MRx102, a triptolide derivative, has potent antileukemic activity in vitro and in a murine model of AML.
Triptolide, isolated from the herb Tripterygium wilfordii, has been shown to potently induce apoptosis in various malignant cells by inhibiting RNA synthesis and nuclear factor-κB activity. Previously, we showed that triptolide promotes apoptosis in acute myeloid leukemia (AML) cells via the mitochondria-mediated pathway, in part, by decreasing levels of the anti-apoptotic proteins XIAP and Mcl-1. MRx102 is a triptolide derivative, currently in preclinical development. Here we show that MRx102 potently promoted apoptosis in AML cell lines, with EC(50) values of 14.5±0.6 nM and 37.0±0.9 nM at 48 h for OCI-AML3 and MV4-11 cells, respectively. MRx102, at low nanomolar concentrations, also induced apoptosis in bulk, CD34(+) progenitor, and more importantly, CD34(+)CD38(-) stem/progenitor cells from AML patients, even when they were protected by coculture with bone marrow derived mesenchymal stromal cells. MRx102 decreased XIAP and Mcl-1 protein levels and inhibited RNA synthesis in OCI-AML3 cells. In vivo, MRx102 greatly decreased leukemia burden and increased survival time in non-obese diabetic/severe combined immunodeficiency mice harboring Ba/F3-ITD cells. Collectively, we demonstrated that MRx102 has potent antileukemic activity both in vitro and in vivo, has the potential to eliminate AML stem/progenitor cells and overcome microenvironmental protection of leukemic cells, and warrants clinical investigation.


Effects of dietary bovine lactoferrin on growth, physiological performance, iron metabolism and non-specific immune responses of Siberian sturgeon Acipenser baeri.
The present experiment was carried out to investigate the effects of different levels of dietary lactoferrin (LF) on growth performance, physiological status, iron absorption and innate immune response of juvenile Siberian sturgeon Acipenser baeri. Fish were fed with six different rations including 0, 100, 200, 400, 800 and 1600 mg LF kg(-1) diet for 8 weeks. At the end of the experiment, samples were collected for estimating the physiological and immunological parameters. Dietary LF did not change the fish growth performance, hematological parameters, serum proteins or hepatic enzymes. Moreover, stress indicators (plasma cortisol, glucose and lactate) were not affected by dietary LF. The iron absorption of fish was considerably affected by LF; thus, plasma iron in LF-treatments greatly declined and the total iron binding capacity (TIBC) significantly increased in fish fed with 800 mg LF kg(-1). In addition, the liver iron content markedly increased in some LF-treatments, but the variation of muscle iron concentration in treatments was insignificant. The amount of mucus secretion and serum bactericidal activity rose in fish fed on dietary LF, although other non-specific immune responses such as mucus bactericidal activity, serum and mucus lysozyme activity, serum peroxidase, serum natural hemolytic complement activity and serum IgM were not influenced by LF. This study revealed the ability of dietary LF to sequester iron, which is an essential nutrient required for the growth of bacteria. LF was also shown to improve some physiological and immunological parameters of Siberian sturgeon, to some extent.


Post-conization endocervical curettage for estimating the risk of persistent or recurrent high-grade dysplasia.
To evaluate the association between post-cone endocervical curettage (ECC) results, either alone or with cone margin status, and persistent/recurrent high-grade dysplasia after conization. The medical records of 250 women who underwent a loop electrosurgical excision procedure with post-cone ECC at Soroka Medical Center, Be'er Sheva, Israel, between January 2001 and July 2011 were reviewed retrospectively. Thirty-one women (12.4%) had evidence of high-grade dysplasia in the ECC sample. Factors associated with positive ECC were being older than 35 years (P=0.004) and positive margin status (P=0.001). Twenty-nine patients (11.6%) had persistent/recurrent high-grade dysplasia. Both high-grade dysplasia in the ECC sample (hazard ratio, 2.31; P=0.032) and positive cone margins (hazard ratio, 23.4; P<0.001) were associated with persistent/recurrent disease. High-grade dysplasia in the ECC sample was associated with positive cone margin status. These 2 factors were both associated with persistent/recurrent disease. Among patients with positive cone margins, a combination of margin status and ECC was superior to margin status alone for estimating the probability of persistent/recurrent disease. For women with negative cone margins, ECC was less useful. Because ECC is valuable for assessing the risk of persistent/recurrent high-grade dysplasia in many cases, post-cone ECC should be performed routinely with conization.


Analysis of temperature distribution over pipe surfaces of air-based cavity linear receiver for cross-linear concentration solar power system.
This analysis is based on the computational fluid dynamics (CFD) of the air-based solar cavity linear receiver (CLR) of the cross-linear concentrated solar power plant. In this study, the temperature distribution along the pipe surface is investigated using a small section of a receiver. To study the variation of temperature over the surface of receiver pipes, a CFD model has been developed in Ansys Fluent. The analysis shows the effect of reflected radiation on the temperature variation over the front and back surfaces of the pipes, as well as the effect of this variation on heat transfer fluid (HTF) outlet temperature. The difference in the HTF outlet temperature and heat transfer rate between experimental data and CFD results has been identified. After rigorous examination, it has been observed that the effective range of length for heat absorbing pipe is from 60 to 600 mm (outlet) as HTF continues to absorb heat in this range. The average heat transfer rate was observed to be around 14108 W. Finally, the effect of variable mass flow rate over thermal efficiency of the receiver has been examined and it has been observed that once the mass flow rate exceeds 0.06 kg/s, further increasing the mass flow rate has little effect on improving the thermal efficiency because after an optimum value of mass flow rate would result in increase in heat loss from the pipe's back wall. In the present study, the results of the CFD analysis have been validated with an experimental test data.


Advanced sternal closure to prevent dehiscence in obese patients.
Sternal dehiscence is a frequent complication after cardiac surgical procedures. The objective was to evaluate a novel method for advanced sternal closure compared with standard techniques for preventing sternal dehiscence. Our investigation comprised 100 patients with a body mass index above 32. Patients were randomly assigned to receive either advanced sternal closure with three stainless steel double wires or standard techniques with stainless steel single wires. The incidence of sternal refixation was 6 of 50 patients in the standard techniques group and 1 of 50 in the advanced sternal closure group during a follow-up period of 6 months.


A model for the excision of introns 1 and 2 from adenoviral major late pre-messenger RNAs.
Total steady-state RNA was extracted from nuclei of HeLa cells late after infection with adenovirus serotype 2. Most of the nuclear RNA is transcribed from the major late transcription unit (16.2 to 100.0 map units). To study the cleavage reactions involved in the splicing of leaders 1 and 2, we have used the S1 nuclease mapping technique with restriction fragments located in the region of intron 1 as DNA probes. The S1 mapping data showed that in total nuclear RNA, RNA species accumulate from which the 5' part of intron 1 has been excised, but which still contain the 3' part of the intron. This indicates that intron 1 can be removed in a stepwise fashion following the 5' to 3' direction. We have compared the nucleotide sequences from the ends of the putative processing intermediates. The internal cleavage sites do not resemble the consensus 5' or 3' splice site sequences. However, they show considerable homology to the sequence 5' A-T-G-A-T-G-G-C-A-T 3', which may act as a signal for internal cleavage. The intermediates are present in both the poly(A)+ and poly(A)- RNA fractions, although with different relative intensities. Primer extension experiments have been performed in which a primer, located with its left end in leader 2, is extended into intron 1. The results show that there may be a cleavage site as short as 35 nucleotides before the 3' splice site. Cleavage at the 3' splice site seems to be rapidly followed by ligation of leader 1 to leader 2. A model for RNA splicing based on these findings and data from the literature is presented.


Efficacy of an agonist of α-MSH, the palmitoyl tetrapeptide-20, in hair pigmentation.
Hair greying (i.e., canities) is a component of chronological ageing and occurs regardless of gender or ethnicity. Canities is directly linked to the loss of melanin and increase in oxidative stress in the hair follicle and shaft. To promote hair pigmentation and reduce the hair greying process, an agonist of α-melanocyte-stimulating hormone (α-MSH), a biomimetic peptide (palmitoyl tetrapeptide-20; PTP20) was developed. The aim of this study was to describe the effects of the designed peptide on hair greying. Effect of the PTP20 on the enzymatic activity of catalase and the production of H2 O2 by Human Follicle Dermal Papilla Cells (HFDPC) was evaluated. Influence of PTP20 on the expression of melanocortin receptor-1 (MC1-R) and the production of melanin were investigated. Enzymatic activity of sirtuin 1 (SIRT1) after treatment with PTP20 was also determined. Ex vivo studies using human micro-dissected hairs allowed to visualize the effect of PTP20 on the expression in hair follicle of catalase, TRP-1, TRP-2, Melan-A, ASIP, and MC1-R. These investigations were completed by a clinical study on 15 human male volunteers suffering from premature canities. The in vitro and ex vivo studies revealed the capacity of the examined PTP20 peptide to enhance the expression of catalase and to decrease (30%) the intracellular level of H2 O2 . Moreover, PTP20 was shown to activate in vitro and ex vivo the melanogenesis process. In fact, an increase in the production of melanin was shown to be correlated with elevated expression of MC1-R, TRP-1, and Melan-A, and with the reduction in ASIP expression. A modulation on TRP-2 was also observed. The pivotal role of MC1-R was confirmed on protein expression analysed on volunteer's plucked hairs after 3 months of the daily application of lotion containing 10 ppm of PTP20 peptide. The current findings demonstrate the ability of the biomimetic PTP20 peptide to preserve the function of follicular melanocytes. The present results suggest potential cosmetic application of this newly designed agonist of α-MSH to promote hair pigmentation and thus, reduce the hair greying process.


Does aquatic exercise relieve pain in adults with neurologic or musculoskeletal disease? A systematic review and meta-analysis of randomized controlled trials.
To evaluate the literature on the effectiveness of aquatic exercise in relieving pain in adults with neurologic or musculoskeletal disease. A systematic literature search of 14 databases was examined for research on aquatic exercise over the period January 1980 to June 2006. Randomized controlled trials (RCTs) that included adults with neurologic or musculoskeletal disease, pain as an outcome measure, and exercise in water were included. Information on the participants, interventions, and outcomes was extracted from the included studies. Quality appraisal was assessed using the Scottish Intercollegiate Guidelines Network criteria for RCTs. Nineteen studies met the inclusion criteria; 8 were of moderate to low risk of bias, and 5 of these had data suitable for meta-analyses. This showed that aquatic exercise has a small posttreatment effect in relieving pain compared with no treatment (P=.04; standardized mean difference [SMD], -.17; 95% confidence interval [CI], -.33 to -.01), but it is not possible to draw a firm conclusion because of the lack of consistency of evidence across studies. Comparable pain-relieving effects were found between aquatic and land-based exercise (P=.56; SMD=.11; 95% CI, -.27 to .50). There is sound evidence that there are no differences in pain-relieving effects between aquatic and land exercise. Compared with no treatment, aquatic exercise has a small pain-relieving effect; however, the small number of good-quality studies and inconsistency of results means that insufficient evidence limits firm conclusions. Future studies should aim for focused research questions on specific aquatic exercise techniques, using robust methodologic designs and detailed reporting of temperature, depth, and care setting.


Prevalence of common aneuploidy in twin pregnancies.
The incidence of chromosomal abnormalities in twin pregnancies is not well-studied. In this retrospective study, we investigated the frequency of chromosomal abnormalities in twin pregnancies and compared the incidence of chromosomal abnormalities in dichorionic diamniotic (DD) and monochorionic diamniotic (MD) twins. We used data from 57 clinical facilities across Japan. Twin pregnancies of more than 12 weeks of gestation managed between January 2016 and December 2018 were included in the study. A total of 2899 and 1908 cases of DD and MD twins, respectively, were reported, and the incidence of chromosomal abnormalities in one or both fetuses was 0.9% (25/2899) and 0.2% (4/1908) in each group (p = 0.004). In this study, the most common chromosomal abnormality was trisomy 21 (51.7% [15/29]), followed by trisomy 18 (13.8% [4/29]) and trisomy 13 (6.9% [2/29]). The incidence of trisomy 21 in MD twins was lower than that in DD twins (0.05% vs. 0.5%, p = 0.007). Trisomy 21 was less common in MD twins, even when compared with the expected incidence in singletons (0.05% vs. 0.3%, RR 0.15 [95% CI 0.04-0.68]). The risk of chromosomal abnormality decreases in twin pregnancies, especially in MD twins.


Successful Sac Embolization to Eliminate a Type 2 Endoleak After Thoracic Endovascular Aortic Repair by Penetration of a Vascular Plug Implanted in a Left Subclavian Artery.
To describe a technique of vascular plug penetration by a guidewire with a heavy tip load for additional embolization of a type 2 endoleak after endovascular aortic aneurysm repair (EVAR). The technique of vascular plug penetration is effective for additional embolization of a type 2 endoleak, when large arteries such as left subclavian artery (LSA) or hypogastric artery remain patent even after the embolization of the vessel has been performed using a vascular plug and are responsible for the endoleak. A tapered guidewire with a heavy tip load enables the penetration of the disk of the plug, followed by introduction of a microcatheter into the endoleak nidus. In the presented case, the technique successfully eliminated a type 2 endoleak in a thoracic aortic aneurysm for which a patent LSA despite the embolization by a vascular plug was responsible. The technique of vascular plug penetration allows an access to an endoleak cavity via a vascular plug placed in an aortic side branch for additional embolization of a type 2 endoleak after EVAR.


Prenatal diagnosis of chorioangioma associated with polyhydramnios using ultrasound.
This paper presents a case of chorioangioma associated with polyhydramnios and premature delivery in which the placental tumour was diagnosed before delivery using ultrasound. In cases of polyhydramnios careful ultrasonic examination not only of the fetus, but also of the placenta, is recommended.


Chemical Biology Toolbox for Studying Pancreatic Islet Function - A Perspective.
The islets of Langerhans represent one of the many complex endocrine organs in mammals. Traditionally, islet function is studied by a mixture of physiological, cell biological, and molecular biological methods. Recently, novel techniques stemming from the ever-increasing toolbox provided by chemical laboratories have been added to the repertoire. Many emerging techniques will soon be available to manipulate and monitor islet function at the single-cell level and potentially in intact model animals, as well as in isolated human islets. Here, we review the most current small-molecule-based and genetically encoded molecular tool sets available to study islet function. We provide an outlook regarding future tool developments that will impact islet research, with a special focus on the interplay between different islet cell types.


Dekkera and Brettanomyces growth and utilisation of hydroxycinnamic acids in synthetic media.
Dekkera and Brettanomyces yeast are important spoilage organisms in a number of food and beverage products. Isolates of both genera were cultured in a defined medium and supplemented with hydroxycinnamic acids and vinylphenols to investigate their influence on growth and the formation of ethyl phenol derivatives. The growth rate of Brettanomyces species in the presence of acids was reduced, and no significant conversion to vinyl or ethyl derivatives was observed. The growth rate and substrate utilisation rates of Dekkera anomala and Dekkera bruxellensis yeast differed depending on strain and the acid precursor present. Growth of D. bruxellensis was slowed by the presence of ferulic acid with the addition of 1 mM ferulic acid completely inhibiting growth. This study provides an insight into the spoilage potential of these organisms and possible control strategies involving hydroxycinnamic acids.


[Differential indications of opioids in pain therapy].
Due to their strong analgesic potency opioids are highly effective in the therapy of acute and particularly cancer-induced chronic pain; however, the individual opioids differ considerably with respect to their pharmacokinetic and physicochemical properties and may therefore not be equally applicable for every patient. Caution should be taken especially in patients with impaired organ function. Furthermore, the metabolism of opioids leads to active or inactive metabolites. This process can be substantially influenced by genetic polymorphisms or drug interactions. Knowledge of all these factors for individual opioids, which influence the efficacy and side effects, is therefore crucial. In this review the pharmacology, clinical applications, metabolism and genetic factors of the most important opioids used for pain management are discussed.


Easing the burden of premenstrual dysphoric disorder.
It's much less common than premenstrual syndrome, but it can have a severe impact on your patient's quality of life. Here's how to recognize it and alleviate the symptoms.


Current trends in venous thromboembolism among persons hospitalized with acute traumatic spinal cord injury: does early access to rehabilitation matter?
To determine the incidence of venous thromboembolism (VTE) among patients with traumatic spinal cord injury (TSCI) in acute care settings that is attributable to extended length of stay (LOS), insurance status, and access to rehabilitation. Population-based, retrospective cohort study. Levels I through III and undesignated trauma centers. Patients with acute TSCI (N=3389) discharged from all acute care hospitals in South Carolina from 1998 through 2009, and a representative sample of patients with TSCI (n=186) interviewed 1 year later. Not applicable. VTE while in acute care. Annual incidence of TSCI is 67.2 per million in the state of South Carolina, while the cumulative incidence of VTE is 4.1%. Patients with TSCI who developed VTE were nearly 4 times more likely (odds ratio [OR], 3.98; 95% confidence interval [CI], 2.57-6.17) to have been those who stayed 12 days or longer in acute care after adjusting for covariates. The adjusted mean LOS in acute care was 32.0 days (95% CI, 27.7-37.2) for patients with TSCI who had indigent insurance versus 11.3 days (95% CI, 4.9-17.6) for Medicare, and 18.5 days (95% CI, 14.5-22.5) for commercial insurance after adjusting for VTE, disposition, and year of discharge. Only 20% of the persons under indigent care received rehabilitation from accredited rehabilitation facilities in contrast to 60% under commercial insurance. Fewer patients with TSCI under indigent care received postacute rehabilitation compared with Medicare or commercial insurance. Insurance status remains a major barrier to timely transfer to rehabilitation, leading to protracted LOS in acute care with increased risk of VTE.


[Correlation between the microbiological (S. aureus) and seismic activities with regard to the sun-earth interactions and neutron flux generation].
The study searched for interactions between the solar activity, seismic energy of the Earth and microbiological processes in the period from 1969 to 1997. Microbiological processes were found dependent on as the solar, so intraterrestrial (e.g. seismic) activity. The 11-year seismic on biological cycles on Earth display a positive inter-correlation and a negative one with the solar activity (sun-spots cycles). There is also correlation between the Earth's seismic energy and neutron fluxes generated at the times of earthquakes on our planet, and microbiological parameters.


Activation of pallidal H2 receptors induces catalepsy in Wistar rats: A regulatory role of CRF1 receptors.
An increased concentration of histamine was found in the globus pallidus of parkinsonian patients. The role of this abnormality in the development of parkinsonism is unclear. We examined cataleptogenic activity of histamine injected into the globus pallidus (GP); also, the role of H2 receptors in histamine effect was evaluated. Given a possible role of the GP in integration and processing of stress signals, we tested the involvement of CRF1 receptors in the regulation of histamine effect. The experiments were conducted with male Wistar rats, catalepsy was assessed using bar test. The entopeduncular nucleus (EPN) was used as a neuroanatomical control. Intrapallidal injections of histamine (1.0 and 10.0 µg) produced clear cataleptic response whereas intra-EPN injections were ineffective. Histamine-induced catalepsy was dose-dependently attenuated by H2 receptor antagonist ranitidine and CRF1 receptor antagonist NBI 35965. The results suggest the involvement of pallidal H2 and CRF1 receptors in the development of catalepsy in rats. These findings may provide novel insight into the mechanism of parkinsonian-like disorders. In light of the presented data, H2 and CRF1 receptors might be potential targets for therapy of parkinsonism.


Identification of a novel 80 kDa antigen associated with cell proliferation.
Exploiting the immunomasking method, a polyclonal antibody has been developed in mice for identification of a novel 80 kDa antigen (P80) in KB cells. The P80 was not detected in normal resting cells but was present in appreciable amount in malignant cells. In a comparative Western transfer the antisera to the immune complexes identified a 80 kDa peptide absent in normal cell extracts. When growth of KB cells were arrested by 48 h of serum starvation the P80 was not detected but after refeeding with serum containing medium, the P80 reappeared within 1 h. This result indicates that the P80 is associated with cell proliferation and appears early in the GI-S phase of the cell cycle.


Mandible and mandibular first molar tooth measurements in dogs: relationship of radiographic height to body weight.
Height measurements of the mandible and the mandibular first molar tooth were obtained from 234 dogs. Statistical analysis was performed to determine possible associations between these measurements and body weight, sex, age, and body condition. There was a statistically significant association between the mandible: mandibular first molar tooth height measurement ratio and body weight (p < 0.0001) in all body weight groups. Small dogs had proportionally larger mandibular first molar teeth relative to mandibular height compared with larger dogs. This relationship may contribute to an increased susceptibility in small dogs for periodontitis and subsequent tooth loss. There was no statistically significant association between the mandible: mandibular first molar tooth height measurement ratio and other parameters evaluated in this study.


Equivalence of binormal likelihood-ratio and bi-chi-squared ROC curve models.
A basic assumption for a meaningful diagnostic decision variable is that there is a monotone relationship between it and its likelihood ratio. This relationship, however, generally does not hold for a decision variable that results in a binormal receiver operating characteristic (ROC) curve. As a result, ROC curve estimation based on the assumption of a binormal ROC-curve model produces improper ROC curves, which have 'hooks', are not concave over the entire domain and cross the chance line. Although in practice this 'improperness' is usually not noticeable, sometimes it is evident and problematic. To avoid this problem, Metz and Pan proposed basing ROC-curve estimation on the assumption of a binormal likelihood-ratio (binormal-LR) model, which states that the decision variable is an increasing transformation of the likelihood-ratio function of a random variable having normal conditional diseased and nondiseased distributions. However, their development is not easy to follow. I show that the binormal-LR model is equivalent to a bi-chi-squared model in the sense that the families of corresponding ROC curves are the same. The bi-chi-squared formulation provides an easier-to-follow development of the binormal-LR ROC curve and its properties in terms of well-known distributions. Copyright © 2015 John Wiley & Sons, Ltd.


Interactions between parasitic helminths and gut microbiota in wild tropical primates from intact and fragmented habitats.
The mammalian gastrointestinal tract harbours a highly complex ecosystem composed of a variety of micro- (bacteria, fungi, viruses, protozoans) and macro-organisms (helminths). Although most microbiota research focuses on the variation of single gut components, the crosstalk between components is still poorly characterized, especially in hosts living under natural conditions. We investigated the gut micro-biodiversity (bacteria, fungi and helminths) of 158 individuals of two wild non-human primates, the Udzungwa red colobus (Procolobus gordonorum) and the yellow baboon (Papio cynocephalus). These species have contrasting diets and lifestyles, but live sympatrically in both human-impacted and pristine forests in the Udzungwa Mountains of Tanzania. Using non-invasive faecal pellets, helminths were identified using standard microscopy while bacteria and fungi were characterized by sequencing the V1-V3 variable region of the 16S rRNA gene for bacteria and the ITS1-ITS2 fragment for fungi. Our results show that both diversity and composition of bacteria and fungi are associated with variation in helminth presence. Although interactions differed by habitat type, in both primates we found that Strongyloides was negatively associated and Trichuris was positively associated with bacterial and fungal richness. To our knowledge, this is one of the few studies demonstrating an interaction between helminth and gut microbiota communities in wild non-human primates.


Association of four gene polymorphisms in Chinese Guangxi population with diabetic retinopathy in type 2 diabetic patients.
Diabetic retinopathy (DR) is one of the most common chronic microvascular complications of diabetes. Many studies have suggested that genetic factors are important in the context of DR. This study evaluated the associations of GWAS (Genome-wide association study) -identified DR-associated SNPs in a Chinese population in Guangxi Province with type 2 diabetes mellitus (T2DM). A total of 386 hospitalized T2DM patients without proliferative diabetic retinopathy (PDR) and 316 hospitalized T2DM patients with PDR were included in this case-control study. Four tag SNPs, including rs1800896 in the IL-10 gene, rs2010963 in the VEGFA gene, rs2070600 in the RAGE gene and rs2910164 in the miR-146a gene, were examined using KASP (kompetitive allele specific PCR) genotyping assays. There were no significant differences in the genotype or allele frequencies of the miR-146a polymorphism (rs2910164) between subjects with PDR and those without DR. The TC genotype of rs1800896 was determined to be associated with an increased risk of PDR (the odds ratio (OR) was 2.366, with a 95% confidence interval (CI) ranging from 1.144 to 4.894). The CG genotypes of rs2010963 was associated with an decreased risk of PDR (the OR was 0.588, with a 95% CI ranging from 0.366 to 0.946). Regarding rs2070600, 2 genotypes (TT and CT) were associated with a decreased risk of PDR (the OR of the TT genotype was 0.180, with a 95% CI ranging from 0.037 to 0.872, and the OR of the CT genotype was 0.448, with a 95% CI ranging from 0.266 to 0.753). The rs1800896 polymorphisms in the IL-10 gene, rs2010963 in the VEGFA gene and rs2070600 in the RAGE gene are associated with the risk of PDR in the Han Chinese population of Guangxi Province. Our findings provide suggestive evidence that these polymorphisms may be involved in the pathogenesis of PDR and should be investigated further.


Children with chest pain visiting the emergency department.
Chest pain is a common complaint in children visiting the emergency department (ED). True organic problems like cardiac disease are rare. We assess and analyze the etiology of chest pain among children visiting a pediatric ED in one medical center. We retrospectively reviewed the medical records of children with chest pain who visited our ED between September 2002 and June 2005. Any case of trauma-associated chest pain was excluded from this study. A total of 103 patients (64 boys, 39 girls; mean age, 13 years; age range, 4-17 years) were enrolled into this study; 101 patients had chest radiograms (98.1%). Pneumonia was identified in five patients and pneumothorax in three. Eighty-seven patients had electrocardiogram study (84.5%) and four of them showed abnormalities. Additional diagnostic tests were performed in 64 patients (62.1%), including complete blood count analysis and echocardiography. Echocardiograms were performed in 15 (14.6%) patients. Six of them showed minor abnormality. Panendoscopy was done in six (5.8%) patients, and gastroesophageal reflux was found in three. Eleven (10.7%) patients were admitted to hospital because of pneumonia, pneumothorax or arrhythmia. Overall, idiopathic chest pain was the most common diagnosis (59.2%). Other associated disorders were pulmonary (24.3%), musculoskeletal (6.7%), gastrointestinal (5.8%), cardiac (2.0%) and miscellaneous (2.0%). The most common cause of chest pain prompting a child to visit the ED is idiopathic chest pain. Careful physical examination can reveal important clues and save much unnecessary examinations.


The Effects of Conspecific Alarm Cues on Larval Cane Toads (Rhinella marina).
Many aquatic organisms detect and avoid damage-released cues from conspecifics, but the chemical basis of such responses, and the effects of prolonged exposure to such cues, remain poorly understood. Injured tadpoles of the cane toad (Rhinella marina) produce chemical cues that induce avoidance by conspecific tadpoles; and chronic exposure to those cues decreases rates of tadpole survival and growth, and reduces body size at metamorphosis. Such effects suggest that we might be able to use the cane toads' alarm cue for biocontrol of invasive populations in Australia. In the present study, we examined behavioral and ecological effects of compounds that are present in cane toad tadpoles and thus, might trigger avoidance of crushed conspecifics. Four chemicals (L-Arg, L-Leu-L-Leu-OH, L-Leu-L-Ile-OH and suberic acid) induced behavioral avoidance in toad tadpoles at some (but not all) dosage levels, so we then exposed toad larvae to these chemicals over the entire period of larval development. Larval survival and size at metamorphosis were decreased by chronic exposure to crushed conspecifics (consistent with earlier studies), but not by exposure to any of the four chemicals. Indeed, L-Arg increased body size at metamorphosis. We conclude that the behavioral response to crushed conspecifics by cane toad tadpoles can be elicited by a variety of chemical cues, but that consistent exposure to these individual chemical cues does not affect tadpole viability or developmental trajectory. The optimal behavioral tactic of a tadpole may be to flee if it encounters even a single chemical cue likely to have come from an injured conspecific (indicative of predation risk), whereas the continuing presence of that single chemical (but no others) provides a less reliable signal of predation risk. Our data are consistent with results from studies on fish, that suggest a role for multiple chemicals in initiating alarm responses to damage-released cues.


The purification and properties of aldose reductase from rat ovary.
Aldose reductase has been highly purified from rat ovary to apparent homogeneity, as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purified enzyme proved to be a monomeric protein with a molecular weight of about 39,900. The enzyme catalyzed the NADPH-dependent reduction of a number of aromatic and aliphatic aldehydes as well as aldo-sugars. The enzyme was potently inhibited by p-chloro-mercuribenzoate and a commercially developed aldose reductase inhibitor, M79175. The result of an immunoinhibition study, using antibody against the purified enzyme, indicated that the enzyme was responsible for more than 50% of the overall catalytic activity of D-glucose reduction in rat ovarian cytosol. Western blotting analysis revealed that immunoreactive proteins to anti-ovarian aldose reductase antibody were present in adrenal gland, various reproductive tissues, brain, lung, and heart of rats. Furthermore, ovarian tissues of various species contained immunoreactive proteins, though in small amounts. The enzyme was primarily localized in the granulosa cells and oocytes of all stages of follicular development during the estrous cycle, though it was also found in the corpora lutea cells in the pregnant rats.


Effects of nutrition intervention on the rehabilitation level and quality of life of patients with diabetes foot: Image observation based on image recognition technology.
Today, the application of CT scanning technology is still limited. Therefore, an image observation method based on image recognition technology is proposed in this paper to study the impact of nutritional intervention on the rehabilitation level and quality of life of diabetic foot patients. Firstly, in view of the noise problems existing in CT images, this paper adopts the denoising technology, in which Gaussian noise and salt and pepper noise denoising algorithms are mainly used. Noise interference in the image can be removed by denoising processing, and the clarity and quality of the image can be improved. Subsequently, in order to improve the recognition and classification accuracy of the image, data enhancement and data standardization techniques are adopted to normalize the pixel values of the image, so as to make different images comparable, so as to improve the stability and classification accuracy of the model. Finally, CNN model is used to study image classification. The effects of nutritional intervention on the rehabilitation level and quality of life of patients with diabetic foot were investigated by setting up a comparative experiment. The results showed that nutrition intervention nursing can effectively improve the rehabilitation level of diabetic foot patients, improve the quality of life, improve nursing satisfaction.


Magnetic resonance neurography and diffusion tensor imaging of the sciatic nerve in hereditary transthyretin amyloidosis polyneuropathy.
The therapeutic advance in hereditary transthyretin amyloidosis (ATTRv amyloidosis) requires quantitative biomarkers of nerve involvement in order to foster early diagnosis and monitor therapy response. We aimed at quantitatively assessing Magnetic Resonance Neurography (MRN) and Diffusion Tensor Imaging (DTI) properties of the sciatic nerve in subjects with ATTRv-amyloidosis-polyneuropathy (ATTRv-PN) and pre-symptomatic carriers (ATTRv-C). Twenty subjects with pathogenic variants of the TTR gene (mean age 62.20 ± 12.04 years), 13 ATTRv-PN, and 7 ATTRv-C were evaluated and compared with 20 healthy subjects (mean age 60.1 ± 8.27 years). MRN and DTI sequences were performed at the right thigh from the gluteal region to the popliteal fossa. Cross-sectional-area (CSA), normalized signal intensity (NSI), and DTI metrics, including fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivity (RD) of the right sciatic nerve were measured. Increased CSA, NSI, RD, and reduced FA of sciatic nerve differentiated ATTRv-PN from ATTRv-C and healthy subjects at all levels (p < 0.01). NSI differentiated ATTRv-C from controls at all levels (p < 0.05), RD at proximal and mid-thigh (1.04 ± 0.1 vs 0.86 ± 0.11 p < 0.01), FA at mid-thigh (0.51 ± 0.02 vs 0.58 ± 0.04 p < 0.01). According to receiver operating characteristic (ROC) curve analysis, cutoff values differentiating ATTRv-C from controls (and therefore identifying subclinical sciatic involvement) were defined for FA, RD, and NSI. Significant correlations between MRI measures, clinical involvement and neurophysiology were found. In conclusion, the combination of quantitative MRN and DTI of the sciatic nerve can reliably differentiate ATTRv-PN, ATTRv-C, and healthy controls. More important, MRN and DTI were able to non-invasively identify early subclinical microstructural changes in pre-symptomatic carriers, thus representing a potential tool for early diagnosis and disease monitoring.


Does panic disorder increase the risk of coronary heart disease? A cohort study of a national managed care database.
The association between panic disorder (PD) and coronary heart disease (CHD) was examined in a large national managed care database. The Integrated Health Care Information Services managed care database is a fully de-identified, Health Insurance Portability and Accountability Act-compliant database and includes complete medical history for more than 17 million managed care lives; data from more than 30 United States health plans covering 7 census regions and from patient demographics, including morbidity, age, and gender. A cohort study was designed with a total of 39,920 PD patients and an equal number of patients without PD. The Cox proportional hazards regression models were used to assess the risk of CHD adjusted for age at entry into the cohort, tobacco use, obesity, depression, and use of medications including angiotensin converting enzyme inhibitors, beta blockers, and statins. Patients with PD were observed to have nearly a 2-fold increased risk for CHD (HR = 1.87, 95% CI = 1.80-1.91) after adjusting for these factors. There was some evidence of a possible trend toward increased risk in a subgroup of patients diagnosed with depression. After controlling for the aforementioned covariates and comparing these patients with those who did not have a diagnosis of depression, it was noted that patients with a comorbid diagnosis of depression were almost 3 times more likely to develop CHD (HR = 2.60, 95% CI = 2.30-3.01). The risk of CHD associated with a diagnosis of PD suggests the need for cardiologists and internists to monitor panic disorder to ensure a reduction in the risk of CHD.


Bone marrow recovery following fetal liver infusion (FLI) in aplastic anaemia: morphological studies.
Twenty-two of 35 patients with aplastic anaemia who received fetal liver infusion (FLI), responded to this treatment. Detailed review of bone marrow aspirates and biopsies was available in 17. There was a good correlation between clinical improvement and blood counts. The bone marrow cellularity increased to 48 percent in about 18 weeks with repopulation by both erythroid and myeloid cells. The erythroid response was predominant and the earliest to occur (1.5-61 weeks); it lasted for 7.5-100 weeks. Marked dyserythropoiesis was observed. Myeloid response occurred simultaneously in 45 percent of the responders; in the others it was delayed by 1.5 to 4 weeks. Significant dysmyelopoiesis with shift to the left, unrelated to infection, was seen 1.5 to 9.5 weeks after FLI lasting for 9-26 weeks in most cases. Megakaryocytic response either did not occur or was delayed, less marked and often transient.


Visual object separation resolves competitive interactions in somatosensory cortex evoked signals during concurrent vibrotactile stimulation of the left and right hand.
We investigated the effect of visual separation of left and right hemispaces within peripersonal space to sustained tactile spatial attention processing and showed that visually perceived object separation weakened the competitive interaction for concurrent vibrotactile stimulation to two hands. Participants received concurrent vibrotactile stimulation at different frequencies on two hands (right: 20Hz; left: 24Hz) for 4500ms to elicit steady-state somatosensory evoked potentials (SSSEPs). They attended to one of the stimulated hands and reacted to rare transient events embedded in the attended ongoing stream. Behavioral and neurophysiological results reveal that separation of spatial representation of tactile event locations could facilitate bilateral tactile spatial selection in sustained attention processing. Visual separation by a gap between hands increased the magnitude of attentional gain in SSSEPs compared to the situation when no gap was present. Results suggest that visual separation resolved the competition between concurrent tactile stimulation on two hands.


Complicated grief: Knowledge, attitudes, skills and training of mental health professionals: A systematic review.
A systematic review and qualitative synthesis was undertaken to deduce the knowledge, attitudes, skills and training of mental health professionals regarding complicated grief (CG). PsychInfo, Embase, Medline, CINAHL, PBSC, Web of Science and ERIC databases were used to identify relevant literature. Searches were executed from inception to September 2014. The electronic search yielded 305 results. Forty-one papers were selected for full text review, 20 were included for analysis. 6 examined primary data, the remaining 14 being reviews, opinion or guideline pieces. Despite the lack of consensus on terminology, criteria and diagnosis, it appears that there is more than sufficient agreement within the CG research community regarding the knowledge and skills required to assist someone presenting with CG. A palpable fear of medicalising grief exists, but this would seem to be based on a conflation of normal grief and CG. This review highlights the mainly unidirectional nature of current research, the voice of the practitioner being largely unheard. A need for and an interest in training in CG was expressed. There is an urgent need to translate research findings into clinical practice. Training must take account of attitudinal barriers to implementation, balancing evidence and stories.


Effect of diethyl pyrocarbonate modification of benzodiazepine receptors on [3H]Ro 15-4513 binding.
The effects of treatment of brain membranes with diethyl pyrocarbonate (DEP), a histidine-modifying reagent, on the binding of 3H-labeled Ro 15-4513 (ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a]- [1,4]benzodiazepine-3-carboxylate) and [3H]diazepam were compared. DEP pretreatment produced a dose-dependent decrease in [3H]diazepam binding, whereas low DEP concentrations enhanced the binding of [3H]Ro 15-4513. These effects were reversed by incubation with hydroxylamine after the treatment. The enhancement of [3H]Ro 15-4513 binding was due to an increase in the affinity of the binding sites (KD), without any effect on binding capacity (Bmax). The enhancement was perceived in cerebral cortical, cerebellar, and hippocampal membranes. DEP treatment decreased the displacement of [3H]Ro 15-4513 binding by diazepam and FG 7142 (N-methyl-beta-carboline-3-carboxamide) but not by Ro 15-4513 and Ro 19-4603 (tert-butyl-5,6-dihydro-5-methyl-6-oxo-4H-imidazol[1,5- a]thieno[2,3-f][1,4]diazepine-3-carboxylate). Although the stimulating effect of gamma-aminobutyric acid (GABA) on [3H]-diazepam binding was not affected by DEP treatment, such treatment reduced the inhibitory effect of GABA on [3H]Ro 15-4513 binding. The enhancement of [3H]Ro 15-4513 binding was observed in membranes pretreated with DEP in the presence of flunitrazepam, whereas such pretreatment reduced significantly the inhibitory effect of DEP on [3H]-diazepam binding.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of parental traumatic brain injury on parenting and child behavior.
To examine (1) the parenting skills of individuals with traumatic brain injury (TBI) and their spouses, (2) the effects of parental TBI on children, and (3) the effects of parental TBI on levels of depression for all family members. Independent two-tailed t tests and Pearson chi-square analyses were utilized to compare parents with TBI versus parents without TBI, spouses of parents with TBI versus spouses of parents without TBI, and children of parents with TBI versus children of parents without TBI. Urban, suburban, and rural New York State. 32 families participated in the study; in 16 families one parent had a TBI and in the remaining 16 families, no parent had a TBI. Eighteen children from families with parental TBI and 26 children from families without TBI were interviewed. On average, parents with TBI were 9 years post-onset of injury at the time of interview. The parents' battery explored parents' perspectives of their own parenting skills (Parent Behavior Form, Parent Practices Questionnaire, Parenting Dimensions Inventory), their mood (Beck Depression Inventory), and the behaviors of their children (Children's Problem Checklist, Behavior Rating Profile). The child's battery tapped the children's perspective of their own behaviors (Behavior Rating Profile), their mood (Children's Depression Inventory), and the parental abilities of both parents (Parent Behavior Form, Parent Practices Questionnaire). Although parents with TBI and their spouses were similar to their comparison group in many parenting skills, parents with TBI reported less goal setting, less encouragement of skill development, less emphasis on obedience to rules and orderliness, less promotion of work values, less nurturing, and lower levels of active involvement with their children. Spouses of individuals with TBI, compared to their counterparts, reported less feelings of warmth, love, and acceptance toward their children. Children from families in which a parent had a TBI perceived both parents as more lax in their discipline, with the parent without TBI perceived as less actively involved in parenting roles. No differences in the frequency of behavioral problems were found between children of parents with TBI and children of parents without TBI. Parents with TBI and their children experienced more symptoms of depression relative to their respective comparison groups. Parental TBI has select consequences for all family members: individuals with TBI, their spouses, and their children. Prospective clinical evaluations of family members and proactive interventions to maximize family adjustment and minimize affective distress are indicated.


Perioral anesthesia disrupts maternal behavior during early lactation in Long-Evans rats.
The role of perioral somatosensory stimulation from pups in maternal behavior was investigated in lactating Long-Evans rats (Rattus norvegicus) during early lactation by local anesthesia of the mystacial pads with lidocaine, which blocks conduction in the infraorbital nerve. It was concluded that (1) acute perioral anesthesia markedly inhibited pup retrieval when the subjects had no formal pretreatment retrieval experience. Further, these dams displayed little tolerance to the lidocaine treatment when they were tested repeatedly. (2) The severity of the effects of perioral anesthesia on retrieval was dependent upon prior experience and the testing situation. Following pretreatment retrieval experience, and in a test cage with dark and light compartments which provided a strong incentive to retrieve, 80% of lidocaine-injected dams did retrieve. However, retrieval efficiency was impaired by perioral anesthesia, largely due to increased time in contact with pups prior to each retrieval and to increased carrying time. (3) Perioral anesthesia also inhibited pup licking, but not self-grooming, suggesting that the former, but not the latter, is largely under peripheral stimulus control and that deficits in maternal oral activities cannot be due to impairment of mouth opening and use. (4) The onset of nursing behavior was delayed until after the recovery of snout sensations and retrieval. This suggests that a maternal behavior not directly involving the mouth is nonetheless dependent upon the dam's receipt of perioral tactile input from pups.


Synergistic interaction of benign prostatic hyperplasia and prostatitis on prostate cancer risk.
The incidence of prostate cancer is much lower in Asian men than in Western men. This study investigated whether prostate cancer is associated with prostatitis, benign prostatic hyperplasia (BPH), and other medical conditions in the low-incidence population. From the claims data obtained from the universal National Health Insurance of Taiwan, we identified 1184 patients with prostate cancer diagnosed from 1997 to 2008. Controls comprised 4736 men randomly selected from a cancer-free population. Both groups were 50 years of age or above. Medical histories between the two groups were compared. Multivariate logistic regression analysis showed that prostatitis and BPH had stronger association with prostate cancer than the other medical conditions tested. Compared with men without prostatitis and BPH, a higher odds ratio (OR) for prostate cancer was associated with BPH (26.2, 95% confidence interval (CI) 20.8-33.0) than with prostatitis (10.5, 95% CI=3.36-32.7). Men with both conditions had an OR of 49.2 (95% CI=34.7-69.9). Men with prostate cancer have strong association with prostatitis and/or BPH. Prostatitis interacts with BPH, resulting in higher estimated relative risk of prostate cancer in men suffering from both conditions.


Detection and identification of medically important alkaloids using the surface-enhanced Raman scattering spectroscopy.
Currently, trace detection of drugs, medicinal products, psychoactive substances, poisons and other natural or synthetic compounds in the human body has become one of the most important areas of interest in medicine, toxicology and forensic research. Due to the rapid development of nanotechnology, applications in forensic and biological sciences, food industry and art preservation there is an increasing interest in surface-enhanced Raman scattering (SERS) spectroscopy as a technique capable of low detection limits in the analysis of small amounts of studied analytes. In this study, different excitation wavelengths (785 nm and 1064 nm) were used to find the appropriate experimental conditions for the detection and identification of medically significant alkaloids - atropine and pergolide - by means of surface-enhanced Raman scattering spectroscopy. SERS spectra of selected alkaloids were measured in the concentration range 10-3-10-9 mol∙L-1 using large-scaled platinum substrates coated with electrochemically prepared gold or silver SERS-active layers. Identification was based on the assignment of surface-enhanced characteristic vibrational bands using theoretical (DFT) calculations and comparing them with normal (non-enhanced) Raman spectra of pure compounds. All sets of spectral data were subjected to multivariate statistical approach (partial least squares regression) aiming at prediction of alkaloids concentration in developed models and its comparison with experimental results.


Phosducin is a protein kinase A-regulated G-protein regulator.
Signal transduction by G-protein-coupled receptors is regulated by various mechanisms acting at the receptor level; those studied most thoroughly are from the beta-adrenergic receptor/Gs/adenylyl cyclase system. We report here a regulatory mechanism occurring at the level of the G proteins themselves. A protein with M(r) 33,000 that inhibits Gs-GTPase activity was purified from bovine brain. This protein is very similar or identical to phosducin, a protein previously thought to be specific for retina and pineal gland. Recombinant phosducin inhibited the GTPase activity of several G proteins, and also inhibited Gs-mediated adenylyl cyclase activation. Blockade of its inhibitory effects by protein kinase A suggests that phosducin may be part of a complex regulatory network controlling G-protein-mediated signalling.


Determination of alcohol content in beverages using short-wave near-infrared spectroscopy and temperature correction by transfer calibration procedures.
This paper reports the utilization of short-wave near-infrared (SW-NIR) transmission spectroscopy for rapid and conclusive analysis of alcoholic content (% v/v) in beverages. This spectral region is interesting because common visible diode array spectrometers can be utilized, reducing time and costs in comparison with traditional near-infrared or mid-infrared instruments. A correction of external temperature influence is necessary, and for this purposes two calibration transfer procedures were compared: piecewise direct standardization (PDS) and orthogonal signal correction (OSC). The RMSEP found for the alcoholic content model at 20 degrees C was 0.13% v/v and, after application of transfer calibration procedures at other temperatures (15, 25, 30 and 35 degrees C) using the model built at 20 degrees C, errors of the same order of magnitude were obtained.


Egg-mimics of Streptanthus (Cruciferae) deter oviposition by Pieris sisymbrii (Lepidoptera: Pieridae).
Streptanthus breweri, a serpentine-soil annual mustard, produces pigmented callosities on its upper leaves which are thought to mimic the eggs of the Pierid butterfly Pieris sisymbrii. P. sisymbrii is one of several inflorescence-infructescence-feeding Pierids which assess egg load visually on individual host plants prior to ovipositing. Removal of the "egg-mimics" from S. breweri plants in situ significantly increases the probability of an oviposition relative to similar, intact plants.


Novel autoxidation and Michael addition of a butenolide-containing sugar leading to a C-branched-chain glucopyranosidulose, and X-ray structure of intermediates.
A butenolide-containing sugar available from the aldol condensation of methyl 4,6-O-benzylidene-alpha-D-glucopyranosid-2-ulose with diethyl malonate is autoxidized at the C-3 position into the corresponding alpha,beta-unsaturated gamma-lactone sugar by air, which subsequently undergoes 1,4-conjugate (Michael) addition of hydroxide ion (or water) leading to a C-branched-chain glucopyranosidulose. The autoxidations are also performed in weakly basic, neutral and weakly acidic medium, respectively.


A simplified assay for the specific diagnosis of paroxysmal nocturnal hemoglobinuria: detection of DAF(CD55)- and HRF20(CD59)- erythrocytes in microtyping cards.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease that is caused by a monoclonal stem cell defect. The affected cells lack the carbohydrate linkage between phosphatidylinositol and a group of membrane proteins of which three protect the cell against complement lysis. The absence of these three proteins, DAF(CD55), C8BP and HRF20(CD59), makes cells from the erythropoiesis, thrombopoiesis and myelopoiesis extensively sensitive to complement attack and affected patients suffer from intravascular hemolysis, thrombosis and increased susceptibility to infections. In this study we describe a swift and specific assay for the detection of CD55- and CD59- erythrocytes, which is suitable for screening of possible PNH patients.


On the Evidence Supporting That AN11127 Encodes an Aspergillus Nidulans Sec12 Orthologous Protein. Reply to Bravo-Plaza et al. Comment on "Dimou et al. Profile of Membrane Cargo Trafficking Proteins and Transporters Expressed under N Source Derepressing Conditions in Aspergillus nidulans. J. Fungi 2021, 7, 560".
Prof. Peñalva and co-workers provided evidence that AN11127 is related by sequence and function to Sec12 [...].


Impact of climate change on formation of nitrogenous disinfection by products. Part I: Sea level rise and flooding events.
Climate change causes heavy rainfall incidents and sea level rise, which have serious impact on the availability and quality of water resources. These extreme phenomena lead to the rise of external and internal precursors in water reservoirs, and consequently affect the formation of disinfection by-products (DBPs). The aim of this study was to investigate the formation of nitrogenous_DBPs (N-DBPs) under extreme conditions caused by climate change. For this reason, two scenarios were adapted: a) sea level rise leading to increase of water salinity and b) heavy rainfall incidents leading to flooding events. The target-compounds were haloacetonitriles (HANs), haloacetamides (HAcAms) and halonitromethane (TCNM). Chlorination and chloramination were employed as disinfection processes under different doses (5 and 10 mg/L) and contact times (24 and 72 h). The results showed enhancement on the formation of N-DBPs and changes in their profile. Sea level rise scenario led to elevated concentrations of brominated species (maximum concentration of dibromoacetonitrile 23 μg/L and maximum concentration of bromoacetamide 57 μg/L), while flooding events scenario led to extended formation of chloroacetamide and bromochloroacetonitrile up to 58 μg/L and 40 μg/L, respectively. At the same time, changes in cytotoxicity and genotoxicity of the samples were observed.


Pre-treatment of porcine pulmonary xenograft with desmopressin: a novel strategy to attenuate platelet activation and systemic intravascular coagulation in an ex-vivo model of swine-to-human pulmonary xenotransplantation.
Von Willebrand factor (vWF) has been proposed as a major contributor to the development of coagulopathy in pulmonary xenotransplantation. Pretreatment of donor swine with 1-deamino-8-d-arginine vasopressin (DDAVP), an analog of vasopressin, can reduce the content of vWF in pulmonary xenografts. Here, we investigate the effects of DDAVP pre-treatment in an ex-vivo perfusion model of pulmonary xenotransplantation. We set up and performed the ex-vivo perfusion using porcine pulmonary accessory lobes and fresh human whole blood (n = 12). Half of the donor swine were given 3 mug/kg DDAVP intravenously for 3 days before ex-vivo perfusion (DDAVP group) and half of them were left untreated (control group). The porcine lung was perfused with fresh blood for 1 h and changes in the following parameters were monitored: pulmonary arterial pressure, pulmonary vascular resistance, blood cell counts, fibrinogen, antithrombin, platelet factor 4, D-dimer, C3a, C4d, and xenoreactive IgM. The release of Galalpha1-3Gal xenoantigen (alphaGal) from porcine lung which had been perfused and retained for 30 min with human blood was assessed by enzyme-linked immunosorbent assay using alphaGal-binding lectin. Both DDAVP and control groups showed typical findings of immediate pulmonary dysfunction: an increase of pulmonary vascular resistance and sequestration of leukocytes and platelets after ex-vivo perfusion. However, in the DDAVP group, the increase of platelet factor 4, C3a, and C4d after perfusion was attenuated compared to that in the control group. The release of alphaGal after blood retention was significantly lower in the DDAVP group than that of the control group. Pre-infusion of DDAVP to the donor swine was beneficial in attenuating platelet activation as well as complement/coagulation activation. These effects of DDAVP are likely to relate to the reduction of porcine vWF content in the xenograft. Therefore, the modulation of vWF secretion in donor lungs could be an additional therapeutic way to reduce systemic coagulopathy in pulmonary xenotransplantation.


Chimeric (alpha-amino acid + nucleoside-beta-amino acid)n peptide oligomers show sequence specific DNA/RNA recognition.
An alpha/beta-peptide backbone oligonucleotide comprising natural alpha-amino acids alternating with a beta-amino acid component derived from thymidine sequence specifically recognizes and binds to deoxy- and ribo-oligoadenylates in triplex mode.


Tracking macrophages in diabetic neuropathy with two-color nanoemulsions for near-infrared fluorescent imaging and microscopy.
The incidence of diabetes and diabetic peripheral neuropathy continues to rise, and studies have shown that macrophages play an important role in their pathogenesis. To date, macrophage tracking has largely been achieved using genetically-encoded fluorescent proteins. Here we present a novel two-color fluorescently labeled perfluorocarbon nanoemulsion (PFC-NE) designed to monitor phagocytic macrophages in diabetic neuropathy in vitro and in vivo using non-invasive near-infrared fluorescent (NIRF) imaging and fluorescence microscopy. Presented PFC-NEs were formulated with perfluorocarbon oil surrounded by hydrocarbon shell carrying two fluorescent dyes and stabilized with non-ionic surfactants. In vitro assessment of nanoemulsions was performed by measuring fluorescent signal stability, colloidal stability, and macrophage uptake and subsequent viability. The two-color PFC-NE was administered to Leprdb/db and wild-type mice by tail vein injection, and in vivo tracking of the nanoemulsion was performed using both NIRF imaging and confocal microscopy to assess its biodistribution within phagocytic macrophages along the peripheral sensory apparatus of the hindlimb. In vitro experiments show two-color PFC-NE demonstrated high fluorescent and colloidal stability, and that it was readily incorporated into RAW 264.7 macrophages. In vivo tracking revealed distribution of the two-color nanoemulsion to macrophages within most tissues of Leprdb/db and wild-type mice which persisted for several weeks, however it did not cross the blood brain barrier. Reduced fluorescence was seen in sciatic nerves of both Leprdb/db and wild-type mice, implying that the nanoemulsion may also have difficulty crossing an intact blood nerve barrier. Additionally, distribution of the nanoemulsion in Leprdb/db mice was reduced in several tissues as compared to wild-type mice. This reduction in biodistribution appears to be caused by the increased number of adipose tissue macrophages in Leprdb/db mice. The nanoemulsion in this study has the ability to identify phagocytic macrophages in the Leprdb/db model using both NIRF imaging and fluorescence microscopy. Presented nanoemulsions have the potential for carrying lipophilic drugs and/or fluorescent dyes, and target inflammatory macrophages in diabetes. Therefore, we foresee these agents becoming a useful tool in both imaging inflammation and providing potential treatment in diabetic peripheral neuropathy.


Routine Troponin Measurements Are Unnecessary to Exclude Asymptomatic Coronary Events in Acute Ischemic Stroke Patients.
Obtaining serum troponin levels in every patient with acute stroke is recommended in recent stroke guidelines, but there is no evidence that these contribute positively to clinical care. We sought to determine the clinical significance of measuring troponin levels in acute ischemic stroke patients. We reviewed 398 consecutive patients with acute ischemic stroke at a large academic institution from 2010 to 2012. Troponin levels were measured as a result of protocol in place during part of the study period. The mean age was 70 years (standard deviation ±16 years) and 197 (49.5%) were men. Chronic kidney disease was present in 78 (19.6%), coronary artery disease in 107 (26.9%), and atrial fibrillation in 107 (26.9%). Serum troponin T was measured in 246 of 398 patients (61.8%). Troponin was elevated (>.01 ng/mL) at any point in 38 of 246 patients (15.5%) and was elevated in 28 patients at all 3 measurements (11.3% of those with troponin measured). Only 4 of 246 patients (1.6%) had a significant uptrend. Two were iatrogenic in the setting of hemodynamic augmentation using vasopressors to maintain cerebral perfusion. One case was attributed to stroke and chronic kidney disease and another case to heart failure from inflammatory fibrocalcific mitral valvular heart disease. Serum troponin elevation in patients with ischemic stroke is not usually caused by clinically significant acute myocardial ischemia unless iatrogenic in the setting of vasopressor administration. Serum troponin levels should be measured judicially, based on clinical context, rather than routinely in all stroke patients.


Evidence for activation of histamine H3 autoreceptors during handling stress in the prefrontal cortex of the rat.
On-line microdialysis of histamine in 10-min samples of the prefrontal cortex of the conscious rat is described. The HPLC-fluorescent assay for histamine in dialysates has been significantly simplified by using only one postcolumn reagent line instead of the three reagent lines described in earlier methods. The method is selective, sensitive (detection limit: 2-3 fmol on column), and linear over a large concentration range. Basal values of histamine decreased to about 50% of basal levels during infusion of tetrodotoxin (5 x 10(-6) M). Handling rats for 15 min increased histamine in dialysates to about 300% of basal levels. When tetrodotoxin (10(-6) M) was applied during handling the increase in histamine release was strongly (about 80%) suppressed. The handling-induced increase in histamine was used as a paradigm to investigate the functional activity of histamine H3 autoreceptors during mild stress or arousal. An H3 receptor specific agonist (alpha-methylhistamine; 10(-5) M) and antagonist (thioperamide; 10(-5) M) were infused into the frontal cortex via the microdialysis probe. The effect of handling on histamine release was potentiated during infusion of thioperamide and fully suppressed during infusion of alpha-methylhistamine. These results clearly illustrate the efficacy of the H3 autoreceptor in modulating stimulated histamine release during natural stimulatory conditions.


[Sub- and intercondylar fractures of the distal humerus in adults].
complete joint fractures of the lower end of the humerus are rare and severe injuries in adults, affecting the functional prognosis of a narrow and complex joint such as the elbow. Multiple therapeutic options are available, but osteosynthesis is widely used provided that it can recover stable, mobile, and painless joint. The purpose of our study was to describe the epidemiological, clinical, radiological and therapeutic features of these fractures, as well as to evaluate functional outcomes in our patients. we conducted a 3-year prospective study (January 2014-December 2016) of 38 patients older than 16 years admitted with complete sub- and intercondylar joint fracture of the lower extremity of the humerus (classified as type C according to the AO classification). They underwent surgery via transolecranian posterior approach with fixation of one or two screw plates based on anatomopathological diagnosis. Patients were followed-up for a mean period of 34 months. these conditions had bimodal distribution, affecting young male subjects on the one hand and elderly female subjects on the other. The main cause of fractures was road accidents (78%). During the follow-up period, one case had superficial surgical site infection and there were no cases of dismantling of equipment or pseudarthrosis. No complications after osteosynthesis for olecranon fractures were recorded in our case series. Stiffness at the elbow-joint was defined as bending/extension arc less than 50°; elbow stiffness was found in 25% of patients. Functional results were assessed using the Mayo-Clinic or Mayo-Clinic Elbow Performance Score (MEPS) with an average score of 86. Conclusion: based on our results, transolecranon posterior approach is the best option for these fractures, since it allows good joint exposure. This is essential for perfect anatomical restitution and stable osteosynthesis in order to undertake early and adapted rehabilitation.


Comparative assessment of standard and immune response criteria for evaluation of response to PD-1 monotherapy in unresectable HCC.
To assess response to programmed death-1 (PD-1) monotherapy (nivolumab) in hepatocellular carcinoma (HCC) patients using RECIST1.1, modified RECIST (mRECIST), and immune RECIST (iRECIST). A secondary objective was to identify clinicolaboratory and imaging variables predictive of progressive disease (PD) and overall survival (OS). Patients with HCC treated with nivolumab at a single institution from 5/2016 to 12/2019 with MRI or CT performed ≥ 4 weeks post treatment were retrospectively assessed. Patients who received concurrent locoregional, radiation, or other systemic therapies were excluded. Response was assessed by 2 observers in consensus using RECIST1.1, mRECIST, and iRECIST at 3/6/9/12-month time points. Time to progression (TTP) and OS were recorded. Clinicolaboratory and imaging variables were evaluated as predictors of PD and OS using uni-/multivariable and Cox regression analyses. Fifty-eight patients (42M/16F) were included. 118 target lesions (TL) were identified before treatment. Baseline mean TL size was 49.1 ± 43.5 mm (range 10-189 mm) for RECIST1.1/iRECIST and 46.3 ± 42.3 mm (range 10-189 mm) for mRECIST. Objective response rate (ORR) was 21% for mRECIST/iRECIST/RECIST1.1, with no cases of pseudoprogression. Median OS and median TTP were 717 days and 127 days for RECIST1.1/mRECIST/iRECIST-iUPD (unconfirmed PD). Older age, MELD/Child-Pugh scores, AFP, prior transarterial radioembolization (TARE), and larger TL size were predictive of PD and/or poor OS using mRECIST/iRECIST. The strongest predictor of PD (HR = 2.49, 95% CI 1.29-4.81, p = 0.007) was TARE. The strongest predictor of poor OS was PD by mRECIST/iRECIST at 3 months (HR = 2.26, 95% CI 1.00-5.10, p = 0.05) with borderline significance. Our results show ORR of 21%, equivalent for mRECIST, iRECIST, and RECIST1.1 in patients with advanced HCC clinically treated with nivolumab.


Birth weight and overweight/obesity in adults: a meta-analysis.
The objective of this study is to assess the association between birth weight and overweight/obesity in adults. The following MeSH terms were used: "birth weight," "obesity," "overweight." Fifteen studies involving a total of 211,457 persons were identified. Low birth weight (<2,500 g), as compared with normal birth weight (2,500-4,000 g), was not associated with increased risk of overweight/obesity (OR = 1.17, 95% CI 0.94, 1.46). High birth weight (≥ 4,000 g), as compared with normal birth weight, was associated with increased risk of overweight/obesity (OR = 1.46, 95% CI 1.27, 1.68). Low birth weight compared with normal birth weight, the total mean difference of BMI decreased 0.14 kg/m(2). High birth weight compared with normal birth weight, the total mean difference of BMI increased 0.76 kg/m(2). Low birth weight, as compared with a birth weight of ≥ 2,500 g, was not significantly associated with decreased risk of obesity (OR = 1.12, 95% CI 0.90-1.40). High birth weight, as compared with a birth weight of <4,000 g, was associated with increased risk of obesity (OR = 1.43, 95% CI 1.25-1.64). Low birth weight compared with birth weight ≥ 2,500 g, the total mean difference of BMI was decreased 0.42 kg/m(2); high birth weight compared with birth weight <4,000 g, the total mean difference of BMI was increased 0.79 kg/m(2). Neither positively linear nor J- or U-shaped relations exist between birth weight and overweight/obesity in adults. It is high birth weight, not low birth weight, that is associated with increased risk of overweight/obesity in adults.


Dendrimer-mediated permeation enhancement of chlorhexidine digluconate: Determination of in vitro skin permeability and visualisation of dermal distribution.
Chlorhexidine digluconate (CHG) is a cationic bisbiguanide used in the UK as the first-line skin antiseptic prior to surgery in the UK due to its favourable efficacy and safety profile, high affinity for skin binding and minimal reports of resistance. Despite this, bacteria remain within deeper skin layers, furrows and appendages that are considered inaccessible to CHG, due to its poor dermal penetration. In this study a third generation, polyamidoamine dendrimer (G3 PAMAM-NH2) was utilised to improve dermal penetration of CHG. A topical gel formulation was optimised to maximise CHG delivery (containing 0.5% gelling agent and 4% drug), followed by drug and dendrimer co-formulation into a commercially viable gel. The gel containing 4% CHG and 1 mM PAMAM dendrimer significantly increased the depth permeation of CHG compared to the commercial benchmark (Hibiscrub®, containing 4% w/v CHG) (p < 0.05). The optimised formulation was further characterised using Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS), which indicated that the depth of dermal penetration achieved was sufficient to reach the skin strata that typically harbours pathogenic bacteria, which is currently inaccessible by commercial CHG formulations. This study therefore indicates that a G3 PAMAM-NH2 dendrimer gel may be viable as a permeation enhancer of CHG, for improved skin antisepsis in those at risk of a skin or soft tissue infection as a result of surgical intervention.


Primary leiomyosarcoma of the cervical spine causing spontaneous compression fracture: report of an autopsy case.
An extremely rare case of the primary leiomyosarcoma of the cervical spine presenting as a compression fracture is reported. A 69-year-old man complained of dysesthesia of both hands. A plain radiograph, computed tomography and magnetic resonance imaging of the cervical spine showed a compression fracture of the vertebral body at C7 without the formation of an obvious mass. From radiological findings, the fracture was considered to be caused by an infiltrative vertebral bone tumor. Biopsy of the tumor revealed a leiomyosarcoma, a metastatic tumor being ruled out by a systemic investigation. The patient died of pleural metastasis 6 months later, and an autopsy confirmed the primary site of the tumor as the cervical spine.


Assessment of circulating immune complexes in canine leishmaniosis and dirofilariosis.
Canine leishmaniosis (CanL) by Leishmania infantum (L.i.) and heartworm disease by Dirofilaria immitis (D.i.) are common zoonotic vector-borne diseases (VBDs) characterized by a variety of pathological and clinical signs. The immunopathology in both VBDs is extremely complex, and their clinical manifestations are strongly dependent on the type of immune response elicited by the parasites. In particular, the formation of circulating immune complexes (CICs) plays an important role in the pathogenesis of these VBDs. Based on the international guidelines, dogs with high anti-L. infantum antibody titres and one or more clinical and/or laboratory signs related to CanL require anti-Leishmania treatment. Consequently, the CICs measurement could be used for improving the clinical staging process of CanL. The aim of the study was to assess the CICs level by a competitive inhibition enzyme immunoassay, in healthy or sick dogs seropositive to L.i. and in healthy dogs positive to D.i.. Out of 51 enrolled dogs, 11 were included in Group A (seronegative to L.i., D.i. negative and healthy), 15 in Group B (exposed to L.i., D.i. negative and healthy), 12 in Group C (seropositive to L.i., D.i. negative and sick) and 13 in Group D (seronegative to L.i, D.i. positive and healthy). The comparison of CIC level in canine sera revealed a significant difference among groups (P < 0.001), with the highest concentration (i.e., median = 104.6 µg/mL) in dogs with CanL. The findings of the study highlight the CICs measurement as a useful tool in the clinical staging of CanL for avoiding misclassification of dogs as leishmaniotic, thus not requiring anti-Leishmania therapy, as well as the possibility of results misuse in geographical areas where both leishmaniosis and heart-worm disease are endemic.


Adrenocorticotropin and glucocorticoid concentrations in fetal and maternal plasma of rabbit does continuously infused with cortisol from day 21 to day 24 of gestation.
Previous studies have suggested that suppression of fetal rabbit adrenocorticotropin (ACTH) secretion results in impaired development of ACTH-specific adenylate cyclase activity. In order to test this hypothesis we measured fetal and maternal plasma ACTH, cortisol, and corticosterone concentrations in control does and does infused with 0.3 mg of cortisol/hour at 21 to 24 days of gestation. This cortisol infusion regimen significantly depressed maternal and fetal plasma ACTH and corticosterone concentrations but did not change fetal serum cortisol concentrations. These findings further support the hypothesis that fetal ACTH plays a role in the normal development of the adenylate cyclase catalytic portion of the ACTH receptor complex and adrenal differentiation during this critical period of fetal life.


Low vs. standard dose computed tomography in suspected acute appendicitis: Is it time for a change?
Clinical diagnosis is accurate in only 80% of patients with suspected appendicitis with negative appendectomy rates of up to 21%. In the UK the use of standard-dose CT (SDCT) is conservative due to concerns over radiation exposure and resource implications. The use of low dose computer tomography (LDCT) instead of standard dose computer tomography (SDCT) may partially address these concerns. To compare LDCT and SDCT in the diagnosis of appendicitis. A literature search of the EMBASE and MEDLINE databases in July 2015 was conducted using the keywords 'low dose CT' and 'appendicitis'. Data were analysed and p values calculated using the Chi-square test. P values less than 0.05 were considered to be significant. LDCT (1.2-5.3 mSv) was not inferior to SDCT (5.2-10.2 mSv) in the diagnosis of acute appendicitis and proposing alternative diagnoses. SDCT was superior to LDCT in the negative predictive value of diagnosis of appendiceal perforation. There was no significant difference between LDCT and SDCT in negative appendectomy rate, appendiceal perforation rate and the need for additional imaging. LDCT is not inferior to SDCT in the diagnosis of acute appendicitis and proposing alternative diagnoses. Further studies are recommended to further assess the potential role of LDCT & its cost effectiveness. Its use may improve the current management of patients with suspected acute appendicitis.


Ultrasmall Fe@Fe3O4 nanoparticles as T1-T2 dual-mode MRI contrast agents for targeted tumor imaging.
Targeted T1-T2 MRI contrast agents, which can eliminate the difficulty of image matching across multiple imaging instruments and permit specific localization of lesions, are promising candidates for more accurate diagnosis of tumors. In this study, ultrasmall Fe@Fe3O4 nanoparticles were designed and synthesized as T1-T2 dual-mode MRI contrast agents for accurate tumor imaging. First, to investigate the influence of nanoparticle size, Fe@Fe3O4 nanoparticles with diameters of 4, 8, and 12 nm were prepared, among which the 8 nm 3-(3,4-dihydroxyphenyl)propionic acid (DHCA)-modified nanoparticles exhibited the optimal T1-T2 dual-mode MRI performance. Next, to develop a tumor-targeted contrast agent, the DHCA-Fe@Fe3O4 nanoparticles were conjugated with the F56 peptide, which targets the vascular endothelial growth factor receptor, and the resulting F56-DHCA-Fe@Fe3O4 nanoparticles were found to exhibit good T1-T2 dual-mode imaging and tumor-targeting performance both in vitro and in vivo, indicating the nanoparticles represent a new research tool for accurate tumor diagnosis.


Etoposide and cisplatinum in resistant lymphomas.
Etoposide and cisplatinum have used separately to treat refractory lymphomas. This report describes 22 patients in whom these two agents were used in conjunction. All had been extensively treated with standard therapies previously. The combination of etoposide and cisplatinum was chosen on the basis of preclinical evidence for synergy and because these agents do not cross-react. Cisplatinum was continuously infused for 5 days at a dose of 15 mg/m2/d. As a push a 100 mg/m2/d dose of etoposide was injected on days 1 and 2 of treatment. This schedule produced good responses in 18 patients, i.e. 15 partial remissions and three complete remissions. The side effects were acceptable.


Inspiration or deflation? Feeling similar or dissimilar to slim and plus-size models affects self-evaluation of restrained eaters.
The present studies examined the effect of perceiving images of slim and plus-size models on restrained eaters' self-evaluation. While previous research has found that such images can lead to either inspiration or deflation, we argue that these inconsistencies can be explained by differences in perceived similarity with the presented model. The results of two studies (ns=52 and 99) confirmed this and revealed that restrained eaters with high (low) perceived similarity to the model showed more positive (negative) self-evaluations when they viewed a slim model, compared to a plus-size model. In addition, Study 2 showed that inducing in participants a similarities mindset led to more positive self-evaluations after viewing a slim compared to a plus-size model, but only among restrained eaters with a relatively high BMI. These results are discussed in the context of research on social comparison processes and with regard to interventions for protection against the possible detrimental effects of media images.


Timing of sequential changes in chromosome configurations during the 1st meiotic division of pig oocytes cultured in vitro.
This study examines the timing of changes in chromosome configurations of pig oocytes derived from small antral follicles of follicular and/or inactive stage donors using modified 199 medium supplemented with gonadotropins (Follicle Stimulating Hormone (FSH), 10 IU/ml; Human Chorionic Gonadotropin (hCG), 10 IU/ml) and Glucosamine (0.539 mg/ml). Oocytes (n = 1,215) were fixed at the end of 3 hourly intervals from 0-48 hr of culture. Results were expressed as the percentage of oocytes at each stage of maturation for each time point. The germinal vesicle (GV) stage was observed for the first 17.6 hr; germinal vesicle breakdown (GVBD) stage between 17.6-26.4 hr; metaphase I (M-I) from 26.4-30.9 hr; anaphase I (A-I) ranged from 30.9-33.4 hr; telophase I (T-I) at 33.4-34.4 hr; and metaphase II (M-II) at 34.4-48 hr.


Microiontophoretic injection of fluorescent tracer combined with simultaneous immunofluorescent histochemistry for the demonstration of efferents from the caudate-putamen projecting to the globus pallidus.
Precise local injections of propidium iodide (PI) were made, using an iontophoretic technique, into various regions of the globus pallidus (GP) of rats. The locations of the injection sites and the position of retrogradely labelled caudate putamen (CP) cell bodies demonstrated a topographic arrangement of efferents from the CP projecting to the pallidum. The PI labelled cell bodies in the CP were also counterstained for met-enkephalin immunofluorescence. Cell bodies labelled with PI, which showed co-existing enkephalin immunofluorescence, were found in CP projections to the pallidum.


Inhibition of the spinal transmission of nociceptive information by supraspinal stimulation in the cat.
In cats anaesthetized with alpha-chloralose or sodium pentobarbitone a study was made of the effects of supraspinal electrical stimulation on the excitation of dorsal horn neurones by noxious and non-noxious cutaneous stimuli. Stimulation near the dorsal raphe of the midbrain non-selectively reduced the responses of neurones to both noxious and non-noxious stimuli. Intravenous naloxone (0.3-0.6 mg/kg) had no effect on this inhibition. Electrical stimulation near the medullary raphe selectively reduced the excitation of dorsal horn neurones by noxious cutaneous stimuli. Excitation of neurones by deflection of hairs was unaffected. The inhibition of nociceptive responses outlasted the period of raphe stimulation by up to 6 min. Intravenous naloxone (0.6-1.0 mg/kg) also failed to affect this selective inhibition.


Murine brain capillary endothelial cells exhibit improved barrier properties under the influence of hydrocortisone.
Hydrocortisone is known to induce barrier properties in porcine primary cultures of microvascular endothelial cells. Here we present similar effects of hydrocortisone on a serum-free in vitro model based on primary cultured mouse brain endothelial cells. These cells in culture express typical blood-brain barrier properties and the transendothelial electrical resistance is enhanced after the addition of hydrocortisone to the medium in physiological concentrations. The improvement of the barrier is accompanied by changes at the cell borders indicated by immunofluorescence staining of tight junction proteins. Transmission electron microscopy imaging indicates morphological changes at the cell-cell contact zones which correlates to the observed changes in the transendothelial electrical resistance after HC supplementation. Phalloidin staining of F-actin shows a rearrangement to "fiber-like" structures in the longitudinal direction of the cell. These findings together with additional electrical impedance analysis of the monolayer suggest that several changes including cell-cell contact alteration, cell-substrate attachment and cytoskeletal rearrangements cause enhanced barrier properties in this murine endothelial culture. The present data are consistent with earlier findings in a porcine serum-free in vitro model. Thus, evidence is given that the barrier enforcement induced by glucocorticoids is not a species-specific effect and that the barrier improvement is correlated with a change of the cell morphology rather than changes in tight junction protein expression.


A theoretical analysis of the influence of wheelchair seat position on upper extremity demand.
The high physical demands placed on the upper extremity during manual wheelchair propulsion can lead to pain and overuse injuries that further reduce user independence and quality of life. Seat position is an adjustable parameter that can influence the mechanical loads placed on the upper extremity. The purpose of this study was to use a musculoskeletal model and forward dynamics simulations of wheelchair propulsion to identify the optimal seat position that minimizes various measures of upper extremity demand including muscle stress, co-contraction and metabolic cost. Forward dynamics simulations of wheelchair propulsion were generated across a range of feasible seat positions by minimizing the change in handrim forces and muscle-produced joint moments. Resulting muscle stress, co-contraction and metabolic cost were examined to determine the optimal seat position that minimized these values. Muscle stress and metabolic cost were near minimal values at superior/inferior positions corresponding to top-dead-center elbow angles between 110 and 120° while at an anterior/posterior position with a hub-shoulder angle between -10 and -2.5°. This coincided with a reduction in the level of muscle co-contraction, primarily at the glenohumeral joint. Deviations from this position lead to increased co-contraction to maintain a stable, smooth propulsive stroke, which consequentially increases upper extremity demand. These results agree with previous clinical guidelines for positioning the seat to reduce upper extremity overuse injuries and pain for wheelchair users.


Glu88 in the non-catalytic domain of acylpeptide hydrolase plays dual roles: charge neutralization for enzymatic activity and formation of salt bridge for thermodynamic stability.
Acylpeptide hydrolase of Aeropyrum pernix K1 is composed of a catalytic alpha/beta hydrolase domain and a non-catalytic beta-propeller domain. The Glu88 residue of the propeller domain is highly conserved in the prolyl oligopeptidase family and forms an inter-domain salt bridge with Arg526, a key residue for substrate binding. We have dissected the functions of Glu88 using site-directed mutagenesis, steady-state kinetics analyses, and molecular dynamics simulations. In E88A and E88A/R526K mutants, with a broken inter-domain salt bridge and a positive charge at position 526, catalytic activities for both a peptidase substrate and an esterase substrate were almost abolished. Analysis of the pH dependence of the mutants' reaction kinetics indicates that these mutations lead to changes in the electrostatic environment of the active site, which can be modulated by chloride ions. These findings indicate that the neutralization at position 526 is favorable for the activity of the enzyme, which is also verified by the catalytic behavior of E88A/R526V mutant. All mutants have lower thermodynamic stability than the wild-type. Therefore, Glu88 plays two major roles in the function of the enzyme: neutralizing the positive charge of Arg526, thereby increasing the enzymatic activity, and forming the Glu88-Arg526 salt bridge, thereby stabilizing the protein.


Effects of seed density and proximity to refuge habitat on seed predation rates for a rare and a common Lupinus species.
Biotic interactions such as seed predation can play a role in explaining patterns of abundance among plant species. The effect of seed predation will depend on how the strength of predation differs across species and environments, and on the degree to which seed loss at one life-cycle phase increases fitness at another phase. Few studies have simultaneously quantified predispersal and postdispersal predation in co-occurring rare and common congeners, despite the value of estimating both for understanding causes of rarity. We quantified predispersal seed predation on the rare, herbaceous species Lupinus tidestromii (Fabaceae) and its common, shrubby congener L. chamissonis across multiple years in the same community. We experimentally measured postdispersal seed predation at two seed densities and locations near or far from an exotic grass housing high densities of deer mice (Peromyscus maniculatus), their primary, native seed predator. The common L. chamissonis had the lowest predispersal seed predation of the two lupine species, potentially because of its height: its high racemes received less predation than those low to the ground. By contrast, the same species experienced higher postdispersal seed predation, and at predators traveled long distances away from refuge habitat to consume their seeds. Across both plant species, mice preferentially predated high-density seed sources. Our results show differences in the magnitude and direction of seed predation between the species across different life-cycle phases. We demonstrated possible roles of proximity to refuge habitat, seed density, and seed size in these patterns. Congeneric comparisons would benefit from a comprehensive framework that considers seed predation across different life-cycle phases and the environmental context of predation.


Combining environment and health information systems for the assessment of atmospheric pollution on human health.
The use of emerging technologies for environmental monitoring with satellite and in-situ sensors have become essential instruments for assessing the impact of environmental pollution on human health, especially in areas that require high spatial and temporal resolution. This was until recently a rather difficult problem. Regrettably, with classical approaches the spatial resolution is frequently inadequate in reporting environmental causes and health effects in the same time scale. This work examines with new tools different levels of air-quality with sensor monitoring with the aim to associate those with severe health effects. The process established here facilitates the precise representation of human exposure with the population attributed in a fine spatial grid and taking into account environmental stressors of human exposure. These stressors can be monitored with innovative sensor units with a temporal resolution that accurately describes chronic and acute environmental burdens. The current understanding of the situation in densely populated areas can be properly analyzed, before commitments are made for reductions in total emissions as well as for assessing the effects of reduced trans-boundary fluxes. In addition, the data processed here with in-situ sensors can assist in establishing more effective regulatory policies for the protection of vulnerable population groups and the satellite monitoring instruments permit abatement strategies that are close to real-time over large geographical areas.


Chlorinated hydrocarbon contaminants in blood of black and turkey vultures from Savannah River Site, South Carolina, USA.
Blood of adult and juvenile black and turkey vultures in the Savannah River Site of South Carolina, USA was analyzed for the presence of 2,3,7,8-chlorine substituted polychlorinated dibenzo-p-dioxins (2,3,7,8-PCDDs), dibenzofurans (2,3,7,8-PCDFs), -dioxin-like and -di-ortho polychlorinated biphenyls. Concentration ranges of 2,3,7,8-PCDD/DFs in blood of black and turkey vultures were 14.2-34.6 and 8.7-56.2 pg/ml wet wt., respectively. Dioxin-like PCBs were in the ranges of 815-4627 and 753-3611 pg/ml wet wt. respectively, in black and turkey vultures. Considerable concentrations of two congeners of di-ortho PCBs were noticed in the ranges of 1415-10325 and 663-7500 pg/ml respectively, in black and turkey vultures. Comparatively, greater toxic equivalency (TEQ) were observed in blood of turkey vultures with the ranges of 3.2-20, whereas black vulture contained 1.8-8.4 pgTEQ/ml wet wt. basis. The species-specific accumulation profiles of PCDD/DFs and dioxin-like PCBs may reflect the different feeding habits, ecology, metabolic capacity and migratory movements of these two scavenging species.


Mutagenicity studies on coffee. The influence of different factors on the mutagenic activity in the Salmonella/mammalian microsome assay.
Recently, mutagenic activity on several strains of Salmonella typhimurium has been found in many heat-processed foodstuffs. The previously reported direct-acting mutagenic activity of coffee in Salmonella typhimurium TA100 (Ames assay) was confirmed in our study. In addition to TA100, a mutagenic effect of coffee was also found by using the newly developed strain TA102. The mutagenic activity was abolished by the addition of rat-liver homogenate. 10% S9 mix completely eliminated the mutagenic activity of 30 mg of coffee per plate. The addition of reduced glutathione to active S9 further decreased the mutagenic activity and also reduced the mutagenicity together with inactivated S9. The compound or compounds responsible for this inactivation are heat-labile and seem to be located in the cytosol fraction of the S9. Part of the mutagenicity of coffee was also lost spontaneously upon incubation at temperatures between 0 degrees and 50 degrees C. The loss of activity was dependent on temperature, being more pronounced at 50 degrees C compared to 0 degrees C (at 50 degrees C approximately 50% of the mutagenic activity was lost after 6 h). As anaerobic conditions prevented this loss of mutagenicity almost totally, oxidative processes are probably responsible for the inactivation. The stability of the mutagen was not influenced by incubation at low pH values (pH 1-3), with or without the addition of pepsinogen. The mutagenic properties of methylglyoxal, which to some extent could be responsible for the mutagenic activity of coffee, were compared with those of coffee. Methylglyoxal was strongly mutagenic towards Salmonella typhimurium TA100 and TA102. Its mutagenic activity was partially inactivated by the addition of 10% S9. Glyoxalase I and II together with reduced glutathione abolished the mutagenic activity of methylglyoxal but reduced the mutagenicity of coffee by only 80%. Since these enzymes occur in mammalian cells, the mutagenic compound(s) of coffee could also be degraded in vivo. This conclusion is supported by the fact that a long-term carcinogenicity study with rats was negative. These results clearly demonstrate that the effects observed in vitro do not necessarily also occur in vivo, but that in vitro experiments may contribute to the understanding of fundamental mechanisms of chemical carcinogenesis.


Axillary nerve palsy after retrograde humeral nailing: clinical confirmation of an anatomical fear.
Locked antegrade or retrograde nailing of humeral shaft and proximal humerus fractures is a well established treatment option. Anatomic-morphological studies revealed a potential high risk of axillary nerve injury within proximal interlocking screw insertion. However, clinical experiences do not seem to confirm this, as there is a lack of interlocking screw insertion associated axillary lesions in literature. We report about a 69-year-old man with a humeral shaft fracture (AO-type 12-A3) stabilized by a retrograde implanted interlocking nail. Proximal interlocking screw insertion was performed in a posterior-to-anterior direction. The fracture healed uneventfully. In a follow-up examination 2 years later, an atrophy and paralysis of the deltoid muscle were visible. Electrophysiological evaluation confirmed an isolated axillary nerve injury. Nevertheless, the patient showed good functional recovery with almost free range of motion. Even for clinical practise proximal interlocking screw insertion is associated with a substantial risk of axillary nerve injury. Particularly for posterior-to-anterior screw insertion anatomic conditions should be considered. In spite of axillary nerve lesion, recovery of almost full shoulder function is possible by compensating the loss of deltoid function by rotator cuff muscles.