Major histocompatibility complex antigens in steroid-responsive nephrotic syndrome.
An increased frequency of specific major histocompatibility complex (MHC) class I, II and III antigens in children with steroid-responsive nephrotic syndrome (SRNS) has been reported. This frequency distortion, in some cases, is thought to affect the outcome of the disorder. We studied the phenotypic frequency of HLA antigens -A, -B, and -DR, as well as complement proteins Bf and C4 in an unrelated population of 25 SRNS children. Complete MHC haplotypes were also derived for four families in which 8 individuals developed SRNS. HLA-DR8, with a relative risk of 4.8, showed the strongest association with SRNS. Nonetheless, the 95% confidence intervals of this and the relative risks for all other antigens fell below 1.0. No common haplotype was found in SRNS patients in whom complete family studies were available, and disease and inheritance of the MHC were discordant in two of these families. In this study of well-characterized SRNS patients we were unable to discover a clear association between this disorder and the MHC.


Treatment of tympanic membrane perforations with hyaluronan in an open pilot study of unselected patients.
Twenty-five unselected tympanic membrane (TM) perforations of varying size and duration, from one day to 10 years, were treated by local application of the glycosaminoglycan, hyaluronan, 1%. The treatment was well tolerated without any side-effects. Seventeen of the perforations were closed, though two drums were re-perforated. Four perforations not completely covered were markedly reduced in size. No effect of hyaluronan could be observed on moist perforations. The scar formed after treatment with hyaluronan 'normal' appearance. Hyaluronan treatment seems to be an alternative to myringoplasty when treating small and medium-sized dry perforations.


Pedicled right atrial-pericardial tissue conduit for bypass of the obstructed superior vena cava in children.
Surgical relief of superior vena caval obstruction with flaps constructed from pedicled right atrium and pedicled pericardium has been performed successfully in 2 children aged 1 and 13 years. Long-term conduit patency 43 and 24 months after the operation has been achieved with this technique, despite continued growth of both patients.


In vivo and in vitro validation of aortic flow quantification by time-resolved three-dimensional velocity-encoded MRI.
Three-dimensional velocity-encoded cine magnetic resonance imaging (3D VEC MRI) allows for calculation of secondary flow parameters that may be used to estimate prognosis of individual cardiovascular diseases. However, its accuracy has not been fully investigated yet. The purpose of this study was to validate aortic flow quantification by 3D VEC MRI in vitro and in vivo using stacked two-dimensional acquisitions. Time-resolved stacks of two-dimensional planes with three-directional velocity-encoding (stacked-2D-3dir-MRI) were acquired in an elastic tube phantom with pulsatile flow simulating aortic flow as well as in 11 healthy volunteers (23 ± 2 years). Previously validated two-dimensional through-plane VEC MRI at six equidistant levels in vitro and three locations in vivo (ascending aorta/aortic arch/descending aorta) was used as reference standard. The percentage difference of the stacked-2D-3dir-MRI measurement to the reference standard was defined as the parameter for accuracy. For in vitro aortic flow, stacked-2D-3dir-MRI underestimated average velocity by -6.8% (p < 0.001), overestimated average area by 13.6% (p < 0.001), and underestimated average flow by -7.4% (p < 0.001). Accuracy was significantly higher in the field of view centre compared to off-centre (p = 0.001). In vivo, stacked-2D-3dir-MRI underestimated average velocity (all three locations p < 0.001) and overestimated average area at all three locations (p = n.s./<0.001/<0.001). Average flow was significantly underestimated in the ascending aorta (p = 0.035), but tended to be overestimated in the aortic arch and descending aorta. In conclusion, stacked-2D-3dir-MRI tends to overestimate average aortic area and to underestimate average aortic velocity, resulting in significant underestimation of average flow in the ascending aorta.


Catabolism of human very low density lipoproteins in vitro: a fluorescent phospholipid method for monitoring lipolysis.
The catabolism of human plasma very low density lipoproteins (VLDL) by purified bovine milk lipoprotein lipase has been measured in vitro using a fluorescent phospholipid as a method to monitor lipolysis. Dansyl phosphatidylethanolamine (DPE) was incorporated into VLDL to form DPE-VLDL, and the rate of catabolism was followed by measuring the increase in fluorescence at 490 nm after the addition of the enzyme. The studies were performed with VLDL isolated from 20 normal individuals. In addition, the VLDL from 8 mildly obese subjects with primary hypertriglyceridemia (Type IV phenotype) was studied. With this in vitro system and with a constant amount of lipoprotein lipase, the rate of lipolysis did not differ in normal and in these hypertriglyceridemic subjects. Furthermore, there was no correlation between the rates of hydrolysis and the plasma levels of triglyceride or high density lipoprotein cholesterol.


Return to intended oncologic therapy after colectomy for stage III colon adenocarcinoma: Does surgical approach matter?
Return to intended oncologic treatment (RIOT) is an important paradigm for surgically resected cancers requiring multimodal treatment. Benefits of minimally invasive colectomy (MIC) may allow earlier initiation of adjuvant chemotherapy (ACT) and have associated survival benefits. We sought to determine if operative approach affects RIOT timing in resected stage III colon cancer. NCDB identified pathological stage III colon adenocarcinoma patients who underwent resection and received ACT. Propensity score matching and kernel density estimation compared operative approaches and conversion impact on intervals to RIOT. A total of 15,132 open colectomies (OC) versus 14,107 MIC were included. MIC patients had two-days shorter median length of stay (LOS) (4 vs. 6 days; p < 0.001), one-week shorter median time to RIOT (6 vs. 7 weeks; p = 0.015) comparing 12,867 matched pairs. There was no difference in time interval to RIOT between the LC versus RC, converted MIC vs. OC groups. MIC was a favourable predictor of earlier RIOT (HR 1.14 [1.07-1.22]; p < 0.001). MIC in stage III colon cancer is associated with a shorter time to RIOT when compared to OC. Since timely initiation of ACT may influence cancer outcome, MIC may be oncologically preferable. Prospective studies are needed to assess RIOT and survival outcomes in stage III colon cancer.


Stereoselective preparation of conjugated E-enynes from E-vinylic tellurides and terminal alkynes via Sonogashira cross-coupling.
E-Vinylic tellurides undergo a direct cross-coupling reaction with terminal alkynes in the presence of palladium(II)/CuI in Et(3)N at room temperature to give E-enynes in good yields. The methodology represents a general and efficient protocol for carrying out the synthesis of E-enynes under mild conditions with complete retention of configuration.


Diffuse posterior leukoencephalopathy in MELAS without stroke-like episodes: A case report.
Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is the most common subtype of mitochondrial encephalopathy. In the past, it was believed that most hereditary white matter lesions were lysosome storage disorders or peroxisome diseases. However, in recent years, white matter lesions have been increasingly regarded as a common feature of patients with mitochondrial diseases. In addition to stroke-like lesions, about half of the patients with MELAS reported white matter lesions in the brain. Herein, we provide a case of A 48-year-old female who presented with episodic loss of consciousness with twitching of extremities. Previous medical history revealed 10 years of history of epilepsy, 10 years of history of diabetes, a history of hearing loss, and unknown etiology. Ancillary findings included brain magnetic fluid-attenuated inversion recovery showed symmetrical lesions in the bilateral parietal lobe with high signal intensity at the edge, and high signal intensity in the bilateral occipital lobe, paraventricular white matter, corona radiata, and the center of semiovale. Mitochondrial deoxyribonucleic acid gene sequencing returned A3243G point mutation and it supports the diagnosis of intracranial hypertension. Considered the diagnosis of symptomatic epilepsy, the patient was treated with mechanical ventilation, midazolam, and levetiracetam, and the limb twitching symptoms were controlled. The patient was comatose, chronically bedridden, with gastrointestinal dysfunction, and was treated prophylactically with antibiotics against infection, parenteral nutrition, and other supportive measures. B vitamins, vitamin C, vitamin E, coenzyme Q10, and idebenone were given, and mechanical ventilation and midazolam were stopped after 8 days. He was discharged from the hospital on 30 days and continued symptomatic treatment with B-vitamins, vitamin C, vitamin E, coenzyme Q10, and idebenone, and antiepileptic treatment with levetiracetam, with outpatient follow-up. No further seizures were recorded and the patient recovered well. MELAS syndrome without stroke-like episodes of diffuse posterior cerebral white matter lesions is rare in clinical practice, and the possibility of MELAS syndrome should be considered in symmetric posterior cerebral white matter lesions.


Contrary choices: possible exploitation of enemy-free space by herbivorous insects in cultivated vs. wild crucifers.
The pressure to escape natural enemies may shape how herbivorous insects use their plant resources. On wild crucifers, ovipositional preferences of the diamondback moth (Plutella xylostella; DBM) were similar to searching preferences of its main parasitoid, an ichneumonid wasp (Diadegma insulare). But on cultivated crucifers, these species had opposite preferences. In addition, DBM ovipositional preferences did not correlate with growth or reproduction on several foodplants. We interpret these patterns as evidence of evolution for use of enemy-free space in agricultural systems.


(3E)-4-[(Naphthalen-1-yl)amino]-pent-3-en-2-one hemihydrate.
The title compound, C15H15NO·0.5H2O, was prepared from α-naphthyl-amine and 2,4-penta-nedione in a 1:1 ratio. An intra-molecular N-H⋯O hydrogen bond in the N-naphthyl-pent-3-en-2-one mol-ecule involving the amine and carbonyl groups strengthens the structure. The water mol-ecule interacts with two symmetry-related N-naphthyl-pent-3-en-2-one mol-ecules viaby O-H⋯O hydrogen bonds.


TIME-Net: Transformer-Integrated Multi-Encoder Network for limited-angle artifact removal in dual-energy CBCT.
Dual-energy cone-beam computed tomography (DE-CBCT) is a promising imaging technique with foreseeable clinical applications. DE-CBCT images acquired with two different spectra can provide material-specific information. Meanwhile, the anatomical consistency and energy-domain correlation result in significant information redundancy, which could be exploited to improve image quality. In this context, this paper develops the Transformer-Integrated Multi-Encoder Network (TIME-Net) for DE-CBCT to remove the limited-angle artifacts. TIME-Net comprises three encoders (image encoder, prior encoder, and transformer encoder), two decoders (low- and high-energy decoders), and one feature fusion module. Three encoders extract various features for image restoration. The feature fusion module compresses these features into more compact shared features and feeds them to the decoders. Two decoders perform differential learning for DE-CBCT images. By design, TIME-Net could obtain high-quality DE-CBCT images using two complementary quarter-scans, holding great potential to reduce radiation dose and shorten the acquisition time. Qualitative and quantitative analyses based on simulated data and real rat data have demonstrated the promising performance of TIME-Net in artifact removal, subtle structure restoration, and reconstruction accuracy preservation. Two clinical applications, virtual non-contrast (VNC) imaging and iodine quantification, have proved the potential utility of the DE-CBCT images provided by TIME-Net.


White matter correlates of reading subskills in children with and without reading disability.
Individual differences in reading ability are associated with characteristics of white matter microstructure in the brain. However, previous studies have largely measured reading as a single construct, resulting in difficulty characterizing the role of structural connectivity in discrete subskills of reading. The present study used diffusion tensor imaging to examine how white matter microstructure, measured by fractional anisotropy (FA), relates to individual differences in reading subskills in children aged 8 to 14 (n = 65). Findings showed positive correlations between FA of the left arcuate fasciculus and measures of single word reading and rapid naming abilities. Negative correlations were observed between FA of the right inferior longitudinal fasciculus and bilateral uncinate fasciculi, and reading subskills, particularly reading comprehension. The results suggest that although reading subskills rely to some extent on shared tracts, there are also distinct characteristics of white matter microstructure supporting different components of reading ability in children.


The thiol proteinase inhibitors, Z-Phe-PheCHN2 and Z-Phe-AlaCHN2, inhibit lysosomal protein degradation in isolated rat hepatocytes.
The effects on protein metabolism of Z-Phe-PheCHN2 and Z-Phe-AlaCHN2 were examined in isolated rat hepatocytes. The two thiol proteinase inhibitors caused a drastic reduction in the degradation of both endogenous and endocytosed (asialo-fetuin) protein. The inhibition was not additive to that of the lysosomotropic base methylamine, indicating that Z-Phe-PheCHN2 and Z-Phe-AlaCHN2 only affect lysosomal degradation. At high concentrations (0.1-1 mM) both inhibitors reduced protein synthesis strongly. This finding indicates non-specific/toxic effects, which may limit the usefulness of the inhibitors.


The expression and distribution of aquaporin 3 in mouse embryos before and after vitrification.
To determine the role of aquaporin 3 (AQP3) isoform in early embryonic development and protecting embryos subjected to freeze-thawing for assisted reproduction, we investigated the expression and distribution of AQP3 in mouse embryos at different developmental stages before and after vitrification. Eight-cell embryos, morulae, and blastocysts were obtained from female mice that had been superovulated by controlled ovarian hyperstimulation. Immunofluorescence staining, laser confocal microscopy, and Western blot were used to determine the expression and distribution of AQP3 in preimplantation mouse embryos before and after vitrification. AQP3 was expressed at the 8-cell to blastocyst stage before and after vitrification. The expression and distribution of AQP3 was developmentally regulated at the 8-cell to blastocyst stage. The expression of AQP3 was significantly decreased in 8-cell embryos and early blastocysts after vitrification. However, at the morulae stage, the expression of AQP3 was increased after vitrification. The developmental and vitrification-dependent changes in AQP3 expression and distribution suggest that this transmembrane channel might regulate mouse embryo development and contribute to the protective response during vitrification.


Prosthetic valve endocarditis due to methicillin-resistant Staphylococcus epidermidis and Micrococcus species successfully treated with rifampicin combined with other antibiotics.
Two patients with prosthetic valve endocarditis due to methicillin-resistant Gram-positive cocci (Staphylococcus epidermidis and Micrococcus spp.) are described. They were successfully treated with rifampicin combined first with an aminoglycoside and later with co-trimoxazole or co-trimoxazole plus vancomycin. The addition of rifampicin to these antibiotics resulted in enhanced serum bactericidal activity. High doses of rifampicin (1200-1800 mg) for 7-8 weeks did not cause any serious side-effect. Surgery was not required. During surveillance for more than 2 years endocarditis did not recur.


Possible applications of reflected UV photography in forensic odontology: Food for thought.
Usually, in forensic sciences, ultraviolet (UV) light is used to induce fluorescence on many samples to identify and evaluate proofs (ex. fibers, gunshot residue, biologic fluids, pigments, inks and fingerprints) and different wavelength are used to better enhance the material characteristics. On the contrary, the potential use of absorbed and reflected UV has not been deeply investigated, especially in forensic odontology. The aim of this study is to evaluate the forensic potential of dental materials UV absorption and reflection and to investigate if different dental tissues and materials interact in different ways with UV radiation. A digital camera modified so to be UV sensible only and a modified flashlight were used to produce images of absorbed/reflected UV radiation of different dental materials. First results show the promising potentials of the technique in detecting dental composite resin materials, in enhancing image contrast between dentin and enamel, in enhancing enamel infractions and in possible age estimation future applications.


Feasibility of Using Volumetric Contrast-Enhanced Ultrasound with a 3-D Transducer to Evaluate Therapeutic Response after Targeted Therapy in Rabbit Hepatic VX2 Carcinoma.
The aim of this study was to assess the feasibility of using dynamic contrast-enhanced ultrasound (DCE-US) with a 3-D transducer to evaluate therapeutic responses to targeted therapy. Rabbits with hepatic VX2 carcinomas, divided into a treatment group (n = 22, 30 mg/kg/d sorafenib) and a control group (n = 13), were evaluated with DCE-US using 2-D and 3-D transducers and computed tomography (CT) perfusion imaging at baseline and 1 d after the first treatment. Perfusion parameters were collected, and correlations between parameters were analyzed. In the treatment group, both volumetric and 2-D DCE-US perfusion parameters, including peak intensity (33.2 ± 19.9 vs. 16.6 ± 10.7, 63.7 ± 20.0 vs. 30.1 ± 19.8), slope (15.3 ± 12.4 vs. 5.7 ± 4.5, 37.3 ± 20.4 vs. 15.7 ± 13.0) and area under the curve (AUC; 1004.1 ± 560.3 vs. 611.4 ± 421.1, 1332.2 ± 708.3 vs. 670.4 ± 388.3), had significantly decreased 1 d after the first treatment (p = 0.00). In the control group, 2-D DCE-US revealed that peak intensity, time to peak and slope had significantly changed (p < 0.05); however, volumetric DCE-US revealed that peak intensity, time-intensity AUC, AUC during wash-in and AUC during wash-out had significantly changed (p = 0.00). CT perfusion imaging parameters, including blood flow, blood volume and permeability of the capillary vessel surface, had significantly decreased in the treatment group (p = 0.00); however, in the control group, peak intensity and blood volume had significantly increased (p = 0.00). It is feasible to use DCE-US with a 3-D transducer to predict early therapeutic response after targeted therapy because perfusion parameters, including peak intensity, slope and AUC, significantly decreased, which is similar to the trend observed for 2-D DCE-US and CT perfusion imaging parameters.


Comparison of fecal microbiota composition of blue sheep fed Lolium perenne versus Sorghum sudanense.
Lolium perenne L. and Sorghum sudanense (Piper) Stapf. are 2 common forages fed to blue sheep (Pseudois nayaur Hodgson, 1833) in captivity. However, the effect of these 2 forages on the gastrointestinal microbiota is largely unknown. We analyzed the diversity of the microbiota in the feces of captive blue sheep fed with L. perenne (group F1) and S. sudanense (group F2) by 16S rRNA sequencing. A total of 20 major phyla and 29 genera fecal bacterial communities were detected in the 2 groups. The F1 and F2 groups shared common microbiota at the phylum level, which mainly consisted of Firmicutes and Bacteroidetes. Ruminococcaceae_UCG-005, Eubacterium_coprostanoligenes_group, Ruminococcaceae_UCG-013, and Ruminococcaceae_UCG-010 were the top 4 dominant taxa at the genus level. The percentage of Ruminococcaceae_UCG-010 was significantly higher in the F2 group (∼2.75-fold) than in F1 group. The diversity and abundance of the microbial community in F2 was higher than that in F1. Although both of L. perenne and S. sudanense affect the metabolism of the gastrointestinal microbiota of blue sheep, the S. sudanense improves more aspects of metabolism and biogenesis. In summary, our results demonstrated that L. perenne and S. sudanense affect blue sheep gastrointestinal microbiota in different ways. But S. sudanense efficiently improved the gastrointestinal microbiota of blue sheep.


Clinical features of new daily persistent headache: A retrospective chart review of 328 cases.
To describe the clinical features of new daily persistent headache (NDPH) at an outpatient neurology clinic with a subspecialty interest in headache in Houston, Texas. A retrospective chart review was performed by a neurologist subspecialty certified in headache medicine of all patients seen from September 1, 2011 through February 28, 2020 (8.5 years) with a provisional diagnosis of NDPH and abstracted charts meeting criteria for primary NDPH. A total of 328 patients met the International Classification of Headache Disorders, 3rd edition criteria including 215 (65.5%) female patients. The mean age of onset was 40.3 years (range 12-87 years) with a mean age at first consultation in the study clinic of 42.6 years (range 12-87 years). The median [25th, 75th] duration of NDPH at initial consultation was 0.7 [0.3, 2.0] years, and at last visit, it was 1.9 [0.7, 4.8] years. The headaches were side-locked unilateral in 28/328 (8.5%). 12/328 cases (3.6%) with a thunderclap onset are reported. There was no obvious seasonal or other cyclical variation. The pain was usually moderate to severe and more often severe for the migraine phenotype (MP; 260/328 [79.3%] of cases) than for the tension-type phenotype (TTP). Precipitating factors were the following: stressful life events, 67/328 (20.4%); upper respiratory infection or flu-like illness, 33/328 (10.1%); and extracranial surgery, 5/328 (1.5%). Exacerbating or aggravating factors similar to migraine triggers were more often reported with the MP than with the TTP in this sample. For the MP, vertigo or dizziness was reported by 19/260 (7.3%) and a visual aura by 21/260 (8.1%) with descriptions provided. The prognostic types were the following for all patients: persisting (refractory), 305/328 (93.0%); relapsing-remitting, 9/328 (2.7%); and remitting (self-limited), 14/328 (4.3%). NDPH is typically of moderate to severe intensity often with migraine features without obvious seasonal or other cyclical variation. Most cases are refractory. 3.6% have a thunderclap onset often with a good response to treatment.


Does the Subject Content of the Pharmacy Degree Course Influence the Community Pharmacist's Views on Competencies for Practice?
Do community pharmacists coming from different educational backgrounds rank the importance of competences for practice differently-or is the way in which they see their profession more influenced by practice than university education? A survey was carried out on 68 competences for pharmacy practice in seven countries with different pharmacy education systems in terms of the relative importance of the subject areas chemical and medicinal sciences. Community pharmacists were asked to rank the competences in terms of relative importance for practice; competences were divided into personal and patient-care competences. The ranking was very similar in the seven countries suggesting that evaluation of competences for practice is based more on professional experience than on prior university education. There were some differences for instance in research-related competences and these may be influenced, by education.


Asbestos contamination on brownfield development sites in the UK.
The development of brownfield sites in the UK requires site investigation for contamination as part of the regulatory planning process. This site investigation includes the collection of soil samples that are analysed for asbestos contamination. This research project analyses this untapped resource of brownfield asbestos data, using site investigation data submitted to a local Borough Council, in Surrey, UK. Over 100 site investigation reports were collected. This paper presents the trends in asbestos testing from 2001 to 2019 and data on the location, concentration, form and type of asbestos found in this Borough. The rate of asbestos detection has increased significantly, reflecting improvements in asbestos measuring techniques, to a rate of 22% for all samples tested between 2016 and 2019. The concentrations of asbestos found were very low, with 74% of samples having concentrations below the limit of detection of the laboratory and were predominantly of fibrous form. A significant proportion of samples contained more carcinogenic amphibole type. Most of the asbestos was found in the top 1 m of Made Ground soil. Site history was found to be important with gas works having the highest asbestos detection rate, though a detection rate of 10% was found in soil samples on former residential sites. This information is important to inform and update risk assessment for site workers and site remediation in relation to asbestos. Hence based upon these results, a qualitative risk chart for asbestos is presented to provide guidance and in-sight into asbestos on brownfield sites for local authorities and developers.


The inhibitory potential of the condensed-tannin-rich fraction of Plathymenia reticulata Benth. (Fabaceae) against Bothrops atrox envenomation.
Ethnobotanical studies have shown that Plathymenia reticulata Benth. (Fabaceae) has been widely used in cases of snake envenomation, particularly in Northern Brazil. In light of this, the aim of this study was to evaluate the inhibitory potential of the condensed-tannin-rich fraction obtained from the bark of P. reticulata against the main biological activities induced by Bothrops atrox venom (BaV). The chemical composition of the aqueous extract of P. reticulata (AEPr) was first investigated by thin-layer chromatography (TLC) and the extract was then fractionated by column chromatography on Sephadex LH-20. This yielded five main fractions (Pr1, Pr2, Pr3, Pr4 and Pr5), which were analyzed by colorimetry to determine their concentrations of total phenolics, total tannins and condensed tannins and to assess their potential for blocking the phospholipase activity of BaV. The Pr5 fraction was defined as the fraction rich in condensed tannins (CTPr), and its inhibitory potential against the activities of the venom was evaluated. CTPr was evaluated in different in vivo and in vitro experimental protocols. The in vivo protocols consisted of (1) pre-incubation (venom:CTPr, w/w), (2) pre-treatment (orally administered) and (3) post-treatment (orally administered) to evaluate the effect on the hemorrhagic and edematogenic activities of BaV; in the in vitro protocol the effect on phospholipase and coagulant activity using pre-incubation in both tests was evaluated. There was statistically significant inhibition (p<0.05) of hemorrhagic activity by CTPr when the pre-incubation protocol was used [55% (1:5, w/w) and 74% (1:10, w/w)] and when pre-treatment with doses of 50 and 100mg/kg was used (19% and 13%, respectively). However, for the concentrations tested, there was no statistically significant inhibition in the group subjected to post-treatment administered orally. CTPr blocked 100% of phospholipase activity and 63.3% (1:10, w/w) of coagulant activity when it was pre-incubated with BaV. There was a statistically significant reduction (p<0.05) in edema induced by BaV in the oral protocols. Maximum inhibition was 95% (pre-treatment). Our findings indicate that CTPr could be a good source of natural inhibitors of the components of snake venom responsible for inducing local inflammation.


Efficient gene delivery using chitosan-polyethylenimine hybrid systems.
Chitosan and chitosan derivatives have been investigated as non-viral vectors because they have several advantages, such as biocompatibility, biodegradability, low cytotoxicity and low immunogenicity. However, low transfection efficiency and low cell specificity must be solved for their use in clinical trials. In this paper, chitosan-polyethylenimine (PEI) hybrid systems such as chitosan/PEI blend and chitosan-graft-PEI are described for efficient gene delivery because the PEI has high transfection efficiency owing to a proton sponge effect and chitosan has biocompatibility. Also, hepatocyte specificity of the galactosylated chitosan is explained after combination with PEI.


Balancing repair and tolerance of DNA damage caused by alkylating agents.
Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for a favourable response of an organism to alkylating agents. Furthermore, the response of an individual to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity.


Rapid histological staining procedures for material from immune-suppressed patients.
Immunocompromised patients require rapid diagnosis of infectious conditions, if treatment is to be effective. This paper describes rapid techniques for the identification of pathogens from transbronchial and other biopsy specimens. Included are rapid procedures for the following stains: Grocott-Gomori methenamine silver; Dieterle silver; periodic acid-Schiff; alcian blue; MacCallum-Goodpasture; and Kinyoun's acid-fast. The clinical usefulness of transbronchial biopsy is discussed.


Interaction of Streptococcus mutans glucosyltransferases with antibodies.
1) The GTF-A and GTF-B activities of serotype (c), (e), and (f) organisms are antigenically more closely related to each other than to the comparable enzymes from organisms of the other four S. mutans serotypes. 2) The adherence-inhibiting antibody in anti-GTF-A appears to be mediated against a heat sensitive cell surface antigen of S. mutans - most likely GTF activity. However, unequivocal proof of this conclusion awaits the preparations of homogeneous GTF-A preparations.


The effects of phosphate supply on growth of plants from the Brasilian Cerrado: experiments with seedlings of the annual weed, Bidens gardneri Baker (Compositeae) and the tree, Qualea grandiflora (Mart.) (Vochysiaceae).
Plants of the cerrado tree species Qualea grandiflora and the annual herb Bidens gardneri were grown from seed in controlled environment rooms at 30/20° C and 12 hour photoperiod. Seedlings were grown in pots or small tubes containing sand and provided with various amounts of mineral solutions based on the formulation of Hoagland and Arnon but with the phosphate content modified in some cases. In a long-term experiment lasting 213 days, plants supplied with full strength Hoagland's solution all died but plants of Qualea given 1/10 strength solution survived, although they grew very slowly. Low relative growth rates (0.008-0.036 d-1) were also a feature of other experiments with Qualea and calculated rates of net assimilation rate gave values of 3-7 mg CO2 dm-2 h-1. Expansion of the photosynthetic surface proceeded slowly and the cotyledons were the main site of photosynthesis for more than 40 days. The low rates of growth occurred despite significant uptake of phosphorus by young plants and in shortterm experiments growth was independent of the amount of phosphate supplied and accumulated. In contrast, the values of R found for plants of Bidens reached 0.24 d-1. Growth of young plants was dependent on the external supply of phosphorus, being reduced when this was low and also when it was very high. Growth of the photosynthetic surface was also much more rapid than for Qualea and also varied with supply of phosphorus. The results are discussed in the context of the occurrence of these species in the Cerrado.


NMR studies of a series of dehydrodermorphins.
The third and fifth aromatic residues of dermorphin, a potent mu-opioid peptide, and of its N-terminal fragments, from the pentapeptide to the parent heptapeptide amide, have been systematically substituted with Z-dehydrophenylalanine (delta-Phe) and/or Phe to investigate the conformation-activity relationship. The characterization in DMSO-d6 at 500 MHz indicates that, in this solvent, all peptides adopt essentially random, extended conformations, as a consequence of the strong solvation. The chemical shift of the methyl group of D-Ala is influenced by the precise orientation of the side chain of the third residue in a fashion that can be correlated to the mu potency, consistently with our model of mu-receptor. However, the complexes of the pentapeptides with 18-crown-6-ether, when dissolved in chloroform, adopt ordered, folded conformations, a behavior that closely parallels the CD observations in methanol.


Health risk implications of iron in wastewater soil-food crops grown in the vicinity of peri urban areas of the District Sargodha.
Irrigation using sewage water can be beneficial, as it can increase the productivity of crops but has negative consequences on crops, soil contamination, and human health. It contains a variety of toxins, such as chemicals and heavy metals, which damage the soil and crops. In this regard, the aim of the research was to assess the potential health hazards of iron (Fe) metal in food crops (leafy and root crops) treated with wastewater (T_1), canal water (T_2), and tube well water (T_3). Water, soil, and edible components of food crops were collected at random from three distinct locations. Fe concentration in samples was estimated using atomic absorption spectrophotometer, following wet digestion method. The Fe concentrations, ranged from 0.408 to 1.03 mg/l in water, 31.55 to 187.47 mgkg-1 in soil and 4.09 to 32.583 mgkg-1 in crop samples; which were within permissible limits of the World Health Organization (WHO). There was a positive correlation between soils and crops. The bioconcentration factor, enrichment factor (EF), daily intake of metals (DIM), health risk index (HRI), and target hazard quotient (THQ) all values were <1, except for a pollution load index >1, which indicated soil contamination, but there was no Fe toxicity in crops, no health risk, and no-carcinogenic risk for these food crops in humans. To prevent the excessive accumulation of Fe metal in the food chain, regular monitoring is needed.


Maintaining Weight Loss by Decreasing Sedentary Time: A Patient and Physician's Perspective.
This article, co-authored by a patient living with obesity and his obesity medicine specialist, reviews how the patient has successfully lost 200 lb and maintained that loss for over a decade. This was achieved primarily with a behavioral intervention including support visits, a structured food plan, and changes in his physical activity. He did not undergo bariatric surgery. For the majority of this time, he was not treated with anti-obesity medication. This article will review how the patient lost the weight and kept it off, particularly in relationship to the importance of decreasing sedentary time.


The use of dCELL (decellularized human dermis) for primary and revision hypospadias repair: A case-control study.
A dartos interposition flap is often used as a waterproofing layer in hypospadias repairs. Recently, acellular dermal matrices (ADMs) have been described as an alternative. In this case-control study we compare the outcomes of using dCELL (an ADM) with dartos flap. A retrospective, case-control study was conducted, comparing the use of dCELL in primary and revision cases to controls. Patients were matched according to age and surgical technique. Data were analysed using an independent t-test. 13 patients undergoing primary distal hypospadias repair using dCELL as an interposition layer were matched with 13 controls. There was no significant difference in the number of complications between the groups (p = 0.296). 5 patients undergoing revision surgery using dCELL were also matched in the same way. Although a statistically significant lower complication rate was shown in the dCELL group compared to controls (p = 0.029), this may represent a type II error due to the small sample size and heterogeneity. Using dCELL as an interposition layer was not associated with any reduction in complication rates for primary distal hypospadias repair and possibly useful in soft tissue-deficient reoperative cases. However, larger randomised controlled trials may be needed to confirm the presence (or absence) of any benefit from using dCELL in hypospadias surgery.


Design, synthesis and biological evaluation of novel aminopyrazole- and 7-azaindole-based Nek1 inhibitors and their effects on zebrafish kidney development.
NIMA-related protein kinase Nek1 is crucially involved in cell cycle regulation, DNA repair and microtubule regulation and dysfunctions of Nek1 play key roles in amyotrophic lateral sclerosis (ALS), polycystic kidney disease (PKD) and several types of radiotherapy resistant cancer. Targeting of Nek1 could reveal a new class of radiosensitizing substances and provide useful tools to better understand the aforementioned diseases. In this report we explore substituted aminopyrazoles and 7-azaindoles as potent inhibitors for the Nek1 kinase domain and examine their effect on kidney organogenesis in Danio rerio.


Pseudophakic and aphakic retinal detachment mimicking cystoid macular edema.
Seventeen eyes of patients who were being followed by their ophthalmologists for aphakic (8 eyes) or pseudophakic (9 eyes) cystoid macular edema (CME) were examined on referral. All eyes showed retinal detachment (RD), and eight eyes had CME with RD. Most RDs were inferior and shallow. Proliferative vitreoretinopathy (PVR) was noted in 15 eyes (88.2%). There was history of vitreous loss during the last intraocular surgery in 88.2% eyes. Visual acuity ranged from 20/40 to hand movements. Fundus view was hazy in most eyes, and indirect ophthalmoscopy was most useful in detecting RD. Retinal reattachment with scleral buckling and/or vitrectomy was achieved in 16 eyes (94.1%). Postoperative visual recovery was jeopardized due to longstanding macular detachment of greater than 1 month in 11 eyes (64.7%). Eight eyes (47%) achieved 20/50 vision whereas 25% did not improve to better than 20/400. Factors leading to failure in making the correct diagnosis and their prevention are discussed.


Menstrual patterns and progesterone circulating levels following different procedures of tubal occlusion.
This study was undertaken to assess the effects of different tubal occlusion procedures on ovarian function. Three groups of subjects randomized to tubal occlusion by laparoscopy and Yoon ring (24 subjects), minilaparotomy and Yoon ring (19 subjects) and minilaparotomy and Pomeroy (22 subjects), and one separate control group of 26 healthy subjects not using any form of contraception were studied in a prospective design. The characteristics of the menstrual patterns were studied for one year after sterilization. Determination of the circulating progesterone levels were made on days 15, 20 and 25 of menstrual cycles initiated 1, 3, 6 and 12 months following the tubal ligation. In the analysis of the bleeding pattern there was a statistically significant difference in the mean segment length and in the longest bleeding-free interval in the subjects who had been sterilized by minilaparotomy with Yoon ring, when compared to the other two study groups and to the control group. However, the magnitude of this difference in number of days was not considered clinically significant. There was no statistically significant difference in the percentage of ovulatory cycles within the study and the control groups, or when the results of the study groups were compared with each other or to the control group.


Cardiovascular protective effects of synthetic isoflavone derivatives in apolipoprotein e-deficient mice.
Dietary flavonoids are thought to protect against cardiovascular disease. We have studied the effects of bioactive isoflavone metabolites on hyperlipidemia, endothelial dysfunction and the development of atherosclerotic lesions in apolipoprotein E-deficient (apoE(0)) mice fed a Western high-fat diet. Supplementation with dihydrodaidzein (DiD), dehydroequol (DeE) (both 25 mg kg(-1) x day(-1)) and their combination (D/D; 12.5 mg kg(-1) x day(-1) for each) for 24 weeks reduced plasma high-density lipoprotein (HDL) and non-HDL cholesterol. D/D also reduced the triglyceride level. In the abdominal aorta of apoE(0) mice, these compounds significantly increased endothelial nitric oxide (NO)-mediated vasorelaxations induced by acetylcholine, but had a minor effect on relaxations induced by the NO donor S-nitroso-N-acetylpenicillamine. Isoflavone treatment for 24 weeks had no effect on the total area of atherosclerotic plaques in the whole aorta, but DeE reduced the plaque thickness in the aortic arch by 29%, although this did not reach statistical significance. The endothelial dysfunction in apoE(0) mice is associated with hyperlipidemia and increased vascular oxidative stress measured as increased superoxide production. Both isoflavones have superoxide-scavenging activities in vitro. We suggest that chronic supplementation with bioactive isoflavone metabolites may protect endothelial NO function in apoE(0) mice, through both lipid-lowering and antioxidant actions.


Associations of polymorphisms in IL-6 and IL-18 with tuberculosis: Evidence from a meta-analysis.
Associations between polymorphisms in interleukin-6 (IL-6)/interleukin-18 (IL-18) and tuberculosis (TB) were already reported by many publications. The aim of this meta-analysis was to better clarify associations between polymorphisms in IL-6/IL-18 and TB by combing the results of all relevant publications. Eligible publications were searched from Pubmed, Embase, WOS and CNKI. We used Review Manager to combine the results of individual studies. Twenty-five studies were included in this study. IL-6 rs1800795 (dominant comparison: OR 1.43, 95% CI 1.23-1.67; recessive comparison: OR 0.48, 95% CI 0.35-0.65; allele comparison: OR 1.43, 95% CI 1.27-1.62), IL-18 rs1946518 (dominant comparison: OR 1.19, 95% CI 1.04-1.35; recessive comparison: OR 0.82, 95% CI 0.71-0.96; allele comparison: OR 1.14, 95% CI 1.05-1.24) and IL-18 rs187238 (dominant comparison: OR 1.35, 95% CI 1.15-1.58; allele comparison: OR 1.31, 95% CI 1.14-1.50) polymorphisms were all significantly associated with TB in the total population. Subgroup analyses showed that positive findings for rs1946518, rs187238 and rs1800795 polymorphisms were mainly driven by the Asians. Collectively, this meta-analysis proved that IL-6 rs1800795, IL-18 rs1946518 and IL-18 rs187238 polymorphisms may confer susceptibility to TB, especially for Asians.


Progestin receptors in meningiomas. Comparison of cytosolic assays with immunocytochemical identification in cryostat and paraffin sections.
The results are reported of ligand binding and enzyme immunoassays in tumour cytosols, and of immunoperoxidase assays in cryostat and paraffin sections measuring oestrogen (ER) and progestin receptors (PR) in 22 meningiomas and three non-meningioma tumours (two neurinomas and one haemangiopericytoma). With regard to the meningioma tissues, cytochemical immunoperoxidase PR-staining was present in all cryostat sections and in all but one of the paraffin sections. There was a good degree of qualitative accordance between all assay methods; they revealed the picture of "typical" meningioma: high PR and low ER. In this series, immunoperoxidase staining for the detection of PR-receptors, both in cryostat and paraffin sections, rendered encouraging results, thus offering a method for the detection of progestin receptors, which can compete with cytosolic methods.


Effective radium concentration in topsoils contaminated by lead and zinc smelters.
Trace elements (TE) are indicative of industrial pollution in soils, but geochemical methods are difficult to implement in contaminated sites with large numbers of samples. Therefore, measurement of soil magnetic susceptibility (MS) has been used to map TE pollutions, albeit with contrasted results in some cases. Effective radium concentration (ECRa), product of radium concentration by the emanation factor, can be measured in a cost-effective manner in the laboratory, and could then provide a useful addition. We evaluate this possibility using 186 topsoils sampled over about 783km(2) around two former lead and zinc smelters in Northern France. The ECRa values, obtained from 319 measurements, range from 0.70±0.06 to 12.53±0.49Bq·kg(-1), and are remarkably organized spatially, away from the smelters, in domains corresponding to geographical units. Lead-contaminated soils, with lead concentrations above 100mg·kg(-1) <3km from the smelters, are characterized on average by larger peak ECRa values and larger dispersion. At large scales, away from the smelters, spatial variations of ECRa correlate well with spatial variations of MS, thus suggesting that, at distance larger than 5km, variability of MS contains a significant natural component. Larger ECRa values are correlated with larger fine fraction and, possibly, mercury concentration. While MS is enhanced in the vicinity of the smelters and is associated with the presence of soft ferrimagnetic minerals such as magnetite, it does not correlate systematically with metal concentrations. When multiple industrial and urban sources are present, ECRa mapping, thus, can help in identifying at least part of the natural spatial variability of MS. More generally, this study shows that ECRa mapping provides an independent and reliable assessment of the background spatial structure which underlies the structure of a given contamination. Furthermore, ECRa may provide a novel index to identify soils potentially able to fix leached components.


A systematic review and meta-analysis of treatment outcomes following antibiotic therapy among patients with carbapenem-resistant Klebsiella pneumoniae infections.
Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a major global public health challenge. This study aimed to systematically review the evidence on treatment outcomes (mortality, clinical and microbiological response) following antibiotic therapy administered for CRKP infections. Medline, EMBASE, the Cochrane Central Register of Controlled Trials, and the International Pharmaceutical Abstracts databases were searched from inception to 26 December 2018. Data were analysed via meta-analysis techniques using random-effects (DerSimonian and Laird) modelling. Fifty-four observational studies involving 3195 CRKP-infected patients who received antibiotic treatment were included. The pooled mortality, clinical and microbiological response rates were 37.2% (95% confidence interval [CI] 33.1-41.4%), 69.0% (95% CI 60.1-78.2%) and 63.7% (95% CI 53.7-74.1%), respectively. Compared with combination therapy, monotherapy was associated with a higher likelihood of mortality (odds ratio [OR] 1.45, 95% CI 1.18-1.78%), but there were no statistically significant differences in the likelihood of achieving clinical and microbiological responses. There were no statistically significant differences in the pooled likelihood of mortality, clinical or microbiological responses between two-drug and three-or-more-drug combination therapies or combination-containing and combination-sparing regimens of polymyxins, tigecycline, aminoglycosides and carbapenems. Moreover, clinical outcomes did not significantly differ among the various monotherapies. These data highlight the need for systematic studies and well-designed randomised clinical trials to identify and evaluate the most appropriate antibiotic therapies for CRKP infections towards informing clinical decision-making. Furthermore, continuous surveillance of antimicrobial susceptibility patterns at local, regional, and national/international levels are important to support empirically-based therapy until susceptibility results for the isolate from the patient are available.


The genetics of tea and coffee drinking and preference for source of caffeine in a large community sample of Australian twins.
To investigate the genetic and environmental influences on tea consumption and their commonalities with coffee consumption; and to further examine the genetic and environmental aetiology of preference for tea/coffee. A classical twin design was used in which the similarity of identical and non-identical twins is compared, enabling estimates of genetic, common environmental and unique environmental influence on the trait. An Australian population-based sample of 1796 identical (i.e. monozygotic) and 2013 non-identical (i.e. dizygotic) twin pairs aged 16-87 years was studied, roughly three-fifths of whom were female. The sample represented approximately 70% of those approached for study participation. As part of a Health and Lifestyle Questionnaire, respondents were asked how many cups of each tea and coffee they consumed per day. Additional measures of 'total tea and coffee consumption' and 'preference for coffee' were calculated. Age was positively associated with tea consumption but negatively associated with coffee preference; women consumed more beverages than men, but showed a lower preference for coffee. An inverse relation between tea and coffee consumption--larger in females (-0.41) than males (-0.34)--was supported. This association was mediated entirely by the unique environment in males, and by both the unique environment (68.3%) and genes (31.7%) in females. Tea and coffee drinking were shown to have similar heritabilities (0.46) in males, but tea consumption was influenced by common environmental factors whereas coffee consumption was not. Coffee preference was shown to be influenced by genes (0.42) and the unique environment (0.58). As the patterns of genetic and environmental variation were shown to differ for tea and coffee consumption it may be more informative to retain them as separate measures of caffeine intake in future studies of stimulant use and taste perception.


The experiences of psychiatric patients, their caregivers and companions in upholding patient dignity during hospitalization: A qualitative study.
The quality of care and patient satisfaction is closely linked with dignity, which is a crucial component of therapy and care. However, there is very little study on dignity in the context of mental health care. Planning for ongoing patient care might benefit from an understanding of the notion of dignity by exploring the experiences of patients, caregivers and companions of patients who have a history of hospitalization in mental health institutions. To retain patients' dignity while they were being treated in mental wards, this study sought to understand the experiences of patients, caregivers and companions of patients. This investigation was qualitative. Semistructured interviews and focus groups were utilized to collect the data. The purposeful sampling method was employed for participant recruitment, which continued until data saturation. Two focus group discussions and 27 interviews were conducted. Participants included 8 patients, 2 patients' family members (companions), 3 psychologists, 4 nurses and 11 psychiatrists. Two focus group discussions were held with seven family members or companions of patients. Thematic analysis was used for data analysis. The primary theme that emerged was the infringement of patients' dignity, through negative guardianship, dehumanization and violations of their rights. Subthemes included dehumanization, worthlessness and namelessness, patient rights violations and stripping patients of authority. Our results suggest that, regardless of the severity of the illness, the nature of psychiatric illness significantly compromises patients' dignity. Mental health practitioners, due to their sense of guardianship, may unintentionally treat patients with mental health disorders, thus compromising the patient's dignity. The research team's experiences as a psychiatrist, doctor and nurse informed the study's objectives. Nurses and psychiatrists who work in the healthcare industry designed and conducted the study. The primary authors, who are healthcare providers, collected and analysed the required data. Furthermore, the entire study team contributed to the writing of the manuscript. Study participants were involved in the data collection and analysis.


Sodium influx rate and ouabain-sensitive rubidium uptake in isolated guinea pig atria.
1. Ouabain-sensitive 86Rb+ uptake by tissue preparations has been used as an estimate of Na+ pump activity. This uptake, however, may be a measure of the Na+ influx rate, rather than capacity of the Na+ pump, since intracellular Na+ concentration is a determinant of the active Na+/Rb+ exchange reaction under certain conditions. This aspect was examined by studying the effect of altered Na+ influx rate on ouabain-sensitive 86Rb+ uptake in atrial preparations of guinea pig hearts. 2. Electrical stimulation markedly enhanced ouabain-sensitive 86Rb+ uptake without affecting nonspecific, ouabain-insensitive uptake. Paired-pulse stimulation studies indicate that the stimulation-induced enhancement of 86Rb+ uptake is due to membrane depolarizations, and hence related to the rate of Na+ influx. 3. Alterations in the extracellular Ca2+ concentration failed to affect the 86Rb+ uptake indicating that the force of contraction does not influence 86Rb+ uptake. 4. Reduced Na+ influx by low extracellular Na+ concentration decreased 86Rb+ uptake, and an increased Na+ influx by a Na+-specific ionophore, monensin, enhanced 86Rb+ uptake in quiescent atria. 5. Grayanotoxins, agents that increase transmembrane Na+ influx, and high concentrations of monensin appear to have inhibitory effects on ouabain-sensitive 86Rb+ uptake in electrically stimulated and in quiescent atria. 6. Electrical stimulation or monensin enhanced ouabain binding to (Na+ + K+)-ATPase and also increased the potency of ouabain to inhibit 86Rb+ uptake indicating that the intracellular Na+ available to the Na+ pump is increased under these conditions. 7. The ouabain-sensitive 86Rb+ uptake in electrically stimulated atria was less sensitive to alterations in the extracellular Na+ concentration, temperature and monensin than that in quiescent atria. 8. These results indicate that the rate of Na+ influx is the primary determinant of ouabain-sensitive 86Rb+ uptake in isolated atria. Electrical stimulation most effectively increases the Na+ available to the Na+ pump system. The ouabain-sensitive 86Rb+ uptake by atrial preparations under electrical stimulation at a relatively high frequency seems to represent the maximal capacity of the Na+ pump in this tissue.


The calcium signal and phosphatidylinositol breakdown in 2H3 cells.
Phosphatidylinositol (PI) and its phosphorylated derivatives are rapidly broken down in 2H3 cells stimulated with antigen, with a time course which coincides with the generation of the Ca signal. Stimulated PI breakdown is absolutely dependent on Ca2+ in the medium with a concentration dependence similar to that of the Ca signal and histamine release described in the preceding paper. However, PI breakdown does not depend on the rise in free cytoplasmic Ca2+ concentration in stimulated cells over the range 100 nM to 1 microM. Thus, stimulation by the ionophore A23187 causes only a small increase in PI breakdown and the Ca signal stimulated by antigen can be selectively blocked with appropriate concentrations of Zn2+ (100 microM) or La3+ (10-100 microM) which have small or negligible effects on stimulated PI breakdown. Both PI breakdown and the Ca signal appear to depend on a common external Ca2+ site (or sites) with Km approximately equal to 0.4 mM, and the data are consistent with either independent activation of PI phosphodiesterase and the Ca signal after antigenic stimulation, or with PI breakdown as a component of the mechanism by which the Ca signal is generated.


Solid phase organic synthesis of polyamine derivatives and initial biological evaluation of their antitumoral activity.
A series of N1-monosubstituted putrescine and spermine derivatives was synthesised using a solid phase methodology. We evaluated their cytotoxicity, calmodulin antagonism and polyamine uptake inhibition, pharmacological properties shared by some antitumoral agents.


Callosal anatomical and effective connectivity between primary motor cortices predicts visually cued bimanual temporal coordination performance.
Default in-phase coupling of hand movements needs to be suppressed when temporal coordination is required for out-of-phase bimanual movements. There is lack of knowledge on how the brain overrides these default in-phase movements to enable a required interval of activity between hands. We used a visually cued bimanual temporal coordination (vc-BTC) paradigm with a constant rhythmical time base of 1 s, to test the accuracy of in-phase and out-of-phase (0.1, 0.2,…,0.9) finger tapping. We hypothesized that (1) stronger anatomical and effective interhemispheric connectivity between the hand areas of the primary motor cortex (M1HAND) predict higher temporal offsets between hands in the out-of-phase conditions of the vc-BTC; (2) patients with relapsing-remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) have reduced interhemispheric connectivity and altered between-hand coupling. Anatomical connectivity was determined by fractional anisotropy of callosal hand motor fibers (FA-hCMF). Effective connectivity was probed by short interval interhemispheric inhibition (S-IHI) using paired-coil transcranial magnetic stimulation (TMS). In healthy subjects, higher FA-hCMF and S-IHI correlated with higher temporal offsets between hands in the out-of-phase conditions of the tapping test. FA-hCMF was reduced in patients with RRMS but not in CIS, while S-IHI was reduced in both patient groups. These abnormalities were associated with smaller temporal offsets between hands leading to less deviation from the required phasing in the out-of-phase tapping conditions. Findings provide multiple levels of evidence that callosal anatomical and effective connectivity between the hand areas of the motor cortices play important roles in visually cued bimanual temporal coordination performance.


[Validity of axis III "Conflicts" of Operationalized Psychodynamic Diagnostics (OPD-1)--empirical results and conclusions for OPD-2].
Using specific psychometric instruments, we investigate criteria-related validity of axis III ("conflicts") of OPD-1 by a priori formulated hypotheses concerning the relations to the main conflict/mode. A consecutive sample of 105 psychotherapy inpatients was examined using self-assessment scales (Inventory of Interpersonal Problems; Rosenberg Self-Esteem Scale, Test of Self-Conscious Affect; Toronto Alexithymia-Scale; Frankfurt Self Concept Scales) and videotaped OPD research interviews in the first week after admission to the hospital. Two OPD-certified raters first rated the interviews independently, then in a consensus rating. Due to the different frequency of the main conflict and mode, evaluation of 4 of 7 conflicts was possible. The a priori hypotheses could be confirmed for the conflicts Dependence versus Autonomy (both modes), Submission versus Control (active mode), Desire for Care versus Autarchy (active mode), and Self-Value (passive mode). Confirmation of the a priori hypotheses indicates validity of axis III (Conflicts) of OPD. We discuss the small numbers of some conflicts, the comparison of expert rating OPD with self-assessment and the meaning of the results for OPD-2.


Immune checkpoint inhibitors: a promising anticancer therapy.
Immune checkpoint inhibitors (ICIs) are revolutionizing the treatment of many cancers and have demonstrated their potential as 'cancer terminators'. However, ICI treatment also has constraints, such as its immune-related adverse events (irAEs) and therapeutic resistance. These drawbacks are gradually being overcome through better knowledge of the immune system, history of disease, duration of treatment, combinational drug regimes, adequate biomarkers, and effective patient response monitoring. In this review, we discuss the present ICI therapy landscape and its therapeutic outcomes for various diseases. We also highlight biomarkers related to the ICI response.


Studies on bovine brain membrane-bound neuraminidase (sialidase).
1) Lipophilic ganglioside GD1a (IV3NeuAc, II3NeuAc-GgOse4-Cer) is taken up by the cell membranes and hydrolyzed faster by membrane-bound neuraminidase than are water soluble substrates of the enzyme. 2) The enzymic breakdown of ganglioside GD1a is enhanced by general anesthetics whereas the degradation of the hydrophilic substrate sialyllactitol is reduced by these same agents. 3) General anesthetics lower the microviscosity of membranes as indicated by studies of fluorescence depolarisation with the indicator 1,6-diphenylhexatrien. Decreased microviscosity can result in a higher lateral diffusion of ganglioside GD1a, increasing its interaction with membrane-bound neuraminidase. 4) In vitro studies indicate that the activity of membrane-bound neuraminidase on gangliosides of brain membranes is regulated by the viscosity of these membranes and their monosialoganglioside content.


PDMS bonding to a bio-friendly photoresist via self-polymerized poly(dopamine) adhesive for complex protein micropatterning inside microfluidic channels.
Protein micropatterned surfaces integrated with microfluidics are useful in numerous bioanalytical and biological applications. In this study, we demonstrated the fabrication of complex protein micropatterned surfaces within poly(dimethylsiloxane) (PDMS) microfluidic channels by attaching the PDMS channels to bio-friendly photoresist films and subsequently performing microscope projection photolithography (MPP). A muscle-inspired poly(dopamine) (PDA) coating was employed to mediate the bonding between the PDMS and the bio-friendly photoresist poly(2,2-dimethoxy nitrobenzyl methacrylate-r-methyl methacrylate-r-poly(ethylene glycol) methacrylate) (PDMP). By adjusting the dip-coating time for the PDA coating, we could successfully introduce sufficient amounts of functional groups on the PDMP surfaces to mediate strong bonding between the PDMS channels and the PDA-coated PDMP thin films with minimal alteration of the surface properties of the PDMP thin films that are critical for protein micropatterning. Using this novel bonding strategy, we successfully fabricated multiple protein micropatterns and gradient micropatterns of proteins within microfluidic channels. The technique developed in this study will be useful for the fabrication of complex biochips for multiplex bioassays and fundamental cell biological studies.


Telephone-based aftercare groups for family carers of people with dementia - results of a mixed-methods process evaluation of a randomized controlled trial.
Caring for a relative with dementia can be demanding and time-consuming. It is not uncommon for them to be overburdened and overworked, which can lead to symptoms of depression or anxiety disorders in 2/3 of cases. One possibility for treating family carers who have these issues is special medical rehabilitation (rehab). However, studies have shown that while such rehab is effective, it is not sustainable. To increase the sustainability of rehab for this target group, structured telephone-based aftercare groups were implemented in the present study. A process evaluation was conducted focusing on the acceptability of the aftercare programme and its perceived benefits by the participating family carers and group moderators. The process evaluation was embedded in a longitudinal randomized controlled trial and followed a mixed methods approach. Quantitative process data were collected using protocols and structured brief evaluations regarding the telephone-based aftercare groups. To assess the acceptability of the aftercare groups as well as their subjective evaluation by the participants, qualitative process data were collected through two longitudinal telephone-based interviews with a subsample of family carers as well as a focus group interview with the group moderators. Telephone-based aftercare groups provide acceptable and supportive experiences, and they are shown to be practicable. The content structure and the procedure of the group sessions could be easily implemented in everyday life after inpatient rehab. The topics addressed with each patient were met with a consistently positive response. Learning from the other group members and sharing a bond based on the experience of caring for a relative with dementia were evaluated as positive outcomes in the group. The universality of suffering as a central effective factor of group psychotherapy also played a decisive role in this telephone-based support group format for a shared bonding and strengthening experience in the groups and thus for their effectiveness. Telephone-based aftercare groups for family carers of people with dementia are a useful and acceptable tool in the context of rehab aftercare. This location-independent aftercare programme could be adapted for other indications, focuses or topics in everyday care. German Clinical Trials Register: DRKS00013736, 14/05/2018.


Renal effects of etoricoxib and comparator nonsteroidal anti-inflammatory drugs in controlled clinical trials.
Based on the experience with selective cyclooxygenase (COX)-2 inhibitors, including rofecoxib, valdecoxib, and celecoxib, it was anticipated that etoricoxib, a new selective COX-2 inhibitor, would display mechanism-based, dose-dependent renal adverse effects (AEs) similar to those observed with nonselective non-steroidal anti-inflammatory drugs (NSAIDs) in long-term treatment. The present analysis examined pooled safety data from the etoricoxib clinical development program with the aim of comparing the renal AE profiles of etoricoxib 60, 90, and 120 mg/d with those of approved therapeutic dosages of the comparator nonselective NSAIDs, naproxen 1000 mg/d and ibuprofen 2400 mg/d, and with that of placebo. The etoricoxib program database included data from 8 placebo-controlled Phase III studies of osteoarthritis, rheumatoid arthritis, and chronic low back pain. As part of the program-wide assessment of etoricoxib, the investigator-reported incidence of and discontinuations due to renal AEs, including hypertension, lower-extremity edema (LEE), elevated serum creatinine concentration (SCC), and congestive heart failure (CHF) were examined. Data from 4770 patients were included in the analysis. Most patients were women (69.0%-80.3%), and most were white (68.0%-83.3%). The mean (SD) age at baseline ranged from 53.6 (12.1) to 62.2 (8.4) years. Overall, the incidence of renal AEs was low and generally similar between the active-treatment groups. In the placebo; etoricoxib 60-, 90-, and 120-mg; naproxen, and ibuprofen groups, the incidences of hypertension were 2.0%, 4.0%, 3.4%, 4.7%, 2.9%, and 6.6%, respectively, and the incidences of LEE were 1.9%, 3.2%, 1.5%, 1.3%, 2.3%, and 1.8%, respectively. The only significant difference found was the incidence of hypertension with etoricoxib 90 mg/d versus that with placebo (P=0.001); however, the rates of hypertension observed with etoricoxib at any dosage were not clinically meaningfully different versus comparator NSAIDs. Also, LEE was rarely of clinical significance with etoricoxib or comparator NSAIDs; related discontinuations were infrequent in all treatment groups. In addition, the incidences of elevated SCC and CHF were low among active-treatment groups (0.0% to 0.8% and 0.0% to 0.2%, respectively). Based on this combined data review, the risks for renal AEs (i.e., hypertension, LEE, elevated SCC changes, and CHF) with etoricoxib 60, 90, and 120 mg/d were low, with a shallow dose response, and were generally similar to those found with the comparator NSAIDs naproxen 1000 mg/d and ibuprofen 2400 mg/d.


Subcutaneous Splenosis Presenting 37 years post-traumatic splenectomy; A Case Report.
The term splenosis refers to autotransplantation of splenic tissue in ectopic sites. Ectopic splenic tissue may be found in the liver, thorax, pelvis and subcutaneous tissues following traumatic splenectomy. Although clinically insignificant, local symptoms such as abdominal pain may arise. In this paper we report a case of subcutaneous splenosis presenting 37 years post-traumatic splenectomy. A 40-year-old medically free lady presented to our institution with a surgical history of post-traumatic splenectomy at the age of three and two cesarean sections. She complained for nonpainful right upper quadrant soft mass that has been stable in size over the years. Her laboratory results, including peripheral blood smear, were all within normal limits and no asplenic changes were detected. SPECT scan confirmed extraperitoneal splenosis in right upper quadrant. Splenosis is an acquired form of ectopic splenic tissue that is defined as an auto-transplantation of a viable splenic tissue. It commonly occurs after traumatic rupture of the spleen.5 Splenosis has been widely reported around the world with an incidence of 16-67% after traumatic splenic rupture or splenectomy. Subcutaneous splenosis is an extremely rare condition, mostly observed in abdominal surgical scars. It is believed to follow laparotomy for splenectomy where splenic cells auto-implant or spread hematogenously at different locations. Subcutaneous splenosis is a rare consequence of post-traumatic splenectomy that can manifest itself up to three decades after. Although concerning to the patient and alarming to the surgeon as it may resemble more serious entities such as abdominal wall sarcoma, surgical removal of asymptomatic splenosis is subject to the location of mass and patients' wishes.


Is mastectomy undertreatment for low-risk breast cancers eligible for breast-conserving therapy?
Biomarkers are routinely used to predict responses to systemic therapies, but their utility for predicting responses to local therapy for breast cancer is not known. This study determined whether biomarkers could predict responses to breast-conserving therapy (BCT) and mastectomy. A review of the Surveillance, Epidemiology, and End Results database identified women diagnosed with early-stage invasive ductal breast cancer and treated with BCT or mastectomy from 1998 to 2008. The estrogen receptor (ER) status and the histologic grade were used to construct 3 biomarker profiles: low risk (ER-positive, low/intermediate grade), intermediate risk (ER-positive, high grade), and high risk (ER-negative, any grade). The primary measured outcome was disease-specific survival (DSS). BCT and mastectomy were performed in 114,486 patients (59.2%) and 79,035 patients (40.8%), respectively. There were 122,420 low-risk patients (63.3%), 34,341 intermediate-risk patients (17.7%), and 36,760 high-risk patients (19.0%). Multivariate analyses were performed separately for patients with low-, intermediate-, and high-risk tumors. The adjusted hazard ratios for DSS for patients who underwent mastectomy versus BCT for low-, intermediate-, and high-risk tumors were 1.66 (95% confidence interval [CI], 1.54-1.79; P < .001), 1.40 (95% CI, 1.29-1.53; P < .001), and 1.27 (95% CI, 1.19-1.35; P < .001), respectively. Patients with ER-positive, low-grade breast cancers who underwent mastectomy had a 66% increase in disease-specific mortality versus those who underwent BCT. Biomarker profiles defined by the ER status and grade may improve the selection of local therapy for breast cancer.


Rabbit kidney function in vitro: the effect of colloids, energy substrate, a vasodilator, perfusion pressure, and bovine serum albumin.
An in vitro perfusion system at 37 degrees C for the assessment of rabbit kidney function is described. The purpose of this assay system is to evaluate the effects of cryobiological manipulation on kidney function. The effect of the colloids dextran (MW = 70,000, 80,000, and 180,000) in the perfusate at 110 mm Hg were compared to a reduced perfusion pressure, colloid-free perfusate. Better function was obtained at lower perfusion pressure with the colloid-free perfusate. Less damage was noted histologically on light and electron microscopy. Investigation of energy substrates on rabbit kidney function demonstrated that butyrate, or lactate, in addition to glucose resulted in increased sodium and glucose reabsorption over glucose alone. Substrate-free perfused kidneys exhibited depressed Na transport. Lactate, and to some extent butyrate, decreased net glucose utilization. An alpha-adrenergic blocking agent, isoxsuprine, in the initial flush solution did not appear to be beneficial. An increase of perfusion pressure from 50 to 75 mm Hg resulted in an increase in GFR. Tubular function was enhanced by inclusion of small amounts of BSA in the perfusate.


Vocal Expression of Affective States in Spontaneous Laughter reveals the Bright and the Dark Side of Laughter.
It has been shown that the acoustical signal of posed laughter can convey affective information to the listener. However, because posed and spontaneous laughter differ in a number of significant aspects, it is unclear whether affective communication generalises to spontaneous laughter. To answer this question, we created a stimulus set of 381 spontaneous laughter audio recordings, produced by 51 different speakers, resembling different types of laughter. In Experiment 1, 159 participants were presented with these audio recordings without any further information about the situational context of the speakers and asked to classify the laughter sounds. Results showed that joyful, tickling, and schadenfreude laughter could be classified significantly above chance level. In Experiment 2, 209 participants were presented with a subset of 121 laughter recordings correctly classified in Experiment 1 and asked to rate the laughter according to four emotional dimensions, i.e., arousal, dominance, sender's valence, and receiver-directed valence. Results showed that laughter types differed significantly in their ratings on all dimensions. Joyful laughter and tickling laughter both showed a positive sender's valence and receiver-directed valence, whereby tickling laughter had a particularly high arousal. Schadenfreude had a negative receiver-directed valence and a high dominance, thus providing empirical evidence for the existence of a dark side in spontaneous laughter. The present results suggest that with the evolution of human social communication laughter diversified from the former play signal of non-human primates to a much more fine-grained signal that can serve a multitude of social functions in order to regulate group structure and hierarchy.


Cytosolic phospholipase A2α sustains pAKT, pERK and AR levels in PTEN-null/mutated prostate cancer cells.
Constitutive phosphorylation of protein kinase B (AKT) is a common feature of cancer caused by genetic alteration in the phosphatase and tensin homolog (PTEN) gene and is associated with poor prognosis. This study determined the role of cytosolic phospholipase A2α (cPLA2α) in AKT, extracellular signal-regulated kinase (ERK) and androgen receptor (AR) signaling in PTEN-null/mutated prostate cancer cells. Doxycycline (Dox)-induced expression of cPLA2α led to an increase in pAKT, pGSK3β and cyclin D1 levels in LNCaP cells that possess a PTEN frame-shift mutation. In contrast, silencing cPLA2α expression with siRNA decreased pAKT, pGSK3β and cyclin D1 levels in both PC-3 (PTEN deletion) and LNCaP cells. Silencing of cPLA2α decreased pERK and AR protein levels. The inhibitory effect of cPLA2α siRNA on pAKT and AR protein levels was reduced by the addition of arachidonic acid (AA), whereas the stimulatory effect of AA on pAKT, pERK and AR levels was decreased by an inhibitor of 5-hydroxyeicosatetraenoic acid production. Pharmacological blockade of cPLA2α with Efipladib reduced pAKT and AR levels with a concomitant inhibition of PC-3 and LNCaP cell proliferation. These results demonstrate an important role for cPLA2α in sustaining AKT, ERK and AR signaling in PTEN-null/mutated prostate cancer cells and provide a potential molecular target for treating prostate cancer.


Endophthalmitis after pars plana vitrectomy.
In three cases of bacterial endophthalmitis following pars plana vitrectomy the important diagnostic findings included increased orbital pain, decreased visual acuity, and the presence of a hypopyon. Despite agressive antibiotic therapy, all three eyes became blind, and two progressed rapidly to phthisis.


High throughput virtual screening and molecular dynamics simulation analysis of phytomolecules against BfmR of Acinetobacter baumannii: anti-virulent drug development campaign.
Acinetobacter baumannii is a notorious multidrug resistant bacterium responsible for several hospital acquired infections assisted by its capacity to develop biofilms. A. baumannii BfmR (RstA), a response regulator from the BfmR/S two-component signal transduction system, is the major controller of A. baumannii biofilm development and formation. As a result, BfmR represents a novel target for anti-biofilm treatment against A. baumannii. The discovery of the high-resolution crystal structure of BfmR provides a good chance for computational screening of its probable inhibitors. Therefore, in this study we aim to search new, less toxic, and natural BfmR inhibitors from 8450 phytomolecules available in the Indian Medicinal Plants, Phytochemistry and Therapeutic (IMPPAT) database by analyzing molecular docking against BfmR (PDB ID: 6BR7). Out of these 8450 phytomolecules 6742 molecules were successfully docked with BfmR with the docking score range -6.305 kcal/mol to +5.120 kcal/mol. Structure based-molecular docking (SB-MD) and ADMET (absorption, distribution, metabolism, excretion, & toxicity) profile examination revealed that Norepinephrine, Australine, Calystegine B3, 7,7 A-Diepialexine, and Alpha-Methylnoradrenaline phytocompounds strongly binds to the active site residues of BfmR. Furthermore, molecular dynamics simulation (MDS) studies for 100 ns and the binding free energy (MM/GBSA) analysis elucidated the binding mechanism of Calystegine B3, 7,7 A-Diepialexine, and Alpha-Methylnoradrenaline to BfmR. In summary, these phytocompounds seems to have the promising molecules against BfmR, and thus necessitates further verification by both in vitro and in vivo experiments. HighlightsBfmR plays a key role in biofilm development and exopolysaccharide (EPS) synthesis in A. baumannii.Computational approach to search for promising BfmR inhibitors from IMPAAT database.The lead phytomolecules such as Calystegine B3, 7,7 A-Diepialexine, and Alpha-Methylnoradrenaline displayed significant binding with BfmR active site.The outcome of BfmR binding phytomolecules has broadened the scope of hit molecules validation.Communicated by Ramaswamy H. Sarma.


REV1 genetic variants associated with the risk of cervical carcinoma.
To explore the REV1 genetic variants effect the risk of cervical carcinoma. Total 543 cases, including 282 carcinoma and 261 CIN, and 480 normal controls were performed. Two single nucleotide polymorphisms (SNPs) (REV1 Phe257Ser and REV1 Asn373Ser) were genotyped by PCR-squencing, and analysis the correlation to clinical character including HPV infection. Compared with the REV1 Phe257Ser, women carrying Ser257Ser and Phe257Ser genotypes had a significantly decreased the risk for cervical carcinoma or cervical squamous cell carcinoma. On contrary, homozygous Ser373Ser increased the risk for carcinoma. In addition, we found that the association of Phe257Ser and Asn373Ser with the risk for cervical carcinoma was specific to squamous cell carcinomas and not relevant for adenocarcinoma. Our results suggest that women carry Phe257Ser variant genotype decrease the risk for cervical carcinoma, more in women that have high-risk sexual reproductive histories, when women who carried Asn373Ser variant genotype and had high-risk sexual and reproductive histories had a significantly elevated risk for cervical carcinoma. Our results support Phe257Ser and Ser257Ser genotypes are associated with a decreased risk for cervical carcinoma, while Asn373Ser and Ser373Ser genotypes increased the risk. In addition, the effects were more significant in the groups with high-risk sexual and reproductive histories.


The human plasma proteome: analysis of Chinese serum using shotgun strategy.
We have investigated the serum proteome of Han-nationality Chinese by using shotgun strategy. A complete proteomics analysis was performed on two reference specimens from a total of 20 healthy donors, in which each sample was made from ten-pooled male or female serum, respectively. The methodology used encompassed (1) removal of six high-abundant proteins; (2) tryptic digestion of low- and high-abundant proteins of serum; (3) separation of peptide mixture by RP-HPLC followed by ESI-MS/MS identification. A total of 944 nonredundant proteins were identified under a stringent filter condition (X(corr) > or = 1.9, > or = 2.2, and > or = 3.75, < or = C(n) > or = 0.1, and R(sp) > or = 4.0) in both pooled male and female samples, in which 594 and 622 entire proteins were found, respectively. Compared with the total 3020 protein identifications confirmed by more than one laboratory or more than one specimen in HUPO Plasma Proteome Project (PPP) participating laboratories recently, 206 proteins were identified with at least two distinct peptides per protein and 185 proteins were considered as high-confidence identification. Moreover, some lower abundance serum proteins (ng/mL range) were detected, such as complement C5 and CA125, routinely used as an ovarian cancer marker in plasma and serum. The resulting nonredundant list of serum proteins would add significant information to the knowledge base of human plasma proteome and facilitate disease markers discovery.


The role of doublesex in the evolution of exaggerated horns in the Japanese rhinoceros beetle.
Male-specific exaggerated horns are an evolutionary novelty and have diverged rapidly via intrasexual selection. Here, we investigated the function of the conserved sex-determination gene doublesex (dsx) in the Japanese rhinoceros beetle (Trypoxylus dichotomus) using RNA interference (RNAi). Our results show that the sex-specific T. dichotomus dsx isoforms have an antagonistic function for head horn formation and only the male isoform has a role for thoracic horn formation. These results indicate that the novel sex-specific regulation of dsx during horn morphogenesis might have been the key evolutionary developmental event at the transition from sexually monomorphic to sexually dimorphic horns.


Determination of sparsomycin in plasma and urine of the dog by means of reversed-phase high-performance liquid chromatography and first pharmacokinetic results.
Sparsomycin--an antibiotic with marked cytostatic activity--was the subject of a clinical Phase I study in 1964. The structure of sparsomycin was elucidated in 1970 and its first total synthesis was reported in 1981. Here we describe a sensitive high-performance liquid chromatographic method of determination. The detection limit was found to be 10 ng/ml of plasma and 20 ng/ml of urine. With this procedure sparsomycin and isosparsomycin can readily be separated. In addition, we performed a first pharmacokinetic study in the dog and found a half-life time t1/2 beta of 1.1 h. Only 25% of the administered dose could be recovered in the urine as sparsomycin. We consider that by now many prerequisites for further preclinical studies have been achieved, and the results of these studies will determine whether sparsomycin deserves reintroduction into clinical use.


[Application of molecular chaperones to soluble expression of e23sFv/His fusion proteins].
To explore the feasibility of applying molecular chaperones to the soluble expression of e23sFv/His fusion proteins. The molecular chaperone plasmid pGro7 or pKJE7 was transformed into BL21 (DE3) competent cells together with the prokaryotic expression vector harboring His-tagged e23sFv. The soluble expression of e23sFv/His proteins was induced at 16 °C. The yield and antigen-binding activity of the soluble products were compared with those of the insoluble products conventionally purified from inclusion bodies. Both the overall yield and the purification ratio of soluble e23sFv/His proteins were relatively lower. The binding affinity of the soluble products to immobilized HER2 was not superior to that of the insoluble products from inclusion bodies. The molecular chaperone plasmids pGro7 and pKJE7 partially facilitate the soluble expression of e23sFv/His proteins, but both the yield and the purification ratio are still limited.


Long and short echo time proton magnetic resonance spectroscopic imaging of the healthy aging brain.
To investigate the relationship between subject age and white matter brain metabolite concentrations and R(2) relaxation rates in a cross-sectional study of human brain. Long- and short-echo proton spectroscopic imaging were used to investigate concentrations and R2 relaxation rates of N-acetyl aspartate (NAA) + N-acetyl aspartyl glutamate (NAAG), choline (Cho), creatine (Cr), and myoinositol (mI) in the white matter of the centrum semiovale of 106 healthy volunteers aged 50-90 years; usable data were obtained from 79 subjects. A major aim was to identify which parameters were most sensitive to changes with age. Spectra were analyzed using the LCModel method. The apparent R2 of NAA and the LCModel concentration of Cr at short echo time were significantly correlated with age after multiplicity correction. Large lipid resonances were observed in the brain midline of some subjects, the incidence increasing significantly with age. We believe this to result from lipid deposits in the falx cerebri. Since only short-echo spectroscopy showed a robust relationship between Cr and subject age, and detects more metabolites than long echo time, we conclude that short-echo is superior to long-echo for future aging studies. Future studies could usefully determine whether the Cr-age relationship is due to changes in concentration, T1, or both.


Large Regenerative Nodules and Focal Nodular Hyperplasia-Like Lesions: Definition, Pathogenesis, and Imaging Findings.
Focal nodular hyperplasia-like (FNH-like) nodules are hepatocellular lesions with similar radiologic and pathologic features as typical FNH but occur within an abnormal liver. They arise due to alteration of hepatic vasculature at both the microscopic and macroscopic levels. Although these nodules are not thought to have malignant potential, their imaging features overlap with premalignant and malignant lesions including hepatocellular carcinoma (HCC) and arise in patients who may be at risk for HCC, posing a diagnostic and management dilemma. It is important to consider these benign entities when reviewing liver imaging of patients at risk for HCC to reduce unnecessary interventions.


Deoxynivalenol loads in matched pair wheat samples in Belgium: comparison of ELISA VERATOX kit against liquid chromatography.
A comparison of matched pairs deoxynivalenol (DON) loads in wheat samples via VERATOX for DON 5/5 performed by two laboratories against two liquid chromatographic methods (LC-MS/MS and HPLC-UV) used by two other laboratories was carried out using biometrical and sum of ranking differences (SRD) procedures. The Lin's Concordance correlation coefficients, the average discrepancies, the limits of agreement and the SRD between ELISA and reference values showed good overall agreement between VERATOX for DON 5/5 and reference methods for the two datasets. The VERATOX kits are valuable for quantitative screening and even for an initial exposure assessment in situations when there are practical or economical reasons not to use sophisticated methods such as HPLC or GC methods (with or without MS). However, networking of laboratories using this rapid method and laboratories with reference analytical methods should be encouraged.


Distinct kinetic mechanisms of the two classes of Aminoacyl-tRNA synthetases.
Aminoacyl-tRNA synthetases are divided into two classes based on both functional and structural criteria. Distinctions between the classes have heretofore been based on general features, such as the position of aminoacylation on the 3'-terminal tRNA ribose, and the topology and tRNA-binding orientation of the active-site protein fold. Here we show instead that transient burst kinetics provides a distinct mechanistic signature dividing the two classes of tRNA synthetases, and that this distinction has significant downstream effects on protein synthesis. Steady-state and transient kinetic analyses of class I CysRS and ValRS, and class II AlaRS and ProRS, reveal that class I tRNA synthetases are rate-limited by release of aminoacyl-tRNA, while class II synthetases are limited by a step prior to aminoacyl transfer. The tight aminoacyl-tRNA product binding by class I enzymes correlates with the ability of EF-Tu to form a ternary complex with class I but not class II synthetases, and the further capacity of this protein to enhance the rate of aminoacylation by class I synthetases. These results emphasize that the distinct mechanistic signatures of class I versus class II tRNA synthetases ensure rapid turnover of aminoacyl-tRNAs during protein synthesis.


A case of a large seminal vesicle cyst associated with ipsilateral renal agenesis.
The diagnosis of seminal vesicle cysts is often delayed or missed as a result of both their rarity and wide spectrum of potentially confusing clinical and imaging findings they can produce. Although rare, they should be considered in men, especially with a history of renal agenesis, who exhibit o inexplicable irritable voiding symptoms, perineal discomfort or other genitourinary complaint of unclear etiology. We introduce such a case, and discuss its symptoms, radiological findings and its therapeutic approach.


Characterization of ethyl (3-quinuclidinyl) acetate (EQA) as a ligand for acetylcholine receptors.
Recent studies suggest that neuronal nicotinic acetylcholine receptors (nAChRs) may play a role in several CNS disorders and that subtype selective nicotinic ligands may be useful in the treatment of these disorders. Ethyl (3-quinuclidinyl)acetate (EQA) is a bulky, reverse-ester analog of ACh, that produces signs of cholinergic stimulation that may be nicotinic in origin The objective of the present study was to further evaluate EQA as a potential cholinergic ligand. Behavioral studies, smooth muscle assays, and radioligand binding assays were performed on this novel ligand. The effects of EQA on blood pressure and acetylcholinesterase activity were also evaluated. The results of the study suggest that EQA is an agonist at peripheral nicotinic acetylcholine receptors and may have antagonist properties at central nicotinic receptors.


RNA uridylyltransferases.
The terminal RNA uridylyltransferases (TUTases) catalyze transfer of UMP residues to the 3' hydroxyl group of RNA. These activities are widespread among eukaryotes and appear to be involved in a variety of RNA-processing pathways. Recent studies of RNA editing in trypanosomatids have provided the first insights into the biological functions of RNA uridylyltransferases, which had eluded biochemical identification despite 30-year-old evidence of such activities in mammals and plants. Comparative sequence analysis of trypanosomal TUTases and their homologs revealed by large-scale genomic projects demonstrates a significant level of biochemical and structural diversity between putative uridylyltransferases. The conserved catalytic domain has acquired additional protein modules and appears to have adapted to perform functionally distinct tasks of guided U-insertion into mRNA and constrained addition of an oligo[U] tail to guide RNAs. Here I discuss the current knowledge of this novel enzyme family and possible roles of RNA uridylylation in the regulation of gene expression.


[Behavior of the bi-parietal diameter (BPD) and antero-posterior diameter of the abdomen (APDA) in insufficient intrauterine development of the fetus: preliminary notes].
Considering the PIFG ultrasonic diagnosis limitations bu the only Biparietal Diameter (BPD) estimation, the autors test the possibilities of a new technique: the serial measurement of Antero-Posterior Diameter of Abdomen (APAD) and especially the head/abdomen diameters ratio. The preliminary data are enough confortable allowing us to improve considerably the success in PIFG diagnosis (44,44% to 80%).


Responses of the intestine of the giant African snail (Achatina fulica) to acetylcholine in Meng's solution with low sodium, potassium and calcium ions.
Decreasing the concentration of sodium in Meng's solution produced a non-parallel shift of the dose-response of acetylcholine on the intestine of the Giant African Snail Achatina fulica. This decrease in sodium decreases the sensitivity of the tissue to acetylcholine and sensitivity was not restored with several washings. The response to decrease calcium is very similar to that of sodium. In the case of potassium however 10% K+ produced less depression in sensitivity than 25% which even caused less depression of sensitivity compared with 50% potassium. The results show an abundance of spare receptors.


Polysaccharide degradation systems of the saprophytic bacterium Cellvibrio japonicus.
Study of recalcitrant polysaccharide degradation by bacterial systems is critical for understanding biological processes such as global carbon cycling, nutritional contributions of the human gut microbiome, and the production of renewable fuels and chemicals. One bacterium that has a robust ability to degrade polysaccharides is the Gram-negative saprophyte Cellvibrio japonicus. A bacterium with a circuitous history, C. japonicus underwent several taxonomy changes from an initially described Pseudomonas sp. Most of the enzymes described in the pre-genomics era have also been renamed. This review aims to consolidate the biochemical, structural, and genetic data published on C. japonicus and its remarkable ability to degrade cellulose, xylan, and pectin substrates. Initially, C. japonicus carbohydrate-active enzymes were studied biochemically and structurally for their novel polysaccharide binding and degradation characteristics, while more recent systems biology approaches have begun to unravel the complex regulation required for lignocellulose degradation in an environmental context. Also included is a discussion for the future of C. japonicus as a model system, with emphasis on current areas unexplored in terms of polysaccharide degradation and emerging directions for C. japonicus in both environmental and biotechnological applications.


Camel milk: a possible alternative for children with cow's milk allergy?
Cow's milk protein allergy (CwMPA) is the most common food allergy during early childhood and its therapy consists in the elimination of cow's milk proteins (CwMP) from the diet and the introduction of alternative formulas. Evidence about clinical use of camel's milk (CM) in CwMPA in children is scarce. The aim of this study was to determine the entity of cross-sensitization between CM and CwM in children with CwMPA. This prospective study was performed in children affected by CwMPA. We evaluated skin prick tests (SPT) for CwM, CwMP (alpha-lactalbumin [ALA], beta-lactoglobulin [BLG] and casein [CAS]) and CM and serum levels of CwM, ALA, BLG, CAS-sIgE. Sixty-seven children with CwMPA were included in this study: twenty-one resulted SPT+ to CM. Mean wheal diameters towards raw CwM, ALA, BLG and CAS resulted significantly larger in the CM SPT+ group than in the CM SPT- group (P<0.02). Likewise, mean IgE titers against CwM, ALA and CAS were significantly higher in the CM SPT+ group than in the CM SPT-group (P<0.01). The mean wheal diameter towards raw CwM was significantly larger than that towards CM (P<0.0001). This study confirms the presence of cross-sensitization between CwM and CM that remains lower if compared to other mammalian milks. Small wheals at the SPT towards CwM antigens together with low IgE titers against them could work as predictors in selecting patients that are expected to have negative CM SPT and then could be fed with CM with lower risks of allergic reactions.


Coenzyme Q system in the classification of some ascosporogenous yeast genera in the families Saccharomycetaceae and Spermophthoraceae.
The Co-Q systems of 11 strains representing the genera Schwanniomyces, Lodderomyces, Lipomyces, Nematospora and Metschnikowia were determined. All the genera were characterized by the Q-9 system except for the genus Nematospora with needle-shaped ascospores. The only species, Nem. coryli, was found to have the Q-6 system. These results are discussed from the taxonomic point of view.