T cell cytokine gene polymorphisms in canine diabetes mellitus.
Insulin-deficiency diabetes in dogs shares some similarities with human latent autoimmune diabetes of adults (LADA). Canine diabetes is likely to have a complex pathogenesis with multiple genes contributing to overall susceptibility and/or disease progression. An association has previously been shown between canine diabetes and MHC class II genes, although other genes are also likely to contribute to the genetic risk. Potential diabetes susceptibility genes include immuno-regulatory TH1/TH2 cytokines such as IFNgamma, IL-12, IL-4 and IL-10. We screened these candidate genes for single nucleotide polymorphisms (SNPs) in a range of different dog breeds using dHPLC analysis and DNA sequencing. Thirty-eight of the SNPs were genotyped in crossbreed dogs and seven other breed groups (Labrador Retriever, West Highland White Terrier, Collie, Schnauzer, Cairn Terrier, Samoyed and Cavalier King Charles Spaniel), which demonstrated substantial intra-breed differences in allele frequencies. When SNPs were examined for an association with diabetes by case:control analysis significant associations were observed for IL-4 in three breeds, the Collie, Cairn Terrier and Schnauzer and for IL-10 in the Cavalier King Charles Spaniel. These results suggest that canine cytokine genes regulating the TH1/TH2 immune balance might play a contributory role in determining susceptibility to diabetes in some breeds.


A new species of Polystomoides ward, 1917 (Monogenea: polystomatidae) from freshwater chelonians (Testudines: chelidae) in Brazil.
This report describes the first occurrence of Polystomoides brasiliensis n. sp. (Monogenea: Polystomatidae), a new monogenean species in the buccal and pharyngeal cavities of the freshwater turtles in Brazil. Live monogeneans were collected from Hydromedusa maximiliani and Phrynops geoffroanus at the Mariano Procópio Museum's lake, in Juiz de Fora, Minas Gerais, Brazil. Polystomoides brasiliensis differs from all other species of this genus in having 8-9 genital spines, except for Polystomoides uruguayensis, which has 8-10 genital spines. However, the new species differs morphometrically from P. uruguayensis in the greater size of the outer and inner hamuli, as well as having a testis that is proportionally greater than the pharynx and oral sucker. The current study is the first report of monogeneans in chelonians of Brazil, and the first record of helminths in H. maximiliani.


Surgery for colorectal cancer guided by radiodetecting probe. Clinical evaluation using monoclonal antibody B72.3.
Radioactive antibodies that react with tumour-associated antigens to "tag" antigen-positive tumour cell deposits were given to 20 patients with primary or recurrent colorectal cancer. The tumour associated antigen TAG 72-specific monoclonal antibody B72.3 labelled with 125-Iodine was used, and the radioactivity in the tumour was sought during operation with a hand-held gamma detecting probe. Tumour was detected by the probe in 7 of 15 patients with primary cancer, with a mean tumour: normal tissue ratio of 3.9, and in 4 of 5 patients with recurrent disease, with a mean tumour: normal tissue ratio of 2.0. Immunohistochemical analysis of surgical specimens confirmed the results of the intraoperative detection. The incidence of TAG 72-positive tumours (11/20, 55%), detected by immunohistochemistry, was lower than the 80% in the other series, possibly because of sampling errors or because the cases studied were uncomplicated with small primary tumours. Results obtained with the probe were instrumental in modifying the operation in two of the four "positive" patients with recurrences, allowing the removal of tumour masses that would otherwise have been overlooked.


Highly efficient blue fluorescent materials based on fluorene derivatives end-capped with arylaminofluorenylethylenes for organic light-emitting diodes.
Multilayered organic light-emitting diodes (OLEDs) were fabricated by using the new fluorine derivatives end-capped with arylaminofluorenylethylenes as dopant materials. The device structure was ITO/NPB/15% blue dopants doped in MADN/Bphen/Liq/Al. Among those, a device shows the maximum luminance of 40800 cd/m2 at 12 V, the luminous efficiency of 12.8 cd/A at 20 mA/cm2, power efficiency of 9.13 Im/W at 20 mA/cm2 and CIE(x,y) coordinates of (x = 0.188, y = 0.372) at 8 V.


Improved oxygen release: an adaptation of mature red cells to hypoxia.
Blood from patients with erythrocytosis secondary to arterial hypoxemia due either to congenital heart disease or to chronic obstructive pulmonary disease was shown to have a decreased affinity for oxygen; the average oxygen pressure required to produce 50% saturation of hemoglobin with oxygen was 29.8 mm Hg (average normal, 26.3 mm Hg). Such a displacement of the blood oxygen equilibrium curve promotes the release of oxygen from blood to the tissues. Studies were also performed upon blood from a man with complete erythrocyte aplasia who received all of his red cells by transfusion from presumably normal persons. With mild anemia (hematocrit, 28%), the affinity of his blood for oxygen was slightly diminished (an oxygen pressure of 27.0 mm Hg was required to produce 50% saturation of hemoglobin with oxygen). With severe anemia (hematocrit, 13.5%), however, his blood had a markedly decreased oxygen affinity (an oxygen pressure of 29.6 mm Hg was required to produce 50% saturation of hemoglobin with oxygen). We conclude that patients with various conditions characterized by an impairment in the oxygen supply system to tissues respond with a diminished affinity of their blood for oxygen. Although the mechanism which brings about this adaptation is not known, the displacement of the oxygen equilibrium curve is associated with an increase in heme-heme interaction. The decrease in blood oxygen affinity need not occur during erythropoiesis, but may be imposed upon mature circulating red cells.


Substrate-dependent gene regulation of self-assembled human MSC spheroids on chitosan membranes.
Three-dimensional (3D) multicellular spheroids of mesenchymal stem cells (MSCs) are generally regarded to have beneficial properties over MSCs in monolayer. Recent literatures have documented that MSCs can self-assemble into 3D spheroids with a greater capacity for differentiation into various cell types when grown on chitosan (CS), a biopolymer. The genomic modulation occurring in these MSC spheroids is thus of essential importance for understanding their uniqueness and therapeutic potentials. In this study, 3D spheroids self-assembled from human umbilical cord MSCs grown on CS membranes were analyzed by mRNA as well as microRNA microarrays, which helped identify the critical signaling events that may alter the cellular functions during the spheroid forming process. Genes screened from mRNA and microRNA cross-correlation analyses were further confirmed with the quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis. Results revealed the regulation of a significant number of calcium-associated genes, which suggested the crucial role of calcium signaling in CS-derived MSC spheroids. In addition, many genes associated with the multilineage differentiation capacities and those associated with the antiinflammatory and antitumor properties of MSCs were upregulated. The genetic modulation was significantly more remarkable and endured longer for MSC spheroids derived on CS substrates compared to those derived on a non-adherent (polyvinyl alcohol) substrate. Based on the study, the culture substrates used to prepare 3D MSC spheroids may predefine their properties through cell-substrate interaction.


Evaluation of dietary Hybanthus enneaspermus (Linn F. Muell.) as a growth and haemato-immunological modulator in Labeo rohita.
This study evaluated the effects of Hybanthus enneaspermus aqueous extract (HEE) as a feed supplement on growth, immune responses, haematological, and biochemical parameters of Labeo rohita and its susceptibility to Aeromonas hydrophila infection. Diets containing five variable concentrations of HEE (g kg-1) (0 [basal diet], 1.0 [H1], 2.0 [H2], 3.0 [H3], and 4.0 [H4]) were fed to fish (average weight: 17.2 ± 0.21 g) for 6 weeks. Growth parameters, immune parameters, and haemato-biochemical parameters were examined 6 weeks post-feeding. The results showed that growth parameters, such as final weight (39.47 ± 3.1 g) and specific growth rate (1.92 ± 0.2), were significantly higher in the H3 group than in the control. Immunological parameters such as serum lysozyme (24.73 ± 2.16 U mg-1), phagocytic activity (19.14± 0.26%), and respiratory burst activity (0.307 ± 0.005) were significantly higher in the H3 group, compared with the control. Among the haematological parameters examined, red blood cells, white blood cells, neutrophils, total serum protein, and albumin levels were significantly higher in the H3 group. However, HEE administration had no significant effect on haematocrit, haemoglobin, monocytes, or eosinophils levels. Blood biochemical parameters, including superoxide dismutase and alkaline phosphatase activities, were higher (P < 0.05) in the H3 group than in the control; however, the opposite result was found for aspartate transaminase, alanine transaminase, glucose, and cholesterol. Supplementation with 3 g kg-1 HEE increased the activities of intestinal digestive enzyme (amylase, protease, and lipase) in fish. Moreover, fish fed diets supplemented with 3 g kg-1 HEE exhibited the highest disease resistance against A. hydrophila infection. These results suggest that dietary administration of HEE (at 3 g kg-1) has several positive effects on growth, immune and haematological responses in L. rohita.


Randomized trial of brief office-based interventions to reduce adolescent alcohol use.
To determine whether office-based interventions change adolescents' alcohol beliefs and alcohol use. Randomized, controlled trial. Five managed care group practices in Washington, DC. Consecutive 12- to 17-year-olds (N = 409) seeing primary care providers (N = 26) for general check-ups. Most of the adolescents (79%) were African American, 44% were male, and 16% currently drank. Usual care (Group I), adolescent priming with alcohol self-assessment just prior to check-up (Group II), adolescent priming and provider prompting with adolescent self-assessment and brochure (Group III). Adolescent alcohol beliefs at exit interview and self-reported behaviors at 6- and 12-month follow-up. At exit interview, Groups II and III reported that less alcohol was needed for impaired thinking and a greater intent to drink alcohol in the next 3 months than Group I. At 6 months, Group III reported more resistance to peer pressure to drink, and Groups II and III reported more bingeing than Group I. At 1-year follow-up, controlling for baseline levels, Groups II (odds ratio [OR], 3.44; 95% confidence interval [CI], 1.44-6.24) and III (OR, 2.86; CI, 1.13-7.26) reported more bingeing in the last 3 months than Group I. Group II reported more drinking in the last 30 days (OR, 2.31; CI, 1.31-4.07) and in the last 3 months (OR, 1.76; CI, 1.12-2.77) than Group I. Brief office-based interventions were ineffective in reducing adolescent alcohol use but may increase adolescent reporting of alcohol use.


Diabetes-induced mechanophysiological changes in the small intestine and colon.
The disorders of gastrointestinal (GI) tract including intestine and colon are common in the patients with diabetes mellitus (DM). DM induced intestinal and colonic structural and biomechanical remodeling in animals and humans. The remodeling is closely related to motor-sensory abnormalities of the intestine and colon which are associated with the symptoms frequently encountered in patients with DM such as diarrhea and constipation. In this review, firstly we review DM-induced histomorphological and biomechanical remodeling of intestine and colon. Secondly we review motor-sensory dysfunction and how they relate to intestinal and colonic abnormalities. Finally the clinical consequences of DM-induced changes in the intestine and colon including diarrhea, constipation, gut microbiota change and colon cancer are discussed. The final goal is to increase the understanding of DM-induced changes in the gut and the subsequent clinical consequences in order to provide the clinicians with a better understanding of the GI disorders in diabetic patients and facilitates treatments tailored to these patients.


Efficacy of omalizumab in chronic spontaneous urticaria refractory to conventional therapy: analysis of 110 patients in real-life practice.
To collect data on the efficacy and safety of omalizumab in 110 patients from 9 Spanish hospitals suffering from chronic spontaneous urticaria (CSU) refractory to conventional treatment. A retrospective, descriptive analysis was performed, showing the data of 110 patients suffering from refractory CSU who received omalizumab as an off-label treatment in 9 Spanish hospitals from October 2009 to September 2012. Ninety (81.8%) patients exhibited a complete or significant response, 12 (10.9%) had partial response, and 8 (7.2%) showed no response. Sixty-six (60%) patients were able to stop all concomitant medications, remaining asymptomatic treated with omalizumab alone. No serious adverse events were reported. Omalizumab shows excellent efficacy and safety profile in a large series of CSU patients in real-life practice. This drug will contribute to settle the debt with CSU patients contributing to restore their quality of life.


[Behcet's disease in France. Apropos of 60 autochtonous subjects].
Based on a retrospective study of a series of 196 patients followed up from 1974, to 1986, 60 cases of Behcet's disease are reviewed in autochthonous French patients, defined as born of French parents in Metropolitan France. The group included 36 men and 27 women (sex ratio 1.45) age range 32 +/- 7 years at time of diagnosis. Semeiology and outcome were compared with those of North African patients, the bias related to their female under-representation being eliminated by analysis of findings in males only. No significant difference was noted between the two groups, particularly with respect to ocular, neurological and vascular lesions. Neither the sex nor the existence of HLA B5 (28/40 tests) had any influence on semeiology. Three deaths related to the disease were reported two pregnancies were conducted to term without neonatal effects despite maternal acute ocular episodes. Treatment was with corticoids (n = 33), immunodeppressants (n = 15), colchicine (n = 29) and anticoagulant and/or anti-aggregant therapy (n = 31). Lasting disappearance of aphthosis was obtained in 34 cases, of cutaneous signs in 27, articular signs in 26 and vascular signs in 16. The ocular lesions present initially in 41 patients had disappeared over long periods in 29 cases, and presented a satisfactory prognosis since less than 39 p. 100 of the patients had any significant handicap at 5 years. Among the relapses, 5 appeared after too hasty withdrawal of colchicine. The diagnosis of Behcet's disease should be evoked in autochthonous subjects if necessary, and confirmed on the basis of usual clinical criteria alone.(ABSTRACT TRUNCATED AT 250 WORDS)


Mapping of powdery mildew resistance gene Pm53 introgressed from Aegilops speltoides into soft red winter wheat.
A powdery mildew resistance gene was introgressed from Aegilops speltoides into winter wheat and mapped to chromosome 5BL. Closely linked markers will permit marker-assisted selection for the resistance gene. Powdery mildew of wheat (Triticum aestivum L.) is a major fungal disease in many areas of the world, caused by Blumeria graminis f. sp. tritici (Bgt). Host plant resistance is the preferred form of disease prevention because it is both economical and environmentally sound. Identification of new resistance sources and closely linked markers enable breeders to utilize these new sources in marker-assisted selection as well as in gene pyramiding. Aegilops speltoides (2n = 2x = 14, genome SS), has been a valuable disease resistance donor. The powdery mildew resistant wheat germplasm line NC09BGTS16 (NC-S16) was developed by backcrossing an Ae. speltoides accession, TAU829, to the susceptible soft red winter wheat cultivar 'Saluda'. NC-S16 was crossed to the susceptible cultivar 'Coker 68-15' to develop F2:3 families for gene mapping. Greenhouse and field evaluations of these F2:3 families indicated that a single gene, designated Pm53, conferred resistance to powdery mildew. Bulked segregant analysis showed that multiple simple sequence repeat (SSR) and single nucleotide polymorphism (SNP) markers specific to chromosome 5BL segregated with the resistance gene. The gene was flanked by markers Xgwm499, Xwmc759, IWA6024 (0.7 cM proximal) and IWA2454 (1.8 cM distal). Pm36, derived from a different wild wheat relative (T. turgidum var. dicoccoides), had previously been mapped to chromosome 5BL in a durum wheat line. Detached leaf tests revealed that NC-S16 and a genotype carrying Pm36 differed in their responses to each of three Bgt isolates. Pm53 therefore appears to be a new source of powdery mildew resistance.


Channel activity caused by a Bacillus thuringiensis delta-endotoxin preparation depends on the method of activation.
The spontaneous insertion of Bacillus thuringiensis Cry delta-endotoxins into planar lipid bilayers to form discrete channels in the absence of receptors is the subject of conflicting reports in the literature. Because these proteins are synthesized as protoxins requiring proteolytic activation for conversion to the active form, differences in the in-vitro protocol used for this activation could be responsible for the contradictory results. To investigate this, CrylA(c) toxin was activated by different procedures, and its ability to release glucose entrapped within liposomes and to form channels in planar lipid bilayers assessed. The toxin preparations exhibited widely differing activities on the lipid membranes; SDS-PAGE and immunoblot analysis suggested that variations in the protein profile of the activated samples could be responsible. These findings raise important practical considerations for further in-vitro studies into the mechanism of action of these toxins.


The physical therapist as a member of the home healthcare team: caring for patients with replacements.
The projected life of a total knee and total hip replacement today is approximately 15 years. Orthopedic surgeons are therefore very cautious to replace joints in patients who are young, believing that if patients receive joint replacements in their mild or early 60s, there is a good possibility they may outlive the replacement and thereby require a revision. One role of physical therapy with the postoperative replacement patient is education of the patient in precautions that should be observed and guidelines to be followed for general activities. This is very valuable information that should be shared with the patient before surgery and reinforced afterward. In the changing healthcare environment of the 1990s, home healthcare professionals are being challenged to provide effective, skilled care that is the most cost effective and appropriate for patients. It is important that all professional home healthcare personnel work as a team to accomplish these goals. The PT is an important member of this team. After an acute illness or injury, or throughout the course of a chronic illness, there are numerous times when home healthcare patients will benefit from skilled PT services. Home healthcare nurses are in a unique position to recognize the need to work with the patient's physician for referral to other members of the healthcare team.


Differences of energy expenditure while sitting versus standing: A systematic review and meta-analysis.
Background Replacing sitting with standing is one of several recommendations to decrease sedentary time and increase the daily energy expenditure, but the difference in energy expenditure between standing versus sitting has been controversial. This systematic review and meta-analysis aimed to determine this difference. Designs and methods We searched Ovid MEDLINE, Ovid Embase Scopus, Web of Science and Google Scholar for observational and experimental studies that compared the energy expenditure of standing versus sitting. We calculated mean differences and 95% confidence intervals using a random effects model. We conducted different predefined subgroup analyses based on characteristics of participants and study design. Results We identified 658 studies and included 46 studies with 1184 participants for the final analysis. The mean difference in energy expenditure between sitting and standing was 0.15 kcal/min (95% confidence interval (CI) 0.12-0.17). The difference among women was 0.1 kcal/min (95% CI 0.0-0.21), and was 0.19 kcal/min (95% CI 0.05-0.33) in men. Observational studies had a lower difference in energy expenditure (0.11 kcal/min, 95% CI 0.08-0.14) compared to randomised trials (0.2 kcal/min, 95% CI 0.12-0.28). By substituting sitting with standing for 6 hours/day, a 65 kg person will expend an additional 54 kcal/day. Assuming no increase in energy intake, this difference in energy expenditure would be translated into the energy content of about 2.5 kg of body fat mass in 1 year. Conclusions The substitution of sitting with standing could be a potential solution for a sedentary lifestyle to prevent weight gain in the long term. Future studies should aim to assess the effectiveness and feasibility of this strategy.


Effect of tamoxifen and D,L-2-difluoromethylornithine on the growth, ornithine decarboxylase activity and polyamine content of mammary carcinomas induced by 1-methyl-1-nitrosourea.
The effect of combined treatment with D,L-2-difluoromethylornithine (DFMO) and tamoxifen on the growth status, ornithine decarboxylase (ODC) activity and polyamine content of established 1-methyl-1-nitrosourea (MNU)-induced mammary tumors was investigated. DFMO treatment, a 0.125% solution provided as drinking water, inhibited the rate of tumor occurrence and reduced the number of mammary tumors induced by a high dose of MNU (50 mg/kg body weight) during the first 120 days post-carcinogen treatment. Tamoxifen was administered daily via s.c. injection (25 micrograms/100 g body weight) to tumor-bearing rats in both treatment groups, i.e. control and DFMO-treated, for a 30-day period beginning 120 days after carcinogen. Tamoxifen treatment induced tumor regression but the percentage of regressing, static or growing tumors was no different in the presence or absence of DFMO. Whereas the mammary tumors of DFMO-treated rats had reduced ODC activity and lower polyamine concentrations in comparison to the tumors of untreated animals, tamoxifen had no effect on these parameters independent of its effect on tumor growth status. DFMO did not increase the efficacy of tamoxifen in inducing tumor regression.


[Survival by a young woman with malnutrition due to alcoholism and eating disorders and with acute respiratory distress syndrome due to severe pneumonia who showed increased serum neutrophil elastase activity].
A 30-year-old woman with malnutrition due to alcoholism and eating disorders was found to have acute respiratory distress syndrome (ARDS) and sepsis due to severe Streptococcus pneumoniae pneumonia. S. pneumoniae was detected by an in vitro rapid immunochromatographic assay for S. pneumoniae antigen in urine on the day of admission and by blood culture 2 days after admission. Symptoms and laboratory findings improved after treatment with sivelestat sodium hydrate, antibiotics, and mechanical ventilation. Treatment with sivelestat sodium hydrate also decreased serum neutrophil elastase activity. This case demonstrates the usefulness of early treatment with sivelestat sodium hydrate in ARDS due to severe pneumonia.


Probing the effect of ethylene carbonate on optimizing the halogen-free electrolyte performance for Mg sulfur batteries.
Magnesium metal batteries attract great attention for their high volumetric capacity and safety as a post-lithium choice. The strategy of adding organic plasticizer may bring new insights into designing halogen-free electrolytes for the further development of magnesium-sulfur batteries. The high charge density of Mg2+ results in a high desolvation barrier and low interfacial Mg2+ transfer kinetics due to the strong coulombic interactions of Mg2+ ions with anions and solvent molecules. In this study, we test the effect of the stoichiometric ratio of ethylene carbonate (EC) as an organic additive on the electrochemical performance of halogen-free electrolyte (HFE) based on Mg(NO3)2 in acetonitrile (ACN) and tetraethylene glycol dimethyl ether (G4). Through various characterization methods, the introduction of EC perturbs the bonding scheme of the HFE electrolyte, enhances the ionic conductivity, reduces the relaxation time, and forms a resistive solid electrolyte interphase (SEI). The assembled Mg-S full cell using modified HFE (HFE_EC) delivers initial specific capacities of 900 m Ag-1 with a cycle life of up to 10 cycles in the case of activating the cell with electrochemical conditioning. This study sheds light on the interplay of EC and the interfacial kinetics in Mg batteries and opens a door for designing novel magnesium electrolytes.


The relationship between albumin and its proportion to other markers in predicting mortality in severe COVID-19 patients.
The aim of the present study was to investigate the relationship between albumin, blood urea nitrogen (BUN)/albumin ratio (BAR), D-dimer/albumin ratio (DAR), C-reactive protein (CRP)/albumin ratio (CAR), and neutrophil/albumin ratio (NAR) levels and prognosis in severe COVID-19 cases. A total of 619 patients diagnosed with severe COVID-19 in the emergency department were retrospectively analyzed. BAR, DAR, CAR, and NAR values were obtained by dividing BUN, neutrophil, CRP, and D-dimer by albumin. All patients were divided into groups [survived and deceased patients, and those who received and did not receive mechanical ventilation (MV) assistance]. These groups were statistically compared with regard to albumin, BAR, DAR, CAR, and NAR. While 350 out of 619 patients survived, 269 patients died. A statistically significant difference was determined between survived and deceased patient groups with regard to BUN, neutrophil, lymphocyte, CRP, D-dimer, albumin, BAR, NAR, DAR, and CAR levels (p<0.001 for all). Also, BAR, NAR, DAR, and CAR were significantly higher in those who received MV support, while albumin was found to be low (p<0.001). According to receiver operating characteristic (ROC) analysis, NAR, BAR, CAR, albumin, and DAR had the highest area under the curve (AUC) values compared to the other parameters (0.825, 0.815, 0.806, 0.772, and 0.770, respectively) (p<0.001 for all). According to logistic regression analysis, BAR, NAR, DAR, and CAR levels were determined as important risk factors for mortality. Low serum albumin levels can be used for severity as an additional tool in severe COVID-19 patients. Moreover, the NAR, BAR, and CAR levels were found to be more valuable than albumin levels in predicting prognosis in these patients.


Retroperitoneal lymph node dissection in clinical stage IIA and IIB nonseminomatous germ cell tumours of the testis.
From 1980 to 1984 inclusive, ninety-one consecutive evaluable patients underwent primary retroperitoneal lymphadenectomy for clinical stage IIA or IIB nonseminomatous germinal testicular cancer. Nodes were negative in twenty cases (22%), and forty-seven patients (52%) were treated with chemotherapy either postoperatively (thirty clinically understaged patients) or at relapse (seventeen cases). After a median follow-up period of nearly 5 years (range 18-78 months) the disease-free survival was 98%. None of thirty patients with radiographic abnormalities greater than or equal to 3 cm in the retroperitoneal nodes had negative histology, and twenty-two (73%) were treated with chemotherapy. Preoperative serum levels of AFP and hCG were not useful in selecting patients with positive nodes. Primary chemotherapy is now used in patients with radiographic evidence of retroperitoneal metastases greater than or equal to 3 cm.


Synthesis of Functionalized 10-nm Polymer-coated Gold Particles for Endothelium Targeting and Drug Delivery.
Gold nanoparticles (AuNPs) have been used extensively in medical research due to their size, biocompatibility, and modifiable surface. Specific targeting and drug delivery are some of the applications of these AuNPs, but endothelial extracellular matrices' defensive properties hamper particle uptake. To address this issue, we describe a synthesis method for ultrasmall gold nanoparticles to improve vascular delivery, with customizable functional groups and polymer lengths for further adjustments. The protocol yields 2.5 nm AuNPs that are capped with tetrakis(hydroxymethyl)phosphonium chloride (THPC). The replacement of THPC with hetero-functional polyethylene glycol (PEG) on the surface of the AuNP increases the hydrodynamic radius to 10.5 nm while providing various functional groups on the surface. The last part of the protocol includes an optional addition of a fluorophore to allow the AuNPs to be visualized under fluorescence to track nanoparticle uptake. Dialysis and lyophilization were used to purify and isolate the AuNPs. These fluorescent nanoparticles can be visualized in both in vitro and in vivo experiments due to the biocompatible PEG coating and fluorescent probes. Additionally, the size range of these nanoparticles render them an ideal candidate for probing the glycocalyx without disrupting normal vasculature function, which may lead to improved delivery and therapeutics.


Current guidelines on prevention with a focus on dyslipidemias.
Examination of the current the American College of Cardiology/American Heart Association (ACC/AHA) and European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines on the prevention of cardiovascular disease and the management of dyslipidemias finds much common ground. Both note that Atherosclerotic cardiovascular disease (ASCVD) is, in most people, the product of a number of risk factors, notably tobacco exposure, hyperlipidemia, hypertension, inactivity, overweight and diabetes. They stress that risk calculators can help in the assessment of risk in apparently healthy persons. Persons with established ASCVD and many with diabetes or renal impairment are at high to very high risk and warrant intensive risk factor advice and guideline-based preventive therapies. The ACC/AHA guidelines favor the universal use of statins in all high-risk subjects and in primary prevention where the global risk exceeds 7.5% in 10 years, with a percentage reduction in low-density lipoprotein cholesterol (LDL-C) based on statin intensity as the "goal". In contrast, the ESC/EAS guidelines favor a goal or percentage-based reduction in LDL-C based on total risk and baseline LDL-C level. Both guidelines consider certain imaging and other measures to stratify risk as well as the use of non-statin therapies in those not achieving recommended targets. Perhaps the most important challenges are to stress similarities rather than differences, and to simplify communications with both healthcare professionals and the public.


RNA-seq transcriptome analysis of the immature seeds of two Brassica napus lines with extremely different thousand-seed weight to identify the candidate genes related to seed weight.
Brassica napus is an important oilseed crop worldwide. Although seed weight is the main determinant of seed yield, few studies have focused on the molecular mechanisms that regulate seed weight in B. napus. In this study, the immature seeds of G-42 and 7-9, two B. napus doubled haploid (DH) lines with extremely different thousand-seed weight (TSW), were selected for a transcriptome analysis to determine the regulatory mechanisms underlying seed weight at the whole gene expression level and to identify candidate genes related to seed weight. A total of 2,251 new genes and 2,205 differentially expressed genes (DEGs) were obtained via RNA-seq (RNA sequencing). Among these genes, 1,747 (77.61%) new genes and 2020 (91.61%) DEGs were successfully annotated. Of these DEGs, 1,118 were up-regulated and 1,087 were down-regulated in the large-seed line. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database analysis indicated that 15 DEGs were involved in ubiquitin-mediated proteolysis and proteasome pathways, which might participate in regulating seed weight. The Gene Ontology (GO) database indicated that 222 DEGs were associated with the biological process or molecular function categories related to seed weight, such as cell division, cell size and cell cycle regulation, seed development, nutrient reservoir activity, and proteasome-mediated ubiquitin-dependent protein catabolic processes. Moreover, 50 DEGs encoding key enzymes or proteins were identified that likely participate in regulating seed weight. A DEG (GSBRNA2T00037121001) identified by the transcriptome analysis was also previously identified in a quantitative trait locus (QTL) region for seed weight via SLAF-seq (Specific Locus Amplified Fragment sequencing). Finally, the expression of 10 DEGs with putative roles in seed weight and the expression of the DEG GSBRNA2T00037121001 were confirmed by a quantitative real-time reverse transcription PCR (qRT-PCR) analysis, and the results were consistent with the RNA sequencing data. This work has provided new insights on the molecular mechanisms underlying seed weight-related biosynthesis and has laid a solid foundation for further improvements to the seed yield of oil crops.


Optimizing Timing of Immunotherapy Improves Control of Tumors by Hypofractionated Radiation Therapy.
The anecdotal reports of promising results seen with immunotherapy and radiation in advanced malignancies have prompted several trials combining immunotherapy and radiation. However, the ideal timing of immunotherapy with radiation has not been clarified. Tumor bearing mice were treated with 20Gy radiation delivered only to the tumor combined with either anti-CTLA4 antibody or anti-OX40 agonist antibody. Immunotherapy was delivered at a single timepoint around radiation. Surprisingly, the optimal timing of these therapies varied. Anti-CTLA4 was most effective when given prior to radiation therapy, in part due to regulatory T cell depletion. Administration of anti-OX40 agonist antibody was optimal when delivered one day following radiation during the post-radiation window of increased antigen presentation. Combination treatment of anti-CTLA4, radiation, and anti-OX40 using the ideal timing in a transplanted spontaneous mammary tumor model demonstrated tumor cures. These data demonstrate that the combination of immunotherapy and radiation results in improved therapeutic efficacy, and that the ideal timing of administration with radiation is dependent on the mechanism of action of the immunotherapy utilized.


A New Mutation of the INSR Gene in a 13-Year-Old Girl with Severe Insulin Resistance Syndrome in China.
Mutations in insulin receptor genes can cause severe insulin resistance syndrome. Compared with Rabson-Mendenhall Syndrome and Donohue's Syndrome, type A insulin resistance syndrome is generally not serious. The main manifestations in woman with type A insulin resistance syndrome are hyperinsulinemia, insulin resistance, acanthosis nigricans, hyperandrogenism, and polycystic ovary. Case Presentation. A 13-year-old girl (Han nationality) visited the hospital due to hairiness and acanthosis nigricans. Further examination revealed severe hyperinsulinemia, insulin resistance, elevated blood glucose, hyperandrogenism, and polycystic ovary. Analysis of the insulin receptor gene by sequencing showed the presence of a nucleotide change in intron 7 (c. 1610+1G > A). The mutation was a splicing mutation, which can obviously affect the mRNA splicing of the insulin receptor and cause its function loss. The patient was finally diagnosed with type A insulin resistance syndrome. After 2 months of metformin treatment, the patient had spontaneous menstrual cramps and significantly improved acanthosis nigricans and sex hormones. We report for the first time a new splicing mutation on the insulin receptor gene at the 7th intron (c.1610+1G > A), which leads to type A insulin resistance syndrome. In clinically suspected patients with polycystic ovary syndrome, if there are extremely high blood levels of insulin in the blood, genetic testing should be performed to detect insulin receptor gene mutation of type A insulin resistance syndrome.


Recurrent intracranial epithelioid hemangioendothelioma associated with multicentric disease of liver and heart: case report.
Epithelioid hemangioendothelioma is an unusual vascular neoplasm with prominent cytoplasmic vacuolization representing primitive lumen formation. A case is presented of this unique vascular neoplasm in a woman with a seizure disorder who had cardiac, hepatic, and recurrent nervous system lesions. To our knowledge, this is the third known case of intracranial epithelioid hemangioendothelioma. Emphasis is placed on the indolent course of this rare neoplasm, with a recommendation for aggressive surgical treatment and diligent follow-up.


Effect of flow rate ratio and positioning on a lighthouse tip ECMO return cannula.
Extracorporeal membrane oxygenation is a life-saving support therapy in the case of cardiopulmonary refractory failure. Its use is associated to complications due to the presence of artificial surfaces and supraphysiological stress conditions. Thus, knowledge of the fluid structures associated to each component can give insight into sources of blood damage. In this study, an experimentally validated numerical study of a conventional lighthouse tip cannula in return configuration was carried out to characterize the flow structures using water or a Newtonian blood analog with different flow rate ratios and cannula positioning and their influence on hemolysis. The results showed that strong shear layers developed where the jets from the side holes met the co-flow. Stationary backflow regions at the vessel wall were also present downstream of the cannula. In the tilted case, the recirculation was much more pronounced on the wide side and almost absent on the narrow side. Small vortical backflow structures developed at the side holes which behaved like obstacles to the co-flow, creating pairs of counter-rotating vortices, which induced locally higher risk of hemolysis. However, global hemolysis index did not show significant deviations. Across the examined flow rate ratios, the holes on the narrow side consistently reinfused a larger fraction of fluid. A radial force developed in the tilted case in a direction so as to recenter the cannula in the vessel.


Touchable Computing: Computing-Inspired Bio-Detection.
We propose a new computing-inspired bio-detection framework called touchable computing (TouchComp). Under the rubric of TouchComp, the best solution is the cancer to be detected, the parameter space is the tissue region at high risk of malignancy, and the agents are the nanorobots loaded with contrast medium molecules for tracking purpose. Subsequently, the cancer detection procedure (CDP) can be interpreted from the computational optimization perspective: a population of externally steerable agents (i.e., nanorobots) locate the optimal solution (i.e., cancer) by moving through the parameter space (i.e., tissue under screening), whose landscape (i.e., a prescribed feature of tissue environment) may be altered by these agents but the location of the best solution remains unchanged. One can then infer the landscape by observing the movement of agents by applying the "seeing-is-sensing" principle. The term "touchable" emphasizes the framework's similarity to controlling by touching the screen with a finger, where the external field for controlling and tracking acts as the finger. Given this analogy, we aim to answer the following profound question: can we look to the fertile field of computational optimization algorithms for solutions to achieve effective cancer detection that are fast, accurate, and robust? Along this line of thought, we consider the classical particle swarm optimization (PSO) as an example and propose the PSO-inspired CDP, which differs from the standard PSO by taking into account realistic in vivo propagation and controlling of nanorobots. Finally, we present comprehensive numerical examples to demonstrate the effectiveness of the PSO-inspired CDP for different blood flow velocity profiles caused by tumor-induced angiogenesis. The proposed TouchComp bio-detection framework may be regarded as one form of natural computing that employs natural materials to compute.


Structural biology of the cell adhesion protein CD2: from molecular recognition to protein folding and design.
CD2 (cluster of differentiation 2) is a cell adhesion molecule expressed on T cells and is recognized as a target for CD48 (rats) and CD58 (humans). Tremendous progress has been achieved in understanding the function of CD2, the mechanism of molecular recognition and protein folding, thus, leading towards the use of this protein as a scaffold for protein design. CD2 has been shown to set quantitative thresholds in T cell activation both in vivo and in vitro. Further, intracellular CD2 signaling pathways and networks are being discovered by the identification of several cytosolic tail binding proteins. In addition, a new method for directly measuring heterophilic adhesion has been developed. The functional "hot spot" for the adhesion surface of CD2 and CD58 has been dissected. Detailed NMR studies reveal that rat CD2 weakly self-associates to form a homodimeric structure in solution. Dynamic interaction of CD2 with the GYF and SH3 domains has been investigated. CD2 has been shown to form fibrils in the presence of 2,2,2-trifluoroethanol (TFE) and at low pH. Furthermore, kinetic studies have been completed to monitor the effect of surface hydrophobic residues and intramolecular bridges on the folding pathways of CD2. Our lab has de novo designed single calcium-binding sites into domain 1 of rat CD2 (CD2-D1) with strong metal selectivity. In addition, the EF-hand motifs have been grafted into CD2 to understand the site-specific calcium-binding affinity of calmodulin and calcium-dependent cell adhesion.


Nutritional aspects of lung disease.
The relationships between dietary intake, ventilatory demand, and respiratory muscle function are now well recognized. Malnutrition in patients with advanced COPD is associated with adverse effects on respiratory muscle function leading to reduced muscle strength and premature mortality. The relationships between nutrient intake and the host inflammatory response are just beginning to be explored. This article summarizes current knowledge regarding the relationship between nutritional status and the lung.


Renal hemodynamic effects of a short-term high protein and low protein diet in patients with renal disease.
The renal hemodynamic effects of short-term protein loading and short term protein restriction were studied in patients with renal disease. Eleven patients adhered to a high protein diet (1.8 g/kg/day) and, subsequently, to a low protein diet (0.6 g/kg/day) for four weeks each. Renal hemodynamics were studied at the end of the respective dietary periods. Glomerular filtration rate (inulin clearance) did not change significantly (delta %: -1.5 +/- 5.4%; mean +/- s.e.m.), whereas endogenous creatinine clearance was lower on the low protein diet (delta %: -7.8 +/- 2.8%; p less than 0.02), suggesting an interference with the tubular secretion of creatinine. Effective renal plasma flow was significantly lower on the low protein diet (223.7 +/- 47.6 ml/min vs 282.1 +/- 67.1 ml/min; delta %: -15.4 +/- 4.9%; p less than 0.02). As a result, filtration fraction increased from 0.18 +/- 0.01 on the high protein diet to 0.22 +/- 0.02 on the low protein diet (p less than 0.01). The low protein diet caused a significant decrease in protein excretion from 4.0 +/- 0.9 g/24 h to 3.1 +/- 0.7 g/24 h (p less than 0.02). Our study demonstrates that renal hemodynamic responses to more sustained protein loading and protein restriction differ from the reported responses to acute protein loading. Different mechanisms may be involved. In this light it is doubtful if the renal hemodynamic response to acute protein loading can predict a beneficial effect of protein restriction.


Immunofluorescence studies on C1Q in mast cells.
Evidence has been obtained of deposition of complement component C1q in mast cells, by the immunofluorscence technique, using biopsy specimens from the scalp from 5 of 7 normal subjects and 14 of 17 patients with alopecia areata and also from skin lesions of 1 of 2 patients with urticaria pigmentosa studied. The fluorescence in mast cells was of a granular pattern in most instances. No deposition of immunoglobulins (IgG, IgA, IgM, IgE) or other complement components (C3, C4, C5, C9) was demonstrable in the mast cells. The specificity of the C1q deposition in mast cells was confirmed by various tests, viz., the blocking test, prerinsing of tissue sections with bovine serum albumin-containing phosphate-buffered saline, absorption test of conjugates, C1q destruction test with urea or by heating, and the Ouchterlony method.


Immunostimulatory activity of Milife, a novel immunomodulator of fungus origin.
Milife is a novel immunomodulator derived from the fungus Fusarium Sambucium. In this study we examined immunomodulatory properties of Milife in 10 months-old BLRB mice. Milife was given to mice orally in a daily dose of 1 mg per mouse, for 2 to 6 days. Groups of mice were sacrificed on days 2, 4, and 6 of treatment, and 3 weeks after completion of a 6 days treatment with Milife, and lymphoid organs were obtained for analysis. Milife administration led to rapid and significant increase in total leukocyte and lymphocyte numbers in peripheral blood that persisted for at least 3 weeks after a 6 days treatment. Cellularity of lymph nodes, bone marrow and thymus increased significantly at days 4 and 6 of treatment, but returned to pretreatment levels after Milife discontinuation. Though total splenocyte numbers did not change dramatically, there occurred delayed increase in CD4+ cells in the spleen 3 weeks following treatment. Preferential accumulation of CD4+ cells was also consistently found in peripheral blood, with the peak being observed at day 6 of treatment. As a result, CD4/CD8 ratio in blood and spleen was significantly higher in treated than in untreated mice. Splenocytes from treated mice proliferated more vigorously in response to Con A. When added in vitro, Milife also mildly costimulated Con A-induced proliferation of splenocytes from intact animals. In conclusion, we have found that Milife can stimulate leuko- and lymphopoesis in BLRB mice, in particular, accumulation of CD4+ T cells in peripheral lymphoid organs. We conclude that Milife may represent an immunomodulator with the potential to correct T cell dysfunction in patients with immunodeficiency.


Cyclophosphamide induction dose and outcomes in ANCA-associated vasculitis with renal involvement: A comparative cohort study.
Treatment of ANCA-associated vasculitis (AAV) improved over the last decades but disease-unspecific agents such as cyclophosphamide are still associated with serious adverse events, including high rates of infectious complications and malignancy with increased mortality.In this comparative cohort study, we included 121 AAV patients with renal involvement from 2 German vasculitis centers. Patients were separated into subsequent groups: 2.5 to 3 g vs >3 g cumulative cyclophosphamide induction dose. We investigated if a cyclophosphamide induction dose of 2.5 to 3 g could maintain efficacy while minimizing adverse events in AAV patients with renal involvement.Patients with 2.5 to 3 g vs >3 g cumulative cyclophosphamide (median 3.0 g vs 5.5 g, P < .001) had a comparable time to remission (median 4.0 vs 3.8 months, log-rank P = .87) with 90.6% and 91.5% achieving remission after 12 months. Refractory disease was low in both groups (median 3.6% vs 6.2%, P = .68) and relapse rate did not differ (median 36% vs 42%, log-rank P = .51). Kidney function was comparable at disease onset in both groups (eGFR, mean ± SD 29 ± 20 mL/min/1.73 m2 vs 35 ± 26 mL/min/1.73 m2, P = .34) and improved after 2 years irrespective of the cyclophosphamide dose (ΔeGFR, mean ± SD +8.9 ± 1.4 mL/min/1.73 m2 vs +6.0 ± 1.1 mL/min/1.73 m2, P = .33). The 2.5-3 g group had a lower rate of leukopenia (HR = 2.73 [95% CI, 1.2-6.3], P = .014) and less infectious episodes per patient (median 1.2 vs 0.7, P = .012), especially urinary tract infections (HR = 2.15 [95% CI, 1.1-4.5], P = .032).A cyclophosphamide induction dose of 2.5 to 3 g was able to induce remission and prevent from relapses with fewer cases of leukopenia and less infectious episodes during follow-up. Especially elderly AAV patients who are particularly susceptible to infectious complications could benefit from minimizing dosing regimens with maintained efficacy to control disease activity.


Analysis of interactions of clinical mutants of catalase-peroxidase (KatG) responsible for isoniazid resistance in Mycobacterium tuberculosis with derivatives of isoniazid.
Isoniazid (INH) resistance is a major contributor to the emergence of multidrug resistance in Mycobacterium tuberculosis (MTB), hampering the success of tuberculosis treatment. This study aimed to identify good leads based on INH derivatives against INH-resistant MTB strains. Mutations at codon 315 in the katG gene encoding catalase-peroxidase (KatG) are the major cause of INH resistance in MTB. The most prevalent substitution is S315T; other substitutions include S315I, S315R, S315N and S315G. In this study, all five naturally occurring mutants (S315T, S315I, S315R, S315N and S315G) of KatG were docked and simulated with 50 INH derivatives in comparison with the wild-type (WT) KatG. The docking results suggested that compounds C30, C45 and C50 gave the highest scores when bound to the mutants of KatG. Of note, C50 produced a high score with the WT as well as with three mutants (S315T, S315I and S315R). Simulation studies indicated that C50 exhibited minimal deviation and fluctuation between WT and three mutants compared with C30 and C45, which displayed significant changes with WT and the S315N and S315G mutants, respectively. C50 can be considered as a better lead for INH-resistant strains. These models demonstrate the binding interaction of all naturally occurring KatG mutants of MTB at position 315 with derivatives of INH. This information will be helpful for lead compound-based identification of derivatives that may be used against INH-resistant MTB strains and may provide a useful structural framework for designing new antitubercular agents that can circumvent INH resistance.


Enhancement of the antibacterial property of amniotic fluid by hyperthermia.
The intrinsic ability of human amniotic fluid to prevent growth of Escherichia coli varies with the test strain employed, but is enhanced by increasing the temperature of incubation, as demonstrated by viable counts of test organisms in amniotic fluid compared with growth media at various temperatures. The antibacterial activity of amniotic fluid is reversed at all temperatures by the addition of potassium phosphate, but residual inhibition is seen at temperatures above 37C. When purified inhibitor preparations are tested, complete reversal by phosphate at the highest temperatures is seen. Thus, the augmented inhibition in whole amniotic fluid depends on the combined effects of phosphate-sensitive and -insensitive inhibitors. Test organisms in the presence of partially purified inhibitor were not adversely affected at 4C, indicating that bacteria must be metabolically active to be inhibited. It is concluded that temperatures above 37C enhance the antibacterial effect. This may enhance protection during pyrexia.


A new layered iron arsenide superconductor: (Ca,Pr)FeAs2.
A new iron-based superconductor, (Ca,Pr)FeAs2, was discovered. Plate-like crystals of the new phase were obtained, and its crystal structure was investigated by single-crystal X-ray diffraction analysis. The structure was identified as the monoclinic system with space group P2₁/m, composed of two Ca(Pr) planes, Fe2As2 layers, and As2 zigzag chain layers. Plate-like crystals of the new phase showed superconductivity, with a T(c) of ~20 K in both magnetization and resistivity measurements.


Theoretical and Experimental Insights into the Dissociation of 2-Hydroxyethylhydrazinium Nitrate Clusters Formed via Electrospray.
Ionic liquids are used for myriad applications, including as catalysts, solvents, and propellants. Specifically, 2-hydroxyethylhydrazinium nitrate (HEHN) has been developed as a chemical propellant for space applications. The gas-phase behavior of HEHN ions and clusters is important in understanding its potential as an electrospray thruster propellant. Here, the unimolecular dissociation pathways of two clusters are experimentally observed, and theoretical modeling of hydrogen bonding and dissociation pathways is used to help rationalize those observations. The cation/deprotonated cation cluster [HEH2 - H]+, which is observed from electrospray ionization, is calculated to be considerably more stable than the complementary cation/protonated anion adduct, [HEH + HNO3]+, which is not observed experimentally. Upon collisional activation, a larger cluster [(HEHN)2HEH]+ undergoes dissociation via loss of nitric acid at lower collision energies, as predicted theoretically. At higher collision energies, additional primary and secondary loss pathways open, including deprotonated cation loss, ion-pair loss, and double-nitric-acid loss. Taken together, these experimental and theoretical results contribute to a foundational understanding of the dissociation of protic ionic liquid clusters in the gas phase.


A child case of Kawasaki with giant coronary aneurysm: percutaneous coronary intervention due to anterior myocardial infarction.
Kawasaki disease is usually self-limited, but it can lead to aneurysm, stenosis, thrombosis, and myocardial infarction in the coronary arteries. The most important complication of Kawasaki disease is coronary artery aneurysm. Coronary artery aneurysm or ectasia may be seen in 15-25% of patients who do not receive treatment. It develops in 5% of children who receive intravenous immunoglobulin at the appropriate time. Acute myocardial infarction is the most important cause of morbidity and mortality in Kawasaki patients with giant aneurysms. We present a 10-year-old girl who had a history of giant aneurysm in the coronary arteries and underwent percutaneous coronary intervention due to anterior myocardial infarction.


Examination and Disruption of the Yeast Cell Wall.
The cell wall of Saccharomyces cerevisiae is a complicated extracellular organelle. Although the barrier may seem like a technical nuisance for researchers studying intracellular biomolecules or conditions, the rigid wall is an essential aspect of the yeast cell. Without it, yeast cells are unable to proliferate or carry out their life cycle. The chemical composition of the cell wall and the biosynthetic pathways and signal transduction mechanisms involved in cell wall remodeling have been studied extensively, but many unanswered questions remain. This introduction describes techniques for investigating abnormalities in the cell and spore walls and performing cell wall disruption.


A Thermodynamic Study of Adenine and Thymine Substitutions in the Loops of the Oligodeoxyribonucleotide HTel.
Guanine-rich DNA oligodeoxyribonucleotides (ODN) can form four-stranded structures named quadruplexes (G4s), which are stabilized via the association of four guanine bases. Quadruplexes have a high level of conformational diversity depending on the molecularity, sequence, and the cation conditions of the G4 formation. Monomolecular G4 structures have nonguanine loops that usually consist of between one and four adenine and thymine residues. In the work reported here, we systematically modified the nucleotides in the loops of the 22 nucleotide ODN, HTel, which contains four repeats of the human telomeric sequence, GGGTTA. We studied the effect of different types of bases in the loops on the stability and topology of the G4s formed. We show that lower steric hindrance of pyrimidine residues increases the stability of G4s with a major enthalpic contribution. Stacking of the loop bases onto tetrads could compensate for the loss of rotational freedom. In addition, in the presence of sodium, the stabilities of the G4s are loop dependent. In the presence of potassium, the stability of G4 depend on the sequences of each loop. Lastly, in the presence of potassium ions, the modified HTel ODNs may exist in equilibrium of the two types of the hybrid topology, and these structures are stabilized by the second loop. Modifications of the bases in this loop change the topology and stability of the folded structures.


Elastomeric polyamide biomaterials with stereochemically tuneable mechanical properties and shape memory.
Biocompatible polymers are widely used in tissue engineering and biomedical device applications. However, few biomaterials are suitable for use as long-term implants and these examples usually possess limited property scope, can be difficult to process, and are non-responsive to external stimuli. Here, we report a class of easily processable polyamides with stereocontrolled mechanical properties and high-fidelity shape memory behaviour. We synthesise these materials using the efficient nucleophilic thiol-yne reaction between a dipropiolamide and dithiol to yield an α,β - unsaturated carbonyl moiety along the polymer backbone. By rationally exploiting reaction conditions, the alkene stereochemistry is modulated between 35-82% cis content and the stereochemistry dictates the bulk material properties such as tensile strength, modulus, and glass transition. Further access to materials possessing a broader range of thermal and mechanical properties is accomplished by polymerising a variety of commercially available dithiols with the dipropiolamide monomer.


Possible protective role of the ABCA4 gene c.1268A>G missense variant in Stargardt disease and syndromic retinitis pigmentosa in a Sicilian family: Preliminary data.
In the wide horizon of ophthalmologically rare diseases among retinitis pigmentosa forms, Stargardt disease has gradually assumed a significant role due to its heterogeneity. In the present study, we aimed to support one of two opposite hypotheses concerning the causative or protective role of heterozygous c.1268A>G missense variant of the ABCA4 gene in Stargardt disease and in syndromic retinitis pigmentosa. This study was based on a family consisting of three members: proband, age 54, with high myopia, myopic chorioretinitis and retinal dystrophy; wife, age 65, with mild symptoms; daughter, age 29, asymptomatic. After genetic counseling, ABCA4 and RP1 gene analysis was performed. The results highlighted an important genetic picture. The proband was found to carry two variant RP1 SNPs, rs2293869 (c.2953A>T) and rs61739567 (c.6098G>A), and, a wild-type condition for four RP1 polymorphisms, rs444772 (c.2623G>A) and three SNPs in the 'hot-spot' region, exon 4. The proband's wife, instead, showed an opposite condition compared to her husband: a homozygous mutated condition for the first four SNPs analyzed, while the last two were wild-type. Regarding the ABCA4 gene, the proband evidenced a wild-type condition. Furthermore, the wife showed a heterozygous condition of ABCA4 rs3112831 (c.1268A>G). As expected, the daughter presented heterozygosity for all variants of both genes. In conclusion, even though the c.1268A>G missense variant of the ABCA4 gene has often been reported as causative of disease, and in other cases protective of disease, in our family case, the variant appears to reduce or delay the risk of onset of Stargardt disease.


Heparinized collagen scaffolds with and without growth factors for the repair of diaphragmatic hernia: construction and in vivo evaluation.
A regenerative medicine approach to restore the morphology and function of the diaphragm in congenital diaphragmatic hernia is especially challenging because of the position and flat nature of this organ, allowing cell ingrowth primarily from the perimeter. Use of porous collagen scaffolds for the closure of surgically created diaphragmatic defects in rats has been shown feasible, but better ingrowth of cells, specifically blood vessels and muscle cells, is warranted. To stimulate this process, heparin, a glycosaminoglycan involved in growth factor binding, was covalently bound to porous collagenous scaffolds (14%), with or without vascular endothelial growth factor (VEGF; 0.4 µg/mg scaffold), hepatocyte growth factor (HGF; 0.5 µg/mg scaffold) or a combination of VEGF + HGF (0.2 + 0.5 µg/mg scaffold). All components were located primarily at the outside of scaffolds. Scaffolds were implanted in the diaphragm of rats and evaluated after 2 and 12 weeks. No herniations or eventrations were observed, and in several cases, growth factor-substituted scaffolds showed macroscopically visible blood vessels at the lung site. The addition of heparin led to an accelerated ingrowth of blood vessels at 2 weeks. In all scaffold types, giant cells and immune cells were present primarily at the liver side of the scaffold, and immune cells and individual macrophages at the lung side; these cell types decreased in number from week 2 to week 12. The addition of growth factors did not influence cellular response to the scaffolds, indicating that further optimization with respect to dosage and release profile is needed.


Mechanical and transport properties of layer-by-layer electrospun composite proton exchange membranes for fuel cell applications.
Composite membranes composed of highly conductive and selective layer-by-layer (LbL) films and electrospun fiber mats were fabricated and characterized for mechanical strength and electrochemical selectivity. The LbL component consists of a proton-conducting, methanol-blocking poly(diallyl dimethyl ammonium chloride)/sulfonated poly(2,6-dimethyl-1,4-phenylene oxide) (PDAC/sPPO) thin film. The electrospun fiber component consists of poly(trimethyl hexamethylene terephthalamide) (PA 6(3)T) fibers in a nonwoven mat of 60-90% porosity. The bare mats were annealed to improve their mechanical properties, which improvements are shown to be retained in the composite membranes. Spray LbL assembly was used as a means for the rapid formation of proton-conducting films that fill the void space throughout the porous electrospun matrix and create a fuel-blocking layer. Coated mats as thin as 15 μm were fabricated, and viable composite membranes with methanol permeabilities 20 times lower than Nafion and through-plane proton selectivity five and a half times greater than Nafion are demonstrated. The mechanical properties of the spray coated electrospun mats are shown to be superior to the LbL-only system and possess intrinsically greater dimensional stability and lower mechanical hysteresis than Nafion under hydrated conditions. The composite proton exchange membranes fabricated here were tested in an operational direct methanol fuel cell. The results show the potential for higher open circuit voltages (OCV) and comparable cell resistances when compared to fuel cells based on Nafion.


Vocal development in captive harbor seal pups, Phoca vitulina richardii: age, sex, and individual differences.
The goal of this research was to determine when harbor seal pup vocalizations become sufficiently distinctive to allow individual recognition. A total of 4593 calls were analyzed from 15 captive pups. Nineteen were harsh, broadband, staccato calls used in an aggressive context. The rest were tonal "mother attraction calls," having an inverted "v"- or "u"-shaped spectrogram with harmonics and a fundamental frequency around 200-600 Hz. Calls were individually distinctive even in pups less than 2 weeks old, suggesting that mothers may be able to recognize pup vocalizations at this early age. Classification rates from discriminant function analysis were generally comparable to those of other phocids and less than in otariids, supporting the theory that recognition is more highly developed in otariids. Significant differences were found between male and female pup calls, and there were significant interactions between pup sex and age. The results of this study should be interpreted with caution until the findings are verified in wild harbor seal pups.


Randomized controlled trial of low dose warfarin in the primary prevention of ischaemic heart disease in men at high risk: design and pilot study.
We report the pilot stage of a double-blind randomized controlled trial of low dose warfarin in the primary prevention of ischaemic heart disease (IHD) in men at high risk. The first objective was to see if levels of factor VII coagulant activity, VIIc, could be reduced without undue difficulty from a mean level of about 115% to about 70% (the level in patients on conventional warfarin doses being about 30%). This was accomplished with a mean daily dose of 4.6 mg warfarin. The international normalized ratio (INR) corresponding to a VIIc value of 70% was about 1.5. The second objective was to assess the risk of bleeding associated with the intended level of anticoagulation. There was no significant excess in the number of actively treated men ever reporting nose bleeds, possible haematuria, rectal bleeding or bruising, although there may have been an increase in the frequency of rectal bleeding in men who did report this symptom. The third objective was to establish the willingness of patients to take part in a trial of this kind. Of those invited to the initial screening examination, 72% attended. Of those invited to enter the treatment phase of the trial, 71% did so. Compliance with trial treatment was at a very high level. The rate of withdrawal from randomized treatment was within acceptable limits, at about 15% over a three- or four-year period. The scientific case for a full trial is strong and the pilot trial shows that it could be accomplished.


Sparse sampling in helical cone-beam CT perfect reconstruction algorithms.
In the current paper we consider the Helical Cone Beam CT. This scanning method exposes the patient to large quantities of radiation and results in very large amounts of data being collected and stored. Both these facts are prime motivators for the development of an efficient, reduced rate, sampling pattern. We calculate bounds on the support in the frequency domain of the collected data and use these to suggest an efficient sampling pattern. A reduction of up to a factor of 2 in sampling rate is suggested. Indeed, we show that reconstruction quality is not affected by this reduction of sampling rates.


Evaluation of parameters related to libido and semen quality in Zebu bulls naturally infected with Trypanosoma vivax.
Trypanosomiasis is a disease caused by Trypanosoma (Dutonella) vivax, a hemoprotozoa that can affect bovines. In South America, the sanguineous form is mechanically transmitted from one mammalian host (ruminant) to another by the bite of a blood-sucking insect or by needles contaminated with infected blood. The negative impact of the parasitosis caused by T. vivax infection on the reproductive activity of male and female ruminants is known to reduce fertility. In males, alterations such as degeneration, diffuse or interlobular inflammatory infiltrate found in ovine and bovine testicles, can affect fertility through decreased sperm quality. This study evaluated the impact of natural infection with T. vivax on Zebu bulls from the Central Station of Artificial Insemination (CSAI) with regard to libido and the negative effects caused by this protozoan on semen quality. Blood samples of 44 animals were collected to evaluate the presence of the trypomastigote form of T. vivax in blood smears obtained from hematocrit and buffy coat, and antibody titer IgG anti T. vivax in indirect Immunoflorescence (IFI). Furthermore, data related to libido, ejaculate volume, spermatic concentration, and seminal vigor were recorded for these animals employing the criteria of the CSAI. Nine animals (20.45 %) showed T. vivax trypomastigotes and parasitemia between 0.02 and 0.07, and antibody titers from 1:80 to 1:320 in IFI. Twenty nine negative animals in parasitological tests were not reactive in IFI, and six animals presented the antibodies IgG anti T. vivax in IFI. Data on reproductive activity showed that animals infected with T. vivax have a decreased libido and an increased spermatic volume, whereas other factors related to the reproductive process such as spermatic concentration, motility and spermatic force, were unchanged in infected bulls. The T. vivax infection in Zebu bulls from CSAI caused patent parasitemia, induced a febrile state, promoted reduction in the libido and increased the ejaculate volume. These conditions together may account to decrease the performance of these animals.


Serum neuron-specific enolase as an early predictor of delayed neuropsychiatric sequelae in patients with acute carbon monoxide poisoning.
Delayed onset of neuropsychiatric symptoms after apparent recovery from acute carbon monoxide (CO) poisoning has been described as delayed neuropsychiatric sequelae (DNS). To date, there have been no studies on the utility of serum neuron-specific enolase (NSE), a marker of neuronal cell damage, as a predictive marker of DNS in acute CO poisoning. This retrospective observational study was performed on adult patients with acute CO poisoning consecutively treated over a 9-month period. Serum NSE was measured after emergency department arrival, and patients were divided into two groups. The DNS group comprised patients with delayed sequelae, while the non-DNS group included patients with none of these sequelae. A total of 98 patients with acute CO poisoning were enrolled in this study. DNS developed in eight patients. The median NSE value was significantly higher in the DNS group than in the non-DNS group. There was a statistical difference between the non-DNS group and the DNS group in terms of CO exposure time, Glasgow Coma Scale (GCS), loss of consciousness, creatinine kinase, and troponin I. GCS and NSE were the early predictors of development of DNS. The area under the curve according to the receiver operating characteristic curves of GCS, serum NSE, and GCS combined with serum NSE were 0.922, 0.836, and 0.969, respectively. In conclusion, initial GCS and NSE served as early predictors of development of DNS. Also, NSE might be a useful additional parameter that could improve the prediction accuracy of initial GCS.


Emission of multiple dispersive waves from a single Raman-shifting soliton in an axially-varying optical fiber.
We provide the experimental demonstration of the generation of multiple dispersive waves from a single soliton propagating in the vicinity of the first zero-dispersion wavelength of an axially-varying optical fiber. The fiber is designed such that the Raman-shifting soliton successively hits three times the longitudinally evolving zero-dispersion wavelength, which results in the emission of three distinct dispersive waves at different fiber lengths. These results illustrate how suitably controlled axially-varying fibers allow to tailor the soliton dynamics in a very accurate way.


Human immunodeficiency virus-1 Tat protein interacts with distinct proteasomal alpha and beta subunits.
The human immunodeficiency virus-1 (HIV-1) Tat protein was previously reported to compete the association of PA28 regulator with the alpha rings of the 20S proteasome and to inhibit its peptidase activity. However, the distinct interaction sites within the proteasome complex remained to be determined. Here we show that HIV-1 Tat binds to alpha4 and alpha7, six beta subunits of the constitutive 20S proteasome and the interferon-gamma-inducible subunits beta2i and beta5i. A Tat-proteasome interaction can also be demonstrated in vivo and leads to inhibition of proteasomal activity. This indicates that Tat can modulate or interfere with cellular proteasome function by specific interaction with distinct proteasomal subunits.


Allescheria (Petriellidium) boydii brain abscess in a child with leukemia.
A 3-year-old boy with acute lymphoblastic leukemia developed a right frontal lobe abscess from which Allescheria (Petriellidium) boydii was cultured. The mycotic infection complicating his underlying disease appeared to be confined to the brain. Surgical drainage and therapy with amphotericin B were followed by eventual recovery with no neurologic deficits.


Lipid diffusion in the plasma membrane of mouse spermatozoa: changes during epididymal maturation, effects of pH, osmotic pressure, and knockout of the c-ros gene.
It is well known that the plasma membranes of mammalian spermatozoa undergo extensive remodeling during maturation in the epididymal duct. In this investigation, we have used fluorescence recovery after photobleaching (FRAP) techniques to: 1) measure rates of lipid diffusion in the plasma membrane of mouse spermatozoa at different stages of maturation; 2) examine the effects of varying external conditions found in the epididymal duct (pH, temperature, and osmotic pressure) on lipid diffusion in mature sperm; and 3) investigate the effects of the c-ros null mutation that causes tail angulation in cauda spermatozoa after ejaculation as a result of cell swelling due to altered membrane function. Our results show that lipid diffusion (as measured using reporter probes 5-(N-octadecanoyl)aminofluorescein [ODAF] and 2-(6-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)hexanoyl-1-hexadecanoyl-sn-glycero-3-phosphocholine [NBD-C6-PC]) is several times faster across the membrane on the sperm head than on the tail and that it increases significantly during passage from caput to cauda. Temperature variations between 20 degrees C and 37 degrees C have a substantial effect on diffusion coefficients, with the sperm head being more responsive than the tail. Changes in external pH (6.5-8.5) or osmotic pressure (202-389 mOsm/kg), however, have little relative effect on lipid diffusion on any region of the sperm. The rate of diffusion of 22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3beta-ol (NBD-cholesterol) is 10-fold higher across the head plasma membrane than across the tail and does not change significantly during epididymal maturation. Similarly, lipid diffusion in hairpin-shaped cauda sperm from c-ros (-/-) males is not significantly different from (+/+) controls. These results suggest that temperature and compositional changes are 2 of the important factors that regulate the dynamics of lipid molecules in the mouse sperm plasma membrane.


Primary synovial sarcoma in fallopian tube: case report and literature review.
Synovial sarcoma, a malignant mesenchymal neoplasm, occurs mostly near the joints of the extremities and occasionally outside the joint such as lung. We report a case of soft tissue sarcoma arising in the fallopian tube origin that showed characteristic pathological appearance of biphasic synovial sarcoma. Molecular analysis detected a fusion gene transcript of synovial sarcoma translocation (SYT) gene from chromosome 18 and synovial sarcoma X chromosome breakpoint 1 (SSX1) gene, which is believed to pathognomonic for synovial sarcoma of joint origin. Recurrent abdominal tumor, observed at 12 month after the initial surgery and following chemotherapy using doxorubicin, cisplatin and ifosfamide, partially responded to chemotherapy using paclitaxel and carboplatin and, then, optimal surgery was performed. This is the first report of a synovial sarcoma arising in the fallopian tube.


Temperature-sensitive defects of the GSP1gene, yeast Ran homologue, activate the Tel1-dependent pathway.
RanGTPase is involved in many cellular processes. It functions in nuclear-cytosolic transport and centrosome formation. Ran also localizes to chromatin as RCC1 does, its guanine nucleotide exchange factor, but Ran's function on chromatin is not known. We found that gsp1, a temperature-sensitive mutant of GSP1, a Saccharomyces cerevisiae Ran homologue, suppressed the hydroxyurea (HU) and ultra violet (UV) sensitivities of the mec1 mutant. In UV-irradiated mec1 gsp1 cells, Rad53 was phosphorylated despite the lack of Mec1. This suppression depended on the TEL1 gene, given that the triple mutant, mec1 gsp1 tel1, was unable to grow. The gsp1 mutations also suppressed the HU sensitivity of the rad9 mutant in a Tel1-dependent manner, but not the HU sensitivity of the rad53 mutant. These results indicated that Rad53 was activated by the Tel1 pathway in mec1 gsp1 cells, suggesting that Gsp1 helps regulate the role switching the ATM family kinases Mec1 and Tel1.


Drug binding to aromatic residues in the HERG channel pore cavity as possible explanation for acquired Long QT syndrome by antiparkinsonian drug budipine.
Budipine is a non-dopaminergic antiparkinsonian drug causing acquired forms of Long QT syndrome (aLQTS). As a consequence, the manufacturer has restricted the use of budipine in patients who exhibit additional risk factors for the development of "Torsades-de-Pointes" tachycardias (TdP). The molecular basis of this serious side effect has not been elucidated yet. Human ether-a-go-go related gene (HERG) channel block being the main cause of drug induced QT prolongation, we investigated the effect of budipine on the rapid component of the delayed-rectifier potassium current (I(K(r))) in guinea pig cardiomyocytes and on HERG potassium channels heterologously expressed in Xenopus oocytes. In guinea pig cardiomyocytes, budipine (10 microM) inhibited I(K(r)) by 86% but was without any effect on calcium currents. In Xenopus oocytes, HERG potassium channels were blocked by budipine with an IC(50) of 10.2 microM. Onset of block was fast and block was only slowly and incompletely reversible upon washout. Budipine blocked HERG channels in the open and inactivated state, but not in the closed states. The half-maximal activation voltage was slightly shifted towards more negative potentials. Steady-state inactivation of HERG was also influenced by budipine. Budipine block was neither voltage- nor frequency-dependent. In HERG channel mutants Y652A and F656A, drug affinity was reduced dramatically. Therefore, these two aromatic residues in the channel pore are likely to form a main part of the binding site for budipine. In summary, this is the first study that provides a molecular basis for the budipine-associated aLQTS observed in clinical practice. Furthermore, these findings underline the importance of the aromatic residues Y652 and F656 in the binding of lipophilic drugs to HERG channels.


High Expression of microRNA-143 is Associated with Favorable Tumor Immune Microenvironment and Better Survival in Estrogen Receptor Positive Breast Cancer.
microRNA-143(miR-143) is a well-known tumor suppressive microRNA that exhibits anti-tumoral function by targeting KRAS signaling pathways in various malignancies. We hypothesized that miR-143 suppresses breast cancer progression by targeting KRAS and its effector molecules. We further hypothesized that high expression of miR-143 is associated with a favorable tumor immune microenvironment of estrogen receptor (ER)-positive breast cancer patients which result in improved survival. Two major publicly available breast cancer cohorts; The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) were used. The miR-143 high expression group was associated with increased infiltration of anti-cancer immune cells and decreased pro-cancer immune cells, as well as enrichment of the genes relating to T helper (Th1) cells resulting in improved overall survival (OS) in ER-positive breast cancer patients. To the best of our knowledge, this is the first study to demonstrate that high expression of miR-143 in cancer cells associates with a favorable tumor immune microenvironment, upregulation of anti-cancer immune cells, and suppression of the pro-cancer immune cells, associating with better survival of the breast cancer patients.


Immunoproteomics: From biomarker discovery to diagnostic applications.
Circulating antibodies reflect a molecular imprint of antigens that are related to autoimmune diseases, cancer or infection. Importantly, serum antibodies are useful clinical markers as they carry diagnostic information from all around the human body. Moreover, the amplification cascade governed by the humoral immune system causes a surplus of circulating antibodies after appearance of the corresponding (low abundance) antigen. In combination with the fact that antibodies are highly stable compared to many other serum proteins, they seem ideal to be implemented in clinical diagnostic assays for the detection of antigen-associated diseases. This review summarises advances in immunoproteomics with respect to technologies for biomarker discovery, with special emphasis on recently developed gel-free MS-based approaches, and looks forward to potential immunoproteomic applications in diagnostic medicine.


Predictors of blood pressure control in patients with resistant hypertension after intensive management in two expert centres: the Brussels-Torino experience.
Background: Management of resistant hypertension (RHTN) is challenging and often implies the use of complex polypharmacy and interventional therapies. The main objectives of this study were (i) to describe the characteristics of patients with RHTN referred to two expert centres; (ii) to identify predictors of blood pressure (BP) control after intensive management. Methods: We reviewed electronic medical files of all patients referred for RHTN to the Brussels and Torino centres, and extracted detailed clinical data, informations on drug adherence and psychological profile. All patients with confirmed diagnosis of RHTN, according to office and ambulatory BP monitoring (ABPM) measurements, were considered eligible. Results: 313 patients (51% men; age: 56 ± 12 years; office BP 177/98 mmHg; 24-hour ABPM 153/90 mmHg) were included. At the end of follow-up (median: 2 years [1-4]), only 26% of patients (n = 81) reached BP control. When compared to patients remaining resistant, patients eventually controlled had lower pulse pressure (71 vs. 82 mmHg, p < 0.001), less often myocardial infarction (6% vs. 20%, p < 0.005) and showed a higher recourse to cognitive reappraisal as far as emotion regulation is concerned (4.8 ± 1.1 vs. 3.9 ± 1.2, p = 0.009; ERQ Questionnaire). In a multivariate analysis looking for predictors of controlled BP, only the psychological characteristic of cognitive reappraisal (i.e., changing one's thoughts about a potentially emotion-eliciting event) remained significant (OR 2.06 [1.10; 3.84], p = 0.02). Conclusions: Even in expert centres, only a minority of patients with RHTN reached BP control, irrespective of the centre involved or the interventions applied. Patients who eventually responded to therapy had lower arterial stiffness and less cardiac organ damage. Furthermore, besides vascular damage, the single predictor of BP control was the ability to modify the emotional impact of stressful situations.


Waldenström's macroglobulinaemia presenting with cold urticaria and cold purpura.
A case of Waldenström's macroglobulinaemia presenting with non-specific dermatological symptoms (cold urticaria and cold purpura) is described in a 37-year-old female patient. Progressive telangiectasia and spider naevi were also observed. Involvement of the skin may be explained by the presence of macroglobulins with cryoprotein-like qualities. This facilitated an early diagnosis.


[Chapter 5. Diagnosis on the embryo and the foetus: its consequences].
The status of the embryo has kept evolving in our minds since we have been able to see it, examine it in detail, determine its normality and competence and above all since we have been able to care for it in utero. The embryo and the fœtus have become patients. But not entirely like others. If they are too ill, we have the right to end their lives, active euthanasia, which is not possible in other branches of medicine. The legal status of the embryo and the fœtus, which is constantly evolving, cannot be confused with the essence of the embryo and the fœtus which is of a philosophical, even theological, nature, but certainly not legal. Human embryos and foetuses are of course potential human beings who have not yet acquired all the rights of a person. These rights of the embryo and fœtus increase progressively until live birth when they become complete.


Samantha Thimmaya v Lancashire NHS Foundation Trust v Mr Firas Jamil.
In Samantha Thimmaya v Lancashire NHS Trust v Mr Firas Jamal (Thimmaya), Mr Jamil, an expert witness acting for the Claimant in a clinical negligence action, was ordered to pay part of the Defendant's costs, amounting to over £88,000. The court determined that his conduct as an expert had been 'improper, unreasonable, or negligent', thus enabling the court to make a third-party costs order against him. Although the case must have raised alarm amongst medical experts, the facts of the case show that it concerned a very unusual set of circumstances. Additionally, the more recent case of Walker and Walker v Tui UK Ltd v Dr Timothy Leigh (Walker), also discussed below, suggests that the threshold to be applied in determining whether costs orders should be made against experts will be higher than that applied in Thimmaya. Both cases serve as a reminder of the duties owed by experts to the court.


Signal characteristics of EMG with special reference to reproducibility of measurements.
Reliability and constancy of recordings of EMG signal characteristics were investigated from the measurements taken with miniature size surface electrodes during submaximal and maximal contraction of the rectus femoris muscle. The following EMG variables were studied: integrated EMG (IEMG) various bandwidths of the power spectral density function, mean power frequency (MPF), and rise time, amplitude and number of spikes of the averaged motor unit potential (AMUP). The results indicated that for most of the variables studied the reproducibility of measurements was better within the test session (reliability) than between the different test days (constancy). The reliability values for IEMG, MPF and AMUP amplitude were rather high (r=0.77-0.93) and it is suggested that these parameters can be recommended for use in EMG studies where recordings are repeated over a period of several days.


Effect of carvedilol on venous return: a mechanism of reduction in blood pressure.
We studied the effect of carvedilol, a beta-blocker with a potent alpha-blocking activity, on venous return in anesthetized dogs. Though 3 micrograms/kg of carvedilol caused a slight increase in blood pressure and total peripheral resistance, these changes disappeared by further doses of the agent. On the other hand, each dose of carvedilol (3-100 micrograms/kg) decreased venous return significantly and dose-dependently. These results indicate that the hypotensive effect of carvedilol mainly depends on the decrease in venous return rather than arterial vasodilation.


Camera traps reveal that terrestrial predators are pervasive at riverscape cold-water thermal refuges.
Perceived predation risks by terrestrial predators are major ecological forces in aquatic systems, particularly for aggregating fish. Riverscape thermal refuges are discrete, localized cold-water patches where fish temporarily aggregate to buffer against heat events. Predation pressures by terrestrial predators at thermal refuges may decrease the thermoregulatory benefits of refuge use, but quantifying such effects can be challenging and controversial when sampling can impose additional stress on fish. We passively monitored terrestrial predator visitation patterns and predation at four thermal refuges in the Housatonic River, Connecticut, USA, between May 18th and September 29th, 2022, with camera traps, a common wildlife monitoring method. Specifically, we (1) assessed diel visitation patterns by different categories of terrestrial predators at thermal refuges and determined if patterns varied among predator categories or with prevailing environmental conditions, and (2) estimated the probability of predation by hour of the day combined across all predator categories, quantifying general predation pressures at refuges. We detected at least one terrestrial predator at a thermal refuge each day, and mean hourly visitation rates (count/h) were highly variable across predator categories and sampling dates. The most supported generalized additive mixed model indicated that terrestrial predator visitation rates (count/h/day) varied with mean daily river discharge and water temperature differential, and relationships differed across categories of terrestrial predators. We observed 22 separate predation attempts on thermoregulating salmonids and predicted that the probability of predation by any terrestrial predator increased from 0.002 to 0.017 throughout a 24 h day (p = .004). Camera traps provided novel evidence that terrestrial predators are pervasive at riverine thermal refuges, which is relevant for refuge conservation and management globally. We recommend the implementation of a coordinated monitoring network across riverine thermal refuges using camera traps, further enriching our ecological understanding of cumulative predator effects in refuges across complex riverscapes.


The quantitative genetics of disgust sensitivity.
[Correction Notice: An Erratum for this article was reported in Vol 16(1) of Emotion (see record 2015-57029-001). In the article, the name of author Joshua M. Tybur was misspelled as Joshua M. Tyber. All versions of this article have been corrected.] Response sensitivity to common disgust elicitors varies considerably among individuals. The sources of these individual differences are largely unknown. In the current study, we use a large sample of female identical and nonidentical twins (N = 1,041 individuals) and their siblings (N = 170) to estimate the proportion of variation due to genetic effects, the shared environment, and other (residual) sources across multiple domains of disgust sensitivity. We also investigate the genetic and environmental influences on the covariation between the different disgust domains. Twin modeling revealed that approximately half of the variation in pathogen, sexual, and moral disgust is due to genetic effects. An independent pathways twin model also revealed that sexual and pathogen disgust sensitivity were influenced by unique sources of genetic variation, while also being significantly affected by a general genetic factor underlying all 3 disgust domains. Moral disgust sensitivity, in contrast, did not exhibit domain-specific genetic variation. These findings are discussed in light of contemporary evolutionary approaches to disgust sensitivity.


Oligomerization of hamster UDP-GlcNAc:dolichol-P GlcNAc-1-P transferase, an enzyme with multiple transmembrane spans.
Hamster UDP-GlcNAc:dolichol-P GlcNAc-1-P transferase (GPT), which initiates N-linked glycosylation by catalyzing the synthesis of GlcNAc-P-P-dolichol, has multiple transmembrane spans and a catalytic site that probably exists on the cytosolic face of the endoplasmic reticulum membrane (Dan, N., Middleton, R. M., and Lehrman, M. A. (1996) J. Biol. Chem. 271, 30717-30725). In this report, we demonstrate that GPT forms functional oligomers, probably dimers. Oligomers were detected by chemical cross-linking of GPT and by a dominant-negative effect caused by co-expression of enzymatically inactive (but properly folded) GPT mutants. The GPT mutants had no effect on two other dolichol-P-dependent endoplasmic reticulum enzymes. Mixing experiments indicated that mature GPT was competent for oligomerization. Oligomerization appeared to be favored in detergent extracts compared with intact microsomes. Detergent treatments were found to prevent, rather than promote, nonspecific aggregation of GPT. These results demonstrate that GPT subunits can physically interact and influence each other. The implications of oligomerization for enzyme function are discussed. From these results, we conclude that GPT is one of a very small number of multitransmembrane span enzymes that can form multimers.


Integration of technologies for hepatic tissue engineering.
The liver is the largest internal organ in the body, responsible for over 500 metabolic, regulatory, and immune functions. Loss of liver function leads to liver failure which causes over 25,000 deaths/year in the United States. Efforts in the field of hepatic tissue engineering include the design of bioartificial liver systems to prolong patient's lives during liver failure, for drug toxicity screening and for the study of liver regeneration, ischemia/reperfusion injury, fibrosis, viral infection, and inflammation. This chapter will overview the current state-of-the-art in hepatology including isolated perfused liver, culture of liver slices and tissue explants, hepatocyte culture on collagen "sandwich" and spheroids, coculture of hepatocytes with non-parenchymal cells, and the integration of these culture techniques with microfluidics and reactor design. This work will discuss the role of oxygen and medium composition in hepatocyte culture and present promising new technologies for hepatocyte proliferation and function. We will also discuss liver development, architecture, and function as they relate to these culture techniques. Finally, we will review current opportunities and major challenges in integrating cell culture, bioreactor design, and microtechnology to develop new systems for novel applications.


Evaluation of a flexible bronchoscope prototype designed for bronchoscopy during mechanical ventilation: a proof-of-concept study.
Bronchoscopy during mechanical ventilation of patients' lungs significantly affects ventilation because of partial obstruction of the tracheal tube, and may thus be omitted in the most severely ill patients. It has not previously been possible to reduce the external diameter of the bronchoscope without reducing the diameter of the suction channel, thus reducing the suctioning capacity of the device. We believed that a better-designed bronchoscope could improve the safety of bronchoscopy in patients whose lungs were ventilated. We designed a flexible bronchoscope prototype with a drumstick-shaped head consisting of a long, thin proximal portion; a short and large distal portion for camera docking; and a large suction channel throughout the length of the device. The aims of our study were to test the impact of our prototype on mechanical ventilation when inserted into the tracheal tube, and to assess suctioning capacity. We first tested the efficiency of the suction channel, and demonstrated that the suction flow of the prototype was similar to that of conventional adult bronchoscopes. We next evaluated the consequences of bronchoscopy when using the prototype on minute ventilation and intrathoracic pressures during mechanical ventilation: firstly, in vitro using a breathing simulator; and secondly, in vivo using a porcine model of pulmonary ventilation. The insertion of adult bronchoscopes into the tracheal tube immediately impaired the protective ventilation strategy employed, whereas the prototype preserved it. For the first time, we have developed an innovative flexible bronchoscope designed for bronchoscopy during invasive mechanical ventilation, that both preserved the protective ventilation strategy, and enabled efficient suction flow.


Gray level transforms and lesion detectability in echographic images.
In search of the optimal display of echographic information for the detection of focal lesions, a systematic study was performed considering a wide range of gray level transforms (i.e., lookup tables). This range comprised power functions of the echo envelope signal (1/8 less than or equal to n less than or equal to 8), power functions of the logarithmic transform and a sigmoid function. The implications of the transforms on the first order statistics (histogram, "point signal-to-noise ratio" SNRp) and on the second order statistics (autocorrelation function) could be derived both analytically, and from the analysis of simulated and experimentally obtained echograms of homogeneously scattering tissue models. These results were employed to estimate the lesion signal-to-noise ratio SNRl, which specifies the detectability of a lesion by an ideal observer. It was found, both theoretically and practically, that the intensity display corresponds to the optimal transform (i.e., n = 2) for a low contrast lesion. When the data were first logarithmically compressed, the lesion SNR appeared to increase with increasing power (1/8 less than or equal to n less than or equal to 8). A logarithmic transform followed by a sigmoid compression did not produce much improvement. These effects of gray level transforms on the SNRl were shown to be relatively small, with the exception of powers n greater than 2 when applied to linear (i.e. amplitude) data. In the case of high lesion contrast, the sequence of log compression, followed by a square law produced the optimum SNRl. This sequence is equivalent to the processing within echographic equipment, where the TV monitor has a gamma of the order of 2.