Plasma protein changes in horse after prolonged physical exercise: a proteomic study.
Physical exercise induces various stress responses and metabolic adaptations that have not yet been completely elucidated. Novel biomarkers are needed in sport veterinary medicine to monitor training levels and to detect subclinical conditions that can develop into exercise-related diseases. In this study, protein modifications in horse plasma induced by prolonged, aerobic physical exercise were investigated by using a proteomic approach based on 2-DE and combined mass spectrometry procedures. Thirty-eight protein spots, associated with expression products of 13 genes, showed significant quantitative changes; spots identified as membrane Cu amine oxidase, α-1 antitrypsin, α-1 antitrypsin-related protein, caeruloplasmin, α-2 macroglobulin and complement factor C4 were augmented in relative abundance after the race, while haptoglobin β chain, apolipoprotein A-I, transthyretin, retinol binding protein 4, fibrinogen γ chain, complement factor B and albumin fragments were reduced. These results indicate that prolonged physical exercise affects plasma proteins involved in pathways related to inflammation, coagulation, immune modulation, oxidant/antioxidant activity and cellular and vascular damage, with consequent effects on whole horse metabolism.


Epidemiology of pediatric out-of-hospital cardiac arrest compared with adults.
Out-of-hospital cardiac arrest (OHCA) is associated with ∼90% mortality rate. In the pediatric population, this would equate to a large number of years of life lost, posing a heavy medical and economic burden to society. The purpose of this study was to outline the characteristics and causes of pediatric OHCA (pOHCA) and associations with survival until discharge in patients enrolled in the End Unexplained Cardiac Death Registry. A prospective statewide multisource registry identified all pOHCAs cases in patients aged 1-18 years in Victoria, Australia (population 6.5 million), from April 2019 to April 2021. Cases were adjudicated using ambulance, hospital, and forensic records; clinic assessments; and interviews of survivors and family members. The analysis included 106 cases after adjudication (62, 58.5% male), 45 (42.5%) of which were due to cardiac causes of OHCA, with unascertained (n = 33 [31.1%]) being the most common cardiac cause reported. Respiratory events (n = 28 [26.4%]) were the most common noncardiac cause of pOHCA. Noncardiac causes were more likely to present with asystole or pulseless electrical activity (P = .007). The overall survival to hospital discharge rate was 11.3% and associated with increasing age, witnessed cardiac arrest, and initial ventricular arrhythmias (P < .05). The incidence of pOHCA in the study population was 3.69 per 100,000 child-years. In contrast to young adults with OHCA, the most common etiology was noncardiac in pediatric patients. Prognostic factors associated with survival to discharge included increasing age, witnessed arrest, and initial ventricular arrhythmias. Rates of cardiopulmonary resuscitation and defibrillation were suboptimal.


Gesture's body orientation modulates the N400 for visual sentences primed by gestures.
Body orientation of gesture entails social-communicative intention, and may thus influence how gestures are perceived and comprehended together with auditory speech during face-to-face communication. To date, despite the emergence of neuroscientific literature on the role of body orientation on hand action perception, limited studies have directly investigated the role of body orientation in the interaction between gesture and language. To address this research question, we carried out an electroencephalography (EEG) experiment presenting to participants (n = 21) videos of frontal and lateral communicative hand gestures of 5 s (e.g., raising a hand), followed by visually presented sentences that are either congruent or incongruent with the gesture (e.g., "the mountain is high/low…"). Participants underwent a semantic probe task, judging whether a target word is related or unrelated to the gesture-sentence event. EEG results suggest that, during the perception phase of handgestures, while both frontal and lateral gestures elicited a power decrease in both the alpha (8-12 Hz) and the beta (16-24 Hz) bands, lateral versus frontal gestures elicited reduced power decrease in the beta band, source-located to the medial prefrontal cortex. For sentence comprehension, at the critical word whose meaning is congruent/incongruent with the gesture prime, frontal gestures elicited an N400 effect for gesture-sentence incongruency. More importantly, this incongruency effect was significantly reduced for lateral gestures. These findings suggest that body orientation plays an important role in gesture perception, and that its inferred social-communicative intention may influence gesture-language interaction at semantic level.


High DSCC1 Level Predicts Poor Prognosis of Lung Adenocarcinoma.
To evaluate the role of DSCC1 in LUAD. Based on TCGA and GTEx, the Wilcoxon rank-sum test was used to compare the expression differences of DSCC1 between the normal samples of GTEx combined TCGA and the unpaired tumor samples of TCGA, and to compare DSCC1 expression values between tumor tissues and paired normal LUAD tissues in the TCGA cohort. Kruskal-Wallis rank-sum test, Wilcoxon rank-sum test, and logistics regression were used to compare the relationship between the expression of DSCC1 and the clinicopathological parameters. The biological function of DSCC1 was annotated by GSEA and ssGSEA, while Kaplan-Meier and Cox regression analysis were used to evaluate the prognostic value of DSCC1. Furthermore, the time-dependent ROC curve was used to analyze the diagnostic efficacy of DSCC1 in LUAD. We downloaded the RNA-Seq data of 513 LUAD cases. The expression of DSCC1 was significantly correlated with T stage (OR = 1.04(1.02-1.07), P = 0.002), pathological stage (OR=1.03 (1.01-1.05), P = 0.008) and TP53 status (OR=1.10 (1.07-1.14), P < 0.001). The high expression of DSCC1 was significantly correlated with DSS (HR=1.56 (1.07-2.26), P = 0.021) and OS (HR=1.53 (1.14-2.05), P = 0.004). Moreover, ROC curve analysis (AUC=0.845, CI (0.820-0.870)) indicated DSCC1 as a potential diagnostic molecule for LUAD. In the group with high DSCC1 expression phenotype, down-regulation of EGFR signal, reduction of IL-6 deprivation, cell cycle, and p53 signal pathway were significantly abundant. Spearman correlation analysis showed that the expression of DSCC1 was positively correlated with the infiltration of Th2 cells, T Helper cells. Our results suggest that DSCC1 may be an important biomarker for the treatment of LUAD.


Evaluation of a novel temperature-sensitive polymer for temporary ureteral occlusion.
Proximal stone migration during ureteroscopic procedures increases operative time and risk. This study was designed to evaluate the ability of a new temperature-sensitive polymer to prevent proximal stone migration during ureteroscopic procedures. Porcine urinary systems were harvested en bloc. The volume of gel needed to occlude the ureter, time to achieve a solid state, length of ureter filled, and pressure needed to dislodge the gel from the ureter were recorded. Radio opacity of the polymer was evaluated. Endoscopic laser lithotripsy was the performed after deploying the urologic polymer, and, after gel application and stone manipulation, all ureters were examined for histologic changes. At 36.7 degrees C, 0.5 mL and 1 mL of polymer sufficiently occluded the ureter. Both amounts solidified in 25 to 40 seconds. The mean length of ureter occluded was 56.3 mm, and the mean pressure needed to dislodge the polymer was 159.2 mm Hg. The polymer was radiopaque and did not cause histologic alterations in the ureter. Proximal migration of stone fragments was not observed during any of the procedures performed. Our in vitro study indicates that this radiopaque, thermosensitive polymer is able to transiently occlude the ureter without damaging the urothelium while withstanding the pressure of ureteroscopic irrigation, stone motion, and laser energy.


Invariant exon skipping in the human alpha-galactosidase A pre-mRNA: Ag+1 to t substitution in a 5'-splice site causing Fabry disease.
Fabry disease, an inborn error of glycosphingolipid catabolism, results from lesions in the X-linked gene encoding the human lysosomal hydrolase, alpha-galactosidase A (alpha-D-galactoside galactohydrolase; EC 18.104.22.168). To detect alpha-galactosidase A RNA processing or stability defects causing Fabry disease, Northern hybridization analyses were performed with poly(A)+ RNA isolated from cultured lymphoblasts from unrelated Fabry hemizygotes. Using a riboprobe complimentary to the normal 1.45-kb alpha-galactosidase A mRNA, a single 1.25-kb transcript was identified in three classically affected brothers from a Japanese Fabry family. Densitometric analysis revealed that the 1.25-kb transcripts were present at 50 to 60% of normal amounts. RNase A analysis identified a deletion of about 200 bp that appeared to include the entire 198 bp of exon 6. Amplification and direct sequencing of a genomic region containing exon 6 from an affected hemizygote revealed a g+1 to t transversion in the invariant gt consensus 5'-splice site of intron 6, which resulted in the deletion of the entire exon 6 sequence. This novel splicing lesion causing Fabry disease is the first g+1 to t transversion of a mammalian 5'-splice site that consistently eliminates the preceding exon.


Transient polarization currents in the squid giant axon.
It has been repeatedly noted that the change of conformation of the molecules that serve as the ion-selective channels for sodium and potassium conductance in the nerve membrane will be accompanied by a change in the dipole moment of the molecule. This time-dependent change of dipole moment will produce transient currents in the membrane. The canonical form for these currents is determined with conventional statistical mechanics formalism. It is pointed out that the voltage dependence of the conductance channel conductance determines the free energy of the system to within a factor that is an unknown function of the voltage. Since the dipole currents do not depend on this unknown function, they are completely determined 0y the observed properties of the conductance system. The predicted properties of these dipole currents, their time constants and strengths, are calculated. By using the observed properties of gating currents, the density of the sodium channels is computed. The predicted properties of the dipole currents are found to compare satisfactorily with the observed properties of gating currents.


The relation between Bulimic symptoms and the social withdrawal syndrome during early adolescence.
The short-term longitudinal study tested the hypothesis that there was a prospective relation between the social withdrawal syndrome and Bulimic symptoms during early adolescence. Ninety-six adolescents (47 males, mean age=13 years - 10 months) completed standardized scales assessing Bulimic symptoms, trust beliefs in others and loneliness at Time 1/T1 and again 5 months later at Time 2/T2. Analyses showed that: (1) Bulimic symptoms were negatively correlated with trust beliefs, (2) Bulimic symptoms were positively correlated with loneliness, and (3) trust beliefs were negatively correlated with loneliness. The SEM and mediation analyses showed that trust beliefs at T1 were negatively and concurrently associated with Bulimic symptoms at T1 and longitudinally (and negatively) predicted changes in Bulimic symptoms. It was found that loneliness at T1 statistically mediated those concurrent and longitudinal relations. The findings yielded support for the conclusion that the social withdrawal syndrome, as assessed by low trust beliefs and resulting experiences of loneliness, contributes to Bulimia nervosa during early adolescence.


Mechanism of ochratoxin A stimulated lipid peroxidation.
Lipid peroxidation, measured as malondialdehyde formation or by oxygen uptake, was stimulated markedly by the mycotoxin ochratoxin A (OTA) in a reconstituted system consisting of phospholipid vesicles, the flavoprotein NADPH-cytochrome P450 reductase, Fe3+, EDTA and NADPH. Deletion of EDTA lowered the extent of lipid peroxidation but did not eliminate it. Fluorometric and spectrophotometric studies demonstrated the formation of a 1:1 Fe3(+)-OTA complex. The rate of reduction of Fe3+ to Fe2+ was enhanced markedly in the presence of OTA, and there was a further increase in the rate when EDTA was also included. The data indicate that OTA stimulates lipid peroxidation by complexing Fe3+ and facilitating its reduction. Subsequent to oxygen binding, an iron-oxygen complex of undetermined nature initiates lipid peroxidation. Free hydroxyl radicals appear not to participate in lipid peroxidation stimulated by Fe3(+)-OTA.


Changes in quality of life after thyroidectomy in subjects with thyroid cancer in relation to the dose of levothyroxine.
Previous studies demonstrated decreased quality of life (QoL) in differentiated thyroid cancer (DTC) survivors and suggested QoL variability related to time from thyroidectomy and levothyroxine dosage. The aims of this study were to evaluate QoL in thyroidectomized subjects in different levothyroxine states and to evaluate the association between TSH and thyroid hormones and QoL. Prospective 5-year study enrolling 208 patients thyroidectomized for DTC, studied in one to four times according to levothyroxine dosage: withdrawal (WITHD), complete (C-SUPP) and mild TSH-suppression (M-SUPP), replacement (REPL). Each patient was allowed to participate into the study more than one time. A total of 300 evaluations were collected, consisting of detailed thyroid hormone profile and QoL assessment through the ThyPRO questionnaire. Comparing the four groups, significant differences were found for anxiety, impaired social and daily life and item 12 (overall impact of thyroid disease) domains (p < 0.05). Interestingly, C-SUPP subjects reported the best scores in almost all ThyPRO scales. Significant correlations were found between QoL and pituitary-thyroid axis function, as well as between QoL and gender, being females more affected. At multiple regression analyses fT3 demonstrated to be the best explanatory factor for overall impact of thyroid disease on the patient's life, followed by gender. TSH-suppressive doses of levothyroxine are more effective in improving QoL in DTC patients after thyroidectomy. These results confirm the urgent need of further studies aimed to define the best treatment of hypothyroidism, effective on well-being and harmless for patients.


Hypophysiotropic activity of histone H3 in vitro.
To assess the effect of histone H3 on pituitary hormone secretion, rat anterior pituitary (AP) cells were used and growth hormone, prolactin, thyrotropin, luteinizing hormone and follicle stimulating hormone measured by radioimmunoassay. Incubation of cells with H3 (1, 6, and 30 microM) stimulated the release of all five hormones in a dose-dependent manner. This effect was blocked by preincubation of H3 with an anti-H3 antibody. Incubation of AP cells with 6 microM H3 in the presence of specific AP hormone secretagogues (GRP-6, thyrotropin-releasing hormone (TRH), gonadotropin-releasing hormone (GnRH)) showed additive effects on hormone secretion. Pharmacological experiments suggested that calcium- and diacylglycerol- (DAG) associated pathways, but not cAMP, participate in the hypophysiotropic activity of H3. Our results confirm previous evidence that histones may act as hypophysiotropic signals.


Fungal endophytes of grasses and their effects on an insect herbivore.
The effects of endophytic fungi (Tribe Balansiae, Clavicipitaceae, Ascomycetes) of grasses on an insect herbivore were studied by feeding paired groups of larvae of the fall armyworm (Spodoptera frugiperda, Noctuidae, Lepidoptera) leaves from either infected or uninfected individuals. Perennial ryegrass infected by "the Lolium endophyte", tall fescue infected by Epichloe typhina, dallisgrass infected by Myriogenospora atramentosa, Texas wintergrass infected by Atkinsonella hypoxylon, and sandbur infected by Balansia obtecta were utilized. The endophytes of ryegrass and fescue previously have been shown to be toxic to mammalian herbivores and to deter feeding of some insect herbivores. In this study we extend the antiherbivore properties of those endophytes to the fall armyworm and demonstrate that fungal endophytes in three other genera have similar antiherbivore properties. For most grasses, survival and weights of fall armyworm larvae fed infected leaves were significantly lower and larval duration was significantly longer compared to larvae fed uninfected leaves. Resistance to herbivores may provide a selective advantage to endophyte-infected grasses in natural populations.


Prevalence and risk factors of herpes zoster infection in patients with rheumatic diseases not receiving biologic or targeted therapies.
The objective was to study the prevalence and risk factors of herpes zoster (HZ) infection in patients with rheumatic diseases. Consecutive patients with rheumatic diseases not receiving biologic/targeted DMARDs who attended our rheumatology clinics between March and August 2019 were retrospectively reviewed. Episodes of HZ infection since their first clinic attendance were identified. Laboratory results (total white cell count, neutrophil-to-lymphocyte ratio (NLR), serum albumin, globulin, and creatinine) and use of immunosuppressive medications were compared between those with (preceding infection) and without (preceding last visit) HZ infection. Cox regression analysis was performed to identify factors associated with the first HZ infection in all patients. 1,479 patients were studied (88.3% women, age 45.0 ± 15.8 years). Systemic lupus erythematosus (SLE) (38.7%) and rheumatoid arthritis (28.3%) were the commonest rheumatic diseases. After a follow-up of 14,715 patient-years (9.9 ± 7.0 years), 219 (14.8%) patients developed 258 episodes of HZ infection, giving an overall prevalence of 1.75/100-patient years. The prevalence rates of HZ were highest in SLE and inflammatory myopathies (2.54 and 2.58 per 100 patient-years, respectively). Patients who experienced HZ reactivation were younger, more likely to have SLE, and had significantly lower serum albumin/globulin levels but higher NLR. Significantly more patients with HZ reactivation were using prednisolone and other immunosuppressive drugs in the visits preceding HZ infection. The cumulative risk of having HZ reactivation at 24 and 48 months was 4.9% and 7.6%, respectively. Cox regression analysis revealed that a diagnosis of SLE, increasing age, higher NLR, use of cyclophosphamide, and increasing doses of prednisolone, azathioprine, hydroxychloroquine and leflunomide were independently associated with HZ infection. Reactivation of HZ is fairly common in patients with rheumatic diseases. Underlying SLE, age, neutrophil/lymphocyte ratio, and immunosuppressive therapies are independent risk factors. Key Points • Herpes zoster (HZ) infection is fairly common in patients with rheumatic diseases undergoing conventional DMARD or immunosuppressive therapies. • Underlying SLE, increasing age, higher neutrophil/lymphocyte ratio and increasing dosages of immunosuppressive drugs are independent risk factors. • Patients with rheumatic diseases, particularly SLE, should be encouraged to receive HZ vaccination.


Molecular characterization of the hepatitis B virus in autochthonous and endogenous populations in the Western Brazilian Amazon.
Hepatitis B virus (HBV) infection is a serious public health issue worldwide. Hepatitis B virus is classified into eight genotypes, varying from A to H, with distinct geographical distributions. In Brazil, the most frequent genotypes are A, D, and F. This study aimed to characterize the HBV genotypes in cases of hepatitis B virus and hepatitis D virus (HDV) co-infections in an endemic area in the Western Brazilian Amazon. We analyzed 86 serum samples reactive for HBsAg from indigenous and non-indigenous populations obtained from previous serological surveys. Of the 86 reactive serum samples, 39 were found to be HBV-DNA-positive by semi-nested PCR. The genotypes were established by sequencing the amplified S gene region. We obtained 20 sequences classified into three genotypes: A, D, and F. Genotype A was the most frequent (60%), followed by D (35%) and F (5%). The distribution of the HBV genotypes reflected the pattern of historical occupation of the region.


Design, synthesis and biological evaluation of novel 1,2,4-triazolo [3,4-b][1,3,4] thiadiazines bearing furan and thiophene nucleus.
Twenty-six novel 1,2,4-triazolo [3,4-b][1,3,4] thiadiazines containing furan and thiophene nucleus were designed, synthesized and evaluated for their antiproliferative activities. The results indicated that most of the compounds showed moderate to potent antiproliferative activities against four cancer cell lines, PC-3, HepG2, A549, and MCF-7. Particularly, compound 32 showed eleven-, three-, and two-fold improvement compared to positive control fluorouracil in inhibiting HepG2, PC-3, and A549 cell proliferation with IC₅₀ values of 5.09, 3.70 and 12.74 μM, respectively. Further flow-activated cell sorting analysis revealed that the most promising compound 32 displayed a significant effect on G2/M cell-cycle arrest in a dose-dependent manner in PC-3 cells. These encouraging results should provide important information for the development of new anticancer agents.


Sex-age differences in association with particulate matter and emergency admissions for cardiovascular diseases: a hospital-based study in Taiwan.
To explore the association between short-term exposure to particulate matter (PM) and cardiovascular diseases (CVDs) emergency room visits. Case-control study. 2785 Emergency visits with presented cardiovascular diseases and 24,572 controls from ten hospitals in 2005 were obtained from a Taiwan's National Health Database. Daily PM10 data and meteorological information collected from an air monitoring station near the ten hospitals were used to calculate the exposure levels. Using multiple logistic regression analysis, adjusted odds ratios (AOR) were estimated for the associations of PM and temperature with ischaemic heart disease (IHD) and hypertension heart disease (HHD). A positive association (AOR = 1.05-1.75) between IHD emergency admission among women older than 65 and exposure to daily levels of PM10 pollution standard index (PSI) ≥50 compared with respondents exposed to PM10 PSI <50. To prevent exacerbation of IHD, people, especially elderly women, should be urged to reduce exposure to unhealthy PSI levels.


Interactions between photoautotrophic and heterotrophic metabolism in photoheterotrophic cultures of Euglena gracilis.
Interactions between photoautotrophic and heterotrophic metabolism in photoheterotrophic culture of Euglena gracilis were studied. Under a low light supply coefficient, these two metabolic activities seem to proceed independently. The cell growth rate in photoheterotrophic culture was about the sum of the growth rates in pure photoautotrophic and heterotrophic cultures. However under a high light supply coefficient, both photoautotrophic and heterotrophic (glucose assimilation) metabolic activities were inhibited, resulting in a low photoheterotrophic growth rate. The photoheterotrophic culture was more sensitive to photoinhibition compared to the pure photoautotrophic culture. Inhibition of glucose assimilation in the photoheterotrophic culture was due to both direct and indirect (through photosynthesis) effects of high light intensity. Cell growth, glucose assimilation and alpha-tocopherol content of the cells were higher when ambient air was used for aeration than when a mixture of carbon dioxide and air was used. Even when photosynthesis was inhibited by addition of 3-(3,4-dichlorophenyl)- 1,1-dimethylurea to photoheterotrophic culture, light stimulated alpha-tocopherol synthesis by E. gracilis.


Management of pharmaceutical micropollutants discharged in urban waters: 30 years of systematic review looking at opportunities for developing countries.
Pharmaceutical micropollutants' contamination of urban waters has been studied globally for decades, but the concentration of innovations in management initiatives is still in developed economies. The gap between the locus of innovations in pharmaceuticals and the relative stagnation in less developed economies to manage waste originating in this activity seems fruitful for investigations on innovation in integrated micropollutant management strategies. These tensions allow for advances in current knowledge for environmental management and, particularly, finding solutions for the contamination by pharmaceutical micropollutants of urban water bodies in developing countries. We aim to list the main strategies for managing pharmaceutical micropollutants discussed to point out opportunities for developing countries to advance in this direction. Methodologically, we conducted a systematic literature review from 1990 to 2020, covering 3027 documents on "pharmaceutical micropollutants management." The framework formed by the macro-approach to integrated management operationalized by the dimensional micro-approaches: technical, organizational, community, and governmental allowed us to understand that (1) the management of pharmaceutical micropollutants tends to occur through a technical approach centered on the removal of aquatic matrices, green chemistry, and urine diversion; (2) management with an organizational approach has enabled removing drugs from water bodies by drug take-back program, collaborative projects, drug use reduction, and better organizational practices; (3) the community approach have helped minimize this type of pollution by reducing the consumption of medicines and the proper destination for medicines that are no longer in use. Finally, the government management approach emerges as a source of legal, economic, and informational instruments to reduce pollution by pharmaceutical micropollutants. Furthermore, these management approaches allowed us to identify 15 opportunities for possible adjustments for developing societies. These opportunities can be promising for practices and research and, in the medium term, contribute to minimizing pollution by pharmaceutical micropollutants in urban waters.


Co-expression pattern of Shh with Prox1 and that of Nkx2.2 with Mash1 in mouse taste bud.
In mammals, taste buds are maintained by continuous turnover of cells, even in adulthood. Cell proliferation and differentiation continue to produce taste cells, which express various genes related to taste reception. We found the co-expression of Sonic hedgehog (Shh) with Prox1 and that of Nkx2.2 with Mash1 in adult mouse taste buds. Whereas Prox1was expressed strongly in cells in the basal region of mouse taste buds where Shh was co-expressed, it was expressed weakly in almost all taste bud cells lacking Shh expression. At 0.5 day after birth, when taste cells have not yet differentiated, the expressions of Shh and Prox1 completely overlapped in the epithelium of circumvallate papillae. Nkx2.2 was observed in cells expressing Mash1, but not in cells expressing genes related to taste reception, such as gustducin and T1R3. Almost all fusiform cells expressing Mash1 co-expressed Nkx2.2, while the majority of round cells expressing Mash1 in the basal region of taste buds lacked Nkx2.2 expression.


Conservation of salivary secretion and facial nerve function in partial superficial parotidectomy.
Conventional total superficial parotidectomy (TP) has commonly been used, but partial superficial parotidectomy (PP) offers the possibility of better preserving glandular function and avoiding palsy of the facial nerves. In this study, the extent to which saliva secretion and facial nerve function were conserved in patients who received TP vs. PP was compared. Data were collected from patients who received a PP (n=163) or a TP (n=105) for benign primary tumours in the superficial lobe of the parotid glands between 1995 and 2009 at a single hospital. The incidence of transient facial paralysis was significantly lower in patients who received PP than in those who received TP. Secretory function was preserved for patients with a conserved Stensen's duct, whereas patients in whom the duct had been ligated lost secretory function. Partial superficial parotidectomy reduces the incidence of postoperative facial nerve dysfunction and is conducive to preserving Stensen's duct and saliva secretion.


Juvenile polyposis: Focus on less described manifestations.
Juvenile polyposis represents an heterogeneous disease as different genetic dominant backgrounds have been evidenced leading to different clinical presentations. It is associated in some patients with a different syndrome, Hereditary Hemorragic Telangiectasia, justifying a complementary and different management. Recent international recommendations help in managing this very rare disease, and this management should probably be restricted to expert centers able to take care of the multiple manifestations and risks of these patients and families. This paper will focus on the poorly known and evaluated aspects of juvenile polyposis, excluding the colonic involvement and epidemiology that are addressed in a different article of this issue.


Spectrophotometric cocaine determination in a biphasic medium employing flow-batch sequential injection analysis.
Quantifying cocaine in apprehended samples is important to the Brazilian Federal Police because the concentration can indicate the origin of the drug and consequently the traffic route. In addition to the other risks of using this drug is the variability in cocaine concentration, which makes large doses lethal. Gas Chromatography with a Flame Ionization Detector (GC-FID) and a Mass Selective Detector (GC-MS) are the techniques usually employed, but these systems are not available in all police laboratories, due to the relatively high cost. In the present work, a flow-system procedure for the spectrophotometric determination of cocaine using cobalt thiocyanate as a complexing reagent was developed. In this reaction, two phases are formed: the superior (pink) contains an excess of cobalt thiocyanate solution and the lower layer (blue) contains the complex cocaine-cobalt thiocyanate. Samples and reagent are inserted through a sequential-injection valve between two air bubbles inside a reaction chamber. An optic fiber sensor connected to the chamber recorded the absorbance at 630 nm signal. The detection and quantification limits were 29.4 mg L(-1) and 98 mg L(-1), respectively. Relative standard deviation was 4.9% for solutions containing 400 mg L(-1) (n=10), with stable baselines. The analytical throughput was 12 determinations per hour.


A bionic cellulose nanofiber-based nanocage wound dressing for NIR-triggered multiple synergistic therapy of tumors and infected wounds.
Tumor recurrence and drug-resistant bacterial infection are the main reasons that wounds heal with difficulty after skin tumor treatment. The near infrared- (NIR-) and pH-responsive, bionic, cellulose nanofiber-based (CNF-based) nanocage wound dressing with biocompatibility, bioviscosity, and shape adaptability is designed for dual NIR-triggered photothermal therapy of tumor and infection-induced wound healing. The wound dressing with the intertwining three dimensional (3D) nanocage network structure is skillfully constructed using NIR-responsive cellulose nanofibers and pH-responsive cellulose nanofibers as the skeleton, which endows the dressing with a high drug-loading capacity of doxorubicin (400 mg·g-1), and indocyanine green (25 mg·g-1). Moreover, the NIR- and pH-responsive bionic "On/Off" switches of the dressing enable a controllable and efficient drug release onto the wound area. The dual NIR-triggered wound dressing with excellent photothermal conversion performance possesses good antibacterial properties against Escherichia coli, Staphylococcus aureus, and drug-resistant Staphylococcus aureus. It could effectively eliminate bacterial biofilms and kill A375 tumor cells. Interestingly, the bionic wound dressing with shape adaptability could adapt and treat irregular postoperative skin tumor wounds and drug-resistant bacterial infection via the synergistic therapy of photothermal, photodynamic, and chemotherapy, which provides an ideal strategy for clinical intervention.


MK2 plays an important role for the increased vascular permeability that follows thermal injury.
We previously reported Rho kinase is involved in vessel hyper-permeability caused by burns. Here we further explore the Rho kinase downstream signaling, it is found that its specific inhibitor Y27632 significantly diminishes the activation of JNK and p38 MAPKs but not ERK that induced by serum from burned rats (burn-serum). JNK activation was found involved in the expression of HUVEC adhesion molecules following thermal injury, although not in the process of stress fiber formation. Inhibition of various MAPKs by specific inhibitors showed that SB203580 (inhibitor of p38), but neither SP600125 (inhibitor of JNK) nor PD98059 (inhibitor of ERK), abolish activation of the p38 downstream kinase MK2. Demonstration of stress fibers by fluorescent-labeled phalloidin showed that inhibition of MK2, either by its specific inhibitor or by dominant negative adeno-viral-carried constructs, significantly reduced burn-serum-induced HUVEC stress-fiber formation, while inhibition of another downstream p38 MAPK kinase, PRAK, had no such effects. Transfection of dominant negative adeno-viral MK2 (Ad-MK2(A)) significantly inhibited thermal injury-induced blood vessel hyper-permeability in rats and, moreover, prolonged the survival of burned rats beyond 72 h following thermal injury. One of the mechanisms behind these phenomena is that Ad-MK2(A) causes a significant depression of burn-serum-induced HSP27-phosphorylation, while the adeno-viral transported dominant negative PRAK (Ad-PRAK(A)) does not block. Although the effect of blockade of MK2 through its adeno-viral approach requires further study and investigation of alternatives to know for sure, we may have found a new pathway behind thermal-injury-induced blood vessel hyper-permeability, namely: Rho kinase>p38>MK2>HSP27.


[Contrast echocardiography and myocardial perfusion: what is the current status?].
Progress in the field of echocardiographic contrast agent combined with progress in imaging techniques (second harmonic imaging, intermittent imaging, Doppler Energy) should allow a real revolution in the field of noninvasive cardiac imaging, and one of the main advantages will probably be myocardial perfusion imaging in ischaemic heart disease.


Comparison of Posterior Lumbar Interbody Fusion and Posterolateral Lumbar Fusion in Monosegmental Vacuum Phenomenon within an Intervertebral Disc.
Retrospective. To compare the clinical and radiological outcomes of posterolateral lumbar interbody fusion (PLIF) and posterolateral lumbar fusion (PLF) in monosegmental vacuum phenomenon within an intervertebral disc. The vacuum phenomenon within an intervertebral disc is a serious form of degenerative disease that destabilizes the intervertebral body. Outcomes of PLIF and PLF in monosegmental vacuum phenomenon are unclear. Monosegmental instrumented PLIF and PLF was performed on 84 degenerative lumbar disease patients with monosegmental vacuum phenomenon (PLIF, n=38; PLF, n=46). Minimum follow-up was 24 months. Clinical outcomes of leg and back pain were assessed using visual analogue scales for leg pain (LVAS) and back pain (BVAS), and the Oswestry disability index (ODI). The radiographic outcome was the estimated bony union rate. LVAS, BVAS, and ODI improved in both groups. There was no significant difference in the degree of these improvements between PLIF and PLF patients (p>0.05). Radiological union rate was 91.1% in PLIF group and 89.4% in PLF group at postoperative 24 months (p>0.05). No significant differences in clinical results and union rates were found between PLIF and PLF patients. Selection of the operation technique will reflect the surgeon's preferences and patient condition.


Neurobiological evidence for thalamic, hippocampal and related glutamatergic abnormalities in bipolar disorder: a review and synthesis.
The thalamus, hippocampus and related glutamatergic neurotransmission pathways have been implicated in the pathophysiology of bipolar disorder. We have reviewed the existing literature over approximately two decades from 1990 to March 2008 for evidence that support structural, functional and chemical neuroimaging abnormalities as well as glutamatergic aberrations of the thalamus and the hippocampus in bipolar disorder. Available structural neuroimaging studies suggest a predominance of negative findings in terms of hippocampal and thalamic volumetric changes in bipolar disorder. Many functional neuroimaging studies however have found activation changes within the thalami, medial temporal lobes, prefrontal regions, and basal ganglia suggesting abnormal limbic-thalamo-cortical circuitry in bipolar disorder. The pattern of findings suggests abnormalities in the regulation of neuronal activity without fixed lesions in the thalamus or hippocampus. This could be related to factors such as cohort heterogeneity, image resolution and whether specific nuclei are examined, or that bipolar disorder is associated with greater neural inefficiency and greater reactivity to emotional stimuli. Chemical neuroimaging studies in bipolar disorder also implicate altered excitatory glutamate neurotransmission as well as cellular and membrane metabolism, especially pronounced within the hippocampus. Within the hippocampus, abnormalities of the ionotropic glutamate receptors were found in bipolar disorder with metabotropic glutamate receptors being relatively understudied. The few immunohistochemical studies performed on the thalamus also suggest the possibility of disturbances of glutamatergic neurotransmission involving intracellular signaling and trafficking processes in bipolar disorder. Overall, the emerging trends from these findings highlight the need for further research to unravel underlying neurobiological changes and clinical correlates of thalamic and hippocampal dysfunction in bipolar disorder.


[Blockade of estradiol benzoate hyperplasia of the adenohypophysis with Deprenon and lisuride - histological findings].
Three-week administering of Estradiolbenzoate to male rats results in hyperplasia of adenohypophysis with increase of Orange G slightly positive cells and chromophobe cells, loosening of structure giving a trabecular picture, and stressed vascularization. Simultaneous administering of Ergoline compounds (Deprenon, Lisuride) rather limited the transformation. However, the differentiation of single pituitary cells due to Estradiolbenzoate remained substantially uninfluenced.


Comprehensive analysis of the expression, prognostic significance, and function of FAM83 family members in breast cancer.
The FAM83 family plays a key role in tumorigenesis and cancer progression. However, the role of the FAM83 family in the development of breast tumors is unclear to date. This report explores the expression, prognostic significance, and function of the FAM83 family members in breast cancer using public databases. UALCAN database was used to explore the expression of FAM83 family members in breast cancer. Furthermore, we validated the expression of FAM83 family members in twenty pairs of breast cancer and normal tissues by RT-PCR. Kaplan-Meier plotter database was used to explore the prognostic significance of FAM83 family members in breast cancer. GeneMANIA and DAVID databases were used for functional and pathway enrichment analysis of genes co-expressed with FAM83A, FAM83D, FAM83F, and FAM83G. MEXPRESS and UALCAN databases were used to analyze the level of DNA promoter methylation of FAM83A, FAM83D, FAM83F, and FAM83G in breast cancer. TIMER database was utilized to explore the relationships between immune cell infiltration and FAM83A, FAM83D, FAM83F, and FAM83G expression. Among FAM83 family members, FAM83A, FAM83D, FAM83F, and FAM83G were higher expressed in breast cancer than in normal tissues. We also validated the significant high expression of FAM83A, FAM83D, FAM83F, and FAM83G mRNA in breast cancer than in normal samples. Their increased expression has an adverse prognostic effect on breast cancer patients. These genes co-expressed with FAM83A, FAM83D, FAM83F, and FAM83G might take part in cell proliferation, G2/M transition of the mitotic cell cycle, regulation of apoptosis process and other cancer-related biological processes. In addition, they were mainly enriched in the Hippo signaling pathway, Hedgehog signaling pathway, PI3K/AKT signaling pathway, and other cancer-related pathways. We also found that promoter DNA methylation might regulate the expression of FAM83A, FAM83D, FAM83F, and FAM83G mRNA in most CpG islands. At last, we found the expression of FAM83A, FAM83D, FAM83F, and FAM83G mRNA was significantly related to immune cell infiltration. FAM83A, FAM83D, FAM83F, and FAM83G were highly expressed in breast cancer tissues and had an adverse effect on the survival outcomes of breast cancer patients. Also, they were involved in breast cancer-related signal pathways. Therefore, they might serve as potential therapeutic targets for breast cancer clinical treatment.


Hypereosinophilic syndrome.
To summarize the identified molecular and cellular mechanisms relevant to clinicians evaluating patients with hypereosinophilic syndrome (HES). Review of relevant peer-reviewed literature. Studies on the pathogenesis of HES in relation to consensus definitions, disease classification, mechanisms of disease, and diagnosis and treatment are included. Changes to the definition of HES have been proposed based on recent studies identifying specific cellular and molecular disease phenotypes. Identification of specific mechanisms of disease may have clinical and therapeutic significance. Despite recent advances, in most cases the molecular pathogenesis of HES remains unknown. Identification of specific HES disease mechanisms empowers the practicing clinician to offer specific mechanism-based treatment options to patients with HES in their clinical practice.


Propylparaben-induced disruption of energy metabolism in human HepG2 cell line leads to increased synthesis of superoxide anions and apoptosis.
The effect of propylparaben (in final concentrations 0.4 ng/ml, 2.3 ng/ml and 4.6 ng/ml) on the energy metabolism of HepG2 hepatocytes, superoxide anion synthesis, apoptosis and necrosis is described. Propylparaben can be toxic to liver cells due to the increased production of superoxide anions, which can contribute to a reduced concentration of superoxide dismutase in vivo and impairment of the body's antioxidant mechanisms. Finally, a further reduction in the mitochondrial membrane potential and uncoupling of the respiratory chain resulting in a reduction in ATP concentration as a result of mitochondrial damage may lead to cell death by apoptosis.


The relationship between persistent organic pollutants and Attention Deficit Hyperactivity Disorder phenotypes: Evidence from task-based neural activity in an observational study of a community sample of Canadian mother-child dyads.
Prenatal exposure to persistent organic pollutants (POPs), widespread in North America, is associated with increased Attention Deficit/Hyperactivity Disorder (ADHD) symptoms and may be a modifiable risk for ADHD phenotypes. However, the effects of moderate exposure to POPs on task-based inhibitory control performance, related brain function, and ADHD-related symptoms remain unknown, limiting our ability to develop interventions targeting the neural impact of common levels of exposure. The goal of this study was to examine the association between prenatal POP exposure and inhibitory control performance, neural correlates of inhibitory control and ADHD-related symptoms. Prospective data was gathered in an observational study of Canadian mother-child dyads, with moderate exposure to POPs, including polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), as part of the GESTation and the Environment (GESTE) cohort in Sherbrooke, Quebec, Canada. The sample included 87 eligible children, 46 with maternal plasma samples, functional magnetic resonance imaging (fMRI) data of Simon task performance at 9-11 years, and parental report of clinical symptoms via the Behavioral Assessment System for Children 3 (BASC-3). Simon task performance was probed via drift diffusion modeling, and parameter estimates were related to POP exposure. Simon task-based fMRI data was modeled to examine the difference in incongruent vs congruent trials in regions of interest (ROIs) identified by meta analysis. Of the 46 participants with complete data, 29 were male, and mean age was 10.42 ± 0.55 years. Increased POP exposure was associated with reduced accuracy (e.g. PCB molar sum rate ratio = 0.95; 95% CI [0.90, 0.99]), drift rate (e.g. for PCB molar sum β = -0.42; 95% CI [-0.77, -0.07]), and task-related brain activity (e.g. in inferior frontal cortex for PCB molar sum β = -0.35; 95% CI [-0.69, -0.02]), and increased ADHD symptoms (e.g. hyperactivity PCB molar sum β = 2.35; 95%CI [0.17, 4.53]), supporting the possibility that prenatal exposure to POPs is a modifiable risk for ADHD phenotypes. We showed that exposure to POPs is related to task-based changes in neural activity in brain regions important for inhibitory control, suggesting a biological mechanism underlying previously documented associations between POPs and neurobehavioral deficits found in ADHD phenotypes.


Immature brain injury via peroxynitrite production induced by inducible nitric oxide synthase after hypoxia-ischemia in rats.
To determine whether, and if so how, iNOS expresses and affects brain injury induced by hypoxia-ischemia in an immature brain. Seven-day-old Wistar rat pups were exposed to right common carotid artery ligation followed by 1.5 hours of hypoxia. The time course of iNOS mRNA expression, enzymatic activity, and protein production in the cerebral cortex were determined. The extent of the infarct area in the cerebral cortex and the production of 3-nitrotyrosine (a biomarker of peroxynitrite) were compared between the control pups and pups treated with S-methyl-isothiourea (a selective iNOS inhibitor). In the cortex ipsilateral to carotid ligation, iNOS mRNA appeared from 6 hours to 24 hours after hypoxia-ischemia and disappeared at 48 hours. The iNOS protein and its activity also increased at 12 hours and reached a maximum level at 48 hours after the insult. The percentage of damage in the cerebral cortex was significantly higher in the control pups than in treated pups (31.9 vs 10.6%). Tri-nitrotyrosine following iNOS expression-positive cells were located predominantly at the infarct and peri-infarct regions. iNOS expression might be an important determinant of ischemic immature brain injury.


Thioredoxin-1 and protein disulfide isomerase catalyze the reduction of similar disulfides in HIV gp120.
HIV-1 enters cells via interaction of the viral glycoprotein gp120, the host cell surface receptor CD4 and the co-receptors CCR5 or CXCR4. For entry, gp120 undergoes conformational changes that depend on the reduction of one or more disulfides. Previous studies indicate that protein disulfide isomerase (PDI), thioredoxin-1 (Trx1), and glutaredoxin-1 (Grx1) catalyze gp120 reduction, but their specific disulfide targets are not known. Here, it was demonstrated that PDI and Trx1 have similar gp120 disulfide targets as determined by labeling after reduction, but with some pattern differences, including overall stronger labeling with Trx1 than with PDI. Furthermore, uneven labeling of the residues of a disulfide may reflect altered accessibility by conformational changes upon the reduction process. Since both PDI and Trx1 may be involved in viral entry, compounds that target the host redox system or the viral gp120 were tested in vitro to investigate whether redox regulation is a target for anti-HIV therapy. Carbohydrate binding agents (CBAs), previously shown to bind gp120 and inhibit HIV entry, were now demonstrated to inhibit gp120 disulfide reduction. Auranofin, an inhibitor of thioredoxin reductase 1 (TrxR1), also showed inhibitory activity towards HIV infection, although close to its cytotoxic concentration. Our results demonstrate that both the host redox system and the viral surface glycoproteins are of interest for the development of new generations of anti-HIV therapeutics.


Measurement of quality of life in head and neck cancer patients utilizing the quality of life radiation therapy questionnaire.
Quality of life (QOL) measures give patients the possibility to express subjective changes in wellbeing. We aimed to translate the radiation specific quality of life questionnaire (QOL-RTI) and the companion head and neck module (H&N) questionnaire into German and to test its reliability, validity and sensitivity. After translation and final revisions based on qualitative interviews with ten patients, 97 head and neck cancer patients were screened for eligibility. Patients answered the 38 items questionnaire at baseline and twice in week 4 of radiotherapy for test-retest reliability. Internal consistency was calculated using Chronbach's alpha. Patients also completed the functional assessment of cancer tool plus head and neck (FACT-G plus H&N) for concurrent validity. Item analyses were performed to test the sensitivity. Chronbach's alpha yielded alpha = 0.85 for the QOL-RTI and alpha = 0.80 for the H&N module, test-retest reliability scores were r = 0.87 and r = 0.83, respectively. The correlation of the QOL-RTI plus H&N and the FACT plus H&N was r = 0.79. Questionnaire sensitivity was supported by significant changes in the mean score of 45.8% of the QOL-RTI items and 78.6% of the H&N items between baseline and week 4 of radiotherapy. The German version of the QOL-RTI was shown to be a reliable, valid and sensitive tool to assess the quality of life of patients undergoing radiotherapy. The H&N module is useful for patients undergoing treatment for head and neck cancer.


Ultrasonic vocalizations by adult prairie voles, Microtus ochrogaster.
Male and female Microtus ochrogaster were presented with anesthetized and awake conspecifics while ultrasonic vocalizations (USVs) were monitored. Males produced significantly more USVs than females during 5-min testing sessions. Males tended to produce more USVs to unfamiliar females than to familiar female siblings. Sexual experience led to increased USV scores by males. These results suggest that USVs by male prairie voles communicate to females the male's gender and his availability for reproductive behavior.


Do We Need to Study Metabolism and Distribution in the Eye: Why, When, and Are We There Yet?
The liver is known to be the principal site of drug metabolism. Depending on the route of administration, especially in cases of topical and local delivery, evaluation of local drug metabolism in extrahepatic tissues is vital to assess fraction of the drug metabolized. This parameter becomes important from the point of view of drug availability or the contribution to overall clearance. Examples include fraction metabolized in the gut for oral drugs and contribution of pulmonary or renal clearance to total clearance of a drug. Diseases of the eye represent a rising unmet medical need and a number of therapeutics are currently being developed in the form of small molecules and biologics. Treatment of ocular diseases has expanded to explore various topical formulations and local short- and long-term therapies by ocular routes of administration. Until recently, metabolism in the eye for any species, including human, was not well documented, but this topic is gaining wide interest. Many in vitro-ex vivo models, each with separate pros and cons, are being used for studying ocular metabolism. This review is aimed at providing a perspective on the relevance and application of ocular metabolism, melanin binding, and the use of tissue- and cell-derived ocular models in discovery and preclinical development.


Molecular typing and genomic characteristic of human adenoviruses in Datong, Northern China.
The molecular prevalence of human adenoviruses (HAdVs) in Datong city and molecular evolution of HAdV-C species is still obscure. Here, we explored the molecular prevalence of HAdVs by simultaneous sequencing of hexon and fiber. Then, the penton gene fragments of HAdV-C species were determined by sequencing. Finally, genomic and proteotyping analysis were performed for exploration of molecular evolution of unique HAdV-6. Our results showed that dominant molecular types of HAdVs were HAdV-3, HAdV-2, and HAdV-1 based on the hexon and fiber genotype. Among H2F2 isolates, P1H2F2 was most common, followed by P2H2F2 and HAdV-89. The clinical symptoms of HAdV-1 or HAdV-2 infected patients were more severe than HAdV-3 infected patients, the prognosis of HAdV-1, HAdV-2, and HAdV-3 infected patients was indifference. Genomic and proteotyping analysis demonstrated that DT15 was different from HAdV-6 prototype, with high-discrepant sequences localized in the E3 region. In conclusion, HAdV-1 and HAdV-2 have a high affinity to infect younger children and cause more severe symptoms than HAdV-3. The E3 gene of HAdV-C species was considered as highly recombination and mutation region.


Potassium concentration influences the gating of K+ channels from sarcoplasmic reticulum.
Gating of K+ channels from the sarcoplasmic reticulum (SR) is influenced by the K+ concentration in the bathing solution. The probability of finding the channel open (Po) increases nonlinearly with the K+ concentration. The current two-state model which considers only voltage-dependent rate constants for the SR K+ channel should be reconsidered in the light of the present results.


[Correlation of the down-regulation of tumor suppressor gene p15 and hematotoxicity from benzene exposure].
To explore the correlation between the expression of tumor suppressor gene p15 and the hematotoxicity from benzene exposure. Twenty cases of patients with chronic benzene poisoning (BP), 17 benzene-exposed workers engaged in the same job with the patients but without BP and 19 matched unexposed controls from Tianjin were recruited. The expression of tumor suppressor gene p15 mRNA was detected by qRT-PCR. Comparing with the unexposed controls, the expression levels of p15 mRNA were significantly down-regulated in BP patients (P < 0.01) and also in benzene-exposed workers (P < 0.01). The expression of p15 was down-regulated with the increased severity of BP (P < 0.01). The expression of p15 mRNA is positively correlated with white blood cell counts and neutrophil counts (r = 0.42, P = 0.002, r = 0.44, P = 0.002, respectively). The expression of p15 mRNA is significantly down-regulated in BP patients. The transcriptional repression of p15 is associated with benzene hematotoxicity.


Phantom pain following limb amputation in a paraplegic. A case report.
The pain of the phantom limb remains a diagnostic and therapeutic challenge. A case is reported in which a paraplegic patient with full sensory ablation below T11 experienced phantom limb pain only after actual amputation of one of his legs. This suggests that the cause in this case could only be central in origin. Visual appreciation seems to be an important step in this process.


Simian virus 40 mutants with amino-acid substitutions near the amino terminus of large T antigen.
A series of amino-acid substitution mutants has been made with changes in the region of simian virus 40 large tumor antigen (T antigen) that is shared with the small tumor antigen (t antigen). Both single and multiple amino-acid replacements were obtained using the heteroduplex deletion loop method and sodium bisulfite as the mutagen. The mutants could be divided into five phenotypic classes on the basis of their biological properties: a) mutants whose changes did not affect their ability to propagate on permissive monkey cells, nor to transform nonpermissive rodent cells; b) mutants that were not viable, replicated their DNA to 5% or less of wild type, but were positive for transformation; c) mutants that were not viable, replicated their DNA to 5% or less of wild type, and were defective for transformation; and d) mutants that completely lost all three activities coordinately. In addition, one mutant with changes in this region, 5002, replicated its DNA to about 50% of wild type, had an impaired transformation activity, and produced virions at a level of about 4% that of wild type.


ENT mucormycosis. Report of 4 cases.
Mucormycosis is an opportunist infection usually affecting immunocompromised patients. It is rare and often fatal. The pathogen is filamentous fungus of the mucorales order. Studies discuss the clinical, diagnostic and therapeutic aspects of ENT mucormycosis, insisting on early clinical diagnosis, laboratory data not being contributive within satisfactory time limits. A retrospective study included 4 patients with ENT mucormycosis diagnosed over a 13-year period, from January 2000 to December 2012. The study included 2 male and 2 female patients, aged from 3 to 77 years. Two patients were diabetic. There were 2 cases of sinonasal mucormycosis and 2 of otologic involvement. Diagnosis was founded on anatomopathologic and mycologic examination. A fatal issue occurred in 1 case with otocerebral involvement. Otorhinolaryngologic mucormycosis is a rare fungal infection, which needs to be borne in mind. Rhinocerebral lesions are the most common clinical manifestations. Involvement of the ear is very rare. Diagnosis is often difficult, but should be as early as possible. Treatment, initiated urgently, associates antifungal treatment, surgical resection and control of risk factors. The prognosis remains in all cases severe.


Comparison of the QuantiFERON-TB® Gold Plus on LIAISON® XL and T-SPOT.TB for the diagnosis of latent Mycobacterium tuberculosis infection in a low tuberculosis incidence population.
The current study compared the QuantiFERON-TB® Gold Plus on LIAISON® XL to the T-SPOT.TB for the diagnosis of latent Mycobacterium tuberculosis infection on 125 patient samples. A high agreement of qualitative results (90%) was observed between both methods with 3% major discrepancies, half of which were false negative results with the T-SPOT.TB.


[Dependence of spermatozoa motility on other ejaculate parameters].
1852 ejaculate specimens were investigated to determine the sperm motility subjectively, and by the motility performance coefficient (Ishii). Statistical analysis shows that motility changes significantly with sperm density.


Activities of Succinate Dehydrogenase and Lactate Dehydrogenase in Blood Lymphocytes in Yakut Ground Squirrels Spermophilus undulatus During Hibernation and in the Active State.
We studied energy metabolism in blood lymphocytes of Yakut ground squirrels Spermophilus undulatus in active state and during hibernation. Activities of succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH), marker enzymes of mitochondrial respiration and glycolysis, were measured by a cytobiochemical method based on quantitative assessment of a product of NBT reduction to diformazan in blood lymphocytes immobilized on glass. To measure SDH and LDH activities, cytobiochemical staining of immobilized cells was performed with succinate, lactate, and NAD. In the state of hibernation, SDH activity decreased by 3 times and LDH activity decreased by 10 times or more. These results suggest that the decrease in metabolic activity in lymphocytes of ground squirrels during hypothermia is associated with inhibition of glycolysis, rather than with mitochondrial energy supply.


Emerging contaminants (pharmaceuticals, personal care products, a food additive and pesticides) in waters of Sydney estuary, Australia.
The current investigation of marine water from 30 sites adjacent to stormwater outlets across the entire Sydney estuary is the first such research in Australia. The number of analytes detected were: 8/59 pharmaceutical compounds (codeine, paracetamol, tramadol, venlafaxine, propranolol, fluoxetine, iopromide and carbamazepine), 7/38 of the pesticides (2,4-dichlorophenoxyacetic acid (2,4-D), 3,4-dichloroaniline, carbaryl, diuron, 2-methyl-4-chlorophenoxyacetic acid (MCPA), mecoprop and simazine) and 0/3 of the personal care products (PCPs) analysed. An artificial sweetener (acesulfame) was detected, however none of the nine antibiotics analysed were identified. Sewage water is not discharged to this estuary, except infrequently as overflow during high-precipitation events. The presence of acesulfame (a recognised marker of domestic wastewater) and pharmaceuticals in water from all parts of the estuary after a dry period, suggests sewage water is leaking into the stormwater system in this catchment. The pesticides are applied to the environment and were discharged via stormwater to the estuary.


Predictors of switch from depression to mania in bipolar disorder.
Manic switch is a relevant issue when treating bipolar depression. Some risk factors have been suggested, but unequivocal findings are lacking. We therefore investigated predictors of switch from depression to mania in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) sample. Manic switch was defined as a depressive episode followed by a (hypo)manic or mixed episode within the following 12 weeks. We assessed possible predictors of switch using generalized linear mixed models (GLMM). 8403 episodes without switch and 512 episodes with switch (1720 subjects) were included in the analysis. Several baseline variables were associated with a higher risk of switch. They were younger age, previous history of: rapid cycling, severe manic symptoms, suicide attempts, amphetamine use and some pharmacological and psychotherapeutic treatments. During the current depressive episode, the identified risk factors were: any possible mood elevation, multiple mania-associated symptoms with at least moderate severity, and comorbid panic attacks. In conclusion, our study suggests that both characteristics of the disease history and clinical features of the current depressive episode may be risk factors for manic switch.


Inhibition of freshwater algal species by co-culture with two fungi.
Microorganisms have attracted worldwide attention as possible agents for the inhibition of water blooms. Algae can usually be inhibited and degraded directly by fungi. In this study, the effects of Trichaptum abietinum 1302BG and Lopharia spadicea on different freshwater algal species, namely, Microcystis aeruginosa, Chlorella vulgaris, Glenodinium sp., Navicula sp., Cryptomonas ovata, and Euglena gracilis, were detected. After 24h, there was a significant inhibitory effect in all algal cultures with T. abietinum 1302BG, except E. gracilis, and all algal cultures with L. spadicea, except Navicula sp. and E. gracilis. The dried masses of two fungi increased while majority of the algal cells disappeared after 72 h of co-incubation with M. aeruginosa, C. vulgaris, Glenodinium sp., and C. ovata. Thus, the two fungi might inhibit the growth of different freshwater algal species and utilize the algal cells for their growth.


The effect of EMD 57033, a novel cardiotonic agent, on the relaxation of skinned cardiac and skeletal muscle produced by photolysis of diazo-2, a caged calcium chelator.
EMD 57033 is thought to produce its potentiating effect by increasing the apparent calcium sensitivity of myofibrils. We have investigated the effect of 10 microM EMD 57033 on relaxation speed, induced by flash photolysis of 2mM diazo-2 (a caged Ca2+ chelator), in skinned semitendinosus frog muscle fibres and guinea-pig trabeculae. 10 microM EMD 57033 has no effect on the relaxation speed of semitendinosus fibres. In trabeculae, EMD 57033 slightly increases the relaxation speed slightly, in contrast to ADP which produces a slowing. 1mM ADP combined with 10 microM EMD 57033 slows relaxation but not to the degree seen with ADP alone. Like ADP, EMD 57033 increases the number of cross-bridges in the force producing state, but unlike ADP does not affect the transition rates involved in relaxation.


Genomic features separating ten strains of Neorhizobium galegae with different symbiotic phenotypes.
The symbiotic phenotype of Neorhizobium galegae, with strains specifically fixing nitrogen with either Galega orientalis or G. officinalis, has made it a target in research on determinants of host specificity in nitrogen fixation. The genomic differences between representative strains of the two symbiovars are, however, relatively small. This introduced a need for a dataset representing a larger bacterial population in order to make better conclusions on characteristics typical for a subset of the species. In this study, we produced draft genomes of eight strains of N. galegae having different symbiotic phenotypes, both with regard to host specificity and nitrogen fixation efficiency. These genomes were analysed together with the previously published complete genomes of N. galegae strains HAMBI 540T and HAMBI 1141. The results showed that the presence of an additional rpoN sigma factor gene in the symbiosis gene region is a characteristic specific to symbiovar orientalis, required for nitrogen fixation. Also the nifQ gene was shown to be crucial for functional symbiosis in both symbiovars. Genome-wide analyses identified additional genes characteristic of strains of the same symbiovar and of strains having similar plant growth promoting properties on Galega orientalis. Many of these genes are involved in transcriptional regulation or in metabolic functions. The results of this study confirm that the only symbiosis-related gene that is present in one symbiovar of N. galegae but not in the other is an rpoN gene. The specific function of this gene remains to be determined, however. New genes that were identified as specific for strains of one symbiovar may be involved in determining host specificity, while others are defined as potential determinant genes for differences in efficiency of nitrogen fixation.


Mixed blessings: cervical cancer screening in Recife, Brazil.
This study examines the effects of a large-scale cervical cancer prevention campaign in Recife, Brazil between 1994 and 1995. It suggests that while this program effectively motivated women to get pap smears, it reinforced local understandings of the pap smear that ultimately had unintended negative consequences for women's health. It argues that because the campaign connected female sexual activity directly with cervical cancer, the program's message was interpreted by many women to mean that cervical cancer was a sexually transmitted disease and that it would behave like one. Women who were no longer sexually active believed that they did not need to be screened. In addition, women who were sexually active believed that they could use pap smears to diagnose and cure sexually transmitted diseases.


Inflammation and the pathological progression of Alzheimer's disease are associated with low circulating choline levels.
Deficiency of dietary choline, an essential nutrient, is observed worldwide, with ~ 90% of Americans being deficient. Previous work highlights a relationship between decreased choline intake and an increased risk for cognitive decline and Alzheimer's disease (AD). The associations between blood circulating choline and the pathological progression in both mild cognitive impairment (MCI) and AD remain unknown. Here, we examined these associations in a cohort of patients with MCI with presence of either sparse or high neuritic plaque density and Braak stage and a second cohort with either moderate AD (moderate to frequent neuritic plaques, Braak stage = IV) or severe AD (frequent neuritic plaques, Braak stage = VI), compared to age-matched controls. Metabolomic analysis was performed on serum from the AD cohort. We then assessed the effects of dietary choline deficiency (Ch-) in 3xTg-AD mice and choline supplementation (Ch+) in APP/PS1 mice, two rodent models of AD. The levels of circulating choline were reduced while pro-inflammatory cytokine TNFα was elevated in serum of both MCI sparse and high pathology cases. Reduced choline and elevated TNFα correlated with higher neuritic plaque density and Braak stage. In AD patients, we found reductions in choline, its derivative acetylcholine (ACh), and elevated TNFα. Choline and ACh levels were negatively correlated with neuritic plaque load, Braak stage, and TNFα, but positively correlated with MMSE, and brain weight. Metabolites L-Valine, 4-Hydroxyphenylpyruvic, Methylmalonic, and Ferulic acids were significantly associated with circuiting choline levels. In 3xTg-AD mice, the Ch- diet increased amyloid-β levels and tau phosphorylation in cortical tissue, and TNFα in both blood and cortical tissue, paralleling the severe human-AD profile. Conversely, the Ch+ diet increased choline and ACh while reducing amyloid-β and TNFα levels in brains of APP/PS1 mice. Collectively, low circulating choline is associated with AD-neuropathological progression, illustrating the importance of adequate dietary choline intake to offset disease.


[Preliminary study of snake fauna in the Lama forest, South Benin].
The following study aims at assessing the ophidian diversity of the Lama Forest, a classified area, situated in the South of Benin. One can distinguish three types of habitat according to the degree of human activity: the remaining dense forest at the centre, the intermediate plantation area, and finally the area around the edge which has been entirely subjected to human habitation. Each day for two weeks we have been working on various plots of study (by day), patrolled along transect routes (by night), and installed a trap in the central area. As a result, we were able to observe 32 snake specimens, 24 of which we captured. Nearly all were able to be identified, and have been classified into 13 genera and 17 species.


Chlorfenapyr metabolism by mosquito P450s associated with pyrethroid resistance identifies potential activation markers.
Chlorfenapyr is a pro-insecticide increasingly used in combination with pyrethroids such as a-cypermethrin or deltamethrin in insecticide treated bednets (ITNs) to control malaria transmitted by pyrethroid-resistant mosquito populations. Chlorfenapyr requires P450 activation to produce tralopyril and other bioactive metabolites. Pyrethroid resistance is often associated with elevated levels of chemoprotective P450s with broad substrate specificity, which could influence chlorfenapyr activity. Here, we have investigated chlorfenapyr metabolism by a panel of eight P450s commonly associated with pyrethroid resistance in An. gambiae and Ae. aegypti, the major vectors of malaria and arboviruses. Chlorfenapyr was activated to tralopyril by An. gambiae CYP6P3, CYP9J5, CYP9K1 and Ae. aegypti, CYP9J32. The Kcat/KM value of 0.66 μM-1 min-1 for CYP9K1 was, 6.7 fold higher than CYP6P3 and CYP9J32 (both 0.1 μM-1 min-1) and 22-fold higher than CYP9J5 (0.03 μM-1 min-1). Further investigation of the effect of -cypermethrin equivalent to the ratios used with chlorfenapyr in bed nets (~ 1:2 molar ratio) resulted in a reduction in chlorfenapyr metabolism by CYP6P3 and CYP6K1 of 76.8% and 56.8% respectively. This research provides valuable insights into the metabolism of chlorfenapyr by mosquito P450s and highlights the need for continued investigation into effective vector control strategies.


A rapid microtiter plate method for the detection of lysozyme release from human neutrophils.
An improved method was devised to measure lysozyme secreted from human neutrophils [polymorphonuclear leukocyte (PMN)] using a microtiter plate reader capable of analyzing enzyme kinetics. The assay is an adaptation of the classical photometric method which detects changes in the turbidity of a bacterial suspension, Micrococcus lysodeikticus, caused by the enzymatic activity of lysozyme. A standard curve using chicken egg white lysozyme was generated, and activity was detectable between the range of 1 and 100 ng/ml. Leukotriene B4 (LTB4)-induced lysozyme release from human PMN was comparable in both the standard assay and the microtiter plate adaptation with EC50 values of 6.5 and 7.2 nM, respectively. Other select stimuli and their receptor antagonists were also used to evaluate the method. Dose-response curves for chemotactic hexapeptide (CHP), recombinant human C5a (rhC5a), and platelet-activating factor (PAF) resulted in EC50 values of 0.14, 0.80, and 542.00 nM, respectively. Inhibition of lysozyme release was studied using receptor antagonists N-t-Boc-L-methionyl-L-leucyl-L-phenylalanine (N-t-Boc), LY223982, and protamine, which are putative inhibitors of formyl peptides (i.e., CHP), LTB4, and C5a, respectively. N-t-Boc inhibited CHP-induced (0.2 nM) enzyme release with an IC50 of 2 microM; LY223982 blocked LTB4-induced (20 nM) release resulting in an IC50 of 52 nM; and protamine inhibited rhC5a-induced (1.5 nM) release with an IC50 of 2 microM. Further studies revealed that CHP, LTB4, and rhC5a were selectively inhibited by their respective antagonists, albeit LY223982 and protamine were also weak inhibitors of CHP and LTB4, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Two-site assay of intact parathyroid hormone in primary hyperparathyroidism: studies in basal conditions, following adenoma removal and during calcium and EDTA infusion.
This study has been carried out in order to investigate parathyroid hormone secretion in patients with primary hyperparathyroidism in basal conditions, during stimulation and suppression tests and following successful surgery. Parathyroid gland secretory activity has been evaluated by a highly sensitive immunoradiometric assay (IRMA) which detects only the biologically intact active hormone and with a well established midmolecule (MM) PTH RIA. There was a good correlation between the two assays in basal state (r = 0.779); however the correlation found between serum PTH levels and total calcium values was better for the intact hormone (P less than 0.001) than for the radioimmunoassay (P less than 0.05). Twenty-four hours following surgery, serum intact PTH levels were in all patients less than 10 pg/ml while midmolecule PTH was still detectable, thereafter remaining at a higher level during the next six days. Serum IRMA PTH levels fell rapidly in response to the increase in serum calcium, then there was a trend to reach a plateau; serum midregion PTH levels fell, although slower than those of intact hormone. The percent increase obtained for serum intact hormone levels was higher than that observed for MM RIA, following EDTA stimulation. The results obtained indicate that the assays of intact and midmolecule parathyroid hormone clearly reflect different aspects of hormone metabolism 'in vivo' and may prove therefore to be useful for its investigation in various calcium disorders.


Purification and characterization of a non-kallikrein arginine esterase from dog urine.
A non-kallikrein arginine esterase (esterase I) has been purified from dog urine and characterized. The enzyme was purified by a three-step procedure, including ion exchange chromatography on DEAE-Sephacel, affinity chromatography on p-aminobenzamidine-Sepharose, and final gel filtration on Ultrogel AcA-54. The purified preparation gave three protein bands on polyacrylamide gel electrophoresis, all of which had esterolytic activity. The enzyme has a specific activity of 601 esterase units/mg protein. It has negligible kininogenase activity. Esterase I gave two closely migrating protein bands on reduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis with molecular weights of 34,000 and 33,300. Esterase I is a glycoprotein with a pH optimum of 9.5 and a pI of 4.62. The enzyme is strongly inhibited by a host of inhibitors including aprotinin, leupeptin, antipain, soybean trypsin inhibitor, lima bean trypsin inhibitor, and DPhe-Phe-Arg-chloromethyl ketone (I50 in the 10(-9)-10(-8) M range). However, p-aminobenzamidine, N alpha-p-tosyl-lysyl chloromethyl ketone and phenylmethylsulfonyl fluoride were weak inhibitors, with I50 values in the 10(-5)-10(-7) M range. The enzyme preferentially hydrolyzes Pro-Arg bonds. Among fluorogenic substrates used in this study, butyloxycarbonyl-Val-Pro-Arg-methylcoumarinamide (alpha-thrombin substrate) was found to be the best, with a Km of 1.7 microM and a kcat/Km of 6.3 s.microM-1. However, esterase I does not convert fibrinogen to fibrin nor activate plasminogen to plasmin. Esterase I is immunologically distinct from dog urinary kallikrein, having no cross-reactivity with antibodies against dog kallikrein.


Retinal pigment epithelial cells produce PDGF-like proteins and secrete them into their media.
Human retinal pigment epithelial cells at confluence were used to condition serum-free Dulbecco's modified Eagle's medium. Conditioned media were exhaustively dialyzed against 0.5 N acetic acid, lyophilized, and subjected to Western blot analysis, using as primary antibody an IgG fraction prepared from goat antiserum directed against human platelet-derived growth factor. Native platelet-derived growth factor was resolved as a band with Mr of 30 kDa under non-reducing conditions, while bands with Mr of 36-38 kDa and 18.5 kDa were resolved from retinal pigment epithelial cell-conditioned media. Acid extracts of retinal pigment epithelial cells also contained bands at 36-38 kDa and media conditioned for 48 hr exhibited much denser bands than media conditioned for 24 hr. No bands were detected when non-immune goat IgG fractions were substituted for primary antibody and when conditioned media were prepared from several human fibroblast lines in the same manner as those prepared from retinal pigment epithelial cells, no detectable bands or only a faint shadow at 36 kDa were seen. Retinal pigment epithelial cell-conditioned media prepared in the presence of [35S]methionine were loaded on an anti-platelet-derived growth factor IgG affinity column, eluted, and subjected to SDS-polyacrylamide gel electrophoresis. Bands with Mr slightly less than 36 kDa and 18 kDa were visualized by autoradiography, demonstrating that the platelet-derived growth factor-like proteins in retinal pigment epithelial cell-conditioned media are newly synthesized. Two fractions eluted from the column also markedly stimulated fibroblast chemotaxis and incorporation of [3H]thymidine, both of which were neutralized by soluble anti-platelet-derived growth factor IgG. These data suggest that retinal pigment epithelial cells in culture produce platelet-derived growth factor-like proteins and secrete them into their media where they are capable of stimulating fibroblast chemotaxis and proliferation.


Efficacy and Safety of Bevacizumab Combined with Other Therapeutic Regimens for Treatment of Recurrent Glioblastoma: A Network Meta-analysis.
Despite the fact that bevacizumab (Bev) has been approved to treat recurrent glioblastoma, patients have failed to demonstrate a significant overall survival (OS) advantage. In recent years, the advent of more Bev combination regimens seems to bring new hope for patients; nevertheless, there is still a lack of intuitive comparison among these therapies. To explore the efficacy and safety of various Bev combination regimens in patients with recurrent glioblastoma and to further explore the differences in the efficacy of each treatment in randomized controlled trials (RCTs) and nonrandomized controlled trials (non-RCTs). We comprehensively searched the PubMed, Cochrane Library, and OVID databases for relevant RCTs and non-RCTs of Bev in combined regimens for recurrent glioblastoma. The Cochrane quality assessment method was used to assess the quality of RCTs, and the Newcastle-Ottawa scale was used to assess the quality of non-RCTs. Excel software was used to extract data from the literature, and a network meta-analysis was performed using RevMan 5.3 and Stata 16 statistical software. In patients with recurrent glioblastoma, the 6-month OS of patients receiving bevacizumab combination therapy was ranked from high to low as follows: Bev + rindopepimut, Bev + lomustine (CCNU), CCNU, tumor treating fields + Bev, Bev, Bev + irinotecan (Iri), Bev + temozolomide (TMZ), Bev + vorinostat, Bev + onartuzumab, Bev + dasatinib, Bev + carboplatin, Bev + trebananib, Bev + VB-111, TMZ, PCV, VB-111, and carboplatin. The 6-month progression-free survival from high to low was ranked as follows: Bev + CCNU, Bev + rindopepimut, Bev + dasatinib, Bev + vorinostat, Bev, Bev + Iri, Bev + TMZ, CCNU, Bev + carboplatin, TMZ, Bev + VB-111, PCV, Bev + trebananib, carboplatin, and VB-111. We compared the total incidence of serious adverse events (≥3) and found that Bev + vorinostat and Bev + trebananib were safer than Bev, while other regimens were not as safe as Bev. A descriptive analysis showed that Bev + rindopepimut also appeared to be safer than Bev. In subgroup analysis, among RCTs, Bev + CCNU therapy had the highest 6-month OS and 6-month progression-free survival. Among non-RCTs, Bev + Iri therapy showed the highest 6-month OS and good 6-month progression-free survival. Both Bev + CCNU and Bev + rindopepimut could be considered as effective therapies for treating the recurrent glioblastoma according to the network meta-analysis results. Among them, Bev + rindopepimut therapy seems to be safer and more effective. Moreover, we found that Bev + Iri also appeared to be an effective therapy in a retrospective study.


Mitochondrial dynamics and division in budding yeast.
Mitochondria adopt a variety of different shapes in eukaryotic cells, ranging from multiple, small compartments to elaborate tubular networks. The establishment and maintenance of different mitochondrial morphologies depends, in part, on the equilibrium between opposing fission and fusion events. Recent studies in yeast, flies, worms and mammalian cells indicate that three high-molecular-weight GTPases control mitochondrial membrane dynamics. One of these is a dynamin-related GTPase that acts on the outer mitochondrial membrane to regulate fission. Recently, genetic approaches in budding yeast have identified additional components of the fission machinery. These and other new findings suggest a common mechanism for membrane fission events that has been conserved and adapted during eukaryotic evolution.


Spectral localization of arbitrarily shaped regions of interest (SLASH) using single voxel signals.
A method for obtaining localized spectra from arbitrarily shaped regions of interest is described. When a sample consists of homogeneous compartments or domains, spectra localized in each compartment can be obtained from signals of single voxels with regular shapes by solving a set of simultaneous linear equations. Experimental demonstrations on a phantom and on human brain in vivo for a two compartment, two voxel case are presented. The issue of signal-to-noise ratio is also discussed.


Fragile X Syndrome Secondary to in Vitro Fertilization With a Family Egg Donor: A Case Report and Review of the Literature.
Objective: To evidence the need for screening fragile X syndrome (FXS) in egg donors in assisted reproduction protocols. Case report : This is the report of a boy with FXS who inherited the mutated allele from an ovule donated by the mother´s sister through an assisted reproduction protocol. Identifying premutation (PM) carriers of FXS amongst gamete donors isn't part of the obligatory genetic analysis for donors and is only considered by most of the in vitro fertility societies and guidelines as part of the extension screening tests. Conclusion: It is cost-effective to do pre-conceptional screening for the PM or full mutation (FM) of the FMR1 gene affected in FXS in every woman undergoing assisted reproductive methods, including gamete donors even without a positive family history of intellectual disabilities. This case supports the need of rethinking the guidelines on the necessary gamete donor screening tests in assisted reproduction protocols.


Solid-phase immunoassay of PO glycoprotein of peripheral nerve myelin.
To explore the immunological properties of PO protein, antibodies were elicited in rabbits against the purified chick PO protein. Peripheral nervous system protein was fractionated on sodium dodecyl sulfate-polyacrylamide slab gels and then transferred electrophoretically ("blotted") onto nitrocellulose sheets. The PO protein was detected by its capacity to bind its specific antibody present in the rabbit serum. The PO-specific antibody complex was then exposed to goat anti-rabbit immunoglobulin G (IgG) coupled to peroxidase or labeled with 125I. The resulting PO antigen-antibody "sandwich" was visualized and quantitated by densitometry of the colored peroxidase reaction product or by autoradiography and gamma-radiation counting of the 125I-IgG complex. The methods permitted quantitation of the PO protein in various nerve extracts. The limit of detection of the PO antigen was about 1 ng of protein. The antibody was specific for the PO glycoprotein in the peripheral nerve extracts. The PO proteins from various species, including human, were also detected by the antibody to chick PO protein. Preliminary experiments indicate the solid-phase immunoassay is a useful method for monitoring PO protein levels in small quantities of tissue extracts under various physiological and pathological conditions.


Disseminated cat-scratch disease in an adult with selective IgA deficiency.
A 51-year-old man with history of undiagnosed pulmonary nodules 4 years prior, presented with right-sided chest pain. Acute cardiac workup was negative, and a chest computed tomography examination demonstrated marked improvement in bilateral pulmonary nodules. A concordant abdominal computed tomography examination showed new subcentimeter hypodense lesions throughout the liver and spleen, mild progressive abdominopelvic lymphadenopathy, and new small lytic lesions of T11 and L4 vertebrae. A positron emission tomography examination demonstrated hypermetabolic activity of these abdominopelvic lesions suggesting metastatic disease. Extensive laboratory workup was negative, aside from IgA deficiency. Eventually, biopsy of a hepatic lesion was performed and compatible with Bartonella species. An elevated Bartonella IgG titer was noted, consistent with Bartonella Hensalae infection, or "cat-scratch disease." Radiographic findings showed marked improvement after clinically appropriate antibiotic therapy.


Percutaneous grafting with bone marrow autologous concentrate for open tibia fractures: analysis of forty three cases and literature review.
Tibial fractures are the most common lower limb fractures. Some criteria such as open fractures and increasing open stage are known to be associated with high delayed union and pseudarthrosis rate. In cases of delayed or nonunion, classical treatment is autologous cancelous bone graft which is associated with high morbidity rate. The ideal treatment would be a percutaneous harvesting and grafting technique. As bone marrow autologous concentrate (BMAC) presents both advantages, we evaluated this technique from 2002 to 2007. This was a retrospective study of 43 cases of open tibial fractures with initial surgical treatment. The criteria of inclusion were open fracture and nonunion, delayed union or suspicion of delayed union. In 23 cases (53.5 %) BMAC was successful. The success group had received significantly more CFU-F than the failure group (469 vs 153.10(3), p = 0.013). A threshold of 360.10(3) CFU-F grafted could be established over which there was 100 % success. BMAC done before 110 days after fracture had 47 % success and BMAC done since 110 days after fracture had 73 % success. BMAC success rate decreased with increasing initial fracture skin open stage. There was no BMAC success in cases of a fracture with a remaining gap of more than 4 mm. We had no complications with the technique at the iliac harvesting zone and tibia injection point. BMAC is a technique that should be considered as one of the different alternatives for management of long-bone delayed and nonunion because of its effectiveness, low complication rate, preservation of bone stock and low cost.


Breast Radiology Advocacy: Responding to the Call-to-Action.
In an increasingly competitive and passionate health care environment, radiology advocacy is imperative, now more than ever. Arguably, it is particularly more crucial in the world of breast cancer, as we as a breast cancer community are tirelessly assembling to advocate for our patients on a variety of levels, whether it is including but not limited to, breast cancer screening, diagnosis, and treatment, access-to-care, education, or research funding. As breast radiologists, it is no longer simply enough to clock in our normal work hours; we must ALL make a concerted effort to vociferously advocate for our patients and profession.


Compliance and diameter in the human abdominal aorta--the influence of age and sex.
Females develop cardiovascular diseases and abdominal aortic aneurysms later in life than males. In this study we investigated the diameter and compliance of the distal abdominal aorta in healthy females of varying ages. The results were compared with those obtained previously from healthy males in order to assess potential sex-related differences in the aging process of the abdominal aorta. An ultrasound phase-locked echo-tracking system was used to determine differences in diameter and pulsatile diameter change of the distal abdominal aorta in 69 Caucasian females from 4 to 74 years. Pressure strain elastic modulus (Ep) and stiffness (beta) were calculated from diameter, pulsatile diameter change and blood pressure obtained by the auscultatory method. Compliance was defined as the inverse of Ep and beta. The pressure dependence of Ep and beta was evaluated in 10 females with intraarterial blood pressure measurement at rest and during isometric exercise. The diameter of the distal abdominal aorta increased not only in the period between the ages of 5 and 25 years, but also by about 24% between 25 and 70 years (p < 0.0001). From about the age of 25 years the diameter was smaller in females than in males (p < 0.01). Ep and beta increased nearly linearly with advancing age in females from 0.18 x 10(5) to 1.17 x 10(5) N/m2 (Ep) and from 1.85 to 8.51 (beta). In males the increase in Ep and beta was greater and exponential in nature (p < 0.001). Ep but not beta increased significantly during blood pressure increase (p < 0.05). Stiffness (beta) may therefore be a more useful index of arterial compliance than Ep. This investigation demonstrates age and sex-related differences in diameter and compliance in the normal human abdominal aorta and implies that degenerative changes appear later in females than in males.


Otto Neurath's Scientific Utopianism Revisited-A Refined Model for Utopias in Thought Experiments.
Otto Neurath's empiricist methodology of economics and his contributions to political economy have gained increasing attention in recent years. We connect this research with contemporary debates regarding the epistemological status of thought experiments by reconstructing Neurath's utopias as linchpins of thought experiments. In our three reconstructed examples of different uses of utopias/dystopias in thought experiments we employ a reformulation of Häggqvist's model for thought experiments and we argue that: (1) Our reformulation of Häggqvist's model more adequately complies with many uses of thought experiments, especially with the open-ended discussions of utopias and dystopias in thought experiments. (2) As a strict logical empiricist, Neurath is committed to a strictly empiricist account of thought experiments. John Norton's empiricist argument view can indeed account for the justifications of empirical beliefs and genuine discoveries targeted by scientific utopianism in three distinct (yet connected) ways, all of which Neurath already contemplated: (2.I) Dealing with utopias and thought experiments on a regular basis increases creativity and inventiveness. (2.II) Particular ways of presenting knowledge facilitate scientific discovery and social progress. (2.III) The use of utopias in thought experiments can prompt conceptual change and allow access to new phenomena. We conclude by highlighting that, even though thought experiments support a positive attitude for exploring new social possibilities, Neurath points out that active decisions are unavoidable. The exploration of alternatives and the awareness of a need for decisions in policy discussion avert a technocratic outlook in social science.


Imaging factors and image optimization.
Optimization of dose and image quality is task-dependent. The three main image quality parameters, sharpness, contrast, and noise, are interdependent in radiographic systems. The need to minimize patient dose imposes further couplings between these factors. This is the reason why there are no universally applicable imaging systems.


Association of TLR3-hyporesponsiveness and functional TLR3 L412F polymorphism with recurrent herpes labialis.
HSV-1 persistently infects almost 90% of our population; however, only 30% of the infected subjects suffer from recurrent herpes lesions, most frequently herpes labialis (HL). We hypothesized that variations in toll-like receptor (TLR) functions might contribute to HL susceptibility. In our study, the TLR-2/1,-3, and -7/8 responses of immune cell subsets derived from asymptomatic HSV-1 carriers were compared with responses of subjects with HL history. Remarkably, natural killer (NK) cells isolated from HL subjects showed significantly lower IFN-γ responses selectively to the TLR3 agonist poly(I:C). Furthermore, the TLR3 L412F genetic polymorphism was found to reduce NK cell TLR3-responsiveness and is associated with susceptibility to recurrent HL. The TLR3 response detected in HL total peripheral blood mononuclear cells (PBMCs), however, was not impaired, indicating restoration of NK cell TLR3-deficiency through co-stimulatory functions. In conclusion, our results suggest that decreased TLR3 response of NK cells is associated with HL susceptibility; and potentially explain why symptomatic outbreak of HL usually occurs after stress or prolonged UV light exposure, when host co-stimulatory functions are disturbed.


Brain amino acids during hyponatremia in vivo: clinical observations and experimental studies.
Hyponatremia is a highly morbid condition, present in a wide range of human pathologies, that exposes patients to encephalopathic complication and the risk of permanent brain damage and death. Treating hyponatremia has proved to be difficult and still awaits safe management, avoiding the morbid sequelae of demyelinizing and necrotic lesions associated with the use of hypertonic solutions. During acute and chronic hyponatremia in vivo, the brain extrudes the excessive water by decreasing its content of electrolytes and organic osmolytes. At the cellular level, a similar response occurs upon cell swelling. Among the organic osmolytes involved in both responses, free amino acids play a prominent role because of the large intracellular pools often found in nerve cells. An overview of the changes in brain amino acid content during hyponatremia in vivo is presented and the contribution of these changes to the adaptive cell responses involved in volume regulation discussed. Additionally, new data are provided concerning changes in amino acid levels in different regions of the central nervous system after chronic hyponatremia. Results favor the role of taurine, glutamine, glutamate, and aspartate as the main amino acid osmolytes involved in the brain adaptive response to hyponatremia in vivo. Deeper knowledge of the adaptive overall and cellular brain mechanisms activated during hyponatremia would lead to the design of safer therapies for the hyponatremic patient.


A game-theoretic approach for decision analysis in end-of-life vehicle reverse supply chain regarding government subsidy.
The presence of end-of-life vehicles (ELV) in the cities creates irreparable damage in environmental and economic terms. Thus, governments have been searching for ways to collect ELVs. An effective way to address ELVs is subsidies' policy. In this study, a supply chain including an ELV take-back center, an inspection center, and a repair center are considered. The decision variables are the purchase price of the ELVs, the sale price of the repaired vehicle, and the level of vehicle repair. In this supply chain, the government pays a subsidy to take-back centers that deliver their used vehicles. A Stackelberg game structure is considered with the government as the leader, the inspection center as the primary follower, and the collection and repair centers as the second followers. Using the game theory approach, the effects of government subsidies on equilibrium values of the decision-making variables of the centers in the ELV supply chain have been investigated in three scenarios. The scenarios comprise profit sharing, revenue sharing, and a centralized (cooperative) scenario. The results indicate that the centralized scenario has the most significant advantage compared to the two contracts of profit sharing and cost sharing. For example, the repair level of the ELVs, the amount of repaired vehicles demand, consumer surplus, and the whole supply chain's profit are at their maximum. The most significant impact of subsidy payment is related to the take-back center's profit and the ELV supply. On the other hand, the subsidy does not affect the profit of the repair center.