevant records were sourced using keywords to search 12 databases (ASSIA, CINAHL, DARE, EMBASE, ERIC, Google Scholar, GreyLit, Ovid-MEDLINE, PsycINFO, PubMed-MEDLINE, Scopus and Web of Science). Records needed to be published between 2000 and 2020 and report qualitative methods and findings in English involving HCP participants regarding primary care for adult patients. Relevant data including participant quotations, authors' observations, interpretations and conclusions were extracted, synthesised and analysed in a phased approach using a modified version of the Joanna Briggs Institute (JBI) Data Extraction Tool, as well as EPPI Reviewer and NVivo software. The JBI Critical Appraisal Checklist for Qualitative Research was used to assess methodological quality of included records. Thirty-one records involving >1032 HCP participants and 1823 HCP-patient encounters were reviewed. Findings included 143 approaches to values integration in clinical care, thematically analysed and synthesised into four themes: (1) approaches of concern; (2) approaches of competence; (3) approaches of communication and (4) approaches of congruence. Confidence in the quality of included records was deemed high. HCPs incorporate patient values and preferences in healthcare through a variety of approaches including showing concern for the patient as a person, demonstrating competence at managing diseases, communicating with patients as partners and tailoring, adjusting and balancing overall care. Themes in this review provide a novel framework for understanding and addressing values integration in clinical care and provide useful insights for policymakers, educators and practitioners. CRD42020166002.


Calcium sensing and signaling are impaired in the lumbar spine of a rat model of congenital kyphosis.
Kyphosis involves spines curving excessively backward beyond their physiological curvature. Although the normal structure of the spinal vertebrae is extremely important for maintaining posture and the normal function of the thoracic and abdominal organs, our knowledge concerning the pathogenesis of the disease is insufficient. We herein report that the downregulation of the calcium signaling pathway is involved in the pathogenesis of congenital kyphosis. The third to fifth lumbar spine segments, the kyphotic region of Ishibashi (IS) rats, which are used as a model of congenital kyphoscoliosis, were collected. A DNA microarray, quantitative PCR, Western blotting, and immunohistochemistry were used to measure the expression of genes and proteins related to intracellular calcium signaling. We found that the expression of calcium-sensing receptor (CaSR) and transient receptor potential vanilloid 1 (Trpv1)-two receptors involved in the calcium signaling-was decreased in the lumbar spine of IS rats. We also observed that the number of CaSR-immunoreactive and Trpv1-immunoreactive cells in the lumbar spine of IS rats was lower than in wild-type rats. Furthermore, the expression of intracellular molecules downstream of these receptors, such as phosphorylated protein kinase C, c-Jun N-terminal kinase, and neural EGFL-like 1, was also reduced. In fact, the calcium content in the lumbar spine of IS rats was significantly lower than that in wild-type rats. These results indicate that adequate calcium signaling is extremely important for the regulation of normal bone formation and may also be a key factor for understanding the pathogenesis of congenital kyphosis.


Ontogeny of relationship of middle ear and temporomandibular (squamomandibular) joint in mammals. III. Morphology and ontogeny in scandentia and primates.
The ontogeny of the mandibular joint and the middle ear region was studied in Tupaia javanica, Microcebus murinus, Nycticebus coucang and Tarsius bancanus. During development, a passage connection was found between the mandibular condyle and Meckel's cartilage that is produced by the primordium of the lateral pterygoid muscle. The articular disk is formed separately, and it appears later in development. A theory is presented on the interpretation of these findings.


Attitudes of medical students toward careers in general surgery.
Changes to general surgical undergraduate curricula, alongside changes in work force and postgraduate training, may be associated with a decline in interest in surgical careers. This study examines the attitudes of students toward surgical training and their career intentions. A prospective, questionnaire-based survey was submitted to final year students at the end of their general surgery attachment over a single academic year at a UK medical school. Career ambitions and reasoning were assessed. Of 223 eligible students, 193 (87%) completed the questionnaire. There were 118 (61%) females and 75 (39%) males with a median (range) age of 23 (21-41) years. Ninety-eight (51%) respondents undertook their placement at a Teaching Hospital, whereas 93 (41%) were attached to a District General Hospital. One-hundred forty-three (74%) students felt that a four-week attachment had given them a satisfactory exposure to General Surgery, and 36 (19%) disagreed. Sixty-eight (53%) students were unable to select a single specialty that they would most like to pursue as a future career. Of the remainder, 23 (12%) chose general surgery, 24 (12%) chose general medicine, and 22 (11%) chose general practice. Seventy-eight (40%) students would consider a career in general surgery, and 75 (39%) would not; 40 (29%) were undecided. The two most popular attractions to general surgery were challenging postgraduate training and highly regarded career esteem. The two most common disincentives were family considerations and the sacrifice of personal time. Fewer than half of the final year medical students surveyed were willing to consider general surgery as a future career choice. Potential disincentives should be targeted to promote recruitment into the specialty.


Reduced mastication during growth inhibits cognitive function by affecting trigeminal ganglia and modulating Wnt signaling pathway and ARHGAP33 molecular transmission.
Binding of brain-derived neurotrophic factor (BDNF) to its receptor tyrosine kinase B (TrkB) is essential for the development of the hippocampus, which regulates memory and learning. Decreased masticatory stimulation during growth reportedly increases BDNF expression while decreasing TrkB expression in the hippocampus. Increased BDNF expression is associated with Wnt family member 3A (Wnt3a) expression and decreased expression of Rho GTPase Activating Protein 33 (ARHGAP33), which regulates intracellular transport of TrkB. TrkB expression may be decreased at the cell surface and affects the hippocampus via BDNF/TrkB signaling. Mastication affects cerebral blood flow and the neural cascade that occurs through the trigeminal nerve and hippocampus. In the current study, we hypothesized that decreased masticatory stimulation reduces memory/learning in mice due to altered Wnt3a and ARHGAP33 expression, which are related to memory/learning functions in the hippocampus. To test this hypothesis, we fed mice a powdered diet until 14 weeks of age and analyzed the BDNF and TrkB mRNA expression in the right hippocampus using real-time polymerase chain reaction and Wnt3a and ARHGAP33 levels in the left hippocampus using western blotting. Furthermore, we used staining to assess BDNF and TrkB expression in the hippocampus and the number of nerve cells, the average size of each single cell and the area of intercellular spaces of the trigeminal ganglion (TG). We found that decreased masticatory stimulation affected the expression of BDNF, Wnt3a, ARHGAP33, and TrkB proteins in the hippocampus, as well as memory/learning. The experimental group showed significantly decreased numbers of neurons and increased the area of intercellular spaces in the TG. Our findings suggest that reduced masticatory stimulation during growth induces a decline in memory/learning by modulating molecular transmission mechanisms in the hippocampus and TG.


Patterns of marihuana smoking among Brazilian students.
Changes in frequency of marihuana smoking over time were investigated by interviewing forty-seven Brazilian students from São Paulo between 18 and 24 years old, of both sexes. From their report, it was concluded that the course of smoking frequency follows two predominant patterns. In one of them, the 'Stable Pattern', subjects report increasing consumption up to a peak frequency where they remain for a relatively long and stable period of time. In the other one, the 'Descending Pattern', subjects report a gradual increase up to a peak, followed by a clear decline in rate of use. Two other patterns were also detected in a small number of subjects. The diversity of patterns identified stresses the difficulty in predicting the course of marihuana smoking frequency by young people. The relationship between marihuana smoking and the use of other drugs was also investigated. The only drugs that were reported to be regularly consumed by the majority of subjects were alcohol and tobacco, while 90% of the subjects reported having tried at least one other illegal drug.


In vitro and in vivo evaluation of a dry powder endotracheal insufflator device for use in dose-dependent preclinical studies in mice.
The aim of this study was to evaluate the ability of the Penn-Century Dry Powder Insufflator for mice (DP-4M) to reproducibly, uniformly, and deeply deliver dry powders for inhalation in the mouse lung. Itraconazole-based dry powder formulations produced by spray-drying were different in terms of composition (different ratios of drug and mannitol, with or without phospholipids), but relatively similar in terms of particle size and mass median aerodynamic diameter. The ability of the dry powder insufflator to disaggregate each formulation was the same, indicated by the absence of a statistically significant difference between the particle size distribution parameters, as measured by laser scattering. The emitted fraction varied in vivo compared to the in vitro condition. Fluorescent particle distribution in the lungs was uniform and reached the alveolar spaces, as visualized by fluorescent microscopy. In terms of drug recovery in lung tissue, a minimum administered powder mass (in this case ∼1 mg) was necessary to recover at least 30% of the emitted dose in the lung and to obtain reproducible pulmonary concentrations. To reduce the dose administered in the lung, it was preferable to dilute the active ingredient within the carrier instead of reducing the dry powder mass inserted in the sampling chamber. Dry powder insufflators are devices usable in dose-dependent preclinical trials but have critical parameters to efficiently deliver reproducible doses depending on the type of formulation.


Characterization of the melanocortin-4-receptor nonsense mutation W16X in vitro and in vivo.
Several genetic diseases are triggered by nonsense mutations leading to the formation of truncated and defective proteins. Aminoglycosides have the capability to mediate a bypass of stop mutations during translation thus resulting in a rescue of protein expression. So far no attention has been directed to obesity-associated stop mutations as targets for nonsense suppression. Herein, we focus on the characterization of the melanocortin-4-receptor (MC4R) nonsense allele W16X identified in obese subjects. Cell culture assays revealed a loss-of-function of Mc4r(X16) characterized by impaired surface expression and defect signaling. The aminoglycoside G-418 restored Mc4r(X16) function in vitro demonstrating that Mc4r(X16) is susceptible to nonsense suppression. For the evaluation of nonsense suppression in vivo, we generated a Mc4r(X16) knock-in mouse line by gene targeting. Mc4r(X16) knock-in mice developed hyperphagia, impaired glucose tolerance, severe obesity and an increased body length demonstrating that this new mouse model resembles typical characteristics of Mc4r deficiency. In a first therapeutic trial, the aminoglycosides gentamicin and amikacin induced no amelioration of obesity. Further experiments with Mc4r(X16) knock-in mice will be instrumental to establish nonsense suppression for Mc4r as an obesity-associated target gene expressed in the central nervous system.


Chemical characterisation and technical assessment of agri-food residues, marine matrices, and wild grasses in the South Mediterranean area: A considerable inflow for biorefineries.
The integration of easily available and under-exploited biomasses is considered a sustainable strategy in biorefining approaches. Mediterranean countries, especially Algeria, Morocco, and Tunisia, offer such under-exploited waste of different origins. This study revealed the chemical composition and phytochemical characteristics of various agri-food side-products, marine residues, and wild grasses collected in the Maghreb region. Results showed that these wastes contained variable proportions of polysaccharides, lignin, constitute molecules (proteins, lipids, and inorganic molecules) and, various secondary metabolites, mainly flavonoids and condensed tannins. Based on this, the Mediterranean waste was divided into three categories. The first category included waste with high lignin content (40 wt%). The second category contained waste with lignin content below 10 wt% and structural carbohydrate content below 50 wt%. Additionally, the waste in this category comprised noticeable amounts of flavonoids and condensed tannins, particularly from thistle, speedwell, and spurge. Finally, the third category included waste with lignin content above 15 wt% and carbohydrate content in the range of 45-55 wt%. The results also showed that the waste in the third category has a chemical composition similar to that of raw materials envisioned for use in European or North American commercial biorefineries. The findings of this study indicate that the biomass waste employed in this study can be used to develop marketable bioproducts and may be a potential raw material for a biorefinery facility.


[Intermediate filaments in the lung macrophages and endothelial cells in chronic alcoholism and suppurative-destructive lung diseases].
Accumulation of intermediate filaments in lung macrophages and endotheliocytes has been found in patients with chronic alcoholism and purulent destructive pulmonary diseases. Excess accumulation of cytoskeletal elements reflects cell dystrophy. The authors believe that impairment of macrophage function may favour the lingering of the suppurative process.


Retrieval of broken intra-medullary guide wire in femoral shaft fracture: A case report and surgical technique.
Intramedullary Nailing is a standard procedure for fixation of various fractures in orthopedic practice. With the procedure also important is being aware of the complications and methods of managing them. A broken or stuck hardware can result in these procedures. We present a case with broken guide wire in a case of femoral shaft fracture in a young individual and the technique we used to retrieve it retrogradely from the fracture site. This technique shall be a useful technique to all the orthopedic surgeons if such a situation arises.


Normalization of cerebellar RNA synthesis and mRNA levels after treatment of graft versus host disease.
We have previously shown that neonatal rats with graft versus host disease (GVHD) (1) synthesize significantly less cerebellar RNA, (2) have RNA that is less translationally active, and (3) have changes in the relative abundance of certain mRNAs, including the induction of one coding for protein r that is present neither in control cerebellum nor in other brain regions at any age. Here we report on the ability of the cerebellum to recover from GVHD-induced changes in the synthesis of total RNA and in the relative levels of specific mRNAs. In order to halt the disease, 11-day-old diseased Fischer animals were injected with hyperimmune alloantiserum daily for 3 days. Cytoplasmic RNAs were isolated from the cerebella of 14-day-old serum-treated animals, their diseased littermates that were not treated with serum, and littermate controls. Comparison, by two-dimensional gel analysis, of the in vitro synthesized mRNA translation products showed that most GVHD-induced alterations in the levels of specific mRNAs were not present in serum-treated animals. In particular, protein r was not synthesized by cerebellar RNAs isolated from serum-treated animals. These results show that the adverse effects of this disease are reversible at the molecular level.


Opioid elevation of intracellular free calcium: possible mechanisms and physiological relevance.
Opioid receptors are seven transmembrane domain Gi/G0 protein-coupled receptors, the activation of which stimulates a variety of intracellular signalling mechanisms including activation of inwardly rectifying potassium channels, and inhibition of both voltage-operated N-type Ca2+ channels and adenylyl cyclase activity. It is now apparent that like many other Gi/G0-coupled receptors, opioid receptor activation can significantly elevate intracellular free Ca2+ ([Ca2+]i), although the mechanism underlying this phenomenon is not well understood. In some cases opioid receptor activation alone appears to elevate [Ca2+]i, but in many cases it requires concomitant activation of Gq-coupled receptors, which themselves stimulate Ca2+ release from intracellular stores via the inositol phosphate pathway. Given the number of Ca2+-sensitive processes known to occur in cells, there are therefore a myriad of situations in which opioid receptor-mediated elevations of [Ca2+](i) may be important. Here, we review the literature documenting opioid receptor-mediated elevations of [Ca2+]i, discussing both the possible mechanisms underlying this phenomenon and its potential physiological relevance.


Impact of coil position and electrophysiological monitoring on determination of motor thresholds to transcranial magnetic stimulation.
We compared motor and movement thresholds to transcranial magnetic stimulation (TMS) in healthy subjects and investigated the effect of different coil positions on thresholds and MEP (motor-evoked potential) amplitudes. The abductor pollicis brevis (APB) 'hot spot' and a standard scalp position were stimulated. APB resting motor threshold (APB MEP-MT) defined by the '5/10' electrophysiological method was compared with movement threshold (MOV-MT), defined by visualization of movements. Additionally, APB MEP-MTs were evaluated with the '3/6 method,' and MEPs were recorded at a stimulation intensity of 120% APB MEP-MT at each position. APB MEP-MTs were significantly lower by stimulation of the 'hot spot' than of the standard position, and significantly lower than MOV-MTs (n=15). There were no significant differences between the '3/6' and the '5/10' methods, or between APB MEP amplitudes by stimulating each position at 120% APB MEP-MT. Coil position and electrophysiological monitoring influenced motor threshold determinations. Performing 6 instead of 10 trials did not produce different threshold measurements. Adjustment of intensity according to APB MEP-MT at the stimulated position did not influence APB MEP amplitudes. Standardization of stimulation positions, nomenclature and criteria for threshold measurements should be considered in design and comparison of TMS protocols.


Different susceptibilities of platelet phospholipids to various phospholipases and modifications induced by thrombin. Possible evidence of rearrangement of lipid domains.
On the membrane surface of the human platelet, phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were hydrolyzed to different extents by the snake venom phospholipases A2 of varying pI values. The susceptibility of platelet phospholipids to basic phospholipase A2 of Naja nigricollis (pI 10.6) has been reported (Wang et al. (1986) Biochim. Biophys. Acta 856, 244-258). The susceptibilities of platelet phospholipids to acidic phospholipase A2 of Naja naja atra (pI 5.2) and to neutral phospholipase A2 of Hemachatus haemachatus (pI 7.3) were investigated in this study. In gel-filtered platelets, acidic phospholipase A2 hydrolyzed 35% PC and 10% PE, while neutral phospholipase A2 hydrolyzed 18% PC and 3% PE. In thrombin-induced shape-changed platelets, acidic phospholipase A2 hydrolyzed 20% PC and 10% PE, while neutral phospholipase A2 hydrolyzed 15% PC and 6% PE. In thrombin-activated platelets, acidic phospholipase A2 hydrolyzed 25% PC and 7% PE, while neutral phospholipase A2 hydrolyzed 25% PC and 10% PE. Sequential lipid hydrolysis experiments showed that basic phospholipase A2 of Naja nigricollis could hydrolyze the remaining PC and PE in the membrane previously treated with the neutral enzyme. The results may mean that: the PC and the PE domains exist on the platelet membrane surface; and the lipid domains on the membrane surface of resting platelets are rearranged by thrombin.


Intestinal uptake of macromolecules. VI. Uptake of protein antigen in vivo in normal rats and in rats infected with Nippostrongylus brasiliensis or subjected to mild systemic anaphylaxis.
Adult Sprague-Dawley rats weighing approximately g were fed bovine serum albumin and sodium bicarbonate by gavage. Serum was obtained at intervals after feeding and tested for immunoreactive bovine serum albumin by radioimmunoassay. Nanogram amounts of immunoreactive bovine serum albumin were detected in serum; peak values were obtained after 4 and 6 hr. The influence of intestinal inflammation on protein uptake was examined in two model systems. Infection of rats with Nippostrongylus brasiliensis was accompanied by partial villous atrophy in the intestinal segments harboring adult worms and mild systemic anaphylaxis in the rat was accompanied by increased intestinal vascular and mucosal permeability. Enhanced uptake of BSA was observed before and shortly after self-cure of infection and during mild systemic anaphylaxis. The molecular size of immunoreactive bovine serum albumin approximated that of the administered bovine serum albumin; no small fragments of bovine serum albumin bearing antigenic determinants were detected.


Serum lipid profiles and dyslipidaemia are associated with retinal microvascular changes in children and adolescents.
The present study aims to assess the relationship between serum lipid parameters and retinal microvascular calibres in children and adolescents. A total of 950 participants aged 7 to 19 years were recruited. Central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) were measured from digital retinal images. Serological testing was performed to obtain lipid profiles. Dyslipidaemia was defined according to the US national expert panel guideline. After adjusted for age, sex, mean arterial blood pressure, axial length, body mass index and the fellow retinal vascular calibre, no significant association was found between retinal vascular diameters and any lipid parameters (all P > 0.05) in children younger than 12 years. Among the adolescents 12 years and older, increased triglycerides, total cholesterol, low-density lipoprotein cholesterol, and apoB were associated with decrease in CRAE (β = -1.33, -1.83, -1.92 and -7.18, P = 0.031, 0.003, 0.006, and 0.009, respectively). Compared with normolipidemic counterparts, adolescents with dyslipidaemia had significantly narrower retinal arteriolar diameters. No significant relationship between lipid subclass levels and CRVE was revealed in adolescents. The present findings suggest that the elevation of atherogenic lipids in adolescents is closely related to the adverse changes of retinal arterioles. Dyslipidaemia may affect systemic microvasculature from childhood on.


How should we assess the impact of genetic changes on ageing in model species?
One of the most active branches of genetic research is the quest for the genetic determinants of ageing. The ultimate goal of much of this effort is to understand ageing in humans. In addition to work on human genetics, many researchers look to model organisms in order to find genetic variation that can affect ageing. The fly Drosophila, the worm Caenorhabditis elegans, rodents, and yeast are among the most widely studied species. However, while great care is given to the genetic aspects of this form of research, the methods used to assess the impact of the genetic changes on the organism in question do not always provide as complete a picture as possible of ageing's multi-facetted nature. In this commentary, I propose a systematic and rigorous approach, and draw attention to research that has already demonstrated the value of such an approach.


Within-visit variability of blood pressure and all-cause and cardiovascular mortality among US adults.
The association between within-visit variability of systolic blood pressure (SBP) and diastolic blood pressure (DBP) and all-cause and cardiovascular (CVD) mortality was examined using the Third National Health and Nutrition Survey (n=15,317). Three SBP and DBP readings were taken by physicians during a single medical evaluation. Within-visit variability for each participant was defined using the standard deviation of SBP and DBP across these measurements. Mortality was assessed over 14 years (n=3848 and n=1684 deaths from all causes and CVD, respectively). After age, sex, and race-ethnicity adjustment, the hazard ratios (95% confidence intervals) for all-cause mortality associated with the 4 highest quintiles of within-visit standard deviation of SBP (2.00-2.99 mm Hg, 3.00-3.99 mm Hg, 4.00-5.29 mm Hg, and ≥5.30 mm Hg) compared with participants in the lowest quintile of within-visit standard deviation of SBP (<2.0 mm Hg) were 1.04 (0.87-1.26), 1.09 (0.92-1.29), 1.06 (0.88-1.28), and 1.13 (0.95-1.33), respectively (P=.136). The analogous hazard ratios for CVD mortality were 0.95 (0.69-1.32), 0.96 (0.67-1.36), 0.95 (0.74-1.23), and 1.04 (0.80-1.35), respectively (P=.566). No association with mortality was present after further adjustment and when modeling within-visit standard deviation of SBP as a continuous variable. Standard deviation of DBP was not associated with mortality.


[Role of Fas and FasL expression in apoptosis of pulmonary artery smooth muscle cells in hypoxia induced by inhibition of Na+/H+ exchanger isoform-1 in rat].
To investigate the role of Fas and FasL expression in apoptosis of pulmonary artery smooth muscle cells (PASMCs) in hypoxia induced by inhibition of Na(+)/H(+) exchanger isoform-1 (NHE-1) in rat. The cells were cultured in hypoxia (<1% O(2)) for 2, 6, 12, 24 and 48 hours respectively. Then cell apoptosis was observed with terminal deoxynudeotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). The changes in fas and fasl mRNA expression in PASMCs were detected by semi-quantitative reverse transcription-polymerase chain reaction (sqRT-PCR) in vitro. The expression of Fas and FasL protein in cells was determined immunohistochemically. No significant changes in the expression of fas/fasL mRNA and protein between cells transfected with NHE-1 ribozyme gene and cells transfected with pLXSN, or non-transfected control in hypoxia. Apoptosis of PASMCs induced by NHE-1 inhibition may occur independently of Fas/FasL death pathway.


Retention of cast endodontic posts: comparison of cementing agents.
Zinc phosphate, glass-ionomer, and polycarboxylate cements were compared with a composite for ability to retain cast gold posts in prepared root canals of extracted teeth. Zinc phosphate and glass-ionomer cements were found to be more retentive than polycarboxylate cement and composite.


Insect response to mixture and monoculture patches of Michigan old-field annual herbs.
1. The response of insects to the presence of discrete arrays of mixture and monoculture plots of weed species normally dominant in first-year Michigan old-fields was studied. 2. Plant species used were Amaranthus retroflexus, Chenopodium album, Panicum capillare and Setaria viridis. 3. Two experiments were implemented, one with pure stands of each species and the other with mixture stands of equiproportionate numbers of each plant species (Fig. 1). 4. Sucking insects had significantly higher weights, lower diversities and greater expressions of dominance in Chenopodium stands (Tables 2 and 3) (Fig. 2). Chewing insects showed a similar response with regard to weight (Fig. 2), but not with respect to diversity and evenness indices (Tables 2 and 3). Non-herbivorous insects did not differentiate between the species when in pure stands. 5. Although there was a significantly greater mean weight of sucking insects in the mixture plots, none of the insect guilds differed significantly among the mixture treatments with respect to the parameters tested (Tables 2 and 3). 6. Results of this study support the C4 avoidance hypothesis (Caswell et al., 1973), especially with regard to sucking insects. 7. Continued studies investigating plant-insect interaction are discussed.


Neuropharmacological potentials of β-carboline alkaloids for neuropsychiatric disorders.
Neuropsychiatric disorders are diseases of the central nervous system (CNS) which are characterised by complex pathomechanisms that including homeostatic failure, malfunction, atrophy, pathology remodelling and reactivity anomaly of the neuronal system where treatment options remain challenging. β-Carboline (βC) alkaloids are scaffolds of structurally diverse tricyclic pyrido[3,4-b]indole alkaloid with vast occurrence in nature. Their unique structural features which favour interactions with enzymes and protein receptor targets account for their potent neuropharmacological properties. However, our current understanding of their biological mechanisms for these beneficial effects, especially for neuropsychiatric disorders is sparse. Therefore, we present a comprehensive review of the scientific progress in the last two decades on the prospective pharmacology and physiology of the βC alkaloids in the treatment of some neuropsychiatric conditions such as depression, anxiety, Alzheimer's disease, Parkinson's disease, brain tumour, essential tremor, epilepsy and seizure, licking behaviour, dystonia, agnosia, spasm, positive ingestive response as demonstrated in non-clinical models. The current evidence supports that βC alkaloids offer potential therapeutic agents against most of these disorders and amenable for further drug design.


[Production of human insulin from proinsulin by a biological catalysis].
The conversion of porcine and human proinsulins to insulin by enzymatic hydrolysis induced by trypsin and carboxypeptidase B was studied. The conditions of reactions in the presence of trypsin (pure or immobilized in PAAG) and carboxypeptidase B were determined. The possibility of insulin production by the use of immobilized trypsin and carboxypeptidase B for practical purposes was shown.


Direct Coupling of Methane and Carbon Dioxide on Tantalum Cluster Cations.
Understanding molecular-scale reaction mechanisms is crucial for the design of modern catalysts with industrial prospect. Through joint experimental and computational studies, we investigate the direct coupling reaction of CH4 and CO2 , two abundant greenhouse gases, mediated by Ta1,4 + ions to form larger oxygenated hydrocarbons. Coherent with proposed elementary steps, we expose products of CH4 dehydrogenation [Ta1,4 CH2 ]+ to CO2 in a ring electrode ion trap. Product analysis and reaction kinetics indicate a predisposition of the tetramers for C-O coupling with a conversion to products of CH2 O, whereas atomic cations enable C-C coupling yielding CH2 CO. Selected experimental findings are supported by thermodynamic computations, connecting structure, electronic properties, and catalyst function. Moreover, the study of bare Ta1,4 + compounds indicates that methane dehydrogenation is a significant initial step in the direct coupling reaction, enabling new, yet unknown reaction pathways.


Assessing the causes for the dentistry selection as a job by Iranian dental students: A Questionnaire Survey.
Objective: The purpose of the current research is to discover the causes for the dentistry selection as a profession by senior dental scholars in Iran. Materials & Methods: Surveys are distributed between the first-year to the sixth-year senior dental scholars at the Scholl of Dentistry in Medical Sciences Qazvin University in Iran. The survey presented in a lecture hall at the terminal of the secondary term in the 2011-2012 academic years. The survey included 30 parts, and the pupils asked to measure the significance of any part for choosing dentistry as a profession, on a 10-points scale. In addition, T-test and ANOVA utilized for the data analysis. Results: The answering ratio in the research is 55% (out of 100%) of the pupils delivered. Ninety-six students (93.2%) selected it as an initial selection. Dentistry as a job which is "insurer of financial independence" was gained a most rate via 82.5% of the pupils raised and a comparable amount of the students (75.7%), assigned a highest rate to the parameter "I love to enhance many money". Dentistry as a "science-based job" was also given a score by 80.6% of the pupils. Conclusion: There are no variations in the motivation between men and women students. It obtained that "insurer of financial independence" and "I love to enhance many money" are critical action parameters in the dental pupils population.


Differential distribution of tau proteins in developing cat cerebellum.
The differential distribution and phosphorylation of tau proteins in cat cerebellum was studied with two well characterized antibodies, TAU-1 and TAU-2. TAU-1 detects tau proteins in axons, and the epitope in perikarya and dendrites is masked by phosphorylation. TAU-2 detects a phosphorylation-independent epitope on tau proteins. The molecular composition of tau proteins in the range of 45 kD to 64 kD at birth changed after the first postnatal month to a set of several adult variants of higher molecular weights in the range of 59 kD to 95 kD. The appearance of tau proteins in subsets of axons corresponds to the axonal maturation of cerebellar local-circuit neurons in granular and molecular layers and confirms previous studies. Tau proteins were also identified in synapses by immunofluorescent double-staining with synapsin I, located in the pinceau around the Purkinje cells, and in glomeruli. Dephosphorylation of juvenile cerebellar tissue by alkaline phosphatase indicated indirectly the presence of differentially phosphorylated tau forms mainly in juvenile ages. Additional TAU-1 immunoreactivity was unmasked in numerous perikarya and dendrites of stellate cells, and in cell bodies of granule cells. Purkinje cell bodies were stained transiently at juvenile ages. During postnatal development, the intensity of the phosphate-dependent staining decreased, suggesting that phosphorylation of tau proteins in perikarya and dendrites may be essential for early steps in neuronal morphogenesis during cat cerebellum development.


Fret studies of conformational changes in heparin-binding peptides.
FRET (Förster Resonance Energy Transfer) was applied to study structural properties of heparin-binding peptides containing the sequence XBBBXXBX where 'X' represents hydropathic or uncharged and 'B' represents basic amino acids. Internally quenched fluorogenic peptides were synthesized containing the fluorescent donor oaminobenzoic acid (o-Abz) and the acceptor dinitrophenyl ethylenediamine (Eddnp) group. Using the CONTIN computational package, distance distributions were recovered from time resolved fluorescence data, associated to end-to-end distances of the peptides. The peptides containing three or four repeat units have random structure in aqueous medium, and the interaction with low molecular weight heparin stabilized short end-to end distances. Experiments in water/trifluoroethanol (TFE) mixtures showed changes in distance distributions compatible with compact conformations stabilized above 40% volume content of TFE in the mixture. Similar changes in distance distributions were also observed for the peptides in interaction with SDS micelles in aqueous suspensions and circular dichroism data revealed alpha-helix formation in the peptides in interaction with heparin, SDS micelles or the co-solvent TFE. The process is dependent on electrostatic and hydrogen bond interactions and the end-to-end distances obtained are smaller than expected for the peptides in linear α-helix conformation, indicating the occurrence of structural arrangements leading to additional decrease in the distances.


A simple method for purification of epoxide hydratase from rat liver.
Rat liver epoxide hydratase was purified 460-fold to homogeneity by detergent solubilization and ion-exchange chromatography. The enzyme obtained in high yield (36%) exhibited a specific activity of 479nmol of styrene glycol formed/min per mg of protein, with styrene oxide as substrate. Only one polypeptide-staining band, mol.wt. 49500, was visible after sodium dodecyl sulphate/polyacrylamide-gel electrophoresis.


Extensive Upper Airway Hematoma Secondary to Supratherapeutic Warfarin Anticoagulation.
A 63-year-old female presented to the emergency department complaining of cough, neck swelling, dysphagia, and dysphonia for two days, with a past medical history of atrial fibrillation managed with warfarin. Investigations revealed a supratherapeutic international normalised ratio (greater than 10). Imaging and endoscopic examination showed an extensive retropharyngeal hematoma with significant mass effect on the airway. A rare but potentially fatal complication of warfarin anticoagulation is upper airway hematoma, with violent coughing described as an inciting cause. Signs of airway compromise necessitate specialist consultation and definitive airway management, while mild cases without airway concerns can be managed conservatively with medical anticoagulation reversal.


The useful agent to have an ideal biological scaffold.
Tissue engineering which is applied in regenerative medicine has three basic components: cells, scaffolds and growth factors. This multidisciplinary field can regulate cell behaviors in different conditions using scaffolds and growth factors. Scaffolds perform this regulation with their structural, mechanical, functional and bioinductive properties and growth factors by attaching to and activating their receptors in cells. There are various types of biological extracellular matrix (ECM) and polymeric scaffolds in tissue engineering. Recently, many researchers have turned to using biological ECM rather than polymeric scaffolds because of its safety and growth factors. Therefore, selection the right scaffold with the best properties tailored to clinical use is an ideal way to regulate cell behaviors in order to repair or improve damaged tissue functions in regenerative medicine. In this review we first divided properties of biological scaffold into intrinsic and extrinsic elements and then explain the components of each element. Finally, the types of scaffold storage methods and their advantages and disadvantages are examined.


Acanthocephaloides irregularis n. sp. (Acanthocephala: Arhythmacanthidae) from marine fishes off the Ukrainian Black Sea coast.
Acanthocephaloides irregularis n. sp. (Arhythmacanthidae) is described from four species of marine fishes in the Gulf of Odessa and Sukhyi Lyman, Ukrainan Black Sea waters, making it the tenth species of the genus. The hosts are the combtooth blenny Parablennius zvonimiri (Kolombatovic) (Blenniidae), the mushroom goby Ponticola eurycephalus (Kessler) (Gobiidae), the tubenose goby Proterorhinus marmoratus (Pallas) (Gobiidae) and the black-striped pipefish Syngnathus abaster Risso (Syngnathidae). The new species is most similar to its closest relative, Acanthocephaloides propinquus (Dujardin, 1845), in proboscis shape and armature (12 longitudinal rows of 5 hooks) and the shape of the trunk, reproductive system and lemnisci, but differs in having randomly distributed trunk spines. These trunk spines are organised in circular rings of individual spines separated by aspinose zones. The new species is also unique in having an anterior trunk collar, a very large triangular cephalic ganglion, nucleated pouches at the posterior end of the proboscis receptacle, and hooks and spines with roots bearing anterior manubria. Valid and invalid species of Acanthocephaloides Meyer, 1932 are listed and a key to all ten species is included.


Recombinant human interferon-alpha induced cytoreduction in chronic myelogenous leukemia. Results of a multicenter study.
Fourteen patients with Ph'-chromosome positive chronic myelogenous leukemia (CML) in first chronic phase were treated with recombinant interferon-alpha 2c. Interferon-alpha 2c 5 to 10 X 10(6) units s.c. was given for 12 weeks as an induction therapy. Maintenance treatment consisted of interferon-alpha 2c 5 X 10(6) units twice weekly s.c.. Two patients (14%) attained a complete clinical remission and 6 (43%) a partial remission, 3 of whom developed progressive disease during maintenance therapy. A complete disappearance of Ph'-chromosome was achieved in 1 patient. All patients had a more than 45% initial decline of the leukocyte count. Four out of ten patients with an initially enlarged spleen demonstrated reduction in spleen size. Influenza-like symptoms, anorexia, nausea, weight loss and fatigue were common side effects. Interferon-alpha is active in CML but additional clinical investigations are warranted to assess more precisely the therapeutic value of the interferons in this disease.


Associated injuries complicating the management of acetabular fractures: review and case studies.
The treatment of acetabular fractures has evolved considerably in the past three decades. Associated injuries to the femoral head, proximal femur, or femoral shaft can complicate the initial management of the acetabular fracture, and mandate a careful treatment strategy for optimal treatment of both the acetabular fracture and associated injury. These injuries may have a large impact on the clinical outcome. The surgeon must consider surgical approaches, timing, and alternative modes of fixation. A discussion with case illustrations is provided.


Practice patterns and outcomes of percutaneous coronary interventions in the United States: 1995 to 1997.
Randomized trials have demonstrated the superiority of coronary stents in combination with a platelet-focused pharmacologic approach in percutaneous coronary intervention (PCI). However, nationally representative data examining the impact of these technologies on patient outcomes and costs remain scarce. This study sought to determine the real-world impact of changes in the use of stents and anticoagulant agents in PCI on outcomes and costs. A nationally representative sample of 37,088 patients who underwent PCI from October 1995 to October 1997 was identified from in-patient hospital claims data acquired from HCIASachs. Utilization of coronary stents, antiplatelet and anticoagulant agents, and outcome measurements of in-hospital death, coronary artery bypass grafting (CABG), repeat PCI, bleeding, and costs were analyzed in 6-month intervals. Acute events (death, urgent CABG, or PCI) decreased (p <0.001), whereas use of stents, abciximab, or both, increased (p <0.001). Dosages of heparin and bleeding complications declined significantly (p <0.001) over the 2-year period. Heparin dosages were higher in patients who experienced bleeding or death than in those who did not (p <0.001). The average hospital length of stay decreased significantly (p <0.001), largely driven by a reduction in time between the procedure and hospital discharge. By the end of the study period, bleeding was the most frequent (5.5%) complication of PCI and was associated with considerable costs, adding $10,225 to baseline costs.


Assessing information and service needs of young adults with cancer at a single institution: the importance of information on cancer diagnosis, fertility preservation, diet, and exercise.
Young adults (YA) with cancer have unique psychosocial and medical needs. The objective of this study was to identify information and service needs important to YA cancer patients. A supportive care needs survey was administered to ambulatory patients (<age 35 years) who were within 5 years of completing therapy at an adult hospital. Participants were asked to rate the importance of 18 sources of information or resources on a scale from 1 to 10. The relationship between gender, type of cancer, current treatment status, and marital status on the importance of these factors was explored using ANOVA. Median age of 243 respondents was 28 years (range 17-35); 61% male. The most common diagnoses were: lymphoma (28%), leukemia (19%), testis (16%), CNS (9.5%), and sarcoma (8.6%). Forty percent were currently receiving treatment; the majority were single/never married (67%). Thirty-eight percent of respondents felt it was important or very important to receive care in a dedicated unit with other young people. More than 80% rated the following items at least 8/10 in importance: information on their specific malignancy (treatment, risk of recurrence), effects of treatment on fertility, information on maintaining a healthy diet, and exercise/physical fitness during cancer treatment. Women were more likely to consider information/service needs more important than men. YA's have clear supportive care preferences and needs. Developing programs that incorporate the services identified as important should improve quality of life, psychosocial adjustment, and other outcomes during and after cancer therapy.


Effects of preparation methods on potato microstructure and digestibility: An in vitro study.
The effects of preparation method (boiled, cooled, and reheated) on the structural characteristics and in vitro digestibility of potato were investigated. The highest equilibrium starch hydrolysis was obtained after boiling (82.21%), followed by reheating (66.98%) and cooling (54.31%). The potato after cooling treatment exhibited a narrower melting temperature range and a higher melting enthalpy compared with the potatoes after boiling and the microwave reheating. X-ray diffraction patterns revealed that the relative crystallinity of the cooled potato was higher than those of the reheated and boiled potatoes, consistent with the results in melting enthalpy. Moreover, compared with the boiled potato, a large number of wrinkles were observed on the surface of the cooled potato, whereas after microwave reheating, larger clearances of starch granule regions were found. This study demonstrated that cooling and microwave reheating significantly affected the potato's microstructure and digestibility and were suggested as alternative choices to prepare potato dishes.


Variation in the management of cT1 renal cancer by surgical hospital volume: A nationwide study.
To analyse variation in clinical management of cT1 renal cell carcinoma (RCC) in the Netherlands related to surgical hospital volume (HV). Patients diagnosed with cT1 RCC during 2014-2020 were identified in the Netherlands Cancer Registry. Patient and tumour characteristics were retrieved. Hospitals performing kidney cancer surgery were categorised by annual HV as low (HV < 25), medium (HV = 25-49) and high (HV > 50). Trends over time in nephron-sparing strategies for cT1a and cT1b were evaluated. Patient, tumour and treatment characteristics of (partial) nephrectomies were compared by HV. Variation in applied treatment was studied by HV. Between 2014 and 2020, 10 964 patients were diagnosed with cT1 RCC. Over time, a clear increase in nephron-sparing management was observed. The majority of cT1a underwent a partial nephrectomy (PN), although less PNs were applied over time (from 48% in 2014 to 41% in 2020). Active surveillance (AS) was increasingly applied (from 18% to 32%). For cT1a, 85% received nephron-sparing management in all HV categories, either with AS, PN or focal therapy (FT). For T1b, radical nephrectomy (RN) remained the most common treatment (from 57% to 50%). Patients in high-volume hospitals underwent more often PN (35%) for T1b compared with medium HV (28%) and low HV (19%). HV is related to variation in the management of cT1 RCC in the Netherlands. The EAU guidelines have recommended PN as preferred treatment for cT1 RCC. In most patients with cT1a, nephron-sparing management was applied in all HV categories, although differences in applied strategy were found and PN was more frequently used in high HV. For T1b, high HV was associated with less appliance of RN, whereas PN was increasingly used. Therefore, closer guideline adherence was found in high-volume hospitals.


Predicting visual outcomes after decompression of pituitary tumours based on stratified inner-retinal layer thickness and age.
The purpose of the study was to evaluate the potential role of stratified preoperative optical coherence tomography (OCT) measurements and age in predicting postoperative visual field (VF) improvement among adult patients with chiasmal compression due to pituitary tumours after decompression surgery. Postoperative visual outcomes were analysed using mean deviation of the VF test. Eyes were divided into three groups based on preoperative OCT parameters including peripapillary retinal nerve fibre layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness: groups 1, 2 and 3 with pRNFL thickness <65 μm, 65 μm or more but <85 μm, and 85 μm or more, respectively. The GCIPL thickness was also divided into three groups based on values ranging from 55 to 77 μm. Each group was further categorized according to age: 20 years or older but younger than 40 years, 40 years or older but younger than 60, and 60 years or older. This study included 197 eyes of 197 patients with chiasmal compression due to pituitary tumours. No patient showed complete VF recovery in group 1 with a preoperative pRNFL thickness <65 μm or a GCIPL thickness <55 μm regardless of age. These groups showed the worst VF outcome (pRNFL, p = 0.0001; GCIPL, p < 0.0001). However, a significant recovery in VF (greater than 2 dB) was observed in 45% of group 1 patients based on pRNFL thickness and in 61.54% of group 1 patients according to GCIPL thickness. In groups 2 and 3 with a preoperative pRNFL thickness of 65 μm or more and a GCIPL thickness of 55 μm or more, the rate of complete VF recovery decreased as subjects' ages increased. Group 3 with a preoperative pRNFL thickness of 85 μm or more and a GCIPL thickness of 77 μm or more were 2.5-fold and 4.0-fold more likely to completely recover VF, respectively, compared with group 2. Stratified preoperative pRNFL and GCIPL thicknesses measured via OCT in different age categories are effective biomarkers for predicting visual functional outcomes.


Contrasting behavior of beta event-related synchronization and somatosensory evoked potential after median nerve stimulation during finger manipulation in man.
Electrical median nerve stimulation during rest results in two cortical responses: the somatosensory evoked potential (SEP); and the induced beta oscillations (beta event-related synchronization (ERS)). Both types of responses were recorded with electroencephalography and studied during rest and motor behavior in eight normal subjects. During manipulation of a cube with the fingers of the right hand, the beta ERS around 20 Hz, induced by right hand median nerve stimulation, is significantly suppressed, whereas the long-latency SEP components are significantly enhanced. The results suggest that both phenomena can be interpreted as responses of different neuronal structures in sensorimotor areas.


Screening for glaucomatous visual field loss with automated threshold perimetry.
We examined 27 glaucomatous eyes and 154 normal eyes with automated threshold perimetry. Previously suggested algorithms for detecting mild to moderate glaucomatous visual field loss, primarily by comparing the sensitivity of corresponding clusters of points above and below the horizontal meridian, yielded results remarkably consistent with those of our earlier series: 93% (25 of 27) of abnormal and 88% (135 of 154) of normal eyes were correctly identified. Excluding unreliable examinations increased specificity from 88% to 93%. Test duration was similar to results with the Field Analyzer's older, purportedly slower operating system.


Early death of mice cloned from somatic cells.
Here we report that the lifespan of mice cloned from somatic cells is significantly shorter than that of genotype- and sex-matched controls, most likely due to severe pneumonia and hepatic failure. This finding demonstrates the possibility of long-term deleterious effects of somatic-cell cloning, even after normal birth.


Association of transport-defective light chains with immunoglobulin heavy chain binding protein.
Immunoglobulin light chains are usually secreted from cells when they are synthesized alone or in molar excess of heavy chains, but, there have been reports of nonsecreted light chains. We wished to determine whether immunoglobulin heavy chain binding protein (BiP), which blocks the transport of free heavy chains, might be responsible for the lack of secretion of some light chains. In two murine lymphoid cell lines that synthesize but do not secrete immunoglobulin light chains, the free light chain polymers were found bound to BiP. Examination of 20 other cell lines and hybridomas failed to disclose any cells synthesizing free or excess light chains that associated with BiP, in all cases the free light chains were secreted as dimers. Despite their association with BiP and their blocked secretion, the aberrant light chains could combine with heavy chains and could be secreted as intact Ig molecules. Thus, while light chains do not usually express signals which allow them to bind to BiP, it appears that such signals can be expressed on certain light chains, resulting in their combination with BiP and blocked secretion. When single chain mutant cell lines are isolated from parental lines producing both heavy and light chains, they are almost always light chain producers suggesting that free heavy chains are much more toxic than free light chains. In both PC700 and P3X63Ag cells, however, clones that have lost either heavy chains or transport-defective light chains are present at the same frequency. Our findings that the light chains in both of these lines are associated with BiP raise the possibility that BiP actually contributes to heavy chain toxicity instead of preventing it.


Cryo-EM structure of the needle filament tip complex of the Salmonella type III secretion injectisome.
Type III secretion systems are multiprotein molecular machines required for the virulence of several important bacterial pathogens. The central element of these machines is the injectisome, a ∼5-Md multiprotein structure that mediates the delivery of bacterially encoded proteins into eukaryotic target cells. The injectisome is composed of a cytoplasmic sorting platform, and a membrane-embedded needle complex, which is made up of a multiring base and a needle-like filament that extends several nanometers from the bacterial surface. The needle filament is capped at its distal end by another substructure known as the tip complex, which is crucial for the translocation of effector proteins through the eukaryotic cell plasma membrane. Here we report the cryo-EM structure of the Salmonella Typhimurium needle tip complex docked onto the needle filament tip. Combined with a detailed analysis of structurally guided mutants, this study provides major insight into the assembly and function of this essential component of the type III secretion protein injection machine.


Center the margin: Equity-Based Assessment and Response Strategies to Reach Underserved Communities Using a Telehealth Service Delivery Model.
While the COVID-19 pandemic has initiated drastic personal, social, organizational, and governmental level changes, it also sparked a unique opportunity. More Behavior Analysis providers had the option to respond to this crisis by offering telehealth services. As providers address their ability to conduct sessions using electronic delivery methods, there is also a need to prioritize those who historically have been forgotten in the formation of systemwide change: Black Indigenous People of Color (BIPOC). This paper outlines barriers to accessing telehealth treatment and includes options for individual providers and organizations to address disparity and other relevant contextual variables within their telehealth models.


IMP3 Expression as a Potential Tumour Marker in High-Risk Localisations of Cutaneous Squamous Cell Carcinoma: IMP3 in Metastatic cSCC.
High IMP3 expression is correlated with a worse outcome. Until now, there have been no data about IMP3 expression and clinical outcome for high-risk localisation of squamous cell carcinoma of the skin (cSCC). One-hundred twenty-two patients with cSCC of the lip and ear were included, and IMP3 expression in the tumours was immunohistochemically assessed in different evaluation approaches. Subsequently, subgroups were analysed in a matched pair approach and correlated with clinical pathologic parameters. In the following, different IMP3 analysis methods were tested for clinical suitability. We found a significant correlation between IMP3 expression and risk for lymph node metastasis, local relapse, and progression-free survival. On basis of our data, we suggest a prognostic benefit cutoff value for high (>50%) and low (<50%) IMP3 expression. Thus, IMP3 expression has a high scientific potential for further studies and could potentially be used as a prognostic marker in diagnostic and therapeutic decision-making.


Translational control: a new dimension in embryonic stem cell network analysis.
Systems biology studies have revealed transcriptional networks and proteomic signatures critical for embryonic stem cell (ESC) function. In this issue of Cell Stem Cell, Sampath et al. (2008) demonstrate that translation is also differentially controlled in undifferentiated versus differentiated ESCs.


Attic retraction pockets: Classification system.
Although attic retractions have previously been classified into Grades 0 through IV, it is often not possible to assign attic retraction pockets into a single specific category. The present study describes an improved classification system based on otoscopic and endoscopic visualization of the retraction pocket fundus, the ossicular status in the attic, degree of scutal erosion, and the presence or absence of cholesteatoma. One hundred and fifty-four patients (200 ears) with different grades of attic retraction pockets who were seen by a tertiary referral otology center between August 2015 and July 2018 were selected for this study. The new classification system (Grades I, IIa, IIb, IIIa, IIIb, IIIc, IVa, IVb, IVc, and V) was applied to these retraction pockets. Pure tone audiometry was obtained. All attic retraction pockets could be classified precisely using the new classification system. Forty-four of 200 (22%) of ears showed Grade I Attic retraction, 18 ears showed Grade IIa (9%), 14 showed Grade IIb (7%), 28 showed Grade IIIa (14%), 12 showed IIIb (6%), 20 showed Grade IIIc (10%), 16 showed grade IVa (8%), 12 showed grade IVb (6%), 28 showed grade IVc (14%), and eight showed grade V (4%) attic retraction pockets. Grades I, IIa, IIb, IIIa, and IVa had no significant hearing loss. Average hearing loss was 42 dB and 52 dB in Grades IIIb and IIIc, 44 dB and 58 dB in Grades IVb and IVc, and 61 dB in Grade V. 5 Laryngoscope, 130: 2034-2039, 2020.


Event-Related Theta Power during Lexical-Semantic Retrieval and Decision Conflict is Modulated by Alcohol Intoxication: Anatomically Constrained MEG.
Language processing is commonly characterized by an event-related increase in theta power (4-7 Hz) in scalp EEG. Oscillatory brain dynamics underlying alcohol's effects on language are poorly understood despite impairments on verbal tasks. To investigate how moderate alcohol intoxication modulates event-related theta activity during visual word processing, healthy social drinkers (N = 22, 11 females) participated in both alcohol (0.6 g/kg ethanol for men, 0.55 g/kg for women) and placebo conditions in a counterbalanced design. They performed a double-duty lexical decision task as they detected real words among non-words. An additional requirement to respond to all real words that also referred to animals induced response conflict. High density whole-head MEG signals and midline scalp EEG data were decomposed for each trial with Morlet wavelets. Each person's reconstructed cortical surface was used to constrain noise-normalized distributed minimum norm inverse solutions for theta frequencies. Alcohol intoxication increased reaction time and marginally affected accuracy. The overall spatio-temporal pattern is consistent with the left-lateralized fronto-temporal activation observed in language studies applying time-domain analysis. Event-related theta power was sensitive to the two functions manipulated by the task. First, theta estimated to the left-lateralized fronto-temporal areas reflected lexical-semantic retrieval, indicating that this measure is well suited for investigating the neural basis of language functions. While alcohol attenuated theta power overall, it was particularly deleterious to semantic retrieval since it reduced theta to real words but not pseudowords. Second, a highly overlapping prefrontal network comprising lateral prefrontal and anterior cingulate cortex was sensitive to decision conflict and was also affected by intoxication, in agreement with previous studies indicating that executive functions are especially vulnerable to alcohol intoxication.


Onco-condensates: formation, multi-component organization, and biological functions.
Numerous cellular processes occur in the context of condensates, a type of large, membrane-less biomolecular assembly generated through phase separation. These condensates function as a hub of diversified cellular events by concentrating the required components. Cancer frequently coopts biomolecular condensation mechanisms to promote survival and/or proliferation. Onco-condensates, which refer to those that have causal roles or are critically involved in tumorigenicity, operate to abnormally elevate biological output of a proliferative process, or to suppress a tumor-suppressive pathway, thereby promoting oncogenesis. Here, we summarize advances regarding how multi-component onco-condensates are established and organized to promote oncogenesis, with those related to chromatin and transcription deregulation used as showcases. A better understanding should enable development of new means of targeting onco-condensates as potential therapeutics.


A Role for the Inflammasome in Spontaneous Labor at Term.
Inflammasomes are signaling platforms that, upon sensing pathogens and sterile stressors, mediate the release of mature forms of interleukin (IL)-1β and IL-18. The aims of this study were to determine (i) the expression of major inflammasome components in the chorioamniotic membranes in spontaneous labor at term, (ii) whether there are changes in the inflammasome components associated with the activation of caspase-1 and caspase-4, and (iii) whether these events are associated with the release of the mature forms of IL-1β and IL-18. Chorioamniotic membranes were collected from women at term with and without spontaneous labor. mRNA abundance and protein concentrations of inflammasome components, nucleotide-binding oligomerization domain-containing (NOD)1 and NOD2 proteins, caspase-1, caspase-4, IL-1β, and IL-18 were quantified by qRT-PCR (n = 28-29 each), ELISA (n = 10 each) or immunoblotting (n = 8 each), and immunohistochemistry (n = 10 each). Active caspase-1 and caspase-4, as well as mature IL-18, were determined by immunoblotting (n = 4 each), and pro- and mature forms of IL-1β were determined by ELISA (n = 4-7 each). Inflammasome components and NOD proteins were expressed in the chorioamniotic membranes obtained from women at term. The chorioamniotic membranes from women who underwent labor had (i) higher concentrations of NLRP3 (NOD-like receptor family, pyrin domain-containing protein 3) and NOD1 protein, (ii) greater immunoreactivity for caspase-1 and caspase-4, (iii) a greater quantity of the active form of caspase-1 (p20), and (iv) higher mRNA abundance and protein concentrations of pro- and mature IL-1β. However, mRNA abundance and protein concentrations of the mature form of IL-18 were not increased in tissues from women who underwent labor at term. Spontaneous labor at term is characterized by the expression of inflammasome components, which may participate in the activation of caspase-1 and lead to the cleavage and release of mature IL-1β by the chorioamniotic membranes. These results support the participation of the inflammasome in the mechanisms responsible for spontaneous parturition at term.


Spontaneous multivessel coronary artery dissection with anomalous coronary artery.
Spontaneous coronary artery dissection (SCAD) is one of the rare causes of acute coronary syndrome in young healthy individuals especially women without having any conventional risk factors for coronary artery disease. We describe a case of 34-year-old healthy man with diffuse multiple SCADs who presented with acute coronary syndrome and was managed conservatively with an uneventful course on long-term follow-up.


Large interindividual variations in the pharmacokinetics of oral 6-mercaptopurine in maintenance therapy of children with acute leukaemia and non-Hodgkin lymphoma.
The concentrations of 6-mercaptopurine were studied in plasma and red blood cells from 10 children with acute leukaemia or non-Hodgkin lymphoma receiving oral maintenance therapy. The doses varied between 25 and 79 mg/m2 body surface once daily. Large interindividual differences were found in the concentrations both in plasma and in red blood cells. There was no clear relationship between the dose administered and the concentrations obtained. However, in each patient the concentrations in plasma and in red blood cells were very similar. In most patients, the peak concentrations were reached 1-2 hours after dose intake and the concentrations then declined with half-lives less than 1 hour. Further studies are necessary to evaluate the potential value of drug level monitoring in optimizing treatment with oral 6-mercaptopurine.


[The rate of recovery of left atrial contractile function after the transition to sinus rhythm in patients with paroxysmal atrial fibrillation].
In the examination of 120 patients without valvular heart disease suffering from atrial fibrillation paroxysms mechanical function of the left atrium (LA) was assessed using Doppler echocardiography. The majority of the examinees had dilated LA which is thought to be arrhythmogenic. The recovery of the sinus rhythm is accompanied by electromechanical dissociation the longest duration of which took place in subjects exposed to electrical defibrillation. An inverse relationship was established between the time of the last fibrillation and recovery of LA mechanical function. The duration of the electromechanical dissociation of the atria holds prognostic importance in relation to recurrent fibrillation.


Pyrazole-5-carboxamides, novel inhibitors of receptor for advanced glycation end products (RAGE).
In an effort to develop novel inhibitors of receptor for advanced glycation end products (RAGE) for the treatment of Alzheimer's disease, a series of pyrazole-5-carboxamides were designed, synthesized and biologically evaluated. Analyses of the extensive structure-activity relationship (SAR) led us to identify a 4-fluorophenoxy analog (40) that exhibited improved in vitro RAGE inhibitory activity and more favorable aqueous solubility than the parent 2-aminopyrimidine, 1. Surface plasmon resonance (SPR) and molecular docking study strongly supported the RAGE inhibitory activity of pyrazole-5-carboxamides. The brain Aβ-lowering effect of 40 is also described.


Estimation of age using aspartic acid racemisation in human dentin in Indian population.
The quest to identify an accurate method of age estimation, had lead to the evaluation of aspartic acid racemisation in hard tissues of the human remains using high performance liquid chromatography (HPLC). Our study is aimed at the applicability of the racemisation technique to use dentin as the sample to estimate the age in South Indian sub-population. Thirty-six non-carious teeth from living individuals distributed among 6 age groups (6 each), sexes (18 each) and jaws (18 each) were analysed for dextro (d) and levo (l) forms of aspartic acid using high performance liquid chromatography (HPLC) technique and their racemisation ratio were calculated for each tooth sample. High correlation was obtained between the aspartic acid racemisation rates in dentin and age of the individual with an error limited to ±3 years. Racemisation rates in teeth did not significantly differ between the sexes or jaws. The d-aspartic acid accumulation in dentin is synchronous with the aging of an individual and can be used as an accurate method of age estimation in our population.


[Cortical organization of different languages with different proficiency levels].
Several studies have enhanced differences and similarities in the processing of early and late acquired languages. Anatomic and functional differences have demonstrated how bilingualism exerts executive functions, dependent of the prefrontal cortex in the frontal lobe. To study the cortical differences, neurophysiologically measured in school-aged children, in the processing of known and unknown languages. We have measured the recognition processes of words in several languages, specifically Spanish, English, Portuguese and Mandarin Chinese, as well as their event-related potentials (ERP) correlates in 10 year-old children. The greater knowledge of a language (in our study, Spanish) associates shorter latencies in ERP and a greater activity in both early (N200) and late (N400) components of temporal regions, demonstrating both a direct relation between practice and speed of processing of the language and the consolidation of the linguistic information in the temporal lobe, while less familiar or unknown languages show longer latencies and a greater involvement of posterior brain areas, as well as a different lateralization probably due to a higher effort put on its integration, mostly in late processing stages of linguistic information, which ultimately reflects a clear effect of the neuroplasticity generated by practice, as more efficient and stable neural networks are created after being trained for a long time, in contrast with what occurs with those which have not been sufficiently stimulated. Mandarin Chinese's organization in the brain cortex shows bilateral with right dominant lateralization as well as longer ERP latencies.


Screening for diabetes among presumptive tuberculosis patients at a tertiary care centre in Pondicherry, India.
Designated microscopy centre (DMC) attached to a tertiary care centre in Pondicherry, India. To determine 1) the proportion of diabetes mellitus (DM), 2) the additional yield of newly diagnosed DM cases, and 3) the number needed to screen (NNS) to find a new case of DM among presumed TB patients. An institution-based cross-sectional study was carried out among 650 presumed TB patients attending the DMC. Capillary blood glucose was measured using fasting blood sugar and/or oral glucose tolerance test, and evaluated according to the World Health Organization criteria. Of 570 presumed TB patients evaluated for DM, 121 (21.2%) were found to be diabetic. Of these, 69 were previously known to have DM, while 52 were newly diagnosed. The additional yield of diabetes was 43%. The NNS to detect a new case of DM was 11; among those aged >40 years, the NNS was 9.3, and among smear-positive TB patients it was 4.6. One fifth of the presumed TB patients had diabetes, and nearly half of these patients were newly diagnosed. Opportunity screening of presumed TB patients for DM in routine care will help in early detection of diabetes and pre-diabetes.


The value of a new ultrasound stress test in assessment and treatment of clinically detected hip instability.
Fifty patients with clinical suspicion of hip dislocation were investigated prospectively with a dynamic ultrasound stress test. A posterior force was applied to hips in flexion and any movement between the femoral head and the acetabulum was measured. The results of this test showed that posterior movement ranged from 0 to 13.0 mm. Hips that were clinically normal had a mean movement of 1.4 mm, hips with minor clinical instability had a mean movement of 0.6 mm, hips with moderate instability had a mean movement of 4.5 mm, and those with major instability had a mean movement of 5.1 mm. This was statistically significant to a 1% confidence interval. We propose two groups of ultrasound-detected movement: group A less than 5.0 mm representing physiologic laxity, and group B greater than or equal to 5.0 mm being pathological and requiring treatment.


Amelioration of immune cell number depletion and potentiation of depressed detoxification system of tumor-bearing mice by curcumin.
The true therapeutic benefit of the use of natural products, especially acceptable dietary components such as curcumin, which can spare the normal cells and boost host immunity, has opened new horizons in cancer prevention and treatment. In our model system we used Ehrlich's ascites carcinoma cells grown in peritoneal carity of Swiss albino mice and curcumin was fed every alternative day. Here, we report that curcumin administration to tumor-bearing mice decreased tumor cell number significantly in a dose-dependent manner. Furthermore, tumor-induced depletion of immune cell number of the host, as was evidenced from the decrease in bone marrow progenitor as well as thymic and splenic mononuclear cell numbers, was reintrated by curcumin. In fact, curcumin inhibited tumor-induced apoptosis of both thymocytes and splenocytes thereby restoring immune cell numbers to normal level in treated Ehrlich's ascites carcinoma-bearing mice. Moreover, curcumin was not toxic to the host; rather in tumor-bearing mice it inhibited hematopoietic toxicity, acted as a hepatoprotective agent and activated depressed anti-oxidant and detoxification systems. The ability of curcumin to regress tumor as well as to protect the host from tumor-induced immunosuppression and toxicity strongly supports the candidacy of curcumin as a potential agent for the dietary therapy of cancer.


Student perceptions of the value they bring to APPE sites.
Partner institutions invest much time and effort into educating pharmacy students, and ideally students should be viewed as valuable to those sites. Prior studies have demonstrated the perceptions that preceptors and administrators have about the value of students at their sites. However, students' perceptions of their own value at practice sites have not been described. Students do have perceptions about their own value to sites, and such information could be useful in learning about potential areas in which students perceive they are making an impact on patient care. Five hundred qualitative student responses to an evaluation question regarding perceived value were analyzed from a United States pharmacy school. Nineteen categories of value were extracted. Responses fit into multiple categories, resulting in 783 data points for analysis. The categories were analyzed overall and with respect to advanced pharmacy practice experience (APPE) type (acute care, community, hospital, ambulatory care, and elective). Descriptive statistics were used. Providing patient counseling (15.7%) and therapeutic recommendations (14.7%) were the highest perceived values. In adult acute care and hospital APPEs, "providing therapeutic recommendations" (24.4% and 19.1% respectively) were rated highest. In community, ambulatory care, and elective APPEs, "providing patient counseling" (25%, 23%, and 13.8%, respectively) was highest rated. Students perceive they are valuable to practice sites in several ways. These results demonstrate that students' self-reported perceptions of the value they bring to their sites are consistent with other literature reports based on perception of preceptors regarding student value to patient care.


Responses of vegetation activity to the daytime and nighttime warming in Northwest China.
Though temperature over the past three decades has shown an asynchronous warming trend between daytime and nighttime, the response of vegetation activity to such non-uniform warming is still not very clear. In this study, the least squares linear trend analysis and geographic information system spatial analysis were conducted to analyze the spatiotemporal patterns of the daytime and nighttime warming based on the daily temperature data from 1982 to 2015 in Northwest China. The normalized difference vegetation index (NDVI) from Global Inventory Monitoring and Modeling System and vegetation type data were used to investigate the responses of vegetation activity to the daytime and nighttime warming using the partial correlation analysis. Our results suggested that (1) there was a very significant increasing trend in both daytime and nighttime temperatures in Northwest China from 1982 to 2015; night temperatures increased about 1.2 times faster than daytime temperatures, showing diurnal asymmetric warming; (2) the responses of vegetation activity to daytime and nighttime warming in Northwest China showed a distinct spatial pattern; the change in night temperatures had a more significant (positive in most regions) effect on vegetation; (3) various types of vegetation responded differently to asymmetric daytime and nighttime warming. Grassland NDVI, broad-leaved, and coniferous forest NDVI significantly responded to daytime warming. Shrub NDVI and desert NDVI significantly responded to night warming. These findings can deepen the understanding of the effects of the daytime and nighttime warming on vegetation activities in arid regions in the context of the current asymmetric warming.