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ObjectiveTo assess imaging utilization practices across clinical specialists in neurofibromatosis type 1 (NF1) for the evaluation of symptomatic and asymptomatic children and adults with or without plexiform neurofibromas (PN).MethodsAn institutional review board–exempt survey was administered to medical practitioners caring for individuals with NF1 at the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) meeting in September 2019. The survey included questions on respondent demographic data (9 questions), type of imaging obtained for asymptomatic (4 questions) and symptomatic (4 questions) people with and without PN, and utilization of diffusion-weighted imaging (2 questions).ResultsThirty practitioners participated in the survey. Most were academic neuro-oncologists at high-volume (>10 patients/week) NF1 centers. Of 30 respondents, 26 had access to whole-body MRI (WB-MRI). The most common approach to an asymptomatic person without PN was no imaging (adults: 57% [17/30]; children: 50% [15/30]), followed by a screening WB-MRI (adults: 20% [6/30]; children: 26.7% [8/30]). The most common approach to a person with symptoms or known PN was regional MRI (adults: 90% [27/30]; children: 93% [28/30]), followed by WB-MRI (adults: 20% [6/30]; children: 36.7% [11/30]). WB-MRI was most often obtained to evaluate a symptomatic child with PN (37% [11/30]).ConclusionsMore than 90% of practitioners indicated they would obtain a regional MRI in a symptomatic patient without known or visible PN. Otherwise, there was little consensus on imaging practices. Given the high prevalence of PN and risk of malignant conversion in this patient population, there is a need to define imaging-based guidelines for optimal clinical care and the design of future clinical trials.

ObjectiveAs part of an evaluation of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration patient representative program, we surveyed REiNS members to (1) identify facilitators and barriers to involving patient representatives and (2) understand whether and how involving patient representatives affected recommendations for clinical trial outcomes.MethodsWe administered an anonymous online survey to all REiNS members. Facilitators and barriers to patient representative involvement were solicited using a modified free listing technique; responses were inductively grouped into higher-order categories and ranked based on saliency score (Smith s). Open-ended questions assessed patient representative expectations for engagement, perceived benefits/costs of patient engagement, and patient representative contributions; responses were analyzed using conventional content analysis.ResultsA total of 63/172 (37%) members responded, including 18/30 (60%) patient representatives. Providing sufficient opportunities to meaningfully engage in research tasks and cultivating a respectful, inclusive atmosphere were key facilitators to patient representatives' satisfaction and ability to make an impact. Respondents perceived that patient representatives directly (through their input on research tasks) and indirectly (through effects on other stakeholders' knowledge and communication style) improved the organization's research, leading to selection of more meaningful, relevant, and feasible clinical trial outcome measures. Ongoing challenges to patient engagement include difficulty scheduling meetings and concerns about the level of scientific knowledge patient representatives needed to effectively engage.ConclusionsInvolving patient representatives in REiNS improved perceived quality of neurofibromatosis clinical trial outcome measures. Negotiating sufficient opportunities to engage, fostering an inclusive atmosphere, and navigating time pressures are key to effective patient engagement.

Significance Bacteriophages (“phages,” viruses that infect bacteria) are an important source of selection for bacterial populations. Phages use various structures to infect bacterial cells, and bacteria often evolve phage resistance by losing or modifying these structures. We examine a phage that uses two structures that also provide Escherichia coli cells with antibiotic resistance. We show that phage selection can result in bacteria evolving phage resistance by losing or modifying the structures. When phage resistance evolves, the bacteria sometimes also show increased antibiotic sensitivity. This result indicates an evolutionary trade-off between phage resistance and antibiotic resistance. However, we also discovered bacterial mutations that avoid the trade-off. We discuss the potential use of phage selection and evolutionary trade-offs in treating bacterial infections., Bacteria frequently encounter selection by both antibiotics and lytic bacteriophages. However, the evolutionary interactions between antibiotics and phages remain unclear, in particular, whether and when phages can drive evolutionary trade-offs with antibiotic resistance. Here, we describe Escherichia coli phage U136B, showing it relies on two host factors involved in different antibiotic resistance mechanisms: 1) the efflux pump protein TolC and 2) the structural barrier molecule lipopolysaccharide (LPS). Since TolC and LPS contribute to antibiotic resistance, phage U136B should select for their loss or modification, thereby driving a trade-off between phage resistance and either of the antibiotic resistance mechanisms. To test this hypothesis, we used fluctuation experiments and experimental evolution to obtain phage-resistant mutants. Using these mutants, we compared the accessibility of specific mutations (revealed in the fluctuation experiments) to their actual success during ecological competition and coevolution (revealed in the evolution experiments). Both tolC and LPS-related mutants arise readily during fluctuation assays, with tolC mutations becoming more common during the evolution experiments. In support of the trade-off hypothesis, phage resistance via tolC mutations occurs with a corresponding reduction in antibiotic resistance in many cases. However, contrary to the hypothesis, some phage resistance mutations pleiotropically confer increased antibiotic resistance. We discuss the molecular mechanisms underlying this surprising pleiotropic result, consideration for applied phage biology, and the importance of ecology in evolution of phage resistance. We envision that phages may be useful for the reversal of antibiotic resistance, but such applications will need to account for unexpected pleiotropy and evolutionary context.

Introduction/Background* Conization is the act of choice for the treatment of pre-malignant lesions of the cervix, enabeling histological diagnosis and the treatment of premelignant and stage 1a1 tumors. Conization is currently performed under general anesthesia with IV analgesia or without anastesia, with local analgesia injected to the cervix. Woelber & co compared the incidence and intensity of pain after conization under general or local anesthesia and found no significant differences. No study has compared the effect of analgesia administered via IV or local routh. The purpose of this study was to determin the pain rating and bleeding when undergoing conization, depending on the routh of analgesia. Methodology A prospective blind-control study comparing 30 women undergoing cervical conization under general anastesia in our hospital between 2019-2020. First 15 women (A) were administered intravenous analgesia, and second 15 women (B) addmited were administered local analgesia injection to cervix. Chi-Square test was used to find the group diffrences. Result(s)* From 30 patients recruited, one fell choosing only local anastesia, leaving 14 in group A and 15 in group B. No demographics differences were found. Extra need of analgesia in the 24 hours post-Op was found in14.3%(A) and 28.6% (B) (p-value Conclusion* Conization of the cervix under local analgesia is as effective in pain prevention as general analgetica and reduce the amount of bleeding during and possibly after the operation. More resurch is needed to conclude the preferred routh of analgesia.

Andres J Lessing describes the worry of incidental findings and how the process of giving consent could be improved

ObjectiveTo assess the perspectives of adults with neurofibromatosis 1 (NF1) regarding cutaneous neurofibroma (cNF) morbidity, treatment options, and acceptable risk–benefit ratio to facilitate the design of patient-centered clinical trials.MethodsAn online survey developed by multidisciplinary experts and patient representatives of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) cNF Working Group was distributed to adults with NF1 (n = 3,734) in the largest international database of individuals with any form of NF. Eligibility criteria included self-reported NF1 diagnosis, age ≥18 years, ≥1 cNF, and ability to read English.ResultsA total of 548 adults with NF1 responded to the survey. Respondents ranked appearance, number, and then location as the most bothersome features of raised cNF. Seventy-five percent of respondents considered a partial decrease of 33%–66% in the number or size of cNF as a meaningful response to experimental treatments. Most respondents (48%–58%) were willing to try available cNF treatments but were not aware of options outside of surgical removal. Regarding experimental agents, respondents favored topical, then oral medications. Most individuals (>65%) reported being “very much” or “extremely willing” to try experimental treatments, especially those with the highest cNF burden. Many respondents were not willing to tolerate side effects like nausea/vomiting (51%) and rash (46%). The greatest barriers to participation in cNF clinical trials were cost of participation and need to take time off work.ConclusionsMost adults with NF1 are willing to consider experimental therapies for treatment of cNF. These data will guide the design of patient-centered clinical trials for adults with cNF.

Bacterial pathogens are increasingly evolving drug resistance under natural selection from antibiotics in medicine, agriculture, and nature. Meanwhile, bacteria ubiquitously encounter bacteriophages and can rapidly evolve phage resistance. However, the role of phages in interacting with drug-resistant and drug-sensitive bacteria remains unclear. To gain insight into such relationships, we screened for and characterized phages that rely on the multi-drug efflux pump genetolC. First, we screened a collection of 33 environmental and commercialEscherichia coliphages for their ability to infect cells that lackedtolC. Our screen revealed two phages that had reduced efficiency of plating (EOP) on thetolCknockout compared to wild type. We further characterized these phages with bacterial growth curves, transmission electron microscopy, and analysis of phage-resistant mutants. Phage U136B is a curly-tailed virus in familySiphoviridaewith no ability to infect atolCknockout, suggesting TolC is the U136B receptor. Phage 132 is a contractile-tailed virus in familyMyoviridaewith reduced EOP on cells lackingompFand its positive regulatorstolCandompR. U136B and 132 differentially effect bacterial growth and lysis, and U136B-resistant mutants contain mutations of thetolCgene. Together, these results show that thetolCgene involved in drug resistance can modify bacteria-phage interactions in multiple ways, altering bacterial lysis and selection. These new phages offer utility for studying evolution, tradeoffs, and infection mechanisms.ImportanceBacteria face strong selection by antibiotics in medicine and agriculture, resulting in increasing levels of drug resistance among bacterial pathogens. Slowing this process will require an understanding of the environmental contexts in which drug resistance evolutionarily increases or decreases. In this study, we investigate two newly-isolated bacteriophages that rely on a bacterial antibiotic resistance gene. These bacteriophages vary in their interactions with drug-resistant bacteria, with one of the phages selecting for phage-resistant mutants that have mutations in the antibiotic resistance gene. Further study of these new phages will be useful to understanding evolutionary tradeoffs and how phages might be applied in natural settings to reverse the problem of drug resistance.

ObjectiveIn autumn 2012, Massachusetts schools implemented comprehensive competitive food and beverage standards similar to the US Department of Agriculture’s Smart Snacks in School standards. We explored major themes raised by food-service directors (FSD) regarding their school-district-wide implementation of the standards.DesignFor this qualitative study, part of a larger mixed-methods study, compliance was measured via direct observation of foods and beverages during school site visits in spring 2013 and 2014, calculated to ascertain the percentage of compliant products available to students. Semi-structured interviews with school FSD conducted in each year were analysed for major implementation themes; those raised by more than two-thirds of participating school districts were explored in relationship to compliance.SettingMassachusetts school districts (2013: n 26; 2014: n 21).SubjectsData collected from FSD.ResultsSeven major themes were raised by more than two-thirds of participating school districts (range 69–100 %): taking measures for successful transition; communicating with vendors/manufacturers; using tools to identify compliant foods and beverages; receiving support from leadership; grappling with issues not covered by the law; anticipating changes in sales of competitive foods and beverages; and anticipating changes in sales of school meals. Each theme was mentioned by the majority of more-compliant school districts (65–81 %), with themes being raised more frequently after the second year of implementation (range increase 4–14 %).ConclusionsFSD in more-compliant districts were more likely to talk about themes than those in less-compliant districts. Identified themes suggest best-practice recommendations likely useful for school districts implementing the final Smart Snacks in School standards, effective July 2016.

The conjugate gradient method is formulated in the Hilbert space for density and non-density dependent Hamiltonians. We apply it to the solution of the Hartree-Fock-Bogoliubov equations with constraints. As a numerical application we show calculations with the finite range density dependent Gogny force. The number of iterations required to reach convergence is reduced by a factor of three to four as compared with the standard gradient method.

Purpose: The evaluation of clinical variables that influence biochemical relapse-free survival in a cohort of patients treated by combined radiotherapy over a fixed interval. Methods and Materials: Three hundred forty-eight patients diagnosed with clinical Stage T1–T3a prostate cancer were treated with a course of 103 Pd or 125 I brachytherapy followed by a limited course of external beam radiation formed the basis for study. All censored patients had a minimum 2-year follow-up. Biochemical relapse-free survival (BRFS) was estimated using a modified American Society for Therapeutic Radiology and Oncology consensus definition. Discrete "risk groups" were developed based on BRFS as influenced by pretreatment parameters. Results: Significant risk factors contributing to biochemical failure were serum prostate-specific antigen (PSA) greater than 20 ng/mL, Gleason sum of 7 or greater, or clinical stage T2c or greater. Five-year biochemical control for those exhibiting no risk factor was 88%; one risk factor, 75%; two or more risk factors, 51%. The differences in BRFS among all three risk groups were statistically significant. Outcomes for patients presenting with PSA 10 to 20 ng/mL, but otherwise low-risk disease, fared no differently from those low risk patients presenting with PSA less than 10 ng/mL. Conclusions: Combined radiotherapy with 103 Pd or 125 I followed by external beam radiotherapy achieves a high rate of biochemical and clinical control in patients with low- to intermediate-risk clinically organ confined disease.

We evaluated the safety and efficacy of the tension-free vaginal tape procedure (TVT) in 20 consecutive women with urodynamically proven genuine stress incontinence. Mean operating time under spinal analgesia was 37.2 +/- 13 minutes and 80% were discharged within 24 hours. There were 5 uncomplicated, intraoperative bladder perforations, but no defects in healing nor tape rejection. The objective cure rate was 95%, while the subjective rate was 100%. Although follow-up was short (9-16 months), the TVT method seems to be safe and effective for stress urinary incontinence.

Adrenal cysts are uncommon lesions. The authors discuss two cases of adrenal pseudocyst, and its classification and possible pathogenesis and complications. The role of radiologic findings in preoperative evaluation of renal/suprarenal masses also is detailed.

Ziel meines Beitrages soll es sein, dem Leser sofort Selbstbedienung in fremder Erfahrung zu ermoglichen. Umsetzungsmoglichkeit zu bieten fur den eigenen Fuhrungsalltag ohne grose Transferprobleme. Es wird verzichtet auf theoretische Erlauterungen. Der praktische Lernprozes fur die strategische Planung soll bereits mit diesen Ausfuhrungen beginnen. Daher wurde eine empirische Form gewahlt. Meine Erfahrungen lassen sich am besten an einem konkreten Beispiel aufzeigen, welches aktuell in einem Tochterunternehmen eines High-Tech- und Technologiekonzerns erfolgreich abgelaufen ist. Das verantwortliche Vorstandsteam hat mit seinen oberen Fuhrungskraften, Stabsleuten und Moderatoren fur Managementtraining erarbeitet, wie strategisches Denken, Fuhlen und Handeln in allen Unternehmensbereichen und auf allen Fuhrungsebenen effizient gelernt und umgesetzt werden kann. Dabei wurde auch sichtbar, das strategische Planung an sich ein Lernprozes derjenigen ist, die sich in einem Team zusammensetzen, um uber die Zukunft des Unternehmens nachzudenken.

We examined the nonluteal production of relaxin in the pregnant baboon. In experimental animals (n = 5), the corpus luteum-bearing ovary was removed in early pregnancy (days 25-30), and intact pregnant baboons served as controls. In both groups of baboons, peripheral, uterine, and ovarian venous blood samples and amniotic fluid were collected immediately before hysterotomy, which was performed late in pregnancy (days 139-142). After hysterotomy, samples of reproductive and control tissues were obtained (placenta, decidua, myometrium, fetal membranes, and omentum). Relaxin concentrations were determined in all samples using an antiporcine relaxin RIA. In unilaterally oophorectomized pregnant baboons, peripheral plasma levels of relaxin were below the limits of detection (less than 157 pg/ml) for 100 days following corpus luteum removal, while levels in control pregnant baboons were greater than 1000 pg/ml. Relaxin levels in uterine venous plasma were comparable to peripheral plasma levels in each group. Relaxin concentrations in amniotic fluid of both groups were below the limits of detection (less than 157 pg/ml). Relaxin was found in decidua, placenta, and myometrium in those pregnant baboons in which the corpus luteum-bearing ovary had been removed over 100 days earlier. This finding together with the absence of a relaxin gradient in uterine venous plasma and undetectable relaxin levels in amniotic fluid is a strong indication of local relaxin production in reproductive tissues without contribution to peripheral plasma levels.

A continuous infusion technique for atracurium was investigated. It provided a stable neuromuscular block, with a mean infusion rate of 0.008 mg/kg/min after an initial bolus of 0.5 mg/kg. A wide individual response was found and an arbitrary infusion rate based on mass alone is therefore not possible. The above rate is thus a starting point and should be adjusted according to individual requirements, preferably by using a peripheral nerve stimulator. The technique obviates the need for repeated increments of atracurium during lengthy surgical procedures.

A technique for postoperative autotransfusion in open-heart surgery, involving minimal blood damage and contamination, is described.

The problem of tamponade due to rupture of an amoebic abscess, although rare, is extremely complex, and in the planning of the anaesthetic technique the following factors should receive attention: (i) the low cardiac output in which bradycardia, vasodilation, high inflation pressures and excessive fluid load must be avoided: (ii) pulmonary complications in which a double-lumen endotracheal tube should be considered; and (iii) sepsis.

Atracurium 0.3 mg/kg was compared with alcuronium 0.25 mg/kg as the sole muscle relaxant for tracheal intubation and abdominal relaxation for gynaecological laparoscopy in 46 patients during nitrous oxide, oxygen and halothane anaesthesia. Speed of onset, intubation conditions, effect on blood pressure and pulse rate, and ease of reversal were compared. Alcuronium had a significantly faster onset of action than atracurium; intubation conditions were adequate and abdominal relaxation was satisfactory for both drugs. The effect of atracurium was readily reversible within 10 minutes; in contrast alcuronium was significantly more resistant and mean recovery time was 28.03 minutes. Although alcuronium provided good muscle relaxation, it is not suitable for short procedures because of difficulty in reversing its action. Atracurium allowed earlier and more complete reversal of neuromuscular block.

A study was undertaken to determine whether a volume of oxygen injected from a 100 ml syringe and inhaled during a 10 m ascent would be exhaled again fully or partially by two experienced male divers. Each performed one apnoeic dive with and another without O2 augmentation. Analyses of mouth gas showed that the injected O2 had disappeared when the divers reached the surface. Any movement of the injected O2 to the alveoli through an open glottis probably resulted from simple diffusion as well as from agitation and mixing of gases by simulated respiratory activity. High-frequency positive-pressure ventilation applied by several authors, whereby sufficient gas exchange is achieved by oscillating small tidal volumes at frequencies of up to 900 per minute, may substantiate this possibility. The injected O2 was found also to have disappeared from the alveolar gas, shown by a comparison of O2 fraction differences between augmented and non-augmented dives. Injection and inhalation of the additional O2 will raise the partial pressure of O2 in the alveoli and increase oxygen transfer across the alveolar membrane into the blood, with more molecules being taken up within seconds during the ascent time. O2 augmentation in larger volumes during apnoeic diving could lead to a burst lung and must be regarded with suspicion. There is evidence that O2 augmentation by means of a small syringe attached to a trained diver's snorkel will help prevent apnoeic blackout.

A pilot study was carried out to determine whether autotransfusion increased the platelet count. Although only a small series was involved significant increases were shown.