Agonist-specific and sexual stage-dependent inhibition of gonadotropin-releasing hormone-stimulated gonadotropin and growth hormone release by ryanodine: relationship to sexual stage-dependent caffeine-sensitive hormone release.
Differential utilization of intracellular Ca2+ stores with specific functional characteristics could be a potential mechanism for coupling various stimuli to specific cellular responses. In the goldfish pituitary, both gonadotropes and somatotropes possess multiple intracellular Ca2+ stores that are differentially coupled to agonist-evoked exocytosis. We investigated the role of ryanodine receptor/Ca2+-release channels (RyR) in basal and gonadotropin-releasing hormone (GnRH)-evoked hormone secretion from cultured gonadotropes and somatotropes using radioimmunoassay for gonadotropin (GTH-II) and growth hormone (GH). As is the case in vivo, the basal and evoked secretion of both hormones varied with seasonal reproductive status. GnRH-stimulated hormone release was three-fold higher in cells from sexually mature animals compared to those in a sexually regressed state. Nanomolar doses of ryanodine evoked significant GTH-II and GH secretion, suggesting that ryanodine-sensitive Ca2+ stores can couple to exocytosis in both cell types. In gonadotropes, 10 microM ryanodine abolished cGnRH-II-evoked GTH-II release in both sexually mature and sexually regressed fish, while sGnRH signalling was mediated by ryanodine-sensitive Ca2+ stores in cells from sexually regressed fish only. Ryanodine-sensitive Ca2+ stores in somatotropes were only involved in cGnRH-II-stimulated GH release during gonadal regression. In contrast, sGnRH-stimulated, but not cGnRH-II-stimulated, GH release was significantly reduced by 1 microM xestospongin C. Although hormone release stimulated by mobilizing caffeine-sensitive Ca2+ pools was also markedly seasonal, it was largely independent of ryanodine-sensitive Ca2+ stores. Ryanodine-sensitive Ca2+ stores in both cell types are not active downstream of ionomycin, BayK 8644, protein kinase C or cyclic adenosine monophosphate signalling pathways, suggesting difference from a classical Ca2+-induced Ca2+ release system. Ours study is the first to suggest that RyR2 may be involved in the seasonal plasticity of pituitary function, which may be related to cyclic changes observed in reproduction and growth.


Inclusion, exclusion: Comparative public policy (France/USA) in access to assisted reproductive technology.
This article examines what French and American societies mean by the principle of personal autonomy/'right to privacy' and the concept of solidarity/'the best interest of the society at large'. It will attempt to show how these two countries translate these concepts into different public policies, more specifically in the field of access to sexual and reproductive rights of women and men. In order to better highlight these differences, I observe what citizens actually experience on the ground, and in so doing, it becomes clear that each country does not fully meet the principles they purport to defend.


In Vitro Induction of Interspecific Hybrid and Polyploidy Derived from Oryza officinalis Wall.
Oryza officinalis Wall is a potential genetic resource for rice breeding; however, its distant genome limits its crossing ability with cultivated rice. The interspecific hybridization of O. officinalis and cultivated rice, establishment of its tissue culture, and induction of polyploidy are ways to improve O. officinalis's poor crossability. We developed an interspecific hybrid and studied its reproductive pollen development process in this work, and the results showed that abortive pollens (81.94%) and embryo sac abnormalities (91.04%) were the key causes of its high sterility. In order to induce callus formation in interspecific hybrid explants, two different culture media, namely Chu's N-6 medium (N6) and 1/2 Murashig and Skoog medium (1/2 MS), were employed. Additionally, two plant growth regulators (PGRs), namely 2,4-dichlorophenoxyacetic acid (2,4-D) and 6-benzylaminopurine (BA), along with L-proline (Pro) and acid hydrolyzed casein, were utilized in the experiment. The optimal N6 medium, supplemented with 2.0 mg·L-1 2,4-D, produced the highest induction rate (80.56 ± 5.44)%. For callus differentiation and proliferation, the MS medium supplemented with 2.0 mg·L-1 BA + 0.2 mg·L-1 NAA produced the highest differentiation rate (75.00 ± 4.97)% and seedling emergence ratio (28.97 ± 4.67)%. The optimal combination for seedling rooting was the 1/2 MS medium supplemented with 2.0 mg L-1 NAA and 0.2 mg L-1 BA, which produced an average of 13.95 roots per plant. For polyploidy induction in the interspecific hybrid, the concentration of colchicine treatment at 400 mg·L-1 for three days is an ideal protocol. We devised tissue culture and interspecific hybrid polyploidy induction to overcome O. officinalis' poor crossability and introduce its favorable features into cultivated rice.


Effect of pregnancy on plasma renin activity and glomerular synthesis of prostaglandins and thromboxane in rats.
Normal pregnancy in women and rats is characterized by an increased glomerular filtration rate. Because prostaglandin glomerular synthesis has been reported to be increased in 2 other circumstances with glomerular hyperfiltration (streptozotocin-induced diabetes and high protein dietary intake in Heymann nephrilis), we studied prostaglandin biosynthesis in glomeruli obtained from pregnant Wistar rats in comparison with non pregnant rats during the estrus cycle. Comparatively to the 3 first phases of the cycle, and wether or not arachidonic acid was present, PGE2 and PGF2 alpha production rates were found significantly higher in diestrus 2 (2-3 fold increase for both) at 15 days of pregnancy (2 fold increase for PGE2, 5-6 fold increase for PGF2 alpha) and at 21 days of pregnancy (5-6 fold increase for both). On the other hand synthesis of TXB2 was not increased during pregnancy nor during diestrus 2. Plasma renin activity (PRA) was increased during pregnancy. It is concluded that in presence of increased PRA, the increased synthesis of PGE2 may be the hormonal factor explaining, at least in part, the hemodynamic mechanism of glomerular hyperfiltration which has been previously described by micropuncture techniques and characterized by increased renal plasma flow, increased glomerular filtration pressure and decreased ultrafiltration coefficient.


Evaluation of certain immunological parameters in the course of autovaccine treatment in patients with chronic ostitis and carbunculosis.
Certain parameters of humoral and cellular immunity were observed in patients with staphylococcal chronic ostitis and carbunculosis treated with autovaccines. It was found out, that due to the application of autovaccine, the immunological indices displayed elevation or normalization as compared with the controls.


Craniofacial Trauma Is Associated With Significant Psychosocial Morbidity 1 Year Post-Injury.
The face and head play critical roles in one's sense of self and body image; as such, facial, head, and scalp injuries and potential associated disfigurement can lead to particular difficulties in coping. This study examined the psychosocial outcomes of patients with craniofacial (CF) trauma 1 year after injury and compared these outcomes with those of other traumatically injured patients who did not sustain such injuries. It was hypothesized that participants in the CF injury group would have worse outcomes than those without CF trauma. This prospective longitudinal study included patients at least 18 years of age admitted to the trauma service of a level I trauma center for at least 24 hours. Demographic and injury-related variables were collected. CF injury was determined by International Classification of Diseases, Ninth Revision codes. Outcomes were measured at baseline and at 12 months and included depression, post-traumatic stress disorder (PTSD), alcohol use, and pain severity. Paired t tests and logistic regression were used for analysis. Fifteen percent (n = 35) of the study sample (N = 230) had CF injuries. Those with CF injuries had lower income, higher injury severity, and higher intensive care unit admission rates. The CF and non-CF trauma groups did not differ in rates of depression or PTSD at either time point. However, participants with CF trauma had higher odds of risky alcohol use than those without CF trauma at baseline and lower odds of a higher pain severity score at baseline and 12 months. The groups did not differ in depression and PTSD. However, rates of depression, PTSD, alcohol use, and physical pain were higher than expected for the 2 groups. Given the high rate of psychological morbidity found after CF trauma, patients with these injuries should be screened for symptoms soon after injury and provided with resources for treatment.


Use of the beta-binomial distribution in dominant-lethal testing for "weak mutagenic activity: part 2.
Experiments in Dominant-Lethal Testing have been simulated on the computer to estimate the type I error rates and the power of the Beta-Binomial test under various models. (1) The mating ratio is one; and p, the probability that an implant will die, is distributed over the couples. (2) The mating ratio is larger than one; and p is distributed over the males, the females mated to the same male being binomial observations of the value p supplied by the male. (3) The mating ratio is larger than one; and p is distributed over the females. The average rates of dead implants have been set at 0.08 and 0.10 for the control and treatment groups, respectively, and a nominal level of significance equal to 0.05 has been chosen. The type I error rate of the traditional chi-square test has also been estimated. A by-product of these simulations is the behaviour of the estimates alpha and beta of the beta-distribution parameters, which discloses that, in the actual experiments with mice, p is distributed over the females. Our results lead to the recommendations that, for a given number of animals per group, a mating ratio larger than one should be adopted and that the males should be considered as the experimental units for the calculations. With 300 and 450 animals per group, average powers of 0.72 and 0.85 are reached, respectively, for the chosen increment of 2% in the rate of dead implants. Under these models, the type I error rate of the traditional chi-square test may grow to 0.30 for the nominal level of 0.05.


Early-onset and robust cerebral microvascular accumulation of amyloid beta-protein in transgenic mice expressing low levels of a vasculotropic Dutch/Iowa mutant form of amyloid beta-protein precursor.
Cerebrovascular deposition of amyloid beta-protein (Abeta) is a common pathological feature of Alzheimer's disease and related disorders. In particular, the Dutch E22Q and Iowa D23N mutations in Abeta cause familial cerebrovascular amyloidosis with abundant diffuse amyloid plaque deposits. Both of these charge-altering mutations enhance the fibrillogenic and pathogenic properties of Abeta in vitro. Here, we describe the generation of several transgenic mouse lines (Tg-SwDI) expressing human neuronal Abeta precursor protein (AbetaPP) harboring the Swedish K670N/M671L and vasculotropic Dutch/Iowa E693Q/D694N mutations under the control of the mouse Thy1.2 promoter. Tg-SwDI mice expressed transgenic human AbetaPP only in the brain, but at levels below those of endogenous mouse AbetaPP. Despite the paucity of human AbetaPP expression, quantitative enzyme-linked immunosorbent assay measurements revealed that Tg-SwDI mice developed early-onset and robust accumulation of Abeta in the brain with high association with isolated cerebral microvessels. Tg-SwDI mice exhibited striking perivascular/vascular Abeta deposits that markedly increased with age. The vascular Abeta accumulations were fibrillar, exhibiting strong thioflavin S staining, and occasionally presented signs of microhemorrhage. In addition, numerous largely diffuse, plaque-like structures were observed starting at 3 months of age. In vivo transport studies demonstrated that Dutch/Iowa mutant Abeta was more readily retained in the brain compared with wild-type Abeta. These results with Tg-SwDI mice demonstrate that overexpression of human AbetaPP is not required for early-onset and robust accumulation of both vascular and parenchymal Abeta in mouse brain.


MXene@Hydrogel composite nanofibers with the photo-stimulus response and optical monitoring functions for on-demand drug release.
The photo-stimulus response has the advantage of non-invasiveness, which could be used to control the "on" and "off" of drug release achieving on-demand release. Herein, we design a heating electrospray during electrospinning to prepare photo-stimulus response composite nanofibers consisting of MXene@Hydrogel. This heating electrospray enables to spray MXene@Hydrogel during the electrospinning process, and the hydrogel is uniformly distributed which cannot be achieved by the traditional soaking method. In addition, this heating electrospray can also overcome the difficulty that hydrogels are hard to be uniformly distributed in the inner fiber membrane.The "on" and "off" state of drug release could be controlled by light. Not only near infrared (NIR) light but also sunlight could trigger the drug release, which could benefit outdoor use when cannot find NIR light. Evidence by hydrogen bond has been formed between MXene and Hydrogel, the mechanical property of MXene@Hydrogel composite nanofibers is significantly enhanced, which is conducive to the application of human joints and other parts that need to move. These nanofibers also possess fluorescence property, which is further used to real-time monitor the in-vivo drug release. No matter the fast or slow release, this nanofiber can achieve sensitive detection, which is superior to the current absorbance spectrum method.


[The experience of realization of health resort rehabilitation programs for children under conditions of "The Central military health resort for children"].
Health resort treatment is one of the stages of rehabilitation for children. The Central Military health resort for children is a dynamic diversified health resort for the treatment of children and adults, using its arsenal all available, at the resort natural factors. In the conditions of sanatorium for the treatment of children apply advanced medical technologies, the development of modern medical equipment.


Androgen receptor expression in breast cancer: relationship with clinicopathological factors and biomarkers.
Breast cancer is a hormone-dependent tumor. Most breast cancer cells have an androgen receptor (AR), but the clinical value of AR expression is unclear. AR expression was evaluated in 227 primary breast cancers using immunohistochemistry. The relation of AR expression to clinicopathological factors and biomarkers was analyzed. AR expression was assessed semiquantitatively, and tumors with more than 10% of stained cells were regarded as positive. The AR-positive rate was higher in smaller tumors (P=0.045), tumors with negative lymph node metastasis (P=0.045), scirrhous-type tumors (P<0.0001), tumors of low histological grade (P=0.0001), and p53-negative tumors (P = 0.0097). Although AR had no relation to menopausal status, 79% of cases of high AR expression (>50% stained cells) were in postmenopausal women. AR was related to estrogen receptor (ER; P=0.027) and progesterone receptor (PR; P=0.016) expression, but showed no relation to human epidermal growth factor receptor type 2 (Her2) expression. Regarding the coexpression of these receptors, 18 of the 42 cases of triple-negative (ER/PR/Her2-negative) tumors (43%) were AR-positive. AR expression is related to low malignancy in breast cancer. The assessment of AR expression may lead to new treatment strategies for breast cancer, especially in postmenopausal women and in women with tumors that show triple negativity for hormone receptors.


Systemic lupus erythematosus in hereditary deficiency of the fourth component of complement.
Three patients from two families with complete hereditary deficiency of the fourth component of complement (C4) and systemic lupus erythematosus are described. The syndrome presented by these patients is characterized by early onset in life; exquisite sensitivity to sunlight and to cold exposure, the latter resulting Raynaud's phenomenon; and skin lesions involving not only exposed areas of the body but also palms and soles and presenting as butterfly rashes, maculopapular eruptions, and lesions similar to those of chronic discoid lupus erythematosus, with marked scaling, atrophy, and scarring. Lupus erythematosus (LE) cell tests were negative and antinuclear antibody (ANA) titers low or negative. The male patient of our series died at the age of 31/2 years from septicemia, whereas the two girls, aged 18 and 11 years, respectively, were alive at the time of writing. The C4-deficient gene is associated with HLA-Aw32, Bw38, and Bf S in one family and with HLA-A30, B18, DR7, and Bf S1 in the other family; the latter is the second family in which this HLA haplotype has been found to be associated with hereditary C4 deficiency.


Perineural invasion in aggressive skin carcinomas of the head and neck. Potentially dangerous but frequently overlooked.
Perineural invasion is a well-recognized form of cancer dissemination. However, it has been reported only in few papers concerning cutaneous carcinomas (basal cell, BCC, and squamous cell, SCC). Moreover, the incidence is considered to be very low. Niazi and Lambert [Br J Plast Surg 1993;46:156-157] reported only 0.18% of perineural invasion among 3,355 BCCs. It is associated with high-risk subtypes, as morphea-like, as well as with an increased risk of local recurrence. No paper was found in the literature looking for perineural invasion in very aggressive skin cancers with skull base extension, with immunohistochemical analysis. This is a retrospective review, including 35 very advanced skin carcinomas with skull base invasion (24 BCCs and 11 SCCs, operated on at a single institution from 1982 to 2000). Representative slides were immunohistochemically evaluated with antiprotein S-100, in order to enhance nerve fibers and to detect perineural invasion. The results were compared to 34 controls with tumors with a good outcome, treated in the same time frame at the same Institution. Twelve (50.0%) of the BCCs with skull base invasion had proven perineural invasion, as opposed to only 1 (4.6%) of the controls, and this difference was statistically significant (p < 0.001). Regarding SCCs, 7 aggressive tumors (63.6%) showed perineural invasion compared to only 1 (10.0%) of the controls, but this difference did not reach significance (p = 0.08), due to the small number of cases. In this series, it was demonstrated that immunohistochemically detected perineural invasion was very prevalent in advanced skin carcinomas. In addition, it was statistically associated with extremely aggressive BCCs with skull base invasion.


Radiographic predictors determined with an objective assessment tool for neonatal patients with necrotizing enterocolitis.
The objective of this study was to develop and validate a computational tool to assist radiological decisions on necrotizing enterocolitis. Patients that exhibited clinical signs and radiographic evidence of Bell's stage 2 or higher were included in the study, resulting in 64 exams. The tool was used to classify localized bowel wall thickening and intestinal pneumatosis using full-width at half-maximum measurements and texture analyses based on wavelet energy decomposition. Radiological findings of suspicious bowel wall thickening and intestinal pneumatosis loops were confirmed by both patient surgery and histopathological analysis. Two experienced radiologists selected an involved bowel and a normal bowel in the same radiography. The full-width at half-maximum and wavelet-based texture feature were then calculated and compared using the Mann-Whitney U test. Specificity, sensibility, positive and negative predictive values were calculated. The full-width at half-maximum results were significantly different between normal and distended loops (median of 10.30 and 15.13, respectively). Horizontal, vertical, and diagonal wavelet energy measurements were evaluated at eight levels of decomposition. Levels 7 and 8 in the horizontal direction presented significant differences. For level 7, median was 0.034 and 0.088 for normal and intestinal pneumatosis groups, respectively, and for level 8 median was 0.19 and 0.34, respectively. The developed tool could detect differences in radiographic findings of bowel wall thickening and IP that are difficult to diagnose, demonstrating the its potential in clinical routine. The tool that was developed in the present study may help physicians to investigate suspicious bowel loops, thereby considerably improving diagnosis and clinical decisions.


A comparison of open-label and deceptive placebo analgesia in a healthy sample.
A small number of studies have supported the efficacy of open-label placebos (OLPs) in reducing pain. However, research comparing the effectiveness of OLPs with deceptive placebos (DPs) is limited, and the relative impact on pain tolerance versus intensity are not yet understood. This study therefore, examined the effectiveness of a nasal placebo administered openly and deceptively on pain intensity and tolerance during a cold pressor test (CPT). 75 healthy participants were allocated to one of three groups; OLP (n = 25), DP (n = 26) and no-treatment (NT; n = 24). A pre-test post-test design was used, with all participants completing a baseline and post-treatment CPT, following placebo administration in the treatment groups. A one-way ANCOVA revealed significant differences between groups for pain intensity, with planned contrasts revealing that this effect was driven by an increase in pain intensity scores for the NT group within the post treatment CPT, which was not evident in the OLP and DP groups. There were no significant differences between groups for changes in pain tolerance. The increase in pain intensity reported within the post-treatment CPT in the NT group was not apparent in either the OLP or DP groups, with no significant differences between OLP and DP effectiveness. These findings suggest that deception may not be necessary for effective placebo treatment and have implications for the management of pain.


Isolation of alveolar type II cells by centrifugal elutriation.
Centrifugal elutriation (counterflow centrifugation) was used to develop a reproducible method for obtaining a nearly pure population of isolated alveolar type II cells. Lung was dissociated into individual cells with recrystallized trypsin, and the type II cells were partially purified by centrifugation on a discontinuous density gradient. The alveolar type II cells were finally purified by centrifugal elutriation. Cells were collected from the elutriator rotor by stepwise increases in flow rates. Cells obtained at flow rates of 7 and 14 ml per min were lymphocytes, other small cells, a few type II cells and cell debris; cells collected at flow rates of 18 and 22 ml per min were mainly type II cells; and cells collected at flow rates of 28, 34 and 43 ml per min were macrophages, some type II cells, other lung cells and cell aggregates. At flow rates of 18 and 22 ml per min, 1.9 +/- 1.0 x 10(6) cells per rat lung (mean +/- S.D., n=30) were recovered of which 86 +/- 6% were type II cells. At these flow rates, 94% of the cells excluded the vital dye erythrosin B from their cytoplasm. They consumed oxygen at a rate of 101 +/- 21 nmol per hr . 10(6) cells (mean +/- S.D., n=4), and their oxygen consumption increased only 10% after 10 mM sodium succinate was added. The cells incorporated [14C]leucine into protein and lipid for 4 hr. Electron micrographs of the cells collected at flow rates of 18 and 22 ml per min show a high percentage of morphologically intact alveolar type II cells. We conclude that centrifugral elutriation is a reproducible method for obtaining nearly pure, metabolically active alveolar type II cells.


Protein heterogeneity in rat CNS myelin subfractions.
Microsomal fraction-free myelin from forebrain and spinal cord of young and mature rats, when subjected to hypo-osmotic shock and slow speed centrifugation, yielded a myelin pellet and a supernatant fraction (SN 4). Fraction SN 4 consisted of small vesicular profiles in which the major myelin proteins were reduced whereas high molecular weight material such as Wolfgram protein, myelin-associated glycoprotein and CNP were substantially increased over myelin. A close correlation of the SN 4 fraction to the myelin-like fraction of Davison and coworkers was suggested. The myelin pellets were subfractioned on zonal sucrose gradients to yield bell-shaped particle distributions. Besides shifts in densities of the maxima between myelin of young and mature forebrain and spinal cord, a decrease was observed from the light to the heavy gradient end in basic proteins, and an increase in Wolfgram protein and other high molecular weight proteins. Proteolipid protein took an intermediate position. Light fractions from adult spinal cord displayed CNP activities below those of the total homogenate. This result, together with the very high CNP activities in fraction SN 4 casts some doubt on CNP being a marker for compact myelin; rather it appears that CNP is a marker for the process of myelin formation.


Treatment of phenolic wastewater in UASB reactor: effect of nitrogen and phosphorous.
Phenolic wastewater representing an industrial wastewater was supplemented with varying amount of nitrogen (N) and phosphorous (P) and treated in upflow anaerobic sludge blanket reactor (UASBR). The variation of COD:N:P from 300:10:1 to 300:1:0.1, did not influence the conversion of phenol COD to methane COD. The concentration of N and P in the influent was reduced from 25.5mgl(-1) to 2.5mgl(-1) and 2.5 to 0.25mgl(-1), respectively. However, on further reducing the nutrients in the feed from 300:1:0.1 to 300:0:0 the (i) CH(4)-COD decreased from 90% to 40%, and (ii) cell yield reduced to 25-50%. The average cell yield was 3.5%. Percent N and P in cells varied from 10% to 14% and 0.6% to 2.4%, respectively. The activity of the sludge assessed as specific methanogenic activity (SMA) was found in the range from 0.15 to 0.66g CH4-CODg(-1) VSSd(-1). The optimum COD:N:P for phenolic wastewater has been estimated to be 300:1:0.1.


Job decision latitude, organizational justice and health: multilevel covariance structure analysis.
A total of 2969 hospital employees from 162 wards participated in a 2-year follow-up study that examined the relationship between job decision latitude, organizational justice and employee health in Finland. We used medically certified sickness absence records as indicators of health problems. Multilevel covariance structure analysis was applied to take into account the hierarchical nature of the data. Responses from individuals within work units seem not always to be independent, and any models that ignore this lack of independence may incorrectly estimate the between individual relationships. Our results suggest that both job decision latitude and organizational justice varied considerably between work units in addition to individual level variation. Furthermore job decision latitude was associated with organizational justice both at individual and work unit level. Justice evaluations predicted sickness absence only at the individual level.


A qualitative study on gender inequality and gender-based violence in Nepal.
Gender inequality and violence are not mutually exclusive phenomena but complex loops affecting each other. Women in Nepal face several inequalities and violence. The causes are diverse, but most of these results are due to socially assigned lower positioning of women. The hierarchies based on power make women face subordination and violence in Nepal. The study aims to explore participants' understanding and experience to identify the status of inequality for women and how violence emerges as one of its consequences. Furthermore, it explores the causes of sex trafficking as an example of an outcome of inequality and violence. The study formulated separate male and female groups using a purposive sampling method. The study used a multistage focus group discussion, where the same groups met at different intervals. Six focus group discussions, three times each with male and female groups, were conducted in a year. Thirty-six individuals, including sixteen males and twenty females, were involved in the discussions. The study used constructivist grounded theory for the data analysis. The study participants identify that a power play between men and women reinforce inequality and increases the likelihood of violence for women. The findings suggest that the subjugation of women occurs due to practices based on gender differences, constricted life opportunities, and internalization of constructed differences among women. The study identifies that interpersonal and socio-cultural violence can result due to established differences between men and women. Sex trafficking, as an example of the outcome of inequality and violence, occurs due to the disadvantageous position of women compounded by poverty and illiteracy. The study has developed a concept of power-play which is identified as a cause and consequence of women's subordination and violence. This power play is found operative at various levels with social approval for men to use violence and maintain/produce inequality. The theoretical concept of power play shows that there are inequitable power relations between men and women. The male-centric socio-cultural norms and practices have endowed men with privilege, power, and an opportunity to exploit women. This lowers the status of women and the power-play help to produce and sustain inequality. The power-play exposes women to violence and manifests itself as one of the worst expressions used by men.


Effects of stellate ganglion block on cerebral haemodynamics as assessed by transcranial Doppler ultrasonography.
Stellate ganglion block (SGB) causes vasodilatation in the skin of the head and neck because of regional sympathetic block. Its effects on cerebral haemodynamics, in health or in disease, are not clear. We evaluated the effects of SGB on ipsilateral middle cerebral artery flow velocity (MCAFV), estimated cerebral perfusion pressure (eCPP), zero flow pressure (ZFP), carbon dioxide reactivity (CO2R) and cerebral autoregulation using transcranial Doppler ultrasonography (TCD). Twenty male patients, with pre-existing brachial plexus injury, and undergoing SGB for the treatment of complex regional pain syndrome of the upper limb, were studied. For SGB, 10 ml of plain lidocaine 2% was used and the onset of block was confirmed by presence of ipsilateral Horner's syndrome. The MCAFV, eCPP, ZFP, CO2R, and cerebral autoregulation were assessed before and after SGB using established TCD methods. The changes in these variables were analysed using Wilcoxon's signed rank test. The block caused a significant decrease in MCAFV from median (inter-quartile range) value of 61 (53, 67) to 55 (46, 60) cm s(-1), a significant increase in eCPP from 59 (51, 67) to 70 (60, 78) mm Hg, and a significant decrease in ZFP from 32 (26, 39) to 25 (16, 30) mm Hg. There were no significant changes in CO2R or cerebral autoregulation. The increase in eCPP, decrease in ZFP, and no changes in CO2R or cerebral autoregulation suggest that the SGB decreases cerebral vascular tone without affecting the capacity of the vessels to autoregulate. These effects may be of therapeutic advantage in relieving cerebral vasospasm in certain clinical settings.


Can dogs serve as stress mediators to decrease salivary cortisol levels in a population of liberal arts college undergraduate students?
The steroid hormone cortisol can be used to measure physiological stress in humans. The hypothalamic-pituitary-adrenal (HPA) axis synthesizes cortisol, and a negative feedback cycle regulates cortisol depending on an individual's stress level and/or circadian rhythm. Chronic stress of college undergraduate students is associated with various adverse health effects, including anxiety and depression. Reports suggest that stress levels have risen dramatically in recent years, particularly among university students dealing with intense academic loads in addition to COVID-19 pandemic-related uncertainty. The increasing rate of mental illness on college campuses necessitates the study of mediators potentially capable of lowering stress, and thus cortisol levels. Research on mediation techniques and coping mechanisms have gained traction to address the concerning levels of stress, including the employment of human-animal interaction sessions on college campuses. In this study, human-canine interaction as a stress mediation strategy for undergraduate students was investigated. We measured salivary cortisol levels in 73 college undergraduate students during a 60-min interaction period with a dog to determine whether human-canine interactions are effective in lowering cortisol levels and potentially reducing chronic stress typical of undergraduate students. Our results indicate that a human-canine interaction for 60 min is an effective method for significantly reducing salivary cortisol and stress levels among undergraduate college students. These findings support the expansion of animal visitation programs on college campuses to help students manage stress.


Characterisation of exposure to airborne fungi: measurement of ergosterol.
In order to gain a clearer understanding of the level of fungal air contamination in indoor environments, we have adapted and tested a method to evaluate fungal biomass. Liquid phase chromatography (HPLC) of ergosterol, a component of the cell membrane of microscopic fungi, was employed. This method permits the detection and identification of ergosterol molecules at a concentration of 40 microg/ml (n=33, sigma=5). By combining this assay with a rotating cup collection apparatus, it was possible to measure fungal flora levels with a limit of quantification of 0.4 ng/m3 or a theoretical value of 150 spores per cubic meter (m3). Measurements of ergosterol levels performed on different sites showed that this method reflected the different situations of exposure of occupants to airborne fungal flora.


[Cutaneous drug reactions imitating dermatoses].
Cutaneous adverse drug reactions are frequent and present with heterogenous clinical manifestations. Increasingly, case reports describe drug reactions which mimic dermatoses, although exact data on prevalence are missing. Psoriasiform, lichenoid and pityriasiform exanthems are most frequent. The differentiation of these variants from the respective authentic dermatoses is difficult and only a few clinical and histological criteria are helpful. Other dermatoses like lupus erythematosus or bullous autoimmune dermatoses (pemphigus vulgaris, bullous pemphigoid) can be induced by drugs as well. These drug-triggered variations are classified as distinct subclasses of the respective dermatosis. Exact history and evaluation of the clinical course are essential for the diagnosis of drug reactions mimicking dermatoses and present an important challenge for the clinician. A clear-cut differentiation between the genuine dermatosis and its drug-driven simulator is not always possible.


Intermediate filaments.
It is likely that future studies involving a molecular biology approach, similar to those described in [7,27,28], will yield fruitful information regarding properties and cellular roles of IF. At this point, our knowledge of the properties and expression of IF remains in stark contrast to our lack of understanding of their biological functions. As pointed out by Franke et al. [29], several lines of investigation have suggested that IF do not serve a general cellular function (i.e. 'housekeeping duties'). Instead, the roles of IF and their constituent proteins are probably related to specific functions of the differentiated cell. Our search for these specific roles will be difficult, but exciting. In the meantime, it is rewarding that IF typing of cells and tumors has already yielded practical information useful in histology and cytology [30].


Perceived stigma and associated factors among people with epilepsy at Gondar University Hospital, Northwest Ethiopia: a cross-sectional institution based study.
Epilepsy is the world's most common neurological disorder, affecting approximately 69 million people worldwide. Perceived stigma affects many domains of the lives of people with epilepsy. However, in Ethiopia there is dearth of study on perceived stigma specifically among people with epilepsy. To assess the prevalence of perceived stigma and associated factors among people with epilepsy (PWE) attending the outpatient department of the University of Gondar hospital, Northwest Ethiopia, 2014. Institution based quantitative cross - sectional study was employed among 408 individuals people with epilepsy. Single population proportion formula was used utilized to calculate sample size. The participants were selected using systematic random sampling technique. Perceived stigma was measured using by the modified Family Interview Schedule (FIS) tool. Binary logistic regression analysis and adjusted odds ratio with 95% confidence interval were used to identify the associated factors with perceived stigma.. Overall, the prevalence of perceived stigma was found to be 71.6%. Marital status [single (AOR = 0.23, CI: 0.25, 0.90), widowed ( AOR = 0.37, CI: 0.15, 0.90) duration of illness [2-5 years (AOR = 4.38, CI:1.98,9.62, 6-10 years (AOR =4.29, CI:1.90,9.64, ≥11 years (AOR = 4.31,CI:1.84,10.00) and seizure frequency of [1-11per year (AOR=2.34, CI:2.21,3.56), ≥1per month (AOR = 5.63, CI:3.42,10.32)] were factors associated with perceived stigma. Overall, the prevalence of perceived stigma was found to be high. Marital status, long duration of illness and seizure frequency were factors associated with perceived stigma.


Peroxynitrite production and activation of poly (adenosine diphosphate-ribose) synthetase in spinal cord injury.
Peroxynitrite formation and the subsequent activation of the nuclear enzyme, poly (adenosine diphosphate [ADP]-ribose) synthetase (PARS), has been implicated in the pathogenesis of several neurodegenerative disorders. Here, we demonstrate that nitrotyrosine, an indicator of peroxynitrite generation, and poly (ADP) ribose, a marker of PARS activation, were selectively localized within tissues from spinal cord-injured rats. Our data implicate a role for peroxynitrite production and PARS activation in the development of spinal cord trauma.


Improved version of a human CD2 minigene based vector for T cell-specific expression in transgenic mice.
A human CD2 minigene cassette has been used in the past to express several reporter genes in the T cell lineage of transgenic mice. However, in order to achieve appreciable levels of expression it has been necessary to integrate many copies of the transgene. In this report we describe an improved version of this cassette. The new cassette directs the expression of a reporter mouse CD8 alpha cDNA on all T cells of transgenic mice with an efficiency ten times higher than the previous cassette. The new cassette includes 5 kb 5' and 5.5 kb 3' flanking sequences containing, respectively, the promoter and locus control region (LCR) of the human CD2 gene. The LCR confers position independent, transgene copy number dependent expression of the genes linked to it in transgenic mice. The cassette also provides a transcription initiation site, the first intron of human CD2 gene and the two polyadenylation signals found in the 3' untranslated region of hCD2 gene.


2-[(3S)-5-Oxooxolan-3-yl]isoindoline-1,3-dione.
The oxolan-2-one ring in the title compound, C(12)H(9)NO(4), has an envelope conformation with the atom linking the two five-membered rings being the flap atom.


Prenatal exclusion of harlequin ichthyosis; potential pitfalls in the timing of the fetal skin biopsy.
Harlequin ichthyosis (HI) is a severe and usually fatal congenital skin disorder with autosomal recessive inheritance. Several cases of HI prenatal diagnosis have been performed using fetal skin biopsy, mainly at around 23 weeks estimated gestational age (EGA), and reported in the literature. However, prenatal testing must be done earlier than 21 weeks EGA in several countries including Japan where the present HI families live, because termination is legally allowed only until 22 weeks EGA. We report the successful prenatal exclusion of HI in two fetuses from two independent families and discuss the technical difficulties and potential pitfalls in the prenatal exclusion of HI at early gestation stages. Fetal skin biopsy specimens and amniotic fluid samples at 19 and 20 weeks EGA from two fetuses at risk of HI were examined by light and electron microscopy. For the prenatal diagnosis in case 1, the fetal skin biopsy samples were obtained at 20 weeks EGA and showed normal keratinization in the hair canals; no abnormalities were observed in the keratinized cells. In case 2, the interfollicular epidermis and the hair follicles in the samples obtained at 19 weeks EGA had not differentiated enough to show proper keratinization. However, lamellar granules were normally formed in the inner root sheath cells of the late bulbous hair pegs. From these ultrastructural findings, the case 1 fetus was diagnosed as unaffected with HI, and the case 2 fetus was diagnosed as unlikely to be affected. Subsequently, both were born as healthy, unaffected babies. The timing of biopsies at 19 weeks EGA is not ideal for fetal skin biopsy because the samples are not always sufficiently differentiated for the prenatal diagnosis of HI. However, morphological observations of lamellar granules gives us important additional information useful for HI prenatal diagnosis.


Correction of protein-energy malnutrition in older adults: effects of a short-term aerobic training program.
Twenty malnourished subjects (average age 67 years old) treated by cyclic enteral nutrition were assigned to an active or control group according to whether they took part or not in a 3-week aerobic training program. Subjects underwent the following tests on d(0)-d(1) and d(20)-d(21): calculation of a global nutritional deficiency index (GND), bioelectrical impedance analysis, evaluation of daily energy expenditures using a 24 h heart rate (HR) recorder and a pedometer, maximal voluntary isometric strength assessment (MVIS), and symptoms limited maximal oxygen uptake ((.)VO(2 max. SL) estimation. Although energy intakes were similar in both groups, active subjects showed greater improvements (P < 0.05) than control subjects regarding GND (-9.8 vs -4.8%), serum albumin and prealbumin. Active subjects also showed a greater increase (P < 0.05) in pedometer readings compared to control subjects. Reduction of resting HR was observed in active (-5 beat/mn, P < 0.05) whereas no significant changes in average HR were noted in either group, reflecting increased metabolic activity. Compared to control, active subjects showed significant (P < 0.05) improvements in MVIS (0.8 vs 0.1 N/kg) and (.)VO(2 max. SL) (5.5 vs 1.4 mL/min/kg). Short-term aerobic training has positive effects on nutritional recovery and functional capacities in elderly malnourished subjects and should be recommended whenever possible.


Phototoxicity of TiO₂ nanoparticles to a freshwater benthic amphipod: are benthic systems at risk?
This study investigated phototoxicity of TiO₂ nanoparticles (nano-TiO₂) to a freshwater benthic amphipod (Hyalella azteca) using 48-h and 96-h bioassays. Thorough monitoring of particle interactions with exposure media (Lake Superior water, LSW) and the surface of organisms was performed using dynamic light scattering, UV/Vis spectroscopy, and Scanning Electron Microscopy. Large agglomeration and sedimentation (>77%) in LSW was observed after 0.5h. A simulated solar radiation (SSR)-favored surface attachment of nanoparticles was observed, indicating enhanced phototoxicity with the increased attachment. A 96-h median lethal concentration (LC50) of 29.9 mg/L in H. azteca was calculated, with a daily 4-h UV exposure of 2.2 W/m(2). Phototoxicity of nano-TiO₂ under SSR had a 21-fold increase as compared to that under ambient laboratory light. This phototoxicity was also dependent on UV dose, with calculated LC50s around 22.9 (95% CI, 20.5-23.3)Wh/m(2) when exposed to 20 mg/L nano-TiO₂. Also, H. azteca exhibited negative phototaxis in the presence of shelters, indicating that other factors might play a role in environmental systems. Finally, the environmental implications of nano-TiO₂ to benthic organisms were illustrated, emphasizing the importance of various environmental factors in the ultimate phototoxicity. This increased phototoxicity and its complex interactions with various environmental factors suggest further investigations are needed for future risk assessment of photoactive nanomaterials to benthic organisms.


Expression and Characterization of a GH38 α-Mannosidase from the Hyperthermophile Pseudothermotoga thermarum.
This study focused on the bio-characterization of a GH38 α-mannosidase from the hyperthermophile Pseudothermotoga thermarum DSM 5069. We aimed to successfully express and characterize this thermophilic α-mannosidase and to assess its functional properties. Subsequently, recombinant α-mannosidase PtαMan was expressed in Escherichia coli BL21(DE3) and purified via affinity chromatography, and native protein was verified as a tetramer by size exclusion chromatography. In addition, the activity of α-mannosidase PtαMan was relatively stable at pH 5.0-6.5 and temperatures up to 75 ℃. α-Mannosidase PtαMan was active toward Co2+ and had a good catalytic efficiency deduced from the kinetic parameters. However, its activity was strongly inhibited by Cu2+, Zn2+, SDS, and swainsonine. In summary, this cobalt-required α-mannosidase is putatively involved in the direct modification of glycoproteins.


Chemical activators of protein phosphatase-1 induce calcium release inside intact cells.
Protein phosphatase-1 (PP1) is a major Ser/Thr phosphatase that is involved in numerous cellular processes. PP1-disrupting peptides (PDPs) are selective chemical tools used to study PP1. They generate catalytically active PP1 inside cells but do not bind to the closely related PP2A. Here, we show that PDPs also do not act directly on PP2B, thus demonstrating the selectivity of PDPs toward PP1. We present PDPs with different properties, enabling reversible versus permanent activation of PP1. We also show that Ca(2+) spiking is an acute effect caused by PDP-induced activation of PP1. The Ca(2+) is released from internal stores. Our data show that PDPs can be used as selective chemical genetics tools to study acute and long-term effects of PP1 activation in intact cells, and PDPs will therefore be valuable tools to study PP1 biology.


A meta-analysis synthesizing the effects of pesticides on swim speed and activity of aquatic vertebrates.
Pesticide contaminants are ubiquitous in aquatic environments and pose a threat to biodiversity. Pesticides also have diverse mechanisms of action that make it difficult to identify impacts on exposed wildlife. Behavioral measures represent an important link between physiological and ecological processes, and are often used to generalize sub-lethal effects of pesticide exposure. In order to bridge the toxicological and behavioral literature, and identify chemical classes that denote the largest threat, we conducted a meta-analysis summarizing the effects of pesticides on swim speed and activity of aquatic vertebrates. We found that exposure to environmentally relevant concentrations of pesticides reduced the swim speed of exposed amphibians and fish by 35%, and reduced overall activity by 72%. There were also differences in the magnitude of this effect across chemical classes, which likely reflect underlying physiological processes. Pyrethroids, carbamates, and organophosphates all produced a large decrease in swim speed, where as phosphonoglycines and triazines showed no overall effect. Pyrethroids, carbamates, organophosphates, organochlorines, and organotins also produced a large decrease in activity, while phosphonoglycines had no overall effect, and triazines had the opposite effect of increasing activity. Our results indicate that even sub-lethal concentrations of pesticides have a strong effect on critical behaviors of aquatic vertebrates, which can affect fitness and alter species interactions. We expect our synthesis can be used to identify chemical classes producing the largest sub-lethal effects for further research and management.


Environment, glucocorticoids, and the timing of reproduction.
Glucocorticoids mediate glucose availability under stressful and non-stressful conditions and, therefore, are essential for life. However, data across taxa demonstrate that chronic or elevated secretion of corticosterone or cortisol (CORT) can have negative effects at many levels and can trigger physiological or behavioral responses that may delay or, even halt reproduction. We present a brief overview of the effects that glucocorticoids, primarily the avian form, corticosterone, can have on the reproductive axis. Considerable data have demonstrated that environmental perturbations can result in elevated CORT levels that alter a bird's investment in current reproduction. Studies in our laboratory have shown a link between CORT and timing of reproduction in Florida scrub-jays: in "bad" years, clutch initiation dates are positively correlated with baseline CORT levels of female breeders. Also, population-level differences in CORT levels may explain timing of reproduction as lower CORT levels in suburban-dwelling jays are coupled with early breeding. Most research on stress and CORT concentrates on transient effects of CORT secretion. However, developmental CORT exposure, either from the yolk or embryo, may have long-term effects upon adult phenotype. For example, CORT levels in nestling scrub-jays predicts later 'personality,' as levels were highly correlated (r(2)=0.84) with fearfulness at 7 months of age. One can imagine that such 'personality' traits might also translate into differential success in gaining a territory or a mate. While speculative, it may be that early CORT exposure effectively programs adult behaviors that have wide ranging effects, including upon reproduction.


Ultrastructure of cardiac muscle of Trochosa terricola Thor., Pardosa amentata Clerck, P. pullata Clerck, and Pisaura mirabilis Clerck (Araneae: Lycosidae, Pisauridae).
The ultrastructure of the cardiac muscle in some araneae has been investigated. The sarcolemma invaginates at the Z band and may extend into the cells through several myofibrils. Numerous T-tubules are given off both from sarcolemmal invaginations and also directly from the cell surface. In passing through the Z band, the luminal diameter of T-tubules greatly increases. Dyadic and a few triadic couplings are found mainly at the A-I level. Peripheral couplings were not seen.


The effect of a novel immunosuppressant, FTY720, in mice without secondary lymphoid organs.
FTY720 is a novel immunosuppressive agent that is thought to reduce the number of peripheral blood lymphocytes (PBL) by directing them toward secondary lymphoid organs such as the lymph nodes and Peyer's patches. We studied the effects of FTY720 on aly/aly mice that do not have either lymph nodes or Peyer's patches, as well as on splenectomized aly/aly mice. FTY720 was orally administered by gavage (1 mg/kg) to aly/aly mice as well as to aly/+ mice with and without a splenectomy on 14 consecutive days. The number of lymphocytes was then counted using True Cell beads and flow cytometry. The number of B220-, CD3-, and CD4-positive cells was also determined. In addition, skin grafts from C3H donor mice were performed on these mice. FTY720 was effective in significantly reducing the total lymphocyte count as well as the B220-, CD3-, and CD4-positive subtypes in the peripheral blood of aly/+ mice as well as in aly/aly mice with and without a splenectomy. While we did observe allograft skin graft rejection in both the aly/+ mice as well as the aly/aly mice recipients and splenectomized aly/aly mice, the graft survival was prolonged in all groups. The skin allografts treated by FTY720 thus demonstrated fewer lymphocytic cells and less infiltration of CD4-positive cells. The administration of FTY720 to mice without lymph nodes, Peyer's patches, or spleens still results in peripheral lymphopenia. In all groups, FTY720 was found to prevent the infiltration of CD4-positive cells in skin allografts while also prolonging skin allograft survival. The fate of these lymphocytes, however, is unclear.


Extracellular ATP: A powerful inflammatory mediator in the central nervous system.
Nucleotides play a crucial role in extracellular signaling across species boundaries. All the three kingdoms of life (Bacteria, Archea and Eukariota) are responsive to extracellular ATP (eATP) and many release this and other nucleotides. Thus, eATP fulfills different functions, many related to danger-sensing or avoidance reactions. Basically all living organisms have evolved sensors for eATP and other nucleotides with very different affinity and selectivity, thus conferring a remarkable plasticity to this signaling system. Likewise, different intracellular transduction systems were associated during evolution to different receptors for eATP. In mammalian evolution, control of intracellular ATP (iATP) and eATP homeostasis has been closely intertwined with that of Ca2+, whether in the extracellular milieu or in the cytoplasm, establishing an inverse reciprocal relationship, i.e. high extracellular Ca2+ levels are associated to negligible eATP, while low intracellular Ca2+ levels are associated to high eATP concentrations. This inverse relationship is crucial for the messenger functions of both molecules. Extracellular ATP is sensed by specific plasma membrane receptors of widely different affinity named P2 receptors (P2Rs) of which 17 subtypes are known. This confers a remarkable plasticity to P2R signaling. The central nervous system (CNS) is a privileged site for purinergic signaling as all brain cell types express P2Rs. Accruing evidence suggests that eATP, in addition to participating in synaptic transmission, also plays a crucial homeostatic role by fine tuning microglia, astroglia and oligodendroglia responses. Drugs modulating the eATP concentration in the CNS are likely to be the new frontier in the therapy of neuroinflammation. This article is part of the Special Issue on 'Purinergic Signaling: 50 years'.


Quantitative structure-activity relationship of phenoxyphenyl-methanamine compounds with 5HT2A, SERT, and hERG activities.
QSAR models have been used to evaluate activities for compounds in the phenoxyphenyl-methanamine (PPMA) class of compounds. These models utilize Hammett-type donating-withdrawing substituent values as well as simple parameters to describe substituent size and elucidate the SAR of the 'A' and 'B' rings. Using this methodology, intuitive QSAR relationships were found for the three biological activities with R(2) values of 0.73, 0.45, and 0.58 for 5HT(2A), SerT, and hERG activities.


Influence of environmental factors on the detection of blood in sheep faeces using visible-near-infrared spectroscopy as a measure of Haemonchus contortus infection.
Existing diagnostic methods for the parasitic gastrointestinal nematode, Haemonchus contortus, are time consuming and require specialised expertise, limiting their utility in the field. A practical, on-farm diagnostic tool could facilitate timely treatment decisions, thereby preventing losses in production and flock welfare. We previously demonstrated the ability of visible-near-infrared (Vis-NIR) spectroscopy to detect and quantify blood in sheep faeces with high accuracy. Here we report our investigation of whether variation in sheep type and environment affect the prediction accuracy of Vis-NIR spectroscopy in quantifying blood in faeces. Visible-NIR spectra were obtained from worm-free sheep faeces collected from different environments and sheep types in South Australia (SA) and New South Wales, Australia and spiked with various sheep blood concentrations. Spectra were analysed using principal component analysis (PCA), and calibration models were built around the haemoglobin (Hb) wavelength region (387-609 nm) using partial least squares regression. Models were used to predict Hb concentrations in spiked faeces from SA and naturally infected sheep faeces from Queensland (QLD). Samples from QLD were quantified using Hemastix® test strip and FAMACHA© diagnostic test scores. Principal component analysis showed that location, class of sheep and pooled versus individual samples were factors affecting the Hb predictions. The models successfully differentiated 'healthy' SA samples from those requiring anthelmintic treatment with moderate to good prediction accuracy (sensitivity 57-94%, specificity 44-79%). The models were not predictive for blood in the naturally infected QLD samples, which may be due in part to variability of faecal background and blood chemistry between samples, or the difference in validation methods used for blood quantification. PCA of the QLD samples, however, identified a difference between samples containing high and low quantities of blood. This study demonstrates the potential of Vis-NIR spectroscopy for estimating blood concentration in faeces from various types of sheep and environmental backgrounds. However, the calibration models developed here did not capture sufficient environmental variation to accurately predict Hb in faeces collected from environments different to those used in the calibration model. Consequently, it will be necessary to establish models that incorporate samples that are more representative of areas where H. contortus is endemic.


Fetal Val108/158Met catechol-O-methyltransferase (COMT) polymorphism and placental COMT activity are associated with the development of preeclampsia.
To evaluate the association between fetal and maternal catechol-O-methyltransferase (COMT) Val158Met and methyl tetrahydrofolate reductase (MTHFR) C677T functional polymorphisms and preeclampsia, examining its influence on placental COMT and in maternal 2-methoxyestradiol (2-ME) plasma levels. Prospective case-control study. University hospital. A total of 53 preeclamptic and 72 normal pregnant women. Maternal and cord blood samples and placental tissue samples were obtained. Maternal and fetal COMT and MTHFR polymorphisms were genotyped. Maternal plasma 2-ME and homocysteine levels, and expression and activity of placental COMT were measured. The odds ratio for the risk of preeclampsia for fetal COMT Met/Met was 3.22, and it increased to 8.65 when associated with fetal MTHFR TT. Placental COMT activity and expression were influenced by genotype, but COMT activity in preeclamptic placentas did not differ from control pregnancies. There was no association between any genotypes and maternal 2-ME. Homocysteine levels were higher in women with preeclampsia than in normal pregnancies, and were inversely correlated with 2-ME plasma levels, indicating that its altered metabolism may lower COMT activity in vivo. Fetal Met-Met COMT genotype reduces COMT placental expression and activity in vitro and increases preeclampsia, risk but it does not explain the difference in maternal 2-ME levels between preeclamptic and normal pregnancies. However, the preeclamptic patients had elevated homocysteine levels that correlated inversely with 2-ME, indicating that an altered methionine-homocysteine metabolism may contribute to reduce COMT activity in vivo and explain the decreased levels of 2-ME in preeclamptic women.


Strongyle infections of small ruminants in Nigeria.
A survey of strongyle infections was conducted in sheep and goats reared in a traditional extensive husbandry system in two ecological zones of Nigeria. One zone had a seasonal pattern of infection. The majority of animals had faecal worm parasite egg counts of below 500 eggs per gram. Kids, and lambs younger than 3 months did not carry strongyle worm burdens, and the highest infection rate was found in the 7-12 month age group. A high proportion of small ruminants shed strongyle eggs during the postparturient period. The helminth species found by the use of larval culture techniques on the faeces were: Haemonchus contortus, Trichostrongylus colubriformis and Oesophagostomum columbianum. Adults of the same species were found in the few animals necropsied. The significance of the findings is discussed.


Production of viable Giardia cysts in vitro: determination by fluorogenic dye staining, excystation, and animal infectivity in the mouse and Mongolian gerbil.
The purpose of this research was to document the formation of viable Giardia cysts in vitro. Viability staining, using fluorogenic dyes that required metabolic conversion for detection, and immunocytochemistry at the light microscopic level provided information on viability and for the identification of formed in vitro. Analysis of cysts formed in vivo and in vitro showed similar morphologic appearances by both light and electron microscopy. Cysts formed in vitro were capable of establishing infections in both mouse and gerbil models for giardiasis. Trophozoites obtained from mice experimentally infected with in vitro-formed cysts could be maintained in culture and induced a second time to form cysts in vitro. This model for the production of viable Giardia cysts in vitro should facilitate research on controlling the complete life cycle of Giardia outside an animal host.


Preferential expression of immunoreactive fucosylceramide in adenocarcinoma of the lung.
The expression of fucosylceramide (PC47H antigen) in 97 lung cancers and 4 extrapulmonary squamous cell carcinomas was examined with the use of a novel monoclonal antibody, PC47H, recognizing fucosylceramide specifically. The observed variation in fucosylceramide content was dependent on the degree of glandular differentiation in adenocarcinoma of the lung. Fucosylceramide was abundantly expressed in well differentiated adenocarcinoma of the lung and poorly expressed in poorly differentiated adenocarcinoma. Some squamous cell carcinomas of the lung reacted with this monoclonal antibody weakly, but the reaction was noted only at the periphery of the epithelial sheets. Extrapulmonary squamous cell carcinoma and small-cell carcinomas did not react with monoclonal antibody PC47H. Interestingly, large cell carcinomas of uncertain cell origin were all positive for fucosylceramide, which accumulated in the cytoplasm. At the ultrastructural level, fucosylceramide was located in the plasma membrane and unit membrane of the rough endoplasmic reticulum. On the other hand, carcinoembryonic antigen as an adenocarcinoma-associated tumor marker was expressed significantly in squamous cell carcinomas as well as adenocarcinomas. Taken together, fucosylceramide seems to be expressed preferentially in adenocarcinomas, and is closely linked to glandular differentiation. Thus it may be a better tumor marker than carcinoembryonic antigen.


Low serum cholesterol is correlated to suicidality in a Korean sample.
The aim of this study was to examine further the association between low total serum cholesterol and suicidal behaviour. We measured the serum cholesterol levels in 231 patients admitted to an emergency room following a suicide attempt, in 231 age-,sex- and diagnosis-matched non-suicidal psychiatric controls, and in 231 age- and sex-matched normal controls. The suicide attempt patients were divided into five grades according to the degree of injury. The mean total cholesterol level of the suicide attempt patients was significantly lower than that of the psychiatric and normal controls. When the suicide attempt patients and non-suicidal psychiatric controls were divided by diagnosis, this significant relationship held true for major depressive disorders and personality disorders, but not for schizophrenia and bipolar disorders. Cholesterol level and the severity of suicide attempt were inversely correlated. The results suggest that cholesterol level may serve as a marker for suicide risk. Possible explanations are discussed.


Phenolic compounds are less degraded in presence of starch than in presence of proteins through processing in model porridges.
Phenolic compounds are known to bind non-covalently with starch, but the impact of this interaction on the stability of the phenolic compounds through processing and digestion has received little attention. In this study, we examined the recovery of intact phenolic compounds (gallic acid-GA, catechin-CAT and epigallocatechin gallate-EGCG) from processed and digested porridges with different formulations (starch or starch/protein). We observed that phenolics were less degraded in presence of starch only than in presence of starch + proteins. This protection seemed to be linked to the ability of the phenolic compounds to form V-type inclusion complexes with starch, with GA, CAT and EGCG in decreasing order of protection. This work could influence formulation of functional cereal-based foods containing phenolic compounds in order to maximize their retention.


Letting the ghosts out of the closet.
This pastoral case study is a reflection on intimidating personalities and how those personalities can effect the leadership style and emotional responses of clergy. When a clergy person finds that he or she is caught in an emotional triangle because of intimidating factors, it becomes necessary to develop a strategy to "unhook" through changing the clergy's behavior. This case study is a reflection regarding a personal experience.


Proteins and peptides as biological nanowires: towards biosensing devices.
The current landscape of nanotechnology is such that attention is being given to those materials that self-assemble, as a mode of "bottom-up" fabrication of nanomaterials. The field of nanotubes and nanowires has long been dominated by carbon nanotubes and inorganic materials. However in more recent years, the search for materials with desirable properties, such as self-assembly, has unsurprisingly led to the biological world, where functional nanoscale biomolecular assemblies are in abundance.Potential has been seen for a number of these assemblies to be translated into functional nanomaterials. The early days of bionanotechnology saw a lot of attention given to DNA molecules as nanowires, and proteins and peptides have now also been seen to have promise in this area. With most of the biological structures investigated having low conductivity in the native state, the use of biomolecules as templates for the formation of metallic and semiconductor nanowires has been the direction taken.This chapter will discuss the use of various biomolecules and biomolecular assemblies as nanowires, with a particular emphasis on proteins, beginning with an introduction into the field of nanotubes and nanowires. Many applications are now recognized for nanowires, but for brevity, this chapter will focus solely on their use as biosensors, using glucose sensors as a case study.


Development of a protective inactivated vaccine against Crimean-Congo hemorrhagic fever infection.
Crimean-Congo hemorrhagic fever (CCHF) is an emerging zoonotic infectious disease caused by Crimean-Congo hemorrhagic fever virus (CCHFV). The first clinical CCHF infection was described in 1944 in the Crimean Peninsula, exclusively in humans, with case-fatality rates exceeding 30%. The increasing number of cases, high mortality rate, and lack of effective therapy make CCHF a serious threat to public health and a potential bioterrorism agent. The present study evaluated the development, immunogenicity, and immune response durations for cell-culture-derived inactivated vaccine (CCVax) formulations in comparison with those of mouse-brain-derived vaccine (MBVax) formulations. In this study, the Kelkit06 CCHF virus strain was propagated in both suckling mice and Vero E6 cells, and purified with a sucrose gradient. Formalin-inactivated vaccine candidates were formulated at various doses [low dose (LD), 5 μg; medium dose (MD), 10 μg; high dose (HD), 20 μg)] and mixed with an alum adjuvant. BALB/c mice received the same doses of the vaccine formulations three times at 3-week intervals. The humoral endpoint IgG responses were evaluated and compared for the MBVax and CCVax treatments. The duration of the presence of IgG and neutralizing antibody (Ab) titers was evaluated and compared until up to 1 year after immunization. The humoral IgG responses indicated that the CCVax and MBVax candidates enhanced the IgG endpoint titers in a dose-dependent manner, which were induced more strongly in all the CCVax groups than in the MBVax mice. The fold changes in neutralizing Ab levels were also found to be higher in the CCVax groups: between 2- and 7.6-fold after the second week of the last immunization. The neutralization titers peaked 4 months after immunization in all the vaccine-receiving groups, but these were still comparable at the end of the first year. The CCVax formulations induced higher IgG and neutralizing Ab titers at all the measured time points. In this study, we showed that cell-culture-purified and formalin-inactivated vaccine candidates induced strong and robust immunity in vaccinated mice dose-dependently, more so than mouse-brain-derived vaccines.


Oxygen-induced pulmonary injury in gamma-glutamyl transpeptidase-deficient mice.
We used mice with a targeted disruption in g-glutamyl transpeptidase (GGT-deficient mice) to study the role of glutathione (GSH) in protection against oxygen-induced lung injury. These mice had reduced levels of lung GSH and restricted ability to synthesize GSH because of low levels of cysteine. When GGT-deficient mice were exposed to 80% oxygen, they developed diffuse pulmonary injury and died within eight days. Ten of 12 wild-type mice were alive after 18 days. Administration of N-acetylcysteine (NAC) to GGT-deficient mice corrected GSH values and prevented the development of severe pulmonary injury and death. Oxygen exposure induced an increase in lung GSH levels in both wild-type and GGT-deficient mice, but induced levels in the mutant mice were <50% of those in wild-type mice. Cysteine levels were approximately 50-fold lower than GSH levels the lungs of both wild-type and GGT-deficient mice. Levels of lung RNA coding for the heavy subunit of g-glutamyl cysteine synthetase rose three- to fourfold after oxygen exposure in both wild-type and GGT-deficient mice. In contrast, oxygen exposure failed to provoke increases in glutathione synthetase, glutathione peroxidase, glutaredoxin, or thioredoxin.


Synthesis, biological evaluation and molecular docking studies of novel 2-(1,3,4-oxadiazol-2-ylthio)-1-phenylethanone derivatives.
In present study, a series of new 2-(1,3,4-oxadiazol-2-ylthio)-1-phenylethanone derivatives (6a-6x) as potential focal adhesion kinase (FAK) inhibitors were synthesized. The bioassay assays demonstrated that compound 6i showed the most potent activity, which inhibited the growth of MCF-7 and A431 cell lines with IC(50) values of 140 ± 10 nM and 10 ± 1 nM, respectively. Compound 6i also exhibited significant FAK inhibitory activity (IC(50)=20 ± 1 nM). Docking simulation was performed to position compound 6i into the active site of FAK to determine the probable binding model.


Preservation Rhinoplasty (Let-Down Technique) for Endonasal Dorsal Reduction.
Preservation rhinoplasty has been a trending topic in the rhinoplasty literature. There is no single technique that can correct all structures; therefore, patient analysis is paramount. This article focuses on the anatomy of the keystone area and the dynamics of the dorsum explained through the biotensegrity concept. Differences between push-down and let-down techniques are addressed from a nasal valve physiology point of view. The let-down technique maintains the tensegrity of the nasal pyramid. Preservation should be preferred, in most cases, over resection, as well as reposition over manipulation.


Characterization of eight Y-STR loci and haplotypes in a Chinese Han population.
In this study we analyzed the eight Y-STR loci, DYS443, DYS444, DYS448, DYS453, DYS455, DYS456, DYS457 (DYS437) and DYS458, investigated haplotype distributions of these Y-STR loci in a Chinese Han population, and sequenced alleles of the eight loci for clarifying the structure. Extracted DNA was amplified by PCR and the PCR products were analyzed by non-denaturing horizontal polyacrylamide gel electrophoresis with a discontinuous buffer system. Alleles were sequenced on an ABI 3700 using a Dye Terminator Cycle sequencing kit. DYS443, DYS453, DYS455 and DYS456 were found to be simple repeat systems, while DYS444, DYS448, DYS457 (DYS437) and DYS458 were complex repeat systems. The gene diversities of DYS443, DYS444, DYS448, DYS453, DYS455, DYS456, DYS457 (DYS437) and DYS458 were 0.7742, 0.7671, 0.7453, 0.3545, 0.0549, 0.6988, 0.6148 and 0.8213, respectively. The haplotype diversity for 8 Y-STR loci was 0.9996, and the discrimination capacity was 0.9815. The results indicate that these eight loci are useful Y-linked markers for forensic applications.


Conception and use of a custom-made facial mask for pressure therapy in complex facial wounds.
Pressure therapy (PT) is commonly used to manage hypertrophic scars. It is often based on the use of elastic pressure garments, which are poorly suited for a facial localization. We describe the conception, fabrication, and use of a custom-made PT facial mask for primary prevention of hypertrophic scarring of complex facial wounds. The main advantage of the device is that it is quick and easy to manufacture in a conventional prosthetics laboratory, with a good level of observance and tolerance in our experience of 20 treated patients.


Testosterone prevents but not reverses anhedonia in middle-aged males and lacks an effect on stress vulnerability in young adults.
Middle-aged male rats are more vulnerable than young adult ones to develop anhedonia when exposed to chronic mild stress (CMS). Clinical studies support the idea that in aged subjects the low testosterone (T) levels are related with their higher stress vulnerability and that this hormone possesses antidepressant-like actions. In this study we evaluated the role of gonadal hormones--mainly T--on the depressive-like behavior of middle-aged and young adult male rats submitted to CMS. In middle-aged rats we analyzed the effect of T restitution (at the levels of young adult animals) given 3 weeks before (experiment 1) or 3 weeks after (experiment 2) anhedonia development (indicated by a reduction in sucrose solution intake). T restitution before CMS effectively prevented anhedonia but failed to reverse it once installed. In young adult rats we studied if orchidectomy increased stress vulnerability and found that it failed to modify sucrose intake. These results indicate a stress-dependent differential effect of T in middle-aged rats an age differential role of gonadal hormones on the vulnerability to develop anhedonia. The results suggest that T is a resilience factor in middle-aged but not in young adult males.


The effectiveness of the early orthodontic correction of functional unilateral posterior crossbite in the mixed dentition period: a systematic review and meta-analysis.
This systematic review and meta-analysis aimed to critically appraise the available evidence of the effectiveness of early intervention of functional unilateral posterior crossbites (FPXB) between the ages of 6 and 12 years. Electronic search in four databases (PubMed, Scopus, Embase, and Google Scholar) for randomized controlled trials (RCTs) and controlled clinical trials (CCTs) was performed between 1st January 1990 and 31st October 2021. Methodological index for non-randomized studies (MINORS) for CCTs and Cochrane's risk of bias tool for RCTs were applied. The certainty of the evidence was evaluated according to the grading of recommendations, assessment, development, and evaluation (GRADE) approach. Nine studies (6 RCTs and 3 CCTs) were included in this review, and six of them were appropriate for quantitative synthesis. The meta-analysis revealed that the quad-helix (QH) was more effective than expansion plates (EP) in increasing the intermolar width (WMD = 1.25; 95% CI 0.75, 1.75; P < 0.001), and decreasing treatment time (WMD = - 3.36; 95% CI - 4.97, - 1.75; P < 0.001). The relapse rate at 5.6 years post-treatment was greater in the QH group than in the EP group (RR = 3.00); however, the difference was statistically insignificant. There was no significant difference between the QH and the EP in other outcome measures. When assessing the rapid maxillary expansion (RME), only one RCT compared the RME with an untreated control group and reported a significant increase in the maxillary intermolar and intercanine width (P < 0.001, P = 0.002, respectively) and a significant decrease in lower midline deviation (P < 0.001). There is weak to moderate evidence that the treatment of functional posterior crossbite (FPXB) by the QH increased the maxillary intermolar width and the success rate and decreased the treatment duration compared to the EP. The relapse percentage was greater in the QH group. There is very weak evidence that the mandibular midline correction rate did not differ significantly between the QH and the EP modalities. The RME using the Hyrax appliance corrected the FPXB successfully; however, the strength of evidence in this regard is very low. As the quality of evidence ranged from very low to moderate in this review, we confirm the need for more RCTs with different expansion appliances in the early treatment of FPXB.


Improving prediction of psychosis in youth at clinical high-risk: pre-baseline symptom duration and cortical thinning as moderators of the NAPLS2 risk calculator.
Clinical implementation of risk calculator models in the clinical high-risk for psychosis (CHR-P) population has been hindered by heterogeneous risk distributions across study cohorts which could be attributed to pre-ascertainment illness progression. To examine this, we tested whether the duration of attenuated psychotic symptom (APS) worsening prior to baseline moderated performance of the North American prodrome longitudinal study 2 (NAPLS2) risk calculator. We also examined whether rates of cortical thinning, another marker of illness progression, bolstered clinical prediction models. Participants from both the NAPLS2 and NAPLS3 samples were classified as either 'long' or 'short' symptom duration based on time since APS increase prior to baseline. The NAPLS2 risk calculator model was applied to each of these groups. In a subset of NAPLS3 participants who completed follow-up magnetic resonance imaging scans, change in cortical thickness was combined with the individual risk score to predict conversion to psychosis. The risk calculator models achieved similar performance across the combined NAPLS2/NAPLS3 sample [area under the curve (AUC) = 0.69], the long duration group (AUC = 0.71), and the short duration group (AUC = 0.71). The shorter duration group was younger and had higher baseline APS than the longer duration group. The addition of cortical thinning improved the prediction of conversion significantly for the short duration group (AUC = 0.84), with a moderate improvement in prediction for the longer duration group (AUC = 0.78). These results suggest that early illness progression differs among CHR-P patients, is detectable with both clinical and neuroimaging measures, and could play an essential role in the prediction of clinical outcomes.


Cognitive changes predict continued recovery of erectile functioning versus relapse after discontinuation of sildenafil treatment for male erectile dysfunction.
To examine whether erectile functioning after termination of sildenafil intake in men with psychogenic ED (erectile dysfunction) can be predicted with psychological measures. The subjects in a nonrandomized controlled trial were 65 heterosexual men with acquired psychogenic ED, aged 54.2 +/- 11 years. Sildenafil medication was taken as required before sexual activity, up to two times per week. Response to a global end point question ("Did the treatment you took during the study improve your physical response during sexual activity in the last 4 weeks?") was recorded after 6 weeks of sildenafil use and, subsequently, 6 weeks without medication. Other measures of sexual functioning and cognitive predictor measures were also administered. Of the 65 participants who commenced sildenafil treatment, 37% withdrew from the study before follow-up assessment. At posttreatment, 89% of participants reported that treatment had improved or cured their erectile functioning. At follow-up, 66% of participants had maintained posttreatment gains. Response at follow-up could be predicted (p <.001) with 96% sensitivity and 50% specificity by entering changes in sexual self-confidence and the participant's rating of his partner's wish to continue treatment in a logistic regression model. Higher odds for recovery of erectile functioning were found in participants reporting increased sexual self-confidence and the estimation that their partner wanted them to continue sildenafil use. High pretreatment sexual desire was found to further increase the odds for positive responding at follow-up. The present results indicate that continued improvement of erectile functioning is possible after discontinuation of sildenafil use in men with psychogenic ED. Maintenance of gains can be predicted from cognitive changes before medication is withdrawn.


Real world application of ocrelizumab in multiple sclerosis: Single-center experience of 128 patients.
Pivotal trials showed good clinical efficiency of the monoclonal antibody ocrelizumab while being well tolerated and manageable in multiple sclerosis (MS). However, data on adverse events in everyday practice are scarce. Hence, our study aims at investigating short-term tolerability of ocrelizumab in a "real-world" setting. In this retrospective cohort study, data of 128 (86 relapsing-remitting, 42 progressive) MS patients at initiation of ocrelizumab were analyzed at the MS center of the University of Erlangen, Germany. Additionally, follow-up data of 68 patients at 6-months retreatment were analyzed. Structured phone interviews were applied after ocrelizumab initiation to report undocumented side effects. Patients predominantly switched from monoclonal antibodies (46%), orals (20%), injectables (10%), steroids or immunosuppressants (each 8%), with a mean interval of 9.0 months after the last application of the previous immunotherapy. Applying a combined premedication with steroids, antihistamines and antipyretics for >90% of patients, ocrelizumab treatment was well tolerated and mainly comprised mild (n = 59/128 at initiation, n = 5/68 at 6 months retreatment) and rarely moderate (n = 7/128 at initiation, n = 2/68 at 6 months) side effects. Predominantly mild infusion related reactions (IRR) were reported with a declining percentage over the follow-up applications. Infections occurred rarely. No severe side effects were observed. Secondary, treatment appeared efficient when looking at clinical surrogates of stable disease. Our study delineates good short-term tolerability of ocrelizumab in a miscellaneous "real-world" MS cohort. Additional studies are warranted to confirm these beneficial findings and to reveal safety concerns in the longer-term follow-up.


A recent chicken repeat 1 retrotransposition confirms the Coscoroba-Cape Barren goose clade.
Chicken repeat 1 (CR1) is a member of the non-long terminal repeat class of retrotransposons. We have isolated a truncated CR1 element within the third intron of the lactate dehydrogenase B gene of the coscoroba and the Cape Barren goose (Anseriformes; Coscoroba coscoroba, Cereopsis novaehollandiae). Because the element was absent in orthologous loci within mallard (Anas platyrhynchos), snow goose (Anser caerulescens), and tundra swan (Cygnus columbianus), it provides strong support to the recent novel proposal by Donne-Goussé et al. [Donne-Goussé, C., Laudet, V., Hänni, C., 2002. A molecular phylogeny of anseriformes based on mitochondrial DNA analysis. Mol. Phylogenet. Evol. 23, 339-356] that Cape Barren goose is the sister taxon to coscoroba. The time of insertion was approximately 10.5 Mya or less estimated from mitochondrial DNA sequence information. Because this is a recent event, the DNA sequence of this CR1 should be close to that existing at the time of its insertion. This is reflected by the consistency of several structural features expected in a new CR1 copy such as the unaltered flanking target site duplication and inverted repeats that lie 22 bp apart near the 3' end of the element. Hybridization experiments show that numerous copies of sequences closely related to the coscoroba CR1 element are dispersed throughout the genomes of tested Anseriformes, but none were detected in representatives of Galliformes and Struthioniformes.


Ablation of neurons expressing agouti-related protein, but not melanin concentrating hormone, in leptin-deficient mice restores metabolic functions and fertility.
Leptin-deficient (Lep(ob/ob)) mice are obese, diabetic, and infertile. Ablation of neurons that make agouti-related protein (AgRP) in moderately obese adult Lep(ob/ob) mice caused severe anorexia. The mice stopped eating for 2 wk and then gradually recovered. Their body weight fell to within a normal range for WT mice, at which point food intake and glucose tolerance were restored to that of WT mice. Remarkably, both male and female Lep(ob/ob) mice became fertile. Ablation of neurons that express melanin-concentrating hormone (MCH) in adult Lep(ob/ob) mice had no effect on food intake, body weight, or fertility, but resulted in improved glucose tolerance. We conclude that AgRP-expressing neurons play a critical role in mediating the metabolic syndrome and infertility of Lep(ob/ob) mice, whereas MCH-expressing neurons have only a minor role.


[The Relationship Between Emotion Recognition and the Symptoms of Attention Deficit and Impulsivity in Adult Patients With Attention Deficit Hyperactivity Disorder].
Interpersonal relationship disorders in adults with Attention Deficit Hyperactivity Disorder (ADHD) can be associated with the impairment of non-verbal communication. The purpose of our study was to compare the emotion recognition, facial recognition and neuropsychological assessments of adult ADHD patients with those of healthy controls, and to thus determine the effect of neuropsychological data on the recognition of emotional expressions. This study, which was based on a case-control model, was conducted with patients diagnosed with ADHD according to the DSM-IV-TR, being followed and monitored at the adult ADHD clinic of the Psychiatry Department of the Istanbul University Istanbul Medical Faculty Hospital. The study group consisted of 40 adults (27.5% female) between the ages of 20-65 (mean age 25.96 ± 6.07; education level: 15.02±2.34 years) diagnosed with ADHD, and 40 controls who were matched/similar with the study group with respect to age, gender, and education level. In the ADHD group, 14 (35%) of the patients had concomitant diseases. Pictures of Facial Affect, the Benton Face Recognition Test, and the Continuous Performance Test were used to respectively evaluate emotion recognition, facial recognition, and attention deficit and impulsivity of the patients. It was determined that, in comparison to the control group, the ADHD group made more mistakes in recognizing all types of emotional expressions and neutral expressions. The ADHD group also demonstrated more cognitive mistakes. Facial recognition was similar in both groups. It was determined that impulsivity had a significant effect on facial recognition. The social relationship disorders observed in ADHD can be affected by emotion recognition processes. In future studies, it may be possible to investigate the effects that early psychopharmacological and psychotherapeutic interventions administered for the main symptoms of ADHD have on the impairment of emotion recognition.


High throughput sequencing of cyclic peptide immobilized on a gel-type single bead.
Relatively larger scale peptide libraries immobilized on a gel-type solid support consisting of 24 natural and non-natural amino acids by the "split and combine method" have been constructed to find interacting molecules. The diversity was ca. 200 millions of hexapeptides with cysteinyl residues forming cyclotide. Selected beads after screening can be sequenced by the conventional Edman degradation, although several restrictions and the problems are known. To resolve these, a novel combinatorial method involving partial acid hydrolysis followed by liquid chromatography with on-line mass spectrometric analyses has been established. Problems were uncovered in an early stage of the process. Uncertain assignment caused by byproducts derived from a cystine residue and other materials could be resolved by optimal hydrolysis conditions and derivatization before mass spectrometric analysis. Discrimination between Leu and Ile could be performed using high energy collision induced dissociation in the high resolution MALDI-TOF-MS/MS. The present optimized protocol is useful for discovery of sequences of interacting molecules and a second library construction.


Differential sensitivity of chicken MM-creatine kinase to trypsin and proteinase-K.
Under several conditions of SDS-PAGE, the chicken MM-creatine kinase (MM-CK) monomer migrated as a approximately 50,000 dalton polypeptide, approx 25% larger than usually reported. Characterization by sedimentation equilibrium indicated that the anomalous molecular weight was an artifact of electrophoresis. Digestion with trypsin caused only moderate reductions in CK activity, despite extensive degradation of the denatured enzyme revealed by SDS-PAGE. Characterization of trypsinized MM-CK under non-denaturing conditions of electrophoresis and HPLC revealed no fragmentation of the native enzyme, suggesting that MM-CK quaternary structure was maintained despite extensive tryptic nicking. In contrast, much lower concentrations of proteinase-K generated only a single fragment in SDS-PAGE while causing a nearly total loss of enzyme activity.


Adult-to-adult living related liver transplantation: preliminary results of the Hepatic Transplantation Group in Algiers.
In the absence of cadaveric grafts, a living donor liver transplant program was started in Algeria in February 2003. The aim of this study is to report the preliminary results. From February 2003 to September 2004, eight adult-to-adult living related liver transplantations were performed. The donors were six women and two men of mean age of 25 years (range, 18 to 48 years). Right hepatectomy was performed in seven patients and left hepatectomy in one patient. The recipients were four women and four men of mean age 33 years (range, 16 to 56 years). Follow-up ranged from 1 month to 18 months (median 7 months). All donors survived the procedure. In the immediate postoperative period, two donors experienced complications. One donor underwent reoperation for hemorrhage and one suffered partial portal vein thrombosis, which was treated medically. The eight donors are alive at home without any late complications. One recipient died on postoperative day 43 due to sepsis. Among the seven other recipients, two experienced complications: one bilioma in relation to a biliary-intestinal fistula and one thrombosis of the splenic vein with a left portal embolus. At present the seven recipients are alive with normal liver function and without complications. Our results are comparable to other reports suggesting that adult-to-adult living related liver transplantation is feasible with no mortality and low morbidity in donors. However, it is important to develop a cadaveric liver transplant program.


Wnt signaling in bone and muscle.
Wnt signaling plays key roles in many aspects of development. In this review, we will briefly describe the components of signaling pathways induced by Wnt ligands and then describe the current state of research as this applies to aspects of development and disease as it relates to skeletal muscle and bone. We will conclude with a discussion of the parallels and differences in Wnt signaling in these two contexts and how these pathways are being (or could potentially be) targeted for therapeutic treatment of musculoskeletal diseases. This article is part of a Special Issue entitled "Muscle Bone Interactions".


Drosophilid assemblages at different urbanization levels in the city of Porto Alegre, state of Rio Grande do Sul, southern Brazil.
The present study analyzed the drosophilid assemblages in different levels of urbanization in the city of Porto Alegre, Rio Grande do Sul, Brazil. Collections were carried out in 2008 in three different environments: a highly urbanized area-"Jardim Botânico," a forested area with intermediary urbanization-"Parque Gabriel Knijnik," and in a relatively well-preserved forested area, although threatened by the urban growth-"Morro Santana." In Jardim Botânico, 36 species belonging to four genera were found, with high abundance of exotic species as Drosophila simulans Sturtevant and Zaprionus indianus (Gupta). In Parque Gabriel Knijnik, 33 species that belonged to four genera were found, with higher abundances of native species belonging to the Drosophila tripunctata species group and Drosophila willistoni species subgroup, and lower abundance of exotic species. As for Morro Santana, 32 species and three genera were found, with higher abundances of native groups, low representativeness of exotic species, and absence of Zaprionus indianus. The analysis of the Jaccard index showed higher similarity in the species composition between samples collected in summer and autumn, and between samples collected in winter and spring. On the other hand, the Morisita index differentiated Jardim Botânico from the other two studied sites. Our results show that Morro Santana is an important area of native biodiversity, reinforcing, therefore, the inclusion of this area in the project for the creation of an ecological corridor as proposed by the Ministry of the Environment of Brazil.


Comparison of three antibiotic protocols for prevention of infection in dental implant surgery: A randomized clinical trial.
This study aimed to compare the rate of post-surgical infection following single-dose antibiotic prophylaxis with or without post-surgical antibiotics versus post-surgical administration of antibiotics alone. The study consisted of three groups; Group 1 received single-dose antibiotic prophylaxis orally (2 g amoxicillin 1 h before surgery). Group 2 received one dose of prophylactic antibiotic (2 g amoxicillin 1 h before surgery) with additional doses after surgery (500 mg amoxicillin, q8h for 5 days). Group 3 received post-surgical antibiotics alone (500 mg amoxicillin, q8h for 5 days). 450 patients were enrolled. Post-surgical infection was seen in 9 patients of group 1, 11 patients of group 2, and 7 patients of group 3. There was no significant difference in the rate of postoperative infection among the study groups (p value = 0.62). The number of failed implants was 2 in group 2, and 1 in group 3. Subgroup analysis showed no significant difference in infection rates among the three groups regarding concomitant guided bone regeneration. However, there was a significant difference in the rate of post-surgical infection between smokers and non-smokers (p < 0.001). Within the limitations of the study, it seems that a single preoperative dose of antibiotics is sufficient for reducing surgical site infections, adequately and should be preferred after implant placement whenever appropriate.


A co-culture-based model of human blood-brain barrier: application to active transport of indinavir and in vivo-in vitro correlation.
The growing array of in vitro models of the blood-brain barrier (BBB) which have been used makes it difficult to draw firm conclusions concerning the BBB penetration of HIV-1 protease inhibitors. What is needed is a combined in vivo and in vitro study on biological models that mimic as closely as possible the normal human BBB, to establish whether and how indinavir crosses the BBB. We developed a new human BBB model using primary endothelial cells and astrocytes. The biological relevance of this model was checked with respect on the one hand, to the close relationship between the log of drug permeability coefficient normalized to molecular weight and the log of the 1-octanol/water partition coefficient, and on the other hand to the functional P-glycoprotein (P-gp) expression. We employed this model to perform transport studies with indinavir and showed that the rate of in vitro indinavir transport from the basal to apical compartment was higher than the rate of apical to basal transport. Pretreatment of the BBB model with the P-gp inhibitor, quinidine, significantly increased apical to basal transport. Intracellular indinavir accumulation was increased in BBB as a result of inhibition of active transport. These data were correlated with the indinavir-mediated P-gp ATPase modulation showing that indinavir specifically interacted with a binding site on P-gp. Moreover, the activation of P-gp ATPase by indinavir was inhibited by quinidine. In addition, the in vivo brain to plasma concentration ratio of indinavir into mice showed that indinavir concentration was up to five times higher in the brain of mdr1a(-/-) mice than in the brain of mdr1a(+/+) mice. All these results confirm the role of P-gp in preventing the passage of indinavir across BBB and thus its entry into the central nervous system (CNS). Our human BBB model represents a useful tool for the evaluation of drug penetration into the CNS.