Vein of Galen aneurysmal malformations. Report of 36 cases managed between 1982 and 1988.
The authors report a series of 36 vein of Galen aneurysmal malformations (VGM) diagnosed in the paediatric (78%) and adult (22%) populations that were referred to them for therapeutic management between 1982 and 1988. The clinical signs leading to the diagnosis were variable: 36% of systemic manifestations, 22% of neurological symptoms, 17% of hydrocephaly and 11% of intracranial haemorrhage. 30 angioarchitectural analyses could be obtained and allowed to classify these VGMs into 5 different types: 44% parenchymatous AVMs, 20% mural AVFs, 30% choroidal arteriovenous fistulas, 3% dural AVFs, 7% vein of Galen varices. This series demonstrates that the paediatric population is most sensitive to shunt effect whatever its type. Systemic manifestations and hydrocephaly are the most common signs encountered in the newborn and infants; whereas neurological signs and symptoms and haemorrhage belong mostly to the adult symptomatology. Because of the poor outcome of VGMs, all authors believe that these malformations have to be treated aggressively. However, we found contra-indications to be represented by pretherapeutic demonstration of cerebral tissue damage, or uncontrollable systemic failure, thus treatment is indicated to compensate for cardiac failure previously responding (even partially) to medical treatment. Secondly, appearance of sub-cortical calcifications, resistance to medication or clinical deterioration will also lead to urgent treatment. The endovascular method represents at present the best treatment with an overall low mortality (13%) and a 0% technical morbidity in children compared to the surgical one of (91% mortality in newborns and 38% in infants). The results achieved by embolization in this series were as follows: 27% satisfactory results with complete or almost complete occlusion of AV Shunt, 53% significant clinical improvement, 7% of patients were unchanged. The authors believe fundamentally that these patients (specially those belonging to the paediatric population) have to be treated in a centre where a paediatric intensive care unit, neurological, neurosurgical and surgical neuro-angiographic departments coexist, in order to assure the best possible management of these children.


Massage parlors and their customers.
Journalistic and sociological studies of massage parlors and massage parlor customers do not serve the development of scientifically sound generalizations. They begin with the assumptions that massage parlors are brothels renamed and that the customers are problematic individuals seeking impersonal sexual exchanges. This standard view of the parlors and customers is here challenged and an alternative approach suggested. The results of an empirical examination of the customers of a West Coast massage parlor are summarized. Data were obtained by a massage parlor worker--an unnamed coauthor--who recorded information about every personal customer during her initial period of work. Both demographic and voluntaristic factors are specified. Included are ethnic origin and occupation, the proposition, the offer of financial reward, the sexual activity desired, and the sexual activity that resulted. A comparison of two views on the nature of the customer demonstrates the limitations the standard view imposes on the potential examination of massage parlors in general. Massage parlors are not brothels renamed and the massage parlor customers are not sex-seeking problematic individuals. Given the results of the empirical examination, the basic complexity of the parlors and their customers is seen as the key aspect on which scientifically sound generalization may be built.


A direct measure of pollinator effectiveness.
A direct measure of pollinator effectiveness, relying on seed set, is proposed, where: [Formula: see text] P i =mean number of seeds set/flower by a plant population receiving a single visit from species i Z=mean number of seeds set/flower by a population receiving no visitation.U=mean number of seeds set/flower by a population receiving unrestrained visitation.The utility and limitations of the proposed measure are discussed and exemplified with a population of Ipomoea trichocarpa (Convoculaceae).


Drug and alcohol use in emergency medicine residency: an impaired resident's perspective.
We share the personal experience of an impaired resident who successfully completed rehabilitation and is about to graduate from an emergency medicine program and perform a brief literature review on drug and alcohol abuse in emergency medicine residencies. Residents in general are less likely than their same-age peers to abuse drugs, but a significant minority starts using drugs during residency. Emergency medicine residents have higher rates of substance use than residents in other specialties and are more likely to report current use of cocaine and marijuana.


Isolation and identification of native yeasts from the spontaneous fermentation of grape musts.
Recently, there has been growing interest in the characterization of native yeasts for their use in production of wines with regional characteristics. This study aimed to investigate Saccharomyces and non-Saccharomyces yeasts present in the spontaneous fermentation of Tannat and Marselan grape musts collected from Concordia (Entre Ríos, Argentina) over 2019, 2020, and 2021 vintages. The evolution of these fermentative processes was carried out by measuring total soluble solids, total acidity, volatile acidity, pH, ethanol concentration, and total carbon content. Isolated Saccharomyces and non-Saccharomyces yeasts were identified based on colony morphology in WL medium, 5.8S-ITS-RFLP analysis, and 26S rDNA D1/D2 gene sequencing. Two hundred and ten yeast colonies were isolated and identified as Pichia kudriavzevii, Saccharomyces cerevisiae, Hanseniaspora uvarum, Metschnikowia pulcherrima, Candida albicans, Candida parapsilosis, Pichia occidentalis, Pichia bruneiensis, Hanseniaspora opuntiae, Issatchenkia terricola, and Hanseniaspora vineae. P. kudriavzevii isolated from all vintages was associated with the spontaneous fermentation of grape musts from the Concordia region.


COVID-19 patients require multi-disciplinary rehabilitation approaches to address persisting symptom profiles and restore pre-COVID quality of life.
Long-COVID diagnosis is prominent, and our attention must support those experiencing debilitating and long-standing symptoms. To establish patient pathways, we must consider the societal and economic impacts of sustained COVID-19. Accordingly, we sought to determine the pertinent areas impacting quality of life (QoL) following a COVID-19 infection. Three hundred and eighty-one participants completed a web-based survey (83% female, 17% male) consisting of 70 questions across 7 sections (demographics, COVID-19 symptoms; QoL; sleep quality; breathlessness; physical activity and mental health). Mean age, height, body mass and body mass index (BMI) were 42 ± 12 years, 167.6 ± 10.4 cm, 81.2 ± 22.2 kg, and 29.1 ± 8.4 kg.m2, respectively. Participant health was reduced because of COVID-19 symptoms ('Good health' to 'Poor health' [P < 0.001]). Survey respondents who work reported ongoing issues with performing moderate (83%) and vigorous (79%) work-related activities. COVID-19 patients report reduced capacity to participate in activities associated with daily life, including employment activities. Bespoke COVID-19 support pathways must consider multi-disciplinary approaches that address the holistic needs of patients to restore pre-pandemic quality of life and address experienced health and wellbeing challenges.Plain Language Summary: The long-term impact of long-COVID has a dramatic impact upon daily activities and lifestyle. The development of bespoke support pathways to support patients must address the physical and psychological considerations to adequately restore pre-COVID quality of life and address broader societal and economic implications, especially for those that are of working age.


Gut Microbiota and Chronic Constipation: A Review and Update.
Background: Chronic constipation, including functional constipation and constipation-type irritable bowel syndrome, is a prevalent, multifactorial gastrointestinal disorder, and its etiology and pathophysiology remain poorly understood. Recently studies using 16S rRNA-based microbiota profiling have demonstrated dysbiosis of gut microbiota in chronic constipation. Aims: To provide an overview of recent studies for microbiota in chronic constipation and treatments for chronic constipation using probiotics, prebiotics, synbiotics, antibiotics and fecal microbiota transplantation (FMT). Methods: PubMed searches were performed up to 1 August 2018 using keywords: "IBS," "IBS-C," "irritable bowel syndrome," "irritable bowel syndrome with constipation," "functional constipation," "chronic constipation" in combination with "gut microbiota," "dysbiosis," "gut microflora" for microbiota in chronic constipation, and in combination with "probiotics," "prebiotics," "synbiotics," "antibiotics," and "fecal microbiota transplantation." Results: The findings of gut microbiota in functional constipation are inconsistent, and currently no consensus exists. Although no clear consensus exists, compared with healthy subjects, IBS-C patients have a lower level of Actinobacteria, including Bifidobacteria, in their fecal samples and a higher level of Bacteroidetes in their mucosa. In most randomized controlled and parallel-group trials, probiotics, prebiotics, synbiotics, antibiotics, and FMT therapy for chronic constipation were effective with few side effects. However, there are many studies in a small number and the types of probiotics are different, it is difficult to evaluate the effect. Conclusions: Evidence indicates that dysbiosis of gut microbiota may contribute to functional constipation and constipation-type irritable bowel syndrome. Targeting treatments for the dysbiosis of constipation by probiotics, prebiotics, synbiotics, antibiotics, and FMT may be a new option, especially for refractory constipation to conventional therapies.


Hepatoprotective effect and its possible mechanism of Coptidis rhizoma aqueous extract on carbon tetrachloride-induced chronic liver hepatotoxicity in rats.
Coptidis rhizoma is traditionally used for heat-clearing and toxic-scavenging and it belongs to liver meridian in Chinese medicine practice. Clinically, Coptidis rhizoma can be used for hepatic and biliary disorders, yet details in the therapies of liver diseases and underlying mechanism(s) remain unclear. Our previous study demonstrated that Coptidis rhizoma aqueous extract (CRAE) against CCl(4)-induced acute liver damage was related to antioxidant property. In the present study, the protection of CRAE on chronic liver damage induced by carbon tetrachloride (CCl(4)) in rats and its related mechanism were explored. The CCl(4)-induced chronic liver damage model was established, and CRAE's protective effect was examined. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity, serum and liver superoxide dismutase (SOD) activity were then measured. The histological changes were observed under microscopy and then computed in numerical score. The normal or damaged cells were isolated and related signaling pathway was evaluated. Serum AST and ALT activities were significantly decreased in rats treated with different doses of CRAE, indicating its protective effect against CCl(4)-induced chronic liver damage. Observation on serum SOD activity revealed that CRAE might act as an anti-oxidant agent against CCl(4)-induced chronic oxide stress. Histological study supported these observations. Erk1/2 inhibition may take part into CRAE's effect on preventing hepatocyte from apoptosis when exposed to oxidative stress. CRAE showed protective effect against CCl(4)-induced chronic liver damage in rats and its potential as an agent in the treatment of chronic liver diseases by protecting hepatocyte from injury.


Hürthle cell carcinoma metastatic to the uvea.
The authors present a case of Hürthle cell carcinoma metastatic to the uvea in a patient with known Hürthle cell tumor of the thyroid. The fluorescein angiogram suggested a neoplastic lesion, and the collar-button configuration resembled a malignant melanoma. However, standardized echography revealed high internal reflectivity and an irregular acoustic structure suggestive of a metastatic carcinoma. The clinical history and examination were consistent with the diagnosis of metastatic Hürthle cell carcinoma of the eye. Results of a fine-needle aspiration biopsy and histopathology of the intraocular lesion confirmed the diagnosis. Because this was the patient's better-seeing eye, the tumor was treated with an 125I radioactive episcleral plaque. Over the subsequent 27 months, the lesion demonstrated a gradual regression. We have not found any previously reported cases of Hürthle cell carcinoma of the thyroid metastatic to the eye. The diagnosis may be confirmed safely by intraocular aspiration biopsy. The lesion is responsive to radioactive plaque application. The origin, pathology, and management of this unusual tumor are reviewed.


CNV analysis in Chinese children of mental retardation highlights a sex differentiation in parental contribution to de novo and inherited mutational burdens.
Rare copy number variations (CNVs) are a known genetic etiology in neurodevelopmental disorders (NDD). Comprehensive CNV analysis was performed in 287 Chinese children with mental retardation and/or development delay (MR/DD) and their unaffected parents. When compared with 5,866 ancestry-matched controls, 11~12% more MR/DD children carried rare and large CNVs. The increased CNV burden in MR/DD was predominantly due to de novo CNVs, the majority of which (62%) arose in the paternal germline. We observed a 2~3 fold increase of large CNV burden in the mothers of affected children. By implementing an evidence-based review approach, pathogenic structural variants were identified in 14.3% patients and 2.4% parents, respectively. Pathogenic CNVs in parents were all carried by mothers. The maternal transmission bias of deleterious CNVs was further replicated in a published dataset. Our study confirms the pathogenic role of rare CNVs in MR/DD, and provides additional evidence to evaluate the dosage sensitivity of some candidate genes. It also supports a population model of MR/DD that spontaneous mutations in males' germline are major contributor to the de novo mutational burden in offspring, with higher penetrance in male than female; unaffected carriers of causative mutations, mostly females, then contribute to the inherited mutational burden.


Effects of Heterogeneity on Cancer: A Game Theory Perspective.
In this study, we explore interactions between cancer cells by using the hawk-dove game. We analyze the heterogeneity of tumors by considering games with populations composed of 2 or 3 types of cell. We determine what strategies are evolutionarily stable in the 2-type and 3-type population games and what the corresponding expected payoffs are. Our results show that the payoff of the best-off cell in the 2-type population game is higher than that of the best-off cell in the 3-type population game. When these mathematical findings are transferred to the field of oncology they suggest that a tumor with low intratumor heterogeneity pursues a more aggressive course than one with high intratumor heterogeneity. Some histological and genomic data on clear cell renal cell carcinomas is consistent with these results. We underline the importance of identifying intratumor heterogeneity in routine practice and suggest that therapeutic strategies that preserve heterogeneity may be promising as they may slow down cancer growth.


Physicochemical characterisation of the ubiquitous bracken fern as useful biomaterial for preconcentration of heavy metals.
Batch experiments with dry bracken fern have been done to determine cadmium and lead sequestering capacity of this biomaterial. Biomass characterisation was done by infrared spectroscopy and potentiometric analysis. The effect of pH of the metal containing solution, contact time and initial metal concentration has been studied, together with the acid-base properties of the biomaterial. Results obtained have been analysed using mathematical and modelling techniques. Effect of pH on metal sequestration has been correlated with observed acid-base properties of the natural substrate. Kinetic data analysis provided relevant information about metal sequestration rate, showing important differences between lead and cadmium. Maximum uptake was found to be the same for both metals 0.410 mmol/g. This value was also clearly correlated to the number of acidic groups determined for this material which was found to be 0.432 mmol of acidic groups per gram of fern. Results obtained indicate that acidic groups are the functional groups responsible of the sequestration of metal ions and that bracken fern is a promising material for metal preconcentration.


Syk inhibitors with high potency in presence of blood.
We describe two series of Syk inhibitors which potently abrogate Syk kinase function in enzymatic assays, cellular assays and in primary cells in the presence of blood. Introduction of a 7-aminoindole substituent led to derivatives with good kinase selectivity and little or no hERG channel inhibition (3b, 10c).


The Value of the "Papillon" Anterolateral Thigh Flap for Total Pharyngolaryngectomy Reconstruction: A Retrospective Case Series.
The tubed, buried anterolateral thigh (ALT) flap is a popular reconstruction method for total pharyngolaryngectomy defects. The "papillon"-designed ALT flap, described by Hayden et al, offers an alternative method of using the ALT flap in this situation. We report our early experience with the papillon ALT flap in a patient cohort. On retrospective review, all patients who underwent reconstruction of circumferential total pharyngolaryngectomy defects with the papillon ALT flap from February 2012 to February 2015 were identified from our departmental database. Demographic and clinical data, operative details, and complications were analyzed from the records. Seven patients were included in this study. The mean length of hospital stay was 15 days (range, 10 to 32 days). Acute complications occurred in 5 of 7 patients, namely, partial flap loss managed by a pectoralis flap (1 of 7 [14%]); an early pharyngocutaneous fistula (4 of 7 [57%]) managed by simple repair, wound packing, or delayed repair; and a donor-site hematoma (1 of 7 [14%]). At follow-up (range, 2 to 24 months), there was 1 stricture formation, but no chronic fistula. All patients were able to swallow orally. Early results using the papillon ALT flap suggest that this technique is a viable alternative to the standard tubed ALT flap design. The advantages of this design include the following: 1) it offers simultaneous vascularized skin to resurface anterior neck skin deficiency without resorting to additional tissue elsewhere; 2) direct monitoring of the ALT flap is possible; and 3) any pharyngocutaneous fistula is exteriorized to the surface without compromising the internal neck structures and can be easily identified and repaired directly in the office.


A Single Amino Acid Substitution in Therminator DNA Polymerase Increases Incorporation Efficiency of Deoxyxylonucleotides.
Deoxyxylonucleic acid (dxNA) is a synthetic polymer that might have potential for heredity and evolution. Because of dxNA's unusual backbone geometry, sequence information stored in it is presumed to be inaccessible to natural nucleic acids or proteins. Despite a large structural similarity with natural nucleotides, incorporation of 2'-deoxyxylonucleotides (dxNTs) through the action of polymerases is limited. We present the identification of a mutant of the DNA polymerase Therminator with increased tolerance to deoxyxylose-induced backbone distortions. Whereas the original polymerase stops after incorporation of two consecutive dxNTs, the mutant is able to catalyse the extension of incorporated dxNTs with 2'-deoxyribonucleotides (dNTs) and the incorporation of up to four dxNTs alternates with dNTs, thereby translocating a highly distorted double helix throughout the entire polymerase. A single His-to-Arg substitution very close to the catalytic site residues is held to be responsible for interaction with the primer phosphate groups and for stabilizing nucleotide sugar-induced distortions during incorporation and translocation.


Microbial and host factors contribute to bloodstream infection in a pediatric acute lymphocytic leukemia mouse model.
Hematological malignancies are the most common cancers in the pediatric population, and T-cell acute lymphocytic leukemia (T-ALL) is the most common hematological malignancy in children. Bloodstream infection (BSI) is a commonly occurring complication in leukemia due to underlying conditions and therapy-induced neutropenia. Several studies identified the gut microbiome as a major source of BSI due to bacterial translocation. This study aimed to investigate changes in the intestinal and fecal microbiome, and their roles in the pathophysiology of BSI in a pediatric T-ALL mouse model using high-throughput shotgun metagenomics sequencing, and metabolomics. Our results show that BSI in ALL is characterized by an increase of a mucin degrading bacterium (Akkermansia muciniphila) and a decrease of butyrate producer Clostridia spp., along with a decrease in short-chain fatty acid (SCFA) concentrations and differential expression of tight junction proteins in the small intestine. Functional analysis of the small intestinal microbiome indicated a reduced capability of SCFA synthesis, while SCFA supplementation ameliorated the development of BSI in ALL. Our data indicates that changes in the microbiome, and the resulting changes in levels of SCFAs contribute significantly to the pathogenesis of bloodstream infection in ALL. Our study provides tailored preventive or therapeutic approaches to reduce BSI-associated mortality in ALL.


Pharmacologic cerebral capillary blood flow improvement after deep hypothermic circulatory arrest: an intravital fluorescence microscopy study in pigs.
Despite meticulous investigation of bypass techniques for deep hypothermic circulatory arrest, unfavorable long-term neurologic deficits have been well documented. Our aim was to improve brain perfusion by reducing platelet plugging with a glycoprotein IIb/IIIa inhibitor (eptifibatide) in an experimental model of deep hypothermic circulatory arrest-reperfusion in pigs. Two groups of 12 piglets each (eptifibatide group [eptifibatide + unfractionated heparin] vs UFH group [only unfractionated heparin]) underwent 10 minutes of normothermic bypass, 40 minutes of cooling during cardiopulmonary bypass (hematocrit, 30%; cardiopulmonary bypass flow, 100 mL x kg(-1) x min(-1)), 60 minutes of circulatory arrest at 15 degrees C, and a 40-minute rewarming period. Intravital fluorescence microscopy of pial vessels at set intervals was performed. During the cooling period, there was a tendency toward reduced functional capillary density values without statistical significance in both groups. During reperfusion, the eptifibatide group demonstrated a significantly decreased platelet adhesion and aggregation (at 30 minutes of reperfusion: functional capillary density, 104% +/- 3% vs 77% +/- 4% relative to baseline, P = .02; red blood cell velocity, 0.65 vs 0.30 mm/s, P < .004). A more rapid recovery of tissue oxygenation (P < .001) was documented. Furthermore, a significant microvascular permeability reduction was achieved compared with that seen in the UFH group (P < .02). The use of eptifibatide resulted in fewer ultrastructural changes in hippocampal tissue, which is demonstrated by histologic examination. Platelet plugging reduction with the glycoprotein IIb/IIIa inhibitor eptifibatide improves cerebral capillary blood flow and reduces cerebral ischemia in the setting of deep hypothermic circulatory arrest. Furthermore, significant endothelial cell injury and perivascular edema reduction can be achieved.


The effects of a periodontal ligament analogue on occlusal contact forces.
Previous bench-top studies examined the details of the mechanical environment of rigidly fixed occluding teeth. It was demonstrated that during each chomp, contacting molar teeth experience in-occlusal-plane forces (Flateral ) that are highly transient in magnitude and direction. The objectives of this study are to identify Flateral behaviours that are attributable to the presence of a visco-elastic periodontal ligament (PDL) analogue, and to assess the necessity of incorporating it into future studies. A weighted maxillary molar denture tooth was lowered onto, and raised from, a matching mandibular molar 10 times. The latter was supported by a load cell that continuously measured Flateral . For statistical purposes, the test was repeated with 21 (n = 21) different occlusal relationships obtained with 0.05 mm incremental shifts of the lower assembly. Overall, the results are similar to those of rigid attachment but the details of the Flateral profiles are very different. The PDL plays a major role in the mechanical environment of occlusion, suggesting that, in general (not necessarily always), it should be integrated into studies of occlusion.


Edwardsiella tarda EsaE (Orf19 protein) is required for the secretion of type III substrates, and pathogenesis in fish.
Type III secretion system (T3SS) is a large macromolecular assembly found on the surface of many pathogenic Gram-negative bacteria. Edwardsiella tarda is an important Gram-negative pathogen that employs T3SS to deliver effectors into host cells to facilitate its survival and replication. EseB, EseC, and EseD, when secreted, form a translocon complex EseBCD on host membranes through which effectors are translocated. The orf19 gene (esaE) of E. tarda is located upstream of esaK, and downstream of esaJ, esaI, esaH and esaG in the T3SS gene cluster. When its domains were searched using Delta-Blast, the EsaE protein was found to belong to the T3SS YscJ/PrgK family. In the present study, it is found that EsaE is not secreted into culture supernatant, and the deletion of esaE abolished the secretion of T3SS translocon proteins EseBCD and T3SS effector EseG. Increased steady-state protein level of EseC and EseD was detected in bacterial pellet of ΔesaE strain although a reduced level was observed for the eseC and eseD transcription. EsaE was found to localize on membrane but not in the cytoplasm of E. tarda by fractionation. In blue gourami fish infection model, 87.88% of blue gourami infected with ΔesaE strain survived whereas only 3.03% survived when infected with wild-type strain. Taken together, our study demonstrated that EsaE is probably an apparatus protein of T3SS, which contributes to the pathogenesis of E. tarda in fish.


Biodegradation of Direct Red 5B, a textile dye by newly isolated Comamonas sp. UVS.
Soil samples collected from the vicinity of "Manpasand textile industry", located near Ichalkaranji, India were studied for screening and isolation of bacterial strains capable of degradation of textile dyes. A potential strain was selected on the basis of rapid dye degradation and later identified as Comamonas sp. UVS. Comamonas sp. UVS showed 100% decolorization of Direct Red 5B (DR5B) dye at 40 degrees C and pH 6.5. The maximum Direct Red 5B concentration decolorized was 1,100 mg/l in nutrient broth within 125 h. A numerical simulation with the Michaelis-Menten kinetics model gives an optimal value of 16.01+/-0.36 mg dye/g cell/h for maximum rate (V(max)) and 7.97+/-0.21 mg/l for the Michaelis constant (K(m)). The induction in the activities of laccase and LiP was observed during decolorization. These enzymes were inhibited by the addition of sodium azide. The biodegradation was monitored by UV-vis, FTIR spectroscopy and HPLC. The GCMS analysis indicated the presence of 7-benzoylamino-3-diazenyl-4-hydroxy-naphthalene-2-sulfonic acid in degraded product of the dye. The germination of Triticum aestivum seeds was inhibited with DR5B treatment but not with the treatment of dye degradation products.


Post-transcriptional suppression of globin gene expression in cells transformed by avian erythroblastosis virus.
Cells transformed by avian erythroblastosis virus were grown in vitro for up to 5 months. After a few days in culture, synthesis of hemoglobin was undetectable and could not be induced by dimethyl sulfoxide. As shown by globin cDNA hybridization to nuclear and cytoplasmic RNA carried to Crot values of 10(5) moles of nucleotide per liter X sec, globin genes in these cells are transcribed into pre-mRNA, but no trace of globin mRNA appears in the cytoplasm. The implications of this observation for schemes of post-transcriptional regulations and viral transformation are discussed.


2015 Guidelines for Establishing Genetically Modified Rat Models for Cardiovascular Research.
The rat has long been a key physiological model for cardiovascular research, most of the inbred strains having been previously selected for susceptibility or resistance to various cardiovascular diseases (CVD). These CVD rat models offer a physiologically relevant background on which candidates of human CVD can be tested in a more clinically translatable experimental setting. However, a diverse toolbox for genetically modifying the rat genome to test molecular mechanisms has only recently become available. Here, we provide a high-level description of several strategies for developing genetically modified rat models of CVD.


Linkage effects in a model for cell survival after radiation.
A thermodynamic treatment for the effects of radiation on cell survival is proposed. The treatment is an extension of the linear-quadratic model (K.H. Chadwick and H.P. Leenhouts, Phys. Med. Biol. 13 (1973) 78) following the principles of linkage thermodynamics (E. Di Cera, S.J. Gill and J. Wyman, Proc. Natl. Acad. Sci. U.S.A. 85 (1988) 5077). Linkage effects between chemical binding to DNA and radiation action are considered, along with the synergism between different types of radiations. A simple mathematical condition is found for the additivity of radiation doses that result in an isoeffect. The resolvability of the model parameter is investigated by simulations and statistical analysis of the distributions obtained.


Injection of fluorosilicone oil and pars plana vitrectomy for complex retinal detachment.
Pars plana vitrectomy can be combined with injection of fluorosilicone oil to treat complex retinal detachments. We describe three cases to illustrate the technique, which is adapted according to the type and location of the retinal breaks.


Management strategies for Mayer-Rokitansky-Kuster-Hauser related vaginal agenesis: a cost-effectiveness analysis.
The optimal method for neovagina creation in patients with vaginal agenesis is controversial. Progressive perineal dilation is a minimally invasive method with high success rates. However, the economic merits of progressive perineal dilation compared to surgical vaginoplasty are unknown. We performed a Markov based cost-effectiveness analysis of 3 management strategies for vaginal agenesis-progressive perineal dilation with and without subsequent vaginoplasty, and up-front vaginoplasty. Cost data were drawn from the Pediatric Health Information System database (2004 to 2009) for inpatient procedures and from governmental cost data (2009) for outpatient procedures and clinical followup. Other model parameters were derived from a systematic literature review and comparison with other congenital and acquired pediatric and/or adolescent gynecologic conditions. Bounded and probabilistic sensitivity analyses were used to assess model stability. Including all procedures, equipment and physician visits, progressive perineal dilation had a mean cost of $796, while vaginoplasty cost $18,520. Up-front vaginoplasty was strongly dominated at any age, ie was more expensive but no more effective than other options. In cases of progressive perineal dilation failure the incremental cost-effectiveness ratio of progressive perineal dilation with subsequent vaginoplasty was $1,564 per quality adjusted life-year. Only the utility weights of life after treatment impacted model outcomes, while frequency of followup and probability of treatment success did not. Initial progressive perineal dilation followed by vaginoplasty in cases of dilation failure is the most cost-effective management strategy for vaginal agenesis. Initial vaginoplasty was less cost-effective than initial progressive perineal dilation in 99.99% of simulations.


Synthesis and In Vitro Study of a Dual-Mode Probe Targeting Integrin αvβ3.
Malignant tumors constitute a serious disease that threaten human life, and early diagnosis and metastasis prediction are critical to the choice of treatment plan and the timing of treatment. Integrin αvβ3, which has received broad attention as a molecular marker of the tumor neovasculature, is an important target for monitoring tumorigenesis and progression in molecular imaging research. This study reports a magnetic resonance (MR)/fluorescence dual-mode molecular probe, cRGD-Gd-Cy5.5, which targets the integrin αvβ3 receptor and uses liposomes as carrier. The obtained nanoprobe had a size of 60.08 ± 0.45 nm, with good dispersion in water, a uniform distribution of sizes, desirable stability, and high relaxivity. Its r1 relaxation rate was 10.515 mM-1 s-1, much higher than that of other Gd chelates in clinical use. The probe showed no cytotoxicity at the tested concentrations in vitro, and its ability to target A549 cells and SUNE-1-5-8F cells was preliminarily evaluated through in vitro fluorescence imaging and MR imaging. The results demonstrated that the cRGD-Gd-Cy5.5 nanoprobe had good characteristics, showing desirable stability and biosafety, a high T1 relaxation rate, and strong targeting and binding to tumors with high expression of integrin αvβ3. Therefore, cRGD-Gd-Cy5.5 is a promising agent for the visual monitoring of tumor metastasis.


[Endoscopic hemostasis by laser coagulation in massive stress ulcer hemorrhage of the stomach in childhood].
Three cases of bleeding ulcers in childhood are described. In children with considerably increased operative risk, laser coagulation has proved a valuable additional therapeutic concept after failure of conservative treatment of stress ulcer bleeding. Advantages and technical problems of this new method are discussed.


Primary biliary cholangitis associated with warm autoimmune hemolytic anemia.
There are many autoimmune diseases associated with primary biliary cholangitis (PBC), known as primary biliary cirrhosis; however, the association between PBC and warm autoimmune hemolytic anemia (wAIHA) has rarely been reported. It is documented that hemolysis is present in over 50% of the patients with chronic liver disease, regardless of the etiologies. Due to the clear and frequent relationship between PBC and many autoimmune diseases, it is reasonable to suppose that wAIHA may be another autoimmune disorder seen in association with PBC. Here we reported a 53-year-old female patient diagnosed with wAIHA associated with PBC.


Air pollutants associated with smoking in indoor/outdoor of waterpipe cafés in Tehran, Iran: Concentrations, affecting factors and health risk assessment.
Despite increasingly growth in waterpipe smoking in Tehran, so far no study has been conducted on the air quality of the waterpipe and cigarette cafés. Thirty-six cafés were selected and the concentration of three pollutants including formaldehyde, carbon monoxide and nicotine were measured in both indoor and outdoor air of cafés two times (week-day and weekend's session). Air sampling was performed for 180 min for each pollutant. It was observed that the concentration of pollutants inside the cafés was higher during weekend session (with a higher number of "active waterpipe heads") compared with findings during the week-day sessions. Furthermore, the concentration of pollutants in the indoor air of the cafés was significantly higher than that of the outdoors (p < 0.05). According to path analysis, the number of "active waterpipe heads" had the maximum impact on generation of pollutants inside the cafés, followed by the type of tobacco as the second influential factor. The average of lifetime cancer risk (LTCR) resulted by formaldehyde exposure through inhalation in waterpipe (WS), cigarette (CS), waterpipe and cigarette (WCS) and none-smoking (NS) cafés in week-day and weekend sessions were estimated to be 111 × 10-5 and 61.2 × 10-5, 33.7 × 10-5 and 39.4 × 10-5, 271 × 10-5 and 322 × 10-5, and 4.80 × 10-5 and 5.90 × 10-5, respectively, which exceed the limit value by the U.S.EPA and WHO. The concentration of pollutants in the indoor air of smoking cafés in Tehran is significantly high, such that it can pose serious risks for the health of both personnel and customers. Therefore, decision makers are expected to enact applicable and strict policies so as to abate this public health risk.


Endovascular Training Using a Simulation Based Curriculum is Less Expensive than Training in the Hybrid Angiosuite.
This study aimed to determine the cost-effectiveness of a PROficiency based StePwise Endovascular Curricular Training (PROSPECT) program, including e-learning and hands on virtual reality simulation. A prospective, single blinded, randomised controlled trial (RCT) was carried out to evaluate the impact of a PROSPECT training program on real life operative performance. Under supervision, all subjects performed two endovascular interventions on patients with symptomatic iliac and/or superficial femoral artery stenosis. Primary outcomes were technical performance (Global Rating Scale, Examiner Checklist), operative metrics, and patient outcomes, adjusted for case difficulty and the trainee's experience. Additionally, an analysis of costs and savings related to implementation of this endovascular training program was performed. Thirty-two general surgery trainees were randomised into three groups: group 1 (n = 11) received e-learning and simulation training (PROSPECT program); group 2 (n = 10) only had access to e-learning; group 3 (n = 11) did not receive supplementary education besides clinical training. Developmental cost, implementation cost, training time cost, and the operational cost of PROSPECT were determined. Time spent studying and practicing was converted to indirect saving of operating time. The costs of logistics, faculty time supervising simulation sessions, and 30 day complication rates were registered. Sensitivity analysis was performed to assess the robustness of the results. Fifty-eight peripheral endovascular interventions, performed by 29 surgical trainees (three dropouts) were included in this RCT from October 2014 to February 2016. Annual costs from the perspective of the hospital were €6589 for curriculum design, €31,484 for implementation, and €1143 in operational costs. Per trainee, simulation based training until proficiency cost €3806. In comparison, if endovascular proficiency levels were obtained with conventional training only, this may have cost €5001 per trainee. Simulation based training in endovascular procedures may be cost saving, because training occurs outside the angiosuite. It is possible that cost savings are underestimated as, in contrast to the literature, prevented costs related to complications could not be defined.


Multiwalled carbon nanotubes-doped polymeric ionic liquids coating for multiple headspace solid-phase microextraction.
Multiple headspace solid-phase microextraction (SPME) has proved high efficiency in analysis of volatile compounds in complex samples. Fibers used in multiple headspace SPME must provide a logarithm relationship between peak areas and extraction times. The aim of this work was to investigate the potential of a carbon nanotube doped-polymeric ionic liquid (PILs) fiber for multiple headspace SPME of 2-naphthol in fruit samples, using gas chromatography (GC) for analysis. Based on theory of multiple headspace SPME, β parameters of fruit and aqueous samples were obtained and used for quantitation. The interference effects of sample matrix on proposed multiple headspace SPME method were investigated and compared with that of headspace SPME by determination of significant differences (P) of peak areas. It showed high independence from matrix effects. The proposed multiple headspace SPME-GC method also exhibited high repeatability (relative standard deviation of 2.56%) and recoveries (81.9-110%) for the analysis of real samples.


Axonal ephrin-As and odorant receptors: coordinate determination of the olfactory sensory map.
Olfactory sensory neurons expressing a given odorant receptor (OR) project with precision to specific glomeruli in the olfactory bulb, generating a topographic map. In this study, we demonstrate that neurons expressing different ORs express different levels of ephrin-A protein on their axons. Moreover, alterations in the level of ephrin-A alter the glomerular map. Deletion of the ephrin-A5 and ephrin-A3 genes posteriorizes the glomerular locations for neurons expressing either the P2 or SR1 receptor, whereas overexpression of ephrin-A5 in P2 neurons results in an anterior shift in their glomeruli. Thus the ephrin-As are differentially expressed in distinct subpopulations of neurons and are likely to participate, along with the ORs, as one of a complement of guidance receptors governing the targeting of like axons to precise locations in the olfactory bulb.


Rational design and characterization of a lateral flow assay for canine C-reactive protein in wound exudate.
C-reactive protein levels may have clinical value in monitoring different phases of healing and in identifying possible states of infection. As a critical step to further investigate this potential connection, we have demonstrated a lateral flow assay (LFA) for canine CRP level assessment in wound exudate that could be used as a tool in the veterinary clinic setting. In the rational design of our cCRP LFA, we have characterized LFA performance for sequential delivery mode vs. the more common premixed delivery mode using several metrics including dynamic range, sensitivity, limit of detection, and time to result. Although the sequential mode assay results indicated modestly improved signal (3-14%) and limit of detection (in the low ng/mL range for both) for this set of cCRP immunoassay reagents, the premixed mode assay's shorter run time with one less delivery step was chosen for use in this application in which analyte levels are substantially elevated. We have defined a straightforward wound exudate processing procedure that includes centrifugation to extract exudate from canine patient bandages, and subsequent sample dilution for cCRP quantification by our LFA. And, we have demonstrated that our cCRP LFA provides comparable cCRP concentrations to that of gold-standard ELISA performed on the same clinical wound exudate, and serum/plasma samples. Finally, we have highlighted some next steps in the assessment of cCRP as a biomarker for wound healing and infection.


[Endocrine and metabolic myocarditis in a young female diabetic with hyperthyroidism (author's transl)].
A 31-year-old female diabetic in hyperthyroidism, after ketoacidosis leading to a hypoglycaemic coma showed diffuse and persistent abnormalities of ventricular repolarization. Arguments are given for myocardial ischemia of metabolic origin by hypersecretion of catecholamines.


An 18 amino acid amphiphilic helix forms the membrane-anchoring domain of the Escherichia coli penicillin-binding protein 5.
Small (10 residue) C-terminal deletions of PBP5 cause release of this inner membrane protein into the periplasm, indicating disruption of the membrane binding domain. To define the extent of the membrane anchoring domain, oligonucleotide-directed mutagenesis was used to introduce both single amino acid changes and novel restriction sites into the DNA, allowing subsequent construction of precise internal deletions. The 10 C-terminal amino acid residues possess very weak membrane anchoring potential. By extending the sequence to 18 residues membrane binding equivalent to that of authentic PBP5 was achieved. A proline substitution in this region, breaking a potential alpha-helix, also disrupts the membrane binding domain. These results are discussed with respect to the amphiphilicity of the C-terminal sequence when arranged in an alpha-helix.


Aberrant expressions of pathogenic phenotype in Alzheimer's diseased transgenic mice carrying NSE-controlled APPsw.
Mutations in the APP gene lead to enhanced cleavage by the beta- and gamma-secretase, and increased Abeta formation, which are tightly associated with Alzheimer's disease (AD)-like neuropathological changes. To examine whether depositions of Abeta by APP mutations are increased, and if this is associated with potential pathogenic phenotypes, the APPsw was expressed in a transgenic line under the control of the neuron-specific enolase (NSE) promoter. A behavioral dysfunction was shown at 12 months, and intensive staining bands, with APP and Abeta-42 antibodies, were visible in the brains of transgenic mice. Of the MAPK family, both JNK and p38 were activated in the brains of transgenic mice, whereas there was no significant activation of the ERK. In parallel, tau phosphorylation was also enhanced in the transgenic relative to the control mice. Moreover, the Cox-2 levels, from Western blot and immunostaining, were increased in the brains of the transgenic line. Furthermore, there were significant caspase-3- and TUNEL-stained nuclei in the transgenic line compared to the age-matched control mice. Thus, these results suggest that NSE-controlled APPsw transgenic mice appear to be a more relevant model in neuropathological phenotypes of AD, and thus could be useful in developing new therapeutic treatments for targeting the aberrant phenotypes that appear in these mice.


Prediction of special education placement from birth certificate data.
The overall goal of this research effort was to develop procedures for accurately identifying children at high risk for special education placement, based on information available at the time of birth. A file containing information on all births in New York City between 1976 and 1986 was matched against the 1992 BIOFILE, which contains information on all children enrolled in the New York City public school system in 1992. A matched file containing birth and school information on 471,165 children resulted from this process. Three sets of risk factors were derived from birth certificate data: parental, pregnancy-related, and child-related. Using these risk factors as independent variables, a survival analysis model was developed predicting special education placement for each of three major disability categories: learning disability, emotional disorder, and mental retardation. A model combining all disability categories was also developed. The significant predictors of special education placement were Medicaid payment for birth (a poverty indicator), unmarried status of mother, large family size, low parental education, a mother born in the United States, a low level of prenatal care, male gender, low birthweight, and a low Apgar score. Male gender was the strongest risk factor in all models. Examination of selected survival curves indicated that the predictive power of the models is substantial. The methodology described in this article can be used to identify at-risk children for whom screening and other early interventions, including preschool programs, may be appropriate.(ABSTRACT TRUNCATED AT 250 WORDS)


Lysosomal Acid Lipase Activity in Non-alcoholic Fatty Liver Disease as a Novel Diagnostic and Therapeutic Target: A Systematic Literature Review of Current Evidence and Future Directions.
Non-alcoholic fatty liver disease (NAFLD) presents with the accumulation of excessive intra-hepatic fat without significant alcohol intake. Multifactorial pathogenesis is reported to be involved. Reduced lysosomal acid lipase (LAL) activity is suggested as one of the novel-involved pathogenic mechanisms. This review summarizes the available evidence on the role of LAL activity in NAFLD pathogenesis. Four databases namely, PubMed/Medline, Science direct, Cochrane Library, and Google scholar were searched to identify relevant observational records evaluating the role of LAL activity in the pathogenesis of NAFLD. All studies were assessed for their quality by using Newcastle-Ottawa Scale or The Joanna Briggs Institute Critical Appraisal tools for cohort and cross-sectional studies, respectively. The estimates of LAL activity and other clinical outcomes were expressed as mean (SD) and number (%) as presented in the primary studies. A total of nine good quality studies with 1711 patients with NAFLD and 877 controls from different groups (healthy volunteers, alcoholics, cryptogenic cirrhosis, and HCV-positive) were included. From the NAFLD group, 59.55% were males and the overall mean age ranged between the studies from 12.6 ± 8.5 months in pediatrics to 58.90 ± 13.82 years in adults. In the NAFLD group, the LAL activity varied from 0.53 ± 0.08 to 1.3 ± 0.70 (nmol/spot/hr) between the studies which was less than all control groups except cryptogenic cirrhosis patients (0.5 ± 0.15 nmol/spot/hr). Of the other outcomes of interest, ALT, AST, total cholesterol, triglyceride, and LDL cholesterol were found elevated in NAFLD patients than in controls. The current evidence suggests a potential correlation of reduced LAL activity with NAFLD pathogenesis according to its severity. Large-scale studies are recommended, more importantly in patients with NAFLD having no metabolic or genetic involvement. Further LAL can act as a new non-invasive diagnostic biomarker to identify that specific NAFLD subgroup.


[Effect of various forms of diet on the nitrosation of sodium metamizole (analgin tablets) under simulated conditions of the human stomach].
The influence of a simple and a more complex diet on the formation of nitrosometamizole from sodium metamizole (analgin tablets) under simulated human gastric conditions was estimated with extremely different nitrite concentrations. Only with the complex diet and only with low nitrite concentrations, the formation of nitrosometamizole was distinctly lowered. The quantitative estimation of the formed amounts was done by a colorimetric method after extraction with dichloromethane.


Subharmonic response of encapsulated microbubbles: conditions for existence and amplification.
The response of encapsulated microbubbles at half the ultrasound insonation frequency, termed subharmonic response, may have potential applications in diagnosis and therapy. The subharmonic signal, emitted by Definity microbubble cloud sonicated by ultrasound was studied theoretically and experimentally. The size distribution of the microbubbles was optically analyzed and resonance frequency of 2.7 MHz was determined. An asymptotic model has been developed that generates subharmonic response of a single and of a cloud of bubbles of various sizes. Threshold conditions for existence and the intensity of the subharmonic signal are predicted to depend on microbubbles size distribution and shell properties, as well as on the driving field frequency and pressure. Thin tubes filled with Definity solution were insonated at acoustic pressures from 100 to 630 kPa. The intensities of the emitted fundamental harmonics and subharmonics were measured. At frequency 5.5MHz, twice the resonance frequency, the subharmonic signals were observed only at pressures greater than 190 kPa. The subharmonic to fundamental harmonics intensity ratio was within -12 to -1 dB. The experimental results showed good correlation with the theoretical results in the range of validity of the asymptotic solution, thus supporting the model assumptions.


Early cognitive development and its relation to maternal physiologic and behavioral responsiveness.
Data are presented which support the hypothesis that infant cognitive development is a function of maternal responsiveness to infant cues. 22 mothers whose physiologic responses to infant signals had been recorded at an earlier date participated in the follow-up study reported here. Mother-infant dyads were videotaped during a feeding session when the infant was 9 months of age. Behavioral data collected were the mother's responses to her infant's facial orientation. The statistic developed to index maternal sensitivity was the rate of maternal responding during infant gaze/the rate of responding during infant looking away. Development of the object concept was assessed at 15 months using the Uzgiris and Hunt scale. The data indicated that the development of the concept of the object is positively related to maternal behavioral sensitivity and that mothers who were behaviorally sensitive to infant cues earlier had exhibited physiologic responses to infant signals.


Solute effects on ice recrystallization: an assessment technique.
Reliable assessment of the effect of a solute upon ice recrystallization is accomplished with "splat cooling," the impaction of a small solution droplet onto a very cold metal plate. The ice disc has extremely small crystals, and recrystallization can be followed without confusing effects caused by grain nucleation. This method confirms the exceptionally strong recrystallization inhibition effect of antifreeze protein from Antarctic fish and shows that grain growth rate is a sensitive function of both grain size and solute concentration.


Updating and evaluating the NH3 gas-phase chemical mechanism of MOZART-4 in the WRF-Chem model.
The accuracy of determining atmospheric chemical mechanisms is a key factor in air pollution prediction, pollution-cause analysis and the development of control schemes based on air quality model simulations. However, the reaction of NH3 and OH to generate NH2 and its subsequent reactions are often ignored in the MOZART-4 chemical mechanism. To solve this problem, the gas-phase chemical mechanism of NH3 was updated in this study. Response surface methodology (RSM), integrated gas-phase reaction rate (IRR) diagnosis and process analysis (PA) were used to quantify the influence of the updated NH3 chemical mechanism on the O3 simulated concentration, the nonlinear response relationship of O3 and its precursors, the chemical reaction rate of O3 generation and the meteorological transport process. The results show that the updated NH3 chemical mechanism can reduce the error between the simulated and observed O3 concentrations and better simulate the O3 concentration. Compared with the Base scenario (original chemical mechanism simulated), the first-order term of NH3 in the Updated scenario (updated NH3 chemical mechanism simulated) in RSM passed the significance test (p < 0.05), indicating that NH3 emissions have an influence on the O3 simulation, and the effects of the updated NH3 chemical mechanism on NOx-VOC-O3 in different cities are different. In addition, the analysis of chemical reaction rate changes showed that NH3 can affect the generation of O3 by affecting the NOx concentration and NOx circulation with radicals of OH and HO2 in the Updated scenario, and the change of pollutant concentration in the atmosphere leads to the change of meteorological transmission, eventually leading to the reduction of O3 concentration in Beijing. In conclusion, this study highlights the importance of atmospheric chemistry for air quality models to model atmospheric pollutants and should attract more research focus.


Esterase 13, a new mouse esterase locus with recessive expression and its genetic location on chromosome 9.
A new esterase locus (Es-13) has been identified in Musculus. Strains AEJ/GnRk, LG/J, SJL/J, and SWR/J carry a recessive allele, Es-13b, for a locus possibly involved in the posttranslational modification of a kidney esterase. All other strains observed carried the dominant Es-13a allele. Es-13 was mapped on Chr 9 by recombinant inbred lines and by conventional backcrossing experiments. Backcross data produced the following gene order and map distances: Lap-1 (31.6 +/- 7.5 cM) Es-13 (2.6 +/- 2.6 cM) Mod-1.


Buprenorphine/naloxone treatment practices in Malaysia: Results of national surveys of physicians and patients.
Medication assisted treatment with buprenorphine/naloxone (Bup/Nx), including prescribing and dispensing practices of general practitioners (GPs) in Malaysia and their patients' experiences with this treatment have not been systematically examined. The current study surveyed GPs providing Bup/Nx treatment and patients receiving office-based Bup/Nx treatment in Malaysia. Two cross-sectional surveys of GPs (N=115) providing outpatient Bup/Nx maintenance treatment and of patients (N=253) currently receiving Bup/Nx treatment throughout peninsular Malaysia. Physicians prescribed Bup/Nx dosages in the range of 2-4mg daily for 70% of patients and conducted urine testing in the past month on approximately 16% of their patients. In the patient survey, 79% reported taking daily Bup/Nx doses of 2mg or less; 82% reported that no urine toxicology testing had been conducted on them in the past month, 36% had an opiate positive urine test at the time of the survey, 43% reported illicit opiate use, 15% reported injection of heroin and 22% reported injection of Bup/Nx in the past month. Low daily Bup/Nx doses, lack of behavioral monitoring or counseling, and high rates of continued drug use, including injection of drugs and medications during Bup/Nx treatment in Malaysia, indicate continuing problems with implementation and less than optimal treatment effectiveness. High cost of Bup/Nx in Malaysia may deter patients from seeking treatment and contribute to taking low Bup/Nx dosages. Improved training of physicians and establishing standards for Bup/Nx dosing, routine toxicology testing, and counseling may be needed to improve care and treatment response.


A new class of type I protein geranylgeranyltransferase (GGTase I) inhibitor.
Replacement of the thiol groups in 1, a potent and highly selective Candida albicans GGTase I inhibitor discovered through screening, with an imidazole ring was achieved by using solid phase synthesis. A non-thiol compound, 7, was found as a representative of a new class of potent C. albicans GGTase I inhibitor with high selectivity against human GGTase I.


Genetic and epigenetic mutations affect the DNA binding capability of human ZFP57 in transient neonatal diabetes type 1.
In the mouse, ZFP57 contains three classical Cys2His2 zinc finger domains (ZF) and recognizes the methylated TGC(met)CGC target sequence using the first and the second ZFs. In this study, we demonstrate that the human ZFP57 (hZFP57) containing six Cys2His2 ZFs, binds the same methylated sequence through the third and the fourth ZFs, and identify the aminoacids critical for DNA interaction. In addition, we present evidences indicating that hZFP57 mutations and hypomethylation of the TNDM1 ICR both associated with Transient Neonatal Diabetes Mellitus type 1 result in loss of hZFP57 binding to the TNDM1 locus, likely causing PLAGL1 activation.


Experimental investigations and the modeling approach for CO2 solubility in aqueous blended amine systems of monoethanolamine, 2-amino-2-methyl-1-propanol, and 2-(butylamino)ethanol.
In this work, new CO2 solubility data on three types of aqueous amine blends were reported to complement existing databases. The experiments were conducted at temperatures of 313 K (absorption condition) and 363 K (desorption condition). The effect of the MEA concentration on the CO2 solubility in several amine blends at low CO2 partial pressure (8 to 50.65 kPa) were studied in this work, including 0.1, 0.3, 0.5 mol/L MEA + 2 mol/L AMP; 0.1, 0.3, 0.5 mol/L MEA + 2 mol/L BEA; and 0.1, 0.3, 0.5 mol/L MEA + 1, 2 mol/L AMP + 1, 2 mol/L BEA. Besides, an additional group of equilibrium CO2 solubility data were conducted at 298 K in order to estimate the heat of CO2 absorption of the blended solvents at a temperature range from 298 to 313 K. A new simplified Kent-Eisenberg model was developed for the predictions of blended solvents, and a multilayer neural network model with Levenberg-Marquardt backpropagation algorithm was developed upon five hundred reliable published experimental data. The predictions from two methods are both in good agreement with the experimental CO2 solubility data.


Renal artery pseudoaneurysm after laparoscopic partial nephrectomy for renal cell carcinoma in a solitary kidney.
Renal artery pseudoaneurysms are a well-documented complication following trauma or percutaneous urological procedures, but are rare after partial nephrectomy. We present the case of a 34-year-old woman who, after undergoing a left nephrectomy in childhood due to Wilms' tumor, had a pseudoaneurysm in a solitary kidney after laparoscopic right partial nephrectomy with extraperitoneal approach for a renal cell carcinoma. The segmental renal artery feeding the pseudoaneurysm was embolized with coils without significant loss of residual renal function.


Generation of cytokine-induced killer cells using exogenous interleukin-2, -7 or -12.
Immunologic effector cells termed cytokine-induced killer (CIK) cells are generated in vitro from peripheral blood lymphocytes by addition of interferon-gamma, interleukin (IL)-2, IL-1 and an antibody against CD3. CIK cells have been shown to eradicate established tumors in a SCID mouse/human lymphoma model. CIK cells are dependent on exogenous cytokines such as IL-2, IL-7, or IL-12. We studied the effect of these cytokines in detail. Cellular proliferation was analyzed using an MTT proliferation assay, surface antigen expression via flow cytometry, cytotoxic activity using an LDH release assay, and apoptosis via flow cytometric analysis. IL-2, IL-7 and IL-12 led to significant growth of lymphocytes. Cells grown in IL-2 and IL-7 showed higher proliferation rates than cells grown in IL-12 according to the MTT assay. Concerning surface antigen expression, exogenous IL-7 led to a decrease in IL-7 receptor expression (4.8% from 60.4%) and exogenous IL-2 to a decrease in IL-2 receptor expression (61.2% from 73.2%). CD28 expression was higher in cells grown in IL-7 (77.3%) than in cells grown in IL-2 (62.5%). IL-12 led to a decrease in ICAM-1 adhesion molecule expression (57.7% from 76.7%) and an increase in CD56 expression compared with exogenous IL-7. IL-7 led to higher number of CD4-positive cells than IL-2 (53.0% vs 49.5%). No significant difference was found between IL-2, IL-7 and IL-12 in cytotoxic activity measured in an LDH release assay. Small amounts of apoptotic cells were found with all cytokines. However, the percentage of necrotic cells was higher with exogenous IL-12 than with IL-2 or IL-7. In summary, CIK cells can be generated using exogenous IL-2, IL-7 or IL-12. No difference in cytotoxic activity was found. However, significant differences were found in cell proliferation rates, antigen expression and percentage of necrotic cells.


Use of sequential ASE extraction to evaluate the bioavailability of DDT and its metabolites to wheat roots in soils with various organic carbon contents.
An accelerated solvent extraction (ASE) procedure using water, n-hexane and a mixture of n-hexane and acetone as solvents in sequence was developed and tested to evaluate the bioavailability of DDT and its metabolites including p,p'-DDT, o,p'-DDT, p,p'-DDE, and p,p'-DDD (SigmaDDTs) to wheat uptake from soils characterized by varied organic carbon contents. Results indicated that the extractability of SigmaDDTs with water was enhanced considerably in the presence of water soluble organic carbon (WSOC), while the amount of SigmaDDTs extracted with n-hexane was negatively correlated to the content of water insoluble organic carbon (WIOC). The interaction between SigmaDDTs and WIOC also reduced the bioavailability of the pesticides to wheat roots during uptake. There was a good positive correlation between the amount of SigmaDDTs extracted by n-hexane and the amount of SigmaDDTs accumulated in wheat roots, suggesting some potential for the use of the n-hexane ASE-extracted fraction as an indicator of SigmaDDTs' bioavailability to plant uptake. As such, the three sequentially extracted fractions may be viewed as representing the mobile, bioavailable, and fixed pools of SigmaDDTs in the soil.


Serum amyloid P component is the major calcium-dependent specific DNA binding protein of the serum.
Serum amyloid P component (SAP), a member of the highly conserved pentraxin family of plasma proteins, was found to be the only protein in whole normal or acute phase serum which underwent specific calcium-dependent binding to either single or double-stranded DNA immobilised on gel. Isolated purified SAP also bound to long chromatin, to H1-stripped chromatin and to native DNA in solution at physiological ionic strength. Pure SAP which had been immobilised on gel, specifically bound nucleosome core particles from solution. These observations strongly suggest that SAP may bind to extracellular chromatin and DNA in vivo and that this may be its physiological role.


Clofibrate and dalargin increase luminol-dependent chemiluminescence of mouse blood.
The effects of hypolipidemic drug clofibrate and polypeptide dalargin on activity of the neutrophil peroxidase system in mice were studied using the method of luminol-enhanced chemiluminescence. Clofibrate and dalargin increased the chemiluminescence of mouse whole blood. Their combined use several-fold potentiated this effect. It is expected that combined use of hypolipidemics and polypeptides will open a new trend in the search for stimulators of oxygen-dependent nonspecific immunity.


Comparison of gait between young adults fitted with the space foot and nondisabled persons.
Prosthetic feet having new keel configurations were specially designed to store deformation energy during early and midstance and release it at push-off. These prosthetic components display longitudinal symmetry favoring good energy storage/release capability in the sagittal plane. The need for inverters/everters either as independent components or within the foot structure has long been recognized. This article documents the walking and slow jogging performances of six young adults wearing below-knee prostheses fitted with the Space Foot, a flexible foot prosthesis that provides medio-lateral control at heel-strike and lateral and forward propulsion at push-off. Results indicate that the Space Foot behaves as a flexible keel foot prosthesis. Its gait performances are also good for fast walking; however, the Space Foot's actual design should be modified if used in sporting activities involving running.


Acute Paronychia and Onychomadesis after a "Russian" Manicure: A New, Aggressive, and Destructive Form of Manicure for Dermatologists to Recognize.
Cuticle reduction and removal techniques are commonly performed by nail technicians for nail cosmesis. However, manipulation of the nail cuticle can lead to localized infection and nail dystrophy. In this case, a 20-year-old woman from the Philadelphia area in the USA presented with onychomadesis secondary to acute paronychia following a "Russian" manicure. In this technique, an electronic filer is used to completely remove the cuticle, leaving the proximal nail fold exposed and vulnerable. As this style of manicure is being inaccurately publicized as safe, it is important that dermatologists are aware of this technique and educate our patients about its potential for harm.


Inactivation of cholecystokinin octapeptide by normal and cirrhotic liver in rats.
In anesthetized rats, a marked decrease in CCK-OP activity and, to a far lesser extent, in the pancreatic secretory effect of CCK-33 were found after portal administration, compared to the femoral route. Changes in the biological activity of CCK-OP were further investigated after 30 min incubation with different subcellular liver fractions (1000 X g, 12,000 X g, microsomal fraction with or without NADPH). All the subcellular liver fractions caused an approximately 70% decrease in the CCK-effect, as calculated from dose-response relationships. The inactivation of CCK-OP after incubation with microsomal fractions of thioacetamide (TAA)-induced cirrhotic liver did not differ from that of control rats. The CCK-OP dose-response curves were similar in cirrhotic and control rats, but the pancreatic secretion was sustained to a greater extent and the inhibitory effect of supramaximal stimulation was delayed in cirrhotic rats. It was concluded that CCK-OP can be inactivated by liver proteins present in microsomal fractions, by a NADPH-independent mechanism. This inactivation did not diminish in liver cirrhosis. There were no changes in CCK-OP elimination in cirrhotic rats in vivo, thus pancreatic hypertrophy in experimental cirrhosis must be explained by other mechanisms.


ICAM-1 expression on chondrocytes in rheumatoid arthritis: induction by synovial cytokines.
The intercellular adhesion molecule-1 (ICAM-1) was found by immunostaining chondrocytes in cartilage from three patients with rheumatoid arthritis. Expression of ICAM-1 was restricted to chondrocytes in areas of erodedcartilage adjacent to the invading synovial tissue. Toluidine blue staining of these areas demonstrated severe depletion of the cartilage extracellular matrix. In areas of undamaged cartilage there was no ICAM-1 expression. Since ICAM-1 is not constitutively expressed on normal human articular cartilage, but could be induced in vitro by exogenous IL-1alpha, TNFalpha and IFNgamma or by co-culturing cartilage with inflammatory rheumatoid synovium, we conclude that the induction of ICAM-1 on rheumatoid chondrocytes results from the synergistic action of a variety of cytokines produced by the inflammatory cells of the invading pannus.


Extrinsic compression of the heart by tumor masquerading as cardiac tamponade.
A patient with known intrathoracic tumor presented with findings suggestive of cardiac tamponade. At cardiac catheterization, the entire heart was displaced superiorly and anteriorly by the tumor mass, and this accounted for the observed cardiac hemodynamics, in the absence of discernible pericardial effusion.


Deep-learning-based automatic facial bone segmentation using a two-dimensional U-Net.
The use of deep learning (DL) in medical imaging is becoming increasingly widespread. Although DL has been used previously for the segmentation of facial bones in computed tomography (CT) images, there are few reports of segmentation involving multiple areas. In this study, a U-Net was used to investigate the automatic segmentation of facial bones into eight areas, with the aim of facilitating virtual surgical planning (VSP) and computer-aided design and manufacturing (CAD/CAM) in maxillofacial surgery. CT data from 50 patients were prepared and used for training, and five-fold cross-validation was performed. The output results generated by the DL model were validated by Dice coefficient and average symmetric surface distance (ASSD). The automatic segmentation was successful in all cases, with a mean± standard deviation Dice coefficient of 0.897 ± 0.077 and ASSD of 1.168 ± 1.962 mm. The accuracy was very high for the mandible (Dice coefficient 0.984, ASSD 0.324 mm) and zygomatic bones (Dice coefficient 0.931, ASSD 0.487 mm), and these could be introduced for VSP and CAD/CAM without any modification. The results for other areas, particularly the teeth, were slightly inferior, with possible reasons being the effects of defects, bonded maxillary and mandibular teeth, and metal artefacts. A limitation of this study is that the data were from a single institution. Hence further research is required to improve the accuracy for some facial areas and to validate the results in larger and more diverse populations.


[3H]BMT-046091 a potent and selective radioligand to determine AAK1 distribution and target engagement.
Adaptor-associated kinase 1 (AAK1), a member of the Ark1/Prk1 family of serine/threonine kinases, plays a role in modulating clatherin coated endocytosis of specific surface receptors. We have demonstrated that AAK1 inhibitors are efficacious in rodent models of neuropathic pain (Kostich et al., 2016). Here we have characterized the binding properties and distribution pattern of the tritiated AAK1 radioligand, [3H]BMT-046091, in rodents and cynomolgus monkeys, and used the radioligand to measure the brain target occupancy following systemic administration of AAK1 inhibitors. We have found that [3H]BMT-046091 is potent and selective AAK1 inhibitor. It inhibits AAK1 phosphorylation of a peptide derived from a physiologic substrate, the μ2 subunit of the adaptor protein complex, with an IC50 value of 2.8 nM, and is inactive at >5 μM in a panel of functional or binding assays for receptors, transporters and enzymes. [3H]BMT-046091 binding in the brain is absent in the AAK1 knockout mouse, and is displaceable with a high concentration of AAK1 inhibitors in wild type mice. Specific [3H]BMT-046091 binding is widespread in the brain and spinal cord with the highest density in the cortex, hippocampus, amygdala, striatum and thalamus. In the spinal cord, [3H]BMT-046091 binding appears enriched in the dorsal horn superficial layers. Oral administration of LP-935509, an AAK1 inhibitor, results in a dose-dependent occupation of AAK1 binding sites in the brain and spinal cord. The increase in AAK1 binding site occupancy by LP-935509 correlates with the decrease in antinociceptive responses in the rat chronic constriction injury model of neuropathic pain.


In vivo imaging of lymph node lymphangiogenesis by immuno-positron emission tomography.
Recently, our group and others found that cancer and inflammation can induce the expansion of the lymphatic vasculature (lymphangiogenesis) in draining lymph nodes in experimental animal models and in cancer patients (Hirakawa et al., J Exp Med 201:1089-1099, 2005; Qian et al., Cancer Res 66:10365-10376, 2006; Halin et al., Blood 110:3158-3167, 2007; Angeli et al., Immunity 24:203-215, 2006; Dadras et al., Mod Pathol 18:1232-1242, 2005). Since then, a growing number of reports have confirmed the importance of lymph node lymphangiogenesis in tumor metastasis, inflammation resolution, and dendritic cell migration to the lymph nodes (Angeli et al., Immunity 24:203-215, 2006; Hirakawa et al., Blood 109:1010-1017, 2007; Harrell et al., Am J Pathol 170:774-786, 2007; Kataru et al. Blood 113:5650-5659, 2009; Kataru et al., Immunity 34:96-107, 2011; Van den Eynden et al., Clin Cancer Res 13:5391-5397, 2007). Conventionally, lymphangiogenesis in mice is detected by extensive quantitative analysis of lymphatic vessels in stained tissue sections. Here we present a noninvasive methodology that we have recently developed to image lymphangiogenesis in vivo in mice (Mumprecht et al., Cancer Res 70:8842-8851, 2010). This technique is based on the intravenous injection of a radioactively labeled antibody against the lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), which is almost exclusively expressed on lymphatic vessels (Banerji et al., J Cell Biol 144:789-801, 1999; Preyo et al., J Biol Chem 276:19420-19430, 2001). The accumulation of the injected anti-LYVE-1 antibody in the lymphatic vessels is subsequently visualized by positron emission tomography (PET). Lymphangiogenic lymph nodes emit a stronger radioactive signal than control lymph nodes because they take up more of the radiolabeled anti-LYVE-1 antibody and thus are distinguishable from normal lymph nodes in the PET images.


Reliable identification of transition zone prostatic adenocarcinoma in preoperative needle core biopsy.
Prostatic adenocarcinomas arising within the transition zone (Tz) are distinct from peripheral zone (Pz) tumors as regards biological aggression and mechanism of extraprostatic extension. Reliable biopsy identification of Tz tumors would allow targeted surgical approaches more likely to preserve erectile function without compromising surgical margins. Previous studies have demonstrated the presence of eosinophilic cytoplasmic granules (prostate secretory granules, or PSGs) after glutaraldehye fixation, with apparent depletion in neoplasia. We investigated PSG content, columnar cells, pale cytoplasm, and luminal secretions of both Pz and Tz tumors in 44 radical prostatectomies (RPs) and 135 biopsies fixed with gluteraldehyde-based fixative. Retention of PSG is characteristic of Tz carcinoma and infrequently seen in Pz tumors, and a combination of PSG greater than 30% with either columnar cells, pale cells, or secretions in biopsies is a reliable marker for Tz origin. When these criteria were prospectively applied to 3929 cases with follow-up RP, 510 Tz tumors were correctly identified on biopsy (sensitivity, 21.4%; specificity, 97.4%). Biopsy-identified Tz tumors had higher volumes (mean, 3.48 versus 1.81 cm(3); P < .001) and higher rates of margin positivity (22.5% versus 17.5%; P = .008) than did Tz tumors not identified preoperatively. Mean Tz tumor length in biopsies was 2.0 mm, with no correlation between tumor volume at RP and tumor length on biopsy. Tz tumors are reliably identified on biopsy, based on a combination of PSG retention with either columnar cells, pale cells, or secretion. Biopsy-identified Tz tumors may not be suitable for active surveillance because of an associated high probability of large tumor volume and increased risk of positive margins at RP.


Atypical carcinoid (moderately differentiated neuroendocrine carcinoma) of the uvula.
Carcinoid (neuroendocrine) tumors of the head and neck rarely occur outside the larynx and, until now, none has been reported in the oral cavity. We describe what we believe is the first reported case of an atypical carcinoid tumor, or any other type of neuroendocrine carcinoma, of the uvula.


[Effect of Different Locations and Genotypes on Yield and Accumulation of Bioactive Constituents in Salvia miltiorrhiza].
The root yield and active constituent contents were analyzed from four Salvia miltiorrhiza cultivars grown at three different locations( Zhuyang, Changqing, and Taian, Shandong Province) to determine the influence of environmental conditions and cultivars. . Phenolic acids and tanshinones were analyzed by HPLC method. Total phenolic acids content were analyzed by FolinCiocalteu method. Klason method was used to determine the content of lignin. The root yield and the active constituent contents were significantly affected by different environments and cultivars of Salvia miltiorrhiza. The root yield was negatively correlated with active constituent contents. Salvia miltiorrhiza of Zhuyang location had the highest active constituent content, but it had the lowest root yield. Salvia miltiorrhiza of Taian location had the lowest active constituent contents, while it had the highest root yield. Salvia miltiorrhiza of Changqing location had relatively higher bio-yields of phenolic acids and tanshinones, which made it suitable for Salvia miltiorrhiza cultivation. Furthermore, compared with three other cultivars,105 cultivar could remain the salvianolic acid B stable, which indicating that 105 cultivar was possible related to resistances. The research provides a theoretical basis for the selecting of the optimal cultivar and the optimal environmental condition.


Copula identifiability conditions for dependent truncated data model.
We provide a copula identifiability condition for dependent truncated data model. The identifiability is characterized by the strong lower-left tail identifiability of the copula family. We show that the commonly used Archimedean copula families with analytic generator functions satisfy this condition.


Injection of muscimol in the posterior hypothalamus reduces the PGE1-hyperthermia in the rat.
The firing rate of the nerves innervating interscapular brown adipose tissue (IBAT), IBAT and colonic temperatures (TIBAT and Tc), heart rate, and oxygen (O2) consumption were monitored in urethane-anesthetized male Sprague-Dawley rats. These variables were measured for 40 min before (baseline values) and 40 min after a 56 ng muscimol injection in the posterior hypothalamus and an intracerebroventricular administration of 500 ng prostaglandin E1 (PGE1). The same variables were monitored in other rats with muscimol injection or PGE1 administration alone. No drug was injected in control rats. The results show that muscimol injection reduces the increases in firing rate, TIBAT, Tc, heart rate, O2 consumption induced by PGE1. These findings suggest that GABAergic tone in the posterior hypothalamus is important in the control of thermogenic changes induced by PGE1.


Biorejuvenation: theory and practice.
The aim of mesotherapy for skin rejuvenation is to increase the biosynthetic capacity of fibroblasts, inducing the reconstruction of an optimal physiologic environment, the enhancement of cell activity, and the synthesis of collagen, elastin, and hyaluronic acid. The desired final effect is a firm, bright, and moisturized skin, and the injection in the superficial dermis of suitable products--perfectly biocompatible and totally absorbable--can achieve these results. In addition to a daily sunscreen application and nonsmoking, mesotherapy is another antiaging strategy helping to maintain a globally firm and bright skin, protecting it from the environmental contributors to aging.


M2 and M3-muscarinic acetylcholine receptors remodelling in patients with a dilated atrium.
Studies have shown that autonomic tone plays an important role in the pathogenesis of atrial fibrillation (AF) and remodelling of I(K, ACh) in chronic AF serves as a compensatory mechanism for the AF. The relation between atrial size and AF has been established. We investigated the remodelling of muscarinic receptors in patients with dilated atrium and assessed the relationship between the muscarinic receptor remodelling and the dilated atrium. A small piece of the tip of the right atrial appendage was obtained from 19 patients in sinus rhythm (SR), 28 patients with mitral stenosis and 10 patients with chronic AF (AF > 6 months). Western-blot was used to determine the expression of M2 and M3 receptors. Patients with mitral stenosis and chronic AF had a larger left atrial diameter than patients in SR. The densities of the M2 receptor in patients with mitral stenosis (with AF and with SR) and chronic AF were lower than that in patients with SR (0.54 +/- 0.08 vs. 0.29 +/- 0.06, 0.26 +/- 0.05 and 0.28 +/- 0.06, P < 0.05). However, the densities of the M3 receptor in patients with mitral stenosis and chronic AF were higher than that in patients with SR (0.07 +/- 0.01 vs. 0.18 +/- 0.02, 0.17 +/- 0.01 and 0.15 +/- 0.01, P< 0.05). Furthermore, there was no significant difference in M2 and M3 receptors between AF and SR in patients with mitral stenosis. Remodelling of M2 and M3 receptors is not associated with AF, but with the dilated left atrium.


Key determinants controlling the seasonal variation of coastal zooplankton communities: A case study along the Yellow Sea.
Zooplankton play key top-down and bottom-up regulatory roles in aquatic food webs, and are also ecologically indicative in marine ecosystems. However, there are relatively limited data on the effects of environmental changes on natural zooplankton communities, especially in coastal ecosystems. In the present study, we systematically evaluated the potential effects of various environmental variables, such as temperature, salinity, and nutrients, on the zooplankton communities along the coastal Yellow Sea during spring, summer, and fall. The results showed that the average abundance of zooplankton decreased in general from spring to autumn, but the biomass exhibited a different seasonal variation trend, with the highest in summer and the lowest in fall. Throughout the three seasons, copepods were the most dominant species within the zooplankton communities, followed by Pelagic larvae and Hydromedusae. However, Noctiluca miliaris accounted for a large proportion of zooplankton abundance during spring. Moreover, the correlation analysis was applied to explore the potential effects of environmental factors on the seasonal variation of zooplankton communities. The results showed that chlorophyll a (Chl a) and salinity were significantly correlated with zooplankton abundance and biomass during spring. The implication is that high phytoplankton biomass (expressed as Chl a) and salinity would benefit the growth of zooplankton in spring. During summer and fall, the effects of dissolved inorganic phosphate (DIP) on the zooplankton abundance and biomass showed a significant positive correlation, indicating that zooplankton were better able to tolerate high DIP during summer and fall. Taken together, Chl a, salinity, and DIP may be the key determinants controlling the seasonal dynamics of zooplankton communities in the coastal Yellow Sea.


p38MAPK suppresses chronic pancreatitis by regulating HSP27 and BAD expression.
Mitogen-activated protein kinases (MAPKs) are ubiquitous proteins that function in both normal and stress-related pathophysiological states of the cell. This study aimed to analyze the importance of p38MAPK in pancreatic injury using WBN/Kob rats with spontaneous chronic pancreatitis. Male WBN/Kob rats were injected with the p38MAPK inhibitor SB203580, starting at the age of 4 weeks, and sacrificed 6 weeks later. Compared with vehicle-treated rats, p38 inhibitor-treated rats exhibited a significant increase in pancreatic cell death and inflammation as assessed by histologic examination and myeloperoxidase activity, respectively. p38 inhibition decreased the expression of heat shock protein 27 (HSP27), an antioxidant protein, and enhanced accumulation of reactive oxygen species (ROS). In addition, the proapoptotic protein BAD was increased in the pancreas of rats treated with p38 inhibitor. In a pancreatic cell line (PANC-1), HSP27 knockdown augmented reactive oxygen species accumulation and cell death induced by tumor necrosis factor-α plus actinomycin D. In conclusion, p38MAPK suppresses chronic pancreatitis by upregulating HSP27 expression and downregulating BAD expression.


A systematic review of genetic variants associated with metabolic syndrome in patients with schizophrenia.
Metabolic syndrome (MetS) is a cluster of factors that increases the risk of cardiovascular disease (CVD), one of the leading causes of mortality in patients with schizophrenia. Incidence rates of MetS are significantly higher in patients with schizophrenia compared to the general population. Several factors contribute to this high comorbidity. This systematic review focuses on genetic factors and interrogates data from association studies of genes implicated in the development of MetS in patients with schizophrenia. We aimed to identify variants that potentially contribute to the high comorbidity between these disorders. PubMed, Web of Science and Scopus databases were accessed and a systematic review of published studies was conducted. Several genes showed strong evidence for an association with MetS in patients with schizophrenia, including the fat mass and obesity associated gene (FTO), leptin and leptin receptor genes (LEP, LEPR), methylenetetrahydrofolate reductase (MTHFR) gene and the serotonin receptor 2C gene (HTR2C). Genetic association studies in complex disorders are convoluted by the multifactorial nature of these disorders, further complicating investigations of comorbidity. Recommendations for future studies include assessment of larger samples, inclusion of healthy controls, longitudinal rather than cross-sectional study designs, detailed capturing of data on confounding variables for both disorders and verification of significant findings in other populations. In future, big genomic datasets may allow for the calculation of polygenic risk scores in risk prediction of MetS in patients with schizophrenia. This could ultimately facilitate early, precise, and patient-specific pharmacological and non-pharmacological interventions to minimise CVD associated morbidity and mortality.


Health-related quality of life in patients treated for hypertension: a review of the literature from 1990 to 2000.
The goals of antihypertensive therapy are to achieve and maintain blood pressure control by the least intrusive means possible to prevent future cardiovascular and renal events. To achieve these goals, pharmacologic agents must be chosen so as to minimize drug-related adverse events, increase patient adherence to treatment regimens, and minimize the negative impact on health-related quality of life (HRQL). Although the effects of antihypertensive therapy on HRQL have been extensively investigated, there is little synthesis of the research findings. This review was undertaken to provide a synthesis of the available data on the impact of antihypertensive therapy on HRQL and to provide recommendations for future research. A MEDLINE literature search was conducted to identify English-language articles published from 1990 to 2000 that included random assignment to antihypertensive treatment and HRQL as an outcome. In addition, reference lists of published reviews and other trials were reviewed to identify other studies of HRQL and antihypertensive therapy. A total of 48 articles were included in the review. Results among studies were frequently inconsistent, which is likely due to the wide variety of dimensions studied and instruments used as well as a number of methodological weaknesses, including small sample sizes, short-term assessments, and failure to account for missing data. A standardized approach to the assessment of HRQL in hypertensive patients is needed so that research in this area can be of value to clinical practice and to hypertensive patients and their families.


Haematuria analysed--a prospective study.
One hundred consecutive cases of haematuria were studied prospectively. The results showed a high proportion (52%) of serious urological disease. The need for thorough investigation of even minor degrees of haematuria is again emphasized.


Waste ashes for use in agricultural production: I. Liming effect, contents of plant nutrients and chemical characteristics of some metals.
The chemical characteristics of 89 municipal waste ashes, including food scrap ash (FSA), animal waste ash (AWA), horticulture waste ash (HWA), sewage sludge ash (SSA) and incinerator bottom ash (IBA), from various locations in Japan were examined with the aim of evaluating their suitability for use in agriculture. Although the waste ashes came from different sources and consisted of various materials, the gross elemental composition was similar. Acid neutralization capacity (liming effect) for the waste ashes was equivalent to 10-30% of CaO and followed the sequence SSA > IBA > AWA > FSA > HWA. Average P concentrations for the five types of waste ashes ranged from 10 to 29 g kg(-1) and average K concentrations ranged from 14 to 63 g kg(-1), respectively. Metal contents in the waste ashes were compared with levels in Japanese agricultural soils. K in the waste ashes was 1.3-6 times higher and Ca was 3-12 times higher; contents of the other metals in FSA, AWA and HWA were generally less than five times higher, but Ni, Cu, Zn, Cd, Sn, Pb in SSA or IBA were approximately 10-200 times higher than those in soils. Moreover, the ceiling amounts of waste ashes that may be applied to main Japanese agricultural soils were calculated by using soil contamination standards for Cu. Water solubility of P and metals in the waste ashes were also examined.


Isolation of Neutrophils from Nonhuman Species.
The development of new advances in understanding the role of neutrophils in inflammation requires effective procedures for isolating and purifying neutrophils. Methods for isolating human neutrophils are fairly standard, and some are covered in other chapters of this volume and previous editions. However, procedures for isolating neutrophils from nonhuman species used to model human diseases vary from those used in isolating human neutrophils and are not as well developed. Since neutrophils are highly reactive and sensitive to small perturbations, the methods of isolation are important to avoid isolation technique-induced alterations in cell function. We present methods here for reproducibly isolating highly purified neutrophils from large animal models (bovine, equine, ovine), small animal models (murine and rabbit), and nonhuman primates (cynomolgus macaques) and describe optimized details for obtaining the highest cell purity, yield, and viability.


Respiratory function in mice lacking or overexpressing the prion protein.
We investigated a possible involvement of the prion protein in ventilatory control in four groups of mice, those deficient for the prion protein (PrP(c)), those overexpressing the prion protein, and two groups of genetically and age-matched controls. Ventilatory patterns of unrestrained mice were measured in a whole-body plethysmograph. Between each genotype and its control, we compared ventilation at rest and the ventilatory response to moderate hypoxia (10-12% O2), hyperoxia and hyperoxic hypercapnia. Mice lacking or overexpressing PrP(c) and their respective controls showed similar ventilatory patterns at rest and similar chemosensory responses when awake and under urethane anesthesia. Our results do not support the view that PrP(c) may play any significant role in basal ventilation or in the chemosensory ventilatory control of adult mice.


Outcomes of customized topographic guided epithelial debridement for corneal collagen cross-linking.
To evaluate the outcomes of corneal collagen cross-linking performed with customized epithelial debridement technique in progressive keratoconic corneas. Forty eyes of 40 patients were included in the study. We performed an ophthalmologic examination and recorded the uncorrected visual acuity, best corrected visual acuity (BCVA), central corneal thickness at the thinnest point (t-CCT), flat meridian keratometry (K1), steep meridian keratometry (K2), endothelial cell density (ECC), hexagonal cells (HEX), and coefficient of variation of cell areas (CV) measured preoperatively and at the 1st, 3rd, 6th and 12th months postoperatively. The mean UCVA and BCVA were increased (p < 0.05). The mean flattest and steepest K readings were decreased (p < 0.05). The mean t-CCT decreased in the first months after treatment and increased after 6 months. The mean t-CCT was thicker at 12 months compared to pretreatment status (p < 0.05). The mean ECC and CV were not significantly different between follow-up intervals (p > 0.05). The mean HEX was statistically increased (p > 0.05). Corneal collagen cross-linking performed with customized epithelial debridement technique is a successful alternative method for stopping the progression of keratoconus after 12 months of treatment.


A conjugation-specific gene (cnjC) from Tetrahymena encodes a protein homologous to yeast RNA polymerase subunits (RPB3, RPC40) and similar to a portion of the prokaryotic RNA polymerase alpha subunit (rpoA).
The cnjC gene from the protozoan Tetrahymena thermophila was completely sequenced. The deduced gene product was found to have significant sequence similarity to the yeast and prokaryotic RNA polymerase subunits involved with subunit assembly. Since cnjC is active only during the sexual stage (conjugation) of Tetrahymena's life cycle, these results indicate it may be part of a novel type of transcriptional control. The yeast proteins to which the Tetrahymena cnjC is homologous are the 40 kd protein of RNA polymerases I and III (coded for by gene RPC40) and the third-largest subunit of RNA polymerase II (coded for by gene RPB3). The degree of similarity of the cnjC protein to the two yeast subunits was found to be greater than the similarity of the two yeast subunits to each other. The alpha subunit of the core RNA polymerase from prokaryotes (coded for by gene rpoA) was found to have regions of similarity to the cnjC protein as well as to the subunits encoded by RPC40 and RPB3. Regions of high conservation among the four proteins are noted. The significance of these results is discussed.


Optimal use of polyethylene glycol for preparation of small bowel video capsule endoscopy: a network meta-analysis.
Standardized strategy of bowel preparation before video capsule endoscopy (VCE) remains controversial. This study aimed to assess the ideal dose of PEG, based on small bowel visualization quality (SBVQ), diagnostic yield (DY), and complete rate (CR) of VCE using a network meta-analysis (NMA) of randomized controlled trials (RCTs). This NMA included RCTs comparing any of the following bowel preparation interventions for VCE: fasting overnight ("Fast"), 1 liter PEG ("PEG 1L"), 2-liter PEG ("PEG 2L"), or 4-liter PEG ("PEG 4L"). The authors searched papers in PubMed, Cochrane Library, and Embase as of June 2016. The cumulative ranking (SUCRA) probabilities to rank different doses of PEG and Fast were used. The search engine provided 102 studies. Nine RCTs including 982 patients were incorporated into this analysis. All studies showed low risk of bias of blinding. SUCRA provided an initial ranking among these strategies, in which PEG 2 L showed the best score in SBVQ (PEG 2 L, 89.4%; PEG 1 L, 62.5%; PEG 4 L, 44.0%; Fast, 4.1%) and DY (PEG 2 L, 74.6%; PEG 1 L 28.1%; PEG 4 L 65.9%; Fast 31.4%) of VCE. No significant difference was shown in the analysis of CR. This study recommends PEG 2 L as the ideal dose, which may improve the SBVQ of VCE and, therefore, diagnostic accuracy. Multi-center randomized controlled trials are required to verify these findings.