In vivo 19F spin relaxation in index finger bones.
19F free induction decay (FID) signals have been observed from the index fingers of four male and two female adult volunteers using a 27-MHz pulsed nuclear magnetic resonance spectrometer equipped with a split ring resonator probe. The value of the in vivo spin-lattice relaxation time T1 of the fluoride ions naturally accumulated in bone mineral has been determined to be 2.0 +/- 0.3 s. The shape of the observed FID signals in the inhomogeneous external magnetic field indicates that the F distribution is not uniform along the length of the finger. The fluoride ion content of the index finger (within a 65-mm length from its distal end) was measured with a sensitivity of +/- 0.5 mg F within a 30-min observation time.


Retrospective analysis of 736 implants inserted without antibiotic therapy.
The routine use of antibiotics in oral implant treatment seems to be widespread. The principle of antibiotic prophylaxis before oral surgical procedures in patients at risk for endocarditis or in those who are severely immunocompromised is well established. Antibiotic therapy in conjunction with implant surgery in fit patients and its correlation with failure and success rates remains poorly documented, however. The debate regarding overprescription of antibiotics raises the need for a critical evaluation of proper antibiotic coverage in association with implant treatment. The purpose of this study was to retrospectively show and value the outcomes of dental implant treatment without antibiotic prophylaxis. The study included 437 consecutively treated patients, in whom a total of 736 implants were placed. The population received no prophylactic antibiotics, but received anti-inflammatory therapy (nimesulide 100 mg twice daily or Arnica montana 5C 3 times a day) for 3 days postoperatively. Healing was evaluated at second-stage surgery (4 to 6 months postoperatively). Failure was defined as removal of the implant due to either signs of infection or nonosseointegration of the implant, according to the criteria for success described by Albrektsson and Coll in 1988. The implant survival rate in the sample (96.2%) was no lower than the high success rates published in the literature using various antibiotic regimens. Our findings support the results of several recent reviews of minor use of antibiotics in oral surgery. These findings suggest that the use of antibiotics for routine oral implants may not be as beneficial as once believed and that clinicians should look forward to the reduction of their unnecessary use. The use of antibiotic prophylaxis before oral surgical procedures remains a controversial issue, poorly documented in the literature.


Cortical mechanisms of movement recovery after freezing in Parkinson's disease.
Involuntary interruptions of upper limb movements, referred to as "upper limb freezing" (ULF) belong to the most disabling symptoms of Parkinson's disease (PD). Our study aimed to explore the cortical neuronal mechanisms underlying the reinstation of regular movement after a freezing episode and to control them by voluntary stops. We hypothesized that this movement recovery after a freeze would be accompanied by a decrease of beta power (13-30 Hz) over the primary sensorimotor cortex (electrode "C3"). We recorded a 62-channel surface EEG in 14 PD patients during a repetitive finger tapping task. After performing time-frequency analysis of the EEG data we segmented it to i) regular finger taps, ii) ULF episodes, and iii) voluntary movement stops (VS). We analysed cortical activity during each movement modality and later focused on the last 500 ms of ULF and VS and the first half of the following regular tap. At the beginning of regular finger taps we found decreased alpha power (6-12 Hz) over C3 (P = 0.01). During ULF, there was no significant activity modulation in the alpha and beta frequency bands, whereas beta power increased over C3 during VS (P = 0.0038). When tapping was reinstated after a freeze, we found that 100 ms before movement onset beta power decreased first present over C3, followed by fronto-central electrodes and then reaching the ipsilateral right fronto-temporal electrodes when reinstating regular tapping (P = 0.0256). Initiating movement after a VS showed a different pattern with a decrease of parieto-occipital beta activity 200 ms prior to the first tap (P = 0.044). Our findings suggest that PD freezers make use of different cortical pathways when re-initiating movement after ULF or VS. This includes either fronto-central or parieto-occipital pathways. These findings may help to customize novel neuromodulation strategies to counteract freezing behaviour.


Cohort profile: a longitudinal regional cohort study to assess COVID-19 seroprevalence in blood donors - baseline characteristics of the SeMaCo study participants.
The SeMaCo study (Serologische Untersuchungen bei Blutspendern des Großraums Magdeburg auf Antikörper gegen SARS-CoV-2), a prospective, longitudinal cohort study with four survey phases spanning 3-5 months each over a period of 22 months, extends the spectrum of seroepidemiological studies in Germany. We present here a careful characterisation of the initial survey phase of the cohort to provide baseline data on infection incidence and obtained from questionnaires, focussing in particular on the attitude towards COVID-19 vaccinations, the vaccination success and the vaccination acceptance. A total of 2195 individual blood donors from the donor pool of the blood donation service of the University Hospital Magdeburg were enrolled in the initial survey phase from 20 January 2021 to 30 April 2021. 2138 participants gave sociodemographic/contact data (51.7% male, mean age 44 years) and 2082 participants answered the vaccination questionnaire. Out of 2195 participants with antibody results, 1909 (87.0%) were antibody negative. The remaining 286 subjects (13.0%) were either antibody-positive and vaccinated (160/286; 55.9%) or antibody-positive without vaccination information (17/286; 5.9%) or antibody-positive and unvaccinated (109/286; 38.1%). The latter result reflects the rate of true or highly probable SARS-CoV-2 infections in our initial study cohort. The study primarily aims to measure the prevalence and long-term kinetics of IgG-antibodies against SARS-CoV-2. Including the baseline, the study foresees four survey periods of 3-4 months each. At each visit, we will assess the blood donors' attitude towards vaccination, the antibody response following vaccination and/or infection, as well as undesired vaccination effects. We aim to test the same participants during the survey periods by repeated invitations for blood donation to ensure a long-term (follow-up) in as many study participants as possible. After the four survey phases, a longitudinal data set will be created that reflects the course of the antibody levels/frequencies as well as the infection and vaccination incidence. DRKS00023263.


The unusual abundance of a rare finding!
We present images (Figure 1A-D) of a preterm girl who had severe anemia due to HDFN caused by maternal anti-C and anti-D alloantibodies. These images show erythrophagocytosis, which is a very interesting and rarely encountered feature. We believe that physicians taking care of such patients should be more aware of this characteristic yet under-detected finding.


S-100 in the central nervous system of rat, rabbit and guinea pig during postnatal development.
The accumulation of the brain-specific S-100 protein has been studied during postnatal development of rat, rabbit and guinea pig quantitatively, using immunoelectrophoresis, and qualitatively, by immunoelectron microscopy. Newborn guinea pigs show high levels of S-100. The distribution was similar to that of adult animals with an enrichment of S-100 to the postsynaptic membranes and to the astrocytic filaments. The neuronal plasma membranes as well as the neuronal nuclear membranes, astrocytic and oligodendroglial plasma membranes, also showed a specific activity for S-100. The amount of S-100 increased linearly from birth until the 3rd and 4th postnatal week of rabbit and rat, respectively. During the 2nd and 3rd week rabbit and rat nervous systems showed an accumulation of S-100, especially in the postsynaptic membranes and in the astrocytic filaments. In this study we present evidence that the S-100 protein quantitatively and ultrastructurally appears according to a pattern which parallels the muturation of brain, showing adult characteristics already at birth in early developing brains (guinea pig) and a change towards adult pattern after birth in late developing brains (rat and rabbit). In the latter two species change towards an adult S-100 distribution pattern proceeds during the postnatal period concomitant with the enzymatic and electrophysiogical maturation of the brain.


Activation of Bone Marrow Adaptive Immunity in Type 2 Diabetes: Rescue by Co-stimulation Modulator Abatacept.
Background: Chronic low-grade inflammation and alterations in innate and adaptive immunity were reported in Type 2 diabetes (T2D). Here, we investigated the abundance and activation of T cells in the bone marrow (BM) of patients with T2D. We then verified the human data in a murine model and tested if the activation of T cells can be rescued by treating mice with abatacept, an immunomodulatory drug employed for the treatment of rheumatoid arthritis. Clinical evidence indicated abatacept can slow the decline in beta-cell function. Methods: A cohort of 24 patients (12 with T2D) undergoing hip replacement surgery was enrolled in the study. Flow cytometry and cytokine analyses were performed on BM leftovers from surgery. We next compared the immune profile of db/db and control wt/db mice. In an additional study, db/db mice were randomized to receive abatacept or vehicle for 4 weeks, with endpoints being immune cell profile, indices of insulin sensitivity, and heart performance. Results: Patients with T2D showed increased frequencies of BM CD4+ (2.8-fold, p = 0.001) and CD8+ T cells (1.8-fold, p = 0.01), with the upregulation of the activation marker CD69 and the homing receptor CCR7 in CD4+ (1.64-fold, p = 0.003 and 2.27-fold, p = 0.01, respectively) and CD8+ fractions (1.79-fold, p = 0.05 and 1.69-fold, p = 0.02, respectively). These differences were confirmed in a multivariable regression model. CCL19 (CCR7 receptor ligand) and CXCL10/11 (CXCR3 receptor ligands), implicated in T-cell migration and activation, were the most differentially modulated chemokines. Studies in mice confirmed the activation of adaptive immunity in T2D. Abatacept reduced the activation of T cells and the levels of proinflammatory cytokines and improved cardiac function but not insulin sensitivity. Conclusions: Results provide proof-of-concept evidence for the activation of BM adaptive immunity in T2D. In mice, treatment with abatacept dampens the activation of adaptive immunity and protects from cardiac damage.


[Myocardial infarction and complications. Longitudinal observation of a population of 280,000 women and men--Project POL-MONICA Krakow. I. Genesis and objectives of the WHO MONICA Project].
The WHO MONICA Project is a multicentre collaborative study coordinated by The World Health Organization. The aim is to measure trends in cardiovascular disease mortality and morbidity and to assess the extent, to which these trends are related to changes in risk factor levels and in medical care measured at the same time in defined communities in different countries. There are 38 participating research centres from 21 countries from 4 continents, including two Polish centres: POL-MONICA Warszawa and POL-MONICA Kraków. Population studied in POL-MONICA Warszawa Project consisted of residents of two districts of Warsaw capital. The interest of the research of the POL-MONICA Kraków focuses on problems of the myocardial infarction in semi-rural population and the population observed consisted of men and women at age 25-64 years residents of one Polish province-Tarnobrzeg Voivodship.


The secretion of adrenal androgens and growth patterns of patients with hypogonadotropic hypogonadism and isiopathic delayed puberty.
Plasma concentrations of adrenal androgens (DHEA and DHEA-S) and the growth patterns of four male patients with hypogonadotropic hypogonadism have been compared and contrasted with those of eight male patients wit idiopathic delayed puberty. As a group the patients with HH presented at an older age with delayed puberty and normal heights; the growth rate and pattern have been normal except for an absence of the pubertal growth spurt. Adrenal androgens were usually normal for chronologic age and high for bone age. The patients with IDP presented at a younger age, usually with short stature, low adrenal androgens relative to the chronologic age, but normal relative to the bone age. Patients with IDP appear to exhibit a delay in maturation of both the adrenal cortex and the hypothalamo-pituitary gonadal axis usually with short stature and retardation of the bone age. The importance in measurements of adrenal androgens in the diagnosis of HH and of IDP is emphasized.


Liquid metal exfoliation of two dimensional polydopamine nanosheets for templated assembly of noble metal nanoparticles.
We report the synthesis of freestanding quasi-2D polydopamine nanosheets through a liquid metal-assisted polymerization-exfoliation process. This material promises a functional platform for tailoring 2D composite materials, which is demonstrated by using it as both the reductant and the template for directing silver nanocubes into shaped metal-polymer frameworks.


Regeneration of Nothofagus pumilio [Poepp. et Endl.] Krasser forests after five years of seed tree cutting.
Nothofagus pumilio [Poepp. et Endl.] Krasser is a deciduous tree species that grows in Chile and adjacent Argentina between 36 and 56 degrees S, often forming the Andean tree line. Silvicultural systems proposed for this species integrate both regeneration and intermediate level operations in an orderly process for managing forest stands. The seed-tree method of regeneration has been used to manage even-aged stands of this species. This paper investigates the effect of seed tree cuttings on the regeneration of Nothofagus pumilio [Poepp. et Endl.] Krasser forest located in the Magallanes region (Chile). The studied forest was managed on an even-aged basis using a seed tree silvicultural system for regeneration with an intensity of cutting of 65-70% of the basal area and a minimum of 15 dominant lenga trees per hectare retained. A regeneration inventory sampling was used to quantify regeneration attributes in the study area. Regeneration was found to be significantly affected by the seed tree cuttings. In fact, the number of established individuals rose from 0.39 to 26.7 plants m(-2) pre-harvest to 9.2-21.5 plants m(-2) post-harvest, depending on the particular development stage. Total regeneration ranged from 9.5 to 48.2 plants m(-2). The number of plants established over the period 1992-1997 was related to the residual basal area, coverage and number of trees. However, mean tree height was not significantly related to any regeneration variable. Significant variables were used to establish a regeneration prediction model using single and multiple linear equations (R2<0.418). Consequently, the seed tree method of regeneration can be considered feasible for commercially valuable lenga forests, although this method, in its strictest application, will create many large, irregularly shaped, even-aged groups.


Factors associated with influenza vaccination acceptance in Mexican healthcare workers: A multicenter cross-sectional study.
Adherence of healthcare workers (HCWs) to influenza vaccination is far from optimal despite its being the most effective intervention for preventing influenza. In order to evaluate factors associated with influenza vaccination acceptance among Mexican HCWs during the 2017-2018 influenza season, a multicenter cross-sectional study spanning public and private hospitals was conducted. Participants were consecutively invited to answer a self-administered questionnaire. A total of 1513 out of 1553 questionnaires were evaluated. The median age of the participants was 32 (26-44) years and 65.8% were women. Nurses and physicians comprised 53.0% of the surveyed population. Total self-reported adherence to influenza vaccination among HCWs during the 2017-2018 season was 63.5% and varied across participating hospitals (P < 0.001). Factors positively associated with influenza vaccination were incremental doses of influenza vaccine received within the last 5 years (aOR = 1.94, 95% CI = 1.78-2.10), City 3 (aOR = 1.62, 95% CI = 1.19-2.20) and City 1 (aOR = 1.39, 95% CI = 1.02-1.91), whereas factors negatively associated were lack of a previous dose of influenza vaccine (aOR = 0.03, 95% CI = 0.01-0.08) and unawareness of the vaccination campaign (aOR = 0.57, 95% CI = 0.44-0.72). Lack of information and poor communication were barriers identified by both vaccinated and unvaccinated personnel. This study concluded that adherence to influenza vaccination in Mexican HCWs is suboptimal and that the factors associated with receipt of influenza vaccine are similar to those reported in other studies.


Three-dimensional reconstruction of granular porous media based on deep generative models.
Reconstruction of microstructure in granular porous media, which can be viewed as granular assemblies, is crucial for studying their characteristics and physical properties in various fields concerned with the behavior of such media, including petroleum geology and computational materials science. In spite of the fact that many existing studies have investigated grain reconstruction, most of them treat grains as simplified individuals for discrete reconstruction, which cannot replicate the complex geometrical shapes and natural interactions between grains. In this work, a hybrid generative model based on a deep-learning algorithm is proposed for high-quality three-dimensional (3D) microstructure reconstruction of granular porous media from a single two-dimensional (2D) slice image. The method extracts 2D prior information from the given image and generates the grain set as a whole. Both a self-attention module and effective pattern loss are introduced in a bid to enhance the reconstruction ability of the model. Samples with grains of varied geometrical shapes are utilized for the validation of our method, and experimental results demonstrate that our proposed approach can accurately reproduce the complex morphology and spatial distribution of grains without any artificiality. Furthermore, once the model training is complete, rapid end-to-end generation of diverse 3D realizations from a single 2D image can be achieved.


A confirmatory factor analysis of specific phobia domains in African American and Caucasian American young adults.
The current study investigated factors related to specific phobia domains and differences in patterns among African American and Caucasian American adults. Subjects were 100 African Americans and 121 Caucasian Americans who completed the Fear Survey Schedule--Second Edition (FSS-II). Fears related to specific phobia domains were first examined, with frequencies differing between African American and Caucasian American samples on three of the six specific phobia domains. A confirmatory factor analysis was conducted to determine the patterns of specific phobias among the African American sample. The trimmed model for the African American sample included natural environment, animal and social anxiety specific phobia factors as latent, exogenous variables. Data from the Caucasian American sample provided a poor fit to this model. Instead, the trimmed model for the Caucasian American sample included the situational, animal and social anxiety factors. The natural environment-type specific phobia factor did not have adequate fit for the Caucasian American sample as in the African American sample. Results indicated that different factor loading patterns of fear-related stimuli may exist among African American and Caucasian American young adults. Potential explanations and future directions are discussed.


Missed dissection as a result of the ascending pharyngeal artery arising from the internal carotid artery.
Unlike high-grade stenosis, dissections of craniocervical arteries are a rare cause of cerebrovascular infarction. If the internal carotid artery (ICA) dissection is verified by duplex scanning or computed tomography angiography (CTA), the therapies of choice are antiplatelet and anticoagulation drugs, and surgical treatment is rarely performed. However, despite distinct clinical and radiological manifestation, carotid dissections are still under-recognized. In this study, we demonstrate the case of a 66-year-old man with dissection of ICA verified by duplex scanning and computed tomography angiography. The cause of missed diagnosis was an ascending pharyngeal artery originating from the ICA that runs parallel to it. Other than being a rare variation, this case may be interesting as a cause of misdiagnosis.


Young drivers vs. non-drivers: are there differences in behaviour?
Traditionally, a first step toward independence for a North American youth has been to obtain a driver's licence. Licensure can be associated with freedom and independence to provide teens opportunities to participate in conventional and health-enhancing behaviours, such as school, work, sporting events and other social activities, and/or provide opportunities to engage in unconventional, risk taking and health compromising behaviours. Yet, recent trends show that youth are delaying getting their licence. The purpose of this study was to use the constructs of conventional and unconventional behaviours identified in Problem Behaviour Theory (PBT) under the behaviour system to examine whether driver licensure status in youth was associated with conventional, health-enhancing behaviours or unconventional, health compromising, risky behaviours. Data were derived from the 2015 and 2017 cycles of the Ontario Student Drug Use Survey (OSDUHS). Analyses are based on a subsample of students who were at least 16 years of age. Included measures: driver's licence (at least a G1 - the first stage of a 3-stage graduated licensing system), conventional behaviours (academic performance, school connectedness, employment, physical activity, and sleep), unconventional behaviours (tobacco use, cannabis use, alcohol use, binge drinking, hazardous drinking, problematic drug use, screen time, and number of antisocial behaviours), and control factors (age, sex, region, family Socio-Economic Status (SES)). 67.97 % of youth 16-19 years of age obtained a driver's licence. Of the sample, 71.80 % of males, 75.05 % not living in the Greater Toronto Area (GTA), and 70.86 % of youth with an average family SES received their driver's licence. In regression analyses, older youth, males, and youth not living in the GTA had significantly higher odds of obtaining a driver's licence than younger youth, females, and youth living in the GTA. Conventional behaviours that were significantly positively associated with licensure status included youth who had high academic achievement, good social connectedness, and who were employed. Unconventional behaviours that were significantly positively associated with licensure status included alcohol use and binge drinking. In agreement with Problem Behaviour Theory, the results show that youth who obtain their licence show limited problematic lifestyle or 'proneness' (Gohari, 2019). Alcohol use and binge drinking were significantly associated with youth obtaining a driver's licence but hazardous drinking was not. This study suggests that a driver's licence for youth could both control but also instigate unconventional behaviours as identified by PBT. A driver's licence could also provide opportunities for conventional behaviours associated with education and school connectedness. However, the independence provided by a driver's licence could offer youth unsupervised social opportunities to drink and binge drink that may be health-compromising. Thus, based on PBT, licensure status is associated with both conventional behaviours, as well as problem behaviours associated with alcohol use.


Rapid dopamine signaling in the nucleus accumbens during contingent and noncontingent cocaine administration.
Cocaine acts as a reinforcer through its pharmacological effects on brain monoaminergic systems, which, through repeated pairings with environmental stimuli, lead to the development of conditioned effects of the drug. Both the pharmacological and conditioned aspects of cocaine are implicated in several facets of acquisition and maintenance of addiction, including drug craving. Here, we compare the effects of contingent (response dependent) and noncontingent (response independent) cocaine on rapid dopaminergic signaling in the core of the nucleus accumbens. Dopamine was monitored using fast-scan cyclic voltammetry. Noncontingent cocaine administered to both naive and animals with a history of self-administration resulted in a profound increase in the frequency of transient dopamine release events that are not time-locked to any specific environmental stimuli. Pharmacological effects were detectable approximately 40 s after cocaine administration. In contrast, when animals where allowed to self-administer cocaine on an FR-1 schedule, dopamine transients (69+/-12 nM) were consistently observed time-locked to each reinforced response (peaking approximately 1.5 s after response completion). Importantly, no pharmacological effect of cocaine was observed within the 10 s following noncontingent cocaine administration, indicating that dopamine signals time-locked to the reinforced response are a result of the pairing of the operant behavior, the drug-associated cues, and cocaine. These data demonstrate that this pharmacological action of cocaine occurs for an extended period following either contingent or noncontingent administration, but is distinct from those dopamine transients that are time-locked to each lever-press in self-administering animals.


Induction of nuclear anomalies in the gastrointestinal tract by polycyclic aromatic hydrocarbons.
A selective list of polycyclic aromatic hydrocarbons (PAH) with varied carcinogenic and mutagenic potencies, which are identified as common contaminants at industrial sites and which often contaminate the neighboring ground water, are investigated for their ability to induce nuclear anomalies (NA) in the mouse gastrointestinal (G.I.) tract. These studies examined the hypothesis that a relationship between NA induction and carcinogenic potency of these PAH exists. Among the PAH tested, 7,12-dimethylbenzanthrene (DMBA) was most effective inducer of NA in all G.I. tract tissues examined, with the relative potency in duodenum of DMBA much much greater than benzo[a]pyrene (B[a]P) much greater than benzo[b]fluoranthene (B[b]F). The induction of NA by benzo[a]anthracene (B[a]A), pyrene (PY) and benzo[e]pyrene (B[e]P) was not different from that elicited by vehicle controls. MNU, a known potent inducer of NA in the mouse G.I. tract, yielded a high level of NA in duodenum and proximal colon but was less effective than DMBA in the forestomach. The data suggest that induction of NA by DMBA and B[a]P PAH are in approximate accordance with their relative carcinogenic potency in the gastrointestinal tract. When binary mixtures of some PAH were administered the yield of NA was less than that expected by simple additivity and closer to that expected by averaging the activities of the two PAH comprising the mixture. Thus, this short-term in vivo assay may be useful as a predictor of the genotoxic or carcinogenic strength of individual PAH and/or mixtures of these compounds.


Anomalous Pancreaticobiliary Duct Junction in an Unusual Case of Synchronous Gallbladder and Bile Duct Malignancy.
Synchronous malignancies involving the gallbladder and the bile duct are exceedingly rare. Moreover, their association with anomalous pancreaticobiliary duct junction (APBDJ) has been reported mostly from the Far Eastern countries. Over time, many studies have suggested the definite risk of malignancy attributable to the 'carcinogenic anatomical configuration' of the long common biliopancreatic channel, allowing reflux of pancreatic juices in the biliary tract. In this report, we present a case of an elderly man from South India who was initially diagnosed with synchronous gall bladder with bile duct malignancy; the patient turned out to have an APBDJ on further evaluation.


Inhibitory effects of Angelica sinensis ethyl acetate extract and major compounds on NF-kappaB trans-activation activity and LPS-induced inflammation.
Previous study showed that the ethyl acetate (EtOAc) fraction from Angelica sinensis (Oliv.) Diels (Apiaceae) (AS) inhibited nitric oxide (NO) and prostaglandin E(2) secretions in vitro. This study was to evaluate anti-inflammatory activity of AS EtOAc extract and its major compounds in vivo and in vitro. NF-kappaB luciferase activity and pro-inflammatory cytokine secretions from lipopolysaccharide (LPS) plus interferon (IFN)-gamma-stimulated RAW 264.7 cells pre-treated with EtOAc extract or compounds were analyzed. For further in vivo study, BALB/c mice were tube-fed with 1.56 (AS1 group), 6.25 (AS2 group) mg/kg body weight/day in 100 microl soybean oil, while the control and PDTC (pyrrolidine dithiocarbamate, an anti-inflammatory agent) groups were tube-fed with 100 microl soybean oil/day only. After 1 week of tube-feeding, the PDTC group was injected with 50 mg/kg BW PDTC and 1 h later, all of the mice were injected with 15 mg/kg BW LPS. The pro-inflammatory cytokine levels and lifespan of LPS-challenged mice were determined. The results showed that AS EtOAc extract significantly inhibited NF-kappaB luciferase activity and TNF-alpha, IL-6, macrophage inflammatory protein-2 (MIP-2) and NO secretions from LPS/IFN-gamma-stimulated RAW 264.7 cells. The AS1 and PDTC groups, but not AS2, had significantly higher survival rate than the control group. This was characterized by the inhibition of the serum TNF-alpha and IL-12p40 levels after LPS injection (p<0.05). The major compounds of AS, ferulic acid and Z-ligustilide, also significantly decreased NF-kappaB luciferase activity, which may contribute to the anti-inflammatory activity of AS. Low dose of AS EtOAc extract that inhibits the production of inflammatory mediators alleviates acute inflammatory hazards and protect mice from endotoxic shock.


Therapeutic hypothermia after cardiac arrest and return of spontaneous circulation: it's complicated.
Providing evidence-based care to patients with return of spontaneous circulation after a cardiac arrest is a recent complex innovation. Once resuscitated patients must be assessed for appropriateness for therapeutic hypothermia, be cooled in a timely manner, maintained while hypothermic, rewarmed within a specified time frame, and then assessed for whether hypothermia was successful for the patient through neuroprognostication. Nurses caring for therapeutic hypothermia patients must be knowledgeable and prepared to provide care to the patient and family. This article provides an overview of the complexity of therapeutic hypothermia for patients with return of spontaneous circulation in the form of a case study.


P2X7 receptor-nitric oxide interaction mediates apoptosis in mouse immortalized mesangial cells exposed to high glucose.
Diabetes mellitus (DM) is a chronic disease characterized by hyperglycemia that leads to diabetic nephropathy (DN). We showed that P2X7, a purinergic receptor, was highly expressed in DM; however, when oxidative stress was controlled, renal NO recovered, and the activation of this receptor remained significantly reduced. The aim of this study was to assess the influence of NO on the P2X7 and apoptosis in mouse immortalized mesangial cells (MiMC) cultured in high glucose (HG) medium. MiMCs were cultured with DMEM and exposed to normal glucose (NG), mannitol (MA), or HG. Cell viability was assessed by an automated counter. Supernatants were collected for NO quantification, and proteins were extracted for analysis of NO synthases (iNOS and eNOS), caspase-3, and P2X7. Cell viability remained above 90% in all groups. There was a significant increase in the proliferation of cells in HG compared to MA and NG. NO, iNOS, caspase-3, and P2X7 were significantly increased in HG compared to NG and MA, with no changes in eNOS. We observed that there was a strong and significant correlation between P2X7 and NO. The main finding was that the production of NO by iNOS was positively correlated with the increase of P2X7 in MCs under HG conditions, showing that there is a common stimulus between them and that NO interacts with the P2X7 pathway, contributing to apoptosis in experimental DM. These findings could be relevant to studies of therapeutic targets for the prevention and/or treatment of hyperglycemia-induced kidney damage to delay DN progression.


Clinical characteristics, predictors of immune reconstitution inflammatory syndrome and long-term prognosis in patients with Kaposi sarcoma.
To investigate the predictive factors for the development of Kaposi sarcoma-related immune reconstitution inflammatory syndrome (KS-IRIS) and long-term prognosis in patients starting combined antiretroviral therapy (cART). We studied a retrospective-cohort of consecutive antiretroviral-naïve patients with KS initiating cART from January 2005 to December 2011 and followed through June 2013. KS-IRIS was defined as ≥2 of the following: abrupt increase in number of KS lesions, appearance or exacerbation of lung-opacities or lymphedema, concomitantly with an increase in CD4+ cell-count ≥50 cells/mm3 and a decrease of >1 log in viral-load once started cART. We compared individuals who met KS-IRIS criteria with those that did not and described the long-term follow-up. We included 89 patients, 88 males; 35 (39%) developed KS-IRIS at a median of 10 weeks (IQR 4-16). KS-IRIS patients had more pulmonary-involvement (60% vs. 16.6% of patients; p < 0.0001), eight died attributed to pulmonary-KS. Thrombocytopenia <100,000/mm3 at follow-up occurred in 36% of KS-IRIS vs. 4% in non-KS-IRIS patients (p = 0.0002), 45% KS-IRIS patients with thrombocytopenia died, non without KS-IRIS. Chemotherapy (bleomicyn-vincristine) was more frequently prescribed in KS-IRIS patients (88.6% vs. 29.6%) with no differences in outcome; 80% of all patients achieve KS complete remission, 52% of them never received chemotherapy. No difference between groups in the long-term follow-up (mean 52.4 ± 27.4 months) was found, only one patient developed a secondary malignancy (1.12%). Lung-involvement was predictive of IRIS development. Thrombocytopenia in KS-IRIS patients at week 12 follow-up after cART initiation was associated with high mortality. Over a third of patients with KS achieve remission without chemotherapy. Individuals that survive the initial period of KS-IRIS adhere to cART had a good long-term prognosis.


The bypass flap: an innovative technique of distal revascularization--anatomical study and clinical application.
Combined surgery for placement of a distal venous bypass and a free flap enables successful treatment of tissue loss caused by ischemia. This complex surgery has limited indications. The multiple anastomoses on the same arterial axis increase the risk of thrombosis and a certain number of venous grafts are likely to undergo mid-term deterioration. Because of these difficulties, we propose a new concept: the bypass flap (BF), which is based on the harvesting of an arterial axis to provide an arterial graft and a free flap supplied by a collateral branch of the graft. The aim of the anatomic part of this study was to evaluate the length and diameter of the arterial graft and its tissue branch and to study the feasibility of the BF. Thirty-two anatomic preparations were made by intraarterial injection of Rhodosil in 16 cadavers. The arterial graft included the subscapular artery and the thoracodorsal artery. The flap consisted of the anterior serrate muscle supplied by the branch of that graft. The distribution, length, and diameter of the arteries were examined. The mean length of the arterial graft line maintaining diameter above 2 mm was 12.5 cm (8.5-15.5). Three clinical applications of the BF based on the thoracodorsal artery axis were performed on three patients with tissue loss caused by severe ischemia of the lower limb. No occlusion of the BF occurred and healing of the tissue loss was achieved after 4, 7, and 10 months, respectively. This technique has the advantage of decreasing vascular distal resistance, which may contribute to improvement of vessel reconstruction patency. It is simpler because the anastomoses are fewer and it presents the advantage of requiring only autologous arterial material of an appropriate diameter.


Vibrational spectroscopic studies and Natural Bond Orbital analysis of 4,6-dichloro-2-(methylthio)pyrimidine based on density functional theory.
The FT-IR and FT-Raman spectra of 4,6-dichloro-2-(methylthio)pyrimidine (DMP) have been recorded and analyzed. The optimized geometry, intramolecular hydrogen bonding, and harmonic vibrational wave numbers of DMP have been investigated with the help of B3LYP density functional theory (DFT) method supplemented with 6-31G** basis set. The infrared and Raman spectra were predicted theoretically from the calculated intensities. Natural Bond Orbital (NBO) analysis of DMP has been performed to indicate the presence of intramolecular C-H⋯Cl hydrogen bonding. The formation of Lewis and non-Lewis orbitals and second-order perturbation energies of DMP have also been reported.


Singing is not associated with social complexity across species.
Based on their social bonding hypothesis, Savage et al. predict a relation between "musical" behaviors and social complexity across species. However, our qualitative comparative review suggests that, although learned contact calls are positively associated with complex social dynamics across species, songs are not. Yet, in contrast to songs, and arguably consistent with their functions, contact calls are not particularly music-like.


Tau-related protein present in paired helical filaments has a decreased tubulin binding capacity as compared with microtubule-associated protein tau.
We have isolated, after exhaustive detergent treatments, a 33 kDa tau-related protein isolated from paired helical filaments from Alzheimer's disease patient brains. The N-terminal sequence of the 33 kDa protein begins at residue 71 of the sequence described for human fetal tau protein. This truncated form of tau is not the consequence of the translation of a tau RNA lacking a region at its 5' end, as measured by primer extension analyses, suggesting that the 33 kDa protein must be generated by proteolysis of previously synthesized tau. This tau-related protein has only one blocked cysteine residue and also has a decreased tubulin binding capacity as compared with that of tau protein.


Synthesis and cytotoxicity studies of steroid-functionalized titanocenes as potential anticancer drugs: sex steroids as potential vectors for titanocenes.
Six titanocenyls functionalized with steroidal esters have been synthesized and characterized by infrared, (1)H, and (13)C NMR spectroscopy and elemental analysis. Among those steroids, dehydroepiandrosterone, trans-androsterone, and androsterone are androgens and pregnenolone is a progesterone precursor. Clionasterol is a natural steroid compound. These steroid-functionalized titanocenyls were tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay for in vitro cytotoxicity for MCF-7 breast cancer and HT-29 colon cancer cells. All complexes exhibited more cytotoxicity than titanocene dichloride. The titanocenyls containing androgen and progesterone derivatives as pendant groups had higher antiproliferative activities than those with cholesterol steroid compounds. Of particular significance is titanocenyl-dehydroepiandrosterone complex, which is 2 orders of magnitude more cytotoxic than titanocene dichloride and also shows much more sensitivity and selectivity for the MCF-7 cell line.


Detection of occult hepatitis B virus infection among subjects with isolated hepatitis B core antibodies: Results from a 3-year survey in an Italian tertiary-care hospital.
Hepatitis B virus (HBV) infection causes hepatitis, liver cirrhosis, hepatocellular carcinoma, and death. This study examines the subjects with isolated anti-HBV core antigen antibody (anti-HBcAg), a pattern characterized by the persistent HBV carriage in the absence of HBV surface antigen (HBsAg) and anti-HBsAg antibody. Based on medical orders, from 2017 to 2019, serological and molecular assays were performed on serum/plasma samples of 33,048 subjects (71.4% Italians, 28.6% foreigners), who referred to the Virology Unit of the University-Hospital of Parma (Northern Italy) for the laboratory diagnosis of HBV infection. The seroprevalence was 4.6% for HBsAg and 11% for anti-HBcAg. The occurrence of the isolated anti-HBcAg status was 3.1%, with higher frequency in males than in females (66.3% vs. 33.7%, P < 0.0001), in Italians than in foreigners (54.8% vs. 45.2%, P < 0.001), and in outpatients than in inpatients (57.4% vs. 42.6%, P < 0.0001). Foreigners with isolated anti-HBcAg came mostly from Africa (67.9%) and Eastern Europe (26.2%). Among subjects with isolated anti-HBcAg, 14.8% had occult HBV infection, 26.3% hepatitis C virus co-infection, 2% human immunodeficiency virus co-infection, and 3.3% both of these latter co-infections. The anti-HBcAg assay accurately evaluates the HBV exposure; subjects with isolated anti-HBcAg antibody should be further analysed for HBV DNA. The HBV infection prevalence in Italy is increasing, due to growing migratory flows from endemic areas.


Bayesian model-based tight clustering for time course data.
Cluster analysis has been widely used to explore thousands of gene expressions from microarray analysis and identify a small number of similar genes (objects) for further detailed biological investigation. However, most clustering algorithms tend to identify loose clusters with too many genes. In this paper, we propose a Bayesian tight clustering method for time course gene expression data, which selects a small number of closely-related genes and constructs tight clusters only with these closely-related genes.


Prediction of the doubly charged ion pattern by modelling the high- and low-resolution mass spectra of isotopomeric forms.
The presence of doubly charged ions in mass spectra is detected only occasionally because their clusters are observed more rarely than singly charged ones. The patterns connected with doubly charged ions are located in the spectrum below M/2. The narrow shapes of such patterns as well as overlapping with other bands generate significant problems in their interpretation. The method described here is based on modelling of the isotopomeric form of single- and double-charged mass ion clusters. The present work attempts to explain the generation of the double charge disotopomeric patterns of high- as well as low-resolution spectra. Predicting the high-resolution mass cluster is simpler than calculations of the low-resolution cluster. The high-resolution cluster may represent the initial form of low-resolution pattern formation.


Understanding and measuring powered wheelchair mobility and manoeuvrability. Part I. Reach in confined spaces.
To determine: (1) what wheelchair manoeuvrability factors are important and (2) the effects of powered wheelchair design on the ability to reach in a confined space. The relative importance of five aspects of wheelchair manoeuvrability was determined through a survey of users of wheelchairs (N = 52) and health care professionals and others (N = 89). A single young, non-disabled subject undertook repeated trials of reach distance on to a counter at the end of a corridor whose width could be adjusted by moving Styrofoam walls. Reaching, moving in confined spaces and avoiding collisions were more important than speed and avoiding the need to drive backwards. The rear wheel drive powered wheelchair was found to allow the greatest reach when driving backwards into the space and the wheelchair which moved in a sideways direction allowed greatest reach in the narrowest corridor. The survey concluded that manoeuvring in small spaces and reaching without collisions were important. The powered wheelchair with sideways capability afforded the greatest reach in confined spaces except when the rear wheel drive chair was driven in backwards. The survey respondents did not place a high priority on avoiding backwards driving but some people find this difficult to do safely.


Multiple representations and algorithms for reinforcement learning in the cortico-basal ganglia circuit.
Accumulating evidence shows that the neural network of the cerebral cortex and the basal ganglia is critically involved in reinforcement learning. Recent studies found functional heterogeneity within the cortico-basal ganglia circuit, especially in its ventromedial to dorsolateral axis. Here we review computational issues in reinforcement learning and propose a working hypothesis on how multiple reinforcement learning algorithms are implemented in the cortico-basal ganglia circuit using different representations of states, values, and actions.


Diameter control of ultrathin zinc oxide nanofibers synthesized by electrospinning.
Electrospinning is a versatile technique, which can be used to generate nanofibers from a rich variety of materials. We investigate the variation of a zinc oxide (ZnO)-polyvinylpyrrolidone (PVP) composite structure in morphology by electrospinning from a series of mixture solutions of ZnO sol-gel and PVP. Calcination conditions for the crystallization of ZnO nanofibers and removal of the PVP component from the ZnO-PVP composite nanofibers were also studied. The progression of the ZnO-PVP composite structure from grains to nanofibers was observed, and ZnO-PVP nanofibers as thin as 29.9 ± 0.8 nm on average were successfully fabricated. The size of the resultant ZnO-PVP composite nanofibers was considerably affected by two parameters: the concentrations of zinc acetate and PVP in the precursor solution. The concentration of zinc acetate particularly influenced the diameter distribution of the ZnO-PVP nanofibers. The ZnO-PVP nanofibers could be subsequently converted into ZnO nanofibers of a pure wurtzite phase via calcination in air at 500°C for 2 h.


Why ultrafast charge separation occurs in bulk-heterojunction organic solar cells: a multichain tight binding model study.
Bulk-heterojunction (BHJ) organic solar cells (OSCs) exhibit ultrafast charge separation (UCS) which enables lower geminate charge recombination and high internal quantum efficiency. Unravelling why UCS occurs in BHJ-OSCs is important for the exploration of devices in future, however it is still far from clear. In this work, we build a multichain tight-binding model to study the conditions for realizing UCS. We propose that two conditions are important: (i) the BHJ-OSC has a morphology with donor and acceptor molecules being individually aggregated; (ii) the ratio of the donor/acceptor interfacial coupling to the internal donor/donor and acceptor/acceptor coupling should be smaller than a threshold. In addition, we suggest that increasing the donor/acceptor energetic offset will boost the UCS efficiency. As a fundamental theoretical analysis on the underlying mechanism of UCS, our work provides design rules for optimizing high-performance BHJ OSCs.


Bioaccumulation and biomagnification of hexabromocyclododecane (HBCDD) in insect-dominated food webs from a former e-waste recycling site in South China.
Hexabromocyclododecane (HBCDD) has frequently been detected in wildlife. However, there is limited research on its bioaccumulation and biomagnification in insect-dominated aquatic and terrestrial food webs. This study investigated the occurrence of HBCDD in insects and their predators collected from a former e-waste contaminated pond and its surrounding region. The concentrations of ƩHBCDD (sum concentrations of α-, β-, and γ-HBCDDs) ranged from nd to 179 ng g-1 lipid weight. α-HBCDD was the predominant diastereoisomer in all biotic samples, and the contribution of α-HBCDD was higher in predators than in prey insects. A significantly positive linear relationship was found between ƩHBCDD concentrations (lipid weight) and trophic levels based on δ15N in aquatic organisms (p < 0.05), while trophic dilution was observed in the terrestrial food web. This result indicates an opposite trophic transfer tendency of HBCDD in terrestrial and aquatic ecosystems. The biomagnification factor (BMF) for α-HBCDD was higher in terrestrial birds (2.03) than in frogs (0.29), toads (0.85), and lizards (0.63). This may be due to differences between poikilotherms and homeotherms in terrestrial ecosystems.


Differential effects of low-dose tissue plasminogen activator and streptokinase on platelet aggregation.
Despite increasing success with low-dose intra-arterial thrombolysis, early rethrombosis still occurs. Platelet aggregation is thought to play a major part in this process. We have therefore investigated the effects of recombinant tissue plasminogen activator (rt-PA) and streptokinase on platelet function at doses currently used for peripheral arterial thrombolysis. Platelet-rich plasma was stirred at 37 degrees C, with either streptokinase (100, 300 or 1000 units ml-1) or rt-PA (10 (T10), 30 (T30) and 100 (T100) mg l-1), with immediate addition of an agonist for platelet aggregation (thrombin, collagen, adenosine diphosphate (ADP) or adrenaline) at a predetermined threshold dose. Significant inhibition of collagen-induced and adrenaline-induced platelet aggregation was produced with rt-PA at all doses used (P less than 0.05). With adrenaline as the agonist, T100 produced disaggregation to a mean (s.d.) level of 26 per cent. Thrombin-stimulated platelet aggregation was significantly reduced by T100 (P less than 0.001) and T30 (P less than 0.01) only, disaggregation being dose-dependent and complete with T100. Using ADP as the agonist, T100 produced a significant reduction in maximum platelet aggregation (P less than 0.01), and disaggregation was achieved to a mean (s.d.) level of 48(13) per cent. Streptokinase did not produce any significant changes in any parameter of aggregation.


Treating where it hurts-a randomized comparative trial of vestibule estradiol for postmenopausal dyspareunia.
To compare efficacies of two strengths of estradiol cream applied to the vulvar vestibule and use of silicone lubricant to reduce intercourse pain scores in postmenopausal women with moderate/severe dyspareunia. This pilot randomized comparative trial assigned 50 women to nightly applications of estradiol cream, 50 or 100 μg, for 12 weeks. We asked women to have lubricated penetration twice weekly, with intercourse or performing a tampon test. Pain, recorded in dairies, was rated using the 0-10 Numerical Rating Scale. We assessed biopsychosocial outcomes, urinary symptoms, and measured serum estradiol levels and endometrial stripe thicknesses. We performed physical examinations to determine tenderness levels of the vestibule, vagina, pelvic floor muscles, bladder, uterus, and adnexa. Comparisons were made using two-sample t test, Wilcoxon rank-sum test, or χ2 /Fisher's exact test. Forty-seven women (94%), with a mean age of 59.7 years, completed the trial. The baseline median intercourse pain score was 8/10 (interquartile range, 6, 8). After 12 weeks, we measured no statistically significant difference between groups in the primary outcome, intercourse pain score, or any secondary outcome measure. For both groups together, the median intercourse pain score diminished by 50% after 4 weeks and 75% after 12 weeks ( P < 0.001). The most tender anatomic area, the vulvar vestibule, improved by 82% to 100% ( P < 0.001) with therapy. We did not measure a statistically significant difference in serum estradiol levels or endometrial stripe thickness between groups. Estradiol cream applied to the vulvar vestibule, paired with precoital silicone lubricant, is a promising alternative to vaginal therapy for dyspareunia.


Influence of general anesthesia on transiently evoked otoacoustic emissions in humans.
The influence of general anesthesia (GA) on transiently evoked otoacoustic emissions (TEOAEs) was studied in 19 normally hearing women undergoing surgery. Emissions were measured on the day before the operation, after premedication but before the beginning of the operation, and during and after the operation. There were no significant differences in TEOAE amplitude or in reproducibility between results obtained the day before the operation and after premedication. Ten patients received nitrous oxide (N2O) during GA (N2O group), and 9 patients did not (non-N2O group). The amplitude of TEOAEs was reduced during GA in 9 of 10 patients in the N2O group and in 7 of 9 patients in the non-N2O group. However, the average decrease of amplitude after the first 10 minutes was greater in the N2O group (4 +/- 3.4 dB) than in the non-N2O group (0.18 +/- 1.4 dB). The corresponding mean reproducibility of the response decreased in 9 of 10 patients of the N2O group (29% +/- 24%) and was nearly unchanged in the non-N2O group (2.3% +/- 7.2%). The time course of the amplitude reduction was similar in both groups. The smallest amplitudes were reached on an average by 19.3 +/- 11.4 minutes in the N2O group and by 17 +/- 13.6 minutes in the non-N2O group. Preoperative and postoperative TEOAEs were comparable in level and reproducibility. Differential frequency effects imply a middle ear effect for the greater reduction of TEOAE amplitudes in the N2O group due to gas diffusion into the middle ear.(ABSTRACT TRUNCATED AT 250 WORDS)


Pivotal role of interleukin-8 in the acute respiratory distress syndrome and cerebral reperfusion injury.
Neutrophil recruitment is one of the hallmarks of acute inflammation. A potent neutrophil chemotactic and activating factor, interleukin-8 (IL-8), has been demonstrated to be elevated in body fluids in various human diseases and experimental animal models. Recent investigations on animal disease models using blocking antibodies to IL-8 have revealed the essential involvement of IL-8 in acute inflammation. We previously reported that the administration of a neutralizing antibody against IL-8 prevented the neutrophil infiltration and neutrophil-mediated tissue injury in several animal studies. In addition, we have recently demonstrated that anti-IL-8 treatment is also effective in prevention of two models that are very relevant to clinical situations: cerebral reperfusion injury and endotoxemia-induced acute respiratory distress syndrome-like lung injury. These results further support the hypothesis that IL-8 has a pivotal role and is a novel target for therapeutic intervention in neutrophil-mediated injury.


Comparison of the blood, bone marrow, and cerebrospinal fluid metabolomes in children with b-cell acute lymphoblastic leukemia.
Metabolomics may shed light on treatment response in childhood acute lymphoblastic leukemia (ALL), however, most assessments have analyzed bone marrow or cerebrospinal fluid (CSF), which are not collected during all phases of therapy. Blood is collected frequently and with fewer risks, but it is unclear whether findings from marrow or CSF biomarker studies may translate. We profiled end-induction plasma, marrow, and CSF from N = 10 children with B-ALL using liquid chromatography-mass spectrometry. We estimated correlations between plasma and marrow/CSF metabolite abundances detected in ≥ 3 patients using Spearman rank correlation coefficients (rs). Most marrow metabolites were detected in plasma (N = 661; 81%), and we observed moderate-to-strong correlations (median rs 0.62, interquartile range [IQR] 0.29-0.83). We detected 328 CSF metabolites in plasma (90%); plasma-CSF correlations were weaker (median rs 0.37, IQR 0.07-0.70). We observed plasma-marrow correlations for metabolites in pathways associated with end-induction residual disease (pyruvate, asparagine) and plasma-CSF correlations for a biomarker of fatigue (gamma-glutamylglutamine). There is considerable overlap between the plasma, marrow, and CSF metabolomes, and we observed strong correlations for biomarkers of clinically relevant phenotypes. Plasma may be suitable for biomarker studies in B-ALL.


Use of strain, strain rate, tissue velocity imaging, and endothelial function for early detection of cardiovascular involvement in patients with beta-thalassemia.
Global ventricular function often remains normal in patients with beta-thalassemia major (β-TM) until late. Tissue Doppler and strain imaging may be useful to assess regional myocardial function abnormalities in these patients. Systolic (Sm), early diastolic (Em), and late diastolic (Am) (Em/Am) myocardial velocities at basal lateral and septal left ventricular (LV) segments, strain (S), and strain rate (SR) in basal and mid LV, right ventricular (RV) and septum were measured in 30 patients (β-TM, 12.4 ± 5.2 years, serum ferritin 2603.1 μg/L) and twenty controls (12.5 ± 5.2 years). Flow-mediated dilatation (FMD) vasodilatation as a measure of endothelial function was also assessed. Patients had significantly higher LV mass index (169.45 ± 61.14 vs. 104.66 ± 24.42; P = 0.009) while global LV Sm and diastolic function was similar to controls. Patients had significantly lower lateral Em velocity, Em (10.12 ± 1.16 vs. 17.9 ± 2.11; P = 0.002), Em/Am ratio (0.811 ± 0.192 vs. 2.06 ± 0.62; P = 0.001) at the basal lateral LV, lower strain values at the basal lateral LV (19.5 ± 4.17 vs. 24.196 ± 1.81; P = 0.002), mid lateral LV (19.07 ± 3.98 vs. 25.56 ± 2.62; P = 0.042), basal septum (17.04 ± 3.44 vs. 25.43 ± 2.53; P = 0.001), and mid septum (20.49 ± 5.34 vs. 24.45 ± 2.20; P = 0.001) as compared to controls. SR at the basal and mid segment of the lateral LV wall and at the basal and mid septum was also significantly lower in patients. SR in basal and mid RV although lower was not significantly different from controls. Patients also had significantly lower FMD (7.57 ± 3.16 vs. 18.08 ± 1.9, P = 0.018) implying endothelial dysfunction. Tissue Doppler, strain and SR imaging are useful to quantify regional myocardial function in asymptomatic β-TM patients with preserved global Sm and diastolic function.


Comprehensive Diagnosis, Management, and Treatment of Sesame Allergy.
Sesame allergy prevalence varies regionally and by age, in the range of 0.1% to 0.9%. Reactions can be severe and potentially fatal. Resolution rates are in the range of 20% to 50%. The diagnosis requires a careful history and the use of tests, such as skin prick tests and serum sesame-specific IgE. The availability of serum IgE testing for the sesame protein Ses i 1 has improved diagnostic accuracy. The emerging potential for sesame basophil activation tests and additional new tests will likely improve diagnosis in coming years, further reducing the need for diagnostic oral food challenges. Although sesame proteins share homology with those in many foods, clinically relevant cross-reactivity appears uncommon. Nevertheless, sesame is a prominent allergen for those with multiple food allergies. Management may include strict avoidance, but sesame products vary dramatically in protein content. Many people with sesame allergy tolerate forms that are low in protein, such as scattered seeds, rather than sesame paste that is protein-dense. Thus, options in the approach to avoidance are possible. Studies suggest that sesame oral immunotherapy may be safe and effective, and this and additional treatment options are emerging. Here, we review the current comprehensive diagnosis, management, and treatment for sesame allergy.


The frequency of lung cancer in patients with pulmonary hamartomas: An evaluation of clinical, radiological, and pathological features and follow-up data of 96 patients with pulmonary hamartomas.
To investigate the frequency of lung cancer in patients with pulmonary hamartomas and to evaluate clinical, radiological, and pathological characteristics of pulmonary hamartomas. We reviewed pathology records of pulmonary hamartomas diagnosed between 2003 and 2014. Medical records and the hospital electronic database were also reviewed for each patient to obtain clinical, radiological, and pathological characteristics of pulmonary hamartomas and accompanying malignancies. Ninety-six patients with pulmonary hamartomas were identified. There were 26 females (27%) and 70 males (73%), with a mean age of 56.2 years (range 22-87 years). Malignancies were detected in 23 patients (24%), which developed previously in five patients (1 synchronous, 4 metachronous lesions), and concomitantly in 18 patients (with origin from the lung in 17 patients and from the pleura in 1 patient). Our results show that patients with pulmonary hamartomas may have coexisting lung malignancies.


HLA-DO is a negative modulator of HLA-DM-mediated MHC class II peptide loading.
Class II molecules of the major histocompatibility complex become loaded with antigenic peptides after dissociation of invariant chainderived peptides (CLIP) from the peptide-binding groove. The human leukocyte antigen (HLA)-DM is a prerequisite for this process, which takes place in specialised intracellular compartments. HLA-DM catalyses the peptide-exchange process, simultaneously functioning as a peptide 'editor', favouring the presentation of stably binding peptides. Recently, HLA-DO, an unconventional class II molecule, has been found associated with HLA-DM in B cells, yet its function has remained elusive. The function of the HLA-DO complex was investigated by expression of both chains of the HLA-DO heterodimer (either alone or fused to green fluorescent protein) in human Mel JuSo cells. Expression of HLA-DO resulted in greatly enhanced surface expression of CLIP via HLA-DR3, the conversion of class II complexes to the SDS-unstable phenotype and reduced antigen presentation to T-cell clones. Analysis of peptides eluted from HLA-DR3 demonstrated that CLIP was the major peptide bound to class II in the HLA-DO transfectants. Peptide exchange assays in vitro revealed that HLA-DO functions directly at the level of class II peptide loading by inhibiting the catalytic action of HLA-DM. HLA-DO is a negative modulator of HLA-DM. By stably associating with HLA-DM, the catalytic action of HLA-DM on class II peptide loading is inhibited. HLA-DO thus affects the peptide repertoire that is eventually presented to the immune system by MHC class II molecules.


Effects of Combined Transplantation of Multipotent Mesenchymal Stromal and Hemopoietic Stem Cells on Regeneration of the Hemopoietic Tissue.
The effect of allogenic combined transplantation of placental multipotent mesenchymal stromal and hemopoietic stem cells on regeneration of the myeloid tissue and spleen after acute blood loss was studied in laboratory mice. Combined transplantation of these cells did not change the content of cytogenetically modified cells in the bone marrow under normal conditions, but reduced their levels after acute blood loss. Combined transplantation of multipotent mesenchymal stromal and hemopoietic stem cells promoted activation of erythropoiesis and granulocytopoiesis. The major morphometric and cytological parameters of the white pulp of the spleen decreased, presumably due to immunosuppressive effect of multipotent mesenchymal stromal cells.


Adenosine A2A receptor activation protects CD4+ T lymphocytes against activation-induced cell death.
Activation-induced cell death (AICD) is initiated by T-cell receptor (TCR) restimulation of already activated and expanded peripheral T cells and is mediated through Fas/Fas ligand (FasL) interactions. Adenosine is a purine nucleoside signaling molecule, and its immunomodulatory effects are mediated by 4 G-protein-coupled receptors: A(1), A(2A), A(2B), and A(3). In this study, we investigated the role of A(2A) receptors in regulating CD4(+) T lymphocyte AICD. Our results showed that the selective A(2A) receptor agonist CGS21680 (EC(50)=15.2-32.6 nM) rescued mouse CD4(+) hybridomas and human Jurkat cells from AICD and that this effect was reversed by the selective A(2A) receptor antagonist ZM241385 (EC(50)=2.3 nM). CGS21680 decreased phosphatidylserine exposure on the membrane, as well as the cleavage of caspase-3, caspase-8 and poly(ADP-ribose) polymerase indicating that A(2A) receptor stimulation blocks the extrinsic apoptotic pathway. In addition, CGS21680 attenuated both Fas and FasL mRNA expression. This decrease in FasL expression was associated with decreased activation of the transcription factor systems NF-kappaB, NF-ATp, early growth response (Egr)-1, and Egr-3. The antiapoptotic effect of A(2A) receptor stimulation was mediated by protein kinase A. Together, these results demonstrate that A(2A) receptor activation suppresses the AICD of peripheral T cells.


Supratentorial recurrences of gliomas. Morphological studies in relation to time intervals with oligodendrogliomas.
On the basis of a three stage grading system we report 23 stage one recurrent oligodendrogliomas (O 1), and 29 stage two recurrent oligodendrogliomas (O 2). In the O 1 group after the first interval 15 became O 2 and 2 became glioblastomas. Twenty tumours of the O 2 group after the first interval were not changed, three became oligodendroglioma-astrocytomas stage 2, and six became glioblastomas. The time relation for the recurrent phase in the primary O 1 group is calculated as 42 months, and in the primary O 2 group as 22 months, but this is without significance. For the development of malignancy, especially for the change to glioblastoma, a prominent participation by transformed local astrocytes seems to be essential. Postoperative irradiation most probably does not favour malignant change. A prolongation of the expectation of life by radiotherapy is not noticed.


Radioscapholunate ligament: a gross anatomic and histologic study of fetal and adult wrists.
The radioscapholunate ligament was studied using fifty-four dissected adult cadaver wrists. Four of these wrists had arterial perfusions with colored latex and serial sections were made of twenty-one wrists from fetuses ranging in size from 23 to 230 millimeters crown-rump length. The radioscapholunate ligament was consistently identified between the long and short radiolunate ligaments, emerging through the palmar capsule of the radiocarpal joint. It was found to be a neurovascular structure surrounded by synovial tissue with vascular origins from the anterior interosseous and radial arteries and a neural origin from the anterior interosseous nerve. On entering the radiocarpal joint it attaches proximally to the interfacet prominence on the articular surface of the radius and distally to form the proximal membrane of the scapholunate interosseous ligament system. We found no anatomic evidence that this structure should be considered a ligament in a traditional mechanical sense. However, this structure may be clinically important as the vascular supply of the scapholunate interosseous ligament, as well as a sensory pathway from the scapholunate articulation.


An imbalance in the methionine content of the maternal diet reduces postnatal growth in the rat.
The pregnant rat fed a low-protein diet has become widely used as a model system in the study of the prenatal programming of adult metabolism and disease. When pregnant rats of the hooded Lister strain were fed semisynthetic diets containing 18% or 9% casein supplemented with 0.5% dl-methionine, there was significant postnatal mortality in the group fed the low-protein diet. In a second experiment, dams were fed diets containing 9% casein supplemented with varying concentrations of dl-methionine up to 0.4% (w/w) and compared with a group fed a diet containing 18% casein supplemented with 0.5% dl-methionine. At birth, the pups from dams fed the low-protein diets supplemented with 0.2% dl-methionine or greater were significantly smaller than those of the dams fed the diet containing 18% protein. By 25 weeks of age, the body weight of the offspring of dams fed the low-protein diet supplemented with 0.2% or 0.3% dl-methionine were approximately 10% lower than those in the control group of offspring from dams fed 18% protein supplemented with 0.5% dl-methionine. There were corresponding changes in the weights of the major organs. These data suggest that increasing the dl-methionine supplement in the low-protein diet retards the growth of the fetus and affects the mature adult body weight. In contrast to the findings of other studies that used different formulas of the low-protein diet, the glucose tolerance in the offspring was unaffected by the protein content of the maternal diet at all levels of dl-methionine supplementation. These results suggest that the changes in metabolism of the offspring result from interactions between protein, lipids, and carbohydrates in the maternal diet, rather than a consequence of postnatal growth retardation per se and highlight the importance of considering all components of the maternal diet in the programming mechanism.


Exploring the Link between Cardiorenal and Metabolic Diseases.
The close link between metabolic diseases, such as obesity and diabetes mellitus, and cardiorenal disease can be attributed not only to direct risk factors, such as hypertension, but also to the intricate interplay of various pathophysiological processes [...].


A mass mimicking pancreatic adenocarcinoma, should hepatobiliary surgeons keep it in mind? a case report.
Isolated metastasis to pancreas from lung cancer is an extremely rare entity, usually reported in case series and case reports in the medical literature; estimated to account for up to 3-5% of all pancreatic lesions. Herein, we describe a case of a male patient suffering from metachronous metastatic lesion to the tail of the pancreas secondary to non small cell lung carcinoma treated 4 years prior to his presentation. The patient underwent pancreatic resection due to high clinical suspicion for the malignant nature of the mass, which was proved to be secondary lesion from its prior primary tumor. To the best of our insight this is one of the few reported cases of such type of pancreatic metastasis that may be misleading for hepatobiliary surgeons during preoperative evaluation.


Quantum dots-based molecular classification of breast cancer by quantitative spectroanalysis of hormone receptors and HER2.
The emerging molecular breast cancer (BC) classification based on key molecules, including hormone receptors (HRs), and human epidermal growth factor receptor 2 (HER2) has been playing an important part of clinical practice guideline. The current molecular classification mainly based on their fingerprints, however, could not provide enough essential information for treatment decision making. The molecular information on both patterns and quantities could be more helpful to heterogeneities understanding for BC personalized medicine. Here we conduct quantitative determination of HRs and HER2 by quantum dots (QDs)-based quantitative spectral analysis, which had excellent consistence with traditional method. Moreover, we establish a new molecular classification system of BC by integrating the quantitative information of HER2 and HRs, which could better reveal BC heterogeneity and identify 5 molecular subtypes with different 5-year prognosis. Furthermore, the emerging 5 molecular subtypes based on simple quantitative molecules information could be as informative as multi-genes analysis in routine practice, and might help formulate a more personalized comprehensive therapy strategy and prognosis prediction.


Incidence and molecular characterization of Glucose-6-Phosphate Dehydrogenase deficiency among neonates for newborn screening in Chaozhou, China.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is highly prevalent in southern China. The aim of this study is to assess the extent of this disease in Chinese neonates and determine its molecular characteristics using a novel molecular screening method. A total of 2500 neonates were routinely screened for G6PD deficiency using a modified fluorescent spot test (FST). PCR-high-resolution melting (HRM) analysis was then used for the molecular assay. The overall incidence of G6PD deficiency was 2.68% in our study cohort. Frequency in male population was 3.22% (44 neonates of 1365 male neonates), and in female population was 2.03% (23 neonates of 1135 female neonates). Of the 67 newborns suspected to be G6PD deficient based on FST (44 males, 23 females), 58 of 67 (87%) were detected with gene alterations. Seven kinds of mutations [c.95A>G, c.392G>T, c.493A>G, c.871G>A, c.1360C>T, c.1376G>T, and c.1388G>A] were identified by HRM analysis. Routine newborn screening in Chaozhou, China with a relatively high prevalence of G6PD deficiency is justified and meets the World Health Organization recommendation. The usage of molecular diagnosis can favor the detection of heterozygotes which can be a supplement to regular newborn screening and useful for premarital and prenatal diagnosis for G6PD deficiency.


Precipitation variability differently affects radial growth, xylem traits and ring porosity of three Mediterranean oak species at xeric and mesic sites.
In the Mediterranean basin, diffuse-porous, semi-ring-porous and ring-porous tree species coexist in the same regions. Climate change might differently affect these types, but a mechanistic understanding of drought effects on their xylem structure is lacking. We investigated tree-ring width and xylem functional traits in ring-porous Quercus boissieri, semi-ring-porous Q. ithaburensis and diffuse-porous Q. calliprinos, at xeric (Galilee) and mesic (Golan) sites in the South-Eastern Mediterranean basin. We quantitatively assessed how dry and wet years affect growth and xylem traits in different porosity type oaks, and evaluated whether porosity type is preserved or altered during these years. We measured, counted or computed tree-ring width, vessel number, maximum lumen area, frequency, tree-ring and xylem theoretical hydraulic conductivity along 40-year ring series of 50 trees in total. We also quantified ring porosity in each year using two indices, the Gini coefficient and the porosity ratio of vessel area, and described vessel area intra-ring variations by distribution profiles. We then compared these parameters in the five driest and five wettest years of the 40-year period. Radial growth and functional trait variations were more similar between species in the same site (strong drought effects in Q. ithaburensis and Q. calliprinos in Galilee, moderate effects in Q. boissieri and Q. calliprinos in Golan) than between sites for the same species (Q. calliprinos was more affected in Galilee than in Golan). Ring porosity indices and distribution profiles showed that diffuse-porous xylem structure of Q. calliprinos was maintained even under dry conditions at both sites. However, Q. boissieri xylem shifted from ring-porous in wet and normal years to semi-ring-porous in dry years, i.e. the porous ring cannot be completely built under water constraint. This suggests that ring porous strategy, typical of temperate regions with strong seasonality, might not be realized under future drier conditions in the Mediterranean basin.


Validation of the eHealthResp online course for pharmacists and physicians: A Delphi method approach.
The inappropriate use of antibiotics for respiratory tract infections is dispersed worldwide, thus being a strong contributor to antibiotic resistances. As the use of educational interventions among health practitioners is shown to have an impact on judicious antibiotic use, an online course (eHealthResp) has been developed, especially targeted to pharmacists and physicians. Thus, the main goal of this study is to validate the contents of the online course eHealthResp. This two-round Delphi study involved the recruitment of a multidisciplinary panel (n = 19), to which the questionnaires of the first round were sent. After the first round, a report summing up the results has been forwarded to the panel, along with a new, reformulated version of the questionnaire. After the two rounds of the Delphi process, consensus was evaluated. Six clinical cases and fifty-one treatments obtained minor consensus [60-75%] or full consensus (≥75%). The question on antibiotic practice has obtained a consensus >90% on both rounds. The validation of the contents based on experts' consensus has been an essential approach to improve eHealthResp's online course, as valuable feedback has been provided by the panel on both rounds.


Mn(II)-Based MRI Contrast Agent Candidate for Vascular Imaging.
Toxicity concerns related to Gd(III)-based magnetic resonance imaging (MRI) agents prompted an intensive research toward their replacement by complexes of essential metal ions, like Mn(II). Here, we report a macrocyclic chelate, [Mn(PC2A-BP)], which possesses high thermodynamic stability (log KMnL = 14.86 and pMn=8.35) and kinetic inertness (t1/2pH=7.4 = 286.2 h) as well as as remarkable relaxivity (r1p = 23.5 mM-1 s-1, 0.49 T, 37 °C) in the presence of human serum albumin, allowing a significant MRI signal intensity increase in the vasculature even at low dose (25 μmol/kg) of the complex.


Single step non-thermal cleaning/sanitation of knives used in meat industry with ultrasound.
The combination of ultrasound (US) with chlorinated water (CW) and neutral detergent (ND) for simultaneous cleaning and sanitation of knives used during cattle slaughter was evaluated as a novel non thermal treatment. The US mode of operation, detergent concentration and time of treatment were studied and the results were compared with the conventional sanitation method used in meat industries. The conventional sanitation method promoted a decrease (p<0.05) in the counts of mesophiles, Enterobacteriaceae, molds and yeasts, and a similar behavior was observed for US+CW (2.05±0.08mg/l of chlorine, and mode operation normal and sweep for 10min) and US+CW+ND (5ml/l and mode operation sweep for 5min) methods. Nevertheless, when detergent concentration and sonication time were increased (20ml/l, 15min) a strong decrease (p<0.05) in the counts of mesophiles, Enterobacteriaceae, Staphylococcus aureus, molds and yeasts. Knife blades presented appropriate hygienic-sanitary properties in such conditions based on the Clean-Trace Surface Protein Plus™ test swab, which were better than the results obtained from conventional method. Kinetic modeling of knife sanitation was performed according to the transfer of organic matter, nitrogen and phosphorus during the process indicated highest migration rate of residues for US+CW+ND method, reaching 1.61mg/l·min. The hardness of knives' surface (Rockwell) was not changed by sonication using US+CW+ND method. These results indicate that both knife cleaning and sanitation processes could be performed in a unique step without the use of heat.


6-Keto-prostaglandin E1 inhibits the aggregation of human platelets.
6-Keto-prostaglandin E1 (6-keto-PGE1) was found to have a similar potency to prostacyclin (PGI2) as an inhibitor of platelet aggregation. It caused a time and concentration dependent inhibition of ADP, collagen and epinephrine induced platelet aggregation, the dose ratios for 70% inhibition by 6-keto-PGE1, PGI2 and PGE1 being approximately 1 : 1 : 13. In doses similar to those of PGI2, 6-keto-PGE1 partially inhibited the release of [3H]-serotonin from platelet-rich plasma induced by collagen.


[Treatment of systemic sclerosis].
Treatment of systemic sclerosis is based upon 3 types of medications modifiers of disease: drugs which prevent vascular damage, antifibrotric agents, and immunomodulators and immunosupressors. Drugs that prevent vascular damage such as: calcium antagonists, prostaglandins analogues, receptors of endothelin blockers (bosentan), inhibitors of angiotensin converting enzyme, receptors of angiotensin antagonists and inhibitors of 5'-phosphodiesterase have been successful in treating the Raynaud's phenomenon, renal crisis and pulmonary arterial hypertension. In contrast, the results of treatment of fibrosis are discouraging and the D-penicilamine continues being a matter of controversy. The immunosupressor therapy with cyclophosphamide and the transplant of hematopoietic cells, may be beneficial. The knowledge of the pathogenesis of systemic sclerosis to molecular level will lead to new treatment strategies.


Listeria monocytogenes is common in wild birds in Helsinki region and genotypes are frequently similar with those found along the food chain.
To evaluate the prevalence and genetic diversity of Listeria monocytogenes in wild birds and to compare the genotypes with isolates previously collected from foods and food processing environments. Samples of wild birds' faeces (n = 212) were collected from a municipal landfill site and from urban areas in the Helsinki region and analysed by two-step enrichment and plating onto L. monocytogenes-selective agar. The overall prevalence of L. monocytogenes in bird faeces was 36% (95% CI 30-43%), and prevalence on the landfill site was significantly higher. All isolates were analysed with pulsed-field gel electrophoresis and compared with the L. monocytogenes profiles in an existing collection. Similar pulsotypes were found in birds and in isolates collected along the food chain. Birds commonly carry L. monocytogenes, and strains are frequently similar with those detected in foods and food processing environments. Thus, birds may disseminate L. monocytogenes in nature and may also contaminate foods when entering the food processing environments and outdoor market places. Populations of L. monocytogenes in wild birds and along the food processing chain overlap. Our findings add to the epidemiological data on this significant foodborne pathogen.


The roles of filtration and expression in the processing of digesta with high solid phase content.
The processes of filtration and expression of suspensions of biological solids are reviewed in the context of vertebrate digestion. We show that the digesta of the brushtail possum and sheep form a contiguous matrix of particles from which a fluid phase can be expressed by the application of pressure. These findings are examined in respect of their possible contribution to phase separation and the sorting of particles within the gastrointestinal tracts of vertebrates. The morphological adaptations and motility of various digestive compartments are related to the processing of digesta with high solid phase content, in particular the formation and dispersion of the particle matrices. A brief description is given of techniques for evaluating the properties of digesta with high solid phase content.


LILRB1+ immune cell infiltration identifies immunosuppressive microenvironment and dismal outcomes of patients with ovarian cancer.
Immune checkpoint inhibitors are commonly used in various types of cancer, but their efficacy in ovarian cancer (OC) is limited. Thus, identifying novel immune-related therapeutic targets is crucial. Leukocyte immunoglobulin-like receptor subfamily B1 (LILRB1), a key receptor of human leukocyte antigen G (HLA-G), is involved in immune tolerance, but its role in tumor immunity remains unclear. In this study, immunofluorescence was used to identify the location of LILRB1 in OC. The effect of LILRB1 expression on clinical outcomes in 217 patients with OC was analyzed retrospectively. A total of 585 patients with OC from the TCGA database were included to explore the relationship between LILRB1 and tumor microenvironment characteristics. LILRB1 was found to be expressed in tumor cells (TCs) and immune cells (ICs). High LILRB1+ ICs, but not LILRB1+ TCs, were associated with advanced FIGO stage, shorter survival outcomes, and worse adjuvant chemotherapy responses in OC patients. LILRB1 expression was also associated with high M2 macrophage infiltration, reduced activation of dendritic cells, and dysfunction of CD8+ T cells, suggesting an immunosuppressive phenotype. The combination of LILRB1+ ICs and CD8+ T cell levels could be used to distinguish patients with different clinical survival results. Moreover, LILRB1+ ICs infiltration with CD8+ T cells absence indicated inferior responsiveness to anti-PD-1/PD-L1 therapy. Tumor-infiltrating LILRB1+ ICs could be applied as an independent clinical prognosticator and a predictive biomarker for therapy responsiveness to OC. Further studies targeting the LILRB1 pathway should be conducted in the future.


Incident knee pain in the Nottingham community: a 12-year retrospective cohort study.
To determine the community incidence of knee pain and associated risk factors over a 12-year period in people over the age of 40 years. A cohort study of knee pain was undertaken in 2156 people from four general practices in North Nottinghamshire, UK. Knee pain was defined as 'pain around the knee for most days of at least a month'. Cumulative incidence over 12 years and person-year incidence rate of knee pain were estimated. Survival analysis was undertaken for time to the onset of knee pain. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for relative risk between exposure and non-exposure. Cox regression model was used to adjust for confounding factors. The 12-year cumulative incidence of knee pain was 34.4% (32% for men and 35% for women), corresponding to an average incidence rate of 32 (31 for men and 34 for women)/1000 person-years. Incident knee pain was associated with female gender (HR 1.27, 95% CI 1.08, 1.49), obesity (1.80; 95% CI 1.37, 2.38), varus (1.68, 95% CI 1.15, 2.47) and valgus (1.83, 95% CI 1.05, 3.20) mal-alignment, and knee injury (2.37, 95% CI 2.98, 2.85). For people over age 40, one in three will develop knee pain within 12 years. On average, the risk of knee pain was 32/1000 person-years. This risk is associated with a variety of constitutional and environmental biomechanical insults to the knee. Some of these could be modified to possibly reduce the incidence of the condition.


Combined Therapy With Polyethylene Glycol-20k and MCC950 Preserves Post-Resuscitated Myocardial Function in a Rat Model of Cardiac Arrest and Cardiopulmonary Resuscitation.
Background To investigate the therapeutic potential of combined therapy with polyethylene glycol-20k (PEG-20k) and MCC950 on post-resuscitation myocardial function in a rat model of cardiac arrest. Methods and Results Thirty rats were randomized into 5 groups: Sham, Control, PEG-20k, MCC950, PEG-20k+ MCC950. Except for sham, animals were subjected to 6 minutes of ventricular fibrillation followed by 8 minutes cardiopulmonary resuscitation. Two milliliters PEG-20k was administered by intravenous injection coincident with the start of cardiopulmonary resuscitation; MCC950 (10 mg/kg), a highly selective NLRP3 inflammasome inhibitor, was delivered immediately after restoration of spontaneous circulation. Myocardial function, sublingual microcirculation, mitochondrial function, plasma cardiac troponin I, and interleukin-1β, expression of proteins in SIRT1 (sirtuin 1)/PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) and NLRP3 (the NOD-like receptor family protein 3) inflammasome pathways were evaluated. Following cardiopulmonary resuscitation, myocardial function was compromised with a significantly decreased cardiac output, ejection fraction, and increased myocardial performance index, cardiac troponin I. Sublingual microcirculation was disturbed with impaired perfused vessel density and microvascular flow index. Cardiac arrest reduced mitochondrial routine respiration, Complex I-linked respiration, respiratory control rates and oxidative phosphorylation coupling efficiency. PEG-20k or MCC950 alone restored mitochondrial respiratory function, restituted sublingual microcirculation, and preserved myocardial function, whereas a combination of PEG-20k and MCC950 further improved these aspects. PEG-20k restored the expression of SIRT1 and PGC-1α, and blunted activation of NLRP3 inflammasomes. MCC950 suppressed expression of cleaved-caspase-1/pro-caspase-1, ASC (apoptosis-associated speck-like protein), GSDMD [gasdermin d], and interleukin-1β. Conclusions Combined therapy with PEG-20k and MCC950 is superior to either therapy alone for preserving post-resuscitated myocardial function, restituting sublingual microcirculation at restoration of spontaneous circulation at 6 hours. The responsible mechanisms involve upregulated expression of SIRT1/PGC1-α in tandem with inhibition of NLRP3 inflammasomes.


Development of a validated HPTLC-bioautographic method for evaluation of aromatase inhibitory activity of plant extracts and their constituents.
Aromatase is a CYP450 enzyme that catalyses the conversion of androgens into oestrogens, where the decrease in the production of oestrogens aided by aromatase inhibitors is considered a target in post-menopausal breast cancer therapy. TLC-bioautography is a technique employed for combining chromatographic separations on TLC plates with bioassays. This is the first report to evaluate aromatase inhibitory activity using this technique. The aim of this study is to develop and validate a new TLC-bioautographic method for determination of aromatase inhibitory activity in 14 plant extracts. Two quantitation methods, the peak area method and reciprocal iso-inhibition volume (RIV) method, were compared and investigated to attain reliable results. Factors affecting the enzymatic reaction (temperature, pH, enzyme and substrate concentrations … etc.) were also investigated to attain the optimum parameters. TLC assisted by digital image processing was implemented for quantitative estimation of the aromatase inhibition of 14 plant extracts using chrysin as positive control. The fluorometric substrate dibenzyl fluorescein (DBF) was utilised for the assay, where inhibitory compounds were visualised as dark spots against a blue fluorescent background. Two software programs, Sorbfil® videodensitometer (in the peak area method) and ImageJ® (in the RIV method), were thoroughly validated using the International Council on Harmonisation (ICH) guideline and used for quantitation. The RIV method showed superiority over the peak area method in the quantitation results of the tracks with non-homogenous background with %RSD values of 0.98 and 1.49 compared with 2.86 and 3.58, respectively. Further, the methods allow the comparison of the activity of different unknown inhibitory compounds without the need for a reference or a positive control. Using the TLC-bioautographic method by image processing combined with the RIV quantitation method, simultaneous separation and quantitation of aromatase inhibitory components could be applied to estimate the relative activity of various plant extracts.


Growth-blocking peptide titer during larval development of parasitized and cold-stressed armyworm.
Growth-blocking peptide (GBP) has been isolated for the first time from the haemolymph of the host armyworm Pseudaletia separata whose development was halted in the last larval instar stage by parasitization with the parasitoid wasp Cotesia kariyai. Recent studies demonstrated that GBP not only exists in the plasma (haemolymph without cells) of parasitized last instar larvae, but also in the plasma of nonparasitized penultimate (5th) instar larvae. Monoclonal antibodies were prepared to measure the titers of GBP in nonparasitized and parasitized larval plasma. One of three monoclonal antibodies raised against GBP, which is the most specific for GBP, was used to quantify the concentration of plasma GBP. As this antibody recognized two plasma peptides other than GBP in crude plasma fractions, each plasma peptide fraction was separated by a reversed phase HPLC, and then plasma GBP level was measured by ELISA. The highest level of plasma GBP detected on Day 0 of the penultimate instar larvae was gradually decreased throughout the larval growth except for the temporary increase on Day 0 of last larval instar. After parasitization on Day 0 of last larval instar, two peaks of plasma GBP titer were detected during the last larval instar, one day and six days after parasitization. This characteristic increase and decrease in plasma GBP level was also observed by transferring last instar larvae of the armyworm from 25 to 10 degrees C, as a result of which larvae delayed pupation by more than 15 days. From these results, it is reasonable to propose that plasma GBP in lepidopteran larvae might control certain upstream steps in a cascade of events leading to pupation; thus, an elevated level of plasma GBP interferes with normal metamorphosis from larvae to pupae.


Relation of growth-differentiation factor 15 to left ventricular remodeling in ST-segment elevation myocardial infarction.
The development of left ventricular remodeling (LVR) after myocardial infarction is associated with a high risk of heart failure and death. LVR is difficult to predict, and limited information is available on the association of cardiac biomarkers and LVR. Growth-differentiation factor-15 (GDF-15) is induced during heart failure development and, in animals models, might influence the different processes involved in cardiac remodeling. The aim of the present investigation was to assess the association between the serum levels of GDF-15 within the first 24 hours of ST-segment elevation myocardial infarction and the development of subsequent LVR at 12 months of follow-up. This prospective study included 97 patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Echocardiography was performed in all patients within the first 96 hours of admission and at 12 months of follow-up. LVR was defined as a >20% increase in the left ventricular end-diastolic volume at 12 months of follow-up compared to baseline. Blood samples for the determination of GDF-15 and brain natriuretic peptide were obtained within the first 24 hours after symptom onset. According to the pre-established criteria, 21 patients (22%) had LVR. Patients with LVR had greater levels of GDF-15 at study entry (median 3,439 pg/ml, interquartile range 2,391 to 6,168 vs median 1998 pg/ml, interquartile range 1,204 to 3,067, respectively; p <0.001). Multivariate analysis showed that GDF-15 (odds ratio 10.1, 95% confidence interval 2.5 to 40.1, p <0.001) and treatment with angiotensin-converting enzyme inhibitors (odds ratio 3.9, 95% confidence interval 1.2 to 12.3, p <0.01) were independents predictors of LVR. Receiving operating characteristics analysis showed an area under the curve of 0.77 for GDF-15 (95% confidence interval 0.67 to 0.84, p <0.001). In conclusion, the results of the present study have identified GDF-15 as an independent marker of LVR in patients with ST-segment elevation myocardial infarction.


[Postembryonic and regenerative growth of cerci and leg segments of Tachycines (Saltatoria)].
The postembryonic and regenerative growth capacities of cerci and legs were investigated inTachycines asynamorus. The normal length and growth of cerci and segments of the middle legs, and the number and duration of normal postembryonic instars were determined in isolated individuals. In the regeneration experiments, the animals were amputated after the molt into the second postembryonic instar.An organotypic cercus is regenerated after 2-3 molts. The increment of length between molts is about constant, normal length is never acquired. If amputation occurs within the first three days after the molt, a papilla or a small regenerate will usually be present after the next molt. The molting rate is decreased during the next 3-4 molts. If the amputation is performed later, no regenerate will usually appear until after two molts. In this case the average molting rate is not significantly decreased.An organotypic tarsus of the middle leg is present 1-3 molts after amputation, an organotypic tibiotarsus 3-4 molts after amputation. Normal proportions are reached after 6-8 molts. If the femur is also removed, no regeneration takes place. Seven potential steps of regenerative differentiation were distinguished. The earlier the amputation, the faster the regeneration. The total duration of development to the ninth instar is about the same in normal and regeneration individuals because in the latter the initial slowing down of molting is compensated by an increased molting rate after the fourth instar.The existence of certain organ-specific critical periods is postulated for each molt interval. Before such a period, regeneration may be elicited and can follow its autonomous course. After the critical period has elapsed, no regeneration blasteme can grow any more during that molt interval. There is evidence, that the critical period for cereal regeneration lies in the first half, for tarsal regeneration in the second half, and for tibiotarsal regeneration in the middle part of the molt interval. The pattern which happens to be determined in the epidermis blasteme, will become expressed in the cuticle through the process of molting.A comparison of the findings onTachycines, Carausius and some blattids leads to the following working hypothesis, inviting histological and further experimental analysis: Cerci have a proximal blasteme which exhibits proliferative growth during normal development and regeneration. In regeneration legs during segmentation the situation is similar, during growth after segmentation and during normal postembryonic growth, there is a self-regulatory control of limp proportions. The causes responsible for all types of growth are to be sought in the cycle of the hormonal system, and in the site and age specific competence of the cells.


Inhibition of bone resorption in vitro by a cartilage-derived anticollagenase factor.
A cartilage-derived factor containing a specific collagenous inhibitor was found to block reversibly parathyroid hormone-stimulated 45Ca release from fetal rat bone in vitro. Morphologic and quantitative histometric examination revealed that this factor modulates osteoclastic activities.


[Determination of glucose with glucoseoxidase-UV, using hexokinase as the reference method (author's transl)].
Results obtained with the commercial test-set "GOD-UV" (Dr. Haury, München) are reported. This method permits the determination of serum-glucose within 3 minutes. The procedure is satisfactory in normal and hyperglycaemic patients. In the hypoglycaemic state, however, there is a danger of misinterpretation. The glucose oxidase-UV is compared with the hexokinase reaction.