Therapeutic prognosis of prostate cancer using surface-enhanced Raman scattering of patient urine and multivariate statistical analysis.
Surface-enhanced Raman scattering (SERS) is highly sensitive and label-free analytical technique based on Raman spectroscopy aided by field-multiplying plasmonic nanostructures. We report the use of SERS measurements of patient urine in conjunction with biostatistical algorithms to assess the treatment response of prostate cancer (PCa) in 12 recurrent (Re) and 63 nonrecurrent (NRe) patient cohorts. Multiple Raman spectra are collected from each urine sample using monodisperse silver nanoparticles (AgNPs) for Raman signal enhancement. Genetic algorithms-partial least squares-linear discriminant analysis (GA-PLS-LDA) was employed to analyze the Raman spectra. Comprehensive GA-PLS-LDA analyses of these Raman spectral features (p = 3.50 × 10-16 ) yield an accuracy of 86.6%, sensitivity of 86.0%, and specificity 87.1% in differentiating the Re and NRe cohorts. Our study suggests that SERS combined with multivariate GA-PLS-LDA algorithm can potentially be used to detect and monitor the risk of PCa relapse and to aid with decision-making for optimal intermediate secondary therapy to recurred patients.


A survey of the role of the dietitian in preparing patients for home enteral feeding.
Teaching home enteral feeding is a complex process involving many activities not traditionally performed by dietitians. This survey was undertaken to investigate (a) tasks performed by the dietitian in preparing patients to receive home enteral feeding, (b) the effect of various demographic factors on the dietitian's role, (c) the amount of dietitian time spent preparing a patient for discharge on home enteral feeding, and (d) the types of home enteral feedings currently in use. A questionnaire was tested for reliability and validity, then mailed to 1,168 nutrition support dietitians. Results of the survey indicated that, more often than nurses or physicians, dietitians were responsible for calculating nutrient and fluid needs, selecting formula, determining the home feeding schedule, teaching the patient to prepare blenderized formulas, and teaching the patient to recognize formula intolerance. Dietitians were less often responsible than nurses for psychomotor skills such as teaching the patient to administer the formula, operate the pump, and flush the feeding tube. Dietitians seemed to have a larger role in hospitals with more than 499 beds, in teaching hospitals, and in hospitals with a nutrition support team. Dietitians reported a smaller role when they reported to a contract foodservice company and when their job duties were divided so that more time was spent in clinical dietetics than in nutrition support. However, dietitians in all demographic groups performed all tasks. The average amount of dietitian time spent preparing patients for discharge on home enteral feeding was 168 minutes (2.8 hours) per patient. More patients received gastric feedings (76%) than intestinal feedings (22%).(ABSTRACT TRUNCATED AT 250 WORDS)


Partial expression of the viable motheaten (mev) mutation in the heterozygous state: abnormal levels of serum immunoglobulins and natural anti-ssDNA antibodies.
The 'viable motheaten' (mev) mutation in the C57BL/6 (B6) mouse causes a rapidly progressive and fatal autoimmune syndrome in mev-homozygous B6 mice, combined with generalized immunodeficiency, whereas the mev-heterozygous B6 mice look phenotypically normal. However, serological analyses of the levels of some spontaneously occurring, natural antibodies and of the levels and distribution of the different classes of immunoglobulins revealed mild but evident dysregulation of the natural humoral immunity of +/mev individuals.


Propafenone disposition in renal insufficiency and renal failure.
The pharmacokinetics of a single intravenous dose of propafenone were studied in subjects with normal renal function (n = 5), renal insufficiency (n = 5), and renal failure (n = 3). No difference in central volume of distribution, total ischemic clearance or terminal half-life existed. None of the pharmacokinetic parameters examined correlated to creatinine clearance. Within the confines of the small number of patients studied, there does not appear to be any effect of renal insufficiency or failure on single-dose propafenone disposition.


AANA Journal course. 5: Update for nurse anesthetists--essential hypertension, anesthesia, and the kidney.
Intraoperative systemic and renal hemodynamics are unpredictable in patients with essential hypertension due to their pharmacologic management, as well as the underlying disease process itself. The purpose of this review is to explore possible mechanisms mediating essential hypertension and describe the ramifications of various therapeutic interventions. Understanding the integrated relationship between blood pressure and the kidney will optimize intraoperative management of patients with essential hypertension.


Selenium Levels in the Whole Blood of Children and Teenagers from Two Riparian Communities at the Madeira River Basin in the Western Brazilian Amazon.
Selenium (Se) is an essential micronutrient that exerts multiple functions in the organism, and both its deficiency and excess can cause health impairments. Thus, it is important to monitor its levels in the population, especially in vulnerable groups, such as children from the Brazilian Amazon region, where there is a lack of information in this regard. The aim of this research was to study Se levels in the whole blood of children and teenagers (5-16 years old) from two riparian communities at the Madeira River (Cuniã RESEX and Belmont). Se level variations related to the communities' location, seasonality, diet, and body mass index (BMI) were assessed. Blood samples were collected in both communities for Se determinations, using ICP-MS and hemogram analyses, during May and September of 2011. Food frequency questionnaires were applied to assess consumption rates of specific food items. Non-parametric tests and linear multiple regressions were applied in the data analyses. Median Se levels were significantly higher during May (Cuniã RESEX 149 μg L-1; Belmont 85 μg L-1) compared to September (Cuniã RESEX 79 μg L-1; Belmont 53 μg L-1). No significant differences were found between the communities regarding BMI measurements and anemia prevalence. However, Se blood levels were significantly higher at the Cuniã RESEX compared to Belmont. In addition, the former showed higher fish and Brazil nut intakes, which may be the main Se sources for this community. These results contribute to a better understanding of Se reference levels for children and teenagers of Western Amazon riparian communities.


A mathematical model reveals the influence of population heterogeneity on herd immunity to SARS-CoV-2.
Despite various levels of preventive measures, in 2020, many countries have suffered severely from the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Using a model, we show that population heterogeneity can affect disease-induced immunity considerably because the proportion of infected individuals in groups with the highest contact rates is greater than that in groups with low contact rates. We estimate that if R 0 = 2.5 in an age-structured community with mixing rates fitted to social activity, then the disease-induced herd immunity level can be ~43%, which is substantially less than the classical herd immunity level of 60% obtained through homogeneous immunization of the population. Our estimates should be interpreted as an illustration of how population heterogeneity affects herd immunity rather than as an exact value or even a best estimate.


Effectiveness of Bazhengsan formula as an adjunctive therapy to ceftriaxone for female patients with uncomplicated gonorrhea: A pilot study.
This pilot study aimed to investigate the feasible effectiveness and safety of Bazhengsan formula (BZSF) as an adjunctive therapy to ceftriaxone for female patients with uncomplicated gonorrhea. This pilot randomized controlled trial compared BZSF as an adjunctive therapy to ceftriaxone with ceftriaxone alone for Chinese female patients with uncomplicated gonorrhea. A total of 40 eligible patients were randomly allocated to a treatment group (received BZSF and ceftriaxone) or a control group (received ceftriaxone alone). All patients in both groups were treated for a total of 10 days. The primary outcome included bacteriological cure. It was assessed by the eradication of urogenital gonorrhea at any site cultured after taken the study medications. The secondary outcome was clinical response. For the safety assessment, adverse events were recorded during the study period. After treatment, patients in both groups achieved promising effectiveness. However, no significant differences in bacteriological cure (P = .34), clinical response (P = .11), and safety were found between 2 groups. The findings of this study showed that BZSF as an adjunctive therapy to ceftriaxone may be not superior to the ceftriaxone alone for Chinese female patients with uncomplicated gonorrhea after 10 days treatment.


Post-infectious leukoencephalopathy as a complication of Mycoplasma pneumoniae infection.
We report a 9-year-old girl with leukoencephalopathy who demonstrated serologic evidence of a Mycoplasma pneumoniae infection. She had a mild upper respiratory tract illness 10 days prior to admission and developed walking difficulty and somnolence. The neurologic symptoms progressed to semicoma and spastic paraplegia over a few days but began to improve on the fourth day. Cranial computed tomography on the eleventh day revealed an area of diffuse low density in the white matter. Cerebrospinal fluid examination was normal. The patient recovered with minimal motor deficits. Cranial computed tomography was normal. She was diagnosed as having leukoencephalopathy complicated by a Mycoplasma pneumoniae infection. The pathogenesis of this infection is believed to be an allergic reaction to Mycoplasma pneumonia of the central nervous system as well as an acute disseminated encephalomyelitis.


Direct detection of nitric oxide in human blood serum by use of 1,3,5,7-tetramethyl-8-(3',4'-diaminophenyl)difluoroboradiaza-s-indacene with HPLC.
To study the relationship between amounts of nitric oxide (NO) in blood and the development of ischemic cardio-cerebrovascular diseases, trace NO in human blood serum has, for the first time, been determined by use of a 1,3,5,7-tetramethyl-8-(3',4'-diaminophenyl)difluoroboradiaza-s-indacene (TMDABODIPY)-based HPLC method. The proposed method is simple, rapid, and efficient, owing to its high sensitivity and good selectivity for NO. TMDABODIPY and its NO derivative are separated to baseline in 4 min, with simple separation conditions, on a C(18) column eluted with 50 mmol L(-1) ethanolamine in methanol. The derivative is detected by fluorescence at an emission wavelength of 507 nm with excitation at 498 nm. The response is a linear function of concentration in the range 0.8-800 nmol L(-1) NO. The detection limit can reach 2 x 10(-11) mol L(-1) (signal-to-noise ratio=3). The method has been used to detect NO in the serum of patients with five kinds of ischemic cardio-cerebrovascular disease and two diseases closely connected with ischemic cardio-cerebrovascular diseases. Recoveries of NO from spiked serum samples were between 96.58 and 105.71% and concentrations of NO observed in real samples were at 10(-7) mol L(-1) levels. Our studies indicate that the proposed TMDABODIPY-based HPLC technique can be developed into a sensitive and new method for clinical assay and pathology research.


NanoUPLC-MS(E) proteomic analysis of osteoclastogenesis downregulation by IL-4.
Bone resorption is an important factor in bone homeostasis and imbalance can cause several diseases. In osteoimmunology, IL-4 has been described as an important factor in promoting M2 macrophage profile. In order to shed some light on the effect of IL-4 on osteoclast precursors in the presence of RANKL, cytokines and nitric oxide (NO) production and the proteomic profile were analyzed. The presence of IL-4 in in vitro osteoclastogenesis provides production of TNF-α, IL-1α, IL-1β, IL-10 and IL-12 at basal cell levels. Regarding NO production, IL-4 was sufficient to increase the basal NO levels. Proteomic analyses identified 877 global proteins. IL-4 in in vitro RANKL-mediated osteoclastogenesis leads to the expression of 118 proteins. The presence of rIL-4 in in vitro rRANKL-mediated-osteoclastogenesis downregulated this process. However, the proteomics findings in the osteoclastogenesis demonstrated a much greater effect on osteoclast precursor cells than on RANKL-differentiated osteoclasts. These results suggest that the main effect of IL-4 in pre-osteoclast cells leads to a M2 macrophage activation, and this probably contributed to a reduction in osteoclastogenesis when both stimuli were used. This study noticed that IL-4 plays an important regulatory role in bone homeostasis due to its suppressive potential of precursor osteoclast cells.


Corneal topography of early keratoconus.
We used a corneal topography analysis system to evaluate nine eyes of seven patients in whom the diagnosis of keratoconus was suspected. There was no slit-lamp evidence of the condition. In seven of nine eyes a cone was identified. Large amounts of corneal distortion were seen in selected patients even though they had excellent spectacle-corrected visual acuity and little or no distortion of the keratometer mires. These findings suggest that corneal topography analysis systems are useful in the detection and description of corneal irregularity in the early stages of keratoconus. The radial keratotomy surgeon should be aware that normal results on slit-lamp examination and normal keratometry and refractive data do not rule out the presence of early keratoconus.


Mapping tidal channel dynamics in the Sundarbans, Bangladesh, between 1974 and 2017, and implications for the sustainability of the Sundarbans mangrove forest.
This study presents the spatial and temporal dynamics of tidal channels in the Bangladesh Sundarbans. Parts of the Passur River system were considered for this investigation. Tidal channel bank layers were extracted from aerial photographs from 1974 and 2011 and a Sentinel-2 image from 2017. On-screen digitizing of a tidal channel was undertaken to create the tidal channel layers, and special care was taken during digitization to obtain more accurate results. Layers were overlaid together so that the tidal channel position could be seen for each date. Tidal channel positions were highlighted to infer the erosion/accretion sectors along the channel, and the tidal channel dynamics were calculated. Remote sensing and Geographic Information System (GIS) platforms were used to analyse, interpret and visualize data on accretion and erosion, as well as the locations of the tidal channel bank over different years. The results revealed that erosion was severe in the larger channels, whereas accretion was dominant in the smaller channels. These erosion and accretion processes played an active role in the displacement of tidal channel banks during the period under investigation. Displacement of the tidal channel bank has had a profound impact on the Sundarbans mangrove ecosystem, and continued erosion and accretion processes are of concern for the future sustainability of biodiversity in the Sundarbans. While in the short term, these changes may not have much impact; over decades, the dynamics of tidal channels may significantly contribute to the imbalance of fauna and flora in the Sundarbans.


Do racial differences in knowledge about urogynecologic issues exist?
The objective of this study is to assess knowledge about urinary incontinence and pelvic organ prolapse in white versus nonwhite women. We hypothesize that there are racial differences in patient knowledge about these issues. One hundred twenty-six women presenting to our institution's gynecology clinic completed a two-scale, validated questionnaire assessing knowledge about incontinence and prolapse. Responses were compared for white versus nonwhite women using nonparametric statistical methods. Logistic regression was used to control for confounding variables. Mean score for white women exceeded that for nonwhite women for the incontinence (p = 0.019) but not the prolapse scale (p = 0.354). Of the white patients, 37.9% versus 19.1% of the nonwhite patients scored > or =80% on the incontinence scale (p = 0.019). This difference remained significant after controlling for potential confounders using logistic regression (p = 0.039). White women may have improved tested urinary incontinence knowledge as compared to nonwhite women.


[Use of buprenorphine as a cornerstone in narcosis and as analgesic in the postoperative period in gynecologic surgery].
In a clinical trial buprenorphine (0.3 mg i.v.) was administered, 20-45 minutes before the surgical operation, to 220 women undergoing gynecological surgery. If necessary buprenorphine (0.2-0.3 mg i.m.) was administered also in the post-operative period. By the pre-operatory administration of buprenorphine, a great stability of life parameters was observed during the surgical operation. In the post-operative period most of the patients showed absence of pain or mild pain.


Protrusion of bladder mucosa in exstrophy mimicking cloacal exstrophy.
An interesting case of bladder exstrophy with protrusion of bladder mucosa mimicking cloacal exstrophy is reported. The child presented with continuous leakage of urine and swelling in the lower abdomen since birth. Before the operation, this was considered to be a variant of cloacal exstrophy.


Methods for reliability and uncertainty assessment and for applicability evaluations of classification- and regression-based QSARs.
This article provides an overview of methods for reliability assessment of quantitative structure-activity relationship (QSAR) models in the context of regulatory acceptance of human health and environmental QSARs. Useful diagnostic tools and data analytical approaches are highlighted and exemplified. Particular emphasis is given to the question of how to define the applicability borders of a QSAR and how to estimate parameter and prediction uncertainty. The article ends with a discussion regarding QSAR acceptability criteria. This discussion contains a list of recommended acceptability criteria, and we give reference values for important QSAR performance statistics. Finally, we emphasize that rigorous and independent validation of QSARs is an essential step toward their regulatory acceptance and implementation.


Highly enantioselective synthesis of isoxazoline N-oxides.
The reaction of cinchonidine (cinchonine)-derived ammonium salts with nitroolefins in the presence of Cs2CO3 to afford optically active isoxazoline N-oxides with excellent ee and high de values has been developed.


Clinical approach to the hyperosmolar patient.
The successful evaluation and treatment of the hypertonic patient depends on a clear understanding of the differences between effective and noneffective solute and the consequences of changes in these solutes for water distribution. Measured osmolality, calculated osmolality, tonicity, and sodium concentration must be evaluated in the approach to these patients.


Microwave-assisted three-component domino reaction: Synthesis of indolodiazepinotriazoles.
A microwave-assisted three-component protocol involving N-1 alkylation of 2-alkynylindoles with epichlorohydrin, ring opening of the epoxide with sodium azide, and an intramolecular Huisgen azide-internal alkyne 1,3-dipolar cycloaddition domino sequence has been described. The efficacy of the methodology has been demonstrated by treating various 2-alkynylindoles (aromatic/aliphatic) with epichlorohydrin and sodium azide furnishing annulated tetracyclic indolodiazepinotriazoles in satisfactory yields.


Identification of a sialic acid containing glycocalyx on the surface of Schistosoma mansoni.
Ruthenium red fixation of adult Schistosoma mansoni revealed the existence of a negatively charged layer external to the outer bilayer, which was morphologically similar to the glycocalyx of other cell types. Regional and sexual differences were found in the extent and organisation of the surface coat, which can be correlated with interfacial free energy, adhesiveness and protection from immune effectors. Neuraminidase treatment confirmed the presence of surface sialic acid. Mechanical or skin penetrated schistosomula, maintained in vitro for 24 h were found not to have a glycocalyx and this may relate to their increased susceptibility to immune killing. Lung stage schistosomula however, did bind ruthenium red to their surface.


A fiber-optic redox sensor for the iron(III)-iron(II) transition.
A phenosafranine-containing Nafion film attached to the distal end of a fiber-optic probe forms a functional redox-sensitive optical sensor. The synthetic cationic photoactive dye phenosafranine, 3,7-diamino-5-phenylphenazinium chloride, responds with changes in light absorbance between its oxidized and reduced forms. This optical property persists when phenosafranine is sorbed into Nafion, a perfluorosulfonate anionic film. Optical properties of the sensor are similar to those seen by others in solution. At high redox conditions, such as an open nitrogen-purged aqueous pH 6.5 solution, optical absorbance of phenosafranine is high, while at low redox conditions, such as an aqueous pH 6.5 iron(II) solution, optical absorbance of phenosafranine is low. Titration of a closed pH 6.5 aqueous solution with a standard iron(II) solution lowers redox potential in a predictable manner and can be followed by the optical redox sensor in parallel with a commercial redox potential electrode.


Surprisingly small effect of antiviral treatment in patients with hepatitis C.
The effect and applicability of interferon-based antiviral therapies in the general population of persons with hepatitis C virus (HCV) infection are unknown. To determine the applicability and usefulness of anti-viral therapy in a metropolitan clinic population. Retrospective case series of consecutively referred patients. A teaching county hospital in Cleveland, Ohio. 327 patients referred to a liver clinic after a positive result for antibody against HCV on enzyme-linked immunosorbent assay (ELISA). Treatment rates; reasons for nontreatment. 34 patients had no detectable HCV RNA. Of the remaining 293 patients, 72% were not treated for the following reasons: 37% did not adhere to evaluation procedures, 34% had medical or psychiatric contraindications, 13% had ongoing substance or alcohol abuse, 11% preferred no treatment, and 5% had normal liver enzyme levels. Only 83 patients (28%) were treated; 13% had a sustained viral response. Most patients with HCV infection are not candidates for interferon-based therapies; alternative interventions should be sought for these patients.


DNA barcodes from four loci provide poor resolution of taxonomic groups in the genus Crataegus.
DNA barcodes can facilitate identification of organisms especially when morphological characters are limited or unobservable. To what extent this potential is realized in specific groups of plants remains to be determined. Libraries of barcode sequences from well-studied authoritatively identified plants represented by herbarium voucher specimens are needed in order for DNA barcodes to serve their intended purpose, where this is possible, and to understand the reasons behind their failure to do so, when this occurs. We evaluated four loci, widely regarded as universal DNA barcodes for plants, for their utility in hawthorn species identification. Three plastid regions, matK, rbcLa and psbA-trnH, and the internal transcribed spacer 2 (ITS2) of nuclear ribosomal DNA discriminate only some of the species of Crataegus that can be recognized on the basis of their morphology etc. This is, in part, because in Rosaceae tribe Maleae most individual plastid loci yield relatively little taxonomic resolution and, in part, because the effects of allopolyploidization have not been eliminated by concerted evolution of the ITS regions. Although individual plastid markers provided generally poor resolution of taxonomic groups in Crataegus, a few species were notable exceptions. In contrast, analyses of concatenated sequences of the 3 plastid barcode loci plus 11 additional plastid loci gave a well-resolved maternal phylogeny. In the ITS2 tree, different individuals of some species formed groups with taxonomically unrelated species. This is a sign of lineage sorting due to incomplete concerted evolution in ITS2. Incongruence between the ITS2 and plastid trees is best explained by hybridization between different lineages within the genus. In aggregate, limited between-species variation in plastid loci, hybridization and a lack of concerted evolution in ITS2 all combine to limit the utility of standard barcoding markers in Crataegus. These results have implications for authentication of hawthorn materials in natural health products.


Combined Bleaching Technique Versus At-home Bleaching-A Single-blind Randomized Controlled Trial.
To compare the efficacy, color stability, and tooth sensitivity (TS) of combined bleaching, using a modified protocol with at-home bleaching. Eighty participants were randomized into two groups. In the combined group, a desensitizing gel was applied (10 minutes) prior to in-office bleaching (35% hydrogen peroxide (H2O2), 2×15 minute applications) and at-home bleaching (4% H2O2, 2×30 minutes for 21 days) started the next day. In the at-home group, only the at-home bleaching was performed. Color was recorded at the beginning and postbleaching with two scales (VITA Classical and Bleachedguide) and Easyshade spectrophotometer. The TS was recorded daily with a 0-10 visual analogue scale (VAS) and five-point numeric rating scale (NRS). A 40% lower risk (RR=1.4; 95% CI 1.1-1.9) was observed in the at-home group. Higher color change and intensity of TS [mean difference 2.3 (95% CI 1.3-3.3) in the VAS] was observed in the first week for the combined group. After the end of the protocol, a bleaching degree was detected for both groups, with no significant difference between both groups (p>0.05). The combined group produced a slightly higher degree of color change than at-home bleaching but with a higher risk and intensity of TS.


Quantitative analysis of bioactive carbazole alkaloids in Murraya koenigii.
Carbazole alkaloids induce apoptosis in HL-60 cells through activation of the caspase-9/caspase-3 pathway and they are targeted as potential anticancer agents. Thus, the naturally occurring carbazole alkaloids become important as precursors for lead optimization in drug development. A method based on ultra performance liquid chromatography coupled with photodiode-array detection was developed using reverse phase isocratic elution with 85:15 acetonitrile and ammonium acetate buffer (5 mM). Seven samples of Murrya koenigii (L.) Spreng. from north-central India (Uttar Pradesh) were analyzed. All three targeted analytes, koenimbidine (mk1), koenimbine (mk2) and mahanimbine (mk3), were well separated within 4.0 min with linearity of the calibration curves (r2 > 0.999). The limits of detection and quantification of mk1, mk2 and mk3 were 0.7, 0.4, 0.04 μg/mL and 2.14, 1.21, 0.12 μg/mL, respectively. The natural abundance of mk1, mk2 and mk3 was 0.06-0.20, 0.04-0.69 and 0.13-0.42%, w/w, respectively, in the dried powdered leaves, whereas, the tissue specific distribution of carbazole alkaloids was observed in the order of predominance, mk1 leaf>root>fruit>stem, mk2 fruit>leaf >stem>root, and mk3 fruit>leaf>root>stem. The developed method was validated for limits of detection and quantification, repeatability, accuracy, precision and stability. This is the first report on the natural abundance of the major carbazole alkaloids in M. koenigii and the method developed can be used in HPLC/UPLC systems.


Labelling of the thymidine and deoxycytidine bases of DNA by [2-14C]deoxycytidine in cultured L1210 cells.
Exposure of cultured L1210 cells to [2-14C]deoxycytidine and analysis or radioactivity incorporated into DNA-pyrimidines revealed that 2.7--5.5-fold more radioactivity is incorporated into DNA-thymine than into cytosine bases. Thus the pathway involving deamination of deoxycytidylate to deoxyuridylate and methylation to thymidylate is highly favored over successive phosphorylation to dCTP. Several modified and endogenous pyrimidines altered the labelling of DNA-thymine and DNA-cytosine with [2-14C]deoxycytidine. 3-Deazauridine at 0.1 mM caused a 56% increase in the labelling of DNA-thymine. Both thymidine and 3-deazauridine (greater than or equal to 10 microM) increased the specific activity of DNA-cytosine by 4-fold. Cytosine arabinoside (ara-C) (greater than or equal to 10 microM) reduced the labelling of both DNA-cytosine and DNA-thymine. Excess cytidine (0.1 mM) reduced the labelling of DNA-cytosine by 40%. Tetrahydrouridine at concentrations up to 1 mM had no effect.


PRMT5 epigenetically regulates the E3 ubiquitin ligase ITCH to influence lipid accumulation during mycobacterial infection.
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), triggers enhanced accumulation of lipids to generate foamy macrophages (FMs). This process has been often attributed to the surge in the expression of lipid influx genes with a concomitant decrease in those involved in lipid efflux. Here, we define an Mtb-orchestrated modulation of the ubiquitination of lipid accumulation markers to enhance lipid accretion during infection. We find that Mtb infection represses the expression of the E3 ubiquitin ligase, ITCH, resulting in the sustenance of key lipid accrual molecules viz. ADRP and CD36, that are otherwise targeted by ITCH for proteasomal degradation. In line, overexpressing ITCH in Mtb-infected cells was found to suppress Mtb-induced lipid accumulation. Molecular analyses including loss-of-function and ChIP assays demonstrated a role for the concerted action of the transcription factor YY1 and the arginine methyl transferase PRMT5 in restricting the expression of Itch gene by conferring repressive symmetrical H4R3me2 marks on its promoter. Consequently, siRNA-mediated depletion of YY1 or PRMT5 rescued ITCH expression, thereby compromising the levels of Mtb-induced ADRP and CD36 and limiting FM formation during infection. Accumulation of lipids within the host has been implicated as a pro-mycobacterial process that aids in pathogen persistence and dormancy. In line, we found that perturbation of PRMT5 enzyme activity resulted in compromised lipid levels and reduced mycobacterial survival in mouse peritoneal macrophages (ex vivo) and in a therapeutic mouse model of TB infection (in vivo). These findings provide new insights into the role of PRMT5 and YY1 in augmenting mycobacterial pathogenesis. Thus, we posit that our observations could help design novel adjunct therapies and combinatorial drug regimen for effective anti-TB strategies.


In vitro susceptibility of recent Chlamydia trachomatis clinical isolates to the CtHtrA inhibitor JO146.
The present study aimed to establish if a previously identified Chlamydia trachomatis HtrA (CtHtrA) inhibitor, JO146, is effective against currently circulating clinical isolates to validate if CtHtrA is a clinically relevant target for future therapeutic development. Inhibition of CtHtrA during the middle of the chlamydial replicative cycle until the completion of the cycle resulted in loss of infectious progeny for six unique clinical isolates representing different serovars. This supports the potential for CtHtrA to be a clinically relevant target for development of new therapeutics and suggests the importance of further investigation of JO146 as a lead compound.


Analysis of the onset phase of olfactory bulb unit responses to odour pulses in the salamander.
1. A method for delivering odour pulses of controlled onset, steady plateau and abrupt termination, has been developed and applied to a single unit study of mitral cell responses in the olfactory bulb of the salamander. The pulses have been monitored during the experiments near the site of stimulation on the olfactory mucosa.2. Responses have been categorized as excitatory or suppressive based on the initial response to the odour pulse.3. Initially excitatory responses had sustained discharges near threshold. With increasing concentration, the discharge changed to a brief burst followed by suppression. The briefest latency of a unit response was 120 msec, using stimulation of medium concentration, after the start of the pulse; the majority of units appeared to be excited within 200-300 msec. Ramp stimuli gave increasing periods of excitation as the rise time of the odour front became less abrupt.4. Initially suppressive responses showed suppression at all levels of concentration. The majority of units appeared to have an onset of suppression about 300-400 msec after the start of the pulse.5. These basic responses, involving suppression or excitatory-suppressive sequences, can be correlated with some basic properties of the synaptic circuits in the olfactory bulb. The time courses of the initial responses appear to be within the time periods of the inhalation cycle of the salamander, and therefore may reflect mechanisms of processing of natural olfactory stimuli.


Alteration of patellofemoral contact during healing of canine patellar tendon after removal of its central third.
Alterations of the patellofemoral (PF) contact pressure and area were assessed using pressure-sensitive film after the removal of the central third of patellar tendon (PT) with healing over time in twelve dogs. The contralateral knee served as control. Histological sections were prepared for descriptive evaluation. No alterations in PT strain, PF contact pressure and area were measured immediately after the removal of the central third of PT compared with that before its removal. Compared with contralateral control, the healing of the donor PF induced a significantly increased PF contact area but not PF contact pressure in the specimens harvested at 6, 12, and 18 months after operation. Increased PF contact area indicated a proximal shift of the PF joint contact during flexion, which was associated with an increased strain of the healing PT under loading. The healing PT became hypertrophic compared with control, but the differences in the cross-sectional area were reduced over time. Histologically, a poorly organized extracellular matrix was observed at 6 months, with a progressive improvement in collagen fiber alignment up to 18 months postoperatively. The results of this study suggest that the removal of the central third of PT does not immediately change PF contact pressure and areas. However, remodeling of the healing tendon may cause an elongated PT, resulting in an increase in PF contact area under a given quadriceps force by knee extension.


Tumor hypoxia has independent predictor impact only in patients with node-negative cervix cancer.
This prospective clinical study was begun in 1994 to validate the independent prognostic impact of tumor hypoxia in patients with cervix cancer treated with definitive radiation therapy. Between May 1994 and January 1999, 106 eligible patients with epithelial cervix cancer had tumor oxygen pressure (PO(2)) measured using the Eppendorf probe. Oxygenation data are presented as the hypoxic proportion, defined as the percentage of PO(2) readings less than 5 mm/Hg (abbreviated as HP(5)) and the median PO(2). The median HP(5) in individual patients was 48%, and the median PO(2) was HP(5). Progression-free survival (PFS) for patients with hypoxic tumors (HP(5) > 50%) was 37% at 3 years versus 67% in those patients with better oxygenated tumors (P =.004). In multivariate analysis, only tumor size (risk ratio [RR], 1.33; P =.0003) and evidence of pelvic nodal metastases on imaging studies (RR, 2.52; P =.0065) were predictive of PFS. However, an interaction between nodal status and oxygenation was observed (P =.006), and further analysis indicated that HP(5) was an independent predictor of outcome in patients with negative nodes on imaging (P =.007). There was a significant increase in the 3-year cumulative incidence of distant metastases in the hypoxic group (41% v 15% in those with HP(5) < 50%; P =.0023), but not in pelvic relapse (37% v 27%; P =.12). Tumor hypoxia is an independent predictor of poor PFS only in patients with node-negative cervix cancer, in addition to tumor size. Its impact appears to be related to an increased risk of distant metastases rather than to an effect on pelvic control.


Early number word learning: Associations with domain-general and domain-specific quantitative abilities.
Cardinal number knowledge-understanding "two" refers to sets of two entities-is a critical piece of knowledge that predicts later mathematics achievement. Recent studies have shown that domain-general and domain-specific skills can influence children's cardinal number learning. However, there has not yet been research investigating the influence of domain-specific quantifier knowledge on children's cardinal number learning. The present study aimed to investigate the influence of domain-general and domain-specific skills on Mandarin Chinese-speaking children's cardinal number learning after controlling for a number of family background factors. Particular interest was paid to the question whether domain-specific quantifier knowledge was associated with cardinal number development. Specifically, we investigated 2-5-year-old Mandarin Chinese-speaking children's understanding of cardinal number words as well as their general language, intelligence, approximate number system (ANS) acuity, and knowledge of quantifiers. Children's age, gender, parental education, and family income were also assessed and used as covariates. We found that domain-general abilities, including general language and intelligence, did not account for significant additional variance of cardinal number knowledge after controlling for the aforementioned covariates. We also found that domain-specific quantifier knowledge did not account for significant additional variance of cardinal number knowledge, whereas domain-specific ANS acuity accounted for significant additional variance of cardinal number knowledge, after controlling for the aforementioned covariates. In sum, the results suggest that domain-specific numerical skills seem to be more important for children's development of cardinal number words than the more proximal domain-general abilities such as language abilities and intelligence. The results also highlight the significance of ANS acuity on children's cardinal number word development.


Selective pancreatic toxicity of palmitoylpentachlorophenol.
Palmitoylpentachlorophenol (PPCP), which is a lipid conjugate of a xenobiotic compound, has been found in human fat. To study the toxicity associated with PPCP, rats were given 100 mg/kg PPCP and sacrificed at 4, 8 and 12 days. The target organ identified was the exocrine pancreas; no other major organs examined showed any gross or histopathological abnormality. At 4 and 8 days after treatment, focal, spotty vacuolation, and loss of pancreatic acini was observed. Acute inflammatory infiltrate was also observed in parenchyma at all time points and the loss of acinar tissue was resolved through fibrous tissue formation by 12 days. The present study indicates that PPCP has a specific target organ toxicity.


Trophoblast cells of ruminant placentas--A minireview.
The ruminant placenta is classified as cotyledonary and synepitheliochorial on the basis of its gross anatomical features and histological characteristics, respectively. The richly vascularized embryonic chorioallantois is lined on its external surface by cells of the trophectodermal epithelium. These cells which assume specialized functions are referred to as trophoblast cells. Two morphologically and functionally distinct cell types have been recognized in the trophectoderm of the placenta of ruminant animals. These are the mononucleate trophoblast cells and the binucleate trophoblast cells. The occurrence, morphological characteristics, and specialized functions of these trophoblast cells, in relation to conceptus nutrition and survival in utero are discussed in this review.


Active commuting to school among adolescents in Ho Chi Minh City, Vietnam: change and predictors in a longitudinal study, 2004 to 2009.
Active commuting (walking or cycling) to/from school is an important part of the overall physical activity levels of children but is on the decline in many countries. Data for adolescents on mode of transportation to and from school are limited for low- and middle-income countries, including Vietnam. This paper aims to describe the changes in the prevalence of active commuting to and from school, and to examine prospectively the predictors of active commuting, among adolescents from Ho Chi Minh City (HCMC). The data are from a 5-year cohort study from 2004 of a representative sample of 759 adolescents from 18 schools in HCMC. Data were obtained at five annual assessments using validated questionnaires to capture commuting behaviors, socioeconomic and demographic factors, individual and family characteristics, and physical and social environmental factors. Height and weight were measured by trained staff using standardized guidelines. Generalized linear latent and mixed models with a hierarchic approach were used to analyze the data in 2011. The results show a remarkable decrease in the prevalence of active commuting in adolescents from 27.8% in 2004 to 19.6% in 2009. Male students, from the least-wealthy families, living in suburban areas, close to school, studying at schools in less-wealthy districts, were more likely to actively commute. In the context of an epidemic of childhood and adolescent obesity in urban Vietnam, the decline in active commuting over the 5 years of this study highlights the need for development of urban physical environments favorable for active commuting and education campaigns to promote active commuting in adolescents.


Precision medicine in public health in India: Nascent but poised in the right direction.
Precision medicine (PM) in public health offers a new paradigm. Over a past few decades, there has been very rapid development in science and technology, especially in medical-clinical research to enhance the likelihood of preventive treatment which is personalized to an individual. This combined with digital health and accessibility of environmental and behavioral data offers a unique opportunity for specific prevention advice to individuals and thus to population at large. Indian with its 1.3 billion population and its ethnic diversity with high burden of disease offers a unique opportunity for the role of PM in public health. The article further explores the status and way forward for PM in India.


Immunolocalization of sex hormone-binding globulin (SHBG) in human ovarian follicles and corpus luteum.
Sex hormone-binding globulin (SHBG), a hepatic carrier protein for sex steroids is expressed in different steroid-sensitive tissues, including Sertoli cells of the testis. It has been suggested that this protein may be one of the local regulators of spermatogenesis. The expression of SHBG in the ovary is currently unknown. We have previously demonstrated the synthesis of SHBG in granulosa-lutein cells from patients undergoing in vitro fertilization. In this study, the presence of SHBG in human ovarian follicles and corpora lutea is investigated, using immunohistochemistry on adult and fetal ovarian tissue sections. SHBG is localized in the whole granulosa layer at all stages of folliculogenesis, whereas, only isolated theca cells are immunostained. In primordial and primary follicles, the oocyte cytoplasm shows an intense immunostaining, which disappears after the secondary stage. In the microenvironment of the mature oocytes, SHBG is present in the surrounding cumulus cells, the perivitelline space, and nearby the oolemma. In the corpus luteum, SHBG is localized in large luteal cells, whereas, small luteal cells do not show any significant staining. By analogy with the testis, these results raise the question of an involvement of SHBG in the regulation of follicular maturation as well as in luteal function.


A butterfly eye's view of birds.
The striking color patterns of butterflies and birds have long interested biologists. But how these animals see color is less well understood. Opsins are the protein components of the visual pigments of the eye. Color vision has evolved in butterflies through opsin gene duplications, through positive selection at individual opsin loci, and by the use of filtering pigments. By contrast, birds have retained the same opsin complement present in early-jawed vertebrates, and their visual system has diversified primarily through tuning of the short-wavelength-sensitive photoreceptors, rather than by opsin duplication or the use of filtering elements. Butterflies and birds have evolved photoreceptors that might use some of the same amino acid sites for generating similar spectral phenotypes across approximately 540 million years of evolution, when rhabdomeric and ciliary-type opsins radiated during the early Cambrian period. Considering the similarities between the two taxa, it is surprising that the eyes of birds are not more diverse. Additional taxonomic sampling of birds may help clarify this mystery.


The vaginal metabolome and microbiota of cervical HPV-positive and HPV-negative women: a cross-sectional analysis.
Characterise the vaginal metabolome of cervical HPV-infected and uninfected women. Cross-sectional. The Center for Health Behavior Research at the University of Maryland School of Public Health. Thirty-nine participants, 13 categorised as HPV-negative and 26 as HPV-positive (any genotype; HPV+ ), 14 of whom were positive with at least one high-risk HPV strain (hrHPV). Self-collected mid-vaginal swabs were profiled for bacterial composition by 16S rRNA gene amplicon sequencing, metabolites by both gas and liquid chromatography mass spectrometry, and 37 types of HPV DNA. Metabolite abundances. Vaginal microbiota clustered into Community State Type (CST) I (Lactobacillus crispatus-dominated), CST III (Lactobacillus iners-dominated), and CST IV (low-Lactobacillus, 'molecular-BV'). HPV+ women had higher biogenic amine and phospholipid concentrations compared with HPV- women after adjustment for CST and cigarette smoking. Metabolomic profiles of HPV+ and HPV- women differed in strata of CST. In CST III, there were higher concentrations of biogenic amines and glycogen-related metabolites in HPV+ women than in HPV- women. In CST IV, there were lower concentrations of glutathione, glycogen, and phospholipid-related metabolites in HPV+ participants than in HPV- participants. Across all CSTs, women with hrHPV strains had lower concentrations of amino acids, lipids, and peptides compared with women who had only low-risk HPV (lrHPV). The vaginal metabolome of HPV+ women differed from HPV- women in terms of several metabolites, including biogenic amines, glutathione, and lipid-related metabolites. If the temporal relation between increased levels of reduced glutathione and oxidised glutathione and HPV incidence/persistence is confirmed in future studies, anti-oxidant therapies may be considered as a non-surgical HPV control intervention. Metabolomics study: Vaginal microenvironment of HPV+ women may be informative for non-surgical interventions.


Myelin basic protein and myelin-associated glycoprotein in chronic, relapsing experimental allergic encephalomyelitis.
One-micron plastic sections of spinal cords from SJL/J mice with chronic relapsing experimental allergic encephalomyelitis (EAE) were reacted immunocytochemically with antiserum to myelin basic protein and myelin-associated glycoprotein. The distribution of myelin basic protein and myelin-associated glycoprotein in myelin sheaths was compared in acute and chronic areas of demyelination. No difference in the size of the lesion was seen with the two antisera. Myelin-associated glycoprotein was seen periaxonally in both normal myelin sheaths and sheaths which showed extensive splitting and ballooning as seen with toluidine blue stain and myelin basic protein antiserum. At least at the level of the light microscope, myelin basic protein antiserum gave intense staining of myelin while antiserum to myelin-associated glycoprotein showed little or no affinity to stain the myelin sheath itself, in contrast to other recent electron microscope observations. A few myelin basic protein or myelin-associated glycoprotein-containing oligodendrocytes were seen in lesion areas and remyelination by oligodendrocytes was rare. These observations are in agreement with findings from other models of EAE and multiple sclerosis where a primary loss of myelin has been implicated.


My Fight or Yours: Stereotypes of Activists From Advantaged and Disadvantaged Groups.
In social movements, activists may belong to either the disadvantaged or the advantaged group (e.g., Black racial justice activists or White racial justice activists). Across three experimental survey studies, we examined the content of these stereotypes by asking participants to freely generate a list of characteristics to describe each target group-a classic paradigm in stereotype research. Specifically, we examined the stereotypes applied to Black and White activists within racial justice movements (Study 1, n = 154), female and male activists within feminist movements (Study 2, n =134), and LBGT and straight activists within Lesbian, Gay, Bisexual, and Transgender movements (Study 3, n =156). We found that the "activist" category was consistently differentiated into subcategories based on group status: Disadvantaged group activists were stereotyped as strong and aggressive, whereas advantaged group activists were stereotyped as altruistic and superficial. These findings underscore the importance of considering status differences to understand the social perception of activists.


Computer-aided quantification of non-contrast 3D black blood MRI as an efficient alternative to reference standard manual CT angiography measurements of abdominal aortic aneurysms.
Non-contrast 3D black blood MRI is a promising tool for abdominal aortic aneurysm (AAA) surveillance, permitting accurate aneurysm diameter measurements needed for patient management. To evaluate whether automated AAA volume and diameter measurements obtained from computer-aided segmentation of non-contrast 3D black blood MRI are accurate, and whether they can supplant reference standard manual measurements from contrast-enhanced CT angiography (CTA). Thirty AAA patients (mean age, 71.9 ± 7.9 years) were recruited between 2014 and 2017. Participants underwent both non-contrast black blood MRI and CTA within 3 months of each other. Semi-automatic (computer-aided) MRI and CTA segmentations utilizing deformable registration methods were compared against manual segmentations of the same modality using the Dice similarity coefficient (DSC). AAA lumen and total aneurysm volumes and AAA maximum diameter, quantified automatically from these segmentations, were compared against manual measurements using Pearson correlation and Bland-Altman analyses. Finally, automated measurements from non-contrast 3D black blood MRI were evaluated against manual CTA measurements using the Wilcoxon test, Pearson correlation and Bland-Altman analyses. Semi-automatic segmentations had excellent agreement with manual segmentations (lumen DSC: 0.91 ± 0.03 and 0.94 ± 0.03; total aneurysm DSC: 0.92 ± 0.02 and 0.94 ± 0.03, for black blood MRI and CTA, respectively). Automated volume and maximum diameter measurements also had excellent correlation to their manual counterparts for both black blood MRI (volume: r = 0.99, P < 0.001; diameter: r = 0.97, P < 0.001) and CTA (volume: r = 0.99, P < 0.001; diameter: r = 0.97, P < 0.001). Compared to manual CTA measurements, bias and limits of agreement (LOA) for automated MRI measurements (lumen volume: 1.49, [-4.19 7.17] cm3; outer wall volume: -2.46, [-14.05 9.13] cm3; maximal diameter: 0.08, [-6.51 6.67] mm) were largely equivalent to those of manual MRI measurements, particularly for maximum AAA diameter (lumen volume: 0.73, [-6.47 7.93] cm3; outer wall volume: 0.98, [-10.54 12.5] cm3; maximal diameter: 0.08, [-3.67 3.83] mm). Semi-automatic segmentation of non-contrast 3D black blood MRI efficiently provides reproducible morphologic AAA assessment yielding accurate AAA diameters and volumes with no clinically relevant differences compared to either automatic or manual measurements based on CTA.


Electrospun nanofibers for the fabrication of engineered vascular grafts.
Attention has recently increased in the application of electrospun fibers because of their putative capability to create nanoscale platforms toward tissue engineering. To some extent, electrospun fibers are applicable to the extracellular matrix by providing a three-dimensional microenvironment in which cells could easily acquire definite functional shape and maintain the cell-to-cell connection. It is noteworthy to declare that placement in different electrospun substrates with appropriate physicochemical properties enables cells to promote their bioactivities, dynamics growth and differentiation, leading to suitable restorative effects. This review paper aims to highlight the application of biomaterials in engineered vascular grafts by using electrospun nanofibers to promote angiogenesis and neovascularization.


[Co-carcinogens or modulators of carcinogenesis. New aspects of the etiology of human tumors and of the molecular mechanisms of carcinogenesis].
Within the last 10 years numerous new and typical exogenous cocarcinogens were identified chemically as well as biologically and characterized biochemically as initiation or tumor promoters. They are highly irritant diterpene esters of plant origin. Promoters of this type were recently detected also in the Euphorbiacea Croton flavens L., the multiple use of which for stimulants according to local habits was previously held responsible for the unusually high rate of esophageal cancer on Curacao. This detection confirms for the first time that in the etiology of human cancer besides solitary carcinogens (first-order carcinogenic risk factors) also cocarcinogens of the promoter type have to be considered (second-order carcinogenic risk factors). -- The active principles of the diterpene ester type are the strongest promoters known so far; they are noninitiators and nonmutagens. Of the manyfold biochemical activities of these promoters the three most actual are: the TPA molecule does not require activation by metabolic alteration, it releases very rapidly prostaglandin E2 from cellular membranes and it activates latent DNA-viral genoms.


Ellagic acid derivatives from Rubus ulmifolius inhibit Staphylococcus aureus biofilm formation and improve response to antibiotics.
Biofilms contribute to the pathogenesis of many forms of Staphylococcus aureus infection. Treatment of these infections is complicated by intrinsic resistance to conventional antibiotics, thus creating an urgent need for strategies that can be used for the prevention and treatment of biofilm-associated infections. This study demonstrates that a botanical natural product composition (220D-F2) rich in ellagic acid and its derivatives can limit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility. The source of this composition is Rubus ulmifolius Schott. (Rosaceae), a plant used in complementary and alternative medicine in southern Italy for the treatment of skin and soft tissue infections. All S. aureus clonal lineages tested exhibited a reduced capacity to form a biofilm at 220D-F2 concentrations ranging from 50-200 µg/mL, which were well below the concentrations required to limit bacterial growth (530-1040 µg/mL). This limitation was therapeutically relevant in that inclusion of 220D-F2 resulted in enhanced susceptibility to the functionally-distinct antibiotics daptomycin, clindamycin and oxacillin. Testing with kidney and liver cell lines also demonstrated a lack of host cell cytotoxicity at concentrations of 220D-F2 required to achieve these effects. These results demonstrate that extract 220D-F2 from the root of Rubus ulmifolius can be used to inhibit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility without toxic effects on normal mammalian cells. Hence, 220D-F2 is a strong candidate for development as a botanical drug for use in the prevention and treatment of S. aureus biofilm-associated infections.


Prognostic value of silent myocardial infarction in patients with chronic kidney disease after kidney transplantation.
We have shown that silent myocardial infarction (SMI) on 12-lead ECG is associated with increased cardiovascular disease (CVD) risk in patients awaiting renal transplantation (RT). In this study, we evaluated the prevalence of SMI in patients undergoing RT and their prognostic value after RT. MI was determined by automated analysis of ECG. SMI was defined as ECG evidence of MI without a history of clinical MI (CMI). The primary outcome was a composite of CVD death, non-fatal MI and coronary revascularization after RT. Of the 1189 patients who underwent RT, a 12-lead ECG was available in >99%. Of the entire cohort 6% had a history of CMI while 7% had SMI by ECG. During a median follow-up of 4.6 years, 147 (12%) experienced the primary outcome (8% CVD death, 4% MI, 4% coronary revascularization) and 12% died. Both SMI and CMI were associated with an increased risk of CVD events and all-cause deaths. In a multivariable adjusted Cox-regression model, both SMI (adjusted hazard ratio 2.03 [1.25-3.30], p = .004) and CMI (2.15 [1.24-3.74], p = .007) were independently associated with the primary outcome. SMI detected by ECG prior to RT is associated with increased risk of CVD events after RT.


Connexin expression patterns in arrhythmogenic right ventricular cardiomyopathy.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inheritable myocardial disease accounting for ventricular tachycardia and sudden death in the young and arising from areas of fibrofatty replacement of predominantly right ventricular myocardium. That some patients manifest life-threatening ventricular tachycardia in the absence of substantial myocardial replacement suggests that gap junction remodeling might be acting synergistically to ventricular remodeling to promote arrhythmogenesis. Hence, we sought to verify gap junction composition and distribution by analyzing the expression and occurrence of specific gap junction proteins (connexins [Cxs]) in patients with ARVC. Right ventricular endomyocardial biopsy specimens were taken from 16 patients with definite ARVC (age 48 ± 16 years) and analyzed for Cx40, Cx43, and Cx45 messenger ribonucleic acid expression (relative to glyceraldehyde-3-phosphate-dehydrogenase messenger ribonucleic acid expression). The results were compared to those obtained from nondiseased donor hearts (n = 6; age 32 ± 11 years). The patients with ARVC showed a significant reduction in the messenger ribonucleic acid expression of Cx40 (p <0.0001) and Cx45 (p <0.0001) compared to that of the controls. The expression of Cx43 was similar in patients with ARVC and controls (p = 0.098). Mutations in plakophilin-2 were identified in 7 of 16 patients (25%). The Cx expression levels were comparable between the mutation carriers and noncarriers (p = NS). In conclusion, ARVC features alterations in the expression of Cxs and their distribution at cardiac intercalated discs. Apart from the deposition of extracellular matrix, the potential loss of gap junctions and shift in the composition of gap junctional Cxs in the ventricular conduction system might further contribute to the development of ventricular arrhythmias in patients with ARVC.


Intratesticular injection of a zinc-based solution for contraception of domestic cats: a randomized clinical trial of efficacy and safety.
It has been reported that a commercial zinc gluconate preparation disrupts spermatogenesis and apparently causes permanent sterilization in male dogs, but there is little information regarding similar approaches in the male cat. The objective of this study was to evaluate zinc gluconate as a permanent contraceptive for domestic male cats. Sixteen sexually mature mixed breed cats were allocated at random, by replicate, into two groups and given a single injection into each testis of either isotonic saline or zinc gluconate, respectively. Clinical and reproductive parameters were assessed immediately before injection and after 60 and 120 days. On day 120 the testis size of treated cats was decreased (P<0.05). Azoospermia occurred in 8/11 (73%) cats, and penile spines were decreased in 6/11 (55%) and absent in 4/11 (36%) cats, and there were substantial reductions in male behavior. However, plasma testosterone concentrations (single samples collected at each assessment) were not significantly different between treated and control cats at any time point. Although additional studies are warranted, intratesticular injection of zinc gluconate might have potential as a permanent contraceptive for cats.


Extraction of 3D quantitative maps using EDS-STEM tomography and HAADF-EDS bimodal tomography.
Electron tomography has been widely applied to three-dimensional (3D) morphology characterization and chemical analysis at the nanoscale. A HAADF-EDS bimodal tomographic (HEBT) reconstruction technique has been developed to extract high resolution element-specific information. However, the reconstructed elemental maps cannot be directly converted to quantitative compositional information. In this work, we propose a quantification approach for obtaining elemental weight fraction maps from the HEBT reconstruction technique using the physical parameters extracted from a Monte Carlo code, MC X-ray. A similar quantification approach is proposed for the EDS-STEM tomographic reconstruction. The performance of the two quantitative reconstruction methods, using the simultaneous iterative reconstruction technique, are evaluated and compared for a simulated dataset of a two-dimensional phantom sample. The effects of the reconstruction parameters including the number of iterations and the weight of the HAADF signal are discussed. Finally, the two approaches are applied to an experimental dataset to show the 3D structure and quantitative elemental maps of a particle of flux melted metal-organic framework glass.


Cell-Free Synthesis and Electrophysiological Analysis of Multipass Voltage-Gated Ion Channels Tethered in Microsomal Membranes.
Cell-free protein synthesis (CFPS) has emerged as a powerful tool for the rapid synthesis and analysis of various structurally and functionally distinct proteins. These include 'difficult-to-express' membrane proteins such as large multipass ion channel receptors. Owing to their membrane localization, eukaryotic CFPS supplemented with endoplasmic reticulum (ER)-derived microsomal vesicles has proven to be an efficient system for the synthesis of functional membrane proteins. Here we demonstrate the applicability of the eukaryotic cell-free systems based on lysates from the mammalian Chinese Hamster Ovary (CHO) and insect Spodoptera frugiperda (Sf21) cells. We demonstrate the efficiency of the systems in the de novo cell-free synthesis of the human cardiac ion channels: ether-a-go-go potassium channel (hERG) KV11.1 and the voltage-gated sodium channel hNaV1.5.


A rapid Percoll gradient procedure for preparation of synaptosomes.
Homogenization of fresh brain tissue in isotonic medium shears plasma membranes causing nerve terminals to become separated from their axons and postsynaptic connections. The nerve terminal membranes then reseal to form synaptosomes. The discontinuous Percoll gradient procedure described here is designed to isolate synaptosomes from brain homogenates in the minimum time to allow functional experiments to be performed. Synaptosomes are isolated using a medium-speed centrifuge, while maintaining isotonic conditions and minimizing mechanically damaging resuspension steps. This protocol has advantages over other procedures in terms of speed and by producing relatively homogeneous synaptosomes, minimizing the presence of synaptic and glial plasma membranes and extrasynaptosomal mitochondria. The purified synaptosomes are viable and take up and release neurotransmitters very efficiently. A typical yield of synaptosomes is between 2.5 and 4 mg of synaptosomal protein per gram rat brain. The procedure takes approximately 1 h from homogenization of the brain until collection of the synaptosomal suspension from the Percoll gradient.


Intraocular hemorrhages: a hemostatic therapeutic approach.
Our knowledge of the local hemostatic factors capable of playing a role in certain intraocular hemorrhages is reviewed as a background to therapy with agents active in hemostasis. Common to hyphemas and subretinal hemorrhages are some conditions which are apt to disturb hemostasis and result in recurrent bleeding. They are: 1) Dilution of blood by aqueous humor or subretinal exudative fluid followed by the formation of hemostatic plugs which are prone to spontaneous lysis; 2) Contiguity of certain structures, such as the iris and the choroid, which are extremely rich in fibrinolytic activators favoring premature dissolution of the hemostatic plug and thereby recurrent bleeding; and 3) Presumptive high local concentration of fibrin degradation products (FDP), which have an anticoagulant action and would counteract hemostasis in the event of rebleeding. Based on these observations, the use of fibrinolytic inhibitors for the treatment of hyphema and subretinal hemorrhages seems warranted. Hemostatic mechanisms in intraocular hemorrhages and their treatment with various agents are discussed.


Nanoparticle assisted magnetic resonance imaging of the early reversible stages of amyloid beta self-assembly.
Co@Pt-Au nanoparticles, which have enhanced magnetism and high stability in aqueous media, are utilized in conjunction with MRI to monitor the structural evolution of Abeta assemblies, especially Abeta protofibrils in the early reversible stages.


[The EU's Precarious Old Normal and the Need for Reform].
The EU has been in crisis mode since 2008. The old normality is the big political goal, but a return to the status quo ante is not really desirable. Unfortunately, European politics has no concept for the future of the Union after the COVID-19 pandemic. This could prove to be an existential problem for the Union in its current form. The article analyses the inner context of the various crises since 2008, points out possibilities for reforming the Union's architecture in the central fields of fiscal and monetary policy and warns against further crises and the marginalisation of the Union on a global scale.


Buprenorphine treatment in an urban community health center: what to expect.
Despite new opportunities to expand buprenorphine treatment for opioid dependence, use of this treatment modality has been limited. Physicians may question their ability to successfully treat opioid-dependent patients with buprenorphine in a primary care setting. We describe a buprenorphine treatment program and treatment outcomes in an urban community health center. We conducted retrospective chart reviews on the first 41 opioid-dependent patients treated with buprenorphine/naloxone. The primary outcome was 90-day retention in treatment. Patients' mean age was 46 years, 70.7% were male, 58.8% Hispanic, 31.7% black, 57.5% unemployed, and 70.0% used heroin prior to treatment. Twenty-nine (70.7%) patients were retained in treatment at day 90. Compared to those not retained, patients retained in treatment were more likely to have used street methadone (0% versus 37.9%) and less likely to have used opioid analgesics (54.6% versus 20.7%) and alcohol (50.0% versus 13.8%) prior to treatment. Of the 25 patients with urine toxicology tests, 24% tested positive for opioids. Buprenorphine treatment for opioid dependence in an urban community health center resulted in a 90-day retention rate of 70.7%. Type of substance use prior to treatment appeared to be associated with retention. These findings can help guide program development.


Role of incentives in the training of the frontal EMG relaxation response.
Male college students were assigned to a feedback condition in which an auditory signal was correlated with forehead electromyographic (EMG) responses or to a control condition in which a constant low tone was provided. Within each condition, half of the subjects were provided with an incentive for successful reductions of EMG levels from session to session. In the control condition incentives were actually given on the basis of performance of yoked feedback partners. The remaining subjects in each condition (no incentive) were instructed that the incentive was available for reliable participation in the experiment. Feedback subjects acquired lower EMG levels than control subjects, and the yoked-incentive subjects acquired lower levels than no-incentive subjects in the control condition. There were no major differences in EMG levels attributable to locus of control orientation. The results are discussed mainly in terms of implications of incentive variables for reinforcement analyses of biofeedback effects and the validity of the locus of control construct in this application.


Outpatient consolidation chemotherapy with intermediate dose cytarabine has similar survival and relapses rates in acute myeloid leukemia as compared to high dose cytarabine: A single center analysis.
The last decade has seen advances in delivering outpatient consolidation therapy for acute myeloid leukemia (AML). The standard of care involves high-dose cytarabine or intermediate-dose cytarabine, given twice daily for three alternating days. At the London Regional Cancer Program, we have transitioned the administration of outpatient cytarabine to a once-daily regimen over six consecutive days. The outcomes of a longer duration interval of high-dose cytarabine and intermediate-dose cytarabine is currently unknown. This study aims to assess the feasibility of administering a continuous 6-day protocol of high-dose (HDAC-16) and intermediate-dose cytarabine (IDAC-16) consolidation therapy in the outpatient setting. This is a retrospective chart review to analyze AML patients treated with outpatient high-dose or intermediate-dose cytarabine consolidation therapy at the London Regional Cancer Program from January 1, 2019, through November 1, 2022. The primary objective was to determine the outcomes of the 6-day outpatient administration of once daily high-dose cytarabine or intermediate-dose cytarabine. Forty-five patients received 89 cycles of cytarabine as outpatients; males were 55.6% of the total population, with a median age of ~57 years. Our overall 2-year survival of HDAC-16 (57.1%) and IDAC-16 (83.3%) is consistent with the reported literature. There was no difference in delays, relapse rates, and nonrelapse mortality between both HDAC and IDAC groups. The 2-year relapse free survival was 57.1% for HDAC-16 and 66.7% for IDAC-16. Outpatient administration of intermediate-dose cytarabine once daily over six consecutive days results in similar overall survival and relapse rates as compared to high dose cytarabine consolidation chemotherapy. Moving to a once daily administration schedule can alleviate logistical and/or accessibility hurdles for outpatient oncology clinics. Prospective randomized trials are needed in this setting to validate our results.


Integration of nutrigenomics, melatonin, serotonin and inflammatory cytokines in the pathophysiology of pregnancy-specific urinary incontinence in women with gestational diabetes mellitus.
Gestational diabetes mellitus is an important public health problem and has been associated with the development of pregnancy-specific urinary incontinence. The interaction is related to hyperglycemia, and inflammatory and hormonal patterns, which favor functional alterations in different organs and systems. Several genes associated with human diseases have been identified and partially characterized. Most of these genes are known to cause monogenic diseases. However, about 3 % of diseases do not fit the monogenic theory due to the complex interactions between multiple genes and environmental factors, as in chronic metabolic diseases such as diabetes. The nutritional, immunological, and hormonal patterns associated with changes in maternal metabolism may influence and contribute to greater susceptibility to urinary tract disorders. However, early systematic reviews have not yielded consistent findings for these associations. This literature review summarizes important new findings from integrating nutrigenomics, hormones, and cytokines in women with Gestational diabetes mellitus and pregnancy-specific urinary incontinence. Changes in maternal metabolism due to hyperglycemia can generate an inflammatory environment with increased inflammatory cytokines. This environment modulated by inflammation can alter tryptophan uptake through food and thus influence the production of serotonin and melatonin. As these hormones seem to have protective effects against smooth muscle dysfunction and to restore the impaired contractility of the detrusor muscle, it is assumed that these changes may favor the onset of urinary incontinence specific to pregnancy.


A Pounding Problem: A Case of Recurrent Headache Caused by Anti-NMDA Receptor Encephalitis.
Anti-N-methyl-d-aspartate receptor (Anti-NMDAR) encephalitis is a serious autoimmune disease in which antibody production against the NMDA receptor results in profound neurotransmitter dysregulation. Patients may present with a wide variety of symptoms, including psychosis, orofacial dyskinesias, dysautonomia, hallucinations, mental status changes, seizures, and headaches. A previously healthy 25-year-old woman presented on several occasions to the Emergency Department with a severe pounding headache that initially responded well to treatment. She later developed signs consistent with meningoencephalitis along with altered mental status and neuropsychiatric changes. She was diagnosed with anti-NMDAR encephalitis after hospitalization. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Anti-NMDAR encephalitis is an under-recognized condition with diverse presentations. Recurrent headaches that improve with treatment may be an early sign of this disorder. Anti-NMDAR encephalitis should be considered in patients with recurrent undifferentiated headaches, and an appropriate work-up should be performed. Early recognition and diagnosis of this condition is critical to optimize favorable patient outcomes, as delays to diagnosis may lead to fatalities and long-term neurologic sequelae.


Aedes aegypti Control Strategies in Brazil: Incorporation of New Technologies to Overcome the Persistence of Dengue Epidemics.
Dengue is considered to be the most important mosquito-borne viral disease in the world. The Aedes aegypti mosquito, its vector, is highly anthropophilic and is very well adapted to urban environments. Although several vaccine candidates are in advanced stages of development no licensed dengue vaccine is yet available. As a result, controlling the spread of dengue still requires that mosquitoes be targeted directly. We review the current methods of dengue vector control focusing on recent technical advances. We first examine the history of Brazil's National Dengue Control Plan in effect since 2002, and we describe its establishment and operation. With the persistent recurrence of dengue epidemics, current strategies should be reassessed to bring to the forefront a discussion of the possible implementation of new technologies in Brazil's mosquito control program.


Immune responses to weakly immunogenic virally induced tumors. I. Overcoming low responsiveness by priming mice with a syngeneic in vitro tumor line or allogeneic cross-reactive tumor.
This report describes model systems which show low primary in vitro syngeneic cytotoxic responses to a Moloney-induced YAC tumor (syngeneic in A mice) and a Rauscher-induced RBL5 tumor (syngeneic in C57BL/6 mice) and examines different approaches to overcome these defects. Two major findings were obtained: (a) spleen cells from A mice, injected with tumor cells from an in vitro tumor line YAC-1, derived from YACL, could generate a significant syngeneic cytotoxic response. In contrast, spleen cells from A mice injected with tumor cells from the in vivo tumor line failed to generate a syngeneic cytotoxic response. Thus, tumor cells from the in vitro line were more immunogeneic that those from the in vivo line. (b) Spleen cells from A mice which were injected with the cross-reactive allogeneic tumor RBL5, could generate significant cytotoxic responses to the syngeneic tumors YAC and YAC-1. Similarly, spleen cells from C57BL/6 mice injected with the cross-reactive allogeneic tumor YAC-1, could generate a significant cytotoxic response to the syngeneic tumor RBL5. Thus, cross-reactive allogeneic tumors could stimulate syngeneic cytotoxicity. The theoretical and the practical implications of these studies are discussed.


Gene expression profiling reveals genes and transcription factors associated with dilated and ischemic cardiomyopathies.
Dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) can cause heart failure, and this study aims to identify genes and transcription factors (TFs) associated with DCM and ICM. Gene expression dataset GSE42955 was generated from GEO database, and it contained 12 DCM, 12 ICM, and 5 control samples. Differentially expressed genes (DEGs) were identified between DCM (or ICM) and controls. Gene functions were investigated, and their associations were analyzed using Enrichmentmap plugin in Cytoscape. Protein-protein interactions (PPIs) between DEGs were determined, and DEGs with high degree were defined as key DEGs. Potential TFs of key DEGs were predicted using iRegulon plugin. Common DEGs were found, and their functional interactions were investigated using GeneMANIA. A total of 362 and 300 DEGs were respectively identified for DCM and ICM in comparison with controls, and these DEGs mainly participated in similar functions about extracellular region, membrane, immune process, and defense response. PPI networks were respectively constructed for DCM and ICM, and 26 key DEGs (e.g. CXCL10, IL6, TLR3, and VCAM1) were found, which might be targeted by 35 TFs (e.g. IRF1). Besides, 47 common up-regulated DEGs were found, which participated in 14 pathways like Apoptosis, Collagen formation, as well as 127 common down-regulated DEGs that involved in 20 pathways like Adaptive immune system, Interferon γ signaling (e.g. IRF1, VCAM1), and Toll-like receptor signaling pathway (e.g. CXCL10, IL6, TLR3). DCM and ICM may share similar mechanism, and TFs (e.g. IRF1) play crucial roles in their development via regulating gene expression.


Chorion-derived perinatal mesenchymal stem cells improve cardiac function and vascular regeneration: Preferential treatment for ischemic heart disease.
Stem cell therapy has emerged as a novel treatment for heart failure after myocardial infarction (Ml). Bone marrow-derived mesenchymal stem cells (BM-MSCs) are commonly considered because of their accessibility and usability. However, their therapeutic potential remains controversial. In our previous in vitro study, chorion-derived mesenchymal stem cells (C-MSCs) and umbilical cord-derived mesenchymal stem cells (UC-MSCs) demonstrated an ability to differentiate into cardiomyocytes and neural cells, respectively. Thus, we examined whether C-MSCs had a better differentiation potential in an MI animal model. MI was induced by ligation of the left anterior descending artery, and DiI-labeled MSCs were injected into the border of the infarcted myocardium. The left ventricular ejection fraction (LVEF) and fractional shortening (FS) were measured using echocardiograms. Masson's Trichrome staining was performed to evaluate the viable myocardium. Alpha-sarcomeric actin (α-SA), cardiac troponin-T (cTnT), and isolectin were immunolabeled to evaluate differentiation and capillary formation. After 8 weeks, the LVEF and FS significantly increased to a greater extent in the C-MSC-injected group with maintenance of viable myocardium, as compared to in the control, UC-MSC-, and BM-MSC-injected groups (p < 0.05). Compared to UC-MSCs and BM-MSCs, C-MSCs significantly increased the capillary density (p < 0.05) and demonstrated higher expressions of cTnT and α-SA. In conclusion, compared to UC-MSCs and BM-MSCs, C-MSCs showed a better therapeutic efficacy in a rat MI model.


[Survival in adults with acute myelogenous leukemia].
Acute myelogenous leukemia is the most common type of acute leukemia in adults. The condition is lethal within a few months without treatment, but most young patients reach complete remission with chemotherapy. Many of them will relapse after a while, but an increasing number of young people survive for a long time. Survival data were retrieved from the Norwegian Registry for Acute Leukemias and Lymphoblastic Lymphomas for patients with acute myelogenous leukemia (aged from 16 to 60 years) who were registered in the period 1.1.2000-31.12.2005. The patients were divided in risk groups according to karyotype and response to initial chemotherapy. Patients with secondary acute myelogenous leukemia were classified as high-risk. 4-year survival was 94.5% in acute promyelocytic leukemia, 77.7% in other low-risk acute myelogenous leukemia, 39.0% in standard risk patients and 29.1% in high-risk patients. For all patients totally 4-year survival was 43.0%. This is an increase of about 15% compared to previous Norwegian studies. The increase is most probably due to an intensification of chemotherapy after remission and to the implementation of all-trans-retinoic acid in the treatment of promyelocytic leukemia.


Normal erectile function.
A complex interaction of neural, vascular, and biomolecular activity results in normal erectile function. Two chambers in the penis, the corpus cavernosa, contain sinusoids, which fill with blood and expand to become rigid when smooth muscle is relaxed. Blood flow out of the penis is temporarily stopped (veno-occlusion) to maintain the erection. Neural control is complex but, in general, the sympathetic nervous system inhibits, and the parasympathetic system excites erectile function. The central nervous system can induce erections without peripheral stimuli, e.g. in nocturnal erections. In general, there are 5 recognized phases in erectile response: latent, tumescent, full erection, rigid erection, and detumescent. The key biochemical event in erectile function is an increase in levels of cyclic guanosine monophosphate, which causes smooth-muscle relaxation and allows an erection to occur. This process is mediated by nitric oxide, produced by neurons and elsewhere, which acts as a gaseous messenger molecule.


Oncolytic H-1 Parvovirus Shows Safety and Signs of Immunogenic Activity in a First Phase I/IIa Glioblastoma Trial.
Oncolytic virotherapy may be a means of improving the dismal prognosis of malignant brain tumors. The rat H-1 parvovirus (H-1PV) suppresses tumors in preclinical glioma models, through both direct oncolysis and stimulation of anticancer immune responses. This was the basis of ParvOryx01, the first phase I/IIa clinical trial of an oncolytic parvovirus in recurrent glioblastoma patients. H-1PV (escalating dose) was administered via intratumoral or intravenous injection. Tumors were resected 9 days after treatment, and virus was re-administered around the resection cavity. Primary endpoints were safety and tolerability, virus distribution, and maximum tolerated dose (MTD). Progression-free and overall survival and levels of viral and immunological markers in the tumor and peripheral blood were also investigated. H-1PV treatment was safe and well tolerated, and no MTD was reached. The virus could cross the blood-brain/tumor barrier and spread widely through the tumor. It showed favorable pharmacokinetics, induced antibody formation in a dose-dependent manner, and triggered specific T cell responses. Markers of virus replication, microglia/macrophage activation, and cytotoxic T cell infiltration were detected in infected tumors, suggesting that H-1PV may trigger an immunogenic stimulus. Median survival was extended in comparison with recent meta-analyses. Altogether, ParvOryx01 results provide an impetus for further H-1PV clinical development.


Oxide thickness and surface contamination of six endosseous dental implants determined by electron spectroscopy for chemical analysis: a preliminary report.
Electron spectroscopy and argon ion etching were used to determine the depth and composition of the oxide layers of six competitive dental implant systems. To minimize problems associated with analyzing the active oxide layers, the implants were removed from their original packaging in an oxygen-free environment. The majority of the six implant systems were found to have similar oxide thickness in the range of 20 to 34 A. Some variation was found in the extent of non-oxide surface contamination.


[The sign of the Cross of Andreas in the iris and Diabetes Mellitus: a longitudinal study].
To compare the development of diabetes mellitus in subjects with and without the sign of the Cross of Andreas in the iris over a period of four years. A prospective, descriptive study of quantitative approach. This cohort study had 91 patients without the disease, with and without the signal. The monitoring was conducted by means of the records in medical charts. At the end of the research, 28.2% of the group with the sign of the Cross of Andreas was diagnosed with diabetes and 56.5% had two or more episodes of impaired glucose tolerance. In the group without the sign, 4.4% was diagnosed with the disease and 24.5% had two or more episodes of glucose intolerance. There was a statistically significant difference between the groups regarding the development of the disease and glucose intolerance. The group with the Cross of Andreas developed more glucose intolerance and diabetes than the group without the sign.


Optimizing the Use of Semiochemical-Based Traps for Efficient Monitoring of Popillia japonica (Coleoptera: Scarabaeidae): Validation of a Volumetric Approach.
Japanese beetle, Popillia japonica Newman, is an invasive insect, native to Japan. The species was detected in the United States in New Jersey in 1916, and then first confirmed in Minnesota in 1968. Since their arrival, P. japonica has become a major pest in turfgrass and several crop agroecosystems. As P. japonica continues to spread throughout the U.S., it's important to discover more efficient ways to monitor adult populations. In 2018-2020, due to the high volume of P. japonica beetles collected in traps, a comparison of weight and volume calibration methods was conducted in Minnesota. Each method yielded a strong goodness of fit with counts of beetles captured. However, with a goal of cost-effective use of traps and in-field estimates, the volume-based approach was the preferred, most efficient method. In addition, a comparison of monitoring systems was conducted to observe differences in trap type, lure age, and check interval. Results from these studies indicate a standard green/yellow trap, and multi-component, semiochemical-based lure used for the duration of the P. japonica flight period, and a weekly check interval will minimize sampling time and resources, while providing accurate population estimates. In addition, results from these studies will benefit growers and researchers as they continue to explore integrated pest management (IPM) strategies for P. japonica. More importantly, by reducing the time required to quantify trap catches and rebait traps, these results may also facilitate area-wide tracking of P. japonica populations in newly invaded regions.


Multiheaded rotating gamma cameras in cardiac single-photon emission computed tomographic imaging.
Multiheaded rotating gamma cameras can do more than simply decrease the time required for cardiac single-photon emission computed tomographic (SPECT) acquisitions. They give their users a flexibility to improve image quality that cannot be achieved so easily with single-headed systems. Multiheaded cameras can be used to acquire quickly those radiopharmaceuticals whose distributions washout very rapidly, increase count levels in noisy images without lengthening imaging time, permit high-resolution collimation or electrocardiographic gating with little or no decrease in counts, or acquire transmission images for attenuation correction concurrently with an emission study. This new generation of SPECT scanners gives the nuclear cardiology community a unique opportunity to create a new generation of cardiac SPECT images.


Effect of wild-type p53 gene transfection on the growth and radiotherapeutic sensitivity of human glioma cells.
To evaluate the effect of wild-type p53 gene on the growth and radiotherapeutic sensitivity of human glioma cells, plasmid PC53-SN3 carrying wild-type p53 gene was transfected into U251 cells. p53 gene expression in transfected cells was detected by RT-PCR, and the cell growth inhibition and apoptosis in the absence or presence of irradiation were assessed by MTT and flow cytometry. The transfection of p53 gene into U251 cells was confirmed by RT-PCR. MTT showed that p53 gene alone induced strong inhibitory effect on the growth of U251 cells (inhibition rate (IR), (79.60 +/- 5.69)%). The killing effect of irradiation alone on U251 cells was not strong (IR: (17.06 +/- 4.35)% (17.39 +/- 1.67)% (18.73 +/- 4.68)%) and increased with the irradiation doses (3, 6, 9 Gy). When combined treatment of wild-type p53 gene transfection and irradiation was used, the effect was significantly increased (IR:(80.60 +/- 5.35)%. (90.30 +/- 1.67)%, (91.30 +/- 2.01)%). The apoptosis rate of U251 cells induced by p53 gene transfection was 17.38%. The rate induced by irradiation increased (4.61%, 4.84%, 5.40%) with the irradiation doses (3, 6, 9 Gy). The apoptosis rate was also significantly increased (17.80%, 20.03%, 22.34%) after combined treatment of p53 and irradiation with different doses (3, 6, 9 Gy). It is concluded that wild-type p53 gene and irradiation could result in synergistic inhibitory effect on the growth of human glioma cells.


Steelmaking in India - new evidence from microscopic and archaeometallurgical analysis from middle Ganga plain, Balirajgarh.
The present study deliberates on the archaeometallurgical examination of 2300 years old excavated iron nail from India's middle Ganga plain of Balirajgarh. The nail was subjected to multianalytical investigations in order to determine the raw materials used, manufacturing technology and preservation state. The combined analytical techniques optical microscopy, scanning electron microscopy-energy dispersive X-ray spectrometry (SEM-EDX), Vickers hardness and X-ray diffractometry shed light towards the characterisation and use of the iron artefact. Special attention was paid for qualitative and quantitative analysis of slag inclusions, metal matrix and corrosion products. The presence of heterogeneous microstructure and inclusion of impurities suggests that nail has been produced through the direct process and work hardened. The noncorroded nail is made of hypereutectoid steel and used for building purpose. The study is important to understand the role of technology in the evolution of cultural changes in India that also provides archaeometric data on the method used in the forging work.


Selective Laser Melting Technique of Co-Cr Dental Alloys: A Review of Structure and Properties and Comparative Analysis with Other Available Techniques.
The aim of this study was to review the effect of selective laser melting (SLM) procedure on the properties of dental structures made of Co-Cr alloys and to evaluate its quality and compare it to those produced by conventional casting and milling fabrication techniques. A computerized database search using PubMed and Scopus was conducted for peer-reviewed scientific research studies regarding the use of SLM in Co-Cr dental alloys with no restrictions for publication years. The search engines provided hundreds of results, and only 48 scientific research papers, case studies, or literature reviews were considered relevant for this review. The innovative manufacturing concept of SLM offers many advantages compared with casting and milling fabrication techniques. SLM provides different microstructure from casting and milling with minimal internal porosity and internal fitting, marginal adaptation, and comparable bond strength to porcelain. Mechanical and electrochemical properties of SLM structures are enhanced compared to cast, while clinical longevity of single-metal ceramic crowns is comparable to Au-Pt dental alloy. The SLM technique provides dental prosthetic restorations more quickly and less expensively without compromising their quality compared with restorations prepared by casting and milling techniques. The current SLM devices provide metallic restorations made of Co-Cr alloys for removable and fixed partial dentures without compromising the alloy or restoration properties at a fraction of the time and cost, showing great potential to replace the aforementioned fabrication techniques in the long term; however, further clinical studies are essential to increase the acceptance of this technology by the worldwide dental community.


[Valgisation osteotomy of unstable pertrochanteric femoral fracture. Results of 92 patients over 7.75 years].
We report on 92 patients (average age: 76.9 years) with unstable trochanteric fractures (Type A2 and subtypes according to the AO/ASIF-Classification) that were treated by valgisation/medial displacement osteotomy and 130 degrees-angled blade plate fixation during a time period of 7.75 years at the Department of Traumatology of the University Clinics of Frankfurt. Average time in the OR was 106 min, average amount of blood necessary was three units. The rate of complications due to the implant was 14.1% taking into account: "cut out" of blade (four patients), loosening of plate (three patients), failure of implant-breakage (two patients)--and development of delayed union (2 patients). There were 4.3% hematomas and 3.3% infections that required revisional surgery. 16 (17.4%) out of 92 patients died during their hospital stay. 77.2% of surviving patients regained walking ability during their hospitalization and only 12% had to be dismissed to a nursing home. "Pros and cons" of our method of treatment for these fracture types against DHS and gamma-nailing are discussed.


Foot care behaviors among adults with type 2 diabetes.
The aim of the study was to determine factors influencing foot care behaviors among adults with type 2 diabetes. A correlational descriptive study was conducted with a random sample of 160 adults with type 2 diabetes from the public hospital between April and July 2014. Just over 15% of the sample had a history of foot ulcers and almost 42% had numbness/tingling and pain in their feet. Positive foot care behaviors were correlated with higher income, higher educational attainment, lower body weight, positive attitude and higher awareness of diabetes and its management. Targeting type 2 diabetes people with low level of education, low income and overweight may help to enhance their foot care and reduce foot complications in similar populations, Implications. Those most at risk of foot problems should be targeted for education to increase their awareness of ways to prevent and to manage foot problems.


Transcutaneous absorption of naproxen gel.
The kinetics of naproxen was studied in healthy volunteers after cutaneous application of gels containing 5 and 10% of the drug. Bioavailability was estimated from serum concentration and cumulative urinary metabolite excretion data, both determined up to 96 hours after drug administration. The mean bioavailability after the 10% gel was 1.1% (serum data) and 1.0% (urine data), and after the 5% gel it was 2.1% (serum data) and 1.8% (urine data). Despite the small amount of naproxen absorbed, a potential pharmacological effect, due to cutaneous accumulation of the drug following topical administration, may be suggested from the course of the serum concentration-time curves.


Individual differences in momentary pain-affect coupling and their associations with mental health in patients with chronic pain.
Pain and affect are generally associated. However, individuals may differ in the magnitude of the coupling between pain and affect, which may have important implications for their mental health. The present study uses ecological momentary assessments (EMA) to examine individual differences in momentary pain-affect coupling and their associations with depressive and anxiety symptoms. This study is a secondary data analysis of three primary EMA studies. Participants were a total of 290 patients with chronic pain. Results were synthesized across studies using meta-analytic techniques. Individuals whose pain was more strongly concurrently coupled with affect (positively associated with negative affect or negatively associated with positive affect) reported higher levels of depressive and anxiety symptoms. Results from lagged analyses suggest that individual differences in affect reactivity to pain were not significantly associated with depressive or anxiety symptoms. These findings suggest that individuals with greater concurrent coupling between pain and affect experience more mental health problems. Potential avenues for future research include intervention strategies that target the decoupling of pain and affect experiences in patients with chronic pain.