Safety and efficacy of terbinafine in a pediatric Iranian cohort of patients with Tinea capitis.
Tinea capitis is a common infection of the scalp and hair shaft caused by dermatophyte fungi that mainly affects prepubescent children. Systemic therapy is required for treatment and to prevent spread. The aim of present study was to assess the effect of terbinafine for Tinea capitis treatment in children. Thirty Iranian pediatric patients with a clinical diagnosis of Tinea capitis were enrolled in the study. The Study was conducted in a general and referral teaching hospital (Imam Medical Centre - Tehran, Iran) from 2006 to 2007. Eligible patients with less than 20 kg of body weight were given 62.5 mg terbinafine, and for patients between 20 and 40 kg the dose was 125 mg, on the first visit. All patients had the second clinical visit and second samples for microscopic study were taken. For each patient, direct mycology test (KOH test) and mycological culture were carried out before the study was started and after second, fourth, fifth, sixth and eighth weeks. Probable drug's adverse effects were also recorded. Based on the results of mycological culture of patients' lesions, Microsporum canis and Trichophyton sheonlini were considered as major causes of Tinea capitis in these children. Out of 30 study patients, KOH test of 93% in the 5th week and 100% in the 6th week was negative. All patients healed completely from signs of infection, after six weeks. Also, no severe side effects were seen in any patients. According to the results of this study, the use of terbinafine is an effective therapy in Iranian cases of Tinea capitis in children without severe side effects.


Ipsilateral projections to the terminal nuclei of the accessory optic system in the albino rat.
The projection of the retinal ganglion cells to the terminal nuclei of the accessory optic system has been re-examined in the albino rat. After intravitreal injection of [3H]leucine the contralateral and ipsilateral terminal nuclei were labeled. This complete ipsilateral projection in the rat has, of yet, not been documented.


Sorption of dispersed petroleum hydrocarbons by activated charcoals: Effects of oil dispersants.
Marine oil spill often causes contamination of drinking water sources in coastal areas. As the use of oil dispersants has become one of the main practices in remediation of oil spill, the effect of oil dispersants on the treatment effectiveness remains unexplored. Specifically, little is known on the removal of dispersed oil from contaminated water using conventional adsorbents. This study investigated sorption behavior of three prototype activated charcoals (ACs) of different particle sizes (4-12, 12-20 and 100 mesh) for removal of dispersed oil hydrocarbons, and effects of two model oil dispersants (Corexit EC9500A and Corexit EC9527A). The oil content was measured as n-alkanes, polycyclic aromatic hydrocarbons (PAHs), and total petroleum hydrocarbons (TPHs). Characterization results showed that the smallest AC (PAC100) offered the highest BET surface area of 889 m2/g and pore volume of 0.95 cm3/g (pHPZC = 6.1). Sorption kinetic data revealed that all three ACs can efficiently adsorb Corexit EC9500A and oil dispersed by the two dispersants (DWAO-I and DWAO-II), and the adsorption capacity followed the trend: PAC100 > GAC12 × 20 > GAC4 × 12. Sorption isotherms confirmed PAC100 showed the highest adsorption capacity for dispersed oil in DWAO-I with a Freundlich KF value of 10.90 mg/g∙(L/mg)1/n (n = 1.38). Furthermore, the presence of Corexit EC9500A showed two contrasting effects on the oil sorption, i.e., adsolubilization and solubilization depending on the dispersant concentration. Increasing solution pH from 6.0 to 9.0 and salinity from 2 to 8 wt% showed only modest effect on the sorption. The results are useful for effective treatment of dispersed oil in contaminated water and for understanding roles of oil dispersants.


Electroconvulsive stimulation alters levels of BDNF-associated microRNAs.
Electroconvulsive therapy (ECT) is the most effective antidepressant treatment available yet its mechanism of action remains incompletely understood. Electroconvulsive stimulation (ECS), a rat model of electroconvulsive therapy, induces expression of brain derived neurotrophic factor (BDNF) within the brain but the precise means by which this occurs and by which it contributes to the antidepressant effects of ECS are unknown. MicroRNAs (miRNAs), a class of endogenous small non-coding RNA species, may play a role as BDNF can both regulate and be regulated by miRNAs. We examined expression of BDNF-associated miRNAs in rat brain and blood following either acute (x1) or chronic (x10) ECS. Fourteen BDNF-associated miRNA species were identified for investigation using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). We found that levels of miRNA miR-212 were significantly increased in rat dentate gyrus following both acute and chronic ECS. MiR-212 levels also increased in whole blood following chronic ECS and this positively correlated with miR-212 levels in the dentate gyrus. Our results suggest that alterations in miRNA expression may be informative about the mechanism of action of ECS/ECT.


Effects of Displacement in Children Exposed to Disasters.
The literature on children's responses to disasters is well developed with increasing attention to the confounding experiences of displacement. This paper presents an overview of the emotional and behavioral effects of displacement on children and adolescents and describes their educational adjustment in terms of both academic achievement and school behavior. A summary of family effects elucidates how children's functioning is influenced through the family system in which they are embedded. The psychosocial impact of displacement reflects the myriad social losses that children and their families may face. Information from this review of the current literature on the effects of displacement may inform the design and delivery of support and intervention services for children and families following disasters.


Persistent environmental contaminants in human milk: concentrations and time trends in Italy.
Breast milk monitoring studies of persistent and toxic environmental contaminants are of primary importance for carrying out an adequate risk assessment at the actual levels of human exposure and represent a major source of information on infant perinatal exposure. Milk specimens from mothers of the general population of the Venice and Rome areas were collected over the 1998-2001 period, pooled, and analyzed for selected persistent organic pollutants such as polychlorodibenzodioxins (PCDDs), polychlorodibenzofurans (PCDFs), polychlorobiphenyls (PCBs), organochlorinated pesticides (p,p'-DDE, p,p'-DDT, hexachlorobenzene), and polybromodiphenyl ethers (PBDEs), and the heavy metals Cd, Co, Cu, Hg, Mn, Pb, Sn, and Zn. The goal was to verify whether mother milk from the Venice area, whose lagoon is partly under direct industrial impact, had a contaminant load greater than that from the Rome area, primarily urban. For mothers from the Venice area, the correlation between fish and fishery product consumption and contaminant concentrations in milk was also explored, with however inconclusive results. The concentrations of PCDDs, PCDFs, dioxin-like PCBs, and organochlorinated pesticides determined in this study were compared with those available from a previous analytical work carried out on 1987 human milk pools of domestic origin: the declining trend of the aforesaid contaminants in milk is confirmed to be in agreement with what was observed in other European countries. The breast milk content of (137)Cs and (40)K radionuclides was also determined and compared with data obtained in other research programmes carried out in Italy: the health risk for breastfed infants was deemed to be not significant.


Efficacy and safety of recombinant human follicle-stimulating hormone in men with isolated hypogonadotropic hypogonadism.
To assess the efficacy and safety of recombinant human follicle-stimulating hormone (rhFSH; follitropin alpha) in increasing sperm concentration in 26 men with severe isolated hypogonadotropic hypogonadism (IHH). Clinical and endocrine studies using an open design. Six university clinical sites in three European countries. Azoospermatic patients aged 16 to 48 years with IHH. Patients received hCG for up to 6 months before 18 months of treatment with rhFSH. Sperm count, motility, and morphology were assessed every 3 months. Achievement of a sperm concentration of 1.5 x 10(6)/mL. Spermatogenesis was achieved in 15 of 19 patients who could be evaluated, 12 achieving a sperm concentration of > or =1.5 x 10(6)/mL. With hCG, rhFSH is effective in initiating spermatogenesis in patients with IHH, and is well tolerated.


MiR-425-5p suppression of Crebzf regulates oocyte aging via chromatin modification.
Female infertility due to declining oocyte quality with age remains a significant challenge for patients and physicians, despite extensive research efforts. Recent studies suggest that microRNAs (miRNAs), which respond to various stressors in the aging process, may provide a promising solution. With the approval of small RNA drugs for clinical use, miRNA-based treatment of oocyte aging appears to be a viable option. Through high-throughput sequencing, miR-425-5p was identified as the only miRNA elevated under natural aging and oxidative stress. Microinjection of inhibitors to inhibit miR-425-5p effectively improved compromised phenotypes of old oocytes in vitro. Further investigation revealed that Crebzf acts as a mediator of miR-425-5p's age-related functions in old oocytes. In vivo treatment with miR-425-5p antagomirs significantly improved impaired oocyte development in reproductively old females by targeting Crebzf. Single-cell RNA sequencing revealed that Crebzf plays a vital role in regulating mRNAs targeting histone H3, trimethylated lysine 4 (H3K4me3), a crucial marker for transcriptional silencing. Overexpression of miR-425-5p could hinder oocyte maturation by downregulating Crebzf expression and disrupting transcriptional regulation. Our findings provide new insights into the potential of miR-425-5p antagomirs as a treatment for female infertility and highlight an elegant mechanism by which miR-425-5p inhibition of Crebzf inhibits a developmental switch in GV oocytes by regulating a group of histone methyltransferase mRNAs.


Identification of a Plasmodium berghei antigen sharing common features with P. falciparum and P. chabaudi parasitophorous-vacuole membrane antigens.
On the basis of immunological cross-reactivity, we identified a 43-kDa Plasmodium berghei antigen with homology to the exp-1 antigen from P. falciparium. The P. berghei antigen was recognized by an antibody directed against an epitope on the C-terminus of the P. falciparum exp-1 protein. This antigen is localized on the surface of the parasite and shares peptide sequence homology with the P. chabudi antigen Ag3008. To investigate further the role of the P. berghei antigen, we designed antisense phosphorothioate oligodeoxynucleotides (PS oligos) complementary to sequences of the exp-1 mRNA from P. falciparum. The PS oligos were capable of inhibiting the development of P. falciparum in vitro by 47%. In vivo, experiments in mice showed that the same PS oligos had the potential to extend the life span of mice infected with P. berghei by a factor of 2-4. The immunological cross-reactivity and the antisense inhibition of P. berghei parasite development in vivo indicate that this antigen may be a homologue of exp-1 from P. falciparum that has functional importance for parasite survival.


Marker half-life analysis as a prognostic tool in testicular cancer.
In a retrospective study we compared the actual half-life of the serum tumor markers alphafetoprotein and human chorionic gonadotropin to the clinical course of patients who underwent an operation or chemotherapy for germ cell cancer. Of the 7 patients with residual disease postoperatively 5 had abnormal half-life values and in 3 this knowledge would have been of clinical value. Only 1 of 10 patients with a complete response to chemotherapy had an unfavorable actual half-life compared to 17 of 19 with a less than complete response. Prolonged marker decay rates during the first month of chemotherapy reflected ineffective chemotherapy and appeared to be independent of tumor bulk. Postoperatively, actual half-lives probably are useful prognostically only if the values are abnormal. Similar calculation may be of prognostic value early in the course of induction chemotherapy.


The reaction of mercaptans with tyrosinases and hemocyanins.
1. Titration of Neurospora tyrosinase with 2-mercaptoethanol shows that the increase of absorbance at 700 nm is directly correlated to the loss of enzymatic activity. Approximately 2 mol of 2-mercaptoethanol per mole of protein are needed for full development of the green, enzymatically inactive complex. The increase of absorbance at 700 nm is also proportional to the intensity of the EPR signal and the amount of non-covalently bound 2-[35S] mercaptoethanol to the enzyme. The maximal EPR intensity reaches 70% of the protein concentration and at most 0.7--0.8 mol of 2-[35S] mercaptoethanol is bound per mol of enzyme. 2. Stopped-flow measurements show that in the reaction between 2-mercaptoethanol and Neurospora tyrosinase a raction intermediate with a strong absorption band at 360 nm is formed in an apparent second-order reaction. This intermediate displays no EPR-detectable signals. The intermediate decays in a similar complex fashion as the absorption band at 700 nm is formed. 3. The reaction of Neurospora tyrosinase with a variety of sulfhydryl compounds was also investigated. In most cases green coloured, enzymatically inactive complexes are formed displaying slightly different EPR signals. However, with cysteine and cysteamine violet coloured, enzymatically inactive complexes are formed which show rather different EPR signals. The integrated EPR intensities amount to 40--70% of the protein concentration. Based on simulations of 9 and 35 GHz spectra all observed EPR spectra can be represented as true S = 1/2 systems. The cysteamine complex can be interpreted as arising from a mixed valence Cu2+ . Cu+ complex. The 2-mercaptoethanol spectra can, however, arise from sulphur radicals. 4. Treatment of Agaricus bispora tyrosinase and Cancer pagures hemocyanin with 2-mercaptoethanol results in green-coloured, EPR detectable complexes similar to the one found with Neurospora tyrosinase. No such complexes are formed when hemocyanins from Helix pomatia and Panulirus interruptus were treated with this reagent.


Biochemical characterization of acetyl-CoA:1-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase in rat spleen microsomes.
Acetyl-CoA:1-alkyl-2-lyso-sn-glycero-3-phosphocholine (lyso-PAF) ultrasonic disruption in the presence of 25% glycerol from rat spleen microsomes. About 26% of the enzymatic activity was recovered in the 225,000 X g supernatant by this treatment, although the specific activity was slightly decreased compared with the original microsomes. The solubilized enzyme was remarkably susceptible to various kinds of metal ions. Sulfhydryl reagents such as p-chloromercuribenzoate and N-ethyl-maleimide significantly inhibited the enzyme reaction, suggesting that the enzyme is an SH enzyme. Based on the sedimentation pattern in sucrose density centrifugation, the isoelectric point, the kinetic characteristics and the sensitivity to tryptic digestion of microsomes, it appears that acetyl-CoA:lyso-PAF acetyltransferase does not differ from the acetyltransferase responsible for the transfer of acetate from acetyl-CoA to 1-acyl-2-lyso-sn-glycero-3-phosphocholine.


Relationship between types of physical activity and depression among 88,522 adults.
Physical activity is associated with depression; however, the influence of physical activity type on this association remains poorly explored. We aimed to investigate the association between various types of leisure-time physical activity and depression among a large and representative sample. Data from the 2019 Brazilian National Health Survey were used (n = 88,522 adults aged between 18 and 107 years, 53% female). Depression was measured using the Patient Health Questionnaire-9; participants' leisure-time physical activity types were self-reported. A four-step hierarchical regression was applied, and the analyses were adjusted for several confounders. Active individuals had lower odds of depression (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.62-0.81); however, only outdoor walking/running (OR, 0.70; 95% CI, 0.60-0.82), cycling (OR, 0.50; 95% CI, 0.34-0.74), and team sports (OR, 0.52; 95% CI, 0.42-0.66) were associated with lower odds of depression than inactivity. Physical activity type may be associated with mental health. The qualitative mechanisms of some physical activities seem to have greater capability than others to reduce depression. Causal inferences could not be made, however, our findings suggest that specific physical activities types have additional benefits that can be used in promoting mental health in clinical intervention and at a population level.


Proteomic and transcriptomic analysis to unravel the influence of high temperature on banana fruit during postharvest storage.
Banana, an important food, incurs significant economic losses due to high storage temperature. Integrative analysis of proteome and transcriptome profiles of the banana peel stored at 20 °C (control) and 30 °C (HT) was used to investigate the molecular mechanism in response to high temperature stress. Critical proteins and genes relating to the response of banana fruit to HT stress were evaluated using partial least squares-discriminant analysis (PLS-DA) and orthogonal signal correction partial least squares-discriminant analysis (OPLS-DA). HT stress influenced proteins/genes related to chlorophyll metabolism, fruit firmness, signal transduction, energy metabolism, and stress response and defense. Together with scanning electron microscopy (SEM) and real time quantitative PCR (RT-qPCR) results, it can be concluded that HT stress resulted in stay-green ripening of banana fruit. Additionally, HT stress accelerated firmness loss and senescence of banana peel, might mainly through regulating hormone signaling pathway, stress protective ability, and energy metabolism in the banana peel. Our study provided a clearer understanding of regulatory mechanisms of HT treatment on banana fruit and potential genetic resources for the improvement of high temperature-tolerant characteristics in banana fruit.


[Predicting individual risk of high healthcare cost to identify complex chronic patients].
To develop a predictive model for the risk of high consumption of healthcare resources, and assess the ability of the model to identify complex chronic patients. A cross-sectional study was performed within a healthcare management organization by using individual data from 2 consecutive years (88,795 people). The dependent variable consisted of healthcare costs above the 95th percentile (P95), including all services provided by the organization and pharmaceutical consumption outside of the institution. The predictive variables were age, sex, morbidity-based on clinical risk groups (CRG)-and selected data from previous utilization (use of hospitalization, use of high-cost drugs in ambulatory care, pharmaceutical expenditure). A univariate descriptive analysis was performed. We constructed a logistic regression model with a 95% confidence level and analyzed sensitivity, specificity, positive predictive values (PPV), and the area under the ROC curve (AUC). Individuals incurring costs >P95 accumulated 44% of total healthcare costs and were concentrated in ACRG3 (aggregated CRG level 3) categories related to multiple chronic diseases. All variables were statistically significant except for sex. The model had a sensitivity of 48.4% (CI: 46.9%-49.8%), specificity of 97.2% (CI: 97.0%-97.3%), PPV of 46.5% (CI: 45.0%-47.9%), and an AUC of 0.897 (CI: 0.892 to 0.902). High consumption of healthcare resources is associated with complex chronic morbidity. A model based on age, morbidity, and prior utilization is able to predict high-cost risk and identify a target population requiring proactive care.


Reducing the influence of non-target stimuli on saccade accuracy: predictability and latency effects.
When the eye saccades to a group of eccentric targets, it tends to land in a position which can be loosely described as the center of gravity of the configuration. By using letter targets within strings of letters, it was shown in two experiments that this "global effect", that is, the influence of the non-target elements on saccade accuracy, can be attenuated when the "where" calculation is facilitated or when the moment of saccade triggering is sufficiently delayed. Arguments are given in order to show that the improvement of saccade accuracy observed is a perceptual and not a motor effect and, some hypotheses are then presented for a possible underlying mechanism. It is also suggested that the exact position where the eye lands can be calculated from a linear combination of two tendencies: a tendency to saccade to the aimed-for target, and a tendency to saccade to a "gaze attraction position". Closer consideration showed that this gaze attraction position is not exactly at the center of gravity of the configuration, but less eccentric than it, possibly due to weighting by a cortical magnification factor.


The role of the superior cervical ganglia in the nocturnal rise of pineal type-II thyroxine 5'-deiodinase activity.
Superior cervical ganglionectomy (SCGx) abolished the nocturnal rise in pineal type-II thyroxine 5'-deiodinase (5'-D) activity in both euthyroid and hypothyroid rats. Isoproterenol induced at least as great a rise in diurnal pineal 5'-D in SCGx as in intact rats. These data suggest that beta-adrenergic stimulation through the superior cervical ganglia is essential for the nocturnal rise in pineal 5'-D activity.


Multi-channel AgNWs-doped interdigitated organic electrochemical transistors enable sputum-based device towards noninvasive and portable diagnosis of lung cancer.
Biochemical monitoring of bodily fluidics such as sweat, urine, and tears have been extensively developed, but reliable biochemical analysis of sputum biospecimens remains limited and challenging due to the low abundance of biomarkers in intrinsically viscous sputum. We reported a portable multi-channel sputum-based interdigitated organic electrochemical transistors (SiOECTs) device for noninvasive sputum diagnosis. We tailored the AgNWs-doped organic electrochemical transistors, integrating with multiplexed aptamer-antigen assays, to realize the signal amplification and simultaneous detection of biomarkers in raw sputum biospecimens from lung cancer patients. Clinical validation studies demonstrated favorable correlation coefficients between the sputum and serum biospecimens. By utilizing our portable multi-channel iOECTs devices, lung cancer patients were differentiated from health control with an optimum area under the curve (AUC) of 0.931, sensitivity of 87.0%, and specificity of 86.5%. Our miniaturized and portable device could even realize the continuous in-home tracking of the biomarkers change for lung cancer patients after radiotherapy/chemotherapy. It is envisaged that the SiOECTs will shed light on noninvasive diagnostics platforms for sputum-related diseases.


Covalent and noncovalent DNA binding by mutants of vaccinia DNA topoisomerase I.
Analysis of vaccinia topoisomerase mutants that are impaired in DNA relaxation has allowed the identification of amino acid residues required for the transesterification step of catalysis. Missense mutations of wild-type residues Gly-132----Asp and Arg-223----Gln rendered the protein inert in formation of the covalent enzyme-DNA complex and hence completely inactive in DNA relaxation. Mutations of Thr-147----Ile and Gly-132----Ser caused severe defects in covalent adduct formation that correlated with the extent of inhibition of relaxation. None of these point mutations had an effect on noncovalent DNA binding sufficient to account for the defect in relaxation. Deletion of amino- or carboxyl-terminal portions of the polypeptide abrogated noncovalent DNA binding. Two distinct topoisomerase-DNA complexes were resolved by native gel electrophoresis. One complex, which was unique to those proteins competent in covalent adduct formation, contained topoisomerase bound to the 5'-portion of the incised DNA strand. The 3'-segment of the cleaved strand had dissociated spontaneously. This complex was isolated and shown to catalyze transfer of the covalently bound DNA to a heterologous acceptor oligonucleotide, thereby proving that the covalent adduct between protein and duplex DNA is a true intermediate in strand breakage and reunion. The role of the active site region of eukaryotic topoisomerase in determining sensitivity or resistance to camptothecin was examined by converting the active site region of the resistant vaccinia enzyme (SKRAY274) to that of the drug-sensitive yeast enzyme (SKINY). The SKINY mutation did not alter the resistance of the vaccinia enzyme to the cleavage-enhancing effects of camptothecin.


Natural or vaccine-induced antibody as a predictor of immunity in the face of natural challenge with influenza viruses.
A study of influenza in residential schools provided the opportunity to assess the significance of antibody as a predictor of immunity. Five hundred and fifty-six pupils from 8 schools were included in the investigations, and the outcome for these children in 27 naturally occurring outbreaks of influenza was analysed. The outbreaks comprised 5 caused by strains of influenza A H3N2, 10 caused by strains of influenza A H1N1, and 12 caused by strains of influenza B. On 8 occasions a second outbreak of the same serotype occurred in a school. There was a general correlation between the presence of antibody to the outbreak strain and protection from infection. For each of the three influenza virus serotypes the infection rate in those with no detectable antibody was approximately 80%. Those with past experience of the virus but no antibody to the outbreak strain experienced lower infection rates (62% overall) but the infection rates were lowest in those with intermediate and high level antibody to the challenge strain (18% overall). Vaccine was used by three of the schools. The effect of antibody derived from recent experience, either natural or vaccine-induced, on subsequent challenge with a drifted strain i.e. one showing antigenic drift away from the previous strain, was compared. Intermediate or high level antibody to the challenge strain in those who had experienced a recent natural infection was associated with a low infection rate (9%). A similar level of antibody produced in response to vaccination was associated with a significantly higher infection rate (23%: P less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)


Aging in Rural Communities.
Population aging is occurring worldwide, particularly in developed countries such as the United States (US). However, in the US, the population is aging more rapidly in rural areas than in urban areas. Healthy aging in rural areas presents unique challenges. Understanding and addressing those challenges is essential to ensure healthy aging and promote health equity across the lifespan and all geographies. This review aims to present findings and evaluate recent literature (2019-2022) on rural aging and highlight future directions and opportunities to improve population health in rural communities. The review first addresses several methodological considerations in measuring rurality, including the choice of measure used, the composition of each measure, and the limitations and drawbacks of each measure. Next, the review considers important concepts and context when describing what it means to be rural, including social, cultural, economic, and environmental conditions. The review assesses several key epidemiologic studies addressing rural-urban differences in population health among older adults. Health and social services in rural areas are then discussed in the context of healthy aging in rural areas. Racial and ethnic minorities, indigenous peoples, and informal caregivers are considered as special populations in the discussion of rural older adults and healthy aging. Lastly, the review provides evidence to support critical longitudinal, place-based research to promote healthy aging across the rural-urban divide is highlighted. Policies, programs, and interventions to reduce rural-urban differences in population health and to promote health equity and healthy aging necessitate a context-specific approach. Considering the cultural context and root causes of rural-urban differences in population health and healthy aging is essential to support the real-world effectiveness of such programs, policies, and interventions.


Mechanobiology of orthodontic tooth movement: An update.
The purpose of this review is to provide an update on the changes at the cellular and tissue level occurring during orthodontic force application. For the understanding of this process, knowledge of the mechanobiology of the periodontal ligament and the alveolar bone are essential. The periodontal ligament and alveolar bone make up a functional unit that undergoes robust changes during orthodontic tooth movement. Complex molecular signaling is responsible for converting mechanical stresses into biochemical events with a net result of bone apposition and/or bone resorption. Despite an improved understanding of mechanical and biochemical signaling mechanisms, it is largely unknown how mechanical stresses regulate the differentiation of stem/progenitor cells into osteoblast and osteoclast lineages. To advance orthodontics, it is crucial to gain a better understanding of osteoblast differentiation from mesenchymal stem/progenitor cells and osteoclastogenesis from the hematopoietic/monocyte lineage.


Spontaneous hypoglycaemia after pancreas transplantation in Type 1 diabetes mellitus.
Hypoglycaemia is an important complication of insulin treatment in Type 1 diabetes mellitus (DM). Pancreas transplantation couples glucose sensing and insulin secretion, attaining a distinctive advantage over insulin treatment. We tested whether successful transplantation can avoid hypoglycaemia in Type 1 DM. Combined kidney and pancreas transplanted Type 1 DM who complied with good function criteria (KP-Tx, n = 55), and isolated kidney or liver transplanted non-diabetic subjects on the same immunosuppressive regimen (CON-Tx, n = 14), underwent 1-day metabolic profiles in the first 3 years after transplantation, sampling plasma glucose (PG) and pancreatic hormones every 2 hours. KP-Tx had lower PG than CON-Tx in the night and in the morning and higher insulin concentrations throughout the day. KP-Tx had lower PG nadirs than CON-Tx (4.40+/-0.05 vs 4.96+/-0.16 mmol l(-1), ANOVA p = 0.001). Nine per cent of KP-Tx had hypoglycaemic values (PG < or = 3.0 mmol l(-1)) in the profiles, both postprandial and postabsorptive, whereas none of CON-Tx did (p < 0.02). In conclusion, after pancreas transplantation, mild hypoglycaemia is frequent, although its clinical impact is limited. Compared to insulin treatment in Type 1 DM, pancreas transplantation improves but cannot eliminate hypoglycaemia.


KRAS mutant allele-specific imbalance is associated with worse prognosis in pancreatic cancer and progression to undifferentiated carcinoma of the pancreas.
KRAS codon 12 mutations are present in about 90% of ductal adenocarcinomas and in undifferentiated carcinomas of the pancreas. The role of KRAS copy number changes and resulting KRAS mutant allele-specific imbalance (MASI) in ductal adenocarcinoma (n=94), and its progression into undifferentiated carcinoma of the pancreas (n=25) was studied by direct sequencing and KRAS fluorescence in situ hybridization (FISH). Semi-quantitative evaluation of sequencing electropherograms showed KRAS MASI (ie, mutant allele peak higher than or equal to the wild-type allele peak) in 22 (18.4%) cases. KRAS FISH (performed on 45 cases) revealed a trend for more frequent KRAS amplification among cases with KRAS MASI (7/20, 35% vs 3/25, 12%, P=0.08). KRAS amplification by FISH was seen only in undifferentiated carcinomas (10/24, 42% vs 0/21 pancreatic ductal adenocarcinoma, 0%, P=0.0007). In 6 of 11 cases with both undifferentiated and well-differentiated components, transition to undifferentiated carcinoma was associated with an increase in KRAS copy number, due to amplification and/or chromosome 12 hyperploidy. Pancreatic carcinomas with KRAS MASI (compared to those without MASI) were predominantly undifferentiated (16/22, 73% vs 9/97, 9%, P<0.001), more likely to present at clinical stage IV (5/22, 23% vs 7/97, 7%, P=0.009), and were associated with shorter overall survival (9 months, 95% confidence interval, 5-13, vs 22 months, 95% confidence interval, 17-27; P=0.015) and shorter disease-free survival (5 months, 95% confidence interval, 2-8 vs 13 months, 95% confidence interval, 10-16; P=0.02). Our findings suggest that in a subset of ductal adenocarcinomas, KRAS MASI correlates with the progression to undifferentiated carcinoma of the pancreas.


The role of temporary biventricular pacing in the cardiac surgical patient with severely reduced left ventricular systolic function.
The objective was to evaluate the effects of atrial synchronous biventricular pacing in postoperative patients with severe cardiomyopathy. Atrial synchronous biventricular pacing epicardial leads were placed during cardiac surgery in patients with an ejection fraction of 30% or less. Patients were randomized to usual care pacing, the mode determined by the surgeon (excluding atrial synchronous biventricular pacing) with a preference for no pacing or atrial pacing (atrial inhibited pacing); atrial synchronous right ventricular pacing; or atrial synchronous biventricular pacing. Pacing was continued until cessation of hemodynamic support. At 12 hours postoperatively, patients were randomly tested in each mode (atrial inhibited, atrial synchronous right ventricular, and atrial synchronous biventricular pacing), and thermodilution outputs were measured. Forty subjects were randomized. Groups were similar in age (66 +/- 11 years), gender (85% were male), ejection fraction (23% +/- 6%), QRS duration (111 +/- 30 ms), and surgical indication. There was no difference in stroke index or cardiac index at 12 hours, duration of inotropic or intra-aortic balloon pump support, intensive care unit, or hospital length of stay. On comparative crossover testing, stroke volume was similar with atrial inhibited pacing and atrial synchronous biventricular pacing (59.3 +/- 13.4 vs 57 +/- 12.1, respectively, P = not significant); however, atrial synchronous right ventricular pacing was inferior (56 +/- 12.9, P < .05 for comparison with atrial inhibited pacing). When compared with atrial inhibited pacing, atrial synchronous biventricular pacing showed a positive response in 17% of subjects (increase in stroke volume >or= 5%), whereas 41% had a 5% or greater decrease in stroke volume. Pacing mode affects stroke volume in patients with severe cardiomyopathy. Atrial synchronous biventricular pacing was helpful in a minority, but in 41% it compromised stroke volume.


[Vascular anatomy of the anorectal transition].
Based on selective dye injection studies, the regions of supply of the 3 rectal arteries have been defined. The cranial portion of the rectum receives its blood supply from the superior rectal artery, the inferior rectal artery supplies the entire rectal wall in a fan-shaped configuration up to the dentate line. A wedge-shaped portion of the muscularis in the proximal distribution of the inferior rectal artery receives a relatively reduced supply. The middle rectal artery can supply a variable portion of the muscularis which is usually supplied by the distal superior rectal artery. Intramural anastomoses between these regions exist only between the superior and inferior rectal arteries at the level of the dentate line in the submucosa.


Mutation of retS, encoding a putative hybrid two-component regulatory protein in Pseudomonas aeruginosa, attenuates multiple virulence mechanisms.
Two-component regulatory systems play an important role in bacterial virulence. We report that mutation of a Pseudomonas aeruginosa gene designated retS (previously designated fimK; accession number PA4856) encoding a putative hybrid two-component regulator, attenuates multiple virulence mechanisms. The retS mutant was selected from a Tn5 transposon library of the cytotoxic P. aeruginosa strain PA103 based upon expression of a small-colony phenotype suggestive of reduced surface-associated "twitching" motility, a property dependent upon type IV pili. Subsequent analysis revealed that the mutant expressed pilin, albeit at lower levels than wild-type PA103. In a murine model of corneal infection, retS mutation was associated with delayed disease development and altered pathology. In vitro, retS mutants demonstrated loss of acute cytotoxic activity towards corneal epithelia as determined by trypan blue exclusion and by LDH release assays (P<0.0001). This coincided with loss of ExsA-regulated type III secretion. Mutation of retS also impaired ExsA-independent pathogenic mechanisms. When compared to the exsA mutant of PA103, retS mutants exhibited reduced epithelial adherence and invasion and reduced intracellular survival within the cells after invasion. Time-lapse video microscopy revealed that retS mutants, compared to exsA mutants, had a reduced capacity to access, and move along, the basal cell surfaces of corneal epithelial cell monolayers. Taken together, these data suggest that the protein encoded by retS regulates various properties of P. aeruginosa including both ExsA-dependent and ExsA-independent virulence mechanisms.


Lifetime Cost-effectiveness of Oral Semaglutide Versus Dulaglutide and Liraglutide in Patients With Type 2 Diabetes Inadequately Controlled With Oral Antidiabetics.
To estimate the incremental cost-utility ratio of oral semaglutide (14 mg once daily) vs other glucagon-like peptide 1 receptor agonist treatments among adults with type 2 diabetes that was inadequately controlled with 1 to 2 oral antidiabetic drugs from a US payer perspective. A state-transition model with a competing risk approach was developed for diabetic complications and risk of cardiovascular events based on the UK Prospective Diabetes Study Outcomes Model 1 equations. Baseline population characteristics reflect the PIONEER 4 trial (Efficacy and Safety of Oral Semaglutide Versus Liraglutide and Versus Placebo in Subjects With Type 2 Diabetes Mellitus) of oral semaglutide. Model comparators included subcutaneous semaglutide, dulaglutide, and liraglutide. Treatment effects (change in glycosylated hemoglobin, weight, and systolic blood pressure) were estimated by network meta-analysis. Drug, management, and event costs (in 2019 US dollars), survival after nonfatal events, and utilities were obtained from the literature. Costs and quality-adjusted life-year (QALY) outcomes were discounted at 3% annually over a lifetime horizon. Probabilistic and 1-way sensitivity analyses were performed. Total estimated costs and QALYs were $144,065 and 12.98 for oral semaglutide, $145,721 and 12.96 for dulaglutide, $145,833 and 12.99 for SC semaglutide, and $149,428 and 12.97 for liraglutide, respectively. Oral semaglutide was less costly and more effective than dulaglutide and liraglutide but less costly than subcutaneous semaglutide with similar effectiveness. Oral semaglutide was favored versus subcutaneous semaglutide in 52.10% of model replications at a willingness-to-pay of $150,000 per QALY. Oral semaglutide is predicted to offer health benefits similar to subcutaneous semaglutide and ahead of dulaglutide and liraglutide. Oral semaglutide is a cost-effective glucagon-like peptide 1 receptor agonist treatment option.


Pursuit of food versus pursuit of information in a Markovian perception-action loop model of foraging.
Efficient coding, redundancy reduction, and other information theoretic optimization principles have successfully explained the organization of many biological phenomena, from the physiology of sensory receptive fields to the variability of certain DNA sequence ensembles. Here we examine the hypothesis that behavioral strategies that are optimal for survival must necessarily involve efficient information processing, and ask whether there can be circumstances in which deliberately sacrificing some information can lead to higher utility? To this end, we present an analytically tractable model for a particular instance of a perception-action loop: a creature searching for a randomly moving food source confined to a 1D ring world. The model incorporates the statistical structure of the creature's world, the effects of the creature's actions on that structure, and the creature's strategic decision process. The underlying model takes the form of a Markov process on an infinite dimensional state space. To analyze it we construct an exact coarse graining that reduces the model to a Markov process on a finite number of "information states". This mathematical technique allows us to make quantitative comparisons between the performance of an information-theoretically optimal strategy with other candidate search strategies on a food gathering task. We find that 1. Information optimal search does not necessarily optimize utility (expected food gain). 2. The rank ordering of search strategies by information performance does not predict their ordering by expected food obtained. 3. The relative advantage of different strategies depends on the statistical structure of the environment, in particular the variability of motion of the source. We conclude that there is no simple relationship between information and utility. Even in the absence of information processing costs or bandwidth constraints, behavioral optimality does not imply information efficiency, nor is there a simple tradeoff between the two objectives of gaining information about a food source versus obtaining the food itself. For a wide range of values of the food source's movement parameter, the strategy of collecting the most information possible about the unknown source location carries an ineliminable structural cost, leading to a situation in which a foraging creature could actually choose to be less well-informed while simultaneously being, on average, better fed.


Prognostic factors for the survival of patients with papillary renal cell carcinoma: meaning of histological typing and multifocality.
We identified prognostic factors of papillary renal cell carcinoma (PRCC) types 1 (PRCC1) and 2 (PRCC2). Between 1985 and 1998, 759 patients underwent surgery for renal cell carcinoma, of whom 88 (11.6%), including 69 males and 19 females with a mean age of 61.8 years (range 21.3 to 85.9) who had PRCC. Multifocality was defined as 2 or greater tumors separated by 10 mm or greater. Small basophilic cells defined PRCC1 and large eosinophilic cells defined PRCC2. Mean followup in 79 cases was 71.1 months (range 1 to 196.6). Survival rates were calculated and statistical analyses were done. The 88 patients underwent radical nephrectomy (65) or conservative surgery (28, that is elective in 17 and imperative in 11). Mean tumor size was 62 mm (range 10 to 190) and 41% of lesions were multifocal, independent of PRCC size, stage, grade or type. Comparing the 56 PRCC1s (63.6%) to the 32 PRCC2s (36.4%) showed that PRCC2 grade and stage were significantly higher (p = 0.024 and 0.025, respectively). A total of 51 patients (64.6%) remained relapse-free and progression-free. Local relapses occurred only after imperative conservative surgery in 2 cases (2.5%). Of the 26 deaths 15 (4 PRCC 1 and 11 PRCC 2) were tumor associated. Mean survival was 26.6 months (range 1 to 112.5). The overall 10-year survival rate was 73% with PRCC1 and PRCC2 10-year rates of 80% and 59%, respectively (p <0.003). Univariate analysis identified stage (p <0.0001), grade (p <0.0001) and histological type (p <0.003) as prognostic factors. Multivariate analysis retained stage (p = 0.006) and grade (p = 0.004). PRCC multifocality was not associated with stage, grade or histological type and it seems not to be an argument against conservative surgery. Univariate analysis of PRCC prognostic factors identified stage, grade and histological type but the latter was not retained on multivariate analysis.


The effect of an elevated level of residual monomer on the whitening of a denture base and its physical properties.
It has been suggested that incomplete or faulty processing leading to a high level of residual monomer is a factor in denture whitening. Laboratory tests which simulate the cleaning procedures used by patients presenting with whitened dentures have been carried out on specimen strips of acrylic denture base material with high or low levels of residual monomer. The results show that these samples exhibit similar changes and that the high level of residual monomer had no effect on the whitening process, this being attributable to the cleaning method. The major factor responsible for whitening is confirmed as a high water temperature irrespective of the presence of the denture cleaning agent. However, some physical properties were adversely affected by a high residual monomer content (due to the processing method) which has serious consequences for denture-wearing patients. The use of short/low temperature curing cycles now common in many dental laboratories should be avoided.


Kaiso mainly locates in the nucleus in vivo and binds to methylated, but not hydroxymethylated DNA.
Kaiso is upregulated in many cancers and proposed to bind with both methylated- and unmethylated-DNA in the nucleus as a transcriptional repressor. The objective is to define its subcellular localization in vivo and exact binding DNA sequences in cells. Compartmentalization of exogenous Kaiso in cells was tracked with enhanced green fluorescence protein (EGFP) tag. The endogenous Kaiso expression in gastric carcinoma tissue was examined with immunohistochemical staining. Kaiso-DNA binding was tested using electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation assay (ChIP). Kaiso mainly localized in the nucleus of cancer and stromal cells in vivo, but remained in the cytoplasm of cultured cells. Most importantly, nuclear Kaiso can bind with the methylated-CGCG-containing sequence in the CDKN2A promoter, but not with the hydroxymethylated-CGCG sequence in HCT116 cells. Kaiso locates mainly in the nucleus in vivo where it binds with the methylated-CGCG sequences, but does not bind with the hydroxymethylated-CGCG sequences.


Mitral valve repair in dogs.
Prognosis for dogs with severe mitral regurgitation is poor with medical therapy alone. Open surgical mitral valve repair consisting of circumferential mitral annuloplasty and artificial chordal replacement confers durability and improved long-term clinical outcome without a need for long-term antithrombotic therapies. This approach has been successfully used in canine patients, including small-breed dogs. Methods for mitral valve repair applicable to small dogs are described.


Measurement of Respiratory Burst Products, Released or Retained, During Activation of Professional Phagocytes.
Activation of professional phagocytes, potent microbial killers of our innate immune system, is associated with an increased cellular consumption of molecular oxygen (O2). The O2 molecules consumed are reduced by electrons delivered by a membrane localized NADPH-oxidase that initially generate one- and two electron reduced superoxide anions (O2-) and hydrogen peroxide (H2O2), respectively. These oxidants can then be processed into other highly reactive oxygen species (ROS) that can kill microbes, but that may also cause tissue destruction and drive other immune cells into apoptosis. The development of basic techniques to measure and quantify ROS generation by phagocytes is of great importance, and a large number of methods have been used for this purpose. A selection of methods (including chemiluminescence amplified by luminol or isoluminol, absorbance change following reduction of cytochrome c, and fluorescence increase upon oxidation of PHPA) are described in detail in this chapter with special emphasis on how to distinguish between ROS that are released extracellularly, and those that are retained within intracellular organelles. These techniques can be valuable tools in research spanning from basic phagocyte biology to diagnosis of diseases linked to the NADPH-oxidase and more clinically oriented research on innate immune mechanisms and inflammation.


Oral administration of tartrazine (E102) accelerates the incidence and the development of 7,12-dimethylbenz(a) anthracene (DMBA)-induced breast cancer in rats.
Despite the considerable advances made in the treatment of cancer, it remains a global threat. Tartrazine (E102) is a synthetic dye widely used in food industries; it has recently been shown to induce oxidative stress (a well known risk factor of cancer) in rat tissues. The present work therefore aimed to assess the impact of a regular consumption of tartrazine on the incidence of breast cancer in rats. Forty (40) Wistar rats aged 55 to 60 days were randomly assigned into 5 groups (n = 8) including two groups serving as normal controls and receiving distilled water (NOR) or tartrazine (NOR + TARZ). The three remaining groups were exposed to the carcinogen DMBA (50 mg/kg) and treated for 20 weeks with either distilled water (DMBA), tartrazine 50 mg/kg (DMBA + TARZ) or a natural dye (DMBA + COL). The parameters evaluated were the incidence, morphology and some biomarkers (CA 15-3, estradiol and α-fetoprotein) of breast cancer. The oxidative status and histomorphology of the tumors were also assessed. A regular intake of tartrazine led to an early incidence of tumors (100% in rats that received TARZ only vs 80% in rats that received DMBA only), with significantly larger tumors (p < 0.001) (mass = 3500 mg/kg and volume = 4 cm3). The invasive breast carcinoma observed on the histological sections of the animals of the DMBA + TARZ group was more developed than those of the DMBA group. The increase in serum α-fetoprotein (p < 0.05) and CA 15-3 (p < 0.01) levels corroborate the changes observed in tumors. The presence of oxidative activity in animals of the DMBA + TARZ group was confirmed by a significant decrease (p < 0.001) in the activity of antioxidant enzymes (SOD and catalase) as well as the level of GSH and increase in the level of MDA compared to the rats of the DMBA and NOR groups. Tartrazine therefore appears to be a promoter of DMBA-induced breast tumorigenesis in rats through its oxidative potential. This work encourages further studies on the mechanisms of action of tartrazine (E102) and its limits of use.


Retroperitoneal fibrosis in a patient with Turner's syndrome.
Retroperitoneal fibrosis rarely affects children. Its clinical manifestations are protean, but if recognized early and properly treated, the prognosis is generally good. This is the report of a 14-year-old girl with Turner's syndrome and retroperitoneal fibrosis.


Recovery of soil ammonia oxidation after long-term zinc exposure is not related to the richness of the bacterial nitrifying community.
A soil sterilization-reinoculation approach was used to manipulate soil microbial diversity and to assess the effect of the diversity of the ammonia-oxidizing bacteria (AOB) on the recovery of the nitrifying community to metal stress (zinc). Gamma-irradiated soil was inoculated with 13 different combinations of up to 22 different soils collected worldwide to create varying degrees of AOB diversity. Two months after inoculation, AOB amoA DGGE based diversity (weighted richness) varied more than 10-fold among the 13 treatments, the largest value observed where the number of inocula had been largest. Subsequently, the 13 treatments were either or not amended with ZnCl2. Initially, Zn amendment completely inhibited nitrification. After 6 months of Zn exposure, recovery of the potential nitrification activity in the Zn amended soils ranged from <10 % to >100 % of the potential nitrification activity in the corresponding non-amended soils. This recovery was neither related to DGGE-based indices of AOB diversity nor to the AOB abundance assessed 2 months after inoculation (p > 0.05). However, recovery was significantly related (r = 0.75) to the potential nitrification rate before Zn amendment and only weakly to the number of soil inocula used in the treatments (r = 0.46). The lack of clear effects of AOB diversity on recovery may be related to an inherently sufficient diversity and functional redundancy of AOB communities in soil. Our data indicate that potential microbial activity can be a significant factor in recovery.


Management of fulminant myocarditis: a diagnosis in search of its etiology but with therapeutic options.
Fulminant myocarditis is a clinical syndrome with signs of acute heart failure, cardiogenic shock, or life-threating rhythm disturbances in the context of suspected myocarditis. It is not an etiological diagnosis, but may have different underlying causes and pathogenetic processes - viral, bacterial, toxic, and autoreactive. Clinical management of the disease entity at the acute stage involves hemodynamic monitoring in an intensive care unit or similar setting. Rapid routine work-up is mandatory with serial EKGs, echocardiography, cardiac MRI, heart catheterization with endomyocardial biopsy for histology, immunohistology, and molecular analysis for the underlying infection and pathogenesis. Heart failure therapy is warranted in all cases according to current guidelines. For fulminant autoreactive myocarditis, immunosuppressive treatment is beneficial; for viral myocarditis, IVIg can resolve the inflammation, reduce the viral load, and even eradicate the microbial agent. ECMO, IABP, ventricular assist devices, LifeVest, or ICD implantation can bridge to recovery or to heart transplantation.


Development of a high-throughput ultra performance liquid chromatography-mass spectrometry assay to profile 18 eicosanoids as exploratory biomarkers for atherosclerotic diseases.
Abundant evidence suggests a prominent role for eicosanoids and metabolites in the pathogenesis and prognosis of inflammatory diseases. A sensitive and high-throughput SPE UPLC-MS/MS method was developed to quantitatively interrogate the levels of 18 eicosanoids in human and monkey plasma samples. A limit of quantitation of 0.25ng/mL was achieved for all 18 investigated compounds with linear ranges spanning four orders of magnitude. Bioanalytical performance of this assay was fully characterized including SPE extraction efficiency, matrix effect, autosampler stability, benchtop stability and freeze-thaw cycle variability. Endogenous levels of the eicosanoids and analogs within a set of monkey plasma samples challenged with lipopolysaccharide and human plasma samples were quantified by this ultra performance liquid chromatography-mass spectrometry (UPLC-MS/MS) assay. Quantitative eicosanoid profiles of the human samples were further analyzed by a non-supervised cluster analysis, which revealed a set of potential positive and negative lipid biomarkers to distinguish the following three groups: healthy individuals, hypertensive patients and severe atherosclerosis patients. The components of the negative biomarker cluster (8-HETE, LTB4, 9-HODE and 13-HODE) are putative ligands of peroxisome proliferator-activated receptors (PPARs), a family of master genes controlling the resolution of inflammatory signaling.


The effect of clonidine on cell survival, glutamate, and aspartate release in normo- and hyperglycemic rats after near complete forebrain ischemia.
The present study was undertaken to investigate the effects of the alpha2 adrenergic agonist, clonidine, on the near complete cerebral ischemia (NCFI) evoked release of glutamate and aspartate from normo- and hyperglycemic rodent brain tissue using microdialysis tissue techniques. Hemodynamic variables, blood lactate, and glucose levels were monitored throughout the 40 min NCFI occlusion period. After 48 h, rats were killed and the extent of neuronal injury was determined in the cortex, striatum, and hippocampus. Hemodynamic variables recorded during ischemia improved with clonidine treatment in both normo- and hyperglycemic groups. Glutamate and aspartate levels were greatly increased over control values during normo- and hyperglycemic NCFI treatment. Clonidine pretreatment suppressed the release of both glutamate and aspartate during NCFI in normo- and hyperglycemic rodents when compared with NCFI-treated normo- and hyperglycemic rats without the drug. Significant neuroprotection of cells in the cortex, striatum, and hippocampus was also observed in drug-treated animals 48 h postischemia. The combined effects of diminished glutamate release after NCFI and reduced neuronal injury in both normo- and hyperglycemic states suggests that clonidine treatment during NCFI is neuroprotective. The neuroprotective effect of clonidine during ischemia may be ascribed to both a sensitization of central sympathetic activity and a reduced release of glutamate thereby reducing NMDA receptor activation and neuronal damage.


Studies in tooth crown temperature gradients with the use of infrared thermography.
With the use of an infrared thermographic camera; temperature patterns over the crowns of teeth were recorded. The temperature of upper incisor teeth decreased from gingival margin to incisal edge by approximately 2.5 degrees C. Vital and nonvital teeth were the same temperature at rest, but after cooling with cold air, nonvital teeth were slower to rewarm than vital teeth. The infrared thermographic camera could provide a method of testing tooth vitality based on blood supply rather than nerve supply.


[Verification of normative values for the Swiss version of the Freiburg speech intelligibility test].
In the Swiss version of the Freiburg speech intelligibility test five test words from the original German recording which are rarely used in Switzerland have been exchanged. Furthermore, differences in the transfer functions between headphone and loudspeaker presentation are not taken into account during calibration. New settings for the levels of the individual test words in the recommended recording and small changes in calibration procedures led us to make a verification of the currently used normative values. Speech intelligibility was measured in 20 subjects with normal hearing using monosyllabic words and numbers via headphones and loudspeakers. On average, 50% speech intelligibility was reached at levels which were 7.5 dB lower under free-field conditions than for headphone presentation. The average difference between numbers and monosyllabic words was found to be 9.6 dB, which is considerably lower than the 14 dB of the current normative curves. There is a good agreement between our measurements and the normative values for tests using monosyllabic words and headphones, but not for numbers or free-field measurements.


Experiences of Stress - A Focus Group Interview Study Among Swedish Adolescents During the COVID-19 Pandemic.
Adolescence can be a stressful period in life. The period contains challenges associated with the transition from childhood to adulthood (body changes, changes in interpersonal relationships, and identity changes). The aim was to investigate experiences of stress among adolescents in addition to stress related to the COVID-19 pandemic. Focus group interviews (n = 8) were conducted with girls (n = 22) and boys (n = 19) aged 13-15 in southern Sweden. The transcribed interviews were analyzed with qualitative content analysis. Analysis of the collected material resulted in two categories with four sub-categories each of which highlights adolescents' experiences of stress. The results show that adolescents' have a variety of experiences of stress, i.e., what they mean are the sources of stress and how stress is manifested. The adolescents experienced how stress was manifested both physically and emotionally. This affected both their sleep and performance. The adolescents reflected on both positive and negative manifestations of stress.


Single-cell ICP-MS for studying the association of inorganic nanoparticles with cell lines derived from aquaculture species.
The current research deals with the use of single-cell inductively coupled plasma-mass spectrometry (scICP-MS) for the assessment of titanium dioxide nanoparticle (TiO2 NP) and silver nanoparticle (Ag NP) associations in cell lines derived from aquaculture species (sea bass, sea bream, and clams). The optimization studies have considered the avoidance of high dissolved background, multi-cell peak coincidence, and possible spectral interferences. Optimum operating conditions were found when using a dwell time of 50 μs for silver and 100 μs for titanium. The assessment of associated TiO2 NPs by scICP-MS required the use of ammonia as a reaction gas (flow rate at 0.75 mL min-1) for interference-free titanium determinations (measurements at an m/z ratio of 131 from the 48Ti(NH)(NH3)4 adduct). The influence of other parameters such as the number of washing cycles and the cell concentration on accurate determinations by scICP-MS was also fully investigated. Cell exposure trials were performed using PVP-Ag NPs (15 and 100 nm, nominal diameter) and citrate-TiO2 NPs (5, 25, and 45 nm, nominal diameter) at nominal concentrations of 10 and 50 μg mL-1 for citrate-TiO2 NPs and 5.0 and 50 μg mL-1 for PVP-Ag NPs. Results have shown that citrate-TiO2 NPs interact with the outer cell membranes, being quite low in the number of citrate-TiO2 NPs that enters the cells (the high degree of aggregation is the main factor which leads to the aggregates being in the extracellular medium). In contrast, PVP-Ag NPs have been found to enter the cells.


Evidence for neuroendocrine regulation of preadipocyte proliferation and differentiation.
Cells in fetal adipose tissue and cells in vitro are characterized by rapid proliferation. Serum factors have been shown to be important for the rapid proliferation of cells in vitro. The present experiment was performed to determine if neuroendocrine regulatory mechanisms of the fetus can influence the actions of serum factors on preadipocyte proliferation and differentiation in vitro. Sera were obtained from decapitated fetal pigs and intact littermates during gestation. Sera were tested for their effects on primary cultures of preadipocytes and stromal-vascular cells derived from inguinal adipose tissue of young Sprague-Dawley rats. Coverslip cultures were used for histochemical analysis of enzymes after 12 days of incubation with test media. Analysis of growth curves produced from sequential [3H]-thymidine labeling indicated that fetal age influences rates of proliferation. Sera from decapitated fetal pigs specifically reduced the number of proliferating preadipocytes in culture. Sera from decapitated fetal pigs induced a minimum of 50% less differentiation of sn-glycerol-3-phosphate dehydrogenase activity than sera from intact pigs at all fetal ages. Histochemical staining for enzymes of differentiating preadipocytes was also reduced in cultures incubated with sera from decapitated fetal pigs in comparison to sera from intact pigs. The present study has demonstrated that the in vivo effect of decapitation on fetal adipose tissue development is a consequence of alterations in systemic factors present in serum in response to removal of central regulation by the hypothalamic-pituitary axis.


Solid pseudopapillary tumor of the pancreas in children: report of a case and review of the literature.
Solid pseudopapillary tumor (SPT) of the pancreas is an infrequent neoplasm of low malignant potential, first described by Frantz in 1933 and representing less than 3% of all exocrine tumors. SPT is rare in children, accounting for 6% of all cases and shows different clinical features compared with adults. Here, a pediatric case is reported and a review of the Literature is provided. A 15-year-old girl with a 12 × 14 × 10 cm solid mass growing from the tail and the body of the pancreas, involving spleen, left adrenal gland and kidney, stomach and some bowel loops, was referred for surgical treatment. A distal pancreasectomy with splenectomy was performed. Histopathological examination revealed that the tumor was a 14-cm well-circumscribed solid mass, with pseudopapillary cell architecture, showing strong cellular immunoreactivity for alpha-1 antitrypsin, vimentin, neurone-specific enolase, progesterone receptors and in part to CD10 and CAM 5.2, but not to sinaptofisin and chromogranin. A 24-month post-surgical follow-up after successful surgical resection showed no evidence of recurrent disease. SPT shows different clinical features in childhood. High survival rates can be achieved in most cases, warranting aggressive treatments even in metastatic disease.


Do the same genetic and environmental effects underlie the covariation of alcohol dependence, smoking, and aggressive behaviour?
We investigated genetic and environmental effects on alcohol dependence, smoking, and aggressive behaviour, as well as sex differences in these effects and whether these effects were the same for the three phenotypes. There were 3141 male (mean age 26.2 [S.E.=0.1]) and 6026 female (mean age 26.1 [S.E.=0.1]) participants in this extended twin study. Alcohol Use Disorder Identification Test (AUDIT), number of cigarettes smoked, and two subscales of Aggression Questionnaire (AQ) were used to assess the phenotypes. All three were positively interrelated with males exhibiting higher levels on each phenotype. Multivariate model fitting identified genetic effects on all phenotypes for both men and women ranging between 69% (aggressive behaviour in women) and 78% (alcohol dependence in men). The effects were stronger in men for alcohol dependence and smoking. There were no qualitative genetic sex differences. Genetic correlations between all phenotypes were substantial.


The neuroendocrine chaperone 7B2 can enhance in vitro POMC cleavage by prohormone convertase PC2.
We previously showed that the neuroendocrine polypeptide 7B2 transiently interacts with prohormone convertase PC2 in the secretory pathway of neuroendocrine cells. Here we demonstrate that the processed, but not the intact, form of 7B2 can enhance the in vitro cleavage of newly synthesized prohormone proopiomelanocortin (POMC) in lysates of Xenopus intermediate pituitary cells. PC2 is presumably the cleavage enzyme involved since intact 7B2 abolishes the enhancing effect of processed 7B2 and is known to act as a specific inhibitor of PC2. Furthermore, processed 7B2 stimulates in vitro POMC cleavage by immunopurified Xenopus PC2. Our results indicate that 7B2 can display chaperone activity towards PC2.


Validity and reliability of a driving simulator for evaluating the influence of medicinal drugs on driving performance.
Although driving simulators (DS) are receiving increasing attention due to concern over traffic accidents under the influences of drugs, few DS are recognized for their reliability and validity. Therefore, the development of an evaluation system using DS for driving performance is urgently needed. To investigate whether the standard deviation of lateral position (SDLP) increases with blood alcohol concentration (BAC) using a DS with reliability and calculate the SDLP threshold from the difference between BAC levels of 0 and 0.05%. Twenty healthy Japanese men performed the DS tasks up to 60 min in Study 1 and DS tasks twice at 1-week intervals in Study 2. Twenty-six healthy men conducted the same DS tasks under BAC level (0, 0.025, 0.05, and 0.09%) in double-blind, randomized, crossover trial in Study 3. The primary outcome was SDLP in a road-tracking test. The test-retest reliability of DS data was assessed, and the estimated difference in SDLP between BAC levels of 0 and 0.05% was calculated using a linear regression model. The cumulative SDLP values at 5-min intervals were stable, and the intraclass correlation coefficient for its values was 0.93. SDLP increased with BAC in a concentration-dependent manner. The predicted ΔSDLP value for the difference between BAC levels of 0 and 0.05% was 9.23 cm. No participants dropped out because of simulator sickness. The new DS used in these studies has reliability, validity, and tolerability and is considered suitable for evaluating the influence of drugs on driving performance.


The organochlorine o,p'-DDD disrupts the adrenal steroidogenic signaling pathway in rainbow trout (Oncorhynchus mykiss).
The mechanisms of action of o,p'-DDD on adrenal steroidogenesis were investigated in vitro in rainbow trout (Oncorhynchus mykiss). Acute exposures to o,p'-DDD inhibited ACTH-stimulated cortisol secretion while cell viability decreased significantly only at the highest concentration tested (200 microM o,p'-DDD). Stimulation of cortisol secretion with a cAMP analogue (dibutyryl-cAMP) was inhibited at a higher concentration than that needed to inhibit ACTH-stimulated cortisol synthesis in cells exposed to o,p'-DDD. Forskolin-stimulated cortisol secretion and cAMP production, and NaF-stimulated cAMP production were inhibited in a concentration-dependent manner by o,p'-DDD. In contrast, basal cortisol secretion was stimulated while basal cAMP production was unaffected by o,p'-DDD. Pregnenolone-stimulated cortisol secretion was enhanced by o,p'-DDD at a physiologically relevant pregnenolone concentration, while o,p'-DDD inhibited cortisol secretion when a pharmacological concentration of pregnenolone was used. Our results suggest that the cAMP generation step is a target in o,p'-DDD-mediated disruption of ACTH-stimulated adrenal steroidogenesis in rainbow trout but that other downstream targets such as steroidogenic enzymes responsible for cortisol synthesis might also be affected.


Healing of acetic acid-induced gastric ulcer and gastric mucosal PGI2 level in rats.
The present study was designed to investigate the changes in gastric mucosal PGI2 level accompanying the healing of acetic acid-induced gastric ulcers in rats. The ulcers, which were observed with an endoscope, were found to undergo periods of decrease, healing and exacerbation during the rat's lifetime. The phases were categorized as follows: (1) the reduction period (days 3-50 after ulcer induction, corresponding to 7-14 weeks of age), (2) healing period (days 35-150 after ulcer induction, corresponding to 12-29 weeks of age), (3) first exacerbation period (days 35-231 after ulcer induction, corresponding to 12-40 weeks of age), (4) inactive period (days 231-365 after ulcer induction, corresponding to 40-60 weeks of age), and (5) second exacerbation period (days 365-550 after ulcer induction, corresponding to 60-86 weeks of age). In normal rats, the level of gastric mucosal PGI2 gradually increased with aging between 7 and 20 weeks, then decreased up to 40 weeks. The PGI2 level in the 60-week-old rat did not differ from that in the 40-week-old rat. The PGI2 level was the lowest in the 86-week-old rat. In ulcer-bearing rats, the PGI2 level showed the same pattern of change as that in normal rats, but the level was higher. The above results indicated a marked decrease in PGI2 level between 20 and 40 weeks of age and between 60 and 86 weeks of age in normal and ulcer-bearing rats. These periods corresponded closely to the first and second exacerbation periods, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Baicalin-induced Akt activation decreases melanogenesis through downregulation of microphthalmia-associated transcription factor and tyrosinase.
Scutellaria baicalensis has been used topically to treat inflammatory skin diseases in traditional East Asian medicine. Because post-inflammatory hyperpigmentation of the skin is difficult to manage, we investigated the effects of baicalin, a major component of S. baicalensis, on melanin synthesis in Mel-Ab cells. Our data showed that baicalin significantly inhibited melanin production and tyrosinase activity in a dose-dependent fashion, but it did not directly influence tyrosinase activity. Moreover, baicalin treatment triggered decreases in both mRNA and protein levels of microphthalmia-associated transcription factor (MITF) and tyrosinase. Although AMP-activated protein kinase (AMPK) and extracellular signal-regulated kinase (ERK) activation were induced in baicalin-treated Mel-Ab cells, they were not responsible for baicalin-induced hypopigmentation. Because the Akt pathway is also known to be involved in regulation of melanogenic protein expression and melanin synthesis, we examined the effects of baicalin on the Akt pathway. Our results showed that baicalin treatment stimulated Akt activation. Treatment with LY294002, a specific Akt inhibitor, restored baicalin-induced melanogenesis inhibition and abolished MITF and tyrosinase downregulation by baicalin. Taken together, our data suggest that Akt activation by baicalin inhibits melanin production via downregulation of MITF and tyrosinase in Mel-Ab cells.


Deletions of chromosomes 3p and 14q molecularly subclassify clear cell renal cell carcinoma.
The short arm of chromosome 3 (3p) harbors the von Hippel-Lindau (VHL) tumor suppressor gene, and the long arm of chromosome 14 (14q) harbors the hypoxia-inducible factor 1α (HIF-1α) gene. The objective of this study was to evaluate the significance of 3p loss (loss VHL gene) and 14q loss (loss HIF-1α gene) in clear cell renal cell carcinoma (ccRCC). In total, 288 ccRCC tumors underwent a prospective cytogenetic analysis for alterations in chromosomes 3p and 14q. Tumors were assigned to 1 of 4 possible chromosomal alterations: VHL +3p/+14q (VHL wild type [VHL-WT]), VHL +3p/-14q (VHL-WT plus HIF2α [WT/H2]), -3p/+14q (HIF1α and HIF2α [H1H2]), and -3p/-14q (HIF2α [H2]). Among patients who had loss of 3p, tumors with -3p/-14q (H2) alterations were larger (P = .002), had higher grade (P = .002) and stage (P = .001), and more often were metastatic (P = .029) than tumors that retained 14q (H1H2). All patients who had tumors with -3p/-14q (H2) had worse cancer-specific survival (P = .014), and patients who had localized disease (P = .012) and primary T1 (pT1) tumors (P = .008) had worse recurrence-free survival. In patients who had pT1 tumors, combined 3p/14q loss was an independent predictor of recurrence-free survival (hazard ratio, 11.19; 95% confidence interval, 1.91-65.63) and cancer-specific survival (hazard ratio, 15.93; 95% confidence interval, 3.09-82.16). The current investigation was limited by its retrospective design, single-center experience, and a lack of confirmatory protein analyses. Loss of chromosome 3p (the VHL gene) was associated with improved survival in patients with ccRCC, whereas loss of chromosome 14q (the HIF-1α gene) was associated with worse outcomes. The results of the current study support the hypothesis that HIF-1α functions as an important tumor suppressor gene in ccRCC.


[Persistent pleural effusion following thoracic surgery].
Persistent postoperative pleural effusion can occur after thoracic surgery and might lead to progressive dyspnea with a subsequent complicated and prolonged hospital stay. The etiology, prevention and therapy of persistent pleural effusion after thoracic surgical interventions are presented. A selective literature search was carried out in Medline (pleural effusion, pleural empyema and chylothorax). Persistent pleural effusions were observed especially after lung resection due to disorders in the pleural fluid balance and reduced postoperative lung expansion. An adequate chest tube management and postoperative physical therapy can reduce the incidence of postoperative pleural effusion. Relevant postoperative bleeding causes a hemothorax. An infection of the pleural effusion is defined as pleural empyema. These patients suffer from a significantly higher postoperative morbidity and require an adjusted multimodal treatment. Intraoperative injury of the thoracic duct can result in a postoperative chylothorax, which should be diagnosed early with specific laboratory investigations of the milky fluid. Interventional radiological procedures have now taken their place alongside conservative measures and surgical procedures in the therapy of chylothorax. Persistent postoperative pleural effusion after thoracic surgical interventions warrant early diagnosis and an adjusted treatment in order to avoid further complications and to shorten the postoperative hospital stay.


PKR and eIF2alpha: integration of kinase dimerization, activation, and substrate docking.
The antiviral RNA-dependent protein kinase, PKR, binds to viral double-stranded RNA in the cell and halts protein synthesis by phosphorylating the alpha subunit of the translation initiation factor eIF2. In this issue of Cell, two complementary papers Dar et al. (2005) and Dey et al. (2005) address the interaction between PKR and eIF2alpha. The structures of eIF2alpha bound to PKR reveal that PKR forms a dimer, the interface of which is essential for kinase activation, and demonstrate how this protein substrate docks to its kinase. The structures, coupled with mutagenesis analysis, also demonstrate how phosphorylation of the activation loop can allosterically couple two distal regions, the dimerization and substrate recognition interfaces.


Wave-function and the concept of a nano-mental element of representation.
Scientific endeavour has often tried to localize superior cerebral functions either in areas like the ones described by Broca as being those connected with language in the left hemisphere, or in the huge array of the hundred billion of interconnected neurons. But in this last case the coined description of the "grandmother" neuron, tends to show humorously that hopes have fallen short of their target. Along the same lines, the specific timing of electric neural activity is known to take place around a few milliseconds, which seems to be insufficient to account for the high potential speed necessary to sustain the very massive and complex process which is involved in mental activity. It is therefore necessary to go down to a much smaller scale to explain the considerable speed of usual mental processes. That is the reason why we have proposed the Nano-Mental Element of Representation (NMER) as a possible candidate for describing these specific nano-indexes of mind. At that level (10(-10) to 10(-9) meter), these mental processes can be associated with, or take the probabilistic aspect of, a wave function. This concept enables us to bring down the problems of temporal scaling to the quantum level and, therefore, make the extremely fast behavioral or sensory answers accessible to our appropriate level of observation.


[Surgical management of post-traumatic strictures of the membranous portion of the urethra].
On the basis of the results of invaginational urethroplasty performed in 22 cases because of the stricture of traumatic origin of the pars membranacea urethrae the authors define the field of indication for operation. Certain elements of the operative technique which play a role in achieving good and permanent results are emphasized.


Highly stable gold(III) complex with a hydantoin ligand in alkaline media.
A novel gold(III) complex with a monodentate 5,5-dimethylhydantoin ligand, [Au(dmh)4]-, is square planar in geometry, inert and highly stable in alkaline solutions because of soft acid-base interactions, and electrochemically reduced near -0.3 V vs Ag/AgCl to give a gold(0) film with a high current efficiency.


The complexity of communication in an environment with multiple disciplines and professionals: communimetrics and decision support.
Accurate and efficient communication among all the parties is an important component of providing efficient and effective medical care to patients who have complex needs. The evolution of clinimetric measurement approaches designed to be congruent with the clinical process into communimetric tools designed to communicate the clinical process to wider audiences allows the use of technology to support improved care. Computerized medicine offers many opportunities for speeding up the communication of data and thereby improving the efficiency and effectiveness of medical care. The use of communimetric tools within this information environment represents an important opportunity to bridge the quality chasm.


Coherent manipulation of Andreev states in superconducting atomic contacts.
Coherent control of quantum states has been demonstrated in a variety of superconducting devices. In all of these devices, the variables that are manipulated are collective electromagnetic degrees of freedom: charge, superconducting phase, or flux. Here we demonstrate the coherent manipulation of a quantum system based on Andreev bound states, which are microscopic quasi-particle states inherent to superconducting weak links. Using a circuit quantum electrodynamics setup, we performed single-shot readout of this Andreev qubit. We determined its excited-state lifetime and coherence time to be in the microsecond range. Quantum jumps and parity switchings were observed in continuous measurements. In addition to having possible quantum information applications, such Andreev qubits are a test-bed for the physics of single elementary excitations in superconductors.


Effect of neurotransmitter release on myocardial cyclic nucleotides during left ventricular tachycardia.
Myocardial levels of neurotransmitters and cyclic nucleotides during left ventricular tachycardia were explored in anesthetized open-chest dogs subjected to heart rates averaging 36% above control. Tachycardia was produced by implanting stimulating electrodes on the epicardial surface of the left ventricle. Arterial systolic (-40%) and diastolic (-45%) blood pressures, cardiac output (-33%), and rate of left ventricular pressure rise (LVdP/dt; -45%) were significantly decreased during a 6-min period of stimulation. These changes were accompanied by a 3.5-times greater efflux of norepinephrine than control, while cardiac muscle norepinephrine declined 34%. In tachycardia, arterial blood levels of norepinephrine and epinephrine were significantly elevated. The increased release of norepinephrine was associated with a 24% rise in myocardial levels of adenosine 3',5'-monophosphate (cAMP). Indicative of a secretion of acetylcholine from the heart was the resulting increase in myocardial concentration of guanosine 3',5'-monophosphate (cGMP; 100%). Although the rise in cGMP was significantly correlated with the decline in LVdP/dt, blockade of the increase in cGMP with atropine did not reverse the decline LVdP/dt. Despite the elevation of norepinephrine and cAMP and their action in stimulating the contractile state of the heart, depressed cardiac function observed in tachycardia can mainly be attributed to global asynchrony of myocardial contraction.


Cross immunity between strains of Cowdria ruminantium.
Cross immunity tests with strains of Cowdria ruminantium from South Africa, the Sudan, São Tomé and Nigeria failed to demonstrate antigenic differences. The antibiotic ampicillin showed no activity against heartwater.


How does doxorubicin interfere with actin polymerization?
It is well known that doxorubicin (adriamycin), an antibiotic with an antitumoral action, has some undesirable side effects. Among these, the most serious is, undoubtedly, damage to myocardial tissue (progressive cardiomyopathy). We have for some time focused our attention on the effect of this drug on cellular contractile systems and, more specifically, on the process of actin polymerization, which we consider to be an extremely delicate key point for the economy of most cellular motor manifestations. In the present study, using capillary viscometry, spectrofluorometry and electron microscopy, we have shown a negative action of doxorubicin on various important chemical events which contribute to the transformation of G-actin into F-actin. Specifically, we found that the drug mainly acts by reducing the polymer size. A possible action mechanism of the antibiotic is proposed and a plausible correlation among the events described in vitro and those observed in vivo is advanced.


Complex Valve Surgery in Elderly Patients: Increasingly Necessary and Surprisingly Feasible.
The increasing proportion of elderly patients in cardiac surgery poses additional challenges for the clinical management and leads to a higher operative risk due to multiple comorbidities of these patients. We reviewed the outcome of patients who were 75 years and older and underwent complex multiple valve surgery at our institution. A retrospective review was performed to identify patients who were 75 years and older and underwent multiple valve surgery between January 2011 and May 2016 at our institution. Patients were assigned to one out of four subgroups: combined aortic and mitral valve surgery (group AM), aortic and tricuspid valve surgery (group AT), mitral and tricuspid valve surgery (group MT), and aortic, mitral, and tricuspid valve surgery (group AMT). A total of 311 patients underwent multiple valve surgery, of whom 119 (38.3%) were 75 years and older (median: 78 [25th-75th quartile: 76-80]). The estimated operative mortality (EuroSCORE II) in the overall cohort was 10.7%. The observed 30-day mortality was 4.2% (7% in group AM, 0% in group AT, 2.2% in group MT, 3.8% in group AMT; p = 0.685). Main complications were reexplorative surgery in 16%, adverse cerebrovascular events in 6.7%, prolonged mechanical ventilation in 10.1%, renal replacement therapy in 15.1%, nosocomial pneumonia in 15.1%, and pacemaker implantation in 18.5%. This study demonstrates the feasibility of complex multiple valve surgery in elderly patients. The observed perioperative mortality was lower than predicted. However, we observed a substantial rate of adverse events; therefore, careful patient selection is required in this high-risk patient population.


Neural stimulation of mitotic activity in the crypts of lieberkühn in rat jejunum.
The influence of nerve stimulation and sham-stimulation on the mitotic rate in epithelial cells lining the crypts of Lieberkühn in the jejunum of anaesthetized rats was studied. Administration of the anaesthetic and opening the abdominal cavity was without significant effect on the crypt cell mitotic rate. However, externalizing a loop of jejunum and applying sham-stimuli to its mesenteric nerves resulted in a significant decrease in the crypt cell mitotic rate in that loop. Application of electrical stimuli to the mesenteric nerves of another externalized jejunal loop resulted in a significant increase in the mitotic rate in the crypt cells of that segment. Similar acceleration of crypt cell proliferation by electrical stimuli applied to mesenteric nerves was also seen in chemically sympathectomized rats.


Comparison of effectiveness of group interventions for depression in women.
The purpose of this study was to evaluate the effectiveness of a structured cognitive-behavioral group intervention designed by Verona Gordon to reduce depression in women. An experimental three group pretest and posttest design was used. Women were randomly assigned to the structured and support groups. The structured group was found to be significantly more effective in reducing depression, hopelessness, anxiety, and improving self-esteem than either the support or untreated control groups.


Potentiometric investigation of the effect of the pH on the ionic transfer of some amino acids at the interface between two immiscible electrolyte solutions.
The effect of the pH on the ionic transfer of glycine and beta-alanine at the interface between two immiscible electrolyte solutions (ITIES) was investigated by a simple potentiometric method. Upon addition of small amounts of solution containing the investigated amino acids, a variation of the potential drop across the interface was recorded, which was found to be pH-dependent. This behavior was explained in terms of a preferential orientation of the amino acid molecules at the ITIES, induced by the different lipoficility of the functional groups. The results enabled the measurement of this voltage variation to be used as the basis for a simple and rapid method for determining the isoelectric point of the investigated compounds. The agreement between the pH(i) values thus estimated and those reported in the literature suggests the possibility of using the method for the interpretation of processes occurring at the level of biological membranes.


Selective Negative Allosteric Modulation Of Metabotropic Glutamate Receptors – A Structural Perspective of Ligands and Mutants.
The metabotropic glutamate receptors have a wide range of modulatory functions in the central nervous system. They are among the most highly pursued drug targets, with relevance for several neurological diseases, and a number of allosteric modulators have entered clinical trials. However, so far this has not led to a marketed drug, largely because of the difficulties in achieving subtype-selective compounds with desired properties. Very recently the first crystal structures were published for the transmembrane domain of two metabotropic glutamate receptors in complex with negative allosteric modulators. In this analysis, we make the first comprehensive structural comparison of all metabotropic glutamate receptors, placing selective negative allosteric modulators and critical mutants into the detailed context of the receptor binding sites. A better understanding of how the different mGlu allosteric modulator binding modes relates to selective pharmacological actions will be very valuable for rational design of safer drugs.


Developmental time of the hemoglobin transition in the anuran Bombina orientalis.
The electrophoretic pattern of the larval hemoglobin of the anuran Bombina orientalis presents two bands. In premetamorphic period gradually appear four other bands, corresponding to those of the adult hemoglobin; they substitute, within 15-16 days after metamorphosis, the larval pattern. The percentage of larval and adult fractions during the development is shown. In Bombina orientalis the change of the hemoglobinic fractions from larval to adult type is total as in most anurans. But it starts earlier than in other species studied and develops slower than most of the other species.


Relationship between trunk intramuscular adipose tissue content and prevalence of metabolic syndrome in middle-aged Japanese men.
The aim of the present study was to examine the dose-response relationship between trunk tissue composition and prevalence of metabolic syndrome (MetS) in middle-aged Japanese men. The 1026 men (between 35 and 59 y of age) who participated in the present study were divided into two groups: those with metabolic syndrome (MetS) and those without (non-MetS). Intramuscular adipose tissue (IntraMAT) content and the cross-sectional areas (CSAs) of visceral adipose tissue and skeletal muscle tissue were calculated using low-dose computed tomography images acquired at the level of the third lumbar vertebra. Height, body mass, body fat, waist circumference, the presence of MetS, and lifestyle habits were also assessed. IntraMAT content was significantly higher in MetS than in non-MetS men. A 10% increase in IntraMAT content correlated with the prevalence of MetS (odds ratio, 4.197; 95% confidence interval, 3.108-7.088; P < 0.001), even after adjustments for age, height, adjusted skeletal muscle CSA, sleeping time, alcohol consumption, exercise habit, and cigarette smoking. Skeletal muscle CSA did not correlate with the prevalence of MetS after adjustments for IntraMAT content and other cofactors. Increase in IntraMAT content, not in skeletal muscle CSA, significantly correlated with the prevalence of MetS. These results suggest that countermeasures against the accumulation of trunk IntraMAT effectively prevent MetS in middle-aged Japanese men.


Impact of Antimicrobial Stewardship Program (ASP) on Outcomes in Patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSIs) in an Acute-Tertiary Care Hospital.
Acute bacterial skin and skin structure infections (ABSSSIs) are among the most common infections treated in hospitals, but to date, there has been little information with regards to the implementation of Antimicrobial Stewardship Programs (ASPs) for patients with ABSSSIs. Hence, we aim to evaluate the impact of ASPs on the following outcomes in patients with ABSSSIs: duration of therapy and hospital stay, 14-day reinfection, infection-related readmissions and mortality. A retrospective review of the ASP database was conducted, focusing on selected outcomes (as above) among all patients in whom the institution's ASP recommended a change in antibiotic regimen-de-escalation of the antibiotic based on culture results; discontinuation of the antibiotic; narrowing of the empirical coverage; and intravenous-to-oral (i.v.-to-p.o.) switch between September 2009 and December 2012. Data were expressed as mean ± standard deviation for continuous variables, and unpaired Student's t test was performed to determine intergroup differences between mean values. For categorical variables, data were presented as number and percentage and analyzed using the χ (2) test or Fisher's exact test, as appropriate. ASP recommended 407 interventions with an overall acceptance rate of 66.8%. ASP interventions significantly reduced median duration of therapy by 2 [from a median (interquartile range, IQR) of 8 (6-12) days to 6 (4-9) days] and median length of stay by 5 days [from median (IQR) of 12 (5-32) days to 7 (3-18) days]. This led to an estimated total cost avoidance of USD 0.7 million. There were no significant differences in the 14-day reinfection, infection-related readmission and mortality rates between patients whose physicians accepted and those who rejected ASP interventions. Interventions recommended by the ASP in Singapore General Hospital were safe and associated with a significant reduction in duration of therapy and hospital stay. The results of our study have affirmed the role of ASP in optimizing the care of patients with ABSSSI.


Reprogramming of TAMs via the STAT3/CD47-SIRPα axis promotes acquired resistance to EGFR-TKIs in lung cancer.
Cross-talk between the tumor microenvironment (TME) and cancer cells plays an important role in acquired drug resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). The role of tumor-associated macrophages (TAMs), the major component of the TME, in acquired resistance remains unclear. In this study, M2-like reprogramming of TAMs and reduced phagocytosis by macrophages were observed in gefitinib-resistant lung cancer cells and tumor xenografts. CD47 was upregulated in TKI-resistant lung cancer cells, and M2 macrophage polarization and cancer cell escape from macrophage phagocytosis were enhanced. Culture medium from TKI-resistant cells led to metabolic reprogramming of TAMs. STAT3 was associated with CD47 expression in TKI-resistant lung cancer cells. Genetic and pharmacological inhibition of STAT3 enhanced the phagocytic activity of TAMs and alleviated the acquired resistance to EGFR-TKIs via inhibiting the CD47-SIRPα signaling axis and M2 polarization in the co-culture system. Moreover, STAT3 transcriptionally regulated CD47 expression by binding to consensus DNA response elements in the intron of the CD47 gene. Furthermore, the combination of gefitinib with a STAT3 inhibitor and an anti-CD47 monoclonal antibody alleviated the acquired resistance to gefitinib in vitro and in vivo. Collectively, our study reveals the role of TAM reprogramming and the CD47-SIRPα axis in acquired EGFR-TKI resistance and provides a novel therapeutic strategy to overcome the acquired resistance to EGFR-TKIs in lung cancer.


An updated insight on testicular hemodynamics: Environmental, physiological, and technical perspectives in farm and companion animals.
In all organs, control of blood flow is important but might be particularly critical for testicular functions. This is because of the very low oxygen concentration and high metabolic rate of the seminiferous tubules, the physiological temperature of the testis, and its location outside the abdominal cavity. Many factors affect the characteristics of TBF in farm and companion animals, such as environment (thermal and seasonal effects) and physiological (species, breeds, age, body weight, and sexual maturity). Thermal environment stress has detrimental effects on spermatogenesis and consequently has more serious impacts on both human and animal fertility. Numerous studies have been performed to assess TBF in different animal species including bulls, rams, bucks, alpacas, stallions, and dogs with varied results. Hence, assessment of TBF by Doppler ultrasonography is of great importance to estimate the effect of high environment temperature on testicular functions. Also, differences observed in the TBF may result from different technical aspects such as the identification of the segment of the testicular artery to be examined. In the current review, we focused on the imperative roles of TBF in various animal species. Besides, we discussed in detail various factors that could affect TBF. These factors can significantly modify the TBF and thus should be considered when establishing reference values in farm animals for better clinical diagnosis. The information provided in this review is valuable for researchers and veterinarians to help them a better understanding of testicular hemodynamics for the proper evaluation of breeding soundness examination in males.