Evaporative mass transfer behavior of a complex immiscible liquid.
A series of laboratory experiments was conducted with a multiple-component immiscible liquid, collected from the Picillo Farm Superfund Site in Rhode Island, to examine liquid-vapor mass-transfer behavior. The immiscible liquid, which comprises solvents, oils, pesticides, PCBs, paint sludges, explosives, and other compounds, was characterized using gas chromatography and gas chromatography/mass spectrometry to determine mole fractions of selected constituents. Batch experiments were conducted to evaluate equilibrium phase-partitioning behavior. Two sets of air-stripping column studies were conducted to examine the mass-transfer dynamics of five selected target compounds present in the immiscible-liquid mixture. One set of column experiments was designed to represent a system with free-phase immiscible liquid present; the other was designed to represent a system with a residual phase of immiscible liquid. Initial elution behavior of all target components generally appeared to be ideal for both systems, as the initial vapor-phase concentrations were similar to vapor-phase concentrations measured for the batch experiment and those estimated using Raoult's law (incorporating the immiscible-liquid composition data). Later-stage removal of 1,2-dichlorobenzene appeared to be rate limited for the columns containing free-phase immiscible liquid and no porous medium. Conversely, evaporative mass transfer appeared to be ideal throughout the experiment conducted with immiscible liquid distributed relatively uniformly as a residual phase within a sandy porous medium.


Non-sentinel lymph node involvement in patients with breast cancer and sentinel node micrometastasis; too early to abandon axillary clearance.
It has been suggested that patients with T1-2 breast tumours and sentinel node (SLN) micrometastases, defined as foci of tumour cells smaller than 2 mm, may be spared completion axillary lymph node dissection because of the low incidence of further metastatic disease. To gain insight into the extent of non-sentinel lymph node (n-SLN) involvement, SLNs and complementary axillary clearance specimens in patients with SLN micrometastases were examined. A set of 32 patients with SLN micrometastases was selected on the basis of pathology reports and review of SLNs. Five hundred and thirteen n-SLNs from the axillary clearance specimens were serially sectioned and analysed by means of immunohistochemistry for metastatic disease. Lymph node metastases were grouped as macrometastases (> 2 mm), and micrometastases (< 2 mm), and further subdivided as isolated tumour cells (ITCs) or clusters. In 11 of 32 patients, one or more n-SLN was involved. Grade 3 tumours and tumours > 2 cm (T2-3 v T1) were significantly associated with n-SLN micrometastases as clusters (grade: odds ratio (OR), 8.3; 95% confidence interval (CI), 1.4 to 50.0; size: T2-3 tumours v T1: OR, 15; 95% CI, 2.18 to 103.0). However, no subgroup of tumours with regard to size and grade was identified that did not have n-SLN metastases. In patients with breast cancer and SLN micrometastases, n-SLN involvement is relatively common. The incidence of metastatic clusters in n-SLN is greatly increased in patients with T2-3 tumours and grade 3 tumours. Therefore, axillary lymph node dissection is especially warranted in these patients. However, because n-SLN metastases also occur in T1 and low grade tumours, even these should be subjected to routine axillary dissection to achieve local control.


Initiation of bone development by osteogenin and promotion by growth factors.
The cellular and molecular basis of bone development and its regulation by differentiation and growth factors is an exciting area of current research. This article briefly reviews the historical progress in the isolation of osteogenin, a novel bone differentiation factor, and its modulation by well known growth factors. Endochondral bone development is a multistep sequential cascade and the process must be operationally dissected. It has been accomplished with the demineralized bone matrix-induced bone formation model. The reproducible development of cartilage and bone in an extraskeletal site permits the study of the initiation of the first cycle of endochondral bone formation and mineralization. Recent progress in the isolation of osteogenin, a specific bone differentiation factor, by heparin affinity chromatography permits the further investigation of the commitment and clonal expansion of the putative osteoprogenitor stem cells. Once initiated, bone formation is promoted by growth factors such as platelet derived growth factor, fibroblast growth factor, insulin like growth factor, transforming growth factor beta and a plethora of non specific cytokines. Finally bone development is further modulated by systemic hormones and nutrition and a host of physical signals including electrical, gravitational and mechanical forces.


Effect of dietary calcium and phosphorus level sequences on performance, structural soundness and bone characteristics of growing-finishing swine.
The effects of feeding various dietary Ca:P level sequences on gain and feed efficiency, leg structural soundness and bone indices of growing-finishing swine were evaluated as an incomplete 3 X 3 factorial arrangement of treatments in a split-plot design. A total of 664 pigs were fed one of three total dietary Ca:P levels (.52:.40, .65:.50, .80:.60%) from 19-kg to 56-kg body weights followed by one of three Ca:P levels (.45:.32, .52:.40, .65:.50%) to market weight. The .80:.60% and .65:.50% Ca:P mineral sequence was not evaluated. Diets were formulated to 14.5% crude protein using a corn-soybean meal mixture with proportions of dicalcium phosphate and limestone altered to attain the desired dietary Ca:P levels. Maximum gains occurred at the .65:.50% and .52:.40% Ca:P level during the grower (P less than .01) and finisher (P less than .01) periods, respectively. No grower X finisher phase pig gain or feed intake interaction resulted, providing evidence of no carry-over response on these measurements from the grower to the finisher period. Serum P concentration increased and plateaued at the same dietary Ca:P level, as did rate of gain at both 56-kg and 95-kg body weights. Leg soundness subjectively evaluated at 56-kg and 95-kg body weights revealed no effect of dietary Ca:P level on soundness scores at 56 kg, but at 95-kg body weight, the interaction between grower and finisher diets was significant. Percentage bone ash of the humerus, shaft thickness and bending moment of the femur increased as dietary Ca:P level increased at both 56-kg and 95-kg body weights.(ABSTRACT TRUNCATED AT 250 WORDS)


Clinical application and utility of genomic assays in early-stage breast cancer: key lessons learned to date.
Early-stage hormone receptor-positive breast cancer is the most common subtype and stage presenting in countries with organized screening programs. Standard clinical and pathologic factors are routinely used to support prognosis and decisions about adjuvant therapies. Hormone receptor and her2 status are essential for decision-making about the use of adjuvant hormonal and anti-her2 therapies respectively. Genomic assays are now commercially available to aid in either further prognostication or in refining the potential benefit of adjuvant chemotherapy. The current genomic assays all generally quantify estrogen receptor and proliferation gene sets (among others) by rna expression, although the specific genes assayed are quite discordant. The present review focuses on the pivotal studies in which each assay attempted to demonstrate clinical utility, with an emphasis on prospective trial data for each assay, if available. Using genomic assays, health care providers will increasingly be able to individualize therapy or de-escalate therapy, optimizing clinic benefit while minimizing toxicities from systemic therapies.


[The prevention of the translocation of intestinal microflora after the rescue of an organism from a terminal state].
In experiments on guinea pigs, the animals were resuscitated from clinical death caused by the acute loss of blood and subsequently treated intragastrically with enterosorbents: activated carbon fibrous material, alone and in combination with polymyxin B, polyphepan (a lignin derivative), polymethyloxan hydrogel and the sorbent Enterocat. In the animals, not treated during the postresuscitation period, a high population level of enterobacteria and Gram-positive aerobic cocci was registered in the contents of the small and large intestines and their translocation to mesenteric lymph nodes, liver, spleen and blood was observed. The amount of lactobacilli in the small intestine was decreased. Enterosorbents were found to decrease a high population level of intestinal microflora, to prevent the translocation of Gram-positive aerobic cocci and to inhibit the penetration of enterobacteria through the enteric barrier in the postresuscitation period. Combined use of activated carbon fibrous material with polymyxin B proved to be most effective for the elimination of enterobacteria.


Thermodynamic functions and intra-particle mass transfer kinetics of structural analogues of a template on molecularly imprinted polymers in liquid chromatography.
The parameters of the thermodynamics and mass transfer kinetics of the structural analogues (L-enantiomers) of the template were measured on an Fmoc-L-tryptophan (Fmoc-L-Trp) imprinted polymer, at different temperatures. The equilibrium isotherm data and the overloaded band profiles of these compounds were measured at temperatures of 298, 313, 323, and 333 K. The isotherm data were modeled. The thermodynamic functions of the different adsorption sites were derived from the isotherm parameters, using van't Hoff plots. The mass transfer parameters were derived by comparing the experimental peak profiles and profiles calculated using the lumped pore diffusion (POR) model for chromatography. These data show that (1) the strength between the substrate molecules and the MIP increases with increasing number of functional groups on the substrates; (2) enthalpy is the driving force for the affinity of the substrates for the MIP; (3) surface diffusion is the dominant mass transfer mechanism of the substrates through the porous MIP. For those substrate molecules that have the same stereochemistry as the template, the energetic surface heterogeneity needs to be incorporated into the surface diffusion coefficients. Heterogeneous surface diffusivities decrease with increasing affinity of the substrates for the MIP.


Different populations of parvalbumin- and calbindin-D28k-immunoreactive neurons contain GABA and accumulate 3H-D-aspartate in the dorsal horn of the rat spinal cord.
The colocalization of parvalbumin (PV), calbindin-D28k (CaBP), GABA immunoreactivities, and the ability to accumulate 3H-D-aspartate selectively were investigated in neurons of laminae I-IV of the dorsal horn of the rat spinal cord. Following injection of 3H-D-aspartate into the basal dorsal horn (laminae IV-VI), perikarya selectively accumulating 3H-D-aspartate were detected in araldite embedded semithin sections by autoradiography, and consecutive semithin sections were treated to reveal PV, CaBP and GABA by postembedding immunocytochemistry. Perikarya accumulating 3H-D-aspartate were found exclusively in laminae I-III, and no labelled somata were found in deeper layers or in the intermediolateral column although the labelled amino acid clearly spread to these regions. More than half of the labelled cells were localized in lamina II. In this layer, 16.4% of 3H-D-aspartate-labelled perikarya were also stained for CaBP. In contrast to CaBP, PV or GABA was never detected in neurons accumulating 3H-D-aspartate. A high proportion of PV-immunoreactive perikarya were also stained for GABA in laminae II and III (70.0% and 61.2% respectively). However, the majority of CaBP-immunoreactive perikarya were GABA-negative. GABA-immunoreactivity was found in less than 2% of the total population of cells stained for CaBP in laminae I-IV. A significant proportion of the GABA-negative but PV-immunoreactive neurons also showed CaBP-immunoreactivity in laminae II and IV. These results show that out of the two calcium-binding proteins, CaBP is a characteristic protein of a small subpopulation of neurons using excitatory amino acids and PV is a characteristic protein of a subpopulation of neurons utilizing GABA as a transmitter. However, both proteins are present in additional subgroups of neurons, and neuronal populations using inhibitory or excitatory amino acid transmitters are heterogeneous with regard to their content of calcium-binding proteins in the dorsal horn of the rat spinal cord.


Pre-natal exposures and breast tissue composition: findings from a British pre-birth cohort of young women and a systematic review.
Breast density, the amount of fibroglandular tissue in the adult breast for a women's age and body mass index, is a strong biomarker of susceptibility to breast cancer, which may, like breast cancer risk itself, be influenced by events early in life. In the present study, we investigated the association between pre-natal exposures and breast tissue composition. A sample of 500 young, nulliparous women (aged approximately 21 years) from a U.K. pre-birth cohort underwent a magnetic resonance imaging examination of their breasts to estimate percent water, a measure of the relative amount of fibroglandular tissue equivalent to mammographic percent density. Information on pre-natal exposures was collected throughout the mothers' pregnancy and shortly after delivery. Regression models were used to investigate associations between percent water and pre-natal exposures. Mediation analysis, and a systematic review and meta-analysis of the published literature, were also conducted. Adjusted percent water in young women was positively associated with maternal height (p for linear trend [p t] = 0.005), maternal mammographic density in middle age (p t = 0.018) and the participant's birth size (p t < 0.001 for birthweight). A 1-SD increment in weight (473 g), length (2.3 cm), head circumference (1.2 cm) and Ponderal Index (4.1 g/cm3) at birth were associated with 3 % (95 % CI 2-5 %), 2 % (95 % CI 0-3 %), 3 % (95 % CI 1-4 %) and 1 % (95 % CI 0-3 %), respectively, increases in mean adjusted percent water. The effect of maternal height on the participants' percent water was partly mediated through birth size, but there was little evidence that the effect of birthweight was primarily mediated via adult body size. The meta-analysis supported the study findings, with breast density being positively associated with birth size. These findings provide strong evidence of pre-natal influences on breast tissue composition. The positive association between birth size and relative amount of fibroglandular tissue indicates that breast density and breast cancer risk may share a common pre-natal origin.


Parental comorbidity and medication use in the USA: a panel study of 785 000 live births.
How prevalent is paternal medication use and comorbidity, and are rates of these rising? Paternal medication use and comorbidity is common and rising, similar to trends previously described in mothers. Maternal medication use and comorbidity has been rising for the past few decades. These trends have been linked to potential teratogenicity, maternal morbidity and mortality and poorer fetal outcomes. This is a Panel (trend) study of 785 809 live births from 2008 to 2016. We used the IBM© Marketscan®™ database to gather data on demographic information and International Classification of Diseases codes and Charlson comorbidity index (CCI) during the 12 months prior to the estimated date of conception for mothers and fathers. We similarly examined claims of prescriptions in the 3 months prior to conception. We performed companion analyses of medications used for >90 days in the 12 months prior to conception and of any medication use in the 12 months prior to conception. We confirmed that both maternal medication use and comorbidity (e.g. hypertension, diabetes, hyperlipidemia) rose over the study period, consistent with prior studies. We found a concurrent rise in both paternal medication use 3 months prior to conception (overall use, 31.5-34.9% during the study period; P < 0.0001) and comorbidity (CCI of ≥1 and 10.6-18.0% over study period; P < 0.0001). The most common conditions seen in the CCI were chronic obstructive pulmonary disease for mothers (6.6-11.6%) and hyperlipidemia for fathers (8.6-13.7%). Similar trends for individual medication classes and specific comorbidities such as hypertension, diabetes and hyperlipidemia were also seen. All primary result trends were statistically significant, making the role of chance minimal. As this is a descriptive study, the clinical impact is uncertain and no causal associations may be made. Though the study uses a large and curated database that includes patients from across the USA, our study population is an insured population and our findings may not be generalizable. Mean parental age was seen to slightly increase over the course of the study (<1 year) and may be associated with increased comorbidity and medication use. As parental comorbidity and certain medication use may impact fecundability, temporal declines in parental health may impact conception, pregnancy and fetal outcomes. None. N/A.


The role of B. pertussis vaccine antigen gene variants in pertussis resurgence and possible consequences for vaccine development.
Whooping cough, or pertussis, caused by Bordetella pertussis is considered resurgent in a number of countries world-wide, despite continued high level vaccine coverage. Among a number of causes for this that have been proposed, is the emergence of B. pertussis strains expressing variants of the antigens contained in acellular pertussis vaccines; i.e. the evolution of B. pertussis toward vaccine escape. This commentary highlights the contradictory nature of evidence for this but also discusses the importance of understanding the role of B. pertussis adaptation to vaccine-mediated immune selection pressures for vaccine-mediated pertussis control strategies.


[Mechanism of regulation of tyrosine metabolism in ethanol poisoning].
Metabolism of tyrosine was impaired after chronic alcoholization of rats with 10% ethanol within 10 months. Within the first 3-4 months activation of tyrosine aminotransferase and a decrease in phenylalanine hydroxylase activity were found in liver tissue. Activity of tyrosine aminotransferase was not increased during the long-term alcohol intoxication. At the same time, activity of tyrosine aminotransferase was decreased within 5-6 months simultaneously with activation of phenylalanine hydroxylase. An increase in the alcohol dehydrogenase activity was also observed in rat liver tissue during the initial period of intoxication. The enzymatic activity was decreased beginning from the 3-4 months of the alcoholization and maintained at the low level. Hyperthermia augmented these alterations observed in chronic alcoholization of rats.


Measured trends in stratospheric ozone.
Recent findings, based on both ground-based and satellite measurements, have established that there has been an apparent downward trend in the total column amount of ozone over mid-latitude areas of the Northern Hemisphere in all seasons. Measurements of the altitude profile of the change in the ozone concentration have established that decreases are taking place in the lower stratosphere in the region of highest ozone concentration. Analysis of updated ozone records, through March of 1991, including 29 stations in the former Soviet Union, and analysis of independently calibrated satellite data records from the Total Ozone Mapping Spectrometer and Stratospheric Aerosol and Gas Experiment instruments confirm many of the findings originally derived from the Dobson record concerning northern midlatitude changes in ozone. The data from many instruments now provide a fairly consistent picture of the change that has occurred in stratospheric ozone levels.


Patterns of Genital Sexual Arousal in Transgender Men.
Most men show genital sexual arousal to one preferred gender. Most women show genital arousal to both genders, regardless of their sexual preferences. There is limited knowledge of whether this difference is driven by biological sex or gender identity. Transgender individuals, whose birth sex and gender identity are incongruent, provide a unique opportunity to address this question. We tested whether the genital responses of 25 (female-to-male) transgender men followed their female birth sex or male gender identity. Depending on their surgical status, arousal was assessed with penile gauges or vaginal plethysmographs. Transgender men's sexual arousal showed both male-typical and female-typical patterns. Across measures, they responded more strongly to their preferred gender than to the other gender, similar to (but not entirely like) 145 cisgender (nontransgender) men. However, they still responded to both genders, similar to 178 cisgender women. In birth-assigned women, both gender identity and biological sex may influence sexual-arousal patterns.


Brain behavior relationships among African Americans, whites, and Hispanics.
There is an increasing racial and ethnic diversity within the elderly population of the United States. Although increased diversity offers unique opportunities to study novel influences on aging and dementia, some aspects of racial and ethnic research have been hampered by the lack of culturally and linguistically consistent testing protocols. Structural brain imaging is commonly used to study the biology of normal aging and cognitive impairment and may therefore serve to explore potential biologic differences of cognitive impairment among racially and ethnically diverse individuals. To test this hypothesis, we recruited a cohort of approximately 400 African American, white, and Hispanic subjects with various degrees of cognitive ability. Each subject was carefully evaluated using standardized diagnostic protocols that included clinical review of brain magnetic resonance image (MRI) to arrive at a clinical diagnosis of normal cognition, mild cognitive impairment or dementia. Each MRI was then independently quantified for measures of brain, white matter hyperintensities, and hippocampal volumes by a technician blind to subject age, sex, ethnicity, race, and diagnostic category. The appearance of infarction on MRI was also rated by examining neurologists. Regression analyses were used to assess associations with various MRI measures across clinical diagnostic categories in relation to racial and ethnic differences. Hispanic subjects were, on average, significantly younger and had less years of education than African Americans or whites. Whites with dementia were significantly older than both African American and Hispanic dementia patients. Highly significant differences in MRI measures were associated with clinical diagnoses for the group as a whole after adjusting for the effects of age, sex, education, race, and ethnicity. Subsequent independent analyses by racial and ethnic status revealed consistent relationships between diagnostic category and MRI measures. Clinical diagnoses were associated with consistent differences in brain structure among a group of racially and ethnically diverse individuals. We believe these results help to validate current diagnostic assessment of individuals across a broad range of racial, ethnic, linguistic, and educational backgrounds. Moreover, interesting and potentially biologically relevant differences were found that might stimulate further research related to the understanding of dementia etiology within an increasingly racially and ethnically diverse population.


A high-energy room-temperature sodium-sulfur battery.
Employing small sulfur molecules as the active cathode component for room-temperature Na-S batteries, reveals a novel mechanism that is verified for the batteries' electrochemistry. The sulfur cathode enables a complete two-electron reaction to form Na2 S, bringing a tripled specific capacity and an increased specific energy compared with traditional high-temperature Na-S batteries. At the same time, it offers better cycling stability endowing the batteries with a longer lifespan.


Immune response to influenza vaccination in community-dwelling Chinese elderly persons.
We investigated the immune antibody response to influenza vaccine in community-dwelling Chinese elderly persons in Hong Kong. One hundred and twenty-eight subjects were recruited in a single-blind, randomized, and placebo-controlled trial. There was no significant baseline difference between the vaccine and placebo groups regarding the seroprotection rates (PR) (haemagglutination inhibition [HI] titre>or=1:40) and geometric mean titres (GMT) of the HI antibody titers. The PR, GMTs and serological response rates increased significantly in the vaccinated versus placebo groups in A-H1N1 at both weeks 4 and month 6. The GMTs and serological response rates but not the PR for A-H3N2 and influenza B increased significantly in vaccinated versus placebo group at week 4 and month 6 post-vaccination. Multivariate logistic regression analyses of the seroconversion rate for A-H3N2 within the vaccinated group showed that gender, coronary heart disease and the serum albumin level were significant predictors (p=0.018, 0.009 and 0.025, respectively). Influenza vaccination provoked a protective HI antibody response in community-living Chinese elderly persons. The mean number of unplanned hospital admissions per subject over 6 months was significantly lower in the vaccinated than in the placebo groups. Hospitalized elderly persons had poorer nutrition, 4-week post-immunization HI antibody titres and lower mini-mental state examination (MMSE) score than non-hospitalized elderly persons. Logistic regression analyses showed that chronic obstructive airway disease significantly increased the risk of hospitalization while the serum albumin level and 4-week A-H3N2 PR (HI>or=40) were independent predictors of a decreased risk of hospitalizations.


Designing the community multi-user health kiosk.
This paper discusses the design and development of a multi-user health kiosk intended for independent use by underserved populations. The modular integration of physiological sensors and psycho-social assessments provides an extensible, customizable platform for research. We present the development of the kiosk's feature set and user interaction mechanisms through iterative user testing, in addition to some technical challenges and solutions resulting from our design choices.


Menstrual Status Is Associated with the Prevalence of Irritable Bowel Syndrome in a Japanese Young Population: A Cross-Sectional Study.
There is evidence regarding the association between dysmenorrhea and irritable bowel syndrome (IBS), although it is lacking in the Asian population. Therefore, the purpose of this study was to investigate the association between menstrual status and IBS in a young Japanese. Overall, 4,693 female college students were included in the analysis of this study. Information regarding lifestyle habits, menstrual status (irregularity, pain severity, and medication), and IBS (Rome III criteria) was obtained using a self-reported questionnaire. Age, body mass index, exercise habits, smoking, drinking habits, and anemia were analyzed as potential confounders. The prevalence of IBS was 6.1%. Moderate {adjusted odds ratio (OR): 1.89 (95% confidence interval [CI]: 1.27-2.91)} and heavy (adjusted OR: 2.14 [95% CI: 1.42-3.45]) menstrual pain were independently positively associated with IBS (p for trend = 0.001). Using medication sometimes (adjusted OR: 1.41 [95% CI: 1.09-1.84]) and often (adjusted OR: 1.60 [95% CI: 1.13-2.24]) was independently positively associated with IBS. There was no association between menstrual cycle and IBS. In subjects without functional dyspepsia, irregular menstrual cycle was independently positively associated with IBS. In the young Japanese population, menstrual pain and medications for menstrual pain may have a significant positive association with IBS.


Lead poisoning in childhood.
We report here a case of lead poisoning in a 20 month old girl who presented with acute encephalopathy and status epilepticus. The major clues leading to the diagnosis were the occupational family history and dense lead lines on X-ray of the long bones. She showed evidence of neurological dysfunction in the initial phase, but she improved steadily, regaining her motor power partially and her vision, although some cognitive and language deficits were already evident. She will need long-term neurological assessment and evaluation to ascertain the extent of permanent brain damage.


Reference 1D and 2D electrophoresis maps for potential disease related proteins in milk whey from lactating buffaloes and blood serum from buffalo calves (Water buffalo, Bubalus bubalis).
The aim of this study was to identify potential disease related proteins in milk whey of lactating buffaloes and blood serum of buffalo calves, in order to define a reference electrophoresis map for 1-DE and 2-DE. Additionally, changes in some protein patterns from buffalo calves during salmonellosis and lactating buffaloes during mastitis are presented. Milk samples were collected and distributed into groups: Milk samples from healthy buffaloes (SCC < 100.000 cells/ml, negative microbiology and CMT) (G1, n = 5) and buffaloes with subclinical mastitis (SCC > 500.000 cells/ml, positive microbiology and CMT) (G2, n = 5). Blood samples from buffalo calves (n = 6) were collected, and three calves were experimentally infected with Salmonella Dublin and samples analyzed before (M0) and 72 h after inoculation (M1). 1-DE was accomplished by loading 10 μg of TP into SDS-PAGE, stained with Coomassie blue. 2-DE was accomplished by loading 200 μg of TP into 11 cm, pH 3-10 non-linear IPG strips, followed by SDS-PAGE, stained with Coomassie blue. Protein bands/spots were excised, subjected to tryptic in-gel digestion and analyzed by LC/ESI-MS/MS. Protein identity was assigned using NCBI databases. After bands/spots from 1-DE and 2-DE were analyzed, a protein map with 35 and 40 different identified proteins in blood serum and milk whey, respectively, was generated. Significant changes in patterns of haptoglobin were observed in buffalo calves with salmonellosis and in patterns of IgLC, β-lactoglobulin and α-lactalbumin of lactating buffaloes during mastitis. The establishment of a protein map for 1-DE and 2-DE, identifying potential disease related proteins, can help to address alterations during diseases in buffaloes.


Substrate-selective repair and restart of replication forks by DNA translocases.
Stalled replication forks are sources of genetic instability. Multiple fork-remodeling enzymes are recruited to stalled forks, but how they work to promote fork restart is poorly understood. By combining ensemble biochemical assays and single-molecule studies with magnetic tweezers, we show that SMARCAL1 branch migration and DNA-annealing activities are directed by the single-stranded DNA-binding protein RPA to selectively regress stalled replication forks caused by blockage to the leading-strand polymerase and to restore normal replication forks with a lagging-strand gap. We unveil the molecular mechanisms by which RPA enforces SMARCAL1 substrate preference. E. coli RecG acts similarly to SMARCAL1 in the presence of E. coli SSB, whereas the highly related human protein ZRANB3 has different substrate preferences. Our findings identify the important substrates of SMARCAL1 in fork repair, suggest that RecG and SMARCAL1 are functional orthologs, and provide a comprehensive model of fork repair by these DNA translocases.


Current progress in shrimp endocrinology-a review.
One problem in aquaculture is obtaining brood because many commercially important species are incapable of spontaneous maturation under artificial conditions. Commercial shrimp hatcheries commonly use eyestalk ablation to stimulate gonadal maturation in shrimps. Research has been conducted on the inhibition of reproductive maturation by hormones originating in the eyestalk glands and on other endocrine sources (e.g.,brain, thoracic ganglion, ovary, mandibular organ, androgenic gland and Y-organs) to determine their roles. Alternate techniques for acceleration of gonad maturation through the use of synthetic hormones or neurotransmitters may benefit aquaculture. Neurohormones and neuroregulators have been shown to accelerate gonadal maturation but an effective delivery technique must be developed for use in a large-scale aquaculture operation.


Kinetic properties of crystalline enzymes. Carboxypeptidase A.
Spectrochemical probes have demonstrated that the conformations of carboxypeptidase A differ in solution and in the crystalline state. Detailed kinetic studies of carboxypeptidase A crystals and solutions now show that the physical state of the enzyme is also a critical parameter that affects this enzyme's function. Thus, for all substrates examined, crystallization of the enzyme markedly reduces catalytic efficiency, kcat, from 20- to 1000-fold. In addition, substrate inhibition, apparent in solution for some di- and depsipeptides, is abolished with crystals, while longer substrates with normal kinetics in solution may exhibit activation with the crystals. The physical state of the enzyme also affects the mode of action of known modifiers of peptidase activity of the enzyme. In solution, addition of benzoylglycine or cinnamic acid markedly increases the rate of hydrolysis of CbzGly-Phe, but, with the crystalline enzyme, their addition hardly alters the activity. This is in accord with the weakening or absence of inhibitory enzyme-substrate binding modes. Kinetic studies on crystals were carried out over a range of enzyme concentrations, substrate concentrations, and crystal sizes, and in all instances the results are in good agreement with the theory developed by Katchalski for enzymes insolubilized by other means. Importantly, these kinetic parameters are determined under conditions which obviate artifacts due to diffusion limitation of substrates or products. The differences in the kinetic behavior of carboxypeptidase crystals, on the one hand, and of their solutions, on the other hand, bear importantly on efforts to interpret the function of the enzyme in structural terms. Hypothetical modes of substrate-enzyme interaction, generated by superimposing substrate models on the crystal structure of carboxypeptidase to stimulate kinetics in solution, have failed to detect all of these changes which affect inhibitory or activating binding modes.


VTOL aircraft in emergency planning and management: a model for a helipad network.
The scientific literature regarding HEMS (Helicopter Emergency Medical Service) planning lacks a method for defining optimal sites for helipads that takes into account risk distribution and hospital location. Such a method could minimise overall rescue time in emergency situations. In this paper a method that supports the decisions taken by disaster planners and managers is developed, focusing on the quantification of necessary air resources for the management of some probable calamities. Given a region characterised by a natural and non-natural disaster risk map, along with a comprehensive transport system (also characterised by a risk map), a set of emergency destinations (hospitals), a set of heliports/helipads dislocated on the territory and a number of available HEMS rotorcraft, the aim of the paper is to assess the adequacy of the VTOL/FATO (Vertical Take-Off and Landing/Final Take-Off and Landing Area) system in order to deal with a set of possible emergencies.


Oligoclonal expansion of memory CD8+ T cells in cerebrospinal fluid from multiple sclerosis patients.
Multiple sclerosis is a chronic inflammatory demyelinating disease of the CNS. Although the aetiology of multiple sclerosis is still unknown, it is widely believed that T cells play a central role in its pathogenesis. To identify and characterize disease-relevant T cells, we analysed CD4+ and CD8+ T cells freshly isolated from the CSF and peripheral blood of 36 multiple sclerosis patients for their T-cell receptor variable beta (TCRBV) chain repertoire. In most patients, we found significant overexpression of individual TCRBV chains on CD8+ T cells from CSF compared with peripheral blood. In contrast, only a few multiple sclerosis patients showed differences between the two compartments in TCRBV expression on CD4+ T cells. The overexpression of specific TCRBV chains on CD8+ T cells was found to be stable over several months in selected patients and involved mainly T cells with a memory phenotype. In two patients studied, individual TCRBV chain overexpression was found to be caused by the expansion of T cell populations with identical or highly similar rearranged T-cell receptor beta- and alpha-chain sequences, which were not found among peripheral blood CD8+ T cells. Our findings demonstrate selective enrichment of memory CD8+ T cells in the CSF of multiple sclerosis patients, suggesting a role for these CD8+ T cells in the pathogenesis of multiple sclerosis. Our study provides a basis for future trials to identify disease-associated antigens and disease pathogenesis in multiple sclerosis.


Comparison of breeding value prediction for two traits in a Nellore-Angus crossbred population using different Bayesian modeling methodologies.
The objectives of this study were to 1) compare four models for breeding value prediction using genomic or pedigree information and 2) evaluate the impact of fixed effects that account for family structure. Comparisons were made in a Nellore-Angus population comprising F2, F3 and half-siblings to embryo transfer F2 calves with records for overall temperament at weaning (TEMP; n = 769) and Warner-Bratzler shear force (WBSF; n = 387). After quality control, there were 34,913 whole genome SNP markers remaining. Bayesian methods employed were BayesB (π̃ = 0.995 or 0.997 for WBSF or TEMP, respectively) and BayesC (π = 0 and π̃), where π̃ is the ideal proportion of markers not included. Direct genomic values (DGV) from single trait Bayesian analyses were compared to conventional pedigree-based animal model breeding values. Numerically, BayesC procedures (using π̃) had the highest accuracy of all models for WBSF and TEMP (ρ̂gĝ = 0.843 and 0.923, respectively), but BayesB had the least bias (regression of performance on prediction closest to 1, β̂y,x = 2.886 and 1.755, respectively). Accounting for family structure decreased accuracy and increased bias in prediction of DGV indicating a detrimental impact when used in these prediction methods that simultaneously fit many markers.


The transcriptome profile of human embryonic stem cells as defined by SAGE.
Human embryonic stem (ES) cell lines that have the ability to self-renew and differentiate into specific cell types have been established. The molecular mechanisms for self-renewal and differentiation, however, are poorly understood. We determined the transcriptome profiles for two proprietary human ES cell lines (HES3 and HES4, ES Cell International), and compared them with murine ES cells and other human tissues. Human and mouse ES cells appear to share a number of expressed gene products although there are numerous notable differences, including an inactive leukemia inhibitory factor pathway and the high preponderance of several important genes like POU5F1 and SOX2 in human ES cells. We have established a list of genes comprised of known ES-specific genes and new candidates that can serve as markers for human ES cells and may also contribute to the "stemness" phenotype. Of particular interest was the downregulation of DNMT3B and LIN28 mRNAs during ES cell differentiation. The overlapping similarities and differences in gene expression profiles of human and mouse ES cells provide a foundation for a detailed and concerted dissection of the molecular and cellular mechanisms governing their pluripotency, directed differentiation into specific cell types, and extended ability for self-renewal.


An autosomal gene that affects X chromosome expression and sex determination in Caenorhabditis elegans.
Recessive mutant alleles at the autosomal dpy-21 locus of C. elegans cause a dumpy phenotype in XX animals but not in XO animals. This dumpy phenotype is characteristic of X chromosome aneuploids with higher than normal X to autosome ratios and is proposed to result from overexpression of X-linked genes. We have isolated a new dpy-21 allele that also causes partial hermaphroditization of XO males, without causing the dumpy phenotype. All dpy-21 alleles show hermaphroditization effects in XO males that carry a duplication of part of the X chromosome and also partially suppress a transformer (tra-1) mutation that converts XX animals into males. Experiments with a set of X chromosome duplications show that the defects of dpy-21 mutants can result from interaction with several different regions of the X chromosome. We propose that dpy-21 regulates X chromosome expression and may be involved in interpreting X chromosome dose for the developmental decisions of both sex determination and dosage compensation.


Chronic arterial occlusive disease.
Cardiovascular disease continues to be a major cause of death in the United States. Although the number of deaths has decreased in the past several years, disability from the disease remains significant because of its systemic nature. As the population continues to age, peripheral vascular disease (PVD) will become increasingly prevalent in society as a result of the process of atherosclerosis. This article focuses on the care of patients with PVD. Risk factors, presenting signs and symptoms, and diagnostic and therapeutic modalities associated with chronic arterial occlusive disease, as well as nursing responsibilities and interventions, are discussed.


Favorable outcome of repeat mechanical thrombectomy in a geriatric patient: illustrative case.
The authors presented their experience with a case of repeat thrombectomy in a 93-year-old patient who showed a favorable outcome after recurrent large vessel occlusion treated with emergency mechanical thrombectomy. Mechanical thrombectomy has been proven to be effective in treating large vessel occlusion types of ischemic stroke. Most of the patient populations involved in the thrombectomy-related studies were younger than 80 years. In addition, recurrent mechanical thrombectomy is not a common procedure in clinical practice. This unusual case demonstrated the potential to achieve a favorable outcome with thrombectomy even in a patient older than 85 years with recurrent large vessel occlusion. There can be a favorable neurological outcome after one or repeat thrombectomies for geriatric patients older than 90 years, and age should not be a deterrent to treatment.


The effectiveness of nurse-delivered aromatherapy in an acute care setting.
To examine the use and effectiveness of essential oil therapeutic interventions on pain, nausea, and anxiety, when provided by nurses to patients in acute hospital settings across a large health system. This study expands upon the limited body of literature on aromatherapy use among inpatients. Retrospective, effectiveness study using data obtained from electronic health records. Ten Allina Health hospitals located in Minnesota and western Wisconsin. Nurse-delivered aromatherapy. Change in patient-reported pain, anxiety, and nausea, rated before and after receiving aromatherapy using a numeric rating scale (0-10). There were 10,262 hospital admissions during the study time frame in which nurse-delivered aromatherapy was part of patient care. The majority of admissions receiving aromatherapy were females (81.71%) and white (87.32%). Over 75% of all aromatherapy sessions were administered via inhalation. Lavender had the highest absolute frequency (49.5%) of use regardless of mode of administration, followed by ginger (21.2%), sweet marjoram (12.3%), mandarin (9.4%), and combination oils (7.6%). Sweet marjoram resulted in the largest single oil average pain change at -3.31 units (95% CI: -4.28, -2.33), while lavender and sweet marjoram had equivalent average anxiety changes at -2.73 units, and ginger had the largest single oil average change in nausea at -2.02 units (95% CI: -2.55, -1.49). Essential oils generally resulted in significant clinical improvements based on their intended use, although each oil also showed ancillary benefits for other symptoms. Future research should explore use of additional essential oils, modes of administration, and different patient populations.


Modeling Renal Cell Carcinoma in Mice: Bap1 and Pbrm1 Inactivation Drive Tumor Grade.
Clear cell renal cell carcinoma (ccRCC) is characterized by BAP1 and PBRM1 mutations, which are associated with tumors of different grade and prognosis. However, whether BAP1 and PBRM1 loss causes ccRCC and determines tumor grade is unclear. We conditionally targeted Bap1 and Pbrm1 (with Vhl) in the mouse using several Cre drivers. Sglt2 and Villin proximal convoluted tubule drivers failed to cause tumorigenesis, challenging the conventional notion of ccRCC origins. In contrast, targeting with PAX8, a transcription factor frequently overexpressed in ccRCC, led to ccRCC of different grades. Bap1-deficient tumors were of high grade and showed greater mTORC1 activation than Pbrm1-deficient tumors, which exhibited longer latency. Disrupting one allele of the mTORC1 negative regulator, Tsc1, in Pbrm1-deficient kidneys triggered higher grade ccRCC. This study establishes Bap1 and Pbrm1 as lineage-specific drivers of ccRCC and histologic grade, implicates mTORC1 as a tumor grade rheostat, and suggests that ccRCCs arise from Bowman capsule cells.Significance: Determinants of tumor grade and aggressiveness across cancer types are poorly understood. Using ccRCC as a model, we show that Bap1 and Pbrm1 loss drives tumor grade. Furthermore, we show that the conversion from low grade to high grade can be promoted by activation of mTORC1. Cancer Discov; 7(8); 900-17. ©2017 AACR.See related commentary by Leung and Kim, p. 802This article is highlighted in the In This Issue feature, p. 783.


Multirule quality control procedures.
Multirule quality control procedures employ combinations of individual quality control rules to increase the probability of error detection without increasing the probability of false rejections to unacceptable levels. Performance characteristics of several example multirule procedures are described, and general recommendations are made for their selection and use. Multistage quality control procedures tailor the control rules employed to the frequency of errors expected during a given phase of analyzer operation. During analyzer startup, sensitive rules are employed; after acceptable analyzer performance is demonstrated, less sensitive rules are used for routine monitoring. As they tend to deteriorate quality control rule performance, between-run variations should be minimized.


Molecular MR Imaging of Prostate Cancer.
This review summarizes recent developments regarding molecular imaging markers for magnetic resonance imaging (MRI) of prostate cancer (PCa). Currently, the clinical standard includes MR imaging using unspecific gadolinium-based contrast agents. Specific molecular probes for the diagnosis of PCa could improve the molecular characterization of the tumor in a non-invasive examination. Furthermore, molecular probes could enable targeted therapies to suppress tumor growth or reduce the tumor size.


[Use of electroacupuncture in the treatment of vibration diseases].
Vibration is known to adversely affect the nervous, cardiovascular and muscular systems, which feature is most liable to lead to decrement of performance. Employed in former times in dealing with the above affections was a complex medicamentous mode of treatment involving the use of vasoactive agents, sympatho- and cholinolytics, neuroplegic agents, physiotherapeutic and sanatorium-and-health resort methods, and other therapeutic modalities. There has been studied efficiency of use of electroacupuncture versus a complex medicamentous therapy in patients presenting with vibration disease. Methods are described for management of patients with acupuncture procedures. With reflexotherapy techniques, electroacupuncture in particular, it takes less time for the clinical-and-physiological indices to return to normal and for the patients to recover their strength after the illness. Electroacupuncture can be recommended for treating vibration disease in an outpatient, in-patient, and sanatorium-and-health resort setting. The above method permits the treatment time to be reduced by 20%, which fact has a major economic effect.


[Dysmorphophobia].
In the ICD-10 classification, the body dysmorphophobic (dysmorphic) disorder is subsumed under the code for somatoform or hypochondriacal disorders (F45.2). To the fore is an excessive preoccupation with an imagined, but not objectifiable, bodily defect, usually affecting a part of the body that is either exposed or considered to be of importance for the patient's attractiveness. In many cases, the patient insistently demands surgical correction. During the further course of the condition, depression, social phobia, obsessive-compulsive and self-destructive behavior may develop. The condition usually begins early in the patient's life, and the lifetime prevalence is estimated to be 5%. Since an involvement of the serotonergic system is assumed, selective serotonin reuptake inhibitors are considered to be the medication of first choice. Surgical interventions do not lead to remission but simply to a transference of symptoms. Referral to a psychiatric specialist with the aim of clarifying the diagnosis is indicated.


Microsurgical Clipping of Carotid-Ophthalmic Tandem Aneurysms: Case Report and Surgical Nuances.
Tandem intracranial aneurysms (TandIAs) are rare but inherently complex, and special technical considerations are required for their surgical management. The present case highlights the key surgical aspects of two carotid-ophthalmic TandIAs incidentally found in a 60-year-old female. Both the aneurysms were superiorly projecting, regular in size, and involved the left ophthalmic segment of the internal carotid artery (ICA). The minimum distance between the necks was 3 mm. The patient underwent microsurgery because of the reported major complications rate of the endovascular treatment in the case of a very short minimum distance between the TandIAs. After cervical ICA exposure, both the aneurysms were excluded through a pterional approach. Intradural anterior clinoidectomy and unroofing of the optic canal allowed the mobilization of the left optic nerve. The more distal aneurysm was clipped before the opening of the distal dural ring of the ICA. The proximal aneurysm was clipped with two straight clips stacked perpendicular to the ICA. A small remnant was intentionally left to avoid the stenosis of the ophthalmic artery. Postoperative angiography showed the exclusion of both the aneurysms with a small dog-ear of the more proximal one. The patient was discharged neurologically intact and, after one year, the remnant remained stable. Microsurgical clipping is a definitive and durable treatment for carotid-ophthalmic TandIAs. In the case of a very short minimum distance between the aneurysms, the distal one should be clipped first to make the anterior clinoidectomy, opening of the distal dural ring of the ICA, and clipping of the more proximal aneurysm easier.


Size-dependent shape distributions of platinum nanoparticles.
While it is well established that nanoparticle shape can depend on equilibrium thermodynamics or growth kinetics, recent computational work has suggested the importance of thermal energy in controlling the distribution of shapes in populations of nanoparticles. Here, we used transmission electron microscopy to characterize the shapes of bare platinum nanoparticles and observed a strong dependence of shape distribution on particle size. Specifically, the smallest nanoparticles (<2.5 nm) had a truncated octahedral shape, bound by 〈111〉 and 〈100〉 facets, as predicted by lowest-energy thermodynamics. However, as particle size increased, the higher-energy 〈110〉 facets became increasingly common, leading to a large population of non-equilibrium truncated cuboctahedra. The observed trends were explained by combining atomistic simulations (both molecular dynamics and an empirical square-root bond-cutting model) with Boltzmann statistics. Overall, this study demonstrates experimentally how thermal energy leads to shape variation in populations of metal nanoparticles, and reveals the dependence of shape distributions on particle size. The prevalence of non-equilibrium facets has implications for metal nanoparticles applications from catalysis to solar energy.


Adult-generated hippocampal neurons allow the flexible use of spatially precise learning strategies.
Despite enormous progress in the past few years the specific contribution of newly born granule cells to the function of the adult hippocampus is still not clear. We hypothesized that in order to solve this question particular attention has to be paid to the specific design, the analysis, and the interpretation of the learning test to be used. We thus designed a behavioral experiment along hypotheses derived from a computational model predicting that new neurons might be particularly relevant for learning conditions, in which novel aspects arise in familiar situations, thus putting high demands on the qualitative aspects of (re-)learning.In the reference memory version of the water maze task suppression of adult neurogenesis with temozolomide (TMZ) caused a highly specific learning deficit. Mice were tested in the hidden platform version of the Morris water maze (6 trials per day for 5 days with a reversal of the platform location on day 4). Testing was done at 4 weeks after the end of four cycles of treatment to minimize the number of potentially recruitable new neurons at the time of testing. The reduction of neurogenesis did not alter longterm potentiation in CA3 and the dentate gyrus but abolished the part of dentate gyrus LTP that is attributed to the new neurons. TMZ did not have any overt side effects at the time of testing, and both treated mice and controls learned to find the hidden platform. Qualitative analysis of search strategies, however, revealed that treated mice did not advance to spatially precise search strategies, in particular when learning a changed goal position (reversal). New neurons in the dentate gyrus thus seem to be necessary for adding flexibility to some hippocampus-dependent qualitative parameters of learning.Our finding that a lack of adult-generated granule cells specifically results in the animal's inability to precisely locate a hidden goal is also in accordance with a specialized role of the dentate gyrus in generating a metric rather than just a configurational map of the environment. The discovery of highly specific behavioral deficits as consequence of a suppression of adult hippocampal neurogenesis thus allows to link cellular hippocampal plasticity to well-defined hypotheses from theoretical models.


Bicarbonate stabilizes isolated D1/D2/cytochrome b559 complex of photosystem 2 against thermoinactivation.
It has been shown that thermoinactivation of the isolated D1/D2/cytochrome b(559) complex (RC) of photosystem 2 (PS-2) from pea under anaerobic conditions at 35°C in 20 mM Tris-HCl buffer (pH 7.2) depleted of HCO(3)(-), with 35 mM NaCl and 0.05% n-dodecyl-β-maltoside, results in a decrease in photochemical activity measured by photoreduction of the PS-2 primary electron acceptor, pheophytin (by 50% after 3 min of heating), which is accompanied by aggregation of the D1 and D2 proteins. Bicarbonate, formate, and acetate anions added to the sample under these conditions differently influence the maintenance of photochemical activity: a 50% loss of photochemical activity occurs in 11.5 min of heating in the presence of bicarbonate and in 4 and 4.6 min in the presence of formate and acetate, respectively. The addition of bicarbonate completely prevents aggregation of the D1 and D2 proteins as opposed to formate and acetate (their presence has no effect on the aggregation during thermoinactivation). Since the isolated RCs have neither inorganic Mn/Ca-containing core of the water-oxidizing complex nor nonheme Fe(2+), it is supposed that bicarbonate specifically interacts with the hydrophilic domains of the D1 and D2 proteins, which prevents their structural modification that is a signal for aggregation of these proteins and the loss of photochemical activity.


Association between serum perfluorooctanoic acid (PFOA) and thyroid disease in the U.S. National Health and Nutrition Examination Survey.
Perfluorooctanoic acid (PFOA, also known as C8) and perfluorooctane sulfonate (PFOS) are stable compounds with many industrial and consumer uses. Their persistence in the environment plus toxicity in animal models has raised concern over low-level chronic exposure effects on human health. We estimated associations between serum PFOA and PFOS concentrations and thyroid disease prevalence in representative samples of the U.S. general population. Analyses of PFOA/PFOS versus disease status in the National Health and Nutrition Examination Survey (NHANES) for 1999-2000, 2003-2004, and 2005-2006 included 3,974 adults with measured concentrations for perfluorinated chemicals. Regression models were adjusted for age, sex, race/ethnicity, education, smoking status, body mass index, and alcohol intake. The NHANES-weighted prevalence of reporting any thyroid disease was 16.18% (n = 292) in women and 3.06% (n = 69) in men; prevalence of current thyroid disease with related medication was 9.89% (n = 163) in women and 1.88% (n = 46) in men. In fully adjusted logistic models, women with PFOA >or= 5.7 ng/mL [fourth (highest) population quartile] were more likely to report current treated thyroid disease [odds ratio (OR) = 2.24; 95% confidence interval (CI), 1.38-3.65; p = 0.002] compared with PFOA <or= 4.0 ng/mL (quartiles 1 and 2); we found a near significant similar trend in men (OR = 2.12; 95% CI, 0.93-4.82; p = 0.073). For PFOS, in men we found a similar association for those with PFOS >or= 36.8 ng/mL (quartile 4) versus <or= 25.5 ng/mL (quartiles 1 and 2: OR for treated disease = 2.68; 95% CI, 1.03-6.98; p = 0.043); in women this association was not significant. Higher concentrations of serum PFOA and PFOS are associated with current thyroid disease in the U.S. general adult population. More work is needed to establish the mechanisms involved and to exclude confounding and pharmacokinetic explanations.


The spin-dependent Seebeck effect and the charge and spin figure of merit in a hybrid structure of single-walled carbon nanotubes and zigzag-edge graphene nanoribbons.
A hybrid structure of carbon nanotubes and graphene nanoribbons was predicted and synthesized (Y. Li et al., Nat. Nanotechnol., 2012, 7, 394-400; P. Lou, J. Phys. Chem. C, 2014, 118, 4475-4482). Herein, using the non-equilibrium Green's function (NEGF) combined with density functional theory (DFT), the thermal spin transport properties and the figure of merit (a material constant proportional to the efficiency of a thermoelectric couple made with the material) of a composite of single-walled carbon nanotubes and zigzag-edge graphene nanoribbons, labeled (6,6)SWCNT/n-ZGNR, are investigated for n = 1, 2, 3, and 8. The results manifest that spin-dependent currents with opposite flow directions were generated when a temperature gradient was applied between two electrodes, indicating the occurrence of the spin-dependent Seebeck effect (SDSE). Remarkably, when n = 3, the charge current is equal to zero, meaning that a perfect SDSE is observed. Moreover, a pure spin-dependent Seebeck diode (SDSD) effect can be observed. Finally, we notice that the device presents an n-type characteristic when n = 1, while the device has a p-type feature when n = 2. In particular, the spin-up thermopower is equal to the spin-down thermopower when n = 3; as a consequence, the charge thermopower is equal to zero, further demonstrating that a perfect SDSE is generated. These discoveries indicate that the (6,6)SWCNT/n-ZGNR is a promising candidate for spin caloritronics devices.


Acute and chronic effects of strenuous exercise on glucose metabolism in isolated, incubated soleus muscle of exercise-trained rats.
Male and female Wistar rats were exercise-trained for 6 or 11 weeks respectively, to examine the effects of acute exercise or exercise training per se on insulin-stimulated glucose utilization in soleus muscles isolated and incubated in vitro. The maximal activities of hexokinase and 2-oxoglutarate dehydrogenase were significantly elevated (by greater than 50%) in gastrocnemius muscle of exercise-trained male and female rats, indicating an adaptation to the training regime. No significant differences in any of the variables studied were observed between appropriately matched male and female rats. There were no significant differences in the sensitivity or responsiveness of the rates of lactate formation or glycogen synthesis in soleus muscles isolated from exercise-trained and sedentary animals at rest (exercise-trained animals were studied 40 h after the last exercise bout). On the other hand, acute exercise caused significant changes in soleus muscle glucose metabolism. Basal and insulin-stimulated rates of glycogen synthesis were significantly elevated in soleus muscles incubated from both sedentary and exercise-trained rats immediately after an exercise bout. In addition, the responsiveness of glucose utilization to insulin in soleus muscles from exercise-trained rats was significantly increased after acute exercise. The results indicate that significant changes in the control of glucose metabolism by insulin in soleus muscle occur as a result of an acute exercise bout, while no adaptive changes in insulin sensitivity occur in soleus muscle after exercise training.


[Conclusions and recommendations of a WHO expert consultation meeting on iron supplementation for infants and young children in malaria endemic areas].
This article presents the results of an expert consultation meeting aimed at evaluating the safety and public health implications of administering supplemental iron to infants and young children in malaria-endemic areas. Participants at this meeting that took place in Lyon, France on June 12-14, 2006 reached consensus on several important issues related to iron supplementation for infants and young children in malaria-endemic areas. The conclusions in this report apply specifically to regions where malaria is endemic.


Development of novel cellular histone-binding and chromatin-displacement assays for bromodomain drug discovery.
Proteins that 'read' the histone code are central elements in epigenetic control and bromodomains, which bind acetyl-lysine motifs, are increasingly recognized as potential mediators of disease states. Notably, the first BET bromodomain-based therapies have entered clinical trials and there is a broad interest in dissecting the therapeutic relevance of other bromodomain-containing proteins in human disease. Typically, drug development is facilitated and expedited by high-throughput screening, where assays need to be sensitive, robust, cost-effective and scalable. However, for bromodomains, which lack catalytic activity that otherwise can be monitored (using classical enzymology), the development of cell-based, drug-target engagement assays has been challenging. Consequently, cell biochemical assays have lagged behind compared to other protein families (e.g., histone deacetylases and methyltransferases). Here, we present a suite of novel chromatin and histone-binding assays using AlphaLISA, in situ cell extraction and fluorescence-based, high-content imaging. First, using TRIM24 as an example, the homogenous, bead-based AlphaScreen technology was modified from a biochemical peptide-competition assay to measure binding of the TRIM24 bromodomain to endogenous histone H3 in cells (AlphaLISA). Second, a target agnostic, high-throughput imaging platform was developed to quantify the ability of chemical probes to dissociate endogenous proteins from chromatin/nuclear structures. While overall nuclear morphology is maintained, the procedure extracts soluble, non-chromatin-bound proteins from cells with drug-target displacement visualized by immunofluorescence (IF) or microscopy of fluorescent proteins. Pharmacological evaluation of these assays cross-validated their utility, sensitivity and robustness. Finally, using genetic and pharmacological approaches, we dissect domain contribution of TRIM24, BRD4, ATAD2 and SMARCA2 to chromatin binding illustrating the versatility/utility of the in situ cell extraction platform. In summary, we have developed two novel complementary and cell-based drug-target engagement assays, expanding the repertoire of pharmacodynamic assays for bromodomain tool compound development. These assays have been validated through a successful TRIM24 bromodomain inhibitor program, where a micromolar lead molecule (IACS-6558) was optimized using cell-based assays to yield the first single-digit nanomolar TRIM24 inhibitor (IACS-9571). Altogether, the assay platforms described herein are poised to accelerate the discovery and development of novel chemical probes to deliver on the promise of epigenetic-based therapies.


Escherichia coli cultures maintain stable subpopulation structure during long-term evolution.
How genetic variation is generated and maintained remains a central question in evolutionary biology. When presented with a complex environment, microbes can take advantage of genetic variation to exploit new niches. Here we present a massively parallel experiment where WT and repair-deficient (∆mutL) Escherichia coli populations have evolved over 3 y in a spatially heterogeneous and nutritionally complex environment. Metagenomic sequencing revealed that these initially isogenic populations evolved and maintained stable subpopulation structure in just 10 mL of medium for up to 10,000 generations, consisting of up to five major haplotypes with many minor haplotypes. We characterized the genomic, transcriptomic, exometabolomic, and phenotypic differences between clonal isolates, revealing subpopulation structure driven primarily by spatial segregation followed by differential utilization of nutrients. In addition to genes regulating the import and catabolism of nutrients, major polymorphisms of note included insertion elements transposing into fimE (regulator of the type I fimbriae) and upstream of hns (global regulator of environmental-change and stress-response genes), both known to regulate biofilm formation. Interestingly, these genes have also been identified as critical to colonization in uropathogenic E. coli infections. Our findings illustrate the complexity that can arise and persist even in small cultures, raising the possibility that infections may often be promoted by an evolving and complex pathogen population.


Within-subject mediation analysis for experimental data in cognitive psychology and neuroscience.
Statistical mediation allows researchers to investigate potential causal effects of experimental manipulations through intervening variables. It is a powerful tool for assessing the presence and strength of postulated causal mechanisms. Although mediation is used in certain areas of psychology, it is rarely applied in cognitive psychology and neuroscience. One reason for the scarcity of applications is that these areas of psychology commonly employ within-subjects designs, and mediation models for within-subjects data are considerably more complicated than for between-subjects data. Here, we draw attention to the importance and ubiquity of mediational hypotheses in within-subjects designs, and we present a general and flexible software package for conducting Bayesian within-subjects mediation analyses in the R programming environment. We use experimental data from cognitive psychology to illustrate the benefits of within-subject mediation for theory testing and comparison.


Assessment of Single-Barrel Superficial Temporal Artery-Middle Cerebral Artery Bypass in Treatment for Adult Patients with Ischemic-Type Moyamoya Disease.
BACKGROUND Moyamoya disease (MMD) is an idiopathic disease caused by progressive steno-occlusion of the distal internal carotid artery. Ideal surgical treatment for adult patients with ischemic-type MMD has not been achieved. The aim of this study was to evaluate the efficacy of single-barrel superficial temporal artery-middle cerebral artery (STA-MCA) bypass in treatment for adult patients with ischemic-type MMD by analyzing clinical and radiological data retrospectively. MATERIAL AND METHODS The present study included 37 patients with non-hemorrhagic MMD, including 21 women and 16 men (21~55 years old, mean age 38.1 years). The bypass surgery was performed on 56 sides in the 37 patients. The clinical charts, angiographic revascularization, and hemodynamic changes were reviewed at 6-60 months after surgery. RESULTS Among the 37 patients, the clinical symptoms and signs of 32 patients were improved or stabilized. Five patients had complications, including 2 cases of acute cerebral infarction, 1 case of epidural hematoma, and 1 case of transient speech disturbance, and 1 patient died. Follow-up computed tomography perfusion (CTP) revealed that cerebral blood flow (CBF) was markedly improved after surgery (P<0.05). Time to peek (TTP) and mean transit time (MTT) were significantly decreased after surgery (P<0.05). No significant change in cerebral blood volume (CBV) was found after surgery (P>0.05). Postoperative patency was clearly verified in 52 bypasses (92.8%) of 56 bypasses on follow-up DSA imaging. CONCLUSIONS Single-barrel STA-MCA bypass can be considered as an effective surgical treatment, which exhibits satisfactory clinical efficacy in ischemic-type MMD patients.


Intraluminal content is required for the maintenance of antigrade proluminal movement of 3H-androgens into rat caput epididymal tubules.
The present study was undertaken to determine whether or not antigrade, proluminal 3H-androgen movement in the caput epididymis occurs in the absence of native lumen content. A single tubule was perfused with artificial caput fluid containing no androgen-binding protein for 30 min and subsequently tubules were perifused with Minimum Essential Medium perifusion fluid containing 26.7 microCi/ml 3H-testosterone and 1.3 microCi/ml 14C-polyethyleneglycol for 1 h. Radioactivity of isotopes in perifusion and intraluminal fluids was determined at 1 h after sustaining perifusion, and the percentage of peritubular isotopes appearing in the intraluminal fluid was determined. Net entry of 3H-androgen into the epididymal tubules in the presence of native intraluminal content was approximately 323%. In contrast, intraluminal 3H-androgen concentrations in the epididymal fluid in the absence of native lumen content were significantly reduced, to 100% of those in the peritubular fluid. Antigrade, proluminal movement of 3H-androgen in the caput epididymis does not occur in the absence of native lumen content. Androgen-binding protein in the epididymal lumen may be required to maintain uphill proluminal movement of 3H-androgen into the tubules.


Clinical implications of the reduced activity of the GH-IGF-I axis in older men.
During the last decade, a significant body of evidence has accumulated, indicating that IGF-I might play a role in several pathological conditions commonly seen during aging, such as atherosclerosis and cardiovascular disease (CVD), cognitive decline, dementia, sarcopenia and frailty. A vascular protective role for IGF-I has been suggested because of its ability to stimulate nitric oxide production from endothelial and vascular smooth muscle cells. In cross sectional studies, low IGF-I levels have been associated with unfavorable CVD risk factors profile, such as atherosclerosis, abnormal lipoprotein levels and hypertension, while in prospective studies, lower IGF-I levels predict future development of ischemic heart disease. The fall in IGF-I levels with aging correlates with cognitive decline and it has been suggested that IGF-I plays a role in the development of dementia. IGF-I is highly expressed within the brain and is essential for normal brain development. IGF-I has anti-apoptotic and neuroprotective effects and promotes projection neuron growth, dendritic arborization and synaptogenesis. Collectively, these data are consistent with a causal link between the age-related decline in GH and IGF-I levels and cognitive deficits in older persons. Finally, there is evidence of a relationship between declining GH and IGF-I levels and age-related changes in body composition and physical function. However, few studies have documented a precise role of IGF-I in the development of sarcopenia, frailty and poor mobility. We have recently documented that serum IGF-I is significantly associated with measures of muscle strength and physical performance in men and to a lesser extent in women. In conclusion, IGF-I is a pleiotropic hormone that in older persons may positively affect the cardiovascular system, the central nervous system and physical function.


Lesson of the month: novel method to quantify neutrophil uptake in early lung cancer using SPECT-CT.
Neutrophils play an important role in the lung tumour microenvironment. We hypothesised that radiolabelled neutrophils coupled to single-photon emission CT (SPECT) may non-invasively quantify neutrophil uptake in tumours from patients with non-small cell lung cancer. We demonstrated increased uptake of radiolabelled neutrophils from the blood into tumours compared with non-specific uptake using radiolabelled transferrin. Moreover, indium-111-neutrophil activity in the tumour biopsies also correlated with myeloperoxidase (MPO)-positive neutrophils. Our data support the utility of imaging with In-111-labelled neutrophils and SPECT-CT to quantify neutrophil uptake in lung cancer.


A role of nerve growth factor in oligodendrocyte growth and differentiation of EAE affected rats.
We have previously shown that the level of nerve growth factor (NGF) undergoes significant changes in the cerebrospinal fluid of patients with Multiple Sclerosis and in the brain of rats affected by Experimental Allergic Encephalomyelitis (EAE). The functional significance of the endogenous disregulation of NGF is not known, though recent studies seem to suggest that NGF might be associated with the ability of oligodendrocytes (OLs) to produce and/or utilise NGF. The aim of the present study was therefore to investigate whether NGF is involved in the development and differentiation of cells of the subventricular zone (SVz) which arbors undifferentiated cells that can give rise to OLs. The results show that NGF injected into the brain of developing rats and of rats affected by EAE is retrogradely transported from the SVz to the brain parenchyma. These findings suggest that during the early phase of brain development and during EAE, NGF, along with other growth factors, is implicated in growth and/or differentiation of OLs and in protecting neuronal injury. The possible functional role of NGF in these events has been discussed.


Open-source platform to benchmark fingerprints for ligand-based virtual screening.
: Similarity-search methods using molecular fingerprints are an important tool for ligand-based virtual screening. A huge variety of fingerprints exist and their performance, usually assessed in retrospective benchmarking studies using data sets with known actives and known or assumed inactives, depends largely on the validation data sets used and the similarity measure used. Comparing new methods to existing ones in any systematic way is rather difficult due to the lack of standard data sets and evaluation procedures. Here, we present a standard platform for the benchmarking of 2D fingerprints. The open-source platform contains all source code, structural data for the actives and inactives used (drawn from three publicly available collections of data sets), and lists of randomly selected query molecules to be used for statistically valid comparisons of methods. This allows the exact reproduction and comparison of results for future studies. The results for 12 standard fingerprints together with two simple baseline fingerprints assessed by seven evaluation methods are shown together with the correlations between methods. High correlations were found between the 12 fingerprints and a careful statistical analysis showed that only the two baseline fingerprints were different from the others in a statistically significant way. High correlations were also found between six of the seven evaluation methods, indicating that despite their seeming differences, many of these methods are similar to each other.


Survival in Older Japanese Adults With Advanced Cancer Before and After Implementation of a Geriatric Oncology Service.
Research studies have demonstrated that comprehensive geriatric assessment (CGA) improves outcomes in older adults with cancer treated with chemotherapy. We compared survival outcomes on older adults with advanced cancer before and after the initiation of a geriatric oncology service (GOS) in a single Japanese cancer center. This was a comparative study of two groups of consecutive patients 70 years and older with advanced cancer who were referred to medical oncology for first-line chemotherapy before (controls; n = 151, September 2015-August 2018) and after (GOS; n = 191, September 2018-March 2021) implementation of the GOS. When the treating physician requested a consultation from the GOS, a geriatrician and an oncologist performed CGA and provided recommendations for cancer treatment and geriatric interventions. Time to treatment failure (TTF) and overall survival (OS) were compared between the two groups. The median age for all patients was 75 (range, 70-95) years, and 85% had GI cancers. In the GOS group, 82 patients received the CGA before a treatment decision and oncologic treatment plans were changed in 49 patients (60%). The overall implementation rate of the CGA-based geriatric interventions was 45%. Two hundred and eighty-two patients received chemotherapy (controls; n = 128 and GOS; n = 154), and 60 patients were treated with best supportive care only (controls; n = 23 and GOS; n = 37). Among patients receiving chemotherapy, TTF event rates for the GOS group compared with the control group were 5.7% versus 14% at 30 days (P = .02) and 13% versus 29% at 60 days (P = .001). The GOS group had longer OS than the control group with a hazard ratio of 0.64 (95% CI, 0.44 to 0.93; P = .02). In this study, older adults with advanced cancer managed after the implementation of a GOS had improved survival outcomes compared with a historical control of patients.


Associations of Bone Mineral Density with Lean Mass, Fat Mass, and Dietary Patterns in Postmenopausal Chinese Women: A 2-Year Prospective Study.
To assess factors associated with bone mineral density (BMD) in postmenopausal women in a longitudinal study, and to examine the relative contribution of lean mass, fat mass, dietary patterns, and years since menopause to BMD. Two hundred and eighty-two postmenopausal women were randomly selected from Hongqi Community Health Center, in Harbin City, China. All participants were followed up from 2009 to 2011. Dietary data were collected using a Food Frequency Questionnaire. BMD of the left hip, the lumbar spine, and the total body, and the body composition were measured by dual-energy X-ray absorptiometry at baseline and follow-up. Lean mass and fat mass were positively associated with BMD of the spine, hip, and the total body at both baseline and follow-up. The association between fat mass and BMD at the spine at baseline (P = 0.210) and at the spine (P = 0.116) and hip (P = 0.073) in the second year was not statistically significant when height was adjusted. Six dietary patterns were identified but only cereal grains-fruits pattern (P = 0.001 in the spine, P = 0.037 in hip) and milk-root vegetables pattern (P = 0.010 in hip) were associated with BMD of the spine and hip. The linear mixed model of follow-up data showed that lean mass, years since menopause, and age of menophania were the significant determinants of BMD of all sites. Moreover, lean mass was the best determinant of BMD (VIP = 1.936). Lean mass, years since menopause, age of menophania and dietary patterns are the important determinants of BMD of the spine, hip, and the total body. Lean mass is the best determinant of BMD.


Adjustable sutures: experimental assessment of final muscle position.
The likelihood of forward "creep" of muscles recessed with the use of adjustable loops of suture in the correction of strabismus was investigated. Twelve orthotropic dogs underwent both regular and loop recessions of the lateral and medial rectus muscles; the data for two of the dogs were excluded because of loss of muscles. Three months later it was found that in the majority of cases the recessed muscles had minimally advanced from the position of surgical placement. Although the type of recession made little difference to the results, the mean forward creep was much greater for the medial rectus muscles (1.55 +/- 0.68 mm [p less than 0.01] and 2.00 +/- 2.44 mm [p = 0.09] for those undergoing regular and loop recessions respectively) than for the lateral rectus muscles (0.35 +/- 0.58 mm and 0.60 +/- 0.62 mm respectively). During the operations the amount of contraction of the medial rectus muscle had been noted to vary. It is likely that in some instances the tension on the suture loops was insufficient to hold them taut, and the muscles therefore adhered to the sclera at variable sites. Hence, adequate intrinsic muscle tone may be important for predictable clinical results of loop recession.


Anesthesia practices for management of labor pain and cesarean delivery in France (EPIDOL): A cross-sectional survey.
This study aimed to collect obstetric anesthesia practice and patient-reported outcomes as an update to the last French Obstetric Anesthesia survey from 1996. Maternity units were randomly selected across France and surveyed for 7 consecutive days from February, 2016, to January, 2017. Data was gathered prospectively by questionnaires filled out by patients and anesthesia providers. There were 1885 questionnaires received from 56 units, with 379 cesarean delivery (CD) and 1506 vaginal delivery (VD) cases analyzed. The overall neuraxial labor analgesia (NLA) rate was 82.5% (95% CI [82.4-82.6]), with 70.3% (95% CI [71.4-71.6]) receiving automated administration (PCEA/PIEB). NLA was effective throughout labor in 68.2% of cases, however, severe pain was reported by 29.4% of patients. The overall rate of alternative approaches for labor analgesia was 19.5% (95%CI [19.2-19.7]). Obesity (OR 2.8; 95% CI [1.0-7.5], p < 0.04) and delivery in level I units (OR 0.6; 95% CI [0.5-0.9], p < 0.01) were associated with severe pain during VD. Satisfaction was found to be similar in patients delivering with or without NLA. The incidence of pain during CD was similar in scheduled versus non-scheduled CD. Failure of NLA during CD was associated with severe pain (OR 10.0; 95% CI [3.1-31.9], p < 0.01) and dissatisfaction (OR 26.2; 95% CI [3.0-225.1], p < 0.01). Despite the high NLA rate in France, a significant proportion of women experience severe pain during labor and delivery. This study emphasizes the need for further practice guidelines in obstetric anesthesia to ensure optimal pain management and improve patients' experience during childbirth. govNCT02853890.


Genes encoding heterotrimeric G-proteins are associated with gray matter volume variations in the medial frontal cortex.
G-protein-coupled signal transduction mediates most cellular responses to hormones and neurotransmitters; this signaling system transduces a large variety of extracellular stimuli into neurons and is the most widely used mechanism for cell communication at the synaptic level. The heterotrimeric G-proteins have been well established as key regulators of neuronal growth, differentiation, and function. More recently, the heterotrimeric G-protein genes group was associated with general cognitive ability. Although heterotrimeric G-proteins are linked to both cognitive ability and neuron signaling, it is unknown whether heterotrimeric G-proteins are also important for brain structure. We tested for association between local cerebral gray matter volume and the heterotrimeric G-protein genes group in 294 subjects; a replication analysis was performed in an independent sample of 238 subjects. Voxel-based morphometry revealed a strong replicated association between 2 genes encoding heterotrimeric G-proteins with specific local increase in medial frontal cortex volume, an area known to be involved in cognitive control and negative affect. This finding suggests that heterotrimeric G-proteins might modulate medial frontal cortex gray matter volume. The differences in gray matter volume due to variations in genes encoding G-proteins may be explained by the role of G-proteins in prenatal and postnatal neocortex development.


Preclinical rationale for combining an EGFR antibody with cisplatin/gemcitabine for the treatment of NSCLC.
Although the addition of epidermal growth factor receptor (EGFR) antibodies to various platinum-based chemotherapy regimens for non-small cell lung cancer (NSCLC) is being actively pursued in the clinic, rationale for the prioritization of specific regimens is lacking. We evaluated the antitumor effects of necitumumab, a recombinant human IgG1 antibody targeting EGFR, in combination with cisplatin plus gemcitabine, pemetrexed, or paclitaxel in a panel of 9 subcutaneous tumor models of NSCLC established in nu/nu athymic mice. Necitumumab in combination with cisplatin/gemcitabine was particularly effective, although interestingly, the mechanisms underlying these benefits were model dependent. For example, increased tumor cell apoptosis contributed towards combination efficacy in the A549 model, in association with increased expression of hsa-miR-29b and reduced expression of antiapoptotic genes including DNA methyltransferase DNMT3B, commonly up-regulated in patients with NSCLC. Such inverse effects of combination therapy on DNMT3B and hsa-miR-29b expression were found in multiple models. Importantly, in the A549 model, hsa-miR-29b down-regulation of DMNT3b reduced promoter methylation of tumor suppressor genes such as Cell adhesion molecule 1 (CADM1), Ras associated (RalGDS/AF-6) domain family member 1 (RASSF1), and Fragile histidine triad gene (FHIT), increasing their expression. These results offer a preclinical rationale for combining an EGFR antibody with cisplatin/gemcitabine for patients with NSCLC, and provide potential molecular biomarkers for tailoring therapy.


Transcorporal artificial urinary sphincter cuff placement in cases requiring revision for erosion and urethral atrophy.
A distal cuff location is often required in patients undergoing artificial urinary sphincter reimplantation after previous erosion or in those requiring revision because of urethral atrophy at the original cuff site. Dissecting the urethra at a more distal site increases the risk of urethral injury and erosion, and often the urethral circumference is so small that a 4 cm. cuff is too large. We present a novel technique for distal cuff placement using transcorporal dissection that leaves corporal tunica albuginea on the dorsal surface of the urethra, allowing for its safer mobilization and adding to its bulk. We reviewed the charts of 31 men who underwent this technique and contacted 26 by telephone. The indications for distal transcorporal cuff placement varied. In 7 men with inadequate urethral coaptation with a 4 cm. proximal cuff at initial implantation a primary transcorporal tandem cuff was implanted distal. In 8 men persistent or recurrent incontinence despite a 4 cm. proximal cuff led to secondary distal reimplantation. Previous artificial urinary sphincter erosion and/or infection in 10 cases, previous urethral surgery at the optimal cuff site in 5 and radiation changes at the optimal cuff site in 1 led to selection of the more distal site and technique. Of the transcorporally placed cuffs 18 were 4 cm. and 13 were 4.5 cm. Preoperatively 5.2 pads were used daily. Of the 31 patients 27 were impotent preoperatively, 1 had normal erections, 1 had partial erections with the MUSE drug delivery system (Vivus, Inc., Menlo Park, California) and 2 had a previously placed penile prosthesis. At a mean followup of 17 months 26 of the 31 patients (84%) had occasional or no stress incontinence requiring 0 to 1 pad daily, 2 with pure urge incontinence used 1 to 2 pads daily and 3 had mixed incontinence requiring 0 to 3 pads daily. Of the 26 men surveyed 25 were very satisfied with the postoperative level of incontinence. Postoperatively erectile function deteriorated in 1 patient and was unchanged in the remainder. There was no erosion or infection of the transcorporally placed cuffs, although 3 were replaced for malfunction. This technique offers significant advantages in cases of revision. The technique protects the urethra from intraoperative dissection injury and decreases the risk of erosion because the urethra is buttressed at its vulnerable location. In addition, bulk is added to the urethra, allowing for better cuff sizing, which is usually a problem at this location where the urethra is small, thereby, improving continence in revised cases. Our success has recently led us to abandon tandem cuff placement altogether. There is a potential for deteriorating erectile function in potent men who undergo implantation in this fashion.


Testosterone levels in men with chronic obstructive pulmonary disease with or without glucocorticoid therapy.
Under the clinical impression that patients with chronic obstructive pulmonary disease (COPD) may demonstrate signs compatible with hypogonadism, we investigated whether oral glucocorticoid therapy is associated with testosterone deficiency. Thirty six men with COPD of whom 16 were receiving oral glucocorticoid medication (mean+/-SEM dose 9.4+/-1.1 mg prednisolone) were investigated in a cross-sectional cohort study. Patients with or without oral glucocorticoid therapy were not different in terms of age, smoking history and additional therapy. Vital capacity, forced expiratory volume in one second, airway resistance, intrathoracic gas volume and blood gases at rest were not different between the groups. However, patients receiving glucocorticoids had a shorter 6 min walking distance (mean+/-SEM 205+/-27 versus 288+/-26 m; p=0.02) compared to patients without oral steroid therapy. Serum levels of testosterone (mean+/-SEM 13.7+/-0.9) were below normal (<12 nM) in 15 of 36 patients. Serum testosterone did not correlate with any other evaluated parameter. Serum levels of free testosterone (free T) (mean+/-SEM 172.3+/-7.8 pM) were decreased in 25 of the 36 patients, including all patients receiving glucocorticoid treatment. In the 16 patients taking glucocorticoids free T was correlated (p=0.016) with the current glucocorticoid dosage (r=-0.504; p=0.007) and the body mass index (r=0.241; p=0.037). All other parameters examined revealed no significant correlations in multiple regression analysis. Glucocorticoid treatment appears to aggravate hypogonadism and a therapeutic study using testosterone in patients with chronic obstructive pulmonary disease receiving glucocorticoid medication appears warranted.


[Efficacy of azithromycin and its impact on cytokine system in urogenital infections].
Seventy five patients with urogenital chlamydial and mycoplasmic infections were enrolled in the trial. In the etiotropic therapy azithromycin was used in the standard dosage (1.0-1.5 g) depending on the infection. The treatment with azithromycin, in addition to the high eradication rates, was also evident of its effect on the cytokine levels in the patients, that was characteristic of a significant increase of the IFN-gamma level and a decrease of the IL-1beta and IL-6 levels in the blood.


Australia's 'fourth hurdle' drug review comparing costs and benefits holds lessons for the United States.
Two decades ago Australia introduced an assessment of value as a prerequisite for adding new medicines to its national drug formulary. Australia's program--a "fourth hurdle" process after a drug is assessed for safety, efficacy, and quality--stands in stark contrast to the situation in the United States, where comparing the clinical and economic value of a proposed new drug to those of existing ones only rarely plays a role in the drug coverage determination process. This article describes the role that Australia's Pharmaceutical Benefits Advisory Committee, a statutory independent expert committee, plays in determining which new drugs the government will help pay for in the nation's pharmaceutical benefit program. The program does not directly control drug prices or ration prescription drugs-policy options that are widely opposed in the United States. Australia's program supports patients' access to important, innovative medications deemed to be cost-effective. The US system could benefit if policy makers examined Australia's experience and adopted a comparative clinical and value review suited to the US political and economic landscape.


[Disappointing effectiveness of population screening for cervical cancer].
Systematical screening by cytological cervix examination has not reduced the mortality from cervical carcinoma as much as was expected. One important cause of this is the varying sensitivity of the screening owing to the large number of smears, most of which are normal. Some improvement of the effect of screening might be achieved by combination with computer-assisted microscopical evaluation and with testing for human papilloma virus (PV).


Association between metabolic syndrome, obesity, diabetes mellitus and oncological outcomes of bladder cancer: a systematic review.
Metabolic syndrome is a cluster of several metabolic abnormalities, its prevalence is increasing worldwide. To summarize the most recent evidence regarding the relationship between metabolic syndrome, its components and the oncological outcomes in bladder cancer patients, a National Center for Biotechnology Information PubMed search for relevant articles either published or e-published up to March 2014 was carried out by combining the following Patient population, Intervention, Comparison, Outcome terms: metabolic syndrome, obesity, body mass index, hyperglycemia, insulin resistance, diabetes, hypertension, dyslipidemia, bladder cancer, risk, mortality, cancer specific survival, disease recurrence and progression. Metabolic syndrome is a complex, highly prevalent disorder, and central obesity, insulin resistance, dyslipidemia and hypertension are its main components. Published findings would suggest that metabolic syndrome per se might be associated with an increased risk of bladder cancer in male patients, but it did not seem to confer a risk of worse prognosis. Considering the primary components of metabolic syndrome (hypertension, obesity and dyslipidemia), available data are uncertain, and it is no possible to reach a conclusion yet on either a direct or an indirect association with bladder cancer risk and prognosis. Only with regard to type 2 diabetes mellitus, available data would suggest a potential negative correlation. However, as the evaluation of bladder cancer risk and prognosis in patients with metabolic disorders is certainly complex, further studies are urgently required to better assess the actual role of these metabolic disorders.


Cardiovascular effects of the intracerebroventricular injection of adrenomedullin: roles of the peripheral vasopressin and central cholinergic systems.
Our objective was to investigate in conscious Sprague-Dawley (6-8 weeks, 250-300 g) female rats (N = 7 in each group) the effects of intracerebroventricularly (icv) injected adrenomedullin (ADM) on blood pressure and heart rate (HR), and to determine if ADM and calcitonin gene-related peptide (CGRP) receptors, peripheral V1 receptors or the central cholinergic system play roles in these cardiovascular effects. Blood pressure and HR were observed before and for 30 min following drug injections. The following results were obtained: 1) icv ADM (750 ng/10 µL) caused an increase in both blood pressure and HR (DMAP = 11.8 ± 2.3 mmHg and ΔHR = 39.7 ± 4.8 bpm). 2) Pretreatment with a CGRP receptor antagonist (CGRP8-37) and ADM receptor antagonist (ADM22-52) blocked the effect of central ADM on blood pressure and HR. 3) The nicotinic receptor antagonist mecamylamine (25 µg/10 µL, icv) and the muscarinic receptor antagonist atropine (5 µg/10 µL, icv) prevented the stimulating effect of ADM on blood pressure. The effect of ADM on HR was blocked only by atropine (5 µg/10 µL, icv). 4) The V1 receptor antagonist [β-mercapto-β-β-cyclopentamethylenepropionyl¹, O-me-Tyr²,Arg8]-vasopressin (V2255; 10 µg/kg), that was applied intravenously, prevented the effect of ADM on blood pressure and HR. This is the first study reporting the role of specific ADM and CGRP receptors, especially the role of nicotinic and muscarinic central cholinergic receptors and the role of peripheral V1 receptors in the increasing effects of icv ADM on blood pressure and HR.