Trends in industrial use of energy.
Industry's use of energy, accounting for approximately 40 percent of U.S. consumption, changed significantly after 1973. In 1982 industry consumed one-third less energy than trends established before 1973 would have predicted. Part of this reduction resulted from improvements in the efficiency of industrial process technologies. Most is attributed, however, to slower growth in industrial economic activity and unprecedented changes in the composition of industrial output away from industries that consume large amounts of energy.


[Bacteriophage MS2 mutants with disrupted phage replicase repressor activity].
A number of ts-mutants with altered characteristics of RNA synthesis in non-suppressor cells at elevated temperatures have been obtained after HNO2-treatment of phage MS2am623 (amber mutation in site 50). The mutant ts130 is studied in detail: its peak of RNA synthesis is displaced 10 min. later and the total amount of RNA is reduced in 5-10 times. No RNA synthesis is observed in ts130-infected cell at 46 degrees C. Changes in the character of RNA synthesis are accompanied by the over-production of phage subunit of replicase: at 42 degrees C the replicase/RNA ratio in ts130 is 20 times higher than that of the original phage MS2am623. It is assumed that there is a decrease in the activity of replicase--RNA repressor complex in ts130 resulting in the loss of replicase control over its own synthesis while the control of coat protein synthesis remains unaffected.


Accuracy of diagnosis of coronary artery disease by radionuclide management of left ventricular function during rest and exercise.
Rest and exercise radionuclide angiocardiographic measurements of left ventricular function were obtained in 496 patients who underwent cardiac catheterization for chest pain. Two hundred forty-eight of these patients also had an exercise treadmill test. An ejection fraction less than 50% was the abnormality of resting left ventricular function that provided the greatest diagnostic information. In patients with normal resting left ventricular function, exercise abnormalities that were optimal for diagnosis of coronary artery disease were an injection fraction at least 6% less than predicted, an increase greater than 20 ml in end-systolic volume and the appearance of an exercise-induced wall motion abnormality. The sensitivity and specificity of the test were lower in patients who were taking propranolol at the time of study and in patients who failed to achieve an adequate exercise end point. In the 387 patients with an optimal study, the test had a sensitivity of 90% and a specificity of 58%. Radionuclide angiocardiography was more sensitive and less specific than the exercise treadmill test. The high degree of sensitivity of the radionuclide test suggests that it is most appropriately applied to patient groups with a high prevalence of disease, including those considered for cardiac catheterization.


Increased levels of microparticles originating from endothelial cells, platelets and erythrocytes in subjects with metabolic syndrome: relationship with oxidative stress.
The Metabolic Syndrome (MetS) is associated with increased cardiovascular risk. Circulating microparticles (MP) are involved in the pathogenesis of atherothrombotic disorders and are raised in individual with CVD. We measured their level and cellular origin in subjects with MetS and analyzed their associations with 1/anthropometric and biological parameters of MetS, 2/inflammation and oxidative stress markers. Eighty-eight subjects with the MetS according to the NCEP-ATPIII definition were enrolled in a bicentric study and compared to 27 healthy controls. AnnexinV-positive MP (TMP), MP derived from platelets (PMP), erythrocytes (ErMP), endothelial cells (EMP), leukocytes (LMP) and granulocytes (PNMP) were determined by flow cytometry. MetS subjects had significantly higher counts/μl of TMP (730.6±49.7 vs 352.8±35.6), PMP (416.0±43.8 vs 250.5±23.5), ErMP (243.8±22.1 vs 73.6±19.6) and EMP (7.8±0.8 vs 4.0±1.0) compared with controls. LMP and PNMP were not statistically different between groups. Multivariate analysis demonstrated that each criterion for the MetS influenced the number of TMP. Waist girth was a significant determinant of PMP and EMP level and blood pressure was correlated with EMP level. Glycemia positively correlated with PMP level whereas dyslipidemia influenced EMP and ErMP levels. Interestingly, the oxidative stress markers, plasma glutathione peroxydase and urinary 8-iso-prostaglandin F(2) α, independently influenced TMP and PMP levels whereas inflammatory markers did not, irrespective of MP type. Increased levels of TMP, PMP, ErMP and EMP are associated with individual metabolic abnormalities of MetS and oxidative stress. Whether MP assessment may represent a marker for risk stratification or a target for pharmacological intervention deserves further investigation.


Electron acceleration driven by sub-cycle and single-cycle focused optical pulse with radially polarized electromagnetic field.
The space-time properties of the expressions of sub-cycle and single-cycle focused optical pulses with radially polarized electromagnetic field based on the Sink-Source model are studied. The self-induced blue shift of the center frequency of spectrum in the center of the pulse field is found to have an important impact on the electrons acceleration. When the electrons approach to the center of pulse, the electrons will obtain a large kinetic energy gain in a short time. The effect of radiation-reaction force can't be ignored if the net kinetic energy gain of electrons is more than GeVs. The electrons will deviate from the original acceleration channel and the gain of kinetic energy that electrons may gain will be greatly reduced if the radiation-reaction effect is considered. In contrast to the few-cycle laser pulse accelerating electrons, the gain of kinetic energy obtained by electrons is a few times higher and the corresponding peak optical power is one order of magnitude lower in the case of the sub-cycle laser pulses accelerating electrons. The maximal kinetic energy gain of electrons is robust against the variation of the incident angles.


Crystal structures of the bacterial solute receptor AcbH displaying an exclusive substrate preference for β-D-galactopyranose.
Solute receptors (binding proteins) are indispensable components of canonical ATP-binding cassette importers in prokaryotes. Here, we report on the characterization and crystal structures in the closed and open conformations of AcbH, the solute receptor of the putative carbohydrate transporter AcbFG which is encoded in the acarbose (acarviosyl-1,4-maltose) biosynthetic gene cluster from Actinoplanes sp. SE50/110. Binding assays identified AcbH as a high-affinity monosaccharide-binding protein with a dissociation constant (K(d)) for β-d-galactopyranose of 9.8±1.0 nM. Neither galactose-containing di- and trisaccharides, such as lactose and raffinose, nor monosaccharides including d-galacturonic acid, l-arabinose, d-xylose and l-rhamnose competed with [(1)(4)C]galactose for binding to AcbH. Moreover, AcbH does not bind d-glucose, which is a common property of all but one d-galactose-binding proteins characterized to date. Strikingly, determination of the X-ray structure revealed that AcbH is structurally homologous to maltose-binding proteins rather than to glucose-binding proteins. Two helices are inserted in the substrate-binding pocket, which reduces the cavity size and allows the exclusive binding of monosaccharides, specifically β-d-galactopyranose, in the (4)C(1) conformation. Site-directed mutagenesis of three residues from the binding pocket (Arg82, Asp361 and Arg362) that interact with the axially oriented O4-H hydroxyl of the bound galactopyranose and subsequent functional analysis indicated that these residues are crucial for galactose binding. To our knowledge, this is the first report of the tertiary structure of a solute receptor with exclusive affinity for β-d-galactopyranose. The putative role of a galactose import system in the context of acarbose metabolism in Actinoplanes sp. is discussed.


[Behçet's disease and cardiovascular pathology].
Behçet's syndrome appears in different localisations. Some of them were at the source of the initial description of the disease and are therefore well known. However, cardiovascular localisations were discovered later on and are worthy of detail. They may enable retrospective diagnosis and are an evolutive turning point in this still mysterious disease.


Do Different Orthodontic Malocclusions Affect Patients' Self-Concept and Psychosocial Status?
The aim of this study was to evaluate the self-concept and psychosocial status measured by the levels of social phobia and loneliness in a sample of adolescent patients with different malocclusions and to explain the relationships, if any, between malocclusions. This study was performed on 90 (41 females and 49 males) orthodontic patients with a mean age of 13.52±1.81 years. The patients were divided into three groups (Class I, Class II, and Class III) according to the different types of malocclusions. Piers-Harris Children's Self-Concept Scale (PHCSCS) was used to determine the self-concepts of patients. In addition, the levels of social phobia and loneliness were measured by Capa Social Phobia Scale for Children and Adolescents (CSPSCA) and University of California Los Angeles (UCLA) Loneliness Inventory, respectively. Data were analyzed statistically. The self-concept, social phobia, and loneliness scores of each group were compared using two-way analysis of variance (ANOVA) and Tukey's post hoc test. Self-concept scores did not significantly differ between the groups, except for the popularity subscale. Patients with Class II malocclusion had the lowest popularity scores. No significant differences were found between the levels of social phobia and loneliness among groups (p>0.05). Our findings demonstrated that different malocclusions do not affect patients' self-concept and psychosocial well-being.


Inadequacy of cardiovascular risk factor management in chronic kidney transplantation - evidence from the FAVORIT study.
Kidney transplant recipients (KTRs) have increased risk of cardiovascular disease (CVD). Our objective is to describe the prevalence of CVD risk factors applying standard criteria and use of CVD risk factor-lowering medications in contemporary KTRs. The Folic Acid for Vascular Outcome Reduction in Transplantation study enrolled and collected medication data on 4107 KTRs with elevated homocysteine and stable graft function an average of five yr post-transplant. CVD risk factors were common (hypertension or use of blood pressure (BP) lowering medication in 92%, borderline or elevated low-density lipoprotein (LDL) or use of lipid-lowering agent in 66%, history of diabetes mellitus in 41%, and obesity in 38%); prevalent CVD was reported in 20% of study participants. National Kidney Foundation BP guidelines (BP <130/80 mmHg) were not met by 69% of participants. Uncontrolled hypertension (BP of 140/90 mmHg or higher) was present in 44% of those taking antihypertension medication; 18% of participants had borderline or elevated LDL, of which 60% were untreated, and 31% of the participants with prevalent CVD were not using an antiplatelet agent. There is opportunity to improve treatment and control of traditional CVD risk factors in kidney transplant recipients.


Correlation between clinical risk factors and tracheal intubation difficulty in infants with Pierre-Robin syndrome: a retrospective study.
Difficult tracheal intubation is a common problem encountered by anesthesiologists in the clinic. This study was conducted to assess the difficulty of tracheal intubation in infants with Pierre Robin syndrome (PRS) by incorporating computed tomography (CT) to guide airway management for anesthesia. In this retrospective study, we analyzed case-level clinical data and CT images of 96 infants with PRS. First, a clinically experienced physician labeled CT images, after which the color space conversion, binarization, contour acquisition, and area calculation processing were performed on the annotated files. Finally, the correlation coefficient between the seven clinical factors and tracheal intubation difficulty, as well as the differences in each risk factor under tracheal intubation difficulty were calculated. The absolute value of the correlation coefficient between the throat area and tracheal intubation difficulty was 0.54; the observed difference was statistically significant. Body surface area, weight, and gender also showed significant difference under tracheal intubation difficulty. There is a significant correlation between throat area and tracheal intubation difficulty in infants with PRS. Body surface area, weight and gender may have an impact on tracheal intubation difficulty in infants with PRS.


Volatiles of Grape Inoculated with Microorganisms: Modulation of Grapevine Moth Oviposition and Field Attraction.
Semiochemicals released by plant-microbe associations are used by herbivorous insects to access and evaluate food resources and oviposition sites. Adult insects may utilize microbial-derived nutrients to prolong their lifespan, promote egg development, and offer a high nutritional substrate to their offspring. Here, we examined the behavioral role of semiochemicals from grape-microbe interactions on oviposition and field attraction of the grapevine moth Lobesia botrana (Denis & Schiffermüller). The volatile constituents released by grape inoculated with yeasts (Hanseniaspora uvarum (Niehaus), Metschnikowia pulcherrima (Pitt.) M.W. Miller, Pichia anomala, Saccharomyces cerevisiae Meyen ex E.C. Hansen, and Zygosaccharomyces rouxii (Boutroux) Yarrow), sour rot bacteria (Acetobacter aceti (Pasteur) Beijerinck and Gluconobacter oxydans (Henneberg) De Ley), and a fungal pathogen (Botrytis cinerea Pers.) all endemic of the vineyard were sampled by solid-phase microextraction and analyzed by gas-chromatography coupled with mass spectrometry. Ethanol, 3-methyl-1-butanol, and ethyl acetate were the most common volatiles released from all microbe-inoculated grapes. In addition, acetic acid was released at a substantial amount following bacteria inoculation and in a three-way inoculation with yeasts and the fungus. 2-phenylethanol, a compound reported to attract tortricid moths when used in combination with acetic acid, was found at a relatively low level in all microbial combinations as well as in the control grape. While grapes inoculated with a consortium of yeasts stimulated oviposition in comparison with uninoculated berries, the phytopathogenic fungus deterred egg-laying. Nonetheless, the highest preference to lay eggs was measured when the yeasts were co-inoculated with the fungus. The lowest preference was obtained when grapes were inoculated with sour rot bacteria and their binary co-inoculation with yeasts and the fungus. Interestingly, oviposition on berries simultaneously inoculated with all the three microbial groups was unaffected. Lures loaded with either acetic acid or 2-phenylethanol were not attractive when placed in traps as single component in vineyards, but a binary blend attracted both sexes of grapevine moth in significant numbers. Further addition of the three most common volatiles released by infected berries (ethanol, 3-methyl-1-butanol, and ethyl acetate) did not significantly increase moth catch with this binary blend. The ecological implications of the grape-microorganism and grapevine moth interaction as well as the possibility to develop a pest monitoring system based on microbial volatiles are discussed.


Chemotactic factors of Flavobacterium columnare to skin mucus of healthy channel catfish (Ictalurus punctatus).
To gain an insight into the chemotactic factors involved in chemotaxis, we exposed a virulent strain of Flavobacterium columnare to various treatments, followed by analysis of its chemotactic activity. The chemotactic activity of F. columnare was significantly (P<0.05) inhibited when cells were pretreated by sodium metaperiodate, and a major portion of the capsular layer surrounding the cells was removed. Pretreatment of F. columnare with D-mannose, D-glucose and N-acteyl-D-glucosamine significantly (P<0.05) inhibited its chemotaxis activity, whereas pretreatment of cells with d-fructose, L-fucose, D-glucosamine, d-galactosamine, D-sucrose and N-acetyl-D-galactosamine failed to inhibit its chemotactic activity. These results indicate that at least three carbohydrate-binding receptors (D-mannose, D-glucose and N-acteyl-D-glucosamine) associated with the capsule of F. columnare might be involved in the chemotactic responses. The relative transcriptional levels of three gliding motility genes (gldB, gldC, gldH) of F. columnare compared with 16S rRNA gene following the exposure of F. columnare to catfish skin mucus were evaluated by quantitative PCR (qPCR). qPCR results revealed that the transcriptional level of gldH was significantly (P<0.001) upregulated in normal F. columnare at 5 min postexposure to the catfish mucus. However, when F. columnare were pretreated with D-mannose, there was no upregulation of gliding motility genes. Taken together, our results suggest that carbohydrate-binding receptors play important roles in the chemotactic response to catfish mucus.


[Method for evaluating effectiveness of simulation trainings in surgical manipulations].
Performance of varies surgical manipulations (SM) is a key skill in surgery. To develop such skills simulation trainings (ST) are used, followed by a training transfer, which is the ultimate goal of ST However, this training goal is not always achievable - the share of doctors using laparoscopic intracorporal suturing after the training ranges from 43.8% to 72.2%. Therefore, to improve training transfer it is necessity to evaluate effectiveness of such training programs. Current methods evaluate training results either outside real practice or in practice but in small groups due to high cost and efforts consumed. The paper presents a new method to evaluate effectiveness of SM simulation training programs in general population of the trainees, evaluate additional effects of the training and analyze personal factors affecting the training results. The method is based on a survey of the ST program participants, and tested at the Training and Accreditation Center «Medical Simulation Center of the Botkin Hospital» within the program on laparoscopic intracorporal suturing. The rate of training transfer added up to 88.9%. The suggested method makes it possible to evaluate effectiveness of SM simulation training in general population of the trainees, analyze factors affecting the training results and use findings for improving ST programs and methods in general. The method can be recommended for a large-scale implementation in simulation training programs.


COL1A1/2 Pathogenic Variants and Phenotype Characteristics in Ukrainian Osteogenesis Imperfecta Patients.
Osteogenesis imperfecta (OI) is a hereditary bone disorder caused by defects of type I collagen. Although up to 90% of patients harbor pathogenic variants in the COL1A1/2 gene, which codes for collagen α1/2 chains, the spectrum of OI genotypes may differ between populations, and there is academic controversy around OI genotype-phenotype correlations. In the current study, 94 Ukrainian OI families were interviewed. Clinical and genealogical information was collected from patients in spoken form, and their phenotypes were described. To identify the spectrum of collagen I pathogenic variants, COL1A1/2 mutational analysis with Sanger sequencing was performed on the youngest affected individual of every family. Of the 143 patients investigated, 67 (46.85%) had type I OI, 24 (16.78%) had type III, 49 (34.27%) had type IV, and III (2.10%) had type V. The mean number of fractures suffered per patient per year was 1.32 ± 2.88 (type I 0.50 ± 0.43; type III 3.51 ± 6.18; type IV 1.44 ± 1.77; and type 5 0.77 ± 0.23). 87.23% of patients had skeletal deformations of different severity. Blue sclera, dentinogenesis imperfecta, and hearing loss were present in 87%, 55%, and 22% of patients, respectively. COL1A1/2 pathogenic variants were harbored by 60 patients (63.83%). 27 pathogenic variants are described herein for the first time. The majority of the pathogenic variants were located in the COL1A1 gene (76.19%). Half (49.21%) of the pathogenic variants were represented by structural variants. OI phenotype severity was highly correlated with type of collagen I defect. The current article presents an analysis of the clinical manifestations and COL1A1/2 mutational spectrum of 94 Ukrainian OI families with 27 novel COL1A1/2 pathogenic variants. It is hoped that this data and its analysis will contribute toward the increased understanding of the phenotype development and genetics of the disorder.


Closed-loop coadministration of propofol and remifentanil guided by bispectral index: a randomized multicenter study.
We have developed a proportional-integral-derivative controller allowing the closed-loop coadministration of propofol and remifentanil, guided by a Bispectral Index (BIS) monitor, during induction and maintenance of general anesthesia. The controller was compared with manual target-controlled infusion. In a multicenter study, 196 surgical patients were randomly assigned to dual closed-loop or manual administration of propofol and remifentanil. Comparison between groups was evaluated by calculating a global score that characterized the overall performance of the controller including the percentage of adequate anesthesia, defined as BIS between 40 and 60, the median absolute performance error, and wobble. Secondary outcomes included occurrence of burst suppression ratio, time to tracheal extubation, and drug consumption. Eighty-three patients assigned to dual-loop control and 84 patients assigned to manual control completed the study. The global score and the percentage of time with BIS between 40 and 60 were better in the dual-loop group (26 ± 11 vs 43 ± 40, P < 0.0001; 82% ± 12% vs 71% ± 19%, P < 0.0001). Overshoot (BIS <40), undershoot (BIS >60), and burst suppression ratio were all significantly less common in the dual-loop group. Modifications to the propofol and remifentanil infusions were more frequent, and adjustments smaller in the dual-loop group. Remifentanil consumption was greater (0.22 ± 0.07 vs 0.16 ± 0.07 μg · kg(-1) · min(-1); P < 0.0001) and the speed to tracheal extubation was shorter (10 ± 4 vs 11 ± 5 minutes; P = 0.02) in the dual-loop group. The controller allows the automated delivery of propofol and remifentanil and maintains BIS values in predetermined boundaries during general anesthesia better than manual administration.


Histone acetylation in insect chromosomes.
Acetylation of histones takes place along the salivary gland chromosomes of Chironomus thummi when RNA synthesis is active. It can be observed but not measured quantitatively by autoradiography of chromosome squashes. The "fixatives" commonly used in preparing squashes of insect chromosomes preferentially extract the highly acetylated "arginine-rich" histone fractions; the use of such fixatives may explain the reported absence of histone acetylation in Drosophila melanogaster.


Incomplete ossification of the humeral condyle in Vietnamese pot-bellied pigs.
The purpose of this study was to evaluate the occurrence of humeral condylar fractures in Vietnamese pot-bellied pigs and to postulate a possible predisposing cause for these fractures. Thirteen Vietnamese pot-bellied pigs (Group A) were evaluated over an eight year period (1990-1998), each with a history of either a unilateral or bilateral forelimb lameness. The cause of lameness was localized to the elbow region. Of the thirteen pigs, twenty-one elbows were evaluated radiographically. Pigs ranged in age from six months to four years old. All pigs over the age of seven months showed radiographic evidence of elbow degenerative joint disease. Fractures involving the medial aspect of the humeral condyle were identified in 8/21 studies (38%). A well-defined linear intracondylar articular lucency was identified in 7/21 studies (33%) on the craniocaudal projection. The site of this lucency corresponded to the location of the articular component of the fractures seen involving the humeral condyle. The elbows of five pot-bellied pigs with no known history of forelimb lameness or trauma (Group B) were evaluated radiographically following euthanasia. All five pigs were of unknown age and gender. An intracondylar vertical linear lucency was identified bilaterally in three pigs (60%). Concurrent degenerative joint disease was present in all instances. The remaining two pigs were radiographically normal. Computed tomography of the elbows was performed in one affected pig from Group B. The radiographic findings in this pig were verified. Histopathology of the right elbow of this affected pig was diagnostic for incomplete endochondral ossification of the humeral condyle. A similar condition involving the humeral condyle has been previously described in Cocker and Brittany Spaniels. These canine breeds also have a high incidence of humeral condylar fractures. It is postulated that Vietnamese pot-bellied pigs are similarly prone to humeral condylar fractures, even in the absence of known trauma, due to incomplete ossification of the humeral condyle.


A novel fluorophore based on the coupling of AIE and ESIPT mechanisms and its application in biothiol imaging.
A novel fluorophore TPE-HBT was designed based on the intersection of tetraphenylethene (TPE) and 2-(2'-hydroxyphenyl)benzothiazole (HBT). Owing to the synergistic effect of aggregation-induced emission (AIE) and excited-state intramolecular proton transfer (ESIPT) mechanisms, this fluorophore exhibits excellent performance with a high solid-state fluorescence quantum yield (ΦF = 0.97) and a large Stokes shift (>200 nm). Moreover, its simple modification with the 2,4-dinitrobenzenesulfonyl group makes it suitable for biothiol imaging.


Time-Dependent Wetting Behavior of PDMS Surfaces with Bioinspired, Hierarchical Structures.
Wetting of rough surfaces involves time-dependent effects, such as surface deformations, nonuniform filling of surface pores within or outside the contact area, and surface chemistries, but the detailed impact of these phenomena on wetting is not entirely clear. Understanding these effects is crucial for designing coatings for a wide range of applications, such as membrane-based oil-water separation and desalination, waterproof linings/windows for automobiles, aircrafts, and naval vessels, and antibiofouling. Herein, we report on time-dependent contact angles of water droplets on a rough polydimethylsiloxane (PDMS) surface that cannot be completely described by the conventional Cassie-Baxter or Wenzel models or the recently proposed Cassie-impregnated model. Shells of sand dollars (Dendraster excentricus) were used as lithography-free, robust templates to produce rough PDMS surfaces with hierarchical, periodic features ranging from 1 × 10(-7) to 1 × 10(-4) m. Under saturated vapor conditions, we found that in the short term (<1 min), the contact angle of a sessile water droplet on the templated PDMS, θ(SDT) = 140 ± 3°, was accurately described by the Cassie-Baxter model (predicted θ(SDT) = 137°); however, after 90 min, θ(SDT) fell to 110°. Fluorescent confocal microscopy confirmed that the initial reduction in θ(SDT) to 110° (the Wenzel limit) was primarily a Cassie-Baxter to Wenzel transition during which pores within the contact area filled gradually, and more rapidly for ethanol-water mixtures. After 90 min, the contact line of the water droplet became pinned, perhaps caused by viscoelastic deformation of the PDMS around the contact line, and a significant volume of water began to flow from the droplet to pores outside the contact region, causing θ(SDT) to decrease to 65° over 48 h on the rough surface. The system we present here to explore the concept of contact angle time dependence (dynamics) and modeling of natural surfaces provides insights into the design and development of long- and short-lived coatings.


Male-female larval interactions in Schistosoma mansoni-infected Biomphalaria glabrata.
This paper investigates Schistosoma mansoni male-female larval interactions in simultaneous bi-miracidial Biomphalaria glabrata infections. Larval interactions were analysed at four levels of infection: (i), miracidial infectivity, estimated by the prevalence of mollusc infection; (ii), mollusc pathology, measured by the mollusc growth and survival; (iii), dynamics of the cercarial sex ratio; and (iv), cercarial infectivity, measured as the success of development into adulthood. Our results showed that larval interactions exist in S. mansoni-infected B. glabrata. These interactions do not occur in miracidial infectivity, but occur in mollusc pathology, cercarial sex ratio dynamics and cercarial infectivity. Regarding mollusc pathology, we showed that the bi-miracidially-infected molluscs were smaller than the mono-miracidially-infected ones. This could be the result of larval competition. Regarding the dynamics of the cercarial sex ratio, we showed larval female superiority as compared with male larvae inducing the shedding of female-biased cercarial sex ratios. These sex ratios were rhythmic and could be the reflection of an external expression of the intramolluscan development. Regarding cercarial infectivity, we showed that the simultaneous presence of both sexes in a mollusc increased the cercarial infectivity. This result could be due to male-female larval synergism.


Use of Nasogastric Feeding Tubes for Children at Home: A Template for Caregiver Education.
There is a lack of knowledge on the part of caregivers who need to place nasogastric (NG) tubes in children for enteral nutrition therapy. This article provides the rationale, best practices, and a template for caregiver education. Canadian and Australian programs have excellent patient education materials. They have shared these step-by-step procedures for healthcare professionals to provide to caregivers to whom they are teaching placement and care of NG tubes.


Thioredoxin inhibits tumor necrosis factor- or interleukin-1-induced NF-kappaB activation at a level upstream of NF-kappaB-inducing kinase.
Gene induction by tumor necrosis factor-alpha (TNFalpha) or interleukin-1beta (IL-1beta) is mediated in part by activation of the transcription factor nuclear factor kappaB (NF-kappaB), and requires signal adaptor molecules such as TNF receptor-associated factor (TRAFs). The latter interact with the NF-kappaB-inducing kinase (NIK), which is believed to be part of the IkappaB kinase complex. Although the precise mechanism is to be elucidated, it is well-known that antioxidant treatments inhibit the inflammatory cytokine-induced NF-kappaB activation. Thioredoxin (TRX) is a 12-kDa endogenous protein that regulates various cellular functions by modulating the redox state of proteins, overexpression of this molecule inhibits NF-kappaB activation. To elucidate the roles of TRX in the signal transduction of the cytokines, we investigated the effects of TRX on NF-kappaB activation induced by cytokine treatment or by overexpression of the signaling molecules. Our data show that TRX treatment inhibits NF-kappaB-dependent transcription at the level of downstream of TRAFs and upstream of NIK: TRX inhibited TRAF2-, TRAF5-, and TRAF6-induced NF-kappaB activation but does not inhibit NIK-, IKKalpha-, and MEKK-induced activation. In addition, we show that TRX inhibits NF-kappaB activation in a manner different from that for SAPK (stress activated protein kinase) inhibition.


Coordination of arm and wrist motion during a reaching task.
An analysis of arm movements involving forward projection of the hand in order to reach for and grasp a target at different orientations is presented. The reaching movements required shoulder flexion, elbow extension, and wrist pronation or supination. The relation between elbow and shoulder instantaneous angular position proved to be consistent from trial to trial of each task, independent of movement speed. Further, this relation was not influenced by the presence or absence of a concomitant wrist rotation. During the deceleratory phase of the movement, the slope of elbow angular velocity to shoulder angular velocity was constant and independent of target orientation. Wrist motion was instead highly variable in timing, course, and duration. Supinatory movements tended to be fractionated. On average, the duration of wrist movements was shorter than that of shoulder and elbow motions. The pattern of biceps EMG activity during supinatory and pronatory movements was different. Since motion at the shoulder and elbow was virtually identical in the two cases, net flexor torque at the elbow was also little different. It is concluded that other elbow flexors and extensors also exhibit a task-dependent patterning of activity so as to produce the same net torque. The results are discussed in the context of the internal constraints present during the movements that we examined. These constraints are the inertial coupling between shoulder and elbow motion and those which derive from the bifunctional nature of many of the muscles participating in the movement.


PC program for comparing tracking indices in several independent groups.
A method for computing a measure of tracking based on Cohen's kappa statistic for one-sample longitudinal data sets was previously described and implemented. This paper shows how one may test the equality of several kappas, each computed from an independent longitudinal sample. Thus, it is possible to formally compare groups of individuals with regard to stability in growth (or adaptive) patterns. Relative assessments of predictability in growth outcomes in different populations can be made with this approach. Also, when a common value of kappa is not contradicted by the data, a method to estimate this value and obtain a confidence interval for it is shown. A menu-driven GAUSS program for carrying out the procedure is described and made available. The method and program are illustrated with three samples of Guatemalan children. © 1992 Wiley-Liss, Inc.


Bacterial conjugation protein MobA mediates integration of complex DNA structures into plant cells.
Agrobacterium tumefaciens transfers T-DNA to plant cells, where it integrates into the genome, a property that is ensured by bacterial proteins VirD2 and VirE2. Under natural conditions, the protein MobA mobilizes its encoding plasmid, RSF1010, between different bacteria. A detailed analysis of MobA-mediated DNA mobilization by Agrobacterium to plants was performed. We compared the ability of MobA to transfer DNA and integrate it into the plant genome to that of pilot protein VirD2. MobA was found to be about 100-fold less efficient than VirD2 in conducting the DNA from the pTi plasmid to the plant cell nucleus. However, interestingly, DNAs transferred by the two proteins were integrated into the plant cell genome with similar efficiencies. In contrast, most of the integrated DNA copies transferred from a MobA-containing strain were truncated at the 5' end. Isolation and analysis of the most conserved 5' ends revealed patterns which resulted from the illegitimate integration of one transferred DNA within another. These complex integration patterns indicate a specific deficiency in MobA. The data conform to a model according to which efficiency of T-DNA integration is determined by plant enzymes and integrity is determined by bacterial proteins.


Galleria mellonella: The Versatile Host for Drug Discovery, In Vivo Toxicity Testing and Characterising Host-Pathogen Interactions.
Larvae of the greater wax moth, Galleria mellonella, are a convenient in vivo model for assessing the activity and toxicity of antimicrobial agents and for studying the immune response to pathogens and provide results similar to those from mammals. G. mellonella larvae are now widely used in academia and industry and their use can assist in the identification and evaluation of novel antimicrobial agents. Galleria larvae are inexpensive to purchase and house, easy to inoculate, generate results within 24-48 h and their use is not restricted by legal or ethical considerations. This review will highlight how Galleria larvae can be used to assess the efficacy of novel antimicrobial therapies (photodynamic therapy, phage therapy, metal-based drugs, triazole-amino acid hybrids) and for determining the in vivo toxicity of compounds (e.g., food preservatives, ionic liquids) and/or solvents (polysorbate 80). In addition, the disease development processes are associated with a variety of pathogens (e.g., Staphylococcus aureus, Listeria monocytogenes, Aspergillus fumigatus, Madurella mycotomatis) in mammals are also present in Galleria larvae thus providing a simple in vivo model for characterising disease progression. The use of Galleria larvae offers many advantages and can lead to an acceleration in the development of novel antimicrobials and may be a prerequisite to mammalian testing.


Germline VH/VL pairing in antibodies.
Antibodies are key molecules of the adaptive immune response and are now a major class of biopharmaceuticals. Pairing of heavy and light chains is one of the ways of generating antibody diversity and, while little is known about mechanisms governing V(H)/V(L) pairing, previous studies have suggested that the germline source from which chains are paired is random. By selecting paired antibody protein sequences from human and mouse antibodies from the KabatMan database and mapping them onto their corresponding germline sequences, we find that pairing preferences do exist in the germline, but only for a small proportion of germline gene segments; others are much more promiscuous showing no preferences. The closest equivalent human and mouse gene families were identified and pairing preferences compared. This work may impact on the ability to generate more stable antibodies for use as biopharmaceuticals.


Is acinic cell carcinoma a variant of secretory carcinoma? A FISH study using ETV6'split apart' probes.
Acinic cell carcinomas (ACCs) and secretory carcinomas (SCs) of the breast are rare, low-grade malignancies that preferentially affect young female patients. Owing to the morphological and immunohistochemical similarities between these lesions, they have been proposed to be two morphological variants of the same entity. It has been demonstrated that SCs of the breast consistently harbour the t(12;15)ETV6-NTRK3 translocation. The aim was to determine whether ACCs also harbour ETV6 gene rearrangements and are thus variants of SCs. Using the ETV6 fluorescence in situ hybridization DNA Probe Split Signal (Dako), the presence of ETV6 rearrangements in three SCs and six ACCs was investigated. Cases were considered as harbouring an ETV6 gene rearrangement if >10% of nuclei displayed 'split apart signals' (i.e. red and green signals were separated by a distance greater than the size of two hybridization signals). Whereas the three SCs displayed ETV6 split apart signals in >10% of the neoplastic cells, no ACC showed any definite evidence of ETV6 gene rearrangement. Based on the lack of ETV6 rearrangements in ACCs, our results strongly support the concept that SCs and ACCs are distinct entities and should be recorded separately in breast cancer taxonomy schemes.


Adalimumab for early rheumatoid arthritis.
Rheumatoid arthritis affects 1% of the population and can result in joint destruction, reduced quality of life and function, loss of work productivity and, in severe cases, early mortality. Recent advances with optimal therapeutic strategies, including early initiation of treatment, tight control of the disease activity aiming for remission of the disease and the advent of biological therapies, have led to improved outcomes for patients with rheumatoid arthritis. It is generally agreed that the best outcomes for patients with rheumatoid arthritis occur when treatment is started early. Adalimumab is a new fully humanized monoclonal antibody that blocks the adverse effects of excess TNF-alpha. New studies using this agent early in the course of rheumatoid arthritis indicate superior rates of remission for patients with this disease.


Design and implementation of a random neural network routing engine.
Random neural network (RNN) is an analytically tractable spiked neural network model that has been implemented in software for a wide range of applications for over a decade. This paper presents the hardware implementation of the RNN model. Recently, cognitive packet networks (CPN) is proposed as an alternative packet network architecture where there is no routing table, instead the RNN based reinforcement learning is used to route packets. Particularly, we describe implementation details for the RNN based routing engine of a CPN network processor chip: the smart packet processor (SPP). The SPP is a dual port device that stores, modifies, and interprets the defining characteristics of multiple RNN models. In addition to hardware design improvements over the software implementation such as the dual access memory, output calculation step, and reduced output calculation module, this paper introduces a major modification to the reinforcement learning algorithm used in the original CPN specification such that the number of weight terms are reduced from 2n/sup 2/ to 2n. This not only yields significant memory savings, but it also simplifies the calculations for the steady state probabilities (neuron outputs in RNN). Simulations have been conducted to confirm the proper functionality for the isolated SPP design as well as for the multiple SPP's in a networked environment.


Discontinuing financial incentives for adherence to antipsychotic depot medication: long-term outcomes of a cluster randomised controlled trial.
In a cluster randomised controlled trial, offering financial incentives improved adherence to antipsychotic depot medication over a 1-year period. Yet, it is unknown whether this positive effect is sustained once the incentives stop. Patients in the intervention and control group were followed up for 2 years after the intervention. Primary and secondary outcomes were assessed at 6 months and 24 months post intervention. Assessments were conducted between September 2011 and November 2014. After the intervention period, intervention and control groups did not show any statistically significant differences in adherence, neither in the first 6 months (71% and 77%, respectively) nor in the following 18 months (68%, 74%). There were no statistically significant differences in secondary outcomes, that is, adherence ≥95% and untoward incidents either. It may be concluded that incentives to improve adherence to antipsychotic maintenance medication are effective only for as long as they are provided. Once they are stopped, adherence returns to approximately baseline level with no sustained benefit. ISRCTN77769281; Results.


C3a/C3aR synergies with TGF-β to promote epithelial-mesenchymal transition of renal tubular epithelial cells via the activation of the NLRP3 inflammasome.
Complement component 3a and its receptor (C3a/C3aR) and the nucleotide-binding oligomerization domain-like receptor protein-3 (NLRP3) inflammasome contribute to epithelial-mesenchymal transition (EMT). However, the relationship between C3a/C3aR and the NLRP3 inflammasome in EMT remains unclear. This study aimed to elucidate the roles of C3a/C3aR and the NLRP3 inflammasome involved in TGF-β-induced EMT. Mouse renal tubular epithelial cells (TCMK-1) were exposed to C3a and TGF-β for 48 h. C3aR antagonist, MCC950, an inhibitor of the NLRP3 inflammasome and PD98059, an inhibitor of ERK signaling, were respectively applied to pretreat the cells at 30 min before C3a and TGF-β administration.The cells were collected for western blot, immunofluorescence staining and ELISA. Unilateral ureteral obstruction (UUO) models were established using male C57BL/6 wild-type (WT) mice and age-matched C3aR-deficient mice. MCC950 was intraperitoneally injected in UUO mice. Kidney samples were collected for immunohistochemistry staining. In vitro, C3a synergized with TGF-β to promote EMT and the activation of the NLRP3 inflammasome. Inhibition of C3aR attenuated EMT and the activation of the NLRP3 inflammasome. Inhibition of the NLRP3 inflammasome alleviated EMT but didn't affect the expression of C3aR. Inhibition of ERK signaling inhibited the activation of the NLRP3 inflammasome. In vivo, the expression of IL-1β was significantly higher in UUO mice compared to the sham-operated mice. C3aR deficiency and inhibition of the NLRP3 Inflammasome contributed to decreased IL-1β in UUO mice. Our data revealed that C3a/C3aR synergies with TGF-β to activate the NLRP3 inflammasome to promote epithelial-mesenchymal transition of renal tubular epithelial cells through ERK signaling, and the way in which C3aR activates the inflammasome is to promote the assembly of the NLRP3 inflammasome.


Increase in hippocampal volume after electroconvulsive therapy in patients with depression: a volumetric magnetic resonance imaging study.
Major depression has traditionally been regarded as a neurochemical disease, but findings of a decreased hippocampal volume in patients with depression have turned the pathophysiological focus toward impairments in structural plasticity. The mechanisms of action of the most effective antidepressive treatment, electroconvulsive therapy (ECT), still remains elusive, but recent animal research has provided evidence for a cell proliferative effect in the hippocampus. The aim of this prospective study was to determine if hippocampal volume changes after ECT in patients with depression. Twelve patients with depression and ongoing antidepressive pharmacological treatment were investigated with clinical ratings and 3 T magnetic resonance imaging within 1 week before and after the ECT series. Each hippocampus was manually outlined on coronal slices, and the volume was calculated. The left as well as the right hippocampal volume increased significantly after ECT. The hippocampal volume increases after ECT, supporting the hypothesis that hippocampus may play a central role in the treatment of depression.


CLINICAL EFFECT OF HEMOPARASITE INFECTIONS IN SNOWY OWLS ( BUBO SCANDIACUS).
Vector-borne hemoparasites are commonly found in avian species. Plasmodium spp., the causative agent of avian malaria, are intraerythrocytic parasites that can cause signs ranging from subclinical infection to severe acute disease. In raptor species, most hemoparasites are associated with subclinical infection and are generally not treated when seen on blood evaluation. This case series reviews five cases of hemoparasite infection in snowy owls ( Bubo scandiacus). These animals were infected with a variety of hemoparasites, including Plasmodium, Haemoproteus, and Leukocytozoon spp. Death of one of these birds due to hemoparasite burden led to a change in the monitoring for and treatment of subclinical hemoparasitic infections in this species. Three subsequently infected snowy owls have been treated with primaquine and chloroquine. The birds that were treated survived infection, and parasite burdens in peripheral blood diminished. Postulated reasons for increased morbidity and mortality associated with hemoparasitic infections in captive snowy owls, as opposed to other raptor species, include stress, concurrent disease, novel pathogen exposure, and elevated environmental temperatures.


A unique pattern of central nervous system leukemia in acute myelomonocytic leukemia associated with inv(16)(p13q22).
Twenty-six patients with inv(16)(p13q22) or del(16)(q22) in association with acute myelomonocytic leukemia (AMML-M4, FAB classification), and abnormal marrow eosinophils have been treated at this institute. Initial bone marrow eosinophilia (greater than or equal to 4%) was observed in 22 of 26 patients (85%), and abnormal eosinophil morphology, characterized by immature cells with some interspersed basophilic granules, was evident in 26 of 26 (100%). Giemsa-banded chromosome analysis performed in all patients revealed 16 cases with inv(16)(p13q22) alone, and ten cases with additional chromosome changes. Twenty-five patients received combination induction chemotherapy, and 23 (92%) achieved complete remission (CR). The median duration of remission was 18 months (range, six to 72 + months), and the median duration of survival was 34 months (range, 0.5 to 133 months). Nine patients (35%) relapsed in the CNS at a median time of 19 months (range, six to 133 months) from first marrow CR. All patients had leptomeningeal disease, and in addition, six of nine (66%) demonstrated two or more enhancing lesions on computed tomography brain scan, consistent with intracerebral myeloblastomas. Review of 384 Giemsa-banded patients with acute myeloid leukemia revealed no other morphologic or cytogenetic subgroup with either an equivalent incidence of CNS leukemia or documented intracerebral myeloblastomas. This series of inv(16)(p13q22)/del(16)(q22) AMML reports a favorable prognosis for such patients and associates a specific clonal cytogenetic subgroup of acute leukemia with a distinct propensity for CNS relapse, manifesting as leptomeningeal disease and intracerebral myeloblastomas.


Time-dependent photoluminescence spectroscopy as a tool to measure the ligand exchange kinetics on a quantum dot surface.
The exchange kinetics of native ligands that passivate CdSe quantum dots (hexadecylamine (HDA), trioctylphosphine oxide (TOPO), and trioctylphosphine (TOP)) by thiols is followed in situ. This is realized by measuring, in real-time, the decrease in emission intensity of the QDs upon addition of hexanethiol (HT) which quenches the emission. The effect of adding an excess of native ligands prior to thiol addition on the capping exchange is studied to provide insight in the bond strength and exchange kinetics of the individual surfactants. Temperature-dependent measurements reveal faster kinetics with increasing temperature. A kinetic model to describe the time-dependent measurements is introduced, taking into account the equilibrium between native ligands before thiol addition and describing the evolution of surface coverage by all ligands over time. The model allows us to extract the quenching rate for a single thiol ligand (0.004 ns(-1)) as well as exchange rates, equilibrium constants, activation energies, and changes in Gibbs free energy for replacement of the different native surfactants by HT. The analysis reveals that the substitution half-time of HDA by HT (72 s) is much shorter than for TOP (5 h) or TOPO (2.5 h) under the same conditions. The temperature dependence of the kinetics shows that the activation energy for exchange of HDA/TOPO by hexanethiol (1.6 kJ/mol) is much smaller than for TOP (20.9 kJ/mol).


Accessory nuclei in insect oogenesis: in search of the function of enigmatic organelles.
This review compiles present knowledge of the structure and molecular composition of the enigmatic cytoplasmic organelles called accessory nuclei. Most typically, they are found in the perinuclear cytoplasm in oocytes of insects and several other invertebrates. Accessory nuclei originate by budding of the oocyte nucleus (germinal vesicle) and are surrounded by an envelope identical to the nuclear envelope. They contain one or several dense inclusions called pseudonucleoli immersed in a translucent ground substance or matrix. Comparative analysis of the morphology, molecular composition and the ultimate fate of accessory nuclei and their inclusions revealed that there are two basic types of these organelles in insect oocytes. In mallophagans, accessory nuclei are associated with the oocyte nucleus throughout entire oogenesis and at least some of them are connected to the germinal vesicle by slender stems. Each accessory nucleus contains a single, dense, RNA-positive inclusion which is likely to correspond to a nucleolus. In hymenopterans, accessory nuclei initially surround the germinal vesicle but during oogenesis they separate from it and migrate toward the peripheral ooplasm. Within the accessory nucleus matrix usually two distinct inclusions develop. One of these is perfectly spherical, contains coilin and small nuclear ribonucleoproteins and is homologous to the Cajal body. In the light of recent discoveries, we discuss the role accessory nuclei play in insect oogenesis and early embryogenesis.


The role of nutritional modifications in the prevention of macrovascular complications of diabetes.
A wide range of dietary changes is likely to reduce the risk of macrovascular complications of diabetes. It is critically important to recommend a balance of macronutrients different from that currently consumed in most Western countries. Saturated fatty acids, especially myristic and palmitic acids, and trans fatty acids must be reduced to lower LDL cholesterol. Intake of polyunsaturated fatty acids should not be excessive (less than 10% total energy). Fiber-rich carbohydrate, derived from cereals, vegetables, and fruit with intact cell walls, and cis monounsaturated fatty acids should provide the bulk of total energy. These changes are likely to be associated with the most favorable lipoprotein profile and increase intake of dietary antioxidants and so reduce the level of oxidative stress. A reduction of sodium to below 6 g per day will help to reduce blood pressure levels. Optimal glycemic control has not yet been proved to reduce the risk of macrovascular complications, though this is a desirable goal for many other reasons. Ensuring appropriate energy balance (so that BMI is within the desirable range), using low glycemic index foods, and appropriately balancing carbohydrate intake with hypoglycemic drug therapy provide the best nutritional means of achieving satisfactory blood glucose levels. Successful implementation of nutritional recommendations requires the availability of dietitians capable of translating appropriate nutrition into appropriate foods acceptable to people with diabetes and their families. Clear food labeling and the availability of appropriate manufactured foods will further help patients with diabetes to achieve the dietary recommendations.


The efficacy of smartphone-based mental health interventions for depressive symptoms: a meta-analysis of randomized controlled trials.
The rapid advances and adoption of smartphone technology presents a novel opportunity for delivering mental health interventions on a population scale. Despite multi-sector investment along with wide-scale advertising and availability to the general population, the evidence supporting the use of smartphone apps in the treatment of depression has not been empirically evaluated. Thus, we conducted the first meta-analysis of smartphone apps for depressive symptoms. An electronic database search in May 2017 identified 18 eligible randomized controlled trials of 22 smartphone apps, with outcome data from 3,414 participants. Depressive symptoms were reduced significantly more from smartphone apps than control conditions (g=0.38, 95% CI: 0.24-0.52, p<0.001), with no evidence of publication bias. Smartphone interventions had a moderate positive effect in comparison to inactive controls (g=0.56, 95% CI: 0.38-0.74), but only a small effect in comparison to active control conditions (g=0.22, 95% CI: 0.10-0.33). Effects from smartphone-only interventions were greater than from interventions which incorporated other human/computerized aspects along the smartphone component, although the difference was not statistically significant. The studies of cognitive training apps had a significantly smaller effect size on depression outcomes (p=0.004) than those of apps focusing on mental health. The use of mood monitoring softwares, or interventions based on cognitive behavioral therapy, or apps incorporating aspects of mindfulness training, did not affect significantly study effect sizes. Overall, these results indicate that smartphone devices are a promising self-management tool for depression. Future research should aim to distil which aspects of these technologies produce beneficial effects, and for which populations.


Prostate volume index and chronic inflammation of the prostate type IV with respect to the risk of prostate cancer.
Benign prostatic hyperplasia and prostate cancer (PCA) alter the normal growth patterns of zonal anatomy with changes of prostate volume (PV). Chronic inflammatory infiltrates (CII) type IV are the most common non-cancer diagnosis of the prostate after biopsy. To evaluate associations of both PV index (PVI), i.e. the ratio of transitional zone volume (TZV) to peripheral zone volume (PZV), and CII with PCA in patients undergoing biopsy. Between January 2007 and December 2008, 268 consecutive patients who underwent prostate biopsy were retrospectively evaluated. PV and TZV were measured by transrectal ultrasound. PZV was computed by subtracting the PV from the TZV. CII were evaluated according to standard criteria. Significant associations of PVI and the presence of CII (CII+) with PCA risk were assessed by statistical methods. We evaluated 251 patients after excluding cases with painful rectal examinations, prostate-specific antigen (PSA) >20 μg/ml and metastases. The PCA detection rate was 41.1%. PVI was a negative independent predictor of PCA. A PVI ≤1.0 was directly [odds ratio (OR) = 2.36] associated with PCA, which was detected more frequently in patients with a PVI ≤1.0 (29.1%) than in those with a PVI >1.0 (11.9%). CII+ was inversely (OR = 0.57) and independently associated with PCA, which was detected less frequently in cases with CII (9.9%) than in those without CII (21.1%). Potential study limitations might relate to the fact that PV was not measured by prostatectomy specimens and there was PSA confounding for CII and PCA. Low values of PVI are directly associated with risk of PCA, which was almost 2.5 times higher in patients with a PVI ≤1.0. The PVI might be an effective parameter for clustering patients at risk of PCA. CII+ was inversely associated with risk of PCA and decreased the probability of detecting PCA by 43%. The role of the PVI and CII in PCA carcinogenesis needs further research.


[An adrenal pseudocyst. A report of a new case].
We report the case of a female young woman with an incidental cystic lesion in the left adrenal gland while during a routine study by her gynecologist. The change of the aspect in the content of the lesion, its limit size and a not definitive study of punction went to the surgical act. This was made with preservation of both, adrenal and renal units. The pathological report was adrenal pseudocyst.


Angiogenesis inhibition in the treatment of colorectal cancer Part 3 of a 3-part series: targeting VEGF--current and future research directions.
Treatment options for advanced colorectal have improved substantially in recent years as a number of agents have been developed that have different targets and mechanisms of action. Significant improvements in outcomes have been observed by combining multiple chemotherapeutic agents instead of the single-agent approach. Some debate still remains regarding which combination is most effective and in what order regimens should be given. In addition to cytotoxic chemotherapy drugs, targeted biologic agents have been developed to inhibit tumor angiogenesis, which may hamper the viability of the tumor. There may also be a synergistic effect between antiangiogenic agents and chemotherapy. Regulation of tumor angiogenesis may actually improve blood flow throughout the tumor, which could enhance delivery of chemotherapy through the circulation. One antiangiogenic agent currently approved for the treatment of advanced colorectal cancer is bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, a ligand known to be important for angiogenesis. The other currently approved biologic agent, cetuximab, targets the epidermal growth factor receptor. The combination of bevacizumab plus cetuximab has a biologic rationale. Randomized trials incorporating combination chemotherapy regimens plus both bevacizumab and cetuximab are currently underway, as are preliminary studies withnovel angiogenesis inhibitors.


High-fidelity gates in quantum dot spin qubits.
Several logical qubits and quantum gates have been proposed for semiconductor quantum dots controlled by voltages applied to top gates. The different schemes can be difficult to compare meaningfully. Here we develop a theoretical framework to evaluate disparate qubit-gating schemes on an equal footing. We apply the procedure to two types of double-dot qubits: the singlet-triplet and the semiconducting quantum dot hybrid qubit. We investigate three quantum gates that flip the qubit state: a DC pulsed gate, an AC gate based on logical qubit resonance, and a gate-like process known as stimulated Raman adiabatic passage. These gates are all mediated by an exchange interaction that is controlled experimentally using the interdot tunnel coupling g and the detuning [Symbol: see text], which sets the energy difference between the dots. Our procedure has two steps. First, we optimize the gate fidelity (f) for fixed g as a function of the other control parameters; this yields an f(opt)(g) that is universal for different types of gates. Next, we identify physical constraints on the control parameters; this yields an upper bound f(max) that is specific to the qubit-gate combination. We show that similar gate fidelities (~99:5%) should be attainable for singlet-triplet qubits in isotopically purified Si, and for hybrid qubits in natural Si. Considerably lower fidelities are obtained for GaAs devices, due to the fluctuating magnetic fields ΔB produced by nuclear spins.


Comparison of immediate and intermediate-term results of intravascular ultrasound versus angiography-guided Palmaz-Schatz stent implantation in matched lesions.
Intravascular ultrasound (IVUS) provides more precise information than angiography about vascular dimensions. This information is used by some centers to optimize intracoronary stent implantation. There are no direct comparisons of the effects on restenosis of optimal IVUS-guided versus angiography-directed high-pressure stenting. Lesions of patients who had a 6-month angiographic follow-up study were eligible for matching. From 445 consecutive lesions treated by Palmaz-Schatz (P-S) stenting guided by IVUS (IVUS group) in Milan, 173 lesions were individually matched with 173 of 476 consecutive lesions treated by P-S stenting directed by angiography (Angio group) in Hamburg. Lesions were selected by a computerized program according to baseline clinical, angiographic, and procedural variables. Immediate and 6-month angiographic results were retrospectively compared, distinguishing an "early phase" from a "late phase." This distinction was based on the more aggressive dilation strategy with larger balloons and more demanding IVUS criteria for optimal stent expansion used in Milan in the early phase. In both phases, a larger minimum lumen diameter (MLD) immediately after stenting and after 6 months was achieved in the IVUS group than in the Angio group. In the early phase, the dichotomous restenosis rate was lower in the IVUS group than in the Angio group (9.2% versus 22.3%; P=.04). In the late phase, there was no difference in restenosis between the groups (22.7% versus 23.7%; P=1.0). In matched lesions treated with high-pressure stenting, IVUS guidance achieved a larger MLD than angiographic guidance. However, in the IVUS group, the restenosis rate was lower only in the early phase, when balloons larger than currently used were selected to maximize the stent lumen area.


ESR and spin-trapping study of free radicals in gamma-irradiated solid lysozyme.
Free radicals produced by gamma-irradiation of solid lysozyme were investigated by a technique combining ESR, spin-trapping and enzymatic digestion. MNP and DMPO were used as spin-trapping reagents. The solid lysozyme was first gamma-irradiated and then dissolved in an aqueous solution containing the spin-trapping reagent to stabilize free radicals. The spin adducts of lysozyme were digested to oligopeptides to get ESR spectra having a well-resolved hyperfine structure. The ESR spectra obtained showed that carbon-centered radicals, -CH-, at the side chains of amino acids, and thiyl radicals, -CH2-S., at disulfide bridges were produced in gamma-irradiated solid lysozyme.


Current Practice for Therapeutic Drug Monitoring of Biopharmaceuticals in Spondyloarthritis.
Treatment of spondyloarthritis (SpA) has greatly improved in the biopharmaceutical era. These compounds, primarily tumor necrosis factor inhibitors, are effective, but some patients may show poor response, sometimes due to the presence of antidrug antibodies (ADAs). In some instances, clinicians may increase or taper the dose, depending on the clinical response. Besides the current clinical practice, a tailored strategy based on drug monitoring is emerging as a way to improve the use of these drugs. However, the relevance of this therapeutic drug monitoring of biopharmaceuticals for SpA is still unknown. In this literature review, we examined the most relevant articles dealing with the concentration-response relation, ADA detection, and pharmacokinetics in SpA treated with biopharmaceuticals. ADAs were associated with low or undetectable concentration of monoclonal antibodies. The relation between drug concentration and clinical response in SpA is debated, some studies showing an association and others not. Therefore, therapeutic drug monitoring of biopharmaceuticals for SpA requires a better understanding of the association among the pharmacokinetics, pharmacodynamics, and immunogenicity of these drugs.


[Cross-cultural adaptation of the instrument Appraisal of Guidelines For Research & Evaluation II (AGREE II) for assessment of clinical guidelines].
This article describes the adaptation of the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument into Portuguese. A cross-cultural adaptation followed internationally accepted standards with the stages of translation, synthesis, back-translation, evaluation by an expert committee, and external evaluation. The translated instrument was published on the official AGREE websites.


Self-reported Vocal symptoms among speech language pathologists dealing with children with hearing impairment and cerebral palsy.
A cross-sectional study was conducted at the Ripah International University, Lahore, Pakistan from January to April, 2022 to evaluate and compare the Self-Reported Vocal symptoms among Speech Language Pathologists (SLP) practicing with children having Hearing Impairment (HI) and Cerebral Palsy (CP). The sample included 141 participants of both genders, aged 25 to 60 years, practicing with children with hearing impairment and cerebral palsy for at least one year. Vocal Tract Discomfort Scale (VTDS) and Voice Activity Participation Profile (VAPP) were utilised for data collection which was analysed using SPSS Ver-23. The study revealed no significant association of self-perceived vocal symptoms for SLPs catering to CP and HI children with p=0.303 and p=0.412 for VTDS and VAPP scores respectively and with higher mean scores for SLPs catering to CP children. Results revealed a total VTDS score of 40.26±13.10 with highest score for dryness, while highest VAPP mean score was noted for daily communication (53.82±23.20). Hence, there is no significant association of the speciality being catered to, while dryness is the commonest self-perceived symptom.


Cairaella henrii gen. n., sp. n., a parasite of Norops trachyderma (Polychrotidae), and Ophiotaenia nicoleae sp. n. (Eucestoda: Proteocephalidea), a parasite of Thecadactylus rapicauda (Gekkonidae), in Ecuador.
Cairaella henrii gen. n., sp. n. (Proteocephalidea: Proteocephalinae) is described from the intestine of Norops trachyderma (Cope) (Polychrotidae) from San Pablo de Kantesiya in Ecuador. The new genus differs from the 12 other known genera of the Proteocephalinae (and all other proteocephalidean genera) by the presence of a dense network of osmoregulatory canals situated in the cortex and by the morphology of the scolex which is flattened dorsoventrally, with elongated deeply embedded suckers possessing a well-developed circular musculature situated in the anterolateral region, and by eggs with a three-layered embryophore possessing small outgrowths on its external surface. Ophiotaenia nicoleae sp. n. is described from the intestine of Thecadactylus rapicauda (Houttuyn) (Gekkonidae) from San Pablo de Kantesiya in Ecuador. This new species is characterised by the testes arranged in two fields, numbering 142-204, the cirrus-sac length representing 21-33% of proglottis width, the genital pore situated in the middle of the proglottis or slightly anteriorly, and the ovary width representing 68-88% of proglottis width. It differs from 20 of 27 Ophiotaenia species parasitic in New World reptiles by the presence of an apical organ and from the remaining species by one to several other morphological characters, such as the number of testes, diameter and shape of the scolex, position of ventral and dorsal osmoregulatory canals, or the presence of a vaginal sphincter. Both taxa represent the first record of proteocephalidean tapeworms in polychrotid and gekkonid lizards, respectively.


Mitochondrial membrane potential and glutamate excitotoxicity in cultured cerebellar granule cells.
The relationship between changes in mitochondrial membrane potential (Deltapsi(m)) and the failure of cytoplasmic Ca(2+) homeostasis, delayed Ca(2+)deregulation (DCD), is investigated for cultured rat cerebellar granule cells exposed to glutamate. To interpret the single-cell fluorescence response of cells loaded with tetramethylrhodamine methyl ester (TMRM(+)) or rhodamine-123, we devised and validated a mathematical simulation with well characterized effectors of Deltapsi(m) and plasma membrane potential (Deltapsi(P)). Glutamate usually caused an immediate decrease in Deltapsi(m) of <10 mV, attributable to Ca(2+) accumulation rather than enhanced ATP demand, and these cells continued to generate ATP by oxidative phosphorylation until DCD. Cells for which the mitochondria showed a larger initial depolarization deregulated more rapidly. The mitochondria in a subpopulation of glutamate-exposed cells that failed to extrude Ca(2+) that was released from the matrix after protonophore addition were bioenergetically competent. The onset of DCD during continuous glutamate exposure in the presence or absence of oligomycin was associated with a slowly developing mitochondrial depolarization, but cause and effect could not be established readily. In contrast, the slowly developing mitochondrial depolarization after transient NMDA receptor activation occurs before cytoplasmic free Ca(2+) ([Ca(2+)](c)) has risen to the set point at which mitochondria retain Ca(2+). In the presence of oligomycin no increase in [Ca(2+)](c) occurs during this depolarization. We conclude that transient Ca(2+) loading of mitochondria as a consequence of NMDA receptor activation initiates oxidative damage to both plasma membrane Ca(2+) extrusion pathways and the inhibition of mitochondrial respiration. Depending on experimental conditions, one of these factors becomes rate-limiting and precipitates DCD.


The Drosophila suppressor of sable gene encodes a polypeptide with regions similar to those of RNA-binding proteins.
The nucleotide sequence of the Drosophila melanogaster suppressor of sable [su(s)] gene has been determined. Comparison of genomic and cDNA sequences indicates that an approximately 7,860-nucleotide primary transcript is processed into an approximately 5-kb message, expressed during all stages of the life cycle, that contains an open reading frame capable of encoding a 1,322-amino-acid protein of approximately 150 kDa. The putative protein contains an RNA recognition motif-like region and a highly charged arginine-, lysine-, serine-, aspartic or glutamic acid-rich region that is similar to a region contained in several RNA-processing proteins. In vitro translation of in vitro-transcribed RNA from a complete cDNA yields a product whose size agrees with the size predicted by the open reading frame. Antisera against su(s) fusion proteins recognize the in vitro-translated protein and detect a protein of identical size in the nuclear fractions from tissue culture cells and embryos. The protein is also present in smaller amounts in cytoplasmic fractions of embryos. That the su(s) protein has regions similar in structure to RNA-processing protein is consistent with its known role in affecting the transcript levels of those alleles that it suppresses.


On the advantage of screening kindergarten children for atherogenesis-related risk indicators.
On the basis of our practical experience we can recommend screening of young children outside the clinic. Our methodology has proven to be appropriate for this purpose. Among young children, three groups are easily accessible: Newborns - since delivery occurs mostly in a clinic; infants up to one year - since these children are provided with basic medical care, and kindergarten children. According to our experience, kindergartens are favorable places for screening children because many children are together in one place. Children of this age can be easily motivated to cooperate during the examination, and since they stay in the kindergartens for a considerable period of the day, they only can be guided by nurses who can provide positive motivation for educational programs. As an additional advantage, the cooperation between nurses and parents, as well as positive influence on the parents, by the nurses might be taken into account. In this context, nurses must be regarded as key persons for strategies when considering life-style changes. Identifying children at risk at this early age could shorten the pathogenetic period and increase the chance for regression of the atherosclerotic disease process. Furthermore, children of this age are willing to learn and to change their habits. There is also a possibility that children may implant in their families experiences and information obtained in the kindergartens. Such parents might be more open to advice from kindergarten personnel, and thus also profit for themselves. An additional and valuable advantage of screening kindergarten children is the possibility of detecting first-degree relatives at risk before clinical manifestation of the disease, thereby having a good chance for successful intervention.


Methods used in internal industry clinical trials to assess tobacco risk reduction.
Methods to assess reduced exposure products should include those that aid in determining likely patterns of human use and exposure. Tobacco industry clinical trial methods may provide insight into strategies to assess potential reduced exposure products (PREP) for public health purposes. Internal tobacco industry documents detailing human clinical research with PREPs were examined to document major research strategies used and identify potentially fruitful methods not currently used in the mainstream arena. Primary data were obtained from records of research conducted internally by tobacco companies and affiliated researchers, and included manuscript drafts, presentations, protocols, and instruments relating to internal clinical trials of human tobacco use and exposure. Tobacco industry clinical research has focused on reduced exposure products, most notably Premier, Accord, and Eclipse. The most widely used strategy observed is switching studies, and details of study designs and protocols favored by the industry are described. Key measures include biomarkers of exposure (e.g., cotinine, CO, and specific carcinogens) and acute health effects such as physical health and fitness. Tobacco industry clinical research has used relatively standard switching study methods, but with a broad set of measures. Clinical switching studies have been conducted by the industry primarily to support existing claims or to develop new claims. Knowledge of prior industry activity can guide and inform future public health research efforts. Although industry clinical trial methods are comparable with current mainstream methods, limited information about the validity of outcome measures used limits their viability for immediate adoption in mainstream science.


Desmoplakin I/II immunohistochemical staining may be a helpful tool in differentiating cutaneous graft versus host disease from the erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis spectrum disorders.
Cutaneous graft versus host disease (cGVHD) has substantial clinical and histopathologic overlap with erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). This overlap can make it difficult to distinguish these disorders in patients who have received hematopoietic transplants. We sought to evaluate the utility of Dp I/II immunohistochemical stain in differentiating EM/SJS/TEN and cGVHD in a large cohort. Skin biopsy specimens from patients with cGVHD (n = 58) and EM/SJS/TEN (n = 60) were evaluated for Dp I/II expression by immunohistochemistry. We found a statistically significant difference in Dp I/II staining between cGVHD (all grades) and EM/SJS/TEN (mean scores 1.62 and 2.14, respectively; p < 0.005), as well as between Grades 2 + 3 cGVHD and EM/SJS/TEN (mean scores 2.26 and 1.62, respectively; p < 0.005), while we did not find a significant difference between Grade 4 cGVHD and EM/SJS/TEN (mean scores 1.69 and 1.62, respectively; p = 0.71). Dp I/II immunostain may be useful for differentiating EM/SJS/TEN from Grade 2 and Grade 3 cGVHD, especially in clinically ambiguous cases without extracutaneous GVHD.


Altered intestinal microflora and barrier injury in severe acute pancreatitis can be changed by zinc.
To investigate the effect of zinc (Zn) supplementation on intestinal microflora changes and bacterial translocation in rats with severe acute pancreatitis (SAP), the rats were divided into the sham surgery (SS), SAP, SS + Zn, and SAP + Zn groups. Saline (0.1 mL/100g) and 5% sodium taurocholate were injected into the pancreaticobiliary duct of the rats in the SS and SAP + Zn groups, respectively. Intraperitoneal injection of 5 mg/kg Zn was performed immediately after injecting saline or 5% sodium taurocholate into the rats in both groups. Serum amylase and Zn levels, plasma endogenous endotoxin, intestinal permeability, and the positive rate of intestinal bacterial translocation were detected, haematoxylin and eosin (H&E) staining was performed, and the pancreatic tissue scores were calculated for each group. In addition, immunohistochemical (IHC) staining was performed to evaluate the expression of IL-1β and TNF-α. Real-time fluorescence quantitative PCR was used to quantify the gene copy numbers of Escherichia, Bifidobacterium, and Lactobacillus in the cecum. The levels of amylase and plasma endotoxin in the SAP group were significantly higher than those in the SS and SS + Zn groups. Intestinal mucosal permeability and intestinal bacterial translocation in the liver, pancreas, and mesenteric lymph nodes were increased in the SAP group. However, the levels of amylase and plasma endotoxin were decreased as a result of zinc supplementation in the SAP group. The expression of IL-1β and TNF-α was also reduced to a greater degree in the SAP + Zn group than in the SAP group. Moreover, alleviated intestinal mucosal permeability and intestinal bacterial translocation in the liver, pancreas, and mesenteric lymph nodes were found in the SAP + Zn group. The results of real-time quantitative PCR showed that the gene copy number of Escherichia increased with time, and the gene copy numbers of Lactobacillus and Bifidobacterium decreased over time. Zn supplementation prevented the release of TNF-α and IL-1β, alleviated intestinal permeability and endotoxemia, reduced bacterial translocation, and inhibited changes in pathogenic intestinal flora in rats with SAP.


Monoclonal antibodies specific for dengue virus type 3.
Mouse lymphocyte hybridomas were prepared by polyethylene glycol-mediated fusion of cells from a mouse plasmacytoma line with lymphocytes from a mouse hyperimmunized with dengue virus type 3 (dengue-3). Media from 50 hybrid colonies were screened; 46 of them showed antibody activity against dengue-3-infected cells as determined by an indirect immunofluorescent antibody technique. Dengue monoclonal antibody obtained after cloning one of these colonies demonstrated activity in hemagglutination inhibition and indirect immunofluorescent antibody assays with dengue-3 antigen, but not type 1, 2, and 4 antigens. In addition, this antibody activity could be removed from culture media only by absorption with dengue-3 antigen.


Position-related differences in cardiorespiratory functional capacity of elite basketball players.
The purpose of this study was to examine possible differences in cardio respiratory functional capacity between perimeter and post elite basketball players. The subjects included 42 highly trained basketball players subdivided into groups of perimeter and post players. Point guards, shooting guards and small forwards were involved in the group of perimeter players, while power forwards and centers represented the group of post players. All players performed a standardized exercise test to evaluate maximal oxygen uptake using a cycle ergometer and automated breath-by-breath system VMAX229C. Collected data of power, heart rate, pulmonary ventilation and gas exchange were compared between the groups of perimeter and post players. Significant differences in anthropometric features between the investigated subgroups were observed. Post players were heavier and taller. Therefore, the perimeter players had significantly higher values of VO2max and relative power. VO2max was related to relative power. Relations between those variables can be described by linear regression. Given regressions can be used as a source of typical values for male basketball players. The results indicate that the empirical repartition of basketball players into perimeter and post players has not only a morphological but a physiological basis as well.


AN INTRATENDINOUS GANGLION CYST OF THE PATELLAR TENDON: A RARE CAUSE OF ANTERIOR KNEE PAIN.
Ganglion cysts in the knee region can manifest as anterior knee pain. Unlike synovial cysts, these lesions lack synovial epithelial lining and occur secondary to mucoid degeneration of connective tissue because, often in response to chronic irritation and repetitive traumas. However, an intratendinous location is a rare finding. In the knee region, infrapatellar fat pad, the alar folds, and the anterior cruciate ligament are recognized to degenerate into ganglion. There are few case reports describing an involvement of the patellar tendon. We present the clinical case of a 72 years old male patient suffering from anterior knee pain attributed to an intratendinous ganglion cyst of the patellar tendon, obviously after a single traumatic event. After aspiration of the ganglion cyst the patient reported no complaints, and there has been no recurrence during the latest follow-up examination.


Evolved genetic and phenotypic differences due to mitochondrial-nuclear interactions.
The oxidative phosphorylation (OxPhos) pathway is responsible for most aerobic ATP production and is the only pathway with both nuclear and mitochondrial encoded proteins. The importance of the interactions between these two genomes has recently received more attention because of their potential evolutionary effects and how they may affect human health and disease. In many different organisms, healthy nuclear and mitochondrial genome hybrids between species or among distant populations within a species affect fitness and OxPhos functions. However, what is less understood is whether these interactions impact individuals within a single natural population. The significance of this impact depends on the strength of selection for mito-nuclear interactions. We examined whether mito-nuclear interactions alter allele frequencies for ~11,000 nuclear SNPs within a single, natural Fundulus heteroclitus population containing two divergent mitochondrial haplotypes (mt-haplotypes). Between the two mt-haplotypes, there are significant nuclear allele frequency differences for 349 SNPs with a p-value of 1% (236 with 10% FDR). Unlike the rest of the genome, these 349 outlier SNPs form two groups associated with each mt-haplotype, with a minority of individuals having mixed ancestry. We use this mixed ancestry in combination with mt-haplotype as a polygenic factor to explain a significant fraction of the individual OxPhos variation. These data suggest that mito-nuclear interactions affect cardiac OxPhos function. The 349 outlier SNPs occur in genes involved in regulating metabolic processes but are not directly associated with the 79 nuclear OxPhos proteins. Therefore, we postulate that the evolution of mito-nuclear interactions affects OxPhos function by acting upstream of OxPhos.


A genetic mouse model of invasive endometrial cancer driven by concurrent loss of Pten and Lkb1 Is highly responsive to mTOR inhibition.
Signals from the tumor suppressors PTEN and LKB1 converge on mTOR to negatively regulate its function in cancer cells. Notably, both of these suppressors are attenuated in a significant fraction of human endometrial tumors. In this study, we generated a genetic mouse model of endometrial cancer driven by concomitant loss of these suppressors to gain pathophysiological insight into this disease. Dual loss of Pten and Lkb1 in the endometrial epithelium led to rapid development of advanced endometrioid endometrial tumors with 100% penetrance and short host survival. The tumors displayed dysregulated phosphatidylinositol 3-kinase (PI3K)/Akt and Lkb1/Ampk signaling with hyperactivation of mTOR signaling. Treatment with a dual PI3K/mTOR inhibitor, BEZ235, extended the time before tumor onset and prolonged overall survival. The PI3K inhibitor GDC-0941 used as a single agent reduced the growth rate of primary tumor implants in Pten/Lkb1-deficient mice, and the mTOR inhibitor RAD001 was unexpectedly as effective as BEZ235 in triggering tumor regression. In parallel, we also found that ectopic expression of LKB1 in PTEN/LKB1-deficient human endometrial cancer cells increased their sensitivity to PI3K inhibition. Together, our results demonstrated that Pten/Lkb1-deficient endometrial tumors rely strongly on deregulated mTOR signaling, and they provided evidence that LKB1 status may modulate the response of PTEN-deficient tumors to PI3K or mTOR inhibitors.


Improved management of the Paget-Schroetter syndrome secondary to thoracic outlet compression.
For years, patients with "effort" thrombosis were treated by anticoagulants and conservative exercise; and if recurrent symptoms developed when they returned to work, they were considered for first-rib resection. Recently, use of thrombolytic agents with early surgical decompression of the neurovascular compression has markedly reduced morbidity, such as postphlebitic syndrome and the necessity for thrombectomy. A review of 67 patients seen over 25 years showed that 34 were initially treated with heparin sodium and then Coumadin (crystalline warfarin sodium). Recurrent symptoms developed in 21 after they returned to work and necessitated transaxillary first-rib resection to relieve symptoms. Eight also underwent thrombectomy. Recently, 33 patients were initially treated with thrombolytic agents and heparin, followed promptly by early first-rib resection. The evaluation and efficacy of this therapy have been established by frequent and repetitive venograms and careful follow-up of patients. Most of the patients showed improvement with thrombolytic agents. Remaining stenoses that suggested intravascular thrombosis were usually secondary to external compression of the vein by the clavicle, costoclavicular ligament, rib, or scalenus anterior muscle. Venous thrombectomy was necessary in only 4 patients in whom the clot was not controlled by thrombolytic therapy and operative release of compression. There were no deaths in the series.


Patterns of HIV care for patients with serious mental illness.
Individuals with serious mental illness are at higher risk for HIV than are members of the general population. Although studies have shown that individuals with serious mental illness experience less adequate care and worse physical health outcomes than comparable patients without serious mental illness, little is known about HIV care among individuals with serious mental illness who become infected with HIV. In the present study, we describe patterns of highly active antiretroviral treatment (HAART) use and physician monitoring received by 154 patients with serious mental illness infected with HIV. Participants were recruited from mental health agencies in Los Angeles, California. Data from 762 HIV-only patients from a separate Western U.S. probability sample were used for comparison. High proportions of serious mental illness patients with HIV in our sample appeared to be receiving adequate HIV care. Fifty-one percent of all serious mental illness patients with serious mental illness with HIV were taking HAART, and the majority received close monitoring of their CD4 counts (84%) and viral loads (82%) throughout a 1-year period. HAART use and patterns of CD4 count and viral load monitoring did not differ significantly between patients with both serious mental illness and HIV, and patients with HIV only (all p > 0.05). Specialized programs providing assistance to serious mental illness populations with HIV may be helping to narrow health care disparities as a result of having serious mental illness.


The clr1 locus regulates the expression of the cryptic mating-type loci of fission yeast.
The mat2-P and mat3-M loci of fission yeast contain respectively the plus (P) and minus (M) mating-type information in a transcriptionally silent state. That information is transposed from the mat2 or mat3 donor locus via recombination into the expressed mating-type locus (mat1) resulting in switching of the cellular mating type. We have identified a gene, named clr1 (for cryptic loci regulator), whose mutations allow expression of the mat2 and mat3 loci. clr1 mutants undergo aberrant haploid meiosis, indicative of transcription of the silent genes. Production of mRNA from mat3 is detectable in clr1 mutants. Furthermore, the ura4 gene inserted near mat3, weakly expressed in wild-type cells, is derepressed in clr1 mutants. The clr1 mutations also permit meiotic recombination in the 15-kb mat2-mat3 interval, where recombination is normally inhibited. The clr1 locus is in the right arm of chromosome II. We suggest that clr1 regulates silencing of the mat2 and mat3 loci, and participates in establishing the "cold spot" for recombination by organizing the chromatin structure of the mating-type region.


Persistent, mobile, and toxic plastic additives in Canada: properties and prioritization.
The hazards of many plastic additives on human and environmental health are well documented. However, little emphasis has been put on plastic additives that are persistent, mobile, and toxic (PMT) rather than persistent, bioaccumulative, and toxic. Due to their high mobility and stability, it is unlikely that wastewater treatment plants will effectively remove PMT plastic additives. Herein, an in silico analysis was performed to (1) assess the retention of PMT plastic additives registered for use in Canada in wastewater treatment plants; and (2) determine whether their physical-chemical properties and structural features can be used as identifiers for PMT plastic additives with particularly low retention. We identified 124 PMT plastic additives of which 52% had less than 20% removal from wastewater treatment based on predictions using the model SimpleTreat. Log Kaw, log Kow/Dow, and log Koc/Doc ranges were defined that are indicative of low retention PMT plastic additives. Furthermore, it was found that non-halogenated PMT plastic additives that contain nitrogen are most likely to be poorly retained in wastewater treatment plants. The results of this study provide screening and prioritization criteria, as well as a suspect list for PMT plastic additives.


Media use and sleep among boys with autism spectrum disorder, ADHD, or typical development.
The current study examined the relationships between media use (television, computer, and video games) and sleep among boys with autism spectrum disorder (ASD) compared with those with attention-deficit/hyperactivity disorder (ADHD) or with typical development (TD). Participants included parents of boys with ASD (n = 49), ADHD (n = 38), or TD (n = 41) (ages 8-17 years). Questionnaires assessed daily hours of media use, bedroom access to media, and average sleep hours per night. Bedroom media access was associated with less time spent sleeping per night, irrespective of diagnostic group. Bedroom access to a television or a computer was more strongly associated with reduced sleep among boys with ASD compared with boys with ADHD or TD. Multivariate models showed that, in addition to bedroom access, the amount of time spent playing video games was uniquely associated with less sleep among boys with ASD. In the ASD group only, the relationship between bedroom access to video games and reduced sleep was mediated by hours of video game play. The current results suggest that media-related variables may be an important consideration in understanding sleep disturbances in children with ASD. Further research is needed to better characterize the processes by which media use may affect sleep among individuals with ASD. Overall, the current findings suggest that screen-based media time and bedroom media access should be routinely assessed and may be important intervention targets when addressing sleep problems in children with ASD.


Cryptic bumblebee species: consequences for conservation and the trade in greenhouse pollinators.
Commercial greenhouse growers in both Japan and China are increasingly using reared orange-tailed bumblebees known previously as Bombus hypocrita Pérez as pollinators. Phylogenetic analysis of the DNA (COI) barcodes with Bayesian methods shows that this "species" is a long-standing confusion of two cryptic species. We find that the orange-tailed bumblebees in North China are actually part of the widespread Russian (otherwise white-tailed) B. patagiatus Nylander (as B. patagiatus ganjsuensis Skorikov, n. comb.), whereas the orange-tailed bees in Japan are true B. hypocrita. This situation has been further complicated because two other cryptic species from North China that were previously confused with the Russian B. patagiatus are now recognised as separate: B. lantschouensis Vogt n. stat. and B. minshanensis Bischoff n. stat.. As demand for pollination services by greenhouse growers inevitably increases, these bees are more likely to be transported between countries. In order to conserve genetic resources of pollinator species for their option value for future food security, we advocate preventing trade and movement of B. patagiatus from China into Japan and of B. hypocrita from Japan into China.


Pediatric Gastrointestinal Endoscopy: Diagnostic Yield and Appropriateness of Referral Based on Clinical Presentation: A Pilot Study.
Objectives: There is a lack of evidence-based consensus for the utility of gastrointestinal endoscopy (GIE) in an array of frequently occurring symptoms in children. We aimed to assess the diagnostic yield of endoscopy in an effort to aid clinical decision making. Methods: Retrospective analysis included patients ≤18 years who underwent GIE during one calendar year at Shaare Zedek Medical Center. We excluded children referred for predefined obvious indications for GIE, planned follow-up procedures, and therapeutic endoscopy. Clinician-assigned indication for endoscopy as well as endoscopic and histologic findings were recorded. Diagnostic yield of GIE was determined according to referral indication. Results: There were 794 endoscopies performed of which 329 were included in the analysis (mean age 9.3 ± 5.0 years, 51% female). No significant complications of GIE were recorded. Six major referral indications were identified among which abdominal pain was the most frequent 88/329 (26%) of whom 32/88 (36%) had a significant diagnostic finding. Among the other major indications, diagnostic findings were found in 36/85 (43%) children with primary indication of chronic diarrhea, 14/33 (42%) failure to thrive, 15/32 (46%) short stature, 30/56 (54%) iron deficiency, and 20/48 (42%) weight loss. Conclusions: Pediatric GIE is a safe procedure with diverse clinical indications. The diagnostic yield of endoscopy is variable, depending on the referral indication. These data can assist formulating judicious referral practices.


Innominate artery bifurcation pseudoaneurysm repair by "kissing stent-grafts technique": a case report.
We introduce the "kissing stent-grafts technique" for a patient who suffered from a pseudoaneurysm in bifurcation of innominate artery. This technique repaired an innominate artery bifurcation pseudoaneurysm; it successfully isolated the pseudoaneurysm and preserved both right subclavian and right common carotid artery. A 60-year-old Asian (Chinese) woman complained of discovering a cervical pulsatile mass. A pseudoaneurysm at the location of innominate artery bifurcation is a rare and difficult situation that should be treated by vascular surgeons. To our knowledge, this is the first case to use the "kissing stent-grafts technique" in treating innominate bifurcation pseudoaneurysm. With this minimally invasive endovascular treatment, our patient avoided open surgery and recovered quickly. When treating vascular lesions with complicated anatomy, endovascular treatment always has the merit of being minimally invasive. "Kissing stent-grafts technique" can be useful in locations other than coronary and aortic bifurcation.


Chronic monoamine oxidase-B inhibitor treatment blocks monoamine oxidase-A enzyme activity.
Patients with Parkinson's disease receive selective irreversible monoamine oxidase (MAO)-B inhibitors, but their effects on MAO-A activity are not known during long-term application. We determined MAO-A inhibition in plasma samples from patients with MAO-B inhibitor intake or without MAO-B inhibitor treatment and from healthy controls. We detected a 70 % reduction of MAO-A activity in patients with MAO-B inhibitor therapy in comparison to the other groups. Our results suggest that treatment with MAO-B inhibitor may also influence MAO-A activity in vivo, when administered daily.