A review of drug-facilitated sexual assault evidence: an Irish perspective.
Drug-facilitated sexual assault (DFSA) is prevalent in Western society. There is a significant degree of confusion regarding the definition and prevalence of DFSA. It is a subject with medical, scientific and legal aspects. These facets are explored in this review through a detailed examination of published data. The legal issues are defined in the context of the Irish judicial system. Several key case-law studies are presented to aid in understanding unresolved difficulties that persist in this complex field of forensics. The aim of this paper is to aid individuals from disparate disciplines to increase their evidence base in the complex and evolving issue of DFSA.


Patent foramen ovale and embolic stroke "en flagrant délit".
Proof of a causal relationship between a patent fossa ovale and cryptogenic stroke has been controversial (Yasaka et al, Intern Med 2005;44:434-8). The authors identified 1 patient in whom the presence of a large migrating thrombus through a moderate-size patent fossa ovale was caught "en flagrant délit," which suggests a direct pathogenic role.


Vasoactive intestinal peptide reduces the inflammatory profile in mice infected with Trypanosoma cruzi.
Vasoactive intestinal peptide (VIP) has gained great prominence because of its therapeutic potential, which is ascribed to its ability to regulate innate immunity, inhibit antigen-specific Th1 cell responses, and generate T regulatory cells. Additionally, VIP may act as a natural antimicrobial peptide, killing bacteria, fungi, and infective forms of Trypanosoma brucei. Despite the possible relevance of VIP during the course of Chagas disease, studies regarding this in human and experimental Trypanosoma cruzi infections remain poorly characterized. In this work, we evaluated the effects of VIP on systemic and cardiac immune responses during experimental acute infection. C57BL/6 mice were infected with 5000 trypomastigotes of the VL-10 strain of T. cruzi and treated with intraperitoneal VIP injection every other day for one month. After 30 days, we observed no reduction in parasitemia levels. However, we observed a reduction in serum levels of IFN-gamma and IL-2 and an increase in that of IL-4. These data suggest that VIP treatment modified immune responses to favor the Th2 response, which had no impact on parasitemia levels although the serum level of IFN-gamma was reduced. However, this change in immune balance reduced heart damage, as noted by the smaller cardiac volume and the moderate inflammatory infiltrate observed in VIP-treated mice. Our results indicate that VIP treatment reduced the inflammatory response at the cardiac site of mice that were experimentally infected with T. cruzi. These data suggest a protective role for VIP in the heart of infected mice.


Virtual screening of approved clinic drugs with main protease (3CLpro) reveals potential inhibitory effects on SARS-CoV-2.
3CLpro is the main protease of the novel coronavirus (SARS-CoV-2) responsible for their intracellular duplication. Based on virtual screening technology and molecular dynamics simulation, we found 23 approved clinical drugs such as Viomycin, Capastat, Carfilzomib and Saquinavir, which showed high affinity with the 3CLpro active sites. These findings showed that there were potential drugs that inhibit SARS-Cov-2's 3CLpro in the current clinical drug library, and these drugs can be further tested or chemically modified for the treatment of COVID-19.Communicated by Ramaswamy H. Sarma.


Arabidopsis ABRE-binding factors modulate salinity-induced inhibition of root hair growth by interacting with and suppressing RHD6.
Soil salinity causes crop losses worldwide. Root hairs are the primary targets of salt stress, however, the signaling networks involved in the precise regulation of root hair growth and development by salinity are poorly understood. Here, we confirmed that salt stress inhibits the number and length of root hairs in Arabidopsis. We found that the master regulator of root hair development and growth, the RHD6 transcription factor, is involved in this process, as salt treatment largely compromised root hair overaccumulation in RHD6-overexpressing plants. Yeast-two-hybrid and co-immunoprecipitation analyses revealed that RHD6 physically interacts with ABF proteins, the master transcription factors in abscisic acid signaling, which is involved in tolerance to several stresses including salinity. Phenotypic analyses showed that ABF proteins, which function upstream of RHD6, positively modulate the salinity-induced inhibition of root hair development. Further analyses showed that ABF3 suppresses the transcriptional activation activity of RHD6, thereby regulating the expression of genes related to root hair development. Overexpression of ABF3 reduced the root hair-overgrowing phenotype of RHD6-overexpressing plants. Collectively, our results demonstrate an essential signaling module in which ABF proteins directly suppress the transcriptional activation activity of RHD6 to reduce the length and number of root hairs under salt stress conditions.


Up-regulation of IAPs by PI-3K: a cell survival signal-mediated anti-apoptotic mechanism.
Under normal cell physiology, a balance between cell survival and apoptosis is crucial for homeostasis. Many studies have demonstrated that apoptosis is modulated by cell survival stimuli. Active Akt, a common mediator of cell survival signals, has been shown to inhibit apoptosis by attenuating activity of pro-apoptotic factors Bad and caspase-9. However, the anti-apoptotic mechanisms mediated by various cell survival signals are poorly understood. Human prostate cancer LNCaP cells, known to contain constitutively activated Akt as a result of a frame-shift mutation in PTEN, an inhibitor of PI-3K/Akt pathway, were observed to be completely resistant to TRAIL-induced apoptosis. In agreement with the known action of Akt, blockade of the PI-3K/Akt pathway rendered LNCaP cells highly susceptible to TRAIL. Importantly, active PI-3K/Akt prevented processing/activation of caspase-3, a phenomenon associated with the function of inhibitor of apoptosis proteins (IAPs). In fact, inhibition of PI-3K activity using Wortmannin significantly decreased the protein levels of IAPs, concomitantly promoting processing/activation of caspase-3 and TRAIL-induced apoptosis. My data indicate that in addition to blocking Bad and caspase-9 through Akt, PI-3K also inhibits caspase-3 through up-regulating IAPs, thereby attenuates apoptosis.


Facing the challenges of competency-based assessment of postgraduate dental training: Longitudinal Evaluation of Performance (LEP).
The evaluation of competence in the health professions is of great importance to the public and professionals alike. Recent efforts to design dependable and accurate systems of assessment for demanding clinical roles are increasingly attempting to focus on all-round competence of practitioners. Many challenges are faced in this field as a balance between robust assessment methodology and feasibility in practice is crucial to implementation and adoption. The authors discuss some of the challenges faced by educators and clinicians involved in the development of systems of assessment for the health professions, and describe a method which aims to address these issues in the assessment of postgraduate dental training in Scotland. Three of the major challenges facing educators and clinicians involved in the design of competency-based systems of assessment are considered: the requirement for evaluation in different areas of competence; the importance of association of assessment with the training objectives, and the types and focus of the assessment introduced. Issues around the use of formative and summative assessment, and the perception that these must always remain completely separate, are discussed in detail. A proposal is made for the introduction of a method of assessment which has been designed keeping these challenges in mind. The rationale behind this assessment method is described.


Hearing Preservation Outcomes Using a Precurved Electrode Array Inserted With an External Sheath.
Describe audiologic outcomes in hearing preservation cochlear implantation (CI) using a precurved electrode array inserted using an external sheath and evaluate association of electrode positioning and preservation of residual hearing. Retrospective review. Tertiary otologic center. Twenty-four adult patients who underwent hearing preservation CI with precurved electrode array. CI, intraoperative computed tomography (CT) OUTCOME MEASURES:: Audiologic measures (consonant-nucleus-consonant [CNC] words, AzBio sentences, low-frequency pure tone averages [LFPTA]) and electrode location (scalar location, electrode-to-modiolus distance ((Equation is included in full-text article.)), angular insertion depth). Twenty-four adults with less than 80 dB LFPTA with a precurved electrode array inserted using an external sheath; 16 underwent intraoperative CT. LFPTA was 58.5 dB HL preoperatively, with a 17.3 dB threshold shift at CI activation (p = 0.005). CNC word scores improved from 6% preoperatively to 64% at 6 months postoperatively (p < 0.0001). There was one scalar translocation and no tip fold-overs. The average angular insertion depth was 388.2 degrees, and the average (Equation is included in full-text article.)across all electrodes was 0.36 mm. Multivariate regression revealed a significant correlation between CNC scores at 6 months and angular insertion depth (p = 0.0122; r = 0.45, adjusted r = 0.35). Change in LFPTA was not significantly associated with angular insertion depth or (Equation is included in full-text article.). A low rate of translocation allows a precurved electrode array inserted using an external sheath to maintain hearing preservation rates comparable to straight electrode arrays. With scala tympani insertion, angular insertion depth is a positive marker of improved speech performance postoperatively but may be a confounder variable based on individual cochlear size.


Clinical use of biocompatible ultrasonic bladder volume sensor.
A biocompatible ultrasonic bladder volume sensor has been developed and successfully employed to sense bladder fullness in healthy volunteers. It is anticipated that it will be of practical use in patients with diabetic autonomic neuropathy as well as in patients employing self-intermittent catheterization.


Amplification of erbB-4 oncogene occurs less frequently than that of erbB-2 in primary human breast cancer.
ErbB-4 protein is a recently discovered member of the ErbB family. The role of ErbB-4 protein in mammary-gland tissue has not been definitively established. To date, the expression of erbB-4 in breast tissue has been determined in only a few cases and, to the best of our knowledge, its amplification has not been examined. We therefore used the double differential polymerase chain reaction (ddPCR) for determination of the amplification profile of erbB-4 and erbB-2, another gene from the ErbB family, in human primary breast cancer specimens. We examined the amplification of the genes in 20 normal breasts and 176 invasive breast cancer samples. Amplification of erbB-2 was detected in 19% and erbB-4 in 13% of the samples studied. Co-amplification of the two oncogenes was found in only five out of 176 samples. Human breast cancer-derived cell lines in most cases overexpress both erbB-2 and erbB-4 (Beerli et al., 1995. Mol. Cell Biol. 15, 6496-6505; Han et al., 1995. Proc. Natl. Acad. Sci. USA 92, 9747-9751), but data on separate erbB-2 overexpression, without overexpression of erbB-4, were also reported (Wosikowski et al., 1997. Clin. Cancer Res. 3, 2405-2414). At the gene level, we found that co-amplification of the genes in the case of human breast cancer is rare. Moreover, an inverse association of the erbB-4 amplification with estrogen receptor activity and direct correlation with the tumor size were found. Due to these correlations, erbB-4 oncogene amplification can be assumed to be of prognostic or predictive value in the diagnosis of breast cancer.


LRP::FLAG Reduces Phosphorylated Tau Levels in Alzheimer's Disease Cell Culture Models.
Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) plaque and neurofibrillary tangle formation, respectively. Neurofibrillary tangles form as a result of the intracellular accumulation of hyperphosphorylated tau. Telomerase activity and levels of the human reverse transcriptase (hTERT) subunit of telomerase are significantly decreased in AD. Recently, it has been demonstrated that the 37 kDa/67 kDa laminin receptor (LRP/LR) interacts with telomerase and is implicated in Aβ pathology. Since both LRP/LR and telomerase are known to play a role in the Aβ facet of AD, we hypothesized that they might also play a role in tauopathy. This study aimed to determine if LRP/LR has a relationship with tau and whether overexpression of LRP::FLAG has an effect on tauopathy-related proteins. We employed confocal microscopy and FRET to determine whether LRP/LR and tau co-localize and interact. LRP::FLAG overexpression in HEK-293 and SH-SY5Y cells as well as analysis of tauopathy-related proteins was assessed by western blotting. We demonstrate that LRP/LR co-localizes with tau in the perinuclear cell compartment and confirmed a direct interaction between LRP/LR and tau in HEK-293 cells. Overexpression of LRP::FLAG in HEK-293 and SH-SY5Y cells decreased total and phosphorylated tau levels with a concomitant decrease in PrPc levels, a tauopathy-related protein. LRP::FLAG overexpression also resulted in increased hTERT levels. This data suggest that LRP/LR extends its role in AD through a direct interaction with tau, and recommend LRP::FLAG as a possible alternative AD therapeutic via decreasing phosphorylated tau levels.


Evidence for an independent relationship between plasma insulin and concentration of high density lipoprotein cholesterol and triglyceride.
Increased plasma insulin and triglycerides and decreased high density lipoprotein concentrations are primary risk factors in the development of coronary artery disease. The aim of the present study was to verify whether there was an independent relationship between plasma insulin levels and both HDL cholesterol and triglyceride in a worker population of 607 subjects, 389 men and 218 women, aged 23-73 years. An oral glucose tolerance test (75 g) was performed. Plasma glucose, insulin, triglyceride and HDL cholesterol were measured at fasting, plasma glucose and insulin were determined also 1 h and 2 h after glucose load. The results, examined separately in men and women documented a significant negative relationship between plasma insulin and HDL cholesterol level, as well as pointing out that both HDL cholesterol and insulin are significantly correlated to degree of hypertriglyceridemia, degree of obesity and level of glucose tolerance. The partial correlation coefficients between HDL cholesterol and plasma insulin levels at fasting in men and post-glucose load in women, demonstrated an independent relationship between increased plasma insulin and decreased plasma HDL concentration. However, the strongest relationship, revealed by partial correlation coefficient analysis, was between the degree of hyperinsulinemia and hypertriglyceridemia.


Modification in media composition to obtain secretory production of STxB-based vaccines using Escherichia coli.
Shiga toxin B-subunit (STxB) from Shigella dysenteriae targets in vivo antigen to cancer cells, dendritic cells (DC) and B cells, which preferentially express the globotriaosylceramide (Gb3) receptor. This pivotal role has encouraged scientists to investigate fusing STxB with other clinical antigens. Due to the challenges of obtaining a functional soluble form of the recombinant STxB, such as formation of inclusion bodies during protein expression, scientists tend to combine STxB with vaccine candidates rather than using their genetically fused forms. In this work, we fused HPV16 E7 as a vaccine candidate to the recombinantly-produced STxB. To minimize the formation of inclusion bodies, we investigated a number of conditions during the expression procedure. Then various strategies were used in order to obtain high yield of soluble recombinant protein from E. coli which included the use of different host strains, reduction of cultivation temperature, as well as using different concentrations of IPTG and different additives (Glycin, Triton X-100, ZnCl(2)). Our study demonstrated the importance of optimizing incubation parameters for recombinant protein expression in E. coli; also showed that the secretion production can be achieved over the course of a few hours when using additives such as glycine and Triton X-100. Interestingly, it was shown that when the culture mediums were supplemented by additives, there was an inverse ratio between time of induction (TOI) and the level of secreted protein at lower temperatures. This study determines the optimal conditions for high yield soluble E7-STxB expression and subsequently facilitates reaching a functionally soluble form of STxB-based vaccines, which can be considered as a potent vaccine candidate for cervical cancer.


Estimation of the infectious viral load required for transfusion-transmitted human T-lymphotropic virus type 1 infection (TT-HTLV-1) and of the effectiveness of leukocyte reduction in preventing TT-HTLV-1.
The risk of transfusion-transmitted human T-lymphotropic virus type 1 infection (TT-HTLV-1) after prestorage leucocyte reduction (LR) remains unknown, as the proviral load in the blood component that would cause TT-HTLV-1 is undetermined. On the basis of the distribution of HTLV-1 proviral load among HTLV-1-sero-positive blood donors, we attempted to estimate the proviral load for transfusion-related infectivity. We also discuss the effectiveness of LR in preventing TT-HTLV-1. The HTLV-1 proviral load in 300 HTLV-1-sero-positive blood donors was determined by real-time polymerase chain reaction analysis. The proviral load required for transfusion-related infectivity was estimated using historical TT-HTLV-1 frequency data from a retrospective study on patients who had received blood from HTLV-1-sero-positive blood donors and the distribution pattern of HTLV-1 proviral load among blood donors. HTLV-1 proviral loads ranged between < 0.01 and 25.0 copies per 100 leucocytes. Historical data showed TT-HTLV-1 frequency to be 80%. Assuming that 80% of the 300 sero-positive samples are infectious, it is estimated that the transfer of ≥ 9 × 10(4) cells containing the HTLV-1 provirus is required to establish TT-HTLV-1. The residual number of HTLV-1-infected cells after LR is substantially lower than the viral load necessary for TT-HTLV-1. LR therefore appears to be effective in minimizing the incidence of TT-HTLV-1.


Studies on binding of HIV-1 p24gag peptide to HLA-Cw3+ cells.
Human major histocompatibility complex class I antigens, HLA-C, are expressed on the cell surface at approximately a tenfold lower level than HLA-A and -B. We hypothesized that the expression of HLA-C is limited by the quantity of high affinity peptides which bind to these molecules, thus allowing only a small fraction of HLA-C molecules to be transported and/or to remain stable on the cell surface. If this assumption is correct, then the addition of exogenous peptide should increase cell surface HLA-C expression. To verify the hypothesis, we pulsed lymphoblastoid cell line PAJ (HLA-Cw3+) with synthetic HIV-1 p24gag 145-152 peptide, known to be presented to T-lymphocytes by HLA-Cw3 molecule. PAJ (HLA-Cw3+) cells bound approximately two times more of the peptide than HAJ (HLA-Cw3-), and four times more than 500/C9 (HLA-Cw3-) cells. Accordingly, overnight pulsing of PAJ cells with the p24gag 145-152 peptide caused an increase in class I HLA expression detected on the cell surface by flow cytofluorimetric analysis with anti-HLA-B,C monoclonal antibodies but not by anti-HLA-A antibody. In contrast, HLA-Cw3- cells treated in the same manner did not show any increase of HLA class I expression. Our data suggest that low concentration of high affinity peptides within the cell may be one of the factors limiting cell surface expression of HLA-C molecules.


Regional differences in symptomatic fever management among paediatricians in Switzerland: the results of a cross-sectional Web-based survey.
In symptomatic fever management, there is often a gap between everyday clinical practice and current evidence. We were interested to see whether the three linguistic regions of Switzerland differ in the management of fever. A close-ended questionnaire, sent to 900 Swiss paediatricians, was answered by 322 paediatricians. Two hundred and fourteen respondents were active in the German speaking, 78 in the French speaking and 30 in the Italian speaking region. Paediatricians from the French and Italian speaking regions identify a lower temperature threshold for initiating a treatment and more frequently reduce it for children with a history of febrile seizures. A reduced general appearance leads more frequently to a lower threshold for treatment in the German speaking than in the French and Italian speaking areas. Among 1.5 and 5-year-old children the preference for the rectal route is more pronounced in the German than in the French speaking region. French speaking respondents more frequently prescribe ibuprofen and an alternating regimen with two drugs than German speaking respondents. Finally, the stated occurrence of exaggerated fear of fever was higher in the German and Italian speaking regions. Switzerland offers the opportunity to compare three different regions with respect to management of febrile children. This inquiry shows regional differences in symptomatic fever management and in the perceived frequency of exaggerated fear of fever. The gap between available evidence and clinical practice is more pronounced in the French and in the Italian speaking regions than in the German speaking region.


Protective efficacy of an AIDS vaccine, a single DNA priming followed by a single booster with a recombinant replication-defective Sendai virus vector, in a macaque AIDS model.
We previously demonstrated the excellent protective efficacy of DNA priming followed by Gag-expressing Sendai virus (SeV) boosting (DNA prime/SeV-Gag boost vaccine) against a pathogenic simian-human immunodeficiency virus (SHIV89.6PD) infection in macaques. Here we show that we established a practical, safer AIDS vaccine protocol, a single DNA priming followed by a single booster with a recently developed replication-defective F deletion SeV-expressing Gag, and show its protective efficacy against SHIV89.6PD infections.


Hereditary Progressive Mucinous Histiocytosis: New Insights Into a Rare Disease.
Hereditary progressive mucinous histiocytosis is a rare, benign, skin-limited form of non-Langerhans cell histiocytosis. We report on a 5-year-old boy who presented in infancy with self-resolving dermal nodules but later developed persistent and progressive erythematous papules on the face and scalp. Histologic evaluation revealed dermal aggregates of S-100/CD1a-negative histiocytes with abundant mucin. We present this case to highlight the evolution of the lesional morphology in infancy and early childhood and to stress the importance of histology in confirming this rare disorder.


Mannosylphosphate transfer to yeast mannan.
Mannoproteins located in the outermost layer of yeast cell wall determine the wall's porosity and thereby regulate leakage of proteins from the periplasmic space and entrance of macromolecules from the environment. In several yeasts, including Saccharomyces cerevisiae, the glycan portion of mannoproteins is composed not only of neutral oligosaccharides containing mannose and N-acetylglucosamine, but also of acidic oligosaccharides containing mannosylphosphate. The mannosylphosphate residues confer a net negative charge on the cell wall, and so change the properties and environment of the cell surface. Progress on mannosylphosphorylation and its regulation in S. cerevisiae is summarized. Two genes required for mannosylphosphate transfer, MNN4 and MNN6, have been cloned, and a functional analysis of these genes suggests a mechanism for mannosylphosphate transfer. Possible functions for mannosylphosphate transfer in yeast are also discussed. These include supply of GMP for sugar nucleotide transport in the Golgi, cross-linking of mannoproteins to beta-glucan, and a cellular stress response to environmental changes. Glycans in pathogenic yeast and protozoa are also modified with mannosylphosphate, and the potential contribution of this modification to the pathogenicity of these organisms is evaluated.


Capecitabine and weekly paclitaxel as first-line therapy in Thai patients with metastatic breast cancer.
The combination of a taxane and capecitabine offers synergistic antitumor activity. This study aimed to determine the efficacy and tolerability of a paclitaxel and capecitabine combination in Thai patients with metastatic breast cancer (MBC) not previously treated for metastatic disease. This open-label, single-center, non-comparative phase II study was conducted between December 2006 and March 2009. In all 40 MBC patients were treated with oral capecitabine 1000 mg/m(2) twice daily on days 1 to 14, and weekly paclitaxel 80 mg/m(2) in a 3-week cycle for a total of six cycles. After a median follow up of 13.4 months, an overall objective response rate of 80%, with a partial response of 74% and a complete response of 5% were achieved. While 8% of patients achieved stable disease, 13% had progressive disease. Median time to progress was 8 months and median overall survival was 24.4 months. One patient discontinued because of hypersensitivity to paclitaxel. There was no grade 4 toxicity. Skin and nail toxicity was found in 75% of patients (with 25% in grade 2 or 3), followed by neutropenia (45% in all with 15% in grades 2 or 3), neuropathy (25% in total with 5% in grade 2) and stomatitis and diarrhea (in both of which 5% experienced grade 1 severity). A first-line regimen of weekly paclitaxel plus capecitabine is effective and tolerable in Thai MBC patients.


Thermal coefficients of the expansion and refractive index in YAG.
The thermal expansion coefficient and dn/dT are measured by interferometry techniques in undoped YAG below 300 K. The thermal expansion coefficient at 125 K is measured to be 2.70 x 10(-6) K(-1) and dn/dT at 633 nm is 2.5 x 10(-6) K(-1), compared with 7 x 10(-6) K(-1) and 9 x 10(-6) K(-1) for these quantities at 300 K.


Advanced oxygenation efficiency and purification of wastewater using a constant partially unsaturated scheme in column experiments simulating vertical subsurface flow constructed wetlands.
The presence of sufficient dissolved oxygen (DO) in a constructed wetland (CW) is vital to the process of removing ammonia nitrogen and organics from wastewater. To achieve total nitrogen removal, which is characterised by enhanced ammonia nitrogen removal, this study offers an efficient strategy to increase the oxygen supply by establishing constant unsaturated zones and baffles in simulating constructed wetlands (SCWs). Henceforth, this strategy is addressed as a partially unsaturated SCW. A centrally located high tube was set up inside the wetland to create an unsaturated zone at a higher level. The effectiveness of the unsaturated zone to supplement the oxygen content was evaluated by comparing with controls (an unaerated SCW and an aerated SCW). The results show the chemical oxygen demand removal rate (85 ± 6%) in the partially unsaturated SCW was equivalent to that in the aerated SCW (83 ± 6%), while the ammonia nitrogen removal rate was 11 times higher compared to that of the unaerated SCW. The removal potential of the partially unsaturated SCW under different HRT (hydraulic retention time)s (12, 24, and 36 h) was examined, and the 36 h-SCW performed the best in the removal of organics and nitrogen. The mechanisms behind the unsaturated zone strategy were studied by analysing water and microbe samples along the pathway. The results from the water quality indicators and the quantitative polymerase chain reactions along the pathway showed the unsaturated zone contributed to the removal of primary organics and ammonia nitrogen. The superior performance of unsaturated zone strategy was discussed further using the enrichment of ammonia-oxidising bacteria, mass of oxygen uptake, and baffle design. The results indicate that the amoA gene/16s rRNA gene abundance ratio and the oxygen uptake (336 ± 44 g m-3 d-1) in the partially unsaturated SCW was higher than that observed in the two controls.


Microarray analysis of miRNA gene expression.
MicroRNAs (miRNAs) are small, noncoding RNAs that regulate the expression of target mRNAs. Although thousands of miRNAs have been identified, few have been functionally linked to specific biological pathways. Microarray-based expression analysis is an ideal strategy for identifying candidate miRNAs that correlate with biological pathways and for generating molecular signatures of disease states. This chapter will describe a simple, low-cost microarray platform optimized for miRNA expression analysis.


Using impedance cardiography to detect asymptomatic cardiovascular disease in prehypertensive adults with risk factors.
Early detection of cardiovascular disease (CVD) in prehypertension could initiate appropriate treatment and prevent progression. Impedance cardiography (ICG) is a noninvasive technology that can be used to assess cardiovascular function. This study used ICG waveform analysis with postural change to detect CVD in asymptomatic prehypertensive adults over 40 years of age with no history of CVD and at least 2 cardiovascular risk factors: cigarette smoking, poor diet, physical inactivity, central obesity, family history of premature CVD, elevated blood glucose, and dyslipidemia. A study group of 25 apparently healthy adults was tested by ICG in standing and supine positions. Criteria for an age-matched control group of 16 healthy subjects included an active lifestyle, no risk factor, and no history of CVD. In addition to hemodynamic measurements of systemic vascular resistance (SVR) and cardiac index (CI), ICG used SVR to assess vascular resistive load, an index of arterial compliance and a widening of the systolic waveform to assess vascular pulsatile load, and waveform analysis and measured wave amplitude to detect ventricular dysfunction. All subjects in the study group had some abnormal ICG data, with an average of 2.9 ± 1.5 abnormalities per person. ICG indicated that 24 (96%) had elevated vascular load, 13 (52%) had some type of ventricular dysfunction, and 12 (48%) had abnormal hemodynamics. For the control group, ICG showed none (0%) with elevated vascular load, none (0%) with ventricular dysfunction, and 7 (44%) with high CI. Prehypertensives over 40 years of age with multiple risk factors have different cardiovascular abnormalities. This ICG test could be used as part of a prevention program for early detection of CVD. An abnormal ICG test could expedite the initiation of customized treatment that targets the subclinical CVD.


The role of soil Phosphorus in differentiation of edaphic ecotypes in Aegilops peregrina.
The role of soil Phosphorus (P) availability on the ecotypic differentiation of plants was investigated. Populations of Aegilops peregrina (Hack.) were collected from four habitats which differed in their soil P. The four soils were: Meron (a P-deficient montmorillonitic xerochrept on dolomite), Malkiya (a P-fertile kaolinitic xerochrept on hard limestone), Har-Hurshan and Bet-Guvrin (lithic xerorthents on soft limestone with appreciable amounts of P, mainly as carbonate-apatite).Plants of the four populations were grown in pots with Meron soil which were previously equilibrated with four different amounts of soluble phosphate to give 1.2, 3.1, 10.7 and 18.9 μgP g-1 soil of sodium-bicarbonate extractable P. Plants originated from Malkiya population produced higher dry matter yields than the other three populations. Dry matter yields of the various populations were analyzed by means of a Mitcherlich's response function, versus sodium-bicarbonate extractable ('available') soil P. The analysis revealed that Malkiya population plants had a significant advantage over Meron population plants in the response parameter c: this express the response rate of the plants to phosphate by means of dry matter production. With regard to the parameter Po, which represents the ability of plants to utilize barely-available fractions of soil P, the opposite was true. Har-Hurshan and Bet-Guvrin populations were intermediate in these two parameters. A version of the Mitcherlich response function is proposed, which expresses plant yield as a function of both soil 'available' P and plant age.Meron plants contained the highest percentage of P in plant material, but compared to the other populations, they were the most inefficient in producing dry matter from the already absorbed P. Plants from the calcareous soils, Har-Hurshan and Bet-Guvrin, did not show any apparent trend.In soils which contain moderate amounts of lime, P may become a major limiting growth factor. Plant populations became adapted to low availability of P by (1) improving their ability to utilize barely-available soil P fractions and (2), by decreasing their productivity.


Removal and biotransformation of 4-nonylphenol by Arthrospira maxima and Chlorella vulgaris consortium.
4-Nonylphenol (4-NP) is an anthropogenic contaminant found in different environmental matrices that has an effect over the biotic and abiotic factors within the environment. Bioremediation by microorganisms can be used as a potential treatment to remove this pollutant. In this work, a consortium of two microorganisms, Arthrospira maxima and Chlorella vulgaris, was employed to remove 4-NP from water. The parameters analyzed included cell growth, removal of 4-NP, and 4-NP remnant in the biomass. In addition, the metabolites produced in the process by this consortium were identified. It was found that C. vulgaris is more resistant to 4-NP than A. maxima (cell growth inhibition by 4-NP of 99%). The consortium used in this study had an IC50 greater than any strain of microalgae or cyanobacteria reported for 4-NP removal (9.29 mg/L) and reduced up to 96% of 4-NP in water in the first 48 h of culture. It was also observed that there is a bio-transformation of 4-NP, comparable with the process carried out by another bacterium, in which three similar metabolites were found (4-(1-methyl-octyl)-4-hydroxy-cyclohex-2-enone, 4-nonyl-4-hydroxy-ciclohexa-2,5-dienone and 4-nonyl-4-hydroxy- ciclohex-2-enone) and one that is similar to plant metabolism (4-nonyl-(1-methyl,6,8-metoxy)-hydroxybenzene). These results indicate that microalgae and cyanobacteria consortium can be used to remove 4-NP from water.


Alteration of plasma phospholipid fatty acid profile in patients with septic shock.
In septic shock patients, alterations of plasma phospholipid fatty acid profile have never been described. The purpose of this monocentric, non-interventional, observational prospective study was to describe this fatty acid profile in the early phase of septic shock in intensive care unit. Thirty-seven adult patients with septic shock were included after the first day of stay in intensive care unit, before any form of artificial nutritional support. Plasma phospholipid fatty acid composition was determined by gas chromatography. All biological data from patients with septic shock were compared with laboratory reference values. Patients presented hypocholesterolemia and hypertriglyceridemia. They had low concentrations of phospholipid fatty acids specifically n-6 and n-3 polyunsaturated fatty acids (PUFAs) with a high n-6/n-3 ratio. Plasma phospholipid PUFA concentrations were strongly correlated with cholesterolemia. PUFAs/SFAs (saturated fatty acids) and PUFAs/MUFAs (monounsaturated fatty acids) ratios were low because of low percentage of n-6 and n-3 PUFAs and high percentage of SFAs and MUFAs. Low levels of plasma long chain PUFAs (≥20 carbons) were significantly associated with mortality at 28th day. In conclusion, plasma phospholipid FA profile of septic patients is very characteristic, close to that of acute respiratory distress syndrome and mortality is associated with long chain PUFA decrease. This profile could be explained by numerous non-exclusive physio-pathological processes 1) an activation of hepatic de novo lipogenesis that could contribute to hepatic steatosis, 2) an elevated adipose tissue lipolysis, 3) an increased free radical attack of FA by oxidative stress, 4) an over-production of inflammatory lipid mediators.


In vivo predictive toxicogenomics.
Reference databases consisting of large sample numbers and high-dimensional microarray data are now available for the investigation of adverse events in animal model systems such as the rat. This large volume of data, accompanied by appropriate study designs, compound and dose selection procedure, and minimization of technical and biological confounding effects, can yield successful predictive models for a variety of hypotheses. The process of training, validating, and implementing predictive models is cyclical and complex. This chapter highlights individual decisions that need to be made before, during, and after a model or set of models has been trained, with an emphasis on proper statistical methods and suitable interpretation of the results.


The salience of cancer and the "survivor" identity for people who have completed acute cancer treatment: a qualitative study.
Globally, there are nearly 33 million persons who have survived 5 or more years after a diagnosis of cancer [1]. We explore the salience of cancer in such people's self-concept as an important element for creating patient-centered care for those living with a cancer history. Our data are responses to a free-listing exercise and subsequent qualitative interviews with 53 individuals aged between 45 and 74 who were diagnosed with non-Hodgkin's lymphoma or breast or prostate cancer at least 3 years prior and had completed acute treatment. Participants lived in the Baltimore-Washington region of the USA. Cancer was not necessarily salient to participants' current self-concept, and espousal of a "survivor" identity is complex. We construct a typology of seven contrasting meanings of "survivor" based upon participants' narratives (factual, beaten, functional, temporary, adversity, passage of time, and lucky or blessed) and present interviewees' rationales as to why they did or did not adopt a survivorship identity. We examine the complexity of "survivorship" as an identity and people's affiliation with it, as well as how this relates to other salient and fluid elements of people's sense of self within a life course perspective. Understanding how cancer factors into people's self-concept throughout the life course is important for designing effective, patient-centered programs that acknowledge diverse experiences and expectations and possible changes with the passage of time.


Prevalence and factors associated with overweight and obesity in adults with cystic fibrosis: A single-center analysis.
The relation between malnutrition and pulmonary death in patients with cystic fibrosis (CF) has resulted in intensive nutritional intervention over the last few decades, leading to a significant decline in underweight and the emergence of overweight/obesity as a potential new problem. We performed a cross-sectional database analysis of 484 adults with CF seen at the University of Minnesota CF Center between January 2015-January 2017, to determine the prevalence and pulmonary/cardiovascular risk factors associated with overweight and obesity in this population. Mean age was 35.2 ± 11.6 years. 5.2% were underweight (BMI<18.5 kg/m2), 62.6% normal weight (BMI ≥ 18.5-24.9 kg/m2), 25.6% overweight (BMI ≥ 25-29.9 kg/m2) and 6.6% obese (BMI ≥ 30 kg/m2). In the subgroup with severe genotypes, 25% had BMI ≥ 25 kg/m2. In the entire cohort, overweight/obese were likely to be older (OR = 1.04, p < 0.0001) and to have a mild CFTR genotype (OR = 3.33, p = 0.0003) and modestly elevated triglyceride levels (OR = 1.008, p < 0.0001). The prevalence of hypertension was higher in overweight (25%) and obese (31%) than normal (17%) or underweight (16%), p = 0.01. Total cholesterol levels were higher in overweight/obese versus normal/underweight (144-147 vs 123-131 mg/dL, p = 0.04) as were LDL levels (70-71 vs 53-60 mg/dL, p = 0.02), but all were within the normal range. Percent predicted FEV1 was higher in overweight/obese (78-81%) versus underweight (59%) and normal (70%), p < 0.0001, and overweight/obese experienced significantly fewer acute pulmonary exacerbations. Overweight/obesity is common in adults with CF including those with severe genotypes. Lung function is better in the overweight/obese and lipid levels are within the normal range, albeit higher than in normal/underweight.


Glycolipid biosurfactants: Potential related biomedical and biotechnological applications.
Glycolipids, consisting of a carbohydrate moiety linked to fatty acids, are microbial surface active compounds produced by various microorganisms. They are characterized by highly structural diversity and have the ability to decrease the surface and interfacial tension at the surface and interface respectively. Rhamnolipids, trehalolipids, mannosylerythritol-lipids and cellobiose lipids are among the most popular glycolipids. Moreover, their ability to form pores and destabilize biological membrane permits their use in biomedicine as antibacterial, antifungal and hemolytic agents. Their antiviral and antitumor effects enable their use in pharmaceutic as therapeutic agents. Also, glycolipids can inhibit the bioadhesion of pathogenic bacteria enabling their use as anti-adhesive agents and for disruption of biofilm formation and can be used in cosmetic industry. Moreover, they have great potential application in industry as detergents, wetting agents and for flotation. Furthermore, glycolipids can act at the surface and can modulate enzyme activity permitting the enhancement or the inhibition of the activity of certain enzymes.


Clinical characteristics of a large cohort of patients with scleritis and episcleritis.
To evaluate the demographic characteristics, clinical features, ocular complications, and disease associations of patients with scleritis and episcleritis; as well as to delineate the risk factors for decreased vision in patients with scleritis. Retrospective case series. Five hundred patients with scleritis and 85 patients with episcleritis. The electronic health records of 500 patients with scleritis and 85 patients with episcleritis seen at 2 tertiary referral centers were reviewed and their clinical features were studied. Clinical features (pain, scleral inflammation), ocular complications (decrease in vision, anterior uveitis, peripheral ulcerative keratitis, ocular hypertension), and disease associations. In a series of 585 patients, 500 patients had scleritis (85.5%) and 85 patients had episcleritis (14.2%). Ocular complications were more frequent overall in patients with scleritis versus in those with episcleritis (45.0% vs. 19.0%), including decrease in vision (15.8% vs. 2.3%), anterior uveitis (26.4% vs. 16.5%), peripheral ulcerative keratitis (7.4% vs. 0%), and ocular hypertension (14.2% vs. 3.5%; P<0.0001 for each). Disease association was observed in 35.8% of patients with scleritis versus 27.1% of episcleritis patients, including connective tissue or vasculitic diseases in 24.8% versus 15.3%, respectively. Scleritis preceded systemic disease diagnosis in 38.7% of patients. Ocular complications (90.0%) and disease association (80.0%) occurred most often in patients with necrotizing scleritis (P<0.0001 for each). Risk factors for decrease in vision in patients with scleritis included necrotizing scleritis (odds ratio [OR], 6.63; P<0.001), posterior scleritis (OR, 2.33; P = 0.042), degree of scleral inflammation of more than 2+ (range, 0-4+; OR, 3.60; P<0.001), anterior uveitis (OR, 1.78; P = 0.033), ocular hypertension (OR, 3.19; P<0.001), and associated disease (OR, 2.66; P<0.001), mainly infectious (OR, 4.44; P<0.001). Scleritis is associated more often with ocular complications than episcleritis, and necrotizing scleritis is the type of scleritis most often associated with ocular complications and disease association. Risk factors for decrease in vision in patients with scleritis include necrotizing scleritis, posterior scleritis, scleral inflammation of more than 2+, anterior uveitis, ocular hypertension, and associated infectious disease. The author(s) have no proprietary or commercial interest in any materials discussed in this article.


Interferons and interleukins in metastatic renal cell carcinoma.
Renal cell carcinoma is diagnosed frequently when it already has metastasized. The use of immunotherapy has provided a new source of drugs to be used in the therapy of renal cell carcinoma. Interferons were the first biologics to be evaluated demonstrating a response rate of 10-30 percent. The second cytokine to be actively developed was interleukin-2, a T-cell growth factor which demonstrated activity in patients with renal cell carcinoma of 20-30 percent alone or in combination with LAK cells and other cytokines (such as interferons and tumor necrosis factor). Biologic response modifiers such as interferons and interleukins alone and in combination with other drugs have opened a new era in the therapy of renal cell carcinoma. Future development of other cytokines may pave the way for higher response rates with durable duration for this disease.


A quantitative analysis of 2-D gels identifies proteins in which labeling is increased following long-term sensitization in Aplysia.
Long-term memory for sensitization of the gill- and siphon-withdrawal reflex in Aplysia, produced by 4 days of training, is associated with increased synaptic efficacy of the connection between the sensory and motor neurons. This training is also accompanied by neuronal growth; there is an increase in the number of synaptic varicosities per sensory neuron and in the number of active zones. Such structural changes may be due to changes in the rates of synthesis of certain proteins. We have searched for proteins in which the rates of [35S]methionine labeling are altered during the maintenance phase of long-term memory for sensitization by using computer-assisted quantitative 2-D gel analysis. This method has allowed us to detect 4 proteins in which labeling is altered after 4 days of sensitization training.


The supression of DOCK family members by their specific inhibitors induces the cell fusion of human trophoblastic cells.
Among the members of the DOCK family, DOCK1-5 function as guanine-nucleotide exchange factors for small GTPase Rac1, which regulates the actin cytoskeleton. It has been reported that in model organisms the Dock-Rac axis is required for myoblast fusion. We examined the role of DOCK1-5 in trophoblast fusion herein. We used a quantitative polymerase chain reaction (qPCR) to examine the mRNA expressions of DOCK1-5 and differentiation-related genes, i.e., fusogenic genes, in human trophoblastic cell lines, BeWo and JEG-3. We treated BeWo cells with TBOPP and C21 to inhibit DOCK1 and DOCK5. Cell dynamics and cell fusion were assessed by live imaging and immunostaining. The signaling pathways induced by DOCK1/5 inhibition were examined by western blotting. DOCK1 and DOCK5 were expressed in BeWo cells. The inhibition of DOCK1 or DOCK5 did not prevent the cell fusion induced by forskolin (a common reagent for cell fusion); it induced cell fusion. DOCK1 inhibition induced cell death, as did forskolin. DOCK1 and DOCK5 inhibition for 24 and 48 h increased the expression of the genes ASCT2 and SYNCYTIN2, which code responsive proteins of trophoblast cell fusion, respectively. DOCK1 and DOCK5 inhibition participates in BeWo cell fusion, probably via pathways independent from forskolin-mediated pathways.


Restoring abutment teeth with cast restorations to fit existing removable partial dentures.
A procedure to restore an abutment tooth with a complete cast crown to fit an existing RPD has been described.


Direct and indirect antiparasitic effects of chloroquine against the virulent RH strain of Toxoplasma gondii: An experimental study.
Toxoplasmosis is a deleterious parasitic disease with harmful impact on both humans and animals. The present study was carried out to evaluate the antiparasitic effect of chloroquine (CQ), spiramycin (SP), and combination of both against the highly virulent RH HXGPRT (-) strain of Toxoplasma gondii (T. gondii) and to explore the mechanisms underlying such effect. We counted the tachyzoites in the peritoneal fluid and liver smears of mice and performed scanning and transmission electron microscopy and immunofluorescence staining of tachyzoites. Moreover, relative caspase 3 gene expression was measured by real time polymerase chain reaction of liver tissues and immunoassay of anti-apoptotic markers [B cell lymphoma-2 (Bcl-2) and X-chromosome linked inhibitor of apoptosis (XIAP)] and interferon gamma (IFN-γ) was done in liver tissues by ELISA. In addition, we estimated serum levels of aspartate transaminase (AST) and alanine transaminase (ALT) and performed histopathological examination of liver sections for scoring of inflammation. We found that both CQ and CQ/SP combination significantly reduced parasitic load in the peritoneal fluid and liver smears, induced apical disruption of tachyzoites, triggered host cell apoptosis through elevation of relative caspase 3 gene expression and suppression of both Bcl-2 and XIAP. Also, they upregulated IFN-γ level, reduced serum AST and ALT, and ameliorated liver inflammation. Either of CQ and CQ/SP combination was more effective than SP alone against T. gondii with the CQ/SP combination being more efficient. Therefore, adding CQ to other anti-Toxoplasma therapeutic regimens may be considered in future research.


The influence of retrograde contrast medium on urinary cytodiagnosis: a preliminary report.
It has been recommended that before retrograde brushing of upper urinary tract lesions to diagnose malignancy the contrast medium should be washed away with saline because of possible cellular distortion. There were 21 paired specimens from 19 patients submitted for urinary cytodiagnosis. One specimen was a contrast medium wash, similar in pH and osmolality to urine, and the other a saline wash. Cellular detail was adequate for cytodiagnosis in 20 of the 21 contrast medium specimens. Of 7 specimens from patients with malignancy 3 were diagnosed correctly as malignant, 1 was classified as suspicious and 3 were falsely negative in the contrast wash group. Of the 3 falsely negative diagnoses 2 were changed to malignant when the paired saline wash specimens were examined. Urologists should not discard the contrast medium specimen prior to retrograde brushing but should send it along with a saline wash specimen for cytodiagnosis because the discarded contrast material and irrigant may have diagnostic cells.


Super-resolution vibrational imaging based on photoswitchable Raman probe.
Super-resolution vibrational microscopy is promising to increase the degree of multiplexing of nanometer-scale biological imaging because of the narrower spectral linewidth of molecular vibration compared to fluorescence. However, current techniques of super-resolution vibrational microscopy suffer from various limitations including the need for cell fixation, high power loading, or complicated detection schemes. Here, we present reversible saturable optical Raman transitions (RESORT) microscopy, which overcomes these limitations by using photoswitchable stimulated Raman scattering (SRS). We first describe a bright photoswitchable Raman probe (DAE620) and validate its signal activation and depletion characteristics when exposed to low-power (microwatt level) continuous-wave laser light. By harnessing the SRS signal depletion of DAE620 through a donut-shaped beam, we demonstrate super-resolution vibrational imaging of mammalian cells with excellent chemical specificity and spatial resolution beyond the optical diffraction limit. Our results indicate RESORT microscopy to be an effective tool with high potential for multiplexed super-resolution imaging of live cells.


Operative treatment of tibial shaft fractures: a comparison of different methods of primary stabilisation.
Segmental fractures of the tibial shaft (AO type 42-C2) often occur after a high energy direct trauma with consecutive severe soft tissue injury and a high rate of open fractures. The blood supply of the intermediate bone fragment can be severely disturbed and therefore operative treatment is demanding. In this retrospective study, we compared three different methods of stabilisation. We reviewed the clinical charts and postoperative problems of 26 patients in a ten year period. Sixteen (62%) fractures were stabilised with an intramedullary nail, five (19%) fractures by plate osteosynthesis and five (19%) fractures with an external fixator. Bony consolidation was obtained in all patients after an average time of 11.4 months. In 17 patients (65.4%) a second operative procedure had to be performed. Pseudarthrosis was seen in 11 fractures (40%), three times in the proximal and eight times in the distal fracture. In the intramedullary nailing group, pseudarthrosis occurred in nine patients. In the group treated with an external fixator, pseudarthrosis was seen three times. After changing to a different implant bony consolidation was achieved in every patient. Conventional intramedullary nailing is not suitable for stabilisation of segmental fracture types with a short metaphyseal fracture fragment. New nails with proximal and distal interlocking in three different planes offer better stability. Bone vascularisation should not be endangered by the stabilisation procedure and optimal reduction of the fracture is an important prerequisite for uneventful fracture healing, especially in this difficult fracture configuration.


Characterization of intestinal microbiota in normal weight and overweight Border Collie and Labrador Retriever dogs.
Obesity in dogs is an emerging issue that affects canine health and well-being. Its development is ascribed to several factors, including genetic predisposition and dietary management, and recent evidence suggests that intestinal microbiota may be involved as well. Previous works have shown obesity to be linked to significant changes in gut microbiota composition in humans and mice, but only limited information is available on the role played by canine gut microbiota. The aim of this exploratory study was to investigate whether composition of canine faecal microbiota may be influenced by overweight condition and breed. All the enrolled companion dogs were young adults, intact, healthy, and fed commercial extruded pet food; none had received antibiotics, probiotics or immunosuppressant drugs in the previous six months. Labrador Retriever (LR) and Border Collie (BC) were chosen as reference breeds and Body Condition Score (BCS) on a 9-point scale as reference method for evaluating body fat. The faecal microbial communities of 15 lean (BCS 4-5/9; 7 LRs and 8 BCs) and 14 overweight (BCS > 5/9; 8 LRs and 6 BCs) family dogs were analysed using 16S rRNA gene sequencing. Moreover, for each dog, the daily intake of energy (kcal/d) and dietary macronutrients (g/d) were calculated according to an accurate feeding history collection. Firmicutes and Bacteroidetes resulted the predominant phyla (51.5 ± 10.0% and 33.4 ± 8.5%, respectively) in all dogs. Bioinformatic and statistical analysis revealed that no bacterial taxon differed significantly based on body condition, except for genus Allisonella (p < 0.05); BC gut microbiota was richer (p < 0.05) in bacteria belonging to phyla Actinobacteria (family Coriobacteriaceae in particular) and Firmicutes (Allobaculum and Roseburia genera). No remarkable differences were recorded either for diversity indices (i.e., alpha diversity, p > 0.10) or for divergence within the sample set (i.e., beta diversity, p > 0.05). PERMANOVA tests performed on single factors demonstrated the tendency of dietary protein to influence the recruited dogs' microbiota beta-diversity at amplicon sequence variant level (p = 0.08). In conclusion, the faecal microbiota of dogs involved in this exploratory study showed no major variations based on body condition. However, our findings suggested that certain bacterial taxa previously acknowledged in obesity-related studies may be detected in dissimilar amounts depending on canine breed.


Determining the feasibility for an overdose prevention line to support substance users who use alone.
The majority of opioid-related deaths occur in suburban communities with people who use alone in their homes. To reach individuals who use substances alone, Grenfell Ministries, a not for profit agency in Hamilton Ontario created a phone-based supervision service to target individuals who use substances alone. Grenfell implemented a phone line service initially as a 3-month pilot eventually operationalized to a 24/7 phoneline to determine utilization of the service and test operational feasibility. Metrics such as timing of use, number of unique clients using the service and substances used were measured. The line was provincially utilized. Between February 1st and December 10, 2020, the line was used 64 times. Most calls occurred in the evening, with fentanyl being the most used substance. EMS was dispatched 3 times for overdoses, of which 2 individuals were successfully resuscitated, and one individual's status being unknown. The overdose prevention line can be implemented to support individuals who use alone. The service can successfully reduce risk of death from individuals who use alone and could be a valuable tool in addressing the opioid crisis. Further study needs to be conducted to determine its efficacy and safety in supporting clients who use alone.


Insulin-like growth factor-induced hypertrophy of cultured adult rat cardiomyocytes is L-type calcium-channel-dependent.
The insulin-like growth factors-I and -II are potent growth stimulators in vivo and for many different cultured cells in vitro. Here IGF-I and -II are shown to directly induce hypertrophy of adult rat ventricular cardiomyocytes in serum-free medium as demonstrated by their increased size, total protein synthesis, and transcription of muscle-specific genes. The cells hypertrophied within 1 day when exposed to as little as 10(-11) M IGF-I or 10(-10) M IGF-II. With 10(-8) M IGF-I, cell size was significantly increased 34% by 1 day of culture and 57% by 2 days. With 10(-8) M IGF-II, cell size was similarly increased 32% by day 1 and 57% by 2 days. During hypertrophy, total protein synthesis was increased 2.3-fold with IGF-I and 2-fold with IGF-II. Gene expression for myosin light chain 2 and troponin I was upregulated with either growth factor. Hypertrophy induced by IGF-I was blocked by IGF binding protein-3, which binds IGF-I, while that induced by IGF-II was blocked by antibodies against IGF-II. Nicardipine, an inhibitor of L-type Ca2+-channels, completely blocked the hypertrophy induced by either IGF showing for the first time that such voltage-dependent channels are necessary for the hypertrophic effects of the IGFs on adult cardiomyocytes.


Simplified method for preparation of concentrated exoproteins produced by Staphylococcus aureus grown on surface of cellophane bag containing liquid medium.
A simplified method for preparation of concentrated exoproteins including protein A and alpha-toxin produced by Staphylococcus aureus was successfully devised. The concentrated proteins were obtained by cultivating S. aureus organisms on the surface of a liquid medium-containing cellophane bag enclosed in a sterilized glass flask. With the same amount of medium, the total amount of proteins obtained by the method presented here was identical with that obtained by conventional liquid culture. The concentration of proteins obtained by the method, however, was high enough to observe their distinct bands stained on polyacrylamide gel electrophoresis. This method was considered quite useful not only for large-scale cultivation for the purification of staphylococcal proteins but also for small-scale study using the proteins. The precise description of the method was presented and its possible usefulness was discussed.


A study by (1)H NMR on the influence of some factors affecting lipid in vitro digestion.
This article focuses on the impact of several experimental factors, including gastric acidification, intestinal transit time, presence of gastric lipase, sample/digestive fluids ratio, concentration and nature of the enzymes in intestinal juice, and bile concentration, on the extent of in vitro lipolysis when using a static model that simulates human digestion processes in mouth, stomach and small intestine. The study was carried out by Proton Nuclear Magnetic Resonance ((1)H NMR). This technique provides a complete molecular picture of lipolysis, evidencing for the first time, whether preferential hydrolysis of certain glycerides over others occurs. A lipolysis degree similar to that reported in vivo was reached by varying certain variables within a physiological range; among them, bile concentration was found to be crucial. The holistic view of this (1)H NMR study provides information of paramount importance to design sound in vitro digestion models to determine the bioaccessibility and bioavailability of lipophilic compounds.


Doxorubicin concentration time course in the myocardium after single administration to the dog. Possible role in the cardiac effects.
Three hours after i.v. administration of doxorubicin, concentrations of the drug in the myocardium are much higher (about 50 times) and decrease much more slowly (drug still detected 21 days later) than those in the plasma, so that storage results from too early readministration, with possible toxic signs.


Determinants of fecal continence in healthy, continent subjects: a comprehensive analysis by anal manometry, rectal barostat and a stool substitute retention test.
This study aimed to identify anal sphincter and rectal factors that determine anorectal filling sensations and continence during rectal filling in health. Measurements of anorectal physiology were collected from 42 continent healthy subjects participating in a prospective trial. Rectal function and capacity were assessed by barostat. Anal sphincter functions were assessed by manometry. A validated stool substitute retention test was performed in which a viscous suspension was infused into the rectum at 60 ml/min to 1,500 ml. Multivariate regression was applied to identify physiologic factors that determine anorectal sensation and continence during rectal filling. The volume at which first awareness of rectal filling occurred associated with age (p < 0.03), rectal capacity (p < 0.06) and anal resting pressure (p < 0.003); urgency associated with rectal capacity (p < 0.0007), anal resting (p < 0.04) and squeeze pressure (p < 0.02); volume at first incontinence with rectal capacity (p < 0.0001) and squeeze pressure (p < 0.04) and the maximum volume retained were closely correlated with rectal capacity only (p < 0.0001). Anorectal filling sensations and continence in health require a rectal reservoir of adequate capacity and effective voluntary anal sphincter function. Complementary associations between continence, motor and sensory function indicate the presence of an adaptive mechanism that enables timely, appropriate responses to events that threaten fecal continence.


Improving research for prostate cancer survivorship: A statement from the Survivorship Research in Prostate Cancer (SuRECaP) working group.
Survivorship care for patients with prostate cancer requires careful consideration of unique disease-specific factors, including the prolonged natural disease history, the potential for competing health risks, and the consequences of long-term androgen deprivation therapy. However, current prostate cancer survivorship research is unfortunately limited by the lack of a robust supportive evidence base, variability in the definitions and measurement of survivorship outcomes, and a heavy reliance on expert opinion. As a result, the conduct of quality prostate cancer survivorship research is of increasing importance for patients, medical providers, and other key stakeholders. This manuscript harmonizes a path forward for improving prostate cancer survivorship by defining prostate cancer survivorship and survivorship research, as well as by highlighting key research priorities and cooperative mechanisms for survivorship studies within prostate cancer, with a particular focus on men with advanced disease.


Use of antispasmodic drugs in double contrast barium enema examination: glucagon or buscopan?
To compare the spasmolytic effect of glucagon and buscopan in double contrast barium enema examination. Three hundred and twenty-four consecutive patients referred for double contrast barium enema examination were randomly allocated to receive an intravenous injection of either 1 mg of glucagon, 20 mg of buscopan or physiological saline. The transit of the barium column from rectum to caecum, the quality of the radiographs and side effects were assessed blindly without knowledge of the injected drug. Antispasmodic drugs (glucagon or buscopan) resulted in better transit of the barium column to the caecum compared to placebo (Mann-Whitney: P < 0.05), but no differences occurred between glucagon and buscopan (Mann-Whitney: P > 0.05). Buscopan produced better distension of the rectosigmoid than glucagon or placebo (P < 0.05). Of 109 patients who received buscopan five complained of blurred vision afterwards. Because buscopan is less expensive and more effective in distending the colon than glucagon, it is preferred for the routine double contrast examination. However, patients should be warned about the possibility of temporary visual impairment.


Provision of simulation-based training (SBT) within UK vascular surgery training programmes.
Simulation based training (SBT) enhances endovascular psychomotor skill acquisition and is a requirement of the UK vascular surgical curriculum. We aimed to assess the provision and obstacles to the delivery of SBT within regional UK vascular surgical training programmes. An electronic survey was distributed to all UK regional vascular surgical training programme directors (TPDs) assessing SBT regional infrastructure and provision. The survey response rate was 12/14 (86%). All regions incorporated SBT into regional training programmes, but with varying regularity: 50% every 6-12 months, 25% every 3-6 months and 25% bi-monthly. Twenty-five percent of regions provide SBT in conjunction with vascular surgery from another region and 33% of regions combine with interventional radiology training programmes. Only seven regions possess a high-fidelity endovascular simulator and a further 2 have access to industry-sponsored facilities. The majority of SBT (92%) is delivered by consultants outside of their NHS or deanery contracts. All TPDs reported a regular reliance (>50%) on industry sponsorship for the provision of SBT and only 3 TPDs reported receiving sufficient deanery funding for the majority of SBT. The provision of SBT within regional vascular surgical training programmes is variable and hindered by insufficient resources and funding. A uniform policy for the provision of SBT is required to address these regional disparities.


Impact of Proximal and Distal Pocket Site-Directed Mutations on the Ferric/Ferrous Heme Redox Potential of Yeast Cytochrome-c-Peroxidase.
Cytochrome-c-peroxidase (CCP) contains a five-coordinate heme active site. The reduction potential for the ferric to ferrous couple in CCP is anomalously low and pH dependent (Eo = ~-180 mV vs. S.H.E. at pH 7). The contribution of the protein environment to the tuning of the redox potential of this couple is evaluated using site directed mutants of several amino acid residues in the environment of the heme. These include proximal pocket mutation to residues Asp-235, Trp-191, Phe-202 and His-175, distal pocket mutation to residues Trp-51, His-52, and Arg-48; and a heme edge mutation to Ala-147. Where unknown, the structural changes resulting from the amino acid substitution have been studied by X-ray crystallography. In most cases, ostensibly polar or charged residues are replaced by large hydrophobic groups or alternatively by Ala or Gly. These latter have been shown to generate large, solvent filled cavities. Reduction potentials are measured as a function of pH by spectroelectrochemistry. Starting with the X-ray derived structures of CCP and the mutants, or with predicted structures generated by Molecular Dynamics (MD), predictions of redox potential changes are modeled using the Protein Dipoles Langevin Dipoles (PDLD) method. These calculations serve to model an electrostatic assessment of the redox potential change with simplified assumptions about heme iron chemistry, with the balance of the experimentally observed shifts in redox potential being thence attributed to changes in the ligand set and heme coordination chemistry, and/or other changes in the structure not directly evident in the X-ray structures (e.g. ionization states, specific roles played by solvent species, or conformationally flexible portions of the protein). Agreement between theory and experiment is good for all mutant proteins with the exception of the mutation Arg 48 to Ala, and His 52 to Ala. In the former case, the influence of phosphate buffer is adduced to account for the discrepancy, and measurements made in a bis-tris propane/2-(N-morpholino)ethanesulfonic acid buffer system agree well with theory. For the latter case, an unknown structural element relevant to His-52, and/or solvent influence in the mutant akin to anion binding in the distal pocket (though lacking proof that it is) manifests in this mutant. The use of exogenous (sixth) ligands in dissecting the contributions to control of redox potential are also explored as a pathway for model building.


First records of the genus Phrurotimpus Chamberlin amp; Ivie, 1935 from China, with two new species and one new combination (Araneae: Phrurolithidae).
The genus Phrurotimpus Chamberlin Ivie, 1935, previously known only from the Nearctic, is found in Asia for the first time, with species recorded from the Yunnan Province of China. Two new species are described from both sexes, P. daliensis sp. n. and P. baoshanensis sp. n., and one new combination, P. lasiolepis (Fu, Chen Zhang, 2016) comb. n., are reported in this study.


The Orbit as Seen Through Different Surgical Windows: Extensive Anatomosurgical Study.
A thorough understanding of the orbit, structures within it, and complex spatial relationships among these structures bears relevance in a variety of neurosurgical cases. We describe the 3-dimensional surgical anatomy of the orbit and fragile and complex network of neurovascular architectures, flanked by a series of muscular and glandular structures, found within the orbital dura.


Primary prophylaxis for Pneumocystis jirovecii pneumonia in patients with connective tissue diseases.
The aim of our study was to examine the primary prophylactic effect of sulfamethoxazole/trimethoprim single strength (SMZ/TM SS) against Pneumocystis jirovecii pneumonia (PCP) in connective tissue disease (CTD) patients with immune dysfunction induced by the long-term use of prednisolone. Prevalence of adverse drug reactions (ADRs) to sulfonamide in these patients was the secondary outcome. This was a retrospective cohort study. Medical records of CTD patients who were treated with prednisolone ≥20 mg per day or equivalent doses of corticosteroid for more than 2 weeks and were followed for at least 12 weeks after receiving this dosage of corticosteroids at the Rheumatology clinic of Ramathibodi Hospital between October 2006 and September 2007 were reviewed. Information regarding clinical status, laboratory features, and clinical course of the enrolled subjects was recorded. There were 138 episodes of PCP risk in 132 CTD patients; 59 episodes received SMZ/TM SS, while 79 episodes did not. All 6 PCP cases developed in patients without prophylaxis with an overall incidence of 4.3%. The incidence of PCP between the 2 groups was significantly different (P = 0.038). Absolute risk reduction and relative risk reduction were 7.3% and 100%, respectively. All ADR developed in 5 systemic lupus erythematosus patients (8.5%): 4 had drug rashes and 1 had mild hepatitis. There was no correlation between the use of, or allergic reactions to, SMZ/TM and lupus flare. Sulfamethoxazole/trimethoprim single strength can be used effectively as a primary prophylaxis against PCP in high-risk CTD patients. Only mild ADR developed at this dosage. Further evaluations in larger groups of CTD patients are warranted.


Before you see it, you see its parts: evidence for feature encoding and integration in preschool children and adults.
Preschool children and adults were compared in two experiments examining the basic issue of whether perceptual representations of objects are built-up from independent features along the dimensions of size and brightness. Experiment 1 was a visual search experiment. Subjects searched for targets which differed from distractors either by a single feature or by a conjunction of features. Results from preschoolers were comparable to those from adults, and were consistent with Treisman and Gelade's (1980, Cognitive Psychology, 12, 97-136) feature-integration theory of attention. Their theory states that independent features are encoded in parallel and are later combined with a spatial attention mechanism. However, children's significantly steeper conjunctive search slope indicated a slower speed of feature integration. In Experiment 2, four mathematical models of pattern recognition were tested against classification task data. The findings from both age groups were again consistent with a model assuming that size and brightness features are initially registered, and then integrated. Moreover, the data from Experiment 2 imply that perceptual growth entails small changes in the discriminability of featural representations; however, both experiments show that the operations performed on these representations are the same developmentally.


Anti-PD-1 therapy plus chemotherapy versus anti-PD-1 therapy alone in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia: a multicenter, retrospective study.
Synergistic antitumor effects of immunotherapy and chemotherapy have been demonstrated in several solid tumors. However, this combination strategy has not been addressed in gestational trophoblastic neoplasia (GTN) cases. We therefore compared the safety and therapeutic effect of anti-programmed cell death 1 (PD-1) therapy combined with chemotherapy versus anti-PD-1 monotherapy among high-risk chemorefractory or relapsed GTN patients. This retrospective cohort study was conducted at three teaching hospitals in China. Chemorefractory or relapsed GTN cases receiving anti-PD-1 therapy combined with chemotherapy or anti-PD-1 monotherapy were selected from each center between August 2018 and March 2022. Study endpoints included objective response rate (ORR), treatment duration, overall survival (OS) and progression-free survival (PFS). The nature, prevalence and severity of treatment-related adverse events (TRAEs) were evaluated. This work enrolled 66 cases. Thirty-five and 31 patients received anti-PD-1 therapy alone and combined with chemotherapy, respectively. The combined treatment dramatically increased the objective response rate from 62.9% (22/35) to 96.8% (30/31) (p < 0.001). The median durations until complete response were 2.2 (interquartile range [IQR], 1.4-4.2) and 2.8 (IQR, 1.8-2.8) months in the anti-PD-1 monotherapy and combined treatment cohorts, respectively (P = 0.299). The complete response rate (CRR) for anti-PD-1-refractory patients to salvage chemotherapy was 84.6% (11/13). No significant difference in OS [HR 0.50 (95% CI 0.07-3.24), p = 0.499] was detected between anti-PD-1 cohort and anti-PD-1 plus chemotherapy cohort. The PFS in combined group was significantly longer than in anti-PD-1 group [HR 0.06 (95% CI 0.02-0.16), p < 0.001]. TRAEs were observed in 27 (77.1%) and 25 (80.6%) patients receiving anti-PD-1 therapy monotherapy and combined therapy, respectively (p = 0.729). Anti-PD-1 therapy combined with chemotherapy exhibits sustainably improved antitumor effect and tolerable toxic effects among high-risk chemorefractory or relapsed GTN cases. Patients not responding to PD-1 inhibitors can be effectively rescued with salvage chemotherapy. The study was supported by National Natural Science Foundation of China (81971475 and 81972451), and the National High Level Hospital Clinical Research Funding (2022-PUMCH-B-083 and 2022-PUMCH-B-084).


Discovery of a spawning ground reveals diverse migration strategies in Atlantic bluefin tuna (Thunnus thynnus).
Atlantic bluefin tuna are a symbol of both the conflict between preservationist and utilitarian views of top ocean predators, and the struggle to reach international consensus on the management of migratory species. Currently, Atlantic bluefin tuna are managed as an early-maturing eastern stock, which spawns in the Mediterranean Sea, and a late-maturing western stock, which spawns in the Gulf of Mexico. However, electronic tagging studies show that many bluefin tuna, assumed to be of a mature size, do not visit either spawning ground during the spawning season. Whether these fish are spawning in an alternate location, skip-spawning, or not spawning until an older age affects how vulnerable this species is to anthropogenic stressors including exploitation. We use larval collections to demonstrate a bluefin tuna spawning ground in the Slope Sea, between the Gulf Stream and northeast United States continental shelf. We contend that western Atlantic bluefin tuna have a differential spawning migration, with larger individuals spawning in the Gulf of Mexico, and smaller individuals spawning in the Slope Sea. The current life history model, which assumes only Gulf of Mexico spawning, overestimates age at maturity for the western stock. Furthermore, individual tuna occupy both the Slope Sea and Mediterranean Sea in separate years, contrary to the prevailing view that individuals exhibit complete spawning-site fidelity. Overall, this complexity of spawning migrations questions whether there is complete independence in the dynamics of eastern and western Atlantic bluefin tuna and leads to lower estimates of the vulnerability of this species to exploitation and other anthropogenic stressors.


Ethical Principles and Guidelines of Global Health Nursing Practice.
Nurses are among the many U.S. health professionals engaged in international learning or service experiences and often travel to low-resource countries lacking guidance for ethical practice, respect for host partners, or collaborative work in different health systems. The aim of this study is to develop evidence-based principles or guidelines for ethical global health nursing practice. A three-round Delphi study was conducted. Global health nurse experts participated in Round 1 focus group, followed by nurses with global health expertise ranking global health nursing statements in Rounds 2 and 3. Findings led to 10 Ethical Principles for Global Health Nursing Practice and 30 statements for Ethical Guidelines in Global Health Nursing. These Ten principles address beneficence, nonmaleficence, dignity, respect, autonomy, social justice, and professional practice. The 30 guidelines offer more specific actions nurses must consider when working in global settings.


Rituximab in treatment of anti-GBM antibody glomerulonephritis: A case report and literature review.
Anti-glomerular basement membrane (GBM) disease is a T cell-mediated disease that has a poor prognosis with conventional therapy. We tested rituximab as a primary therapy to reduce anti-GBM antibody produced by B cells. A 53-year old woman with complaints of a fever, headache and abdominal discomfort showed renal failure with elevated anti-GBM antibody, and renal biopsy revealed crescentic necrotizing glomerulonephritis with linear immunoglobulin G (IgG) 1 deposition along GBM. The patient's plasma contained autoantibodies against Goodpasture antigen, which is the NC domain of collagen IVα3, and CD4-positive helper T cells were found surrounding crescent glomeruli with the coexistence CD20-positive B cells. Rituximab with steroid and plasma exchange. The levels of autoantibody for Goodpasture antigen were reduced, and the patient was able to temporarily withdraw from hemodialysis. B cell depletion with rituximab is effective as an initial therapy for anti-GBM disease.


Sterically stabilized gelatin microassemblies of noscapine enhance cytotoxicity, apoptosis and drug delivery in lung cancer cells.
Noscapine, recently identified as anticancer due to its microtubule-modulating properties. It is presently in Phase I/II clinical trials. The therapeutic efficacy of noscapine has been established in several xenograft models. Its pharmacokinetic limitations such as low bioavailability and high ED50 impede development of clinically relevant treatment regimens. Here we present design, synthesis, in vitro and in vivo characterization of sterically stabilized gelatin microassemblies of noscapine (SSGMS) for targeting human non-small cell lung cancer A549 cells. The average size of the sterically stabilized gelatin microassemblies of noscapine, SSGMS was 10.0±5.1 μm in comparison to noscapine-loaded gelatin microassemblies, GMS that was 8.3±5.5 μm. The noscapine entrapment efficiency of SSGMS and GMS was 23.99±4.5% and 24.23±2.6%, respectively. Prepared microassemblies were spherical in shape and did not show any drug and polymer interaction as examined by FTIR, DSC and PXRD. In vitro release data indicated that SSGMS and GMS follow first-order release kinetics and exhibited an initial burst followed by slow release of the drug. In vitro cytotoxicity evaluated using A549 cells showed a low IC50 value of SSGMS (15.5 μM) compared to GMS (30.1 μM) and free noscapine (47.2 μM). The SSGMS can facilitate a sustained therapeutic effect in terms of prolonged release of noscapine as evident by caspase-3 activity in A549 cells. Concomitantly, pharmacokinetic and biodistribution analysis showed that SSGMS increased the plasma half-life of noscapine by ~9.57-fold with an accumulation of ~48% drug in the lungs. Our data provides evidence for the potential usefulness of SSGMS for noscapine delivery in lung cancer.


The Effects of Different Pressure Pneumoperitoneum Models Created By Standard or Heated-Humidified CO2 Insufflation on Ovary and Peritoneum: an Experimental Study in Rats.
There is still controversy over whether structural and morphological changes can be observed in tissues depending on the carbon dioxide (CO2) nature or the applied intra-abdominal pressures (IAP). This study aimed to investigate the effects of different pressure or CO2 nature used for pneumoperitoneum in gynecological laparoscopic surgery on inflammation, DNA damage, oxidative stress, and histopathological changes in ovarian and peritoneal tissue. For this purpose, forty female rats were randomly divided into 6 groups and different pneumoperitoneum models were created in these groups. Rats in group other than control and sham groups received standard (CD) or heated-humidified CO2 (HH) insufflations at low (4 mmHg) or high pressure (8 mmHg). The ovary and peritoneum sections were evaluated microscopically for apoptotic index (API) and API scoring was calculated. Tissue and plasma interleukin-6 (IL-6), tumor necrotizing factor-alpha (TNF-α), anti-Mullerian hormone (AMH) and 8-hydroxydeoxyguanosine (8-OHdG) levels were analyzed with enzyme-linked immunosorbent assay (ELISA). The most severe changes occurred in the 8CD group microscopically, while the least severe changes occurred in the 4HH group. All histopathological parameters except for ovarian apoptotic index and peritoneal PCNA at low pressure were higher in the CD group. TNF-α and 8-OHdG levels were higher in the CD group at both low and high pressures. Standard CO2 caused more prominent histopathological changes at high pressures and systemic inflammation in both pressure groups. The least change between the experimental study groups in terms of histopathological and biochemical was observed in the low-pressure heated-humidified group.


Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients.
An increasing amount of experimental and epidemiological evidence implicates the involvement of oxygen derived radicals in the pathogenesis of cancer development. Oxygen derived radicals are able to cause damage to membranes, mitochondria, and macromolecules including proteins, lipids and DNA. Accumulation of DNA damages has been suggested to contribute to carcinogenesis. It would, therefore, be advantageous to pinpoint the effects of oxygen derived radicals in cancer development. In the present study, we investigated the relationship between oxidative stress and breast cancer development in tissue level. Breast cancer is the most common malignant disease in Western women. Twenty-one breast cancer patients, who underwent radical mastectomy and diagnosed with infiltrative ductal carcinoma, were used in the study. We determined coenzyme Q10 (Q) concentrations, antioxidant enzyme activities (mitochondrial and total superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase), and malondialdehyde (MDA) levels in tumor and surrounding tumor-free tissues. Q concentrations in tumor tissues significantly decreased as compared to the surrounding normal tissues (p < 0.001). Higher MDA levels were observed in tumor tissues than noncancerous tissues (p < 0.001). The activities of MnSOD, total SOD, GSH-Px and catalase in tumor tissues significantly increased (p < 0.001) compared to the controls. These findings may support that reactive oxygen species increased in malignant cells, and may cause overexpression of antioxidant enzymes and the consumption of coenzyme Q10. Increased antioxidant enzyme activities may be related with the susceptibility of cells to carcinogenic agents and the response of tumor cells to the chemotherapeutic agents. Administration of coenzyme Q10 by nutrition may induce the protective effect of coenzyme Q10 on breast tissue.


Robot Assisted Trans Axillary Thyroidectomy: A Subcontinent Experience.
To evaluate the outcome and initial hurdles of transaxillary robotic thyroidectomy in the Indian subcontinent. A total of seven (n = 7) patients were operated from August 2016 to February 2017. Ultrasonography was used as a tool to decide the size of thyroid lobe and fine needle aspiration cytology for the type of lesion. All patients underwent ipsilateral brachial plexus nerve conduction studies preoperatively. Two arm positions were evaluated. The robot was docked at the contralateral side of the surgical field. Before discharge from hospital, all patients were given a questionnaire evaluate outcome. Set 1 was answered on the day of discharge and Set 2 at one-month follow up. The most common pathology in our case series was colloid goiter (n = 4) followed by follicular lesion (n = 3). The mean console time was 167 min, with initial two cases taking more than 200 min. The maximum and minimum length of the axillary tunnel was 16 and 27 cm respectively. There was no difference with regard to complication rate with either arm position. None of the patients developed brachial plexus injury and was confirmed by normal nerve conduction study done on postoperative day three. In our experience with transaxillary robotic thyroidectomy, the problems we faced in our population were unique considering the varied physical parameters. Use of malleable retractors comes handy in these situation and we recommend the use of these over the rigid ones. Though both the arm positions had similar outcomes, the one with sideways position was more favorable.


Negative body image components as risk factors for orthorexia nervosa: Prospective findings.
Emerging theoretical and empirical evidence indicates that negative body image might be implicated in the onset or maintenance of ON symptoms. However, existing research investigating associations between negative body image and ON is limited to cross-sectional designs and has failed to consider the independent role of distinct components of body image. To overcome these limitations, the present study examined the prospective associations between five components of body image (i.e., overvaluation, dissatisfaction, preoccupation, body checking, and body image avoidance) and ON symptoms in community-based adult women. Participants were assessed at baseline and at a three-month follow-up, with 558 women included in the final analyses. After adjusting for baseline ON symptoms, higher scores on each of the five body image components at baseline significantly predicted greater increases in ON symptoms in univariate analyses. However, in multivariate analyses, overvaluation with weight and shape was the only component of body image to uniquely predict ON symptoms. Findings suggest that certain components of negative body image may increase the risk for ON symptoms. Findings also lend support to recent proposals that ON may be better viewed as a variant of an existing eating disorder, given that both appear to share similar underlying risk factors.


Quantification of P21 mRNA in biopsy specimens of colon tissue at different stages of neoplastic transformation.
Induction of the P21 protein is an integral part of cell growth arrest associated with the cellular response to senescence or damage. Changes in the P21 protein level are often observed in tumour cells and it is suggested, that they correlate with malignancy. We studied the P21 gene expression at the mRNA level in biopsy specimens from colitis ulcerosa, adenomas and adenocarcinomas using TaqMan assay. Our results showed, that quantity of the P21 transcript was evidently lower in the cases with adenocarcinomas than in the cases with colitis ulcerosa or adenomas.


Cell surface coat of human and rat bladder urothelium. I. Ruthenium-red studies in non-neoplastic and neoplastic cells.
We have studied the ultrastructure of glycocalyx at the luminal surface of normal and diseased urothelium from humans and rats with ruthenium red staining. A correlation between the thickness and staining intensity of the glycocalyx and the surface topography of the luminal surface was observed. An intensely stained thick glycocalyx was associated with prominent surface microvilli seen in the following conditions in humans: some control urothelium, inverted papilloma, well and moderately differentiated transitional cell carcinomas and mucin producing adenocarcinomas. These changes were also present in rats with FANFT-induced preneoplastic and neoplastic changes. A thin glycocalyx was associated with a scalloped luminal surface containing asymmetric unit membrane plaques and was found in some control humans urothelium and in normal rat urothelium. A thin glycocalyx was also associated with the relatively smooth surface seen in poorly differentiated transitional cell carcinomas as well as in some mucin producing adenocarcinomas. We suggest that urothelial glycocalyx, as demonstrated by ruthenium red staining, correlates with the luminal surface topography rather than specific pathological conditions of the bladder.


Identifying obese women most at risk from cardiovascular disease.
In Western countries, more women than men die every year of cardiovascular disease (CVD) and women spend more life years with cardiovascular disease than men. Fortunately, premature cardiovascular disease in women is preventable. Evidence-based guidelines for the prevention of cardiovascular disease in women recommend an initial risk assessment. However, recommended risk-assessment tools such as the Systematic Coronary Risk Evaluation (SCORE) system may not be sufficient to detect risk in women with obesity. A further barrier to prevention in women is the fact that physicians may underestimate the effects of risk factors that are particularly dangerous or prevalent in women. These include type 2 diabetes, hypertension, smoking, abdominal obesity, poor exercise capacity and the metabolic syndrome. Several of these factors, as well as some novel biomarkers, may increase the risk of cardiovascular disease relatively more in women than in men. To assess risk in obese women, a multifactorial assessment that encompasses assessment of body-fat distribution should be undertaken. Weight loss and lifestyle changes that have been shown to improve risk-factor profiles are crucial interventions and should be considered, even if standard risk calculators do not indicate an elevated cardiovascular risk.


Diagnostic value for coronary artery disease of chest pain during dipyridamole-thallium stress testing.
Intravenous dipyridamole with thallium imaging permits stress testing for coronary artery disease (CAD) without exercise. Chest pain may occur with dipyridamole-thallium testing, but its diagnostic significance is uncertain. Forty-five patients who had coronary angiography, no revascularization and chest pain during dipyridamole-thallium testing were identified. These patients were matched blindly by sex and age to 45 patients who had coronary angiography, no revascularization and no chest pain reported during the dipyridamole-thallium test. In the groups with versus without chest pain, 9 versus 24% had no CAD, 16 versus 16% had 1-vessel disease, 38 versus 29% had 2-vessel CAD and 38 versus 29% had 3-vessel CAD. These differences did not achieve statistical significance. Also, there were no evident differences in the severity of angiographic CAD by vessel or by percent of stenosis (p greater than 0.50). There was only a moderate association with ischemic ST changes (40 versus 16%, p less than 0.02). Chest pain with concurrent ischemic ST changes also failed to predict any difference in distribution or severity of angiographic stenoses. We conclude that chest pain during dipyridamole-thallium testing is not closely related to the severity of CAD and has little diagnostic value.


Evaluation of anesthetic effects on parameters for the in situ rat brain perfusion technique.
Studies of drug distribution to brain should be controlled for the experimental method used. Numerous methods have been employed to ascertain brain distribution and many of these approaches use anesthetic agents. The in situ rat brain perfusion method is one of the most sensitive and widely used methods for evaluating brain distribution profiles. There has been no evaluation of the effects of anesthetic agents on parameters associated with this method (i.e. cerebral perfusion fluid flow, brain vascular volume and blood-brain barrier permeability). We evaluated the effects of the anesthetic agents pentobarbital and ketamine combinations on these baseline parameters. The results suggest that the anesthetic agent has no effect on these parameters and anesthetic selection is open to the choice of the investigator when using the perfusion method.


Transfer of human membrane surface components by incorporating human cells into intact animal tissue by cell-tissue electrofusion in vivo.
Current animal models employed for the study of the obligate human pathogen Neisseria gonorrhoeae fail to utilize specific human gonococcal attachment receptors required to initiate pathogenesis in a clinically meaningful way. This communication presents evidence that suggests that cell-tissue electrofusion may be employed to create an animal model for this human specific pathogen. This new biotechnology was used to incorporate human membrane gonococcal receptors directly into epithelium of laboratory animals and subsequently infecting the histologically modified tissue with N. gonorrhoeae strain Pgh 3-2.


Inhibition of nitric oxide formation does not protect murine cortical cell cultures from N-methyl-D-aspartate neurotoxicity.
We examined the role of nitric oxide in N-methyl-D-aspartate (NMDA) receptor-mediated neurotoxicity in rat and mouse primary cortical cell cultures. In rat and mouse cultures, the NO synthase inhibitor, NG-Nitro-L-arginine, blocked cGMP formation but not neuronal cell death following a 5-10 min exposure to 300-500 microM NMDA. NG-Monomethyl-L-arginine was also unable to prevent neuronal death. In contrast, the non-competitive NMDA receptor antagonist, dextrorphan, prevented both cGMP formation and cell death. While other data suggest that the synthesis of nitric oxide can mediate NMDA receptor-mediated neurotoxicity, present results suggest that such synthesis is not necessarily required.


Traumatic injuries: an online study guide.
The Editorial Board of the Journal of Endodontics has developed a literature-based study guide of topical areas related to endodontics. This study guide is intended to give the reader a focused review of the essential endodontic literature and does not cite all possible articles related to each topic. Although citing all articles would be comprehensive, it would defeat the idea of a study guide. This section will present classification of traumatic injuries, crown/root and root fractures, canal obliteration secondary to traumatic injuries, root resorption secondary to traumatic injuries (internal resorption, invasive cervical resorption, and external resorption), horizontal root fractures, treatment of the avulsed tooth, splinting, pulp vitality secondary to traumatic injuries, alternative methods for testing for pulp vitality, and treatment of the intruded tooth.


Protection by opioid ligands against modification of the opioid receptor by a carbodiimide.
Opioid receptors in membranes prepared from guinea-pig cerebellum were modified irreversibly by treatment with a water soluble carbodiimide, 1-ethyl,3-(3-dimethylaminoethyl)carbodiimide (EDAC). This decreased the number of [3H]bremazocine binding sites (Bmax reduced from 140 to 100 fmol/mg by 1 mM EDAC) without changing their affinity. When the EDAC concentration used was sufficient (500 mM) to inactivate almost all of the opioid receptors, the modification was partly prevented by inclusion of high concentrations (100 microM) of opioid agonists ([D-Ala2, MePhe4, Glyol5]-enkephalin, [D-Ala2, D-Leu5]-enkephalin,(+)-trans-N-methyl-N-[2-(1-pyrrolidinyl)- cyclohexyl]benzo(b)thiophene-4-acetamide hydrochloride), although they exhibited equal efficacy irrespective of their mu, delta or kappa type selectivity. However, almost all of the opioid binding sites were protected when a guanine nucleotide analogue (GppNHP, 100 microM) was also included with the agonists during carbodiimide treatment.