Vanishing endometrial cancer in hysterectomy specimens: a myth or a fact.
The incidence of endometrial cancers diagnosed on biopsy that have no residual cancer identified at hysterectomy is not well studied. The aim of our study was to determine the incidence and long-term follow-up of this "vanishing cancer" phenomenon. All slides from the initial biopsy/curettage and hysterectomy specimens were reviewed and the diagnosis confirmed by a gynecologic pathologist. The entire endometrium was serially sectioned and submitted for histologic examination. Clinical and pathologic variables were analyzed, including patient demographics, tumor histologic type and grade, stage, biopsy method, adjuvant therapy, surgical procedure, recurrence, and disease-specific survival. We identified 23 biopsy-proven cases of endometrial cancer with no residual disease on hysterectomy specimen. Of the 23 patients, 15 (65.2%) were diagnosed as endometrioid, 6 (26%) serous, 1 clear cell (4.3%), and 1 (4.3%) serous intraepithelial carcinoma. Seventeen underwent dilatation and curettage, and 6 had endometrial biopsy as the primary procedure. The median follow-up was 8.8 years (range, 1.2 to 17 y). Only 2 cases with serous carcinoma underwent adjuvant chemotherapy, and none received radiation therapy. Only 1 patient died of disease after 27 months and was diagnosed as FIGO grade II endometrioid carcinoma on dilatation and curettage. The inability to identify cancer in a hysterectomy specimen for biopsy-confirmed carcinoma does not indicate technical failure. Although there is no specific standard treatment for patients with "vanishing endometrial cancer," the prognosis is excellent; however, close follow-up is suggested.


LightCycler-based differentiation of Mycobacterium abscessus and Mycobacterium chelonae.
In this study we introduce a rapid procedure to identify Mycobacterium abscessus (types I and II) and M. chelonae using LightCycler-based analysis of the hsp65 gene. Results from 36 clinical strains were compared with hsp65 gene restriction analysis and biochemical profiles of bacilli. As all three methods yielded identical results for each isolate, this procedure offers an excellent alternative to previously established nucleic acid amplification-based techniques for the diagnosis of mycobacterial diseases.


The efficiency of fabricated Ag/ZnO nanocomposite using Ruta chalepensis L. leaf extract as a potent protoscolicidal and anti-hydatid cysts agent.
As a consequence of their eco-friendliness, simplicity and non-toxicity, the fabrication of metal and metal oxide nanoparticles using greener chemistry has been a highly attractive research area over the last decade. In this study focused on the fabrication of silver-Zinc oxide nanocomposite (Ag-ZnO NCs) using Ruta chalepensis leaf extract and evaluating its potential biological activities, against Echinococcus granulosus in an in vitro and in vivo model using BALB/c mice. In this study, the synthesis of Ag-ZnO NCs was accomplished using local R. chalepensis leaf extracts. The synthesized nanocomposites were identified using UV-Vis, SEM-EDX, XRD, and FTIR. For a short-term assessment of acute toxicity, BALB/c mice were given the prepared NCs orally. Dual sets of mice were also intraperitoneally injected with protoscoleces for secondary echinococcosis infection. Furthermore, a blood compatibility test was carried out on the nanocomposites. The synthesized Ag-ZnO NCs presented a surface plasmon peak at 329 and 422 nm. The XRD, SEM, and EDX confirmed the purity of the Ag-ZnO NCs. The FTIR spectra indicated the formation of Ag-ZnO NCs. Compared to the untreated infected mice, the treated-infected animals displayed an alteration in the appearance of the hepatic hydatid cysts from hyaline to whitish cloudy with a rough surface appearance. Lysis of RBCs at various doses of Ag-ZnONCs was significantly less than the positive contro,. These findings revealed that the Ag-ZnO NCs didn't cause any adverse symptoms and no mortality was observed in all administered groups of mice. The obtained outcomes confirmed that concentrations of up to 40 μg/mL of the bio-fabricated Ag-ZnONCs induced no notable harm to the red blood cells.


[Density and dynamic of frontal sharp waves (encoches pointues frontales) during sleep in new-borns and infants (author's transl)].
Frontal sharp waves (encoches pointues frontales) identified by Monod (1960) were studied in 110 neonates and infants. Three pattern were described: typical, related and degraded. They were recorded in all subjects, the reason why the frequency of each pattern varied was discussed. Pathological states did not increase the occurrence of those frontal sharp waves since most of them were recorded in children either normal or suffering from a minor pathology. Incidence of maturation seemed to be probable since the highest proportion of frontal sharp waves occurred in infants whose gestational and legal age were respectively greater than 43 weeks and between 20 and 40 days at the time of investigation. Typical and degraded forms were predominant in transitional period towards quiet sleep; they were less numerous during falling asleep in active sleep and totally absent during active sleep following quiet sleep. This could suggest that the two states of active sleep are different in nature.


Diminished sensitivity of the insulin response to glucose following growth hormone influsion in man.
The acute effect of growth hormone (GH) administration on the dose-kinetics of glucose-stimulated insulin release was investigated in eight healthy, non-obese male subjects. The glucose-insulin dose-response relationship in these subjects was established by performing glucose infusions at three different dose levels. In a second series of experiments, the glucose infusions were preceded by a 30 min infusion of GH (40 mug/kg body weight), terminated 60 min before administration of glucose. GH induced small but significant reductions in the basal levels of blood glucose and plasma insulin. The glucose tolerance (k-value) was diminished after GH at all glucose doses. Both the initial late phases of insulin response to glucose were impaired following GH treatment. This effect was most pronounced when the intermediary glucose dose (eliciting a blood glucose level around 300 mg/100 ml) was used. Thus, the insulinogenic index (whole period of stimulation) was reduced by GH to 88.9 +/- 7.6, 60.4 +/- 7.1 and 74.3 +/- 11.0% of the respective controls when the smallest, the intermediate, and the largest glucose loads, respectively, were given. The blood glucose-plasma insulin dose-response curves were shifted to the right of the control ones when glucose infusion was preceded by GH. These findings suggest that GH diminishes the sensitivity of the islet for the insulin releasing action of glucose. Some possible mechanisms by which GH may modify insulin release are discussed.


Urinary oestriol and serum activities of human placental lactogen and heat stable alkaline phosphatase as indicators of fetoplacental function.
The accuracy of urinary oestriol and serum levels of human placental lactogen (HPL) and heat stable alkaline phosphatase (HSAP) as indicators of feto-placental function was studied in 76 patients with high risk pregnancy. Feto-placental dysfunction was predicted correctly by plasma HPL in 80%, by urinary oestriol in 70%, by serum HSAP in 47%, and by the complementary use of HPL and oestriol in 90% of the cases. Normal fetoplacental function was predicted correctly by plasma HPL in 94%, by urinary oestriol in 96%, by serum HSAP in 80%, and by the complementary use of oestril and HPL in 100% of the patients. The probability of feto-placental dysfunction with a pathological value was 88% with urinary oestriol, 84% with plasma HPL and 100% with the parallel use of oestriol and HPL. A normal value assured undisturbed feto-placental function in 89% with urinary oestriol, in 92% with plasma HPL and in 96% with the parallel use of oestriol and HPL.


Low-level laser treatment accelerated hair regrowth in a rat model of chemotherapy-induced alopecia (CIA).
Chemotherapy-induced alopecia (CIA) is one of the most distressing side effects of antineoplastic chemotherapy for which there is no effective interventional approach. A low-level laser (LLL) device, the HairMax LaserComb®, has been cleared by the FDA to treat androgenetic alopecia. Its effects may be extended to other settings; we have demonstrated that LaserComb treatment induced hair regrowth in a mouse model for alopecia areata. In the current study, we tested whether LLL treatment could promote hair regrowth in a rat model for CIA. Chemotherapy agents cyclophosphamide, etoposide, or a combination of cyclophosphamide and doxorubicin were administered in young rats to induce alopecia, with or without LLL treatment. As expected, 7-10 days later, all the rats developed full body alopecia. However, rats receiving laser treatment regrew hair 5 days earlier than rats receiving chemotherapy alone or sham laser treatment (with the laser turned off). The accelerated hair regrowth in laser-treated rats was confirmed by histology. In addition, LLL treatment did not provide local protection to subcutaneously injected Shay chloroleukemic cells. Taken together, our results demonstrated that LLL treatment significantly accelerated hair regrowth after CIA without compromising the efficacy of chemotherapy in our rat model. Our results suggest that LLL should be explored for the treatment of CIA in clinical trials because LLL devices for home use (such as the HairMax LaserComb®) provide a user-friendly and noninvasive approach that could be translated to increased patient compliance and improved efficacy.


Influence of sensory quality on preferences for apples of primary school children.
In this research work, sensorial features of four varieties of fresh apples have been investigated by children aged 6-10 years (n = 336) of the Centre-East region of Italy (Abruzzo). The examined sensory properties were visual appealing, aromatic flavour, sourness, sweetness, firmness and crunchiness. Statistical analysis was performed by means of principal component analysis which underlined the differences and similarities between the examined fruits and the most responsive variables. Results are very interesting and allow to better understand the most important descriptors which influence the appreciation of the different tested varieties. Furthermore, it has been noted that different varieties influence each other for the perception of some sensory characteristics. Thus, improving the knowledge of the most appreciated organoleptic properties of apples by young consumers would be very useful and it might stimulate the development of new and more appealing cultivars in the future.


A clinical perspective on a pain neuroscience education approach to manual therapy.
In recent years, there has been an increased interest in pain neuroscience education (PNE) in physical therapy. There is growing evidence for the efficacy of PNE to decrease pain, disability, fear-avoidance, pain catastrophization, limited movement, and health care utilization in people struggling with pain. PNE teaches people in pain more about the biology and physiology of their pain experience including processes such as central sensitization, peripheral sensitization, allodynia, inhibition, facilitation, neuroplasticity and more. PNE's neurobiological model often finds itself at odds with traditional biomedical models used in physical therapy. Traditional biomedical models, focusing on anatomy, pathoanatomy, and biomechanics have been shown to have limited efficacy in helping people understand their pain, especially chronic pain, and may in fact even increase a person's pain experience by increasing fear-avoidance and pain catastrophization. An area of physical therapy where the biomedical model is used a lot is manual therapy. This contrast between PNE and manual therapy has seemingly polarized followers from each approach to see PNE as a 'hands-off' approach even having clinicians categorize patients as either in need of receiving PNE (with no hands-on), or hands-on with no PNE. In this paper, we explore the notion of PNE and manual therapy co-existing. PNE research has shown to have immediate effects of various clinical signs and symptoms associated with central sensitization. Using a model of sensitization (innocuous, noxious, and allodynia), we argue that PNE can be used in a manual therapy model, especially treating someone where the nervous system has become increasingly hypervigilant. Level of Evidence: VII.


Embryonic development and the physiological factors that coordinate hatching in domestic chickens.
Embryonic growth and development is influenced by both endogenous and exogenous factors. The purpose of this review is to discuss the critical stages of chick embryonic development in relation to functional maturation of numerous organ systems, the acquisition of thermoregulation, and the hatching process. In addition, the mechanism of hatching, including sound synchronization and hormonal and environmental stimulation, will be discussed. Finally, the importance of effective hatching synchronization mechanisms will also be highlighted.


The Whitehead hemorrhoidectomy. An unjustly maligned procedure.
The Whitehead technique of hemorrhoidectomy has developed a reputation as an undesirable procedure since its description in 1882. The chief criticisms have been considerable blood loss, disturbance of continence, formation of an ectropion, and poor healing of the mucocutaneous junction followed by stricture formation. Five hundred fifty-six patients underwent a modified Whitehead hemorrhoidectomy, performed by one author (C.E.C.), between 1963 and 1983. Seventy-two of these patients had unclaimed follow-up letters, leaving 484 patients available for review. Four hundred forty of these patients were followed for over three years. Postoperative complications included fistula or abscess in 1.1 percent, flap loss in 6.9 percent, and a nonhealing wound in one patient. There were no recurrences and there was no ectropion formation, or "Whitehead deformity." Mortality was zero and total morbidity, including 7.2 percent flap detachment, was 12.2%. A modified Whitehead technique has become the authors' procedure of choice for circumferential prolapsing and bleeding hemorrhoids and mucosa.


Inattentional blindness and pattern-matching failure: The case of failure to recognize clinical cues.
Eye-tracking methodology was used to investigate lapses in the appropriate treatment of ward patients due to not noticing critical cues of deterioration. Forty nursing participants with different levels of experience participated in an interactive screen-based simulation of hypovolemic shock. The results show that 65% of the participants exhibited at least one episode of non-fixation on clinically relevant, fully visible cues that were in plain sight. Thirty-five percent of participants dwelt for sufficient time (>200 ms) on important cues for perception to take place, but no action followed, indicating they had pattern-matching failure. When participants fail to notice what, they should notice in patient status until it is too late, this can have serious consequences. Much work needs to be done, since these human perceptual limitations can affect patient safety in general wards.


Do Women's Orgasms Function as a Masculinity Achievement for Men?
Orgasms have been promoted as symbols of sexual fulfillment for women, and have perhaps become the symbol of a woman's healthy sex life. However, some research has suggested that this focus on women's orgasms, though ostensibly for women, may actually serve men; but the mechanisms of this are unclear. In the present experiment, we hypothesized that women's orgasms specifically function as a masculinity achievement for men. To test this, we randomly assigned 810 men (M age = 25.44, SD = 8.31) to read a vignette where they imagined that an attractive woman either did or did not orgasm during a sexual encounter with them. Participants then rated their sexual esteem and the extent to which they would feel masculine after experiencing the given situation. Our results showed that men felt more masculine and reported higher sexual esteem when they imagined that a woman orgasmed during sexual encounters with them, and that this effect was exacerbated for men with high masculine gender role stress. These results suggest that women's orgasms do function-at least in part-as a masculinity achievement for men.


Behavioral factors to include in guidelines for lifelong oral healthiness: an observational study in Japanese adults.
The aim of this study was to determine which behavioral factors to include in guidelines for the Japanese public to achieve an acceptable level of oral healthiness. The objective was to determine the relationship between oral health related behaviors and symptoms related to oral disease and tooth loss in a Japanese adult community. Oral health status and lifestyle were investigated in 777 people aged 20 years and older (390 men and 387 women). Subjects were asked to complete a postal questionnaire concerning past diet and lifestyle. The completed questionnaires were collected when they had health examinations. The 15 questions included their preference for sweets, how many between-meal snacks they usually had per day, smoking and drinking habits, presence of oral symptoms, and attitudes towards dental visits. Participants were asked about their behaviors at different stages of their life. The oral health examinations included examination of the oral cavity and teeth performed by dentists using WHO criteria. Odds ratios were calculated for all subjects, all 10 year age groups, and for subjects 30 years or older, 40 years or older, 50 years or older, and 60 years or older. Frequency of tooth brushing (OR = 3.98), having your own toothbrush (OR = 2.11), smoking (OR = 2.71) and bleeding gums (OR = 2.03) were significantly associated with number of retained teeth in males. Frequency of between-meal snacks was strongly associated with number of retained teeth in females (OR = 4.67). Having some hobbies (OR = 2.97), having a family dentist (OR = 2.34) and consulting a dentist as soon as symptoms occurred (OR = 1.74) were significantly associated with number of retained teeth in females. Factors that were significantly associated with tooth loss in both males and females included alcohol consumption (OR = 11.96, males, OR = 3.83, females), swollen gums (OR = 1.93, males, OR = 3.04, females) and toothache (OR = 3.39, males, OR = 3.52, females). Behavioral factors that were associated with tooth retention were frequency of eating snacks between meals, tooth brushing frequency, having one's own toothbrush, smoking and drinking habits, having hobbies, having a family dentist and when they had dental treatment. Clinical factors included bleeding gums, swollen gums, and toothache.


Do risk factors for elective cesarean section differ from those of cesarean section during labor in low risk pregnancies?
As the rate of cesarean sections has continuously increased over the last three decades, we sought to identify the factors related to elective cesarean section (ECS) and cesarean section during labor (LCS) in low risk pregnancies and to determine if they differ for the two types of cesarean. We conducted an observational study that included all maternity units in metropolitan France. Using the sample from the National Perinatal Survey 2003, we included 5393 women who met the criteria of a low risk pregnancy. The odds ratios (OR) corresponding to ECS and LCS were calculated for various characteristics for the women, fetus and maternity units, using a multinomial logistic regression model. For each factor, the adjusted OR corresponding to ECS and LCS were compared using the Wald's test. The rates of ECS and LCS in our population were 2.9% and 4.3%, respectively. Maternal age >or=30 years, body mass index >or=25 kg/m(2), primiparity and nationality from an African country were associated with an increased risk for both ECS and LCS. Those maternity units registering a low volume of deliveries (<1000/year) and those with a high rate of cesarean section during the previous year had an increased rate of LCS. Women with low risk pregnancies at term may present several factors that appear to create an "environment" favorable for cesarean section, leading to an increase in the likelihood of both ECS and LCS. Furthermore, several characteristics concerning maternity units are associated with an increased likelihood of LCS. Understanding the impact of various factors on the decision about the mode of delivery is essential for obstetrical teams concerned with controlling the progressive increase in the rate of cesarean sections.


Effect of rapid HIV testing on HIV incidence and services in populations at high risk for HIV exposure: an equity-focused systematic review.
To assess the effects of rapid voluntary counselling and testing (VCT) for HIV on HIV incidence and uptake of HIV/AIDS services in people at high risk for HIV exposure. Cochrane systematic review and meta-analysis. We searched PubMed, EMBASE, AIDSearch, LILACS, Global Health, Medline Africa, PsychInfo, CINAHL, Cochrane CENTRAL, Cochrane HIV/AIDS Group Specialized Register and grey literature from 1 January 2001 to 5 June 2014 without language restriction. We included controlled studies that compared rapid VCT with conventional testing among people at risk for HIV exposure. Two reviewers extracted data. We used Cochrane risk of bias tool and GRADE criteria: risk of bias, inconsistency, indirectness, imprecision and publication bias. For observational studies we used the Newcastle-Ottawa Scale. We used the PRISMA-Equity reporting guideline. From 2441 articles, we included 8 randomised controlled trials and 5 observational studies. Rapid VCT was associated with a threefold increase in HIV-testing uptake (relative risk (RR)=2.95 95% CI 1.69 to 5.16) and a twofold increase in the receipt of test results (RR=2.14, 95% CI 1.08 to 4.24). Women accepted testing more often than men in rapid VCT arm, but no differences in effect for age or socioeconomic status. Observational studies also showed rapid VCT led to higher rates of uptake of testing. Heterogeneity was high. A cluster-randomised trial reported an 11% reduction in HIV incidence in intervention communities (RR=0.89, 95% CI=0.63 to 1.24) over 3 years trial. Rapid VCT in health facilities and communities was associated with a large increase in HIV-testing uptake and receipt of results. This has implications for WHO guidelines. The routine use of rapid VCT may also help avoid human rights violations among marginalised populations where testing may occur without informed consent and where existing stigma may create barriers to testing.


LRRK2 knockdown in zebrafish causes developmental defects, neuronal loss, and synuclein aggregation.
Although mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of genetic Parkinson's disease, their function is largely unknown. LRRK2 is pleiotropic in nature, shown to be involved in neurodegeneration and in more peripheral processes, including kidney functions, in rats and mice. Recent studies in zebrafish have shown conflicting evidence that removal of the LRRK2 WD40 domain may or may not affect dopaminergic neurons and/or locomotion. This study shows that ∼50% LRRK2 knockdown in zebrafish causes not only neuronal loss but also developmental perturbations such as axis curvature defects, ocular abnormalities, and edema in the eyes, lens, and otic vesicles. We further show that LRRK2 knockdown results in significant neuronal loss, including a reduction of dopaminergic neurons. Immunofluorescence demonstrates that endogenous LRRK2 is expressed in the lens, brain, heart, spinal cord, and kidney (pronephros), which mirror the LRRK2 morphant phenotypes observed. LRRK2 knockdown results further in the concomitant upregulation of β-synuclein, PARK13, and SOD1 and causes β-synuclein aggregation in the diencephalon, midbrain, hindbrain, and postoptic commissure. LRRK2 knockdown causes mislocalization of the Na(+) /K(+) ATPase protein in the pronephric ducts, suggesting that the edema might be linked to renal malfunction and that LRRK2 might be associated with pronephric duct epithelial cell differentiation. Combined, our study shows that LRRK2 has multifaceted roles in zebrafish and that zebrafish represent a complementary model to further our understanding of this central protein. © 2016 Wiley Periodicals, Inc.


Non-Newtonian granular hydrodynamics. What do the inelastic simple shear flow and the elastic fourier flow have in common?
We describe a special class of steady Couette flows in dilute granular gases admitting a non-Newtonian hydrodynamic description for strong dissipation. The class occurs when viscous heating exactly balances inelastic cooling, resulting in a uniform heat flux. It includes the Fourier flow of ordinary gases and the simple or uniform shear flow (USF) of granular gases as special cases. The rheological functions have the same values as in the USF and generalized thermal conductivity coefficients can be identified. These points are confirmed by molecular dynamics simulations, Monte Carlo simulations of the Boltzmann equation, and analytical results from Grad's 13-moment method.


The Contact Angle Variation of Floating Particles Makes It Difficult to Use the Neumann Condition To Quantify the Air-Water Interface Deformation in Three-Dimensional Space.
Capillary force is critical to the floatability of particles at the air-water interface. Quantification of the capillary force requires solving the Young-Laplace equation using suitable boundary conditions (BCs) at the triple contact line. For axisymmetric (two-dimensional, 2D) systems, such as single spheres floating at an initially flat air-water surface, both the Dirichlet (constant contact depth) and Neumann (constant contact angle) BCs can be applied. For three-dimensional (3D) systems, Neumann BCs (NBCs) have been successfully used. In this paper, we have challenged the use of NBCs for the 3D deformation of the air-water surface induced by floating particles, which always exhibit intrinsic contact angle (CA) hysteresis that is significantly amplified in 3D systems. Specifically, we designed and conducted the experiments using single prismatic particles, which allowed for the determination of two characteristic CAs at the two diagonal axes with a high degree of certainty. We calibrated the numerical solution to the 3D Young-Laplace equation using the deformed air-water interface profiles at the two diagonal axes and then validated the numerical solution for the capillary force on the floating particles with the measured force. We obtained reliable data for the CA along the three-phase contact line (TPCL), which displayed a significant distribution. We also discussed the findings that were significant to floating spheres in asymmetric systems, such as pairs of floating spheres. This paper provides experimental and theoretical evidence that the CA is not constant along the contact line in a 3D geometry, which invalidates the use of NBCs for 3D systems of floating particles. This study highlights the significance of the CA variation known as CA hysteresis, which should be considered when predicting the floatability of particles at the air-water interface.


Safety and tolerability of tegaserod in patients with irritable bowel syndrome and diarrhea symptoms.
Tegaserod is a selective serotonin (5-HT4) receptor partial agonist effective in providing relief from abdominal pain, bloating, and constipation in patients with irritable bowel syndrome. Tegaserod therapy may be associated with early transient diarrhea, which is related to its mechanism of action. This study was performed in patients with irritable bowel syndrome and symptoms of diarrhea to further assess the safety of tegaserod. After a 2-wk baseline, patients were randomized (2:2:1) in a double-blind manner to receive 4 mg of tegaserod a day (n = 35), 12 mg of tegaserod a day (n = 34), or placebos (n = 17) for 8 wk. Patients had to fulfill > or =2 Rome diarrhea criteria > or =25% of the time. Adverse events were recorded. Diarrhea, abdominal pain, headache, flatulence, and fatigue were the most frequently reported adverse events. The frequency rates of diarrhea were 49%, 18%, and 35% for the 4 mg/day, 12 mg/day, and placebo groups, respectively; when the tegaserod data were pooled, the frequency of diarrhea was similar to that of the placebo group (33% and 35%, respectively). No complications of diarrhea (e.g., dehydration and electrolyte abnormalities) were reported. Five patients (6%), all from the tegaserod groups, discontinued study participation because of diarrhea and/or abdominal pain. No serious adverse events were reported. In this study, tegaserod at doses of 4 and 12 mg/day was safe and not associated with complications of diarrhea or serious adverse events.


Regional contributions of D-serine to Alzheimer's disease pathology in male AppNL-G-F/NL-G-F mice.
Neurodegenerative processes in Alzheimer's disease (AD) are associated with excitotoxicity mediated by the N-methyl-D-aspartate receptor (NMDAR). D-Serine is an endogenous co-agonist necessary for NMDAR-mediated excitotoxicity. In the mammalian brain, it is produced by serine racemase (SRR) from L-serine, suggesting that dysregulation of L-serine, D-serine, or SRR may contribute to AD pathogenesis. We examined the contributions of D-serine to AD pathology in the AppNL-G-F/NL-G-F gene knock-in (APPKI) mouse model of AD. We first examined brain SRR expression levels and neuropathology in APPKI mice and then assessed the effects of long-term D-serine supplementation in drinking water on neurodegeneration. To further confirm the involvement of endogenous D-serine in AD progression, we generated Srr gene-deleted APPKI (APPKI-SRRKO) mice. Finally, to examine the levels of brain amino acids, we conducted liquid chromatography-tandem mass spectrometry. Expression of SRR was markedly reduced in the retrosplenial cortex (RSC) of APPKI mice at 12 months of age compared with age-matched wild-type mice. Neuronal density was decreased in the hippocampal CA1 region but not altered significantly in the RSC. D-Serine supplementation exacerbated neuronal loss in the hippocampal CA1 of APPKI mice, while APPKI-SRRKO mice exhibited attenuated astrogliosis and reduced neuronal death in the hippocampal CA1 compared with APPKI mice. Furthermore, APPKI mice demonstrated marked abnormalities in the cortical amino acid levels that were partially reversed in APPKI-SRRKO mice. These findings suggest that D-serine participates in the regional neurodegenerative process in the hippocampal CA1 during the amyloid pathology of AD and that reducing brain D-serine can partially attenuate neuronal loss and reactive astrogliosis. Therefore, regulating SRR could be an effective strategy to mitigate NMDAR-dependent neurodegeneration during AD progression.


Assessment of Sprint Parameters in Top Speed Interval in 100 m Sprint-A Pilot Study Under Field Conditions.
Improving performances in sprinting requires feedback on sprint parameters such as step length and step time. However, these parameters from the top speed interval (TSI) are difficult to collect in a competition setting. Recent advances in tracking technology allows to provide positional data with high spatio-temporal resolution. This pilot study, therefore, aims to automatically obtain general sprint parameters, parameters characterizing, and derived from TSI from raw speed. In addition, we propose a method for obtaining the intra-cyclic speed amplitude in TSI. We analyzed 32 100 m-sprints of 7 male and 9 female athletes (18.9 ± 2.8 years; 100 m PB 10.55-12.41 s, respectively, 12.18-13.31 s). Spatio-temporal data was collected with a radio-based position detection system (RedFIR, Fraunhofer Institute, Germany). A general velocity curve was fitted to the overall speed curve (vbase), TSI (upper quintile of vbase values) was determined and a cosine term was added to vbase within TSI (vcycle) to capture the cyclic nature of speed. This allowed to derive TSI parameters including TSI amplitude from the fitted parameters of the cosine term. Results showed good approximation for vbase (error: 5.0 ± 1.0%) and for vcycle (2.0 ± 1.0%). For validation we compared spatio-temporal TSI parameters to criterion values from laser measurement (speed) and optoelectric systems (step time and step length) showing acceptable RMSEs for mean speed (0.08 m/s), for step time (0.004 s), and for step length (0.03 m). Top speed interval amplitude showed a significant difference between males (mean: 1.41 m/s) and females (mean: 0.71 m/s) and correlations showed its independence from other sprint parameters. Gender comparisons for validation revealed the expected differences. This pilot study investigated the feasibility of estimating sprint parameters from high-quality tracking data. The proposed method is independent of the data source and allows to automatically obtain general sprint parameters and TSI parameters, including TSI amplitude assessed here for the first time in a competition-like setting.


A simple method for determining metronidazole resistance of Helicobacter pylori.
The reliability of methods for determination of Helicobacter pylori resistance to metronidazole has been found to depend upon the incubation time. Because the disk diffusion method is more vulnerable than other methods to prolonged incubation, this method has not been recommended for H. pylori. However, because media designed for rapid growth of H. pylori have been introduced, the time has come to look at the clinical usefulness of this inexpensive and simple method again. The correlation of readings obtained with the E test (AB Biodisk, Solna, Sweden) and Rosco's (Taastrup, Denmark) disk diffusion method for in vitro metronidazole resistance determination for H. pylori with a short incubation time (24 to 31 h) was studied. Plates which could not be read after 24 to 31 h were reincubated for another night. Fifty-seven consecutive clinical strains were tested. Because the rate of regrowth of H. pylori depends upon the age of the colonies inoculated, the reproducibility of resistance test results for young colonies versus old colonies was also studied. Resistance plates could be read after 24 to 31 h of incubation for 28 of 29 strains when the inoculum consisted of young colonies (3 to 4 days old). For these 29 strains, a high correlation (r = -0.937) was found between results obtained with the E test and those obtained with the disk diffusion test. A poorer correlation was found for old colonies (> or = 5 days old) (r = -0.742), which required a prolonged incubation for 8 of 23 strains. In conclusion, short incubation was successfully applied with young colonies. Results obtained with the simple and inexpensive disk diffusion method correlated well with those obtained with the E test.


Restoration of glutamatergic transmission by dopamine D4 receptors in stressed animals.
The prefrontal cortex (PFC), a key brain region for cognitive and emotional processes, is highly regulated by dopaminergic inputs. The dopamine D4 receptor, which is enriched in PFC, has been implicated in mental disorders, such as attention deficit-hyperactivity disorder and schizophrenia. Recently we have found homeostatic regulation of AMPA receptor-mediated synaptic transmission in PFC pyramidal neurons by the D4 receptor, providing a potential mechanism for D4 in stabilizing cortical excitability. Because stress is tightly linked to adaptive and maladaptive changes associated with mental health and disorders, we examined the synaptic actions of D4 in stressed rats. We found that neural excitability was elevated by acute stress and dampened by repeated stress. D4 activation produced a potent reduction of excitatory transmission in acutely stressed animals and a marked increase of excitatory transmission in repeatedly stressed animals. These effects of D4 targeted GluA2-lacking AMPA receptors and relied on the bi-directional regulation of calcium/calmodulin kinase II activity. The restoration of PFC glutamatergic transmission in stress conditions may enable D4 receptors to serve as a synaptic stabilizer in normal and pathological conditions.


Effect of donor age on the outcome of living-related kidney transplantation.
The study compared the results of kidney transplantation from living-related donors older and younger than 60 years. The 273 kidney graft recipients were divided into group 1 (115 recipients of older grafts) and group 2 (158 recipients of younger grafts). The frequency of acute rejection (AR) episodes was similar in both groups but slow graft function occurred more frequently in group 1. The frequency of chronic renal allograft dysfunction in the first post-transplant year was significantly higher in group 1 than in group 2. Patient and graft survival was significantly worse in group 1. Risk factors for graft loss were the difference between donor and recipient age and AR. Donor age and graft function were risk factors for patient death. Although kidneys from older donors provide a statistically poorer transplant outcome, they are clinically acceptable, especially when waiting time is prolonged and access to dialysis limited.


When do changes in cancer survival mean progress? The insight from population incidence and mortality.
It is often assumed that increases in cancer survival reflect true progress against cancer. This is true when these increases are accompanied by decreased burden of disease: Fewer people being diagnosed or dying from cancer (ie, decreased incidence and mortality). But increased survival can also occur even when incidence is increasing and mortality is unchanged. To use trends in cancer burden-incidence and mortality-to illustrate when changes in survival reflect true progress. Using data from 1975 to 2010 collected by the Surveillance, Epidemiology, and End Results Program (incidence, survival) and the National Center for Health Statistics (mortality), we analyzed US trends in five-year relative survival, age-adjusted incidence, and mortality for selected cancers to identify patterns that do and do not reflect progress. Among the nine common cancers examined, survival increased in seven, and changed little or not at all for two. In some cases, increased survival was accompanied by decreased burden of disease, reflecting true progress. For example, from 1975 to 2010, five-year survival for colon cancer patients improved (from 48% to 68%) while cancer burden fell: Fewer cases (incidence decreased from 60 to 41 per 100,000) and fewer deaths (mortality decreased from 28 to 16 per 100,000), a pattern explained by both increased early detection (with removal of cancer precursors) and more effective treatment. In other cases, however, increased survival did not reflect true progress. In melanoma, kidney, and thyroid cancer, five-year survival increased but incidence increased with no change in mortality. This pattern suggests overdiagnosis from increased early detection, an increase in cancer burden. Changes in survival must be interpreted in the context of incidence and mortality. Increased survival only represents progress when accompanied by a reduction in incidence, mortality, or ideally both.


Bisporphyrins with bischlorin features obtained by direct anodic coupling of porphyrins.
The proximity of two or more porphyrin or chlorin-like structures has been shown to be crucial in numerous biological processes, such as electron transfers. The one-pot electrochemical synthesis of a dimeric tetraphenylporphyrin with one 1,2-(diphenylphosphonium)benzene as a spacer and of its porphyrin-monomer precursor are reported. These new compounds have been characterized by (1)H and (31)P NMR, ESR, and UV-visible spectroscopy and microanalysis. Electrochemical data are reported, and the redox behavior is analyzed for the monomers and the dimers. Important interactions between the two chromophores and a phosphonium-phosphonium interaction have been observed. UV-visible and (1)H NMR data along with electrochemical behavior suggest that the positive charge carried by the two phosphonium units is in part delocalized onto the pi system of the porphyrins, this gives an unexpected bis-porphyrin with bischlorin spectroscopic features.


The complete mitochondrial genome structure of Schizothorax waltoni (Cypriniformes:Cyprinidae).
In this study, we sequenced and annotated the complete mitochondrial genome of Schizothorax waltoni (Cypriniformes:Cyprinidae). The mitogenome is 16,587 bp in length, which contains 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and 2 non-coding regions: origin of light-strand replication (O(L)) and control region (D-loop). The overall nucleotide base composition of S. waltoni mtDNA is A 29.96%, C 27.07%, G 17.58%, and T 25.39%, with an A + T content of 55.35%. Except for ND6 gene and eight tRNA genes, all other mitochondrial genes were encoded on the heavy strand. The mitochondrial genome of S. waltoni can contribute to the studies on conservation genetics and stock evaluation of S. waltoni resource, as well as molecular phylogeny and species identification of Cyprinidae.


Blood tranfusion in critically ill patients: state of the art.
Anemia is one of the most common abnormal findings in critically ill patients, and many of these patients will receive a blood transfusion during their intensive care unit stay. However, the determinants of exactly which patients do receive transfusions remains to be defined and have been the subject of considerable debate in recent years. Concerns and doubts have emerged regarding the benefits and safety of blood transfusion, in part due to the lack of evidence of better outcomes resulting from randomized studies and in part related to the observations that transfusion may increase the risk of infection. As a result of these concerns and of several studies suggesting better or similar outcomes with a lower transfusion trigger, there has been a general tendency to decrease the transfusion threshold from the classic 10 g/dL to lower values. In this review, we focus on some of the key studies providing insight into current transfusion practices and fueling the current debate on the ideal transfusion trigger.


[The effect of the tear film on the results of a direct assessment of the sensitivity of the cornea].
Attempts to find clinical application for esthesiometry are associated with studying sensitivity disorders that occur in various diseases (diabetes mellitus, keratitis of various etiologies, corneal erosion, dry eye syndrome), as well as after surgical interventions. To evaluate the influence of the tear film on the results of direct assessment of corneal sensitivity. The study was conducted in a group of 20 healthy volunteers. Criteria for inclusion in the group: absence of any ocular and general systemic diseases in the anamnesis, normal indicators of tear production and stability of the tear film according to Schirmer and Norn tests. The process of testing involved a specially designed device that was used to exert a dosed force by jets of air on the frontal corneal surface and the pressure was recorded at the moment of tactile sensations and at the breakup time of tear film, as an indicator of its biomechanical stability. A strong correlation have been found between the pressure of the air stream at the moment of getting tactile sensations and at the breakup of the tear film (R=0.91, p=0.0094). The obtained data indicate that the biomechanical resistance of the lacrimal film is a significant factor preventing the correct assessment of the results of direct corneal esthesiometry in the range of values close to conditionally normal sensitivity. In this regard, in their current technical implementation, modern esthesiometers can only be used for monitoring (not for diagnosis!) of pathological processes by analyzing relative (compared to each other) - rather than absolute - sensitivity measures (optimally in combination with analysis of the structural changes in the corneal nerves based on laser confocal microscopy).


Clinical Concepts for Triple Therapy Use in Patients with COPD: A Delphi Consensus.
Role of triple therapy in chronic obstructive pulmonary disease (COPD) management is supported by growing evidence, but consensus is lacking on various aspects. We conducted a Delphi survey in respiratory experts on the effects of triple therapy on exacerbation reduction, early optimization, pneumonia risk, and mortality benefits in COPD management. The study comprised 2-round online surveys and a participant meeting with 21 respiratory experts from 10 countries. The 31-statement questionnaire was prepared using Decipher software after literature review. Responses were recorded using Likert scale ranging from 1 (disagreement) to 9 (agreement) with a consensus threshold of 75%. All experts participated in both surveys and 14/21 attended participant meeting. Consensus was reached on 13/31 questions in first survey and 4/14 in second survey on: mortality benefits of triple therapy; comparable pneumonia risk between single inhaler triple therapy (SITT) and multiple inhaler triple therapy (81%); preference of SITT for patients with high eosinophil count (95%); exacerbation risk reduction and healthcare cost benefits with early initiation of SITT post exacerbation-related hospitalization (<30 days) (86%). No consensus was reached on first line SITT use after first exacerbation resulting in COPD diagnosis (62%). This study demonstrated that there is consensus among experts regarding many of the key concepts about appropriate clinical use and benefits of triple therapy in COPD. More evidence is required for evaluating the benefits of early optimisation of triple therapy.


The Sufi, his headdress and its significance.
Etymologically Sufi, as an Arabic word, means woolen-clad. This is unsuitable in designating a devotee who tries to have union with God. When the word is taken to Chinese it means (my) master-and-father, my Guru. There are at least nine more words used in addressing the Sufi or speaking of him, all of Chinese origin. This leaves no word specially used for the sufi which is not derived from Chinese. Next comes a rite special to the sufis, it is whirling-dancing. It has no precedence in traditional Islam. On the contrary "Dancing in ancient China was a powerful means of seeking divine will, and producing ecstasy for calling down spirits from the invisible word." Thus sufism would be an adaptation from Chinese Shamanism. The headdress, rather than the dress covering the body, is special to the sufis; it is a long hat made to resemble the male generative organ. In ancient times this organ was sanctified and, as sacred object, its emblem formed the headdress of male and female deities. Even sages were buried with emblem of the male organ on their heads. The earlier form of Hindu Trinity was called Trai-Linga-Ishwara, where Linga literally means the male organ but semantically connotes creative power. To understand creation man had projected Birth as Creation when the male organ of reproduction was sublimated as power of creation. The prehistoric word was Chhiu, meaning phallus. This was pronounced as Shiu or Shew and later became Shiva, who was Phallus-god. In Greece Hermes was Phallus-god. With Shiva there was the Trinity Trai-Linga-Ishwara; Hermes was correspondingly called Tris-Majestis. The headdress, originally formed to resemble the male organ of reproduction underwent modifications. It grew in length while the top, from being round became flat. In this form it could be used without a cloth wrapped round to support it on the head. This was again unique and used only by the Sufis. Its past took it to the emblem of male generative organ but in all stages represented creative power.


Case Report: Ectopic Liver (Choristoma) Discovered During Laparoscopic Cholecystectomy.
BACKGROUND Ectopic liver (EL) is liver tissue that is not attached to the mother liver, and is also known as choristoma and hepar succenturiatum. According to Watanabe's 1060-patient series, it has an incidence rate of less than 1% (0.47%). The absence of an anatomical attachment to the hepatic proper is a rare congenital departure from the norm, known as EL. EL is thought to be caused by abnormal hepatic tissue growth from the foregut diverticulum, particularly at cystic structures. CASE REPORT We report the successful management of a 47-year-old male patient, not known to have any medical illness, who was referred to the surgical team with a clinical picture of biliary colic. An ultrasound (US) abdomen was performed, and cholecystitis was confirmed. During a laparoscopic cholecystectomy, ET was identified by chance. He tolerated the operation well. Gallbladder histological examination revealed significant mucosal and wall ulcers, chronic inflammation, many black stones, no dysplasia or malignancy, and connected liver tissue measuring 12×5 mm. As a result, chronic calcular cholecystitis was confirmed, as was normal EL architecture and no evidence of malignancy. CONCLUSIONS We conclude that EL is a rare condition, but there have been cases reported in the literature. Imaging modalities such as US and computed tomography scans are recommended to rule out other underlying diagnoses and should be tailored to each individual when necessary. Because the presence of EL attached to the vesicle is a rare occurrence in the literature, a histological examination is required due to the elevated risk of hepatocellular carcinoma. Keeping such an abnormality in mind can help surgeons demarcate the embryological plane of dissection during cholecystitis to avoid tumor cell spillages if present.


[Myelopathy due to vitamin B12 deficiency presenting only sensory disturbances in upper extremities: a case report].
We report a 54-year-old man with vitamin B12 deficiency myelopathy limited to the upper extremity region. He was well until October, 1995, when he had an onset of exertional dyspnea and general fatigue. Then he noted tingling sensation in bilateral upper extremities in March, 1996. He had undergone total gastrectomy due to gastric ulcer 15 years ago. Neurological examination revealed superficial and vibratory sensory loss in the upper extremities distal to elbows, and pseudoathetoid movement of the left fingers. Otherwise neurological examination was unremarkable. Laboratory examination revealed macrocytic anemia, and low serum vitamin B12. However, serum folate was within the normal range. In SEP studies, median nerve stimulation evoked peripheral N9 and N13 potentials, but not cortical N20 one. Posterior tibial nerve stimulation elicited normal responses. MEP, VEP, needle EMG, and nerve conduction studies gave normal findings. T2-weighted MRI showed high signal intensity lesions at the C1-Th1 level in the posterior column, especially in the cuneate fascicles. The gracile fascicles were spared. This is a very rare case of myelopathy due to vitamin B12 deficiency presenting only sensory disturbances in both upper extremities. The lesions limited in the cuneate fascicle were confirmed by electrophysiological, and neuroradiological examinations.


Pharmacokinetics of estradiol and of estrone during application of a new 7-day estradiol transdermal patch with active matrix.
The pharmacokinetic patterns of estradiol (CAS 50-28-2) and of estrone (CAS 53-16-7) were investigated in 18 women in natural or surgical menopause during the application of a new estradiol transdermal patch with active matrix and without absorption enhancers designed for epicutaneous applications of 7 days (hereinafter called "patch 7D"). The study was made with randomized and balanced sequences of applications in cross-over of either patch 7D or of an authorized estradiol transdermal patch with a nominal release rate of 50 micrograms/day estradiol designed for a twice-a-week epicutaneous application (hereinafter called "patch 50"). The sequences consisted of applications for 3 weeks either of 3 patches 7D or of 6 patches 50. The patches were applied on the skin of the hips or upper buttocks. The serum samples were obtained during the 1st and during the last week of application of the patches. Estradiol (E2) was assayed in serum by a double-antibody RIA method selective for free estradiol. Estrone (E1) was assayed in serum using a 3H-estrone RIA method. The steady state with regard to E2 and E1 was achieved already during the application of the 2nd patch. Patch 7D provided within 6 h an increase of the E2 concentrations in serum from the basal postmenopausal level of less than 3 pg/ml to therapeutically effective concentrations. The Cmax of E2 of 45 pg/ml was reached on average after 25 h, the concentrations of E2 remaining at sustained and therapeutically effective levels during the whole application of patch 7D. At steady state, during the 3rd week of application, the Cav was on average 31 pg/ml. With a small delay, E1 also increased from the basal 15 pg/ml to a Cmax of 41 pg/ml after 44 h. At steady state, during the 3rd week of application, the Cav was on average 38 pg/ml. Patch 7D provided a similar bioavailability as patch 50 with regard to the rate and the extent of absorption of E2, as shown by the AUCs during the 7-day applications of one patch 7D compared to those during the 7-day applications of 2 patches 50. The release of E2 from patch 7D is therefore similar to that of patch 50, i.e. on an average of 50 micrograms/day over a 7-day period of application. The E2/E1 ratio increased from the postmenopausal values lower than 0.2 found before the application of patch 7D to average values of 0.67, i.e., to values that are normally found during the fertile life of the woman. The improvement of the E2/E1 ratio occurred already in the first 6-12 h of application of patch 7D. The E2/E1 ratio returned rapidly to the initial low postmenopausal levels after removal of the patch. Patch 7D was well tolerated by the skin, probably because it does not contain absorption enhancers. It provoked, however, some systemic adverse reactions typical of E2 overdosing. In the therapeutic practice these adverse reactions can easily be avoided using patches 7D of lower strength. No drop-out due to systemic or local intolerance occurred. The adhesion of patch 7D on the skin was good. During the application of a total of 54 patches, only in one occasion one patch became partially detached (about 40% of the total area) from the 3rd to the 7th day during the first 7-day period of application.


[Sensitivity and specificity of noninvasive prenatal fetal RhD genotesting: a meta-analysis].
To explore the sensitivity, specificity and clinical validity of fetal Rh genotyping from maternal blood. A comprehensive literature search of PubMed, Embase and Web of Science was performed for describing fetal RhD determination from maternal blood. The inclusion criteria were established based on the validity criteria for diagnostic research. And the eligible entries were collected and analyzed with MetaDisc4.0. This meta-analysis included 55 studies with a total of 17 138 samples. The random-effect model was used for analysis because of heterogeneity. The pooled sensitivity and specificity were 98.5% and 97.3% respectively. The SROC curve was plotted and the area under the curve (AUC) calculated (AUC = 0.994). The subgroup and sensitivity analyses were performed. The sensitivity of 25 studies with samples<100 (94.6%) was significantly lower than those of 19 studies with samples 100-300 (98.5%) and 11 studies with samples>300 (99.0%) (χ² = 36.800, 106.062, P < 0.05). The sensitivity of 19 studies with samples 100-300 (98.5%) was not different from that of 11 studies with samples >300 (99.0%)( χ² = 3.068, P > 0.05). Noninvasive prenatal diagnosis of fetal RhD status from maternal blood represents a significant achievement in the application of research with high sensitivity and specificity. It may be applied for screening testing of all RhD⁻ negative pregnant women.


Influences of electric field on living cells in a charged water-in-oil droplet under electrophoretic actuation.
We experimentally investigate the effects of high electric field on living cells inside a charged droplet under electrophoretic actuation. When an aqueous droplet suspended in a dielectric liquid contacts with electrified electrode, the droplet acquires charge. This charged droplet undergoes electrophoretic motion under strong electric field (1-3 kV/cm), which can be used as a droplet manipulation method in biomicrofluidic applications. However, because strong electric field and use of dielectric oil can be a harmful environment for living cells, the biological feasibilities have been tested. Trypan blue test and cell growth test have been performed to check the viability and proliferation of cells in a droplet under various electric field strengths and actuation times. We have not observed any noticeable influence of electric field and silicone oil on the viability and proliferation of cells, which indicates that electrophoresis could be safely used as a manipulation method for a droplet containing living biological system.


Predictive data mining in clinical medicine: current issues and guidelines.
The widespread availability of new computational methods and tools for data analysis and predictive modeling requires medical informatics researchers and practitioners to systematically select the most appropriate strategy to cope with clinical prediction problems. In particular, the collection of methods known as 'data mining' offers methodological and technical solutions to deal with the analysis of medical data and construction of prediction models. A large variety of these methods requires general and simple guidelines that may help practitioners in the appropriate selection of data mining tools, construction and validation of predictive models, along with the dissemination of predictive models within clinical environments. The goal of this review is to discuss the extent and role of the research area of predictive data mining and to propose a framework to cope with the problems of constructing, assessing and exploiting data mining models in clinical medicine. We review the recent relevant work published in the area of predictive data mining in clinical medicine, highlighting critical issues and summarizing the approaches in a set of learned lessons. The paper provides a comprehensive review of the state of the art of predictive data mining in clinical medicine and gives guidelines to carry out data mining studies in this field. Predictive data mining is becoming an essential instrument for researchers and clinical practitioners in medicine. Understanding the main issues underlying these methods and the application of agreed and standardized procedures is mandatory for their deployment and the dissemination of results. Thanks to the integration of molecular and clinical data taking place within genomic medicine, the area has recently not only gained a fresh impulse but also a new set of complex problems it needs to address.


Polarized-Light-Emitting Quantum-Rod Diodes.
For the first time, polarized-light-emitting quantum-rod diodes have been successfully produced, using thin layers of quantum rods oriented by a rubbing technique. Diode emission at 620 nm with a luminance efficiency of 0.65 Cd A-1 and an external quantum efficiency of 0.49 % is obtained.


cAMP-dependent protein kinase A mediation of vasopressin gene expression in the hypothalamus of the osmotically challenged rat.
We have tested the hypothesis that 3', 5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) is involved in the regulation of the vasopressin (VP) gene in the magnocellular neurons of the paraventricular nucleus (PVN) of the osmotically challenged rat. An adenoviral vector expressing a potent peptide inhibitor of PKA, Ad.CMV.PKIalpha, was demonstrated to be highly efficient in vitro. Ad.CMV.PKIalpha was then introduced into the PVN of rats bearing a VP reporter transgene (3-VCAT-3) consisting of the VP structural gene containing an epitope reporter in exon III, flanked by 3 kb of upstream and 3 kb of downstream sequence Robust transgene expression is seen in VP neurons of the PVN, and this increases following 72 h of dehydration. Ad.CMV.PKIalpha significantly blunted 3-VCAT-3 expression in the osmotically stimulated PVN. Our evidence suggests that PKA mediates changes in VP gene expression in response to dehydration through sequences contained within the 3-VCAT-3 transgene.


Molecular-level insights into intrinsic peroxidase-like activity of nanocarbon oxides.
Nanocarbon oxides have been proved to possess great peroxidase-like activity, catalyzing the oxidation of many peroxidase substrates, such as 3,3',5,5'-tetramethylbenzidine (TMB) and o-phenylenediamine dihydrochloride (OPD), accompanied by a significant color change. This chromogenic reaction is widely used to detect glucose and occult blood. The chromogenic reaction was intensively investigated with density functional theory and molecular-level insights into the nature of peroxidase-like activity were gained. A radical mechanism was unraveled and the carboxyl groups of nanocarbon oxides were identified as the reactive sites. Aromatic domains connected with the carboxyl groups were critical to the peroxidase-like activity.


Letting a typical mouse judge whether mouse social interactions are atypical.
Diagnosis of an autism spectrum disorder (ASD) requires a qualitative assessment of social aptitude: one person judging whether another person interacts in a "typical" way. We hypothesized that mice could be used to make a similar judgment if they prefer "typical" over "atypical" social interactions with mouse models relevant to ASD. We used wild-type C57BL/6 (B6) mice as "judges" and evaluated their preference for a chamber containing a "typical" (B6 or 129S6) or an "atypical" mouse. For our atypical mouse stimuli, we chose two inbred strains with well-documented social phenotypes (BTBR and BALB/c), as well a mutant line with abnormal social behavior and seizures (Gabrb3 +/-). Overall, we observed a stimulus by time interaction (P < 0.0001), with B6 mice preferring the typical mouse chamber during the last 10 min of the 30-min test. For two of the individual stimulus pairings, we observed a similar chamber by time interaction (BALB/c vs. 129S6, P = 0.0007; Gabrb3 +/- vs. 129S6, P = 0.033). For the third stimulus pairing, we found a trend for preference of the typical mouse across time (BTBR vs. B6, P = 0.051). We repeated the experiments using 129S6 mice as judges and found a significant overall interaction (P = 0.034), but only one stimulus pairing reached significance on its own (BALB/c vs. 129S6, P = 0.0021). These data suggest that a characteristic pattern of exploration in B6 mice can distinguish some socially atypical animals from controls.


Changes in thyroid function and immunological parameters long after subtotal thyroidectomy for Graves' disease.
To find out whether subtotal thyroidectomy results in long term stable functional and immunological remission in patients with Graves' disease. Retrospective study. Teaching hospital, Japan. 176 patients who underwent subtotal thyroidectomy for Graves' disease, 1970-79. Follow up surveys in 1984 and 1992. Changes in thyroid function, antibody titres, and lymphocyte subsets. 29/79 patients (39%) who were euthyroid in 1984 had evidence of thyroid dysfunction in 1992. Of the 8 patients with latent hypothyroidism in 1984, 3 (38%) had become euthyroid by 1992, and none required treatment. Of the 29 patients who were hypothyroid in 1984, 5 had latent hypothyroidism and 1 was euthyroid in 1992, and of the 18 patients with recurrent hyperthyroidism in 1984, 1 had become euthyroid by 1992. The number of positive titres to TSH-binding inhibitory immunoglobulin was significantly higher in the recurrence group (31/36, 86%) compared with the hypothyroid (7/26, 27%), latent hypothyroidism (8/37, 22%), and euthyroid (22/77, 29%) groups (p < 0.01). There were also significant differences in the mean (SD) number of Leu HLA DR subsets between the control (17 (3), n = 18) and recurrence (21 (6), n = 38), hypothyroid (22 (6), n = 35), latent hypothyroidism (22 (6), n = 22), and euthyroid (22 (9), n = 64) groups (p < 0.002). There were no differences in the number of T cell subsets among the groups. Treatment of Graves' disease by subtotal thyroidectomy does not necessarily result in stable late functional or immunological remission. Long term follow up of such patients may be necessary.


Low-temperature and atmospheric pressure plasma for palm biodiesel hydrogenation.
Partially hydrogenated fatty acid methyl ester (H-FAME) is conventionally produced through partial hydrogenation under high pressure and elevated temperature in the presence of a catalyst. Herein, a novel green, catalyst-free, non-thermal and atmospheric pressure dielectric barrier discharge (DBD) plasma was employed instead of a conventional method to hydrogenate palm FAME. H-FAME became more saturated with the conversion of C18:2 and C18:3 of 47.4 and 100%, respectively, at 100 W input power, 1 mm gas-filled gap size and 80% H2 in the mixed gas at room temperature for 5 h, causing a reduction of the iodine value from 50.2 to 43.5. Oxidation stability increased from 12.8 to 20 h while a cloud point changed from 13.5 to 16 °C. Interestingly, DBD plasma hydrogenation resulted in no trans-fatty acid formation which provided a positive effect on the cloud point. This green DBD plasma system showed a superior performance to a conventional catalytic reaction. It is an alternative method that is safe from explosion due to the mild operating condition, as well as being highly environmentally friendly by reducing waste and energy utilization from the regeneration process required for a catalytic process. This novel green plasma hydrogenation technique could also be applied to other liquid-based processes.


Toward the synthetic control of the HOMO-LUMO gap in binuclear systems: insights from density functional calculations.
Computational methods based on density functional theory have been applied to address the design of tailored HOMO-LUMO gap bimetallic complexes. We focus our attention on the [Cp*Fe-(L)-FeCp*] system, where two ferrocenyl units are linked through the dianion of fused ring ligands such as pentalene, s-indacene, dicyclopenta-[b,g]-naphthalene, dicyclopenta-[b,i]-anthracene and dicyclopenta-[b,l]-tetracene. Our DFT calculations on the title organometallic complexes suggest a controlled decrease in the HOMO-LUMO gap, which is desirable for studies on electron-transfer phenomena, as well as the design potential devices for molecular electronic purposes.


Evolution of a pheochromocytoma.
To present a case that demonstrates the evolution of a pheochromocytoma over a several-year period and to emphasize the importance of a thorough work-up for pheochromocytoma in patients with neurofibromatosis type 1 (NF1) and hypertension. We review the long-term clinical, biochemical, and imaging findings in a man with a complex medical history of hypertension, NF1, and cardiomyopathy. A 44-year-old man, with a well-documented history of headaches, hypertension, and NF1, was referred for evaluation of a right adrenal enlargement. He had developed cardiomyopathy and undergone an evaluation for cardiac transplantation. Initial computed tomography revealed subtle asymmetry in the upper right adrenal gland. Biochemical studies for pheochromocytoma yielded equivocal findings, with a 1.5-fold elevation in the urinary norepinephrine and near-normal urinary metanephrine level. Because 131I-metaiodobenzylguanidine imaging showed no tracer uptake in the area of the right adrenal gland, the patient was thought not to have a pheochromocytoma. The patient eventually underwent cardiac transplantation and did well. On reassessment 3 1/2 years later, he was found to have a larger right adrenal mass. The second endocrine evaluation demonstrated substantial elevation in the urinary metanephrine level, and the patient underwent laparoscopic right adrenalectomy to remove the tumor (3.5 by 3.0 by 2.5 cm), which proved to be a pheochromocytoma. This case shows that a pheochromocytoma can be difficult to diagnose and can evolve to become a large, biochemically active tumor. It is imperative that patients with an adrenal tumor undergo periodic reevaluation to ensure that the tumor remains stable in size. If the tumor enlarges, further biochemical testing is warranted.


The effects of a web-based intervention on psychosocial well-being among adults aged 60 and older with diabetes: a randomized trial.
The purpose of this study is to investigate the impact of a 6-month Web-based intervention on the psychosocial well-being of older adults with diabetes. This study was a randomized controlled trial (N - 62) comparing the effects of a 6-month Web-based intervention plus usual care with usual care alone among adults aged 60 years or older with diabetes. The outcomes included quality of life, depression, social support, and self-efficacy. The intervention group showed significant improvement, F(4.48) - 4.03 P - .007, when compared with the control group on measures of depression, quality of life, social support, and self-efficacy when controlling for all baseline outcome variables (age, gender, and number of years with diabetes). These findings provide support for the conclusion that a Web-based intervention is effective in improving the psychosocial well-being of participants at a 6-month follow-up. Future research needs to investigate the long-term effectiveness of Web-based interventions for sustaining psychosocial well-being, including factors that may affect quality of life, such as diabetes-specific beliefs, attitudes, social support, and disease-specific coping skills.


[Data coding in the Israeli healthcare system - do choices provide the answers to our system's needs?].
The IsraeLi healthcare system has undergone major processes for the adoption of health information technologies (HIT), and enjoys high Levels of utilization in hospital and ambulatory care. Coding is an essential infrastructure component of HIT, and ts purpose is to represent data in a simplified and common format, enhancing its manipulation by digital systems. Proper coding of data enables efficient identification, storage, retrieval and communication of data. UtiLization of uniform coding systems by different organizations enables data interoperability between them, facilitating communication and integrating data elements originating in different information systems from various organizations. Current needs in Israel for heaLth data coding include recording and reporting of diagnoses for hospitalized patients, outpatients and visitors of the Emergency Department, coding of procedures and operations, coding of pathology findings, reporting of discharge diagnoses and causes of death, billing codes, organizational data warehouses and national registries. New national projects for cLinicaL data integration, obligatory reporting of quality indicators and new Ministry of Health (MOH) requirements for HIT necessitate a high Level of interoperability that can be achieved only through the adoption of uniform coding. Additional pressures were introduced by the USA decision to stop the maintenance of the ICD-9-CM codes that are also used by Israeli healthcare, and the adoption of ICD-10-C and ICD-10-PCS as the main coding system for billing purpose. The USA has also mandated utilization of SNOMED-CT as the coding terminology for the ELectronic Health Record problem list, and for reporting quality indicators to the CMS. Hence, the Israeli MOH has recently decided that discharge diagnoses will be reported using ICD-10-CM codes, and SNOMED-CT will be used to code the cLinical information in the EHR. We reviewed the characteristics, strengths and weaknesses of these two coding systems. In summary, the adoption of ICD-10-CM is in line with the USA decision to abandon ICD-9-CM, and the Israeli heaLthcare system could benefit from USA heaLthcare efforts in this direction. The Large content of SNOMED-CT and its sophisticated hierarchical data structure will enable advanced cLinicaL decision support and quality improvement applications.


Oxidative stress and inflammation in iron-overloaded patients with beta-thalassaemia or sickle cell disease.
Blood transfusion therapy is life-saving for patients with beta-thalassaemia and sickle cell disease (SCD), but often results in severe iron overload. This pilot study examined whether the biomarkers of tissue injury or inflammation differ in these two diseases. Plasma malondialdehyde (MDA) was significantly increased 1.8-fold in thalassaemia relative to control patients. In contrast, MDA in SCD was not significantly different from controls. In multivariate analysis, the strongest predictors of elevated MDA were liver iron concentration (P < 0.001) and specific diagnosis (P = 0.019). A significant 2-fold elevation of non-transferrin bound iron (NTBI) was observed in thalassaemia relative to SCD. NTBI was not a significant predictor of high MDA in multivariate analysis. SCD patients showed a significant 2.2-fold elevation of the inflammatory marker interleukin (IL)-6 relative to controls, and a 3.6- and 1.7-fold increase in IL-5 and IL-10 relative to thalassaemia. Although alpha-tocopherol was significantly decreased by at least 32% in both thalassaemia and SCD, indicating ongoing oxidant stress and antioxidant consumption, gamma-tocopherol, a nitric oxide-selective antioxidant, was increased 36% in SCD relative to thalassaemia. These results demonstrate that thalassaemia patients have increased MDA and circulating NTBI relative to SCD patients and lower levels of some cytokines and gamma-tocopherol. This supports the hypothesis that the biology of SCD may show increased inflammation and increased levels of protective antioxidants compared with thalassaemia.


Manual acupuncture plus usual care versus usual care alone in the treatment of endometriosis-related chronic pelvic pain: study protocol for a randomised controlled feasibility study.
Endometriosis is the most common cause of chronic pelvic pain worldwide. Non-surgical treatments are effective for only 30-50% of women and have a significant side effect burden that leads to high discontinuation rates. Surgery can be effective but is expensive and invasive, and symptoms tend to recur within 5 years. There is early evidence that acupuncture may be effective in treating endometriosis-related chronic pelvic pain, showing clinically significant analgesia. Both levels of inflammation and pain processing have been shown to be altered in women with chronic pelvic pain. Acupuncture has been shown to reduce inflammation and change central pain processing in other conditions, but research on women with endometriosis is currently lacking. The aim of this feasibility study is to provide data on recruitment rates, retention, appropriateness of outcome measures, minimal clinically important difference in numeric rated scales for pain and the potential effect of acupuncture on pain processing and markers of inflammation in endometriosis-related CPP. We will include women aged 18-45 years with a diagnosis of endometriosis via laparoscopy in the past 5 years. A total of 30 participants will be recruited and randomly allocated in a 1:1 ratio to receive acupuncture or usual care. Women in the acupuncture group will receive two 45-min treatment sessions per week for 8 weeks (total of 16 sessions). Women in the usual care group will continue with their current treatment regimen. The primary feasibility outcomes are recruitment rates, retention rates and the safety and acceptability of the intervention; secondary patient-centred outcomes include a change in 0-10 daily pelvic pain ratings, the Endometriosis Health Profile 30 (EHP-30) and changes in conditioned pain modulation, resting and task-related EEG activity and inflammatory markers. Analyses will be performed blind to group allocation. This is a two-armed, assessor blind, randomised controlled feasibility trial. Data will be compared at baseline and trial completion 8 weeks later. Outcomes from this feasibility study will inform a larger, fully powered clinical trial should the treatment show trends for potential effectiveness. Australian New Zealand Clinical Trials Registry, ACTRN12617000053325 (http://www.ANZCTR.org.au/ACTRN12617000053325.aspx).


Comparing LD50/LC50 Machine Learning Models for Multiple Species.
The lethal dose or concentration which kills 50% of the animals (LD50 or LC50) is an important parameter for scientists to understand the toxicity of chemicals in different scenarios that can be used to make go-no-go decisions, and ultimately assist in the choice of the right personal protective equipment needed for containment. The LD50 assessment process has also required the use of many animals although modern methods have reduced the number of rats needed. Since a compound is usually considered highly toxic when the LD50 is lower than 25 mg/kg, such a classification provides potentially valuable safety information to synthetic chemists and other safety assessment scientists. The need for finding alternative approaches such as computational methods is important to ultimately reduce animal use for this testing further still. We now summarize our efforts to use public data for building in vivo LD50 or LC50 classification and regression machine learning models for various species (rat, mouse, fish and daphnia) and their 5-fold cross validation statistics with different machine learning algorithms as well as an external curated test set for mouse LD50. These datasets consist of different molecule classes, may cover different activity ranges, and also have a range of dataset sizes. The challenges of using such computational models are that their applicability domain will also need to be understood so that they can be used to make reliable predictions for novel molecules. These machine learning models will also need to be backed up with experimental validation. However, such models could also be used for efforts to bridge gaps in individual toxicity datasets. Making such models available also opens them up to potential misuse or dual use. We will summarize these efforts and propose that they could be used for scoring the millions of commercially available molecules, most of which likely do not have a known LD50 or for that matter any data in vitro or in vivo for toxicity.


Markets in women's reproductive labor.
Much of the evolution of social policy in the twentieth century has occurred around conflicts over the scope of markets. To what extent, under what conditions, and for what reasons should we limit the use of markets? Recently, American society has begun to experiment with markets in women's reproductive labor. Many people believe that markets in women's reproductive labor, as exemplified by contract pregnancy, are more problematic than other currently accepted labor markets. I will call this the asymmetry thesis because its proponents believe that there ought to be an asymmetry between our treatment of reproductive labor and our treatment of other forms of labor. Advocates of the asymmetry thesis hold that treating reproductive labor as a commodity, as something subject to the supply-and-demand principles that govern economic markets, is worse than treating other types of human labor as commodities. Is the asymmetry thesis true? And, if so, what are the reasons for thinking that it is true? My aims in this article are to criticize several popular ways of defending the asymmetry thesis and to offer an alternative defense....I focus my discussion on those arguments against contract pregnancy that depend on the asymmetry thesis. I believe that the asymmetry thesis both captures strong intuitions that exist in our society and provides a plausible argument against contract pregnancy.


Limb body wall complex.
Limb body wall complex (LBWC) is a rare clinicopathological entity, representing a compound anomaly pattern in ventral body wall defects. The authors report a case of LBWC diagnosed in early antenatal period. The pregnancy was terminated following the diagnosis. Fetal autopsy findings were typical of LBWC.


Altered lipid content inhibits autophagic vesicular fusion.
The autophagic/lysosomal system includes a variety of vesicular compartments that undergo dynamic fusion events. However, the characteristics and factors modulating these interactions remain, for the most part, unknown. To gain insights on the properties that govern lysosomal fusion events, we have established an in vitro fusion assay using different lysosomal/autophagic compartments isolated from mouse liver. We have found that autophagosome/lysosome fusion is a temperature-dependent process (fusion increment of 0.2+/-0.01%/degrees C), which requires ATP (1-3 mM), GTP (1-2 mM), Ca(2+) (0.2-2 mM), and an acidic lysosomal pH (pH 5.2). Furthermore, changes in membrane lipid composition, induced either in vitro, by treatment with 25 mM methyl-beta-cyclodextrin, or in vivo, by subjecting animals to a high-fat-diet challenge (60% kcal in fat) reduce autophagosome/lysosome fusion up to 70% of that observed in untreated fractions or from animals under a normal regular diet. These findings reveal a novel role for lipids in autophagic fusion and provide a mechanism for the reduced macroautophagic rates observed during exposure to a chronic lipid challenge. Changes in the intracellular lipid content (i.e., metabolic disorders) may thus have pronounced effects on the fusion step of macroautophagy and affect the overall activity of this intracellular proteolytic pathway.


Dietary Buglossoides Arvensis Oil Increases Circulating n-3 Polyunsaturated Fatty Acids in a Dose-Dependent Manner and Enhances Lipopolysaccharide-Stimulated Whole Blood Interleukin-10-A Randomized Placebo-Controlled Trial.
Buglossoides arvensis (Ahiflower) oil is a dietary oil rich in stearidonic acid (20% SDA; 18:4 n-3). The present randomized, double blind, placebo-controlled clinical trial investigated the effects of three Ahiflower oil dosages on omega-3 polyunsaturated fatty acid (PUFA) content of plasma and mononuclear cells (MCs) and of the highest Ahiflower dosage on stimulated cytokine production in blood. Healthy subjects (n = 88) consumed 9.7 mL per day for 28 days of 100% high oleic sunflower oil (HOSO); 30% Ahiflower oil (Ahi) + 70% HOSO; 60% Ahi + 40% HOSO; and 100% Ahi. No clinically significant changes in blood and urine chemistries, blood lipid profiles, hepatic and renal function tests nor hematology were measured. Linear mixed models (repeated measures design) probed for differences in time, and time × treatment interactions. Amongst significant changes, plasma and MC eicosapentaenoic acid (EPA, 20:5 n-3) levels increased from baseline at day 28 in all Ahiflower groups (p < 0.05) and the increase was greater in all Ahiflower groups compared to the HOSO control (time × treatment interactions; p < 0.05). Similar results were obtained for α-linolenic acid (ALA, 18:3 n-3), eicosatetraenoic acid (ETA, 20:4 n-3), and docosapentaenoic acid (DPA, 22:5 n-3) content; but not docosahexaenoic acid (DHA, 22:6 n-3). Production of interleukin-10 (IL-10) was increased in the 100% Ahiflower oil group compared to 100% HOSO group (p < 0.05). IL-10 production was also increased in lipopolysaccharide (LPS)-stimulated M2-differentiated THP-1 macrophage-like cells in the presence of 20:4 n-3 or EPA (p < 0.05). Overall; this indicates that the consumption of Ahiflower oil is associated with an anti-inflammatory phenotype in healthy subjects.


Racial/Ethnic Group Differences in Older Adults' Involvement with Adult Protective Services.
This paper represents the first study to focus on quantifying racial/ethnic group differences in older adults' involvement with adult protective services (APS). Across 3 independent county programs, the rate of APS reports was about twice as high for Black older adults compared to White older adults. These differences were greater for clients who were older and male but remained similar across allegation type. The percent of reports validated was slightly but consistently lower for Black clients than for White clients, and a lower percentage of Black clients' cases were closed due to investigation or service refusal. Findings for Hispanic clients differed by county, so it was impossible to generalize about their APS experience. Researchers should distinguish racial/ethnic group differences that persist across multiple programs from those that are program-specific. Further studies with larger data sets are needed to guide APS practice and ensure equity for all clients served. .


Selective oxidation of benzylic alcohols via synergistic bisphosphonium and cobalt catalysis.
A synergistic photocatalytic system using a bisphosphonium catalyst and a cobalt catalyst has been developed, enabling the selective oxidation of benzylic alcohols under oxidant-free and environmentally benign conditions. High efficiencies have been obtained for a variety of alcohol substrates, and exclusive selectivity for aldehyde products has been achieved across the board. Furthermore, this photocatalytic system proved to be efficient when performed under continuous-flow conditions, even using a simple and easily assembled continuous-flow setup.


The α5 subunit regulates the expression and function of α4*-containing neuronal nicotinic acetylcholine receptors in the ventral-tegmental area.
Human genetic association studies have shown gene variants in the α5 subunit of the neuronal nicotinic receptor (nAChR) influence both ethanol and nicotine dependence. The α5 subunit is an accessory subunit that facilitates α4* nAChRs assembly in vitro. However, it is unknown whether this occurs in the brain, as there are few research tools to adequately address this question. As the α4*-containing nAChRs are highly expressed in the ventral tegmental area (VTA) we assessed the molecular, functional and pharmacological roles of α5 in α4*-containing nAChRs in the VTA. We utilized transgenic mice α5+/+(α4YFP) and α5-/-(α4YFP) that allow the direct visualization and measurement of α4-YFP expression and the effect of the presence (α5+/+) and absence of α5 (-/-) subunit, as the antibodies for detecting the α4* subunits of the nAChR are not specific. We performed voltage clamp electrophysiological experiments to study baseline nicotinic currents in VTA dopaminergic neurons. We show that in the presence of the α5 subunit, the overall expression of α4 subunit is increased significantly by 60% in the VTA. Furthermore, the α5 subunit strengthens baseline nAChR currents, suggesting the increased expression of α4* nAChRs to be likely on the cell surface. While the presence of the α5 subunit blunts the desensitization of nAChRs following nicotine exposure, it does not alter the amount of ethanol potentiation of VTA dopaminergic neurons. Our data demonstrates a major regulatory role for the α5 subunit in both the maintenance of α4*-containing nAChRs expression and in modulating nicotinic currents in VTA dopaminergic neurons. Additionally, the α5α4* nAChR in VTA dopaminergic neurons regulates the effect of nicotine but not ethanol on currents. Together, the data suggest that the α5 subunit is critical for controlling the expression and functional role of a population of α4*-containing nAChRs in the VTA.


Successful chimera production in the Hungarian goose (Anser anser domestica) by intracardiac injection of blastodermal cells in 3-day-old embryos.
The conservation of genetic resources of avian species has become increasingly important over the past decade. The aim of the present study was to develop a genome preservation technique for the Hungarian goose Anser anser domestica. To this end, we developed a novel approach combining the simplicity of isolating a blastodermal cell suspension, which includes forming primordial germ cells (PGCs), with the efficiency of targeting future gonads by injecting these cells into the cardiac vein of the developing host embryo. First, we determined that the migratory period of PGCs in goose embryos was between 69 and 84h of development. Then, we injected the blastodermal cell suspension into the bloodstream of recipient embryos at this stage of development and monitored donor cell transmission into the genital tract. In all, 249 embryos were injected; three were found to be chimeras in gonadal tissues, whereas only one was a chimera in other tissues. Based on these results, it is concluded that this method is suitable for producing chimeras in the domestic goose. The optimal time of cell injection was found to be between 74 and 76h. The present study is the first report of the generation of chimeras in the domestic goose using intracardiac transplantation of embryonic cells.


The potential role of adult stem cells in the management of the rheumatic diseases.
Adult stem cells are considered as appealing therapeutic candidates for inflammatory and degenerative musculoskeletal diseases. A large body of preclinical research has contributed to describing their immune-modulating properties and regenerative potential. Additionally, increasing evidence suggests that stem cell differentiation and function are disrupted in the pathogenesis of rheumatic diseases. Clinical studies have been limited, for the most part, to the application of adult stem cell-based treatments on small numbers of patients or as a 'salvage' therapy in life-threatening disease cases. Nevertheless, these preliminary studies indicate that adult stem cells are promising tools for the long-term treatment of rheumatic diseases. This review highlights recent knowledge acquired in the fields of hematopoietic and mesenchymal stem cell therapy for the management of systemic sclerosis (SSc), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and osteoarthritis (OA) and the potential mechanisms mediating their function.


Effects of Crocin on Learning and Memory in Rats Under Chronic Restraint Stress with Special Focus on the Hippocampal and Frontal Cortex Corticosterone Levels.
Chronic stress adversely influences brain functions while crocin, as an effective component of saffron, exhibits positive effects on memory processes. This study investigated the effects of different doses of crocin on the improvement of learning and memory as well as corticosterone (CORT) levels in the hippocampus and frontal cortex of rats subjected to chronic stress. Forty male rats were randomly allocated to five different groups (n = 8): Control, sham; stress (6 h/day for 21 days) groups, and two groups receiving daily intraperitoneal injections of one of two doses (30 and 60 mg/kg) of crocin accompanied by 21 days of restraint stress. Latency was evaluated as a brain function using the passive avoidance test before and one-day after a foot shock. CORT levels were measured in the homogenized hippocampus and frontal cortex. Results revealed that chronic stress had a significantly (P < 0.01) negative effect on memory. Crocin (30 and 60 mg/kg), however, gave increase to significantly (P < 0.01 and P < 0.05; respectively) improved memory functions in the stressed rats. Furthermore, the CORT levels in the hippocampus and frontal cortex declined significantly (P < 0.05) in the stress group compared to the control. Only a crocin dose of 30 mg/kg was observed modulate significantly (P < 0.05) the CORT levels in the hippocampus and frontal cortex in the stressed group. It was found that the lower crocin dose (30 mg/kg) had more beneficial effects than its higher (60 mg/kg) dose on learning and memory under chronic stress conditions. Moreover, it was speculated that different doses of crocin act on different neurotransmitters and biochemical factors in the brain.


Target specific inhibition of West Nile virus envelope glycoprotein and methyltransferase using phytocompounds: an in silico strategy leveraging molecular docking and dynamics simulation.
Mosquitoes are the primary vector for West Nile virus, a flavivirus. The virus's ability to infiltrate and establish itself in increasing numbers of nations has made it a persistent threat to public health worldwide. Despite the widespread occurrence of this potentially fatal disease, no effective treatment options are currently on the market. As a result, there is an immediate need for the research and development of novel pharmaceuticals. To begin, molecular docking was performed on two possible West Nile virus target proteins using a panel of twelve natural chemicals, including Apigenin, Resveratrol, Hesperetin, Fungisterol, Lucidone, Ganoderic acid, Curcumin, Kaempferol, Cholic acid, Chlorogenic acid, Pinocembrin, and Sanguinarine. West Nile virus methyltransferase (PDB ID: 2OY0) binding affinities varied from -7.4 to -8.3 kcal/mol, whereas West Nile virus envelope glycoprotein affinities ranged from -6.2 to -8.1 kcal/mol (PDB ID: 2I69). Second, substances with larger molecular weights are less likely to be unhappy with the Lipinski rule. Hence, additional research was carried out without regard to molecular weight. In addition, compounds 01, 02, 03, 05, 06, 07, 08, 09, 10 and 11 are more soluble in water than compound 04 is. Besides, based on maximum binding affinity, best three compounds (Apigenin, Curcumin, and Ganoderic Acid) has been carried out molecular dynamic simulation (MDs) at 100 ns to determine their stability. The MDs data is also reported that these mentioned molecules are highly stable. Finally, advanced principal component analysis (PCA), dynamics cross-correlation matrices (DCCM) analysis, binding free energy and dynamic cross correlation matrix (DCCM) theoretical study is also included to established mentioned phytochemical as a potential drug candidate. Research has indicated that the aforementioned natural substances may be an effective tool in the battle against the dangerous West Nile virus. This study aims to locate a bioactive natural component that might be used as a pharmaceutical.


Acute lung injury/acute respiratory distress syndrome in 15 foals.
Few reports exist in the veterinary medical literature describing clinical and pathological findings resembling conditions described as (ALI) and acute respiratory distress syndrome (ARDS) in man. To document history, clinical, laboratory and diagnostic findings, treatment and outcome of foals age 1-12 months diagnosed with ALI/ARDS at a referral hospital. Medical records, including radiographic, cytological, microbiological, serological and post mortem findings, were reviewed in a retrospective manner to identify foals with acute onset of respiratory distress, a partial pressure of arterial oxygen (PaO2) to fraction of oxygen in inspired gases (FiO2) ratio of < or = 300 mmHg, pulmonary infiltrates on thoracic radiographs or post mortem findings consistent with ALI/ARDS. Fifteen foals age 1.5-8 months were included in the study. Seven foals had previously been treated for respiratory disease, and all foals developed acute respiratory distress <48 h prior to presentation. Findings on presentation included tachycardia and tachypnoea in all foals, with fever recorded in 8 cases. Eight cases met the criteria for ALI and 7 for ARDS. Radiographic findings demonstrated diffuse bronchointerstitial pattern with focal to coalescing alveolar radiopacities. An aetiological agent was identified in foals ante mortem (n = 6) and post mortem (n = 4). All foals were treated with intranasal oxygen and antimicrobial drugs; 13 received corticosteroids. Nine patients survived, 4 died due to respiratory failure and 2 were subjected to euthanasia in a moribund state. Follow-up was available for 7 foals; all performed as well as age mates or siblings, and one was racing successfully. A condition closely meeting the human criteria for ALI/ARDS exists in foals age 1-12 months and may be identical to previously described acute bronchointerstitial pneumonia in young horses. ALI/ARDS should be suspected in foals with acute severe respiratory distress and hypoxaemia that is minimally responsive to intranasal oxygen therapy. Treatment with systemic corticosteroids, intranasal oxygen and antimicrobials may be beneficial in foals with clinical signs compatible with ALI/ARDS.


Optical Stark and Zeeman Spectroscopy of Thorium Fluoride (ThF) and Thorium Chloride (ThCl).
Experimentally and theoretically determined magnetic and electric dipole moments, bond distances, and vibrational spacings are used for a comparative study of the bonding in ThF and ThCl. Numerous bands in the visible electronic spectra between 16 400 and 18 800 cm-1 of supersonically cooled molecular beam samples have been detected using medium-resolution (Δν ≈ 0.1 cm-1) 2D spectroscopy. High-resolution (Δν < 20 MHz) field-free, Stark, and Zeeman spectroscopy of the detected [18.6]Ω = 3/2 - X2Δ3/2 band of ThF near 538.4 nm and the [18.2]Ω = 3/2 - X2Δ3/2 band of ThCl near 551.0 nm have been recorded and analyzed. Stark shifts and splitting were analyzed to produce | μ⃗el| values of 1.453(7) D and 0.588(9) D for the X2Δ3/2 and [18.6]Ω = 3/2 states of ThF, respectively, and 2.022(35) D and 3.020(55) D for the X2Δ3/2 and [18.2]Ω = 3/2 states of ThCl. Zeeman splittings and shifts were analyzed to produce ge values of 1.038(4) and 1.079(4) for the X2Δ3/2 and [18.6]Ω = 3/2 states of ThF and 1.130(4) and 1.638(4) for the X2Δ3/2and [18.2]Ω = 3/2 states of ThCl. Analysis of ge values demonstrates that the X2Δ3/2 and [18.6]Ω = 3/2 states of ThF and the X2Δ3/2 state of ThCl are predominately 2Δ3/2 spin-orbit components, whereas the [18.2]Ω = 3/2 state of ThCl is an admixture of 2Δ3/2 and 2Π3/2 spin-orbit components. A molecular orbital description of the ground states is used to rationalize the observed | μ⃗el|values for the ThX (X = F, Cl, O, and S) series and garner insight into the bonding mechanism. The dipole moments in the ground state of ThF and ThCl have been calculated using relativistic coupled-cluster methods. It is demonstrated that the systematic inclusion of electron-correlation contributions plays an essential role in obtaining accurate predictions for the dipole-moment values in ThF and ThCl.