Effects of tea polyphenols on cardiac function and myocardial ultrastructure in rats after repeated +Gz stress.
Objective. To observe the effects of tea polyphenols (TP) on cardiac function and myocardial ultrastructure in rats after repeated +10 Gz stress. Method. Twenty four male Wistar rats were randomly divided into three groups (n=8 each): group A (control), group B (+10 Gz), group C (+Gz with TP). Group B and C were repeatedly exposed to +10 Gz (each for 30 s, onset rate about 0.5 G/s, 3 times/d with +1 Gz 1 min intervals, 3 d/wk, 4 weeks in total), but group A was only submitted to +1 Gz. TP (200 mg kg-1) was given orally to group C about 1 h prior to the +Gz experiment, and distilled water was given to group A and B. Function of isolated rat working hearts and myocardial ultrastructure were observed. Result. A significant decrease of left ventricular systolic pressure (LVSP) and injury of myocardial structure in rats were demonstrated after repeated +10 Gz stress. But TP could remarkably elevate the LVSP and improve myocardial ultrastructural injury in +10 Gz stressed rats. Conclusion. These results indicated that repeated high G exposure may produce cardiac structural and functional injuries in rats which might be partly related to free radical metabolism; and antioxidant TP had significant protective effects on the hearts of +Gz stressed rats.


cGMP-dependent protein kinase. Autophosphorylation changes the characteristics of binding site 1.
cGMP-dependent protein kinase binds 4 mol cGMP/mol enzyme to two different sites. Binding to site 1 (apparent Kd 17 nM) shows positive cooperativity and is inhibited by Mg . ATP, whereas binding to site 2 (apparent Kd 100-150 nM) is non-cooperative and not affected by Mg . ATP. Autophosphorylation of the enzyme abolishes the cooperative binding to site 1 and the inhibitory effect of Mg . ATP. The association (K1) and dissociation (K-1) rate constant for site 2 and K1 for site 1 are not affected significantly by Mg . ATP or autophosphorylation. The dissociation rate from site 1 measured in the presence of 1 mM unlabelled cGMP is decreased threefold and over tenfold by Mg . ATP and autophosphorylation, respectively. In contrast, the dissociation rate from site 1 measured after a 500-fold dilution of the enzyme-ligand complex is 100-fold faster than that determined in the presence of 1 mM cGMP and is only slightly influenced by Mg . ATP or autophosphorylation. Only Kd values calculated with the latter K-1 values are similar to the Kd values obtained by equilibrium binding. These results suggest that autophosphorylation of cGMP-dependent protein kinase affects mainly the binding characteristics of site 1.


Metabolic regulation by the PGC-1α and PGC-1β coactivators in larval zebrafish (Danio rerio).
The peroxisome proliferator activated receptor γ coactivator-1 (PGC-1) family is composed of three coactivators whose role in regulating mammalian bioenergetics regulation is clear, but is much less certain in other vertebrates. Current evidence suggests that in fish, PGC-1α and PGC-1β may exhibit much less redundancy in the control of fatty acid oxidation and mitochondrial biogenesis compared to mammals. To assess these roles directly, we knocked down PGC-1α and PGC-1β expression with morpholinos in zebrafish embryos, and we investigated the resulting molecular and physiological phenotypes. First, we found no effects of either morpholinos on larval hatching, heart rates and oxygen consumption over the first few days of development. Next, at 3 days post fertilization (dpf), we confirmed by real time PCR a specific knock down of both coactivators, that resulted in a significant reduction in the transcript levels of citrate synthase (CS), 3-hydroxyacyl-CoA dehydrogenase (HOAD), and medium-chain acyl-coenzyme A dehydrogenase (MCAD) in both morphant groups. However, there was no effect on transcription factors' gene expression except for a marked reduction in estrogen related receptor α (ERRα) transcripts in PGC-1α morphants. Finally, we assessed whole embryonic enzyme activity for CS, cytochrome oxidase (COX), HOAD and carnitine palmitoyltransferase I (CPT-1) at 4 dpf. The only significant effect of the knockdown was a reduced CS activity in PGC-1α morphants and a counterintuitive increase of cytochrome oxidase activity in PGC-1β morphants. Overall, our results indicate that in larval zebrafish, PGC-1α and PGC-1β both play a role in regulating expression of important mitochondrial genes potentially through ERRα.


Habitual physical activity measured by accelerometer and survival in maintenance hemodialysis patients.
The association between mortality and physical activity based on self-report questionnaire in hemodialysis patients has been reported previously. However, because self-report is a subjective assessment, evaluating true physical activity is difficult. This study investigated the prognostic significance of habitual physical activity on 7-year survival in a cohort of clinically stable and adequately dialyzed patients. A total of 202 Japanese outpatients who were undergoing maintenance hemodialysis three times per week at the hemodialysis center of Sagami Junkanki Clinic (Japan) from October 2002 to February 2012 were followed for up to 7 years. Physical activity was evaluated using an accelerometer at study entry and is expressed as the amount of time a patient engaged in physical activity on nondialysis days. Cox proportional hazard regression was used to assess the contribution of habitual physical activity to all-cause mortality. The median patient age was 64 (25th, 75th percentiles, 57, 72) years, 52.0% of the patients were women, and the median time on hemodialysis was 40.0 (25th, 75th percentiles, 16.8, 119.3) months at baseline. During a median follow-up of 45 months, 34 patients died. On multivariable analysis, the hazard ratio for all-cause mortality per 10 min/d increase in physical activity was 0.78 (95% confidence interval, 0.66-0.92; P=0.002). Engaging in habitual physical activity among outpatients undergoing maintenance hemodialysis was associated with decreased mortality risk.


Partial inhibition of the early and late asthmatic response by a single dose of salmeterol.
The long-acting beta 2-agonist salmeterol has been suggested to have other pharmacologic activities, that is, antiinflammatory capacities, in addition to its bronchodilator properties. We investigated the protective effect of 50 micrograms salmeterol in a placebo-controlled study on house dust mite-induced early- and late-phase reactions in 19 atopic asthmatic subjects. FEV1 and methacholine airway reactivity (AR) were measured. Eosinophils and their activation markers in peripheral blood were counted as indirect parameters of inflammation. Corrections were made for confounding of bronchodilator effects by salmeterol and the spontaneous diurnal variation, using saline inhalation as a control. Salmeterol completely inhibited the fall in FEV1 up to 10 h after the house dust mite challenge. Nevertheless, after correction, a biphasic response was present in the salmeterol group. Salmeterol protected against the allergen-associated increase in AR 3 h after the challenge, but no protection was observed after 24 h. Salmeterol did not inhibit the allergen-induced changes in total number of eosinophils and their activation markers in peripheral blood. These data suggest that a single dose of salmeterol modifies allergen-induced airway responses, above all by sustained bronchodilation.


Glycemic dispersion: a new index for screening high glycemic variability.
For patients with diabetes, high-frequency and -amplitude glycemic variability may be more harmful than continuous hyperglycemia; however, there is still a lack of screening indicators that can quickly and easily assess the level of glycemic variability. The aim of this study was to investigate whether the glycemic dispersion index is effective for screening high glycemic variability. A total of 170 diabetes patients hospitalized in the Sixth Affiliated Hospital of Kunming Medical University were included in this study. After admission, the fasting plasma glucose, 2-hour postprandial plasma glucose, and glycosylated hemoglobin A1c were measured. The peripheral capillary blood glucose was measured seven times in 24 h, before and after each of three meals and before bedtime. The standard deviation of the seven peripheral blood glucose values was calculated, and a standard deviation of > 2.0 was used as the threshold of high glycemic variability. The glycemic dispersion index was calculated and its diagnostic efficacy for high glycemic variability was determined by the Mann-Whitney U test, receiver operating characteristic (ROC) curve and, Pearson correlation analysis. The glycemic dispersion index of patients with high glycemic variability was significantly higher than that of those with low glycemic variability (p < 0.01). The best cutoff value of the glycemic dispersion index for screening high glycemic variability was 4.21. The area under the curve (AUC) was 0.901 (95% CI: 0.856-0.945) and had a sensitivity of 0.781 and specificity of 0.905. It was correlated with the standard deviation of blood glucose values (r = 0.813, p < 0.01). The glycemic dispersion index had good sensitivity and specificity for screening high glycemic variability. It was significantly associated with the standard deviation of blood glucose concentration and is simple and easy to calculate. It was an effective screening indicator of high glycemic variability.


Spontaneously disappearing gallstones.
A case of spontaneously disappearing gallstones, in a patient who had no evidence of a biliary fistula or gallbladder surgery, is presented.


Influenza B infection and Kawasaki disease in an adolescent during the COVID-19 pandemic: a case report.
We report a case of Influenza B infection and Kawasaki disease in an adolescent, diagnosed during the COVID-19 pandemic. An asthmatic female adolescent presented with fever and flu-like symptoms for 7 days and was admitted with acute respiratory failure requiring mechanical ventilation. She progressed with hemodynamic instability responsive to vasoactive drugs. Antibiotic therapy and support measures were introduced, showing progressive hemodynamics and respiratory improvement, however with persistent fever and increased inflammatory markers. During the hospitalization, she developed bilateral non-purulent conjunctivitis, hand and feet desquamation, strawberry tongue, and cervical adenopathy, and was diagnosed with Kawasaki disease. She was prescribed intravenous immunoglobulin and, due to the refractory clinical conditions, corticosteroid therapy was added; 24 hours later, the patient was afebrile. No coronary changes were found. A full viral panel including COVID-19 C-reactive protein and serology could only isolate the Influenza B virus. During the hospitalization, she was diagnosed with pulmonary thromboembolism; coagulopathies were investigated, and she was diagnosed with heterozygous factor V Leiden mutation. There is a potential association between Kawasaki disease and infection with Influenza B or with other viruses such as coronavirus. Therefore, this association should be considered in pediatric patients, adolescents included, with prolonged febrile conditions.


[Correlation of slime production and pathogenicity of coagulase-negative staphylococci].
Coagulase-negative staphylococci have been increasingly recognized as pathogens in patients with indwelling medical devices. Slime production may be an important virulence factor. Slime production and antibiotic susceptibility were studied of 117 coagulase-negative staphylococci isolated from clinical specimens. The frequency of slime production among 26 coagulase-negative staphylococci was about three times higher than among 91 isolates regarded as contaminants. The former strains were isolated from 10 patients, 8 of which had device related infections. Multiply resistant cultures occurred in 22.2%, but all strains were susceptible to vancomycin.


Proper RPA acetylation promotes accurate DNA replication and repair.
The single-stranded DNA (ssDNA) binding protein complex RPA plays a critical role in promoting DNA replication and multiple DNA repair pathways. However, how RPA is regulated to achieve its functions precisely in these processes remains elusive. Here, we found that proper acetylation and deacetylation of RPA are required to regulate RPA function in promoting high-fidelity DNA replication and repair. We show that yeast RPA is acetylated on multiple conserved lysines by the acetyltransferase NuA4 upon DNA damage. Mimicking constitutive RPA acetylation or blocking its acetylation causes spontaneous mutations with the signature of micro-homology-mediated large deletions or insertions. In parallel, improper RPA acetylation/deacetylation impairs DNA double-strand break (DSB) repair by the accurate gene conversion or break-induced replication while increasing the error-prone repair by single-strand annealing or alternative end joining. Mechanistically, we show that proper acetylation and deacetylation of RPA ensure its normal nuclear localization and ssDNA binding ability. Importantly, mutation of the equivalent residues in human RPA1 also impairs RPA binding on ssDNA, leading to attenuated RAD51 loading and homologous recombination repair. Thus, timely RPA acetylation and deacetylation likely represent a conserved mechanism promoting high-fidelity replication and repair while discriminating the error-prone repair mechanisms in eukaryotes.


Clinician Perceptions of Implementing the Cultural Formulation Interview on a Mixed Forensic Unit.
The use of the Cultural Formulation Interview (CFI), a 16-item, semistructured, patient cultural assessment, in a forensic mental health setting has not been examined. Using a mixed-methods approach, we performed a pilot test of the CFI in an inpatient service that treats both forensic and nonforensic adult patients. Clinicians' attitudes toward adoption of the CFI was assessed quantitatively with the Evidence-Based Practices Attitudes Scale, which is used to measure provider attitudes toward adopting new treatments, and qualitatively with a semistructured interview. Assessments occurred up to five times to analyze changes with increasing CFI use. In the quantitative measures we observed a general openness to implementing the CFI throughout the implementation period. Compared with clinicians on civil units, forensic clinicians indicated they were less likely to implement the CFI over time if it were required rather than voluntary. Interviews with clinicians revealed concerns about the skills, ability, and confidence needed to implement the CFI, external requirements, and the ease of integrating the CFI into their practice. Based on our findings, forensic units could encourage CFI use after the clinician has determined that the patient is clinically stable, rather than at admission. Units could also incorporate information obtained from the CFI into current documentation to reduce administrative burden.


How diagnostic is ultrasound-guided neck mass biopsy (fine-needle capillary sampling biopsy technique)?: evaluation of 132 nonthyroid neck mass biopsies with pathologic analysis over 7 years at a single institution.
The purpose of this study was to evaluate the diagnostic value of ultrasound-guided neck mass biopsy (fine-needle capillary sampling biopsy [FNC] technique). With Institutional Review Board approval, all patients who had an ultrasound-guided neck mass FNC biopsy between January 2000 and December 2006 were retrieved from the ultrasound database. A total of 132 neck mass biopsies were performed in 124 patients. Patient demographics, procedure characteristics, and pathologic diagnoses were recorded. Of the 124 patients, 73 were female (mean age, 51.4 years). Biopsies were performed twice in 8 patients. A significant 200% increase from 2000 through 2002 to 2003 through 2004 and from 2003 through 2004 to 2005 through 2006 was found (P < .05). The most biopsied location was in the lymph nodes (34.8%), followed by perithyroid soft tissue masses (28.0%). A 25-gauge needle was used most frequently (97.7%). A total of 41 biopsies were diagnostic for thyroid diseases (31.1%), with the most common being thyroid papillary carcinoma. We found metastases in 31 biopsies (23.5%). Following these 2 were 29 lymph node biopsies. No major complications were noted. Of the 132 neck masses biopsied, 8 were pathologically nondiagnostic (93.9% diagnostic yield), yielding sensitivity, specificity, and accuracy of greater than 95% (97.1%, 95.2%, and 95.8%, respectively). Ultrasound-guided FNC of neck masses is highly diagnostic. The diagnostic yield is especially high for detection of malignancy, including metastases. Together with a high clinical suspicion, ultrasound-guided needle biopsy should be performed to form a correct diagnosis and make appropriate management plans.


[Cloning and characterization of genes differentially expressed in human dental pulp cells and gingival fibroblasts].
To study the biological properties of human dental pulp cells (HDPC) by cloning and analysis of genes differentially expressed in HDPC in comparison with human gingival fibroblasts (HGF). HDPC and HGF were cultured and identified by immunocytochemistry. HPDC and HGF subtractive cDNA library was established by PCR-based modified subtractive hybridization, genes differentially expressed by HPDC were cloned, sequenced and compared to find homogeneous sequence in GenBank by BLAST. Cloning and sequencing analysis indicate 12 genes differentially expressed were obtained, in which two were unknown genes. Among the 10 known genes, 4 were related to signal transduction, 2 were related to trans-membrane transportation (both cell membrane and nuclear membrane), and 2 were related to RNA splicing mechanisms. The biological properties of HPDC are determined by the differential expression of some genes and the growth and differentiation of HPDC are associated to the dynamic protein synthesis and secretion activities of the cell.


Attachment security, values, and prosocial attitudes.
The objective of this study was to determine whether individuals with different attachment styles held different prosocial values and attitudes given their different models of self and of others. A sample of 717 university students completed the ECR-S (Experiences in Close Relationships-Spanish) and the PVQ (Portrait Values Questionnaire), and evaluated different prosocial attitudes. The results showed that secure individuals reported higher scores on self-transcendence and in the value self-directions of the dimension openness to change, whereas insecure individuals had higher scores on conservation and self-enhancement. No differences were found in the attitudes of individuals with different attachment styles. These findings show a link between the dimensions of the universal values theory, and the models of self and of others.


Infant and maternal responses to emotional facial expressions: A longitudinal study.
The current longitudinal study (N = 107) examined mothers' facial emotion recognition using reaction time and their infants' affect-based attention at 5, 7, and 14 months of age using eyetracking. Our results, examining maternal and infant responses to angry, fearful and happy facial expressions, show that only maternal responses to angry facial expressions were robustly and positively linked across time points, indexing a consistent trait-like response to social threat among mothers. However, neither maternal responses to happy or fearful facial expressions nor infant responses to all three facial emotions show such consistency, pointing to the changeable nature of facial emotion processing, especially among infants. In general, infants' attention toward negative emotions (i.e., angry and fear) at earlier timepoints was linked to their affect-biased attention for these emotions at 14 months but showed greater dynamic change across time. Moreover, our results provide limited evidence for developmental continuity in processing negative emotions and for the bidirectional interplay of infant affect-biased attention and maternal facial emotion recognition. This pattern of findings suggests that infants' affect-biased attention to facial expressions of emotion are characterized by dynamic changes.


Incorporation and effect of arachidonic acid on the growth of human myeloma cell lines.
The objectives of this work are to investigate the incorporation of arachidonic acid (AA) in the human myeloma cell lines OPM2, U266 and IM9, and to assess the effect of AA and lipoxygenase products of AA on their growth. The kinetics of acylation of [3H]AA indicates that myeloma cells incorporate AA into their membrane phospholipids and triglycerides. PLA2-treatment and base hydrolysis experiments confirm that [3H]AA is incorporated unmodified in U266, IM9 and OPM2 phospholipids, and is linked by an ester bond. Prelabeling-chase experiments indicate no trafficking of labeled AA among the various phospholipid species. Addition of AA and lipoxygenase products of AA (leukotriene B4 and C4, lipoxin A4 and B4, 12- and 15-hydroxyeicosatetraenoic acid) have no effect on U266, IM9 and OPM2 proliferation assessed by [3H]thymidine incorporation into DNA. In conclusion, while human myeloma cells readily incorporate AA in their membrane phospholipids and triglycerides, AA and lipoxygenase products are not important modulators of their proliferation.


Photoelasticity for Stress Concentration Analysis in Dentistry and Medicine.
Complex stresses are created or applied as part of medical and dental treatments, which are linked to the achievement of treatment goals and favorable prognosis. Photoelasticity is an optical technique that can help observe and understand biomechanics, which is essential for planning, evaluation and treatment in health professions. The objective of this project was to review the existing information on the use of photoelasticity in medicine and dentistry and determine their purpose, the areas or treatments for which it was used, models used as well as to identify areas of opportunity for the application of the technique and the generation of new models. A literature review was carried out to identify publications in dentistry and medicine in which photoelasticity was used as an experimental method. The databases used were: Sciencedirect, PubMed, Scopus, Ovid, Springer, EBSCO, Wiley, Lilacs, Medigraphic Artemisa and SciELO. Duplicate and incomplete articles were eliminated, obtaining 84 articles published between 2000 and 2019 for analysis. In dentistry, ten subdisciplines were found in which photoelasticity was used; those related to implants for fixed prostheses were the most abundant. In medicine, orthopedic research predominates; and its application is not limited to hard tissues. No reports were found on the use of photoelastic models as a teaching aid in either medicine or dentistry. Photoelasticity has been widely used in the context of research where it has limitations due to the characteristics of the results provided by the technique, there is no evidence of use in the health area to exploit its application in learning biomechanics; on the other hand there is little development in models that faithfully represent the anatomy and characteristics of the different tissues of the human body, which opens the opportunity to take up the qualitative results offered by the technique to transpolate it to an application and clinical learning.


Three new species of free-living marine nematodes (Nematoda: Enoplida) from the Clarion-Clipperton Fracture Zone (CCFZ), North Pacific.
Three new species of free-living marine nematodes, Phanodermopsis dordi sp. nov., Halalaimus shinkai sp. nov., and Oxystomina hakureiae sp. nov. are described from the abyssal sediments of the Clarion-Clipperton Fracture Zone, North Pacific. Phanodermopsis dordi sp. nov. differs from the congeners by having papilliform anterior sensilla and a long conical tail with an acute tip. Halalaimus shinkai sp. nov., belonging to Keppner's group 2 based on the presence of caudal alae and the absence of precloacal sensillum or pore, can be distinguished from all of the members of this group by the presence of lateral pieces of gubernacula. Oxystomina hakureiae sp. nov. differs from the congeners by the short setiform anterior sensilla, the amphid located posterior to cephalic sensilla, the conico-cylindrical tail in both sexes, the spicules with a velum and a capitulum, the presence of the gubernacula and the precloacal setae, and the diorchic and monodelphic reproductive systems. The amended dichotomous keys to the species of Phanodermopsis, Halalaimus group 2, and Oxystomina are provided. A new combination Nemanema arenaria (Bussau, 1990) comb. nov. transferred from Oxystomina is also provided.


Serum Samples from Co-Infected and Domestic Cat Field Isolates Nonspecifically Bind FIV and Other Antigens in Enzyme-Linked Immunosorbent Assays.
We evaluated enzyme-linked immunosorbent assay (ELISA) specificity for measuring seroantibody responses to two types of retroviral infections in domestic cats: feline immunodeficiency virus (FIV) and feline foamy virus (FFV). We compared the seroreactivity of specific pathogen-free (SPF) cat sera, sera from SPF cats inoculated with either FIV or FFV, and field isolates (e.g., shelter or privately owned cats). Sera from SPF cats experimentally infected with the cognate virus had significantly lower background in both FIV and FFV ELISAs compared to sera from negative field isolates. ELISA values for SPF cats exposed to either FIV or FFV tended to have higher OD values on the opposite ELISA antigen plate. FIV nonspecific background absorbance was greater than that of FFV, and 10 of 15 sera samples from FIV seronegative field samples were measured in the indeterminant range. These findings highlight that exposure to off-target pathogens elicit antibodies that may nonspecifically bind to antigens used in binding assays; therefore, validation using sera from SPF animals exposed during controlled infection results in the setting of a cutoff value that may be inappropriately low when applied to field samples. Our work also suggests that infection of domestic cats with pathogens other than FIV results in antibodies that cross-react with the FIV Gag antigen.


Effects of egg yolk and cooling rate on the survival of refrigerated red deer (Cervus elaphus hispanicus) epididymal spermatozoa.
Egg yolk is a common component to sperm refrigeration for most of the deer species, the role of which is to protect sperm membranes against cold shock. In addition, there have been many studies of conservation of ejaculated semen from stags, but few have been reported for epididymal spermatozoa. This work was designed to investigate the combined effects of cooling rates (slow: 0.23 degrees C/min vs rapid: 4.2 degrees C/min) from room temperature to 5 degrees C, and egg-yolk concentration (0, 5 or 20%) in the extender on the survival of Iberian red deer epididymal spermatozoa refrigerated at 5 degrees C. Heterospermic sperm samples were diluted to a final sperm concentration approximately 400x10(6) sperm/ml with a Tris-citrate-fructose (TCF)-egg-yolk diluent. Sperm quality was in vitro judged by microscopic assessments of individual sperm motility [sperm motility index (SMI)], and of plasma membrane (hypo-osmotic swelling test) and acrosome (NAR) integrities. Our results first showed that the presence of egg yolk in the extender significantly improves (p=0.01) the viability and sperm motility after sperm dilution. In addition, acrosome and plasma membrane integrities post-refrigeration did not differ significantly between cooling procedures; however, the SMI differed significantly between cooling procedures (slow: 46.6% vs rapid: 50.0%; p=0.01). Our results also showed that sperm quality was significantly (p<0.01) affected by the combined effects of egg-yolk concentration and cooling procedure, being rapid cooling with 20% of egg yolk the most suitable combination for epididymal sperm refrigeration. In conclusion, egg-yolk improved red deer epididymal spermatozoa characteristics after dilution. Rapid cooling protocol using TCF with 20% egg-yolk significantly improved sperm motility of red deer epididymal spermatozoa after cooling.


Massive incisional hernia of the bowel and urinary bladder: a case report.
Abdominal hernias are not rare in women, but incisional bladder herniation is uncommon. Incisional hernias are an iatrogenic condition caused by protrusion of the abdominal viscera through the abdominal fascia. Omentum and small intestines are by far the most common viscera involved, and the condition is diagnosed on clinical examination either visually or by palpation of an abdominal bulge. We describe a case of bladder and bowel herniation through a lower transverse abdominal incision (Pfannenstiel), which followed emergent operative intervention for ectopic pregnancy.


Isolation of the Pneumocystis carinii dihydrofolate synthase gene and functional complementation in Saccharomyces cerevisiae.
The Pneumocystis carinii gene encoding the enzyme dihydrofolate synthase (DHFS), which is involved in the essential biosynthesis of folates, was isolated from clones of the Pneumocystis genome project, and sequenced. The deduced P. carinii DHFS protein shares 38% and 35% identity with DHFS of Schizosaccharomyces pombe and Saccharomyces cerevisiae, respectively. P. carinii DHFS expressed from a plasmid functionally complemented a S. cerevisiae mutant with no DHFS. Comparison of available DHFSs with highly similar folylpolyglutamate synthases allowed the identification of potential signatures responsible for the specificities of these two classes of enzymes. The results open the way to experimentally analyse the structure and function of P. carinii mono-functional enzyme DHFS, to investigate a possible role of DHFS in the resistance to antifolates of P. jirovecii, the species infecting specifically humans, and to develop a new class of antifolates.


Silylation-based kinetic resolution of monofunctional secondary alcohols.
The nucleophilic small molecule catalyst (-)-tetramisole was found to catalyze the kinetic resolution of monofunctional secondary alcohols via enantioselective silylation. Optimization of this new methodology allows for selectivity factors up to 25 utilizing commercially available reagents and mild reaction conditions.


Oxidative Metabolism in Pediococcus pentosaceus III. Glucose Dehydrogenase System.
Lee, Chin K. (North Carolina State of the University of North Carolina, Raleigh), and Walter J. Dobrogosz. Oxidative metabolism in Pediococcus pentosaceus. III. Glucose dehydrogenase system. J. Bacteriol. 90:653-660. 1965.-A method was developed for the purification of glucose dehydrogenase from Pediococcus pentosaceus Az-25-5. The procedures included treatments with protamine sulfate, ammonium sulfate, and heat in addition to acid precipitation, calcium phosphate adsorption and elution, and diethylaminoethyl-Sephadex column chromatography. The final preparation thus obtained was purified 255-fold and exhibited both similarities and dissimilarities to the same enzyme isolated from other sources. The enzyme is absolutely specific for nicotinamide adenine dinucleotide phosphate (NADP) as a cofactor, and oxidizes only glucose or its analogue 2-deoxyglucose via the following reversible reaction: beta-d-glucose + NADP right harpoon over left harpoon d-glucono-delta-lactone + NADPH(2) + H(+). K(m) values were 2.3 x 10(-2) for glucose and 2 x 10(-4) for NADP. Monovalent cations were required for stability of the enzyme and stimulated activity. The pH optimum was 7.0, and the equilibrium constant was determined to be 13.4 x 10(-7) at pH 6.4. Among the Lactobacillaceae, glucose dehydrogenase activity was found to be essentially limited to members of the genus Pediococcus. Studies on the enzymatic composition of P. pentosaceus viewed in conjunction with other available data led to the conclusion that this enzyme is not involved to any significant extent in the energy metabolism of this organism.


[Therapeutic outcome of spasmodic torticollis].
We investigated 117 patients with spasmodic torticollis who had visited us to seek for appropriate treatment in these 14 years. They were 71 men and 46 women, aged 44 +/- 14 (mean +/- SD) years, and suffered from this disorder during 4 +/- 5 years, maximum 26 years. Involuntary abnormal head positions, not only torticollis but also laterocollis and antero- or retrocollis, were contained in this study. Most of them were torticollis due to idiopathic focal dystonia. One or more courses of alcoholization therapy was accomplished in 82 patients who wished to be done. This therapy course consisted of about ten times totally of 99% ethanol injection to the motor point of two most hypertonic neck muscles, either side of the sternocleidomastoideus and the opposite side of the splenius in most cases, repeated every 2 or 3 weeks. One patient received as many as 98 times of this injection and resolved completely. Training to reinforce antagonistic muscles was also instructed. Twenty-one patients (26%) were resolved completely after this treatment. Fifty-four patients (66%) were ameliorated and satisfied partially, but 18 of them relapsed in 1 to 4 years after the treatment and were obliged to repeat one more course of this treatment. On the other hand, in five patients their torticollis improved under certain drug therapy alone. Sixteen patients (14%) gave up to continue the treatment within two months, and 14 patients (12%) dropped out before starting the therapy. This alcoholization therapy resulted in amelioration of torticollis in about 90% of the patients with a long effective period. Nevertheless, this alcohol injection is painful, and requires 5 to 6 months to be completed. In 2 patients who had already received many times of this injection, sudden hoarseness occurred one day immediately after the alcohol injection to the sternocleidomastoideus. This complication was presumably brought about by the unexpected infiltration of alcohol to the laryngeal area, located posterior to that muscle. They recovered in two months, but careful attention should be paid to the adverse effects. If botulinum toxin be available also in our country, we will be able to have another choice of therapy and the treatment of this disorder will become easier.


[Therapy of obesity. Setting realistic goals].
Every third German needs to lose weight for health reasons. Risk assessment of obesity is based on the BMI, the distribution pattern of body fat, and the presence of concomitant diseases and sequelae of obesity. The most important prerequisites are personal motivation and the ability of the patient to self-manage his/her problem. The basic long-term weight-reduction program includes a low-calory diet, increased physical activity, and specific measures aimed at modifying eating habits. Should the basic programs fail to produce the necessary results, the two weight-reducing drugs Sibutramine and Orlistat are available--with appropriate consideration being given to contraindications. Surgical measures, such as gastric banding and gastroplasty are reserved for patients that prove resistant to conservative measures.


[Functional interrelationships between dehydrogenases and transaminases in various regions of the rat brain as affected by small doses of gamma-radiation].
Wistar rats were exposed to 10, 20 and 40 sGy of gamma-irradiation. Maximal activity of 2-oxoglutarate- and succinate dehydrogenases, as well as of aspartate-2-oxoglutarate and pyruvate-2-oxoglutarate in the brain tissue was measured within 30 days after the exposure. Dehydrogenase activity was measured in the brain cortex, limbic system and in the cerebellum; transaminase activity was determined in the brain cortex, diencephalic zone and in the hypophysis. It was found that small doses of irradiation resulted in an oscillating increase of dehydrogenase activity with a decrease of the amplitude by the 30th day of the experiment. As the dose of irradiation increases, the periods of normal activity change into phases of inhibition of dehydrogenase action, the period of oscillations diminishes. Transaminase activity, as a rule, changes in a phase in a reversible manner as compared with dehydrogenase activity. These observations are discussed from the point of view of structural relations between these two systems in the intramitochondrial supramolecular structures, the so-called metabolons.


Exploring the Nexus Between Mindfulness, Gratitude, and Wellbeing Among Youth With the Mediating Role of Hopefulness: A South Asian Perspective.
This study investigates the relationship between mindfulness, gratitude, and psychological wellbeing of young individuals in Pakistan with the potential role of hopefulness as a mediator between mindfulness, gratitude, and wellbeing. Data were collected from young individuals (18-40 years old) from Pakistan. A total sample of 500 participants was collected by employing the online survey questionnaire, and 374 questionnaires were duly filled and returned. The PLS-SEM technique was used to test the proposed hypotheses. The results of the study found that there is a strong direct relationship between gratitude, mindfulness, and hopefulness, and mindfulness is also strongly correlated with wellbeing. However, the relationship between gratitude and wellbeing was not statistically significant. Moreover, the mediation results reveal that the relationship between mindfulness, gratitude, and wellbeing is significantly mediated by hopefulness. This shows that gratitude and mindfulness are crucial in enhancing wellbeing through hopefulness. This study is an important contribution to validating the broaden-and-build theory, which suggests that hopelessness is a significant factor of a depressive state. It can be indicated that inducing hopefulness could be a significant element of the treatment plan of professional clinical psychologists.


Rotational dynamics and transition mechanisms of surface-adsorbed proteins.
Assembly of biomolecules at solid–water interfaces requires molecules to traverse complex orientation-dependent energy landscapes through processes that are poorly understood, largely due to the dearth of in situ single-molecule measurements and statistical analyses of the rotational dynamics that define directional selection. Emerging capabilities in high-speed atomic force microscopy and machine learning have allowed us to directly determine the orientational energy landscape and observe and quantify the rotational dynamics for protein nanorods on the surface of muscovite mica under a variety of conditions. Comparisons with kinetic Monte Carlo simulations show that the transition rates between adjacent orientation-specific energetic minima can largely be understood through traditional models of in-plane Brownian rotation across a biased energy landscape, with resulting transition rates that are exponential in the energy barriers between states. However, transitions between more distant angular states are decoupled from barrier height, with jump-size distributions showing a power law decay that is characteristic of a nonclassical Levy-flight random walk, indicating that large jumps are enabled by alternative modes of motion via activated states. The findings provide insights into the dynamics of biomolecules at solid–liquid interfaces that lead to self-assembly, epitaxial matching, and other orientationally anisotropic outcomes and define a general procedure for exploring such dynamics with implications for hybrid biomolecular–inorganic materials design.


Characterisation of AIDS presenters and their response to antiretroviral therapy at legnano general hospital (Italy) during the period 2000-2008.
The aim of this study was to characterise the AIDS presenters diagnosed between 2000 and 2008 in Legnano (Italy), and describe their initial response to highly active antiretroviral therapy (HAART) and trends over time. Seventy-six (48.7%) of 156 patients diagnosed as having AIDS in the period 2000-2008 were AIDS presenters. The proportion of AIDS presenters increased from 23.8% in 2000 to 70.6% in 2008 (p = 0.009). The major risk factors were heterosexual transmission and a foreign place of birth, and did not significantly change over time. The median CD4+ cell count at diagnosis was 30 cells/microl and the median level of HIV RNA was 5.38 log copies/ml, with no differences between the transmission risk groups. Fifteen AIDS presenters died of AIDS-defining diseases; the others started HAART (72% with 2 NRTIs + boosted PI), and 40% after a drug resistance test. The median duration of the initial HAART was 107 days. After three months, 34% of the patients had undetectable HIV-RNA levels and the median CD4+ cell count was 140 cells/microl; the corresponding figures after 12, 24 and 48 months were respectively 84%, 82.3% and 94.1%, and 310, 370 and 380 cells/microl. In conclusion, the AIDS presenters were mainly heterosexual men and immigrants. Their proportion increased significantly over time, and a substantial proportion maintained an immunovirological response to HAART.


Recovery of valuable metals from mixed spent lithium-ion batteries by multi-step directional precipitation.
The novel strategy of multi-step directional precipitation is proposed for recovering valuable metals from the leachate of cathode material obtained by mechanical disassembly from mixed spent lithium-ion batteries. Based on thermodynamics and directional precipitation, Mn2+ is selectively precipitated under conditions of MRNM (molar ratio of (NH4)2S2O8 to Mn2+) = 3, pH = 5.5 and 80 °C for 90 min. Ni2+ was then selectively precipitated using C4H8N2O2 under conditions of pH = 6, MRCN (molar ratio of C4H8N2O2 to Ni2+) = 2, 30 °C and 20 min. Then, the pH was adjusted to 10 to precipitate Co2+ as Co(OH)2. Finally, Li+ was recovered by Na2CO3 at 90 °C. The precipitation rates of Mn, Ni, Co, and Li reached 99.5%, 99.6%, 99.2% and 90%, respectively. The precipitation products with high purity can be used as raw materials for industrial production based on characterization. The economical and efficient recovery process can be applied in industrialized large-scale recycling of spent lithium-ion batteries.


Variable N-terminal regions of muscle myosin heavy chain modulate ATPase rate and actin sliding velocity.
We integratively assessed the function of alternative versions of a region near the N terminus of Drosophila muscle myosin heavy chain (encoded by exon 3a or 3b). We exchanged the alternative exon 3 regions between an embryonic isoform and the indirect flight muscle isoform. Each chimeric myosin was expressed in Drosophila indirect flight muscle, in the absence of other myosin isoforms, allowing for purified protein analysis and whole organism locomotory studies. The flight muscle isoform generates higher in vitro actin sliding velocity and solution ATPase rates than the embryonic isoform. Exchanging the embryonic exon 3 region into the flight muscle isoform decreased ATPase rates to embryonic levels but did not affect actin sliding velocity or flight muscle ultrastructure. Interestingly, this swap only slightly impaired flight ability. Exchanging the flight muscle-specific exon 3 region into the embryonic isoform increased actin sliding velocity 3-fold and improved indirect flight muscle ultrastructure integrity but failed to rescue the flightless phenotype of flies expressing embryonic myosin. These results suggest that the two structural versions of the exon 3 domain independently influence the kinetics of at least two steps of the actomyosin cross-bridge cycle.


Inhibiting TRAF2-mediated activation of NF-kappaB facilitates induction of AP-1.
The compound 5-(4-methoxyarylimino)-2-N-(3,4-dichlorophenyl)-3-oxo-1,2,4-thiadiazolidine (P(3)-25) is known to possess anti-bacterial, anti-fungal, and anti-tubercular activities. In this report, we provide evidence that P(3)-25 inhibits NF-kappaB, known to induce inflammatory and tumorigenic responses. It activates AP-1, another transcription factor. It inhibits TRAF2-mediated NF-kappaB activation but not TRAF6-mediated NF-kappaB DNA binding by preventing its association with TANK (TRAF for NF-kappaB). It facilitates binding of MEKK1 with TRAF2 and thereby activates JNK and AP-1. We provide evidence, for the first time, that suggests that the interaction of P(3)-25 with TRAF2 leads to inhibition of the NF-kappaB pathway and activation of AP-1 pathway. These results suggest novel approaches to design of P(3)-25 as an anti-cancer/inflammatory drug for therapy through regulation of the TRAF2 pathway.


G328E and G409E sialin missense mutations similarly impair transport activity, but differentially affect trafficking.
Two disease-associated missense mutations in the sialin gene (G328E and G409E) have recently been identified in patients with lysosomal free sialic acid storage disease. We have assessed the effect of these mutations and find complete loss of measurable transport activity with both and impaired trafficking of the G409E protein. These results suggest that the two residues are important for proper function of sialin and confirm the association of loss of transport with disease causative mutations.


Risk profile of patients developing nonunion of the clavicle and outcome of treatment--analysis of fifty five nonunions in seven hundred and twenty nine consecutive fractures.
The most common complication following treatment of a clavicle fracture is nonunion. Most nonunions are symptomatic and treatment is mostly operative. The aim of this study was to describe risk profiles of patients developing nonunion and what outcome is observed following operative treatment of clavicle nonunions. In a consecutive series of 729 clavicle fractures we retrospectively identified 55 that developed nonunion (49 diaphysial and six lateral). All were treated operatively by reconstruction with (n = 28) or without (n = 27) autologous bone graft. Assessment of functionality and patient reported satisfaction and remission of symptoms was done a minimum of six months post-operatively by mail. Response rate was 60%. The overall nonunion rate was 7.5%. Nine nonunions were initially treated operatively. Risk factors associated with nonunion of our series was anatomic site, fracture complexity, female gender, smoking habits and initial treatment. A total of eight post-operative complications were found. Remission of symptoms was reported by 29 of the 33. Outright satisfaction with current shoulder condition was reported by 24. The overall median DASH was 8 (range 0-61). Following revision of the eight complications a total of 53 united successfully. Operative treatment of a clavicular nonunion seems to be effective as most patients unite and experience remission of symptoms. However, complications in close to 15% and lack of satisfaction of approximately 27% have to be acknowledged and thoroughly explained to the patient prior to treatment.


[Nifurtimox, a bright future for treatment of Chagas disease].
Nifurtimox is one of the two molecules used for treatment of Chagas disease. Although posology has not yet been clearly defined, nifurtimox is increasingly used, especially in combination with eflonithin. Nifurtimox is perfectly suited to the WHO's Chagas disease eradication program.


Multifarious feed additives on lamb performance on Kuwait farms.
A change in the livestock feeding strategy is of utmost importance for the stability of animal health and sustainable livestock productivity to overcome the problem of subsiding the environmental effects of sheep production. Supplementing dietary feed with safe and efficient additives provides optimal animal performance and maximizes productivity. This study aimed to assess the effects of adding various feed additives to lamb rations for optimizing feed efficiency in weaned lambs for meat production in Kuwait. The feed additives, namely, ammonium chloride, urea, algae, fishmeal, and humic acid, were investigated on the physical performance of lambs for their effect on body weight, length, height, and waist length. The total feed consumption rate and feed efficiency were also measured. Each treatment comprising five healthy lambs was randomly allocated into six treatments comprising 30 lambs. The six treatments were the basal ration supplemented with ammonium chloride (50-100 g/day/head), urea (30 g/day/head), fishmeal (35 g/day/head), algae (Spirulina platensis) powder (50 g/day/head), humic acid (2.5 g/day/head), control group with only basal ration. The study was conducted for around 27 months and the data were recorded once in 2 weeks. The results indicated a positive elevation in the physique of lambs with all tested additives, showing an affirmative insignia for lamb fattening. The growth parameters in terms of augmented length, height, and waist length of lambs' bodies amplified significantly with ammonium chloride and fishmeal supplement, while the other additives reported a non-significant increment. The feed consumption was significantly elevated for ammonium chloride, algae, and fishmeal supplementation, while humic acid was recorded the least. Concerning feed efficiency of young lambs, fish meal and ammonium chloride were reported best, followed by urea. In contrast, algae and humic acid exhibited a non-significant effect on feed efficiency. This study exposed noteworthy influence on a lamb body's performance with the addition of fish meal and ammonium chloride in lamb rations, trailed by urea and algae.


[Groin hernia in the patients receiving CAPD].
Continuous ambulatory peritoneal dialysis (CAPD) is a popular way of treatment of the patients with renal failure. There were 1365 patients on CAPD in Poland in the year 2001. Higher frequency of groin and abdominal hernias was reported in those patients. 10% of dialysed patients developed hernia in the first five years of the therapy. The main problems of hernia repair in the CAPD patients are: increased pressure in abdominal cavity caused by dialysate volume, higher risk of peritonitis, poor prognosis in the complicated cases temporarily or permanently converted to hemodialysis (HD) and the insufficiency of healing process. Complications accorded to hernia repair are the third most often reason of conversion to HD. Conducted studies on hernia repair did not lead to the introduction of the world standard. Authors propose to introduce an unified protocol to improve treatment results. Main guidelines of hernia treatment in CAPD patients are: 1) consultation of the surgeon cooperating with dialysis center in qualification to CAPD, and in the case of hernia symptoms in CAPD patients, 2) application of tension-free methods (PHS recommended), 3) administration of antibiotic prophylaxis, 4) application of local or epidural anesthesia, 5) no necessity of discontinuation of CAPD procedures.


An Orwellian scenario: court ordered caesarean section and women's autonomy.
Between 1992 and 1996, a small number of women in the UK were forced by the courts to undergo caesarean section against their expressed refusal. Analysis of the reported cases reveals the blanket assumption of maternal incompetence and the widespread use of thinly veiled coercion. Such attitudes and practices are themselves frequently compounded by inadequate communication. Medical discretion in such problematic cases seems to err on the side of safety and so appears to favour the life of the fetus over maternal autonomy. Despite current policy's placement of the pregnant woman at the centre of maternity care, obstetricians' concerns appear to lie more with the unborn fetus. In other words, there seems to be a point at which the value of fetal life begins to outweigh, not so much the life of the woman, but her right to self-determination, her plans and her choices. While it is important to acknowledge that these court ordered caesareans represent an unusual extreme within contemporary maternity care in this country, that they have happened brings into sharp relief some of the stereotypical assumptions about women. These are assumptions that underlie much of current medical practice and may compromise or disempower women in other ways during their experience of pregnancy and labour. Using the first and last of the six reported cases as contextual illustrations, this article focuses on the complex interplay of processes that have brought the medical profession to a position in which their own self-conviction and determination to do what they believe is best for their patients has resulted in gross denial of women's autonomy and the use of the law to override pregnant women's refusal of consent.


Hematopoietic stem cell potential from umbilical cord blood.
We studied the conditions of collection and isolation of hematopoietic cells from cord blood in order to optimise the sampling. A statistically significant correlation was found between the total stem cell content of the samples and the time of delivery suggesting that the quantity of hematopoietic stem cells available is higher when cord blood collection is performed earlier during pregnancy. Attempt to isolate the white cells resulted in a dramatic loss of stem cells. Factors affecting cell recovery and purification must be investigated in order to optimize cord blood cell banking.


[A three-months follow up of a randomized controlled trial of Assisted Walking Program for in-hospital geriatric patients].
. A three-months follow up of a randomized controlled trial of Assisted Walking Program for in-hospital geriatric patients. Functional decline is common among older hospitalized patients. In fact, low mobility and bed rest during hospitalization have been considered as predictable causes of independent ambulation decline in older hospitalized patients. the older patients' walking ability change, compared with usual care, from hospital pre-admission/admission to discharge and 90 days follow-up, assessed with the Braden Activity subscale. The secondary end point was the occurrence of re-hospitalization and mortality. A 90-days follow-up randomized controlled trial, open labeled was conducted in a geriatric ward. A total of 307 hospitalized patients (>65 years) were included. The intervention group received an Individualized Assisted Walking Program (IAWP), which significantly improved walking ability at discharge (p<.001) and 90-day follow-up (p=0.009), compared to the control group, which received the usual care. There were no significant differences in terms of mortality and re-hospitalizations. An individualized assisted walking program improves walking abilitiy during hospitalization and over time. For this, a nurse staffing and workload reorganization, a multidisciplinary approach, and an early nurses' planning, could be relevant factors in influencing successfully the older patients' healthcare.


Asthma education: the perceptions of family physicians.
Education and training are important for people with asthma and for their family doctors in order to reduce the morbidity and mortality associated with the disease, but the most appropriate educational strategies have not been clarified. This study was conducted as a needs-assessment survey to examine the perceptions of 193 family physicians in Sydney (Australia) regarding various aspects of asthma management and patient education. Part of this sample of physicians were subsequently involved in a communitywide asthma education program. Although the measurement of airway function by doctors and patients is the cornerstone of the national asthma strategy in Australia, only 43% of family physicians surveyed regularly measured airway function in their offices and most considered that their patients rarely used a peak flow meter. Most physicians agreed with statements suggesting that asthma education was useful but some felt that education could be dangerous, or might result in fewer consultations by asthma patients. These results have provided clear directions for educating family physicians about optimal asthma management. They also provide some insight into potential barriers to the successful implementation of asthma education programs.


Vitamin E increases natural cytotoxic activity in seabream (Sparus aurata L.).
The natural cytotoxic activity of head-kidney leucocytes from gilthead seabream (Sparus aurata L.), after in vitro and in vivo vitamin E treatment, against tumor cells was studied by flow cytometry. Leucocytes were incubated in culture medium with different vitamin E supplementations (0.01-10 microg ml(-1)) for 6, 24 or 48 h and the results demonstrate that all the assayed vitamin E supplementations significantly enhanced the natural cytotoxic activity of leucocytes. To determine the effect of a high dietary level of vitamin E on this activity, fish were fed with 0 (control), 600, 1200 or 1800 mg of vitamin E supplementation kg(-1) diet for 2, 4 or 6 weeks. After 2 and 4 weeks of treatment, the natural cytotoxic activity was significantly enhanced at the highest (1.8 g kg(-1) diet) and lowest (600 mg kg(-1) diet) vitamin E supplement dosage, respectively. No effect of the vitamin E supplemented diet on seabream leucocyte natural cytotoxic cell activity was observed after 6 weeks of treatment.


[Prevention of athletic injuries by changing the regulations. Experiences with a military obstacle track].
During a period of 12 months of military conscription, all of the injuries occurring on the obstacle track at the Antvorskov Barracks in Slagelse were registered. During the period of investigation, the regulations for employing the track were altered so that the heights of jumping down from obstacles were considerably reduced. The object of this investigation was to demonstrate any possible effect on the pattern of injuries. During the period, a total of 26 injuries were registered (3.78 injuries/conscript/1,000 hours activity). As compared with previous investigations, the frequency of injuries was reduced and practically all of the serious injuries were prevented. The proposed alterations in the techniques are recommended in future when conscripts employ the military obstacle track.


The Role of the Vasculature in Heart Failure.
The contribution of the vasculature in the development and progression of heart failure (HF) syndromes is poorly understood and often neglected. Incorporating both arterial and venous systems, the vasculature plays a significant role in the regulation of blood flow throughout the body in meeting its metabolic requirements. A deterioration or imbalance between the cardiac and vascular interaction can precipitate acute decompensated HF in both preserved and reduced ejection fraction phenotypes. This is characterised by the increasingly recognised concept of ventricular-arterial coupling: a well-balanced relationship between ventricular and vascular stiffness, which has major implications in HF. Often, the cause of decompensation is unknown, with international guidelines mainly centred on arrhythmia, infection, acute coronary syndrome and its mechanical complications as common causes of decompensation; the vascular component is often underrecognised. A better understanding of the vascular contribution in cardiovascular failure can improve risk stratification, earlier diagnosis and facilitate earlier optimal treatment. This review focuses on the role of the vasculature by integrating the concepts of ventricular-arterial coupling, arterial stiffness and venous return in a failing heart.


The impact of opioid administration on resuscitation volumes in thermally injured patients.
Administration of resuscitation volumes far beyond the estimates established by burn-body weight resuscitation formulas has been well documented. The reasons behind this increase are not clear. We sought to determine if our resuscitation volumes had increased and, if so, what factors were related to their increase. A retrospective chart review identified 154 patients admitted with burns greater than 20% of their BSA during the years of 1975-1976 (period 1), 1990-1991 (period 2), and 2006-2007 (period 3). Charts were reviewed for total fluids (crystalloid, colloid, and blood products) and opioids given before admission, during the first 8 hours of treatment, the next 16 hours of treatment, and the following 24 hours of treatment. Opioids were converted to opioid equivalents (OE). Multiple regression analysis was performed to determine the effects of variables of interest and control for confounders. Significance was assumed at the P < .05 level. Resuscitation fluid volumes increased significantly among adults from 3.97 ml/kg/%BSA during the first period to 6.40 ml/kg/%BSA during the third period (P < .01). The same trend in children <30 kg was not seen (P = .72). Fluid administered during the first 24 hours was significantly associated with age, BSA, intubation, latter two study periods, and opioid administration. Fluid administration was consistently associated with opioid administration at all measured time points. At 24 hours postburn, patients who received 2 to 4 OE/kg required an average of additional 3,650 +/- 1,704 ml of fluid, those receiving 4 to 6 OE/kg had required an average of 25,154 +/- 4,386 ml, and those who received >6 OE kg had required an average of 32,969 +/- 3,982 ml. In this single center retrospective study, we have shown a statistically significant increase in resuscitation fluids (from 1975 to 2007) and an association of resuscitation volumes with opioids. Opioids have been shown to increase resuscitation volumes in critically ill patients through both central and peripheral effects on the cardiovascular system. Because increased fluid resuscitation has been associated with adverse consequences in other studies, further research on alternative pain control strategies in thermally injured patients is warranted.


Functional Diversity of the Litter-Associated Fungi from an Oxalate-Carbonate Pathway Ecosystem in Madagascar.
The oxalate-carbonate pathway (OCP) is a biogeochemical process linking oxalate oxidation and carbonate precipitation. Currently, this pathway is described as a tripartite association involving oxalogenic plants, oxalogenic fungi, and oxalotrophic bacteria. While the OCP has recently received increasing interest given its potential for capturing carbon in soils, there are still many unknowns, especially regarding the taxonomic and functional diversity of the fungi involved in this pathway. To fill this gap, we described an active OCP site in Madagascar, under the influence of the oxalogenic tree Tamarindus indica, and isolated, identified, and characterized 50 fungal strains from the leaf litter. The fungal diversity encompassed three phyla, namely Mucoromycota, Ascomycota, and Basidiomycota, and 23 genera. Using various media, we further investigated their functional potential. Most of the fungal strains produced siderophores and presented proteolytic activities. The majority were also able to decompose cellulose and xylan, but only a few were able to solubilize inorganic phosphate. Regarding oxalate metabolism, several strains were able to produce calcium oxalate crystals while others decomposed calcium oxalate. These results challenge the current view of the OCP by indicating that fungi are both oxalate producers and degraders. Moreover, they strengthen the importance of the role of fungi in C, N, Ca, and Fe cycles.


How many species are there on Earth?
This article surveys current answers to the factual question posed in the title and reviews the kinds of information that are needed to make these answers more precise. Various factors affecting diversity are also reviewed. These include the structure of food webs, the relative abundance of species, the number of species and of individuals in different categories of body size, along with other determinants of the commonness and rarity of organisms.


Muscle-fiber characteristics in adult mouse-tongue muscles.
To clarify functions of the mouse-tongue muscles, proteins such as myocin heavy chain (MHC) 2a and MHC-2b, which are isoforms of the fast-twitch fiber type myosin heavy chain, in the lateral margin of the tongue were observed by reverse transcription polymerase chain reaction and immunohistochemical analyses. The main MHC isoform in the superior longitudinal muscle of the tongue was MHC-2b, with the fastest function and the main MHC isoform in the transverse muscle of the tongue was MHC-2a. These findings suggested that the fastest function is necessary for the superior longitudinal muscle of the tongue, which is useful for moving the tongue in and out of the mouth in the sagittal direction, showing different cellular biological properties of the myofibers from those of the transverse muscle of the tongue.


Electron Spin Resonance Dosimetry Studies of Irradiated Sulfite Salts.
The study of new materials for radiation dosimetry is important to improve the present state of the art and to help in cases of accidents for retrospective dosimetry. Sulfites are compounds that contain a sulfur ion, widely used in the food industry. Due to the significant application of these compounds, sulfites are interesting candidates for accidental dosimetry, as fortuitous radiation detectors. The presence of the SO3- anion enables its detection by electron spin resonance (ESR) spectroscopy. The Dose-Response behavior, signal stability and other spectral features were investigated for sodium sulfite, sodium bisulfite, sodium metabisulfite and potassium metabisulfite, all in crystalline forms. The ESR spectrum of salts presented stability and proportional response with dose, presenting potential for dosimetry applications.


Persistent negative symptoms in schizophrenia: an overview.
Persistent negative symptoms represent an alternative approach for assessing negative symptoms in the context of clinical trials. Persistent negative symptoms are designed to capture those symptoms that lead to functional impairment but are currently understudied and for which there are no currently available effective treatments. Persistent negative symptoms differ from the 2 most commonly used approaches: primary, enduring negative symptoms or deficit symptoms and negative symptoms broadly defined to include negative symptoms, regardless of their etiology or duration. In contrast to deficit symptoms, persistent negative symptoms may include secondary negative symptoms. However, in contrast to negative symptoms broadly defined, the secondary negative symptoms included in the assessment of persistent negative symptoms only include those that have failed to respond to usual treatments for secondary negative symptoms. In consequence, the presence of persistent negative symptoms identifies a patient population with clinically relevant symptomatology, which is larger than the one with the deficit syndrome but less heterogeneous than that captured through the use of a nonrestrictive definition of negative symptoms. This may facilitate the selection of subjects for inclusion into research and efforts to develop new pharmacological treatments and enhance our understanding of a relevant clinical problem. Ultimately, the investigation of the different entities characterized by negative symptoms, such as persistent negative symptoms, and the enhanced understanding of their biological and clinical characteristics may help to unravel the psychopathological and biological heterogeneity of schizophrenia.


Hydrolysis of serine-containing peptides at neutral pH promoted by [MoO4]2- oxyanion.
Hydrolysis of the dipeptides glycylserine (GlySer), leucylserine (LeuSer), histidylserine (HisSer), glycylalanine (GlyAla), and serylglycine (SerGly) was examined in oxomolybdate solutions by means of (1)H, (13)C, and (95)Mo NMR spectroscopy. In the presence of a mixture of oxomolybdates, the hydrolysis of the peptide bond in GlySer proceeded under neutral pD conditions (pD = 7.0, 60 °C) with a rate constant of k(obs) = 5.9 × 10(-6) s(-1). NMR spectra did not show evidence of the formation of paramagnetic species, excluding the possibility of Mo(VI) reduction to Mo(V), indicating that the cleavage of the peptide bond is purely hydrolytic. The pD dependence of k(obs) exhibits a bell-shaped profile, with the fastest cleavage observed at pD 7.0. Comparison of the rate profile with the concentration profile of oxomolybdate species implicated monomolybdate MoO(4)(2-) as the kinetically active complex. Kinetics experiments at pD 7.0 using a fixed amount of GlySer and increasing amounts of MoO(4)(2-) allowed for calculation of the catalytic rate constant (k(2) = 9.25 × 10(-6) s(-1)) and the formation constant for the GlySer-MoO(4)(2-) complex (K(f) = 15.25 M(-1)). The origin of the hydrolytic activity of molybdate is most likely a combination of the polarization of amide oxygen in GlySer due to the binding to molybdate, followed by the intramolecular attack of the Ser hydroxyl group.


Successful onco-testicular sperm extraction from a testicular cancer patient with a single testis and azoospermia.
Onco-testicular sperm extraction is used to preserve fertility in patients with bilateral testicular tumors and azoospermia. We report the case of a testicular tumor in the solitary testis of a patient who had previously undergone successful contralateral orchiectomy and whose sperm was preserved by onco-testicular sperm extraction. A 35-year-old patient presented with swelling of his right scrotum that had lasted for 1 month. His medical history included a contralateral orchiectomy during childhood. Ultrasonography revealed a mosaic echoic area in his scrotum, suggesting a testicular tumor. The lesion was palpated within the normal testicular tissue along its edge and semen analysis showed azoospermia. Radical inguinal orchiectomy and onco-testicular sperm extraction were performed simultaneously. Motile spermatozoa were extracted from normal seminiferous tubules under microscopy and were frozen. Eventual intracytoplasmic sperm injection using the frozen spermatozoa is planned. Onco-testicular sperm extraction is an important fertility preservation method in patients with bilateral testicular tumors or a history of a previous contralateral orchiectomy.


5-HT3 receptor antagonism and psychoactivity.
The purpose of this study was to assess the acute psychoactive and physiological properties of 5-HT( 3) antagonism using ondansetron as a probe. Ondansetron is used clinically as an anti-emetic but is also under treatment consideration for a range of psychiatric disorders including drug abuse. A 15 min infusion of 40 mg ondansetron, a 1 min infusion of 25 mg of cocaine (positive control) and their respective placebos were tested intravenously in eight volunteers with histories of drug abuse in a blinded cross-over study. Ondansetron responses could not be distinguished from the placebo. Cocaine produced typical subjective and physiological effects. These findings indicate that the prototypic 5-HT( 3) receptor antagonist ondansetron does not produce acute psychoactive effects when infused at doses of up to 40 mg and has no rewarding effects with this regime.


Assessment of nicorandil therapy in ischemic myocardial injury by using contrast-enhanced and functional MR imaging.
To determine the potential of mesoporphyrin- and gadopentetate dimeglumine-enhanced and functional magnetic resonance (MR) imaging in the assessment of the acute effect of nicorandil on ischemic injury of the myocardium. Spin-echo MR imaging was used to monitor changes in myocardial contrast and function in reperfused myocardial injury. Inversion-recovery echo-planar MR imaging was used to depict the injured region. Myocardial injury in rats was produced by using 30 minutes of coronary occlusion followed by 24 hours reperfusion. Nicorandil (n = 9) was infused during occlusion and early reperfusion. Control animals (n = 11) received no therapy. At 24 hours, after administration of mesoporphyrin and gadopentetate dimeglumine and histochemical staining, the function and size of the injured region of the left ventricle (LV) were determined. A t test was used to compare data between groups of animals, whereas regression and Bland-Altman analyses were used to determine correlation and agreement between MR imaging and histomorphometry, respectively. Treated animals showed reduced infarction size as compared with the control group from 25.6% +/- 7.9 (SD) to 7.9% +/- 6.8 of LV myocardial area (P < .001), as defined with mesoporphyrin-enhanced MR imaging; while the size of the rim increased from 10.8% +/- 10.0 to 16.1% +/- 14.4 (P < .05). The diastolic-midventricular cavity area was smaller in treated animals (15.2 mm(2) +/- 4.3) compared with the control group (28.5 mm(2) +/- 7.9; P < .001). At functional MR imaging, nicorandil improved systolic reduction in LV cavity area (57.5% +/- 17.3) compared with the control group (38.0% +/- 16.0; P < .05) and preserved regional LV wall thickening at the site of injury (12.2% +/- 11.1 in treated group vs 0.3% +/- 8.6 in the control group; P < .05). Contrast material-enhanced MR imaging has the potential to demonstrate reduction in size of ischemically injured myocardium, whereas functional MR imaging demonstrated the recovery of LV function 24 hours after nicorandil therapy.


The relationship among side effects associated with anti-epileptic medications in those with intellectual disability.
Seizures are fairly common in those with intellectual disabilities. In order to treat these seizures, antiepileptic drugs (AEDs) are often used and in many cases are effective. However, these medications often create a variety of associated side effects. In order to monitor these side effects, measures such as the SEIZES-B have been used. While many side effects have been found to occur with the use of AEDs, research has not explored if certain side effects are more likely to co-occur. For the current study, 281 people with intellectual disability were administered the SEIZES-B to monitor side effects associated with AEDs. Correlations between side effect subscales were then computed. Several subscales were found to be significantly correlated: hepatic disturbance with dermatological changes and cognitive disturbance; respiratory disturbance with dermatological changes, sedation, and electrolyte disturbance; and cognitive disturbance with sedation and dermatological disturbance. Possible implications of these findings are discussed.


Enrichment enhances the expression of sgk, a glucocorticoid-induced gene, and facilitates spatial learning through glutamate AMPA receptor mediation.
We have previously demonstrated that the serum and glucocorticoid-inducible kinase (sgk) gene plays a causal role in facilitating memory performance in rats. Environment enrichment is known to facilitate spatial learning. We therefore examined the effect of enrichment on sgk expression. We also examined the role of sgk in spatial and nonspatial learning and the regulation of sgk expression by activation of different glutamate receptors. Both real-time polymerase chain reaction and Western blot analyses revealed that enrichment training preferentially increased sgk mRNA and protein levels in the hippocampus. Transfection of sgk mutant DNA to the hippocampal CA1 area markedly impaired spatial learning, fear-conditioning learning and novel object-recognition learning in rats, but enrichment training effectively reversed these learning deficits. Meanwhile, S422A mutant DNA transfection prevented enrichment-induced spatial learning facilitation. In studying glutamate receptor regulation of sgk expression, we found that blockade of N-methyl-d-aspartate (NMDA) receptors in general, and the NR2B subunit in particular both effectively blocked enrichment-induced spatial learning facilitation, but they did not block enrichment-induced sgk expression. Upon various glutamate agonist infusions, only alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) increased sgk mRNA levels significantly in the hippocampus. Furthermore, blockade of AMPA receptors effectively blocked both enrichment-induced spatial learning facilitation and sgk expression. These results indicate that there is a dissociation between NMDA receptor activation and sgk expression. Enrichment enhanced spatial learning through both NMDA and AMPA receptor activation, whereas enrichment-induced sgk expression is specifically mediated through AMPA receptors. These results suggest that sgk could serve as a novel molecular mechanism, in addition to the NMDA receptor NR2B, underlying enrichment-induced learning facilitation.


Phytochemicals from Red Onion, Grown with Eco-Sustainable Fertilizers, Protect Mammalian Cells from Oxidative Stress, Increasing Their Viability.
Red onion, a species of great economic importance rich in phytochemicals (bioactive compounds) known for its medicinal properties, was fertilized with sulphur-bentonite enriched with orange residue or olive pomace, with the aim of producing onion enriched in health beneficial compounds. There is a worldwide great demand of minimally processed food or food ingredients with functional properties because of a new awareness of how important healthy functional nutrition is in life. Phytochemicals have the capacity to regulate most of the metabolic processes resulting in health benefits. Red onion bioactive compound quantity and quality can vary according to cultivation practices. The main aims of the current research were to determine the chemical characteristics of the crude extracts from red onion bulbs differently fertilized and to evaluate their biological activity in normal and oxidative stress conditions. The lyophilized onion bulbs have been tested in vitro on two cellular models, i.e., the H9c2 rat cardiomyoblast cell line and primary human dermal fibroblasts, in terms of viability and oxygen radical homeostasis. The results evidenced different phytochemical compositions and antioxidant activities of the extracts obtained from red onions differently fertilized. Sulphur-bentonite fertilizers containing orange waste and olive pomace positively affected the red onion quality with respect to the red onion control, evidencing that sulphur-bentonite-organic fertilization was able to stimulate plant a secondary metabolism inducing the production of phytochemicals with healthy functions. A positive effect of the extracts from red onions treated with fertilizers-in particular, with those containing orange waste, such as the reduction of oxidative stress and induction of cell viability of H9c2 and human fibroblasts-was observed, showing a concentration- and time-dependent profile. The results evidenced that the positive effects were related to the phenols and, in particular, to chlorogenic and p-coumaric acids and to the flavonol kaempferol, which were more present in red onion treated with low orange residue than in the other treated ones.


Medical and public health professionals' perceived facilitators and barriers of human papillomavirus (HPV) vaccination among African American adolescents in Shelby County, Tennessee.
Human papillomavirus (HPV) infects nearly 85% of sexually active Americans during their lifetime, causing most cervical and five other cancers. Routine HPV vaccination is recommended for adolescents to prevent HPV-attributable cancers, but HPV vaccination coverage remains low, especially in Tennessee. In 2021, 54.6% of the population in Shelby County, Tennessee was Black or African American, reporting higher rates of new cervical cancer cases than other counties in Tennessee. While medical and public health professionals (HPs) play a critical role in promoting vaccination coverage, little is known about the factors HPs perceive to influence HPV vaccination for this population. This study sought to explore HPs' perceived facilitators and barriers of HPV vaccination among African American adolescents. Qualitative individual interviews with 26 HPs in Shelby County were conducted between October 2019 and February 2020. Interpretive content analysis of the interview data guided by the socio-ecological model revealed several important themes regarding the facilitators and barriers across the individual, interpersonal, and community levels. At the individual level, parental vaccine hesitancy emerged as a leading barrier to HPV vaccination, while appropriate education facilitated the vaccination. At the interpersonal level, a lack of strong provider recommendations impeded HPV vaccination, whereas improved communication skills with patients facilitated the vaccination. Finally, the community-level barriers included a lack of education and social/religious norms; the community-level facilitators included community outreach efforts. HPs should consider development of comprehensive community-based approaches that leverage the facilitators and barriers at multiple levels to increase HPV vaccination among African American adolescents in this region.


Development of a fucoidan-specific antibody and measurement of fucoidan in serum and urine by sandwich ELISA.
Fucoidan exhibits various biological properties. We raised a novel antibody against fucoidan extracted from Cladosiphon okamuranus and developed a sandwich ELISA method to measure fucoidan. The fucoidan antibody was specific and did not cross-react with other polysulfated polysaccharides. Fucoidan recovery from serum and urine by ELISA was 86-113%. Intra- and inter-assay CVs were 1.5-13.4%. Assay linearity was maintained after 3-fold dilution of each sample with phosphate-buffer saline (PBS). In the serum and urine of healthy volunteers (n=10), fucoidan was not detected before administration, and the levels markedly increased 6 and 9 h after oral administration. The molecular weight of the serum fucoidan determined by HPLC gel filtration remained unchanged, whereas that of urine fucoidan was significantly reduced. This is the first ELISA method of measuring serum and urine fucoidan levels after oral administration. The method is simple, reliable, and practical for the analysis of samples, especially urine samples.


Utility of bronchoscopic sampling techniques for cryptococcal disease in AIDS.
Although cryptococcal pneumonia is a well recognized complication of the acquired immunodeficiency syndrome, optimal diagnostic approaches remain to be defined. During a 32-month period (October 1984 to June 1987), 11 patients were diagnosed with CP at our institution. The diagnosis was established in all 11 patients from specimens obtained via fiberoptic bronchoscopy (ten) and/or double-lumen catheter lavage (one). Direct stains of sedimented bronchoalveolar lavage were positive for organisms characteristic of Cryptococcus neoformans in nine of 11 patients. Transbronchial biopsies were positive (special histologic stains) in six of eight patients; bronchial washings were positive (direct smear) in seven of ten patients, the bronchial brushings were positive on stain in six of nine patients, and in one patient, a Wang transbronchial needle aspirate was positive on stain. Fungal cultures were positive on the BAL in seven of 11 patients, and on the bronchial washings in four of ten patients; the TBBx culture samples were all negative (zero of three). The serum cryptococcal antigen titer was elevated (median = 1:1024) in all eight patients in which it was assayed. Our data suggest that BAL and bronchial washings have a combined sensitivity on smear equal to that of TBBx and superior to that of TBBx fungal culture. The TBBx does not appear to be necessary in this setting. In addition, an elevated serum cryptococcal antigen titer appears to be an important adjunct in the evaluation of pulmonary infiltrates in AIDS.


A model to determine the feasibility of a pediatric practice.
A major concern of urban and rural citizens of the United States is the availability of adequate pediatric health care in their community. Community leaders attempting to recruit health care providers and pediatricians considering locating their practice in a specific community need a method by which they can evaluate a community's potential for supporting a new primary care practice. A detailed survey was conducted in early 1988 of pediatric practices geographically dispersed throughout the state of Oklahoma. Data collected from the physicians and their administrative staff reflected the volume of office and hospital visits and practice costs over the prior 12 months. Using the capital costs and direct operating cost data with information obtained on the number of patient visits and revenue generated collected in this survey, we designed a model to project the economic feasibility of establishing a pediatric practice in a specific community. This model can be used to project the number of annual pediatric primary care visits a community can generate, the direct and indirect costs to establish and maintain a clinic, and the gross revenue and net income of the practice.


On the usefulness of an airborne lidar for O3 layer analysis in the free troposphere and the planetary boundary layer.
Ozone vertical profiling with a lidar is well adapted to the spatial and temporal O3 variability analysis either in the free troposphere, when studying the respective impact of chemical production and dynamical processes, or in the planetary boundary layer (PBL) when characterizing the diurnal evolution of ozone plumes during pollution episodes. Comparisons with other measuring techniques (ozonesonde and aircraft in-situ measurements) demonstrate the lidar ability to characterize narrow layers (< 500 m) with a good accuracy (deltaO3 < 5-10 ppb). Application of airborne or ground-based operation of the CNRS airborne ozone lidar show its ability (i) to observe O3 layering above the PBL during two field experiments held to study air pollution in the Po Valley, Northern Italy, and the city of Marseille, Southern France, (ii) to improve airborne campaign planning (real time information on position of O3 layers) and analysis (three-dimensional perspective for layers detected by in-situ measurements) when chemical characterization of narrow O3 layers in the free troposphere is sought, (iii) to map O3 inhomogeneity down to an horizontal scale of 10-20 km within or above the polluted PBL by airborne measurements. For O3 pollution studies, understanding the origin and the life cycle of O3 layering is the first priority, and in this case the optimum use of the lidar remains the continuous operation of a ground-based instrument.


Single-channel activity and expression of atrial L-type Ca(2+) channels in patients with latent hyperthyroidism.
Patients with "latent hyperthyroidism" (suppressed thyroid-stimulating hormone and normal circulating thyroid hormones) are at risk to develop atrial fibrillation. In animal models, hyperthyroidism is associated with increased cardiac L-type Ca(2+) current. Therefore, we assessed L-type channel function and expression in right atria from patients undergoing cardiac surgery. Single L-type channels were studied in the cell-attached condition. Voltage dependence of gating was similar in patients with and without latent hyperthyroidism. With use of a pulse protocol leading to maximum channel availability, single-channel activity was further analyzed. Average peak current was significantly enhanced in latent hyperthyroidism, mainly because of an increased channel availability (P < 0.05). Protein expression was analyzed by Western blot. In latent hyperthyroidism, expression of Ca(2+) channel alpha(1)-subunits was increased more than threefold (P < 0.01). In contrast, sarco(endo)plasmic reticulum Ca(2+)-ATPase and phospholamban levels were not significantly changed. We only observed a trend toward increased sarco(endo)plasmic reticulum Ca(2+)-ATPase expression (P = 0.085). Function and expression of human atrial L-type Ca(2+) channels are increased in latent hyperthyroidism. These endocrine effects on the heart may be clinically relevant.


Rhizosphere effect on survival of Escherichia coli O157:H7 and Salmonella enterica serovar Typhimurium in manure-amended soil during cabbage (Brassica oleracea) cultivation under tropical field conditions in Sub-Saharan Africa.
The effect of cabbage (Brassica oleracea) rhizosphere on survival of Escherichia coli O157:H7 and Salmonella Typhimurium in manure-amended soils under tropical field conditions was investigated in the Central Agro-Ecological Zone of Uganda. Three-week old cabbage seedlings were transplanted and cultivated for 120 days on manure-amended soil inoculated with 4 or 7 log CFU/g non-virulent E. coli O157:H7 and S. Typhimurium. Cabbage rhizosphere did not affect survival of the 4log CFU/g inocula in manure-amended soil and the two enteric bacteria were not detected on/in cabbage leaves at harvest. The 7 log CFU/g E. coli O157:H7 and S. Typhimurium survived in bulk soil for a maximum of 80 and 96 days, respectively, but the organisms remained culturable in cabbage rhizosphere up to the time of harvest. At 7 log CFU/g inoculum, E. coli O157:H7 and S. Typhimurium contamination on cabbage leaves occurred throughout the cultivation period. Leaf surface sterilisation with 1% AgNO(3) indicated that the organisms were present superficially and in protected locations on the leaves. These results demonstrate that under tropical field conditions, cabbage rhizosphere enhances the persistence of E. coli O157:H7 and S. Typhimurium in manure-amended soil at high inoculum density and is associated with long-term contamination of the leaves.


Early natural stimulation through environmental enrichment accelerates neuronal development in the mouse dentate gyrus.
The dentate gyrus is the primary afferent into the hippocampal formation, with important functions in learning and memory. Granule cells, the principle neuronal type in the dentate gyrus, are mostly formed postnatally, in a process that continues into adulthood. External stimuli, including environmental enrichment, voluntary exercise and learning, have been shown to significantly accelerate the generation and maturation of dentate granule cells in adult rodents. Whether, and to what extent, such environmental stimuli regulate the development and maturation of dentate granule cells during early postnatal development is largely unknown. Furthermore, whether natural stimuli affect the synaptic properties of granule cells had been investigated neither in newborn neurons of the adult nor during early development. To examine the effect of natural sensory stimulation on the dentate gyrus, we reared newborn mice in an enriched environment (EE). Using immunohistochemistry, we showed that dentate granule cells from EE-reared mice exhibited earlier morphological maturation, manifested as faster peaking of doublecortin expression and elevated expression of mature neuronal markers (including NeuN, calbindin and MAP2) at the end of the second postnatal week. Also at the end of the second postnatal week, we found increased density of dendritic spines across the entire dentate gyrus, together with elevated levels of postsynaptic scaffold (post-synaptic density 95) and receptor proteins (GluR2 and GABA(A)Rγ2) of excitatory and inhibitory synapses. Furthermore, dentate granule cells of P14 EE-reared mice had lower input resistances and increased glutamatergic and GABAergic synaptic inputs. Together, our results demonstrate that EE-rearing promotes morphological and electrophysiological maturation of dentate granule cells, underscoring the importance of natural environmental stimulation on development of the dentate gyrus.


Nonlinear optical switching properties in the furylfulgide aberchrome 540-dihydrobenzofuran derivative pair of photochromic materials.
Time-dependent density functional theoretical investigation has been carried out to justify the switching action of nonlinear optical properties in the furylfulgide Aberchrome 540 (FFA) and dihydrobenzofuran derivative (DHBF) photochromic pair of molecules. The effect of solvents on this switching action has also been addressed. The calculations suggest that DHBF has a higher optical coefficient compared to that of FFA. Notably, a dramatic increase in DHBF is observed in the second harmonic data, particularly in the solvent phase. The ratio of SHG tensor gradually decreases as the polarity of the solvent is decreased using a coulomb-attenuating functional irrespective of the basis sets used. An exploration of the excitation parameters suggests that high excited-state dipole moments are responsible for the observed large beta value in the case of the DHBF system relative to that of the FFA system.


Contribution of MEK/MAPK and PI3-K signaling pathway to the malignant behavior of Ewing's sarcoma cells: therapeutic prospects.
Insulin-like growth factor receptor I (IGF-I)-mediated circuit is a major autocrine loop for Ewing's sarcoma (ES) cells and appears to be particularly important in the pathogenesis of this tumor. In this study, we analyzed the contribution of the 2 major pathways of the intracellular IGF-IR signaling cascade to the overall effects elicited by IGF-I in ES. Both the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3-K) signaling pathways appeared to be constitutively activated in ES, likely due to the presence of the IGF-IR-mediated autocrine loop. We demonstrated that both MEK/MAPK (PD98059 or U0126) and PI3-K inhibitors (LY294002) profoundly impaired ES cell growth in monolayer and soft agar basal conditions. Both PD98059 and LY294002 inhibited ES cell cycle progression by inducing G1 blockage, whereas only LY294002 significantly affected the survival of ES cells. Exogenous IGF-I completely reverted LY294002-induced growth inhibition by abrogating antiproliferative and proapoptotic effects of the PI3-K inhibitor. By contrast, IGF-I could not rescue cells from growth inhibition induced by PD98059. MEK/MAPK blockade also significantly reduced the migratory ability of ES cells, both in basal and IGF-I-induced conditions, and increased chemosensitivity to doxorubicin, a leader drug in the treatment of ES patients. Our findings therefore identify MAPK pathway as a promising target for pharmacologic intervention in ES.


Investigating the role of P38, JNK and ERK in LPS induced hippocampal insulin resistance and spatial memory impairment: effects of insulin treatment.
Despite the consensus that neuro-inflammation and insulin resistance (IR) are two hallmarks of Alzheimer disease (AD), the molecular mechanisms responsible for the development of IR remain uncharacterized. MAPKs are signaling molecules that are implicated in the pathology of AD and have a role in IR development. Given that inflammatory mediators are shown to interfere with insulin signaling pathway in different cell types, the present work aimed to investigate whether neuro-inflammation induced memory loss is associated with hippocampal IR and whether insulin treatment protects against this IR. Subsequently, possible roles of MAPKs in this situation were investigated. Male Wistar rats were cannulated, and LPS (15 µg, day 0), insulin (3 mU) or saline (vehicle) were administered intra-cerebroventricularly (ICV) (days 1-6). Spatial memory performance was assessed during days 7-10 by Morris Water Maze test. Consequently, analysis of the amount of hippocampal phosphorylated forms of P38, JNK, ERK, IRS1 (ser307) and Akt (ser473) were done by Western blot. The outcomes indicated that while LPS induced memory loss and hippocampal IR (shown by elevated IRS1 and decreased Akt phosphorylation), insulin treatment nullified these effects. Molecular results also showed that LPS mediated IR and memory loss are associated with P38 but not JNK and ERK activation; this P38 activation was reversed by insulin treatment. These observations implied that one of the ways by which neuro-inflammation participates in AD is via induction of IR. It seems that this IR is mainly mediated by P38. Therefore, P38 could be considered as a molecular target for preventing IR development.


Biological Adaptations Associated with Dehydration in Mosquitoes.
Diseases that are transmitted by mosquitoes are a tremendous health and socioeconomic burden with hundreds of millions of people being impacted by mosquito-borne illnesses annually. Many factors have been implicated and extensively studied in disease transmission dynamics, but knowledge regarding how dehydration impacts mosquito physiology, behavior, and resulting mosquito-borne disease transmission remain underdeveloped. The lapse in understanding on how mosquitoes respond to dehydration stress likely obscures our ability to effectively study mosquito physiology, behavior, and vectorial capabilities. The goal of this review is to develop a profile of factors underlying mosquito biology that are altered by dehydration and the implications that are related to disease transmission.


Phytochemical investigation and evaluation of in vitro free radical scavenging activity of Tabernaemontana divaricata Linn.
We evaluate the in vitro free radical scavenging activity of the leaves of Tabernaemontana divaricata Linn. Petroleum ether, ethanol and aqueous extracts of T. divaricata were prepared with successive extraction in a soxhlet apparatus. Each extract was selected to study the free radical scavenging activity by superoxide scavenging assay method. It was found that the aqueous extract contained carbohydrates, glycosides, amino acids, flavonoids, tannins, alkaloids, and steroids, and the ethanolic extract contained glycosides, amino acids, flavonoids, tannins, alkaloids and steroids. The ethanolic extract of T. divaricata showed 58.7 +/- 0.62% inhibition in the superoxide scavenging model. The aqueous extract also showed almost similar activity (54.9 +/- 0.53% compared to the ethanolic extract), while petroleum ether extract showed poor inhibition of superoxide scavenging activity. All extracts showed the dose- and time-dependent inhibition of the superoxide scavenging activity.