Minimally invasive application of botulinum toxin A in patients with idiopathic rhinitis

<p>Abstract</p> <p>Background</p> <p>Nasal hypersecretion due to idiopathic rhinitis can often not be treated sufficiently by conventional medication. Botulinum toxin A (BTA) has been injected into the nasal mucosa in patients with nasal hypersecretion with a reduction of rhinorrhea lasting for about 4 to 8 weeks. Since the nasal mucosa is well supplied with glands and vessels, the aim of this study was to find out if the distribution of BTA in the nasal mucosa and a reduction of nasal hypersecretion can also be reached by a minimally invasive application by sponges without an injection.</p> <p>Methods</p> <p>Patients were randomly divided into two groups. The effect of BTA (group A, C, D) or saline as placebo (group B) was investigated in 20 patients with idiopathic rhinitis by applying it with a sponge soaked with BTA (40 units each nostril) or saline. Subgroups C and D contained these patients of group A and B who did not improve in symptoms one week after the original treatment (either BTA or saline) who then received the alternative medication. Changes of symptoms (rhinorrhea, nasal obstruction) were scored by the patients in a four point scale and counted (consumption of tissues, sneezing) in a diary. The patients were followed up weeks 1, 2, 4, 8 and 12.</p> <p>Results</p> <p>There was a clear reduction of the amount of secretion in group A compared to group B, C and D. This did not correlate with the tissue consumption, which was comparably reduced in group A and B, but reduced less in group C and D. Sneezing was clearly reduced in group A but comparably unchanged in group B and C and increased in group D. Nasal congestion remained unchanged.</p> <p>Conclusion</p> <p>In some patients with therapy-resistant idiopathic rhinitis BTA applied with a sponge is a long-lasting and minimal invasive therapy to reduce nasal hypersecretion.</p

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

Valproate, thalidomide and ethyl alcohol alter the migration of HTR-8/SVneo cells

BACKGROUND: Valproate, thalidomide and alcohol (ethanol) exposure during the first trimester of pregnancy is known to cause several developmental disorders. All these teratogens are known to pass the placental barrier and interfere directly with the normal development of the fetus. However, these teratogens also alter the formation and function of the placenta itself which may in turn affect the proper nourishment and development of the fetus. Optimum development of the placenta requires adequate invasion of trophoblast into the maternal uterine tissues. Changes in the migratory behavior of trophoblast by maternal exposure to these teratogens during placentogenesis may therefore alter the structure and function of the placenta. METHODS: In the present study, the effects of sodium valproate, thalidomide and alcohol on the migration of human first trimester trophoblast cell line (HTR-8/SVneo) were examined in vitro. Cells were cultured in the wells of 48-well culture plates as mono or multilayers. Circular patches of cells were removed from the center of the wells by suction, and the migration of cells into the wound was studied using microscopy. Effects of low and high concentrations of valproate, thalidomide and alcohol were examined on the healing of wounds and on the migration rate of cells by determining the wound areas at 0, 3, 6, 12, 24 and 48 h. Effects of drugs and alcohol on the proliferation and the expression levels of integrin subunits beta1 and alpha5 in cells were examined. RESULTS: The migration rates of trophoblast differed between wounds created in mono and multilayers of cells. Exposure to teratogens altered the migration of trophoblast into mono and multilayer wounds. The effects of valproate, thalidomide and alcohol on the proliferation of cells during the rapid migratory phase were mild. Drug exposure caused significant changes in the expression levels of beta1 and alpha5 integrin subunits. CONCLUSION: Results suggest that exposure to valproate, thalidomide or alcohol during the first trimester of pregnancy may change the ultrastructure of the placenta by altering the migration of trophoblast cells and this effect may be mediated by drug- or alcohol-induced changes in the expression levels of beta1 and alpha5 integrin subunits

Will Patients Benefit from Regionalization of Gynecologic Cancer Care?

OBJECTIVE: Patient chances for cure and palliation for a variety of malignancies may be greatly affected by the care provided by a treating hospital. We sought to determine the effect of volume and teaching status on patient outcomes for five gynecologic malignancies: endometrial, cervical, ovarian and vulvar carcinoma and uterine sarcoma. METHODS: The Florida Cancer Data System dataset was queried for all patients undergoing treatment for gynecologic cancers from 1990-2000. RESULTS: Overall, 48,981 patients with gynecologic malignancies were identified. Endometrial tumors were the most common, representing 43.2% of the entire cohort, followed by ovarian cancer (30.9%), cervical cancer (20.8%), vulvar cancer (4.6%), and uterine sarcoma (0.5%). By univariate analysis, although patients treated at high volume centers (HVC) were significantly younger, they benefited from an improved short-term (30-day and/or 90-day) survival for cervical, ovarian and endometrial cancers. Multivariate analysis (MVA), however, failed to demonstrate significant survival benefit for gynecologic cancer patients treated at teaching facilities (TF) or HVC. Significant prognostic factors at presentation by MVA were age over 65 (HR = 2.6, p<0.01), African-American race (HR = 1.36, p<0.01), and advanced stage (regional HR = 2.08, p<0.01; advanced HR = 3.82, p<0.01, respectively). Surgery and use of chemotherapy were each significantly associated with improved survival. CONCLUSION: No difference in patient survival was observed for any gynecologic malignancy based upon treating hospital teaching or volume status. Although instances of improved outcomes may occur, overall further regionalization would not appear to significantly improve patient survival

Talking Less during Social Interactions Predicts Enjoyment: A Mobile Sensing Pilot Study

Can we predict which conversations are enjoyable without hearing the words that are spoken? A total of 36 participants used a mobile app, My Social Ties, which collected data about 473 conversations that the participants engaged in as they went about their daily lives. We tested whether conversational properties (conversation length, rate of turn taking, proportion of speaking time) and acoustical properties (volume, pitch) could predict enjoyment of a conversation. Surprisingly, people enjoyed their conversations more when they spoke a smaller proportion of the time. This pilot study demonstrates how conversational properties of social interactions can predict psychologically meaningful outcomes, such as how much a person enjoys the conversation. It also illustrates how mobile phones can provide a window into everyday social experiences and well-being

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Recombination and positive selection identified in complete genome sequences of Japanese encephalitis virus

The mosquito-borne Japanese encephalitis virus (JEV) causes encephalitis in man but not in pigs. Complete genomes of a human, mosquito and pig isolate from outbreaks in 1982 and 1985 in Thailand were sequenced with the aim of identifying determinants of virulence that may explain the differences in outcomes of JEV infection between pigs and man. Phylogenetic analysis revealed that five of these isolates belonged to genotype I, but the 1982 mosquito isolate belonged to genotype III. There was no evidence of recombination among the Thai isolates, but there were phylogenetic signals suggestive of recombination in a 1994 Korean isolate (K94P05). Two sites of the genome under positive selection were identified: codons 996 and 2296 (amino acids 175 of the non-structural protein NS1 and 24 of NS4B, respectively). A structurally significant substitution was seen at NS4B position 24 of the human isolate compared with the mosquito and pig isolates from the 1985 outbreak in Thailand. The potential importance of the two sites in the evolution and ecology of JEV merits further investigation

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

A comparison of polarized and non-polarized human endometrial monolayer culture systems on murine embryo development

BACKGROUND: Co-culture of embryos with various somatic cells has been suggested as a promising approach to improve embryo development. Despite numerous reports regarding the beneficial effects of epithelial cells from the female genital tract on embryo development in a co-culture system, little is known about the effect of these cells when being cultured under a polarized condition on embryo growth. Our study evaluated the effects of in vitro polarized cells on pre-embryo development. METHODS: Human endometrial tissue was obtained from uterine specimens excised at total hysterectomy performed for benign indications. Epithelial cells were promptly isolated and cultured either on extra-cellular matrix gel (ECM-Gel) coated millipore filter inserts (polarized) or plastic surfaces (non-polarized). The epithelial nature of the cells cultured on plastic was confirmed through immunohistochemistry, and polarization of cells cultured on ECM-Gel was evaluated by transmission electron microscopy (TEM). One or two-cell stage embryos of a superovulated NMRI mouse were then flushed and placed in culture with either polarized or non-polarized cells and medium alone. Development rates were determined for all embryos daily and statistically compared. At the end of the cultivation period, trophectoderm (TE) and inner cell mass (ICM) of expanded blastocysts from each group were examined microscopically. RESULTS: Endometrial epithelial cells cultured on ECM-Gel had a highly polarized columnar shape as opposed to the flattened shape of the cells cultured on a plastic surface. The two-cell embryos cultured on a polarized monolayer had a higher developmental rate than those from the non-polarized cells. There was no statistically significant difference; still, the blastocysts from the polarized monolayer, in comparison with the non-polarized group, had a significantly higher mean cell number. The development of one-cell embryos in the polarized and non-polarized groups showed no statistically significant difference. CONCLUSION: Polarized cells could improve in vitro embryo development from the two-cell stage more in terms of quality (increasing blastocyst cellularity) than in terms of developmental rate