Providers' perspectives on the reproductive decision-making of BRCA-positive women.

BACKGROUND: Reproductive decision-making is difficult for BRCA-positive women. Our objective was to assess the complexities of decision-making and identify decisional supports for patients and providers when discussing reproductive options prior to risk-reducing salpingo-oophorectomy (RRSO). METHODS: This study was of qualitive design, using data collection via semi-structured interviews conducted from November 2018 to October 2020. Individuals were included if they were identified to provide care to BRCA-positive women. In total, 19 providers were approached and 15 consented to participate. Providers were recruited from three clinics in Toronto, Ontario located at academic centers: [1] A familial ovarian cancer clinic, [2] A familial breast cancer clinic and [3] A fertility clinic, all of which treat carriers of the BRCA1/BRCA2 genetic mutation. The interview guide was developed according to the Ottawa Decision Support Framework and included questions regarding reproductive options available to patients, factors that impact the decision-making process and the role of decisional support. Interviews were transcribed and transcripts were analyzed thematically using NVIVO 12. RESULTS: Providers identified three major decisions that reproductive-aged women face when a BRCA mutation is discovered: [1] "Do I want children?"; [2] "Do I want to take the chance of passing on this the mutation?"; and [3] "Do I want to carry a child?" Inherent decision challenges that are faced by both providers and patients included difficult decision type, competing options, scientifically uncertain outcomes, and challenging decision timing. Modifiable decisional needs included: inadequate knowledge, unrealistic expectations, unclear values and inadequate support or resources. Identified clinical gaps included counselling time constraints, lack of reliable sources of background information for patients or providers and need for time-sensitive, geographically accessible, and centralized care. CONCLUSION: Our study identified a need for a patient information resource that can be immediately provided to patients who carry a BRCA genetic mutation. Other suggestions for clinical practice include more time during consultation appointments, adequate follow-up, value-centric counseling, access to psychosocial support, and a specialized decisional coach.

Patient engagement study to identify and improve surgical experience.

BACKGROUND: Patient engagement is the establishment of active partnerships between patients, families, and health professionals to improve healthcare delivery. The objective of this project was to conduct a series of patient engagement workshops to identify areas to improve the surgical experience and develop strategies to address areas identified as high priority. METHODS: Faculty surgeons and patients were invited to participate in three in-person meetings. Evaluation included identifying and developing strategies for three priority areas to improve the surgical experience and level of engagement achieved at each meeting. RESULTS: Sixteen faculty surgeons and 32 patients participated. Some 63 themes to improve the surgical experience were identified; the three highest-priority themes were physician communication, discharge process, and expectations at home after discharge. Individual improvement strategies for these three prioritized themes (12, 36 and 6 respectively) were used to develop a formal strategic plan, and included a physician communication survey, discharge process worksheet and video, and guideline regarding what to expect at home after discharge. Overall, the level of engagement achieved was considered high by over 85 per cent of the participants. CONCLUSION: A high level of patient engagement was achieved. Priorities were identified with patients and surgeons to improve surgical experience, and strategies were developed to address these areas.

Serum-free light chains adjusted for renal function are a potential biomarker for post-transplant lymphoproliferative disorders.

Post-transplant lymphoproliferative disease (PTLD) is a serious complication of solid organ transplantation. As early diagnosis remains challenging, we investigated the utility of serum-free light chain (FLC) and heavy chain/light chain pairs (HLC) as diagnostic biomarkers. Pre-treatment serum FLC and HLC levels were measured in 20 patients at their first diagnosis of B cell PTLD and in 14/20 patients during follow-up. Results were compared to serum FLC/HLC levels of 90 matched PTLD-free transplanted controls. Renal dysfunction was common in both cohorts, and combined FLC levels were often elevated above the conventional upper limit of normal (45.7 mg/L). Combined FLC levels were higher in patients with PTLD than in transplant controls (p = 0.013), and levels above the conventional ULN were associated with PTLD (OR 3.2, p = 0.05). Following adjustment to cystatin C as a marker of renal function an even stronger association was found for a (dimensionless) threshold value of 37.8 (OR 8.9, p < 0.001). In addition, monoclonal proliferation (abnormal FLC ratio, using an established renal range cutoff) was more common in PTLD than in controls (3/20 vs. 2/90, p = 0.04). Following therapy, at the time of protocolised restaging, patients experiencing subsequent sustained complete remission displayed lower FLC levels than those not experiencing such remission (p = 0.053). No relationship with HLC results was seen. Elevated polyclonal FLC levels (especially when adjusted for renal function) and monoclonal proliferation are a potential biomarker for PTLD diagnosis and disease surveillance. However, prospective validation is necessary before FLC measurement should be incorporated in follow-up of transplant recipients and PTLD management.

Tissue Factor Pathway Inhibitor Gene Polymorphism -33T → C Predicts Improved Disease-Free Survival in Colorectal Cancer.

BACKGROUND: Tissue factor pathway inhibitor (TFPI) is an anticoagulant with antimetastatic properties. The homozygous CC polymorphism of TFPI (-33T â†’ C) is associated with higher TFPI levels and lower venous thromboembolism risk. This study was the first to evaluate the impact of this polymorphism on disease-free survival (DFS) in cancer patients after curative resection. METHODS: A prospectively maintained tumor bank with clinical data was used to identify patients who underwent curative surgery for colorectal cancer between 1994 and 2006. Germline DNA was extracted from formalin-fixed, paraffin-embedded normal colonic mucosa. Single nucleotide polymorphisms for TFPI (-33T â†’ C), factor V Leiden (G1691A), and prothrombin (G20210A) were determined by polymerase chain reaction. Survival analysis was described using the Kaplan-Meier method. Multivariable regression analysis was performed using the Cox proportional hazard model. RESULTS: Of the 127 patients identified, the CC genotype was found in 11 %. Venous thromboembolism incidence was 18 % in the TT/TC (wild type/heterozygous) genotypes and 7 % in the CC genotype (p = 0.46). The CC genotype was associated with superior DFS (hazard ratio 0.34, 95 % confidence interval 0.14-0.84; p = 0.02) with 5-year DFS of 63 vs. 24 % for CC vs. TT/TC, respectively. In multivariate analysis, CC polymorphism (hazard ratio 0.28, p = 0.008) was independently associated with improved DFS. The prevalence of factor V Leiden (0.8 %) and prothrombin (1.6 %) polymorphisms was too low to detect interaction with TFPI polymorphism or DFS. CONCLUSIONS: These findings indicate that the inherited anticoagulant homozygous -33T â†’ C TFPI polymorphism may protect against colon cancer recurrence and suggests a mediating role for the coagulation system in cancer outcomes.

A Review of the Effectiveness of Breast Surgical Oncology Fellowship Programs Utilizing Kirkpatrick's Evaluation Model.

It has been 10 years since the first class of Society of Surgical Oncology (SSO) fellowship trained Breast Surgical Oncologist entered practice. To date, there has been no publications examining the effectiveness of these training programs that are today throughout North America and Europe. This evaluative review examines the effectiveness of these fellowship training programs through the lens of the Kirkpatrick Evaluation Model. An extensive review of the literature was performed, and articles were categorized to capture how fellows are reacting to the program, what they are learning, and how the program is effecting their career path and impacting their patients. We can conclude that there is both direct and indirect evidence to support the effectiveness of this training program, but there is a paucity of direct evidence as one progresses from a level 1 Kirkpatrick analysis to a level 4. This review sets the framework for program evaluation in surgical fellowships and should encourage stakeholders to constantly evaluate the impact their program is having on trainees and oncology patients.

Temporary anion states of three herbicide families.

Electron scattering studies are used to locate the energies of temporary negative ion states of three chloro-substituted molecular families of herbicidal importance: salicylic and phenoxyacetic acids and acetamides. The correlation between these energies and the computed virtual orbital energies of the compounds is examined and used to put the latter on an absolute energy scale. Such scaling of orbital energies permits the anion states of other members of these families, for which experimental data may not be available, to be estimated from the calculated orbital energies. Studies of electron reduction rates often rely on calculated LUMO energies as molecular descriptors. The use of measured anion energies as well as appropriately scaled orbital energies should serve to improve such studies in these and in related herbicides.

Understanding umbilical venous catheter insertion practices through a prospective multicenter observational study.

OBJECTIVE: To understand practices of umbilical venous catheter (UVC) insertion in tertiary level neonatal intensive care units (NICU) and investigate the outcomes of subsequent attempts following a failed initial attempt. STUDY DESIGN: Prospective, multi-center observational study of UVC insertions at tertiary level NICUs between March 2019 and January 2020. RESULTS: Of the 101 UVCs inserted at 4 centers, seventy-two (71%) were central at the first attempt and 50% were central at subsequent attempts. Patients with at least 1 failed attempt at insertion were less likely to have a centrally placed UVC (p = .009). Manipulations were less likely to be required when UVC was centrally placed during the first attempt. Maneuvers such as posterior liver mobilization used during insertion were likely to be associated with successful central placement of UVC (p = .0243). The time to complete the procedure was significantly less when the UVC was central at the first attempt (34.2 ± 20.2 vs 46.9 ± 33.8) (p = .0292). Gestational age, birth weight, and age of the baby at the insertion of the UVC, experience of the provider, and type of catheter were comparable among groups. The Shukla formula was most commonly used by providers to measure the depth of UVC placement. CONCLUSION: Repetitive attempts and manipulations were less likely to be beneficial in the successful central placement of UVC in neonates. Additionally, repetitive attempts at insertion prolonged the overall duration of the procedure.

Assignments of normally unoccupied orbitals to the temporary negative ion states of several lanthanide NMR shift reagents and comments on resonance involvement in electron circular dichroism.

We have measured the total electron scattering cross sections of several NMR shift reagent molecules X(hfc)3, where X = Yb, Er, Eu and Pr, by means of electron transmission spectroscopy (ETS) to determine their vertical attachment energies. A strong low-energy resonance (<1 eV) is observed in all of the compounds except for Yb(hfc)3. We explain this anomaly in terms of the ground-state electron configuration of each molecule. Also, with the aid of restricted open-shell Hartree-Fock (ROHF) calculations on analogous molecules with truncated fluorocarbon chains, we have assigned specific normally unoccupied orbitals to the resonances observed in ETS. To our knowledge, these molecules are the largest for which this procedure has been successfully completed. Nolting et al. (J. Phys. B 1997, 30, 5491) have demonstrated that the above NMR shift reagents exhibit electron circular dichroism (ECD) between 1 and 10 eV. Using our new total cross section data, we comment on the possibility of resonance involvement in the generation of ECD.

Farnesylcysteine analogues inhibit chemotactic peptide receptor-mediated G-protein activation in human HL-60 granulocyte membranes.

Analogues of S-prenylated cysteine like N-acetyl-S-trans,trans-farnesyl-L-cysteine (AFC) have previously been shown to inhibit the carboxyl methylation of proteins carrying a C-terminal S-prenylated cysteine residue and to block the endotoxin-activated serum-elicited chemotactic response of mouse macrophages. Here, we show that AFC inhibits both basal and formyl peptide receptor-stimulated binding of guanosine 5'-O-(3-thiotriphosphate) (GTP[S]) to and hydrolysis of GTP by membranes of myeloid differentiated HL-60 granulocytes. Receptor-stimulated GTP[S] binding and GTP hydrolysis are more sensitive to AFC inhibition than basal G-protein functions. Inhibition of formyl peptide receptor-mediated G-protein activation is also observed for S-trans,trans-farnesyl-3-thiopropionic acid, but not for N-acetyl-S-trans-geranyl-L-cysteine, N-acetyl-L-cysteine, or the methyl ester of AFC, suggesting that the farnesyl moiety and the carboxyl group, but not the peptide bond of AFC are required for inhibition. The observations that exogeneous S-adenosyl-L-methionine is apparently not required for and S-adenosyl-L-homocysteine does not attenuate the inhibitory action of AFC raise the distinct possibility that AFC inhibits receptor-mediated G-protein interaction by a mechanism other than inhibition of protein carboxyl methylation.

A review of 308 cases of revision stapedectomy.

OBJECTIVE/HYPOTHESIS: Identify causes of primary and revision stapedectomy failure in 308 patients, assess whether these are different based on source of initial surgery, and evaluate hearing results in revision stapedectomy to improve outcome. STUDY DESIGN: Retrospective, nonrandomized chart review of patients undergoing revision stapedectomy in a referral otology practice in a large metropolitan region. MATERIALS AND METHODS: Intraoperative findings, preoperative and postoperative revision stapedectomy air and bone conduction pure-tone averages, speech discrimination scores, postoperative air-bone gaps, complications, and repeated revisions were noted in 308 patients. RESULTS: Leading causes of primary stapedectomy failure included dislocated prosthesis (24.4%), inadequate prosthesis length (14%), long process resorption (14%), and fibrous adhesions (13.6%). Revision stapedectomy air-bone gaps were less than 10 dB in 80% and greater than 30 dB in 6.8% of cases. Increased sensorineural hearing loss occurred in 0.8% of revision stapedectomy cases. Five of seven cases of vertigo associated with primary stapedectomy resolved after revision surgery. CONCLUSION: Revision stapedectomy by experienced surgeons is highly effective in attaining successful air-bone gap closure in 80% and improved closure in 84.8% of operative cases. Risk of vertigo and/or sensorineural hearing loss was not any higher in this patient population when compared with reports of primary stapedectomy.

Molecular mechanisms involved in the activation and regulation of the alpha 1-adrenergic receptor subtypes.

The adrenergic receptors (ARs) belong to the superfamily of membrane-bound G protein coupled receptors (GPCRs). Our investigation has focused on the structure-function relationship of the alpha 1b-AR subtype used as the model system for other GPCRs. Site-directed mutagenesis studies have elucidated the structural domains of the alpha 1b-AR involved in ligand binding, G protein coupling or desensitization. In addition, a combined approach using site-directed mutagenesis and molecular dynamics analysis of the alpha 1b-AR has provided information about the potential mechanisms underlying the activation process of the receptor, i.e. its transition from the 'inactive' to the 'active' conformation.

Inspection qualification (IQ) and operational qualification (OQ) for a vacuum freeze-dryer--Part II: Inspection qualification.

This paper demonstrates the importance of the inspection qualification (IQ). It was shown that the facilities were adequate to house the dryer and its associated instrumentation, and that the facilities had sufficient utilities to operate the dryer. The IQ established that the design and construction of the dryer was in agreement with the proposed hardware and design specifications. It was verified that the dryer was constructed in accordance with specifications set-forth by the equipment manufacturer.

Inspection qualification (IQ) and operational qualification (OQ) for a vacuum freeze-dryer--Part I. General discussion.

The principle objectives of this paper are (a), to develop the rationale for conducting an inspection qualification (IQ) and operational qualification (OQ) of a vacuum freeze-dryer; (b), to identify the key elements that require verification for completion of the IQ; and (c), to establish the necessary environmental and operational parameters necessary for the OQ of the vacuum freeze-dryer.

Desenvolvimento da camomila, rendimento e qualidade do óleo essencial em diferentes idades de colheita / Development of chamomile and essential oil yield and quality at different harvesting times

A camomila é uma planta herbácea, anual e aromática com várias propriedades medicinais. No Brasil, vem sendo cultivada em área representativa na região Sul devido, principalmente, às exigências climáticas da espécie, e por ter sido introduzida por imigrantes europeus nesta região. A colheita da camomila é realizada em várias colheitas, contudo, a idade adequada da planta para o início desta atividade, objetivado a maior produção de capítulos florais, bem como o rendimento e qualidade de óleos essenciais, ainda não foi determinada para a espécie. Neste trabalho, investigou-se o efeito de diferentes épocas de colheita no desenvolvimento de capítulos florais e no acúmulo e qualidade do óleo essencial da camomila. O experimento foi conduzido no município de Piraquara (PR). O delineamento experimental foi inteiramente casualizado, com cinco tratamentos (85, 92, 99, 106 e 113 dias após a emergência das plântulas) e cinco repetições. Após cada colheita, avaliou-se o acúmulo de massa seca de capítulos, rendimento, produção e composição do óleo essencial. A extração de óleo foi realizada por hidrodestilação e as amostras analisadas por cromatografia gasosa. Concluiu-se que aos 85 dias após a emergência (DAE) os capítulos apresentaram maior rendimento de óleo. Porém, após três semanas ocorreu a maior produção de massa de capítulos, resultando em maiores médias de produtividade de óleo essencial. A partir de 113 DAE houve redução do rendimento de óleo essencial e no teor de alguns constituintes.

Chamomile is an aromatic herb with many medicinal properties. In Brazil, it is cultivated on an extensive area in the Southern region mainly because of its climatic conditions for this culture. Chamomile harvesting is done by several cuttings of the entire plant, but the ideal starting point of this activity to obtain high production of flower heads has not been determined. This work investigated the effect of the harvesting period of chamomile on flower head development and essential oil accumulation. The experiment was carried out at field conditions in Piraquara, Paraná, Brazil. The experimental design was completely randomized with five treatments (85, 92, 99, 106 and 113 days after emergency) and five replications. After each harvest, dry mass accumulation and essential oil yield and quality were evaluated. Essential oil extraction was performed by hydrodistillation, and the sample was analyzed by gas chromatography. When harvested 85 days after emergency, the flower heads presented the highest essential oil content, but three weeks later the highest flower head dry mass was obtained, which resulted on great essential oil productivity. From 113 days after emergency, there is a reduction in essential oil yield and production.

Desenvolvimento vegetativo e produção de óleo essencial de patchouli (Pogostemon cablin (Blanco) Benth. ) após a aplicação de ácido giberélico e extrato de alga marinha / Development and essential oil production of Pogostemon cablin (Blanco) Benth. patchouli after applying gibberellic acid and seaweed extract

Pogostemon cablin (Blanco) Benth., comumente conhecido como patchouli, é uma espécie aromática utilizada pela indústria de perfumes devido a fragrância amadeirada e propriedade fixadora do óleo essencial. Fatores que afetam o teor dos constituintes do óleo essencial devem ser avaliados visando obter matéria prima de melhor qualidade. O experimento foi conduzido em casa de vegetação com delineamento inteiramente casualizado em esquema fatorial 2x3 e 4 repetições, sendo dois níveis de giberelina (0 e 200 mg L-1) e três níveis de extrato de alga marinha (0, 15 e 30 mg L-1). A aplicação dos reguladores vegetais foi realizada 30 dias após o plantio das mudas, e a avaliação do experimento deu-se 45 dias após a aplicação dos tratamentos. Não houve diferença significativa para a altura das plantas, a concentração de extrato de alga marinha de 15 mg L-1 promoveu aumento no número de folhas em relação à testemunha e a concentração de 30 mg L-1 promoveu decréscimo. Em relação à área foliar e ao número de folhas houve relação inversa para os níveis de extrato de alga marinha, onde o tratamento com maior concentração do regulador resultou em aumento da área foliar e redução do número de folhas. O teor de óleo essencial foi superior após a aplicação de 15 mg L-1 de extrato alga marinha isoladamente ou combinado com GA3. A produtividade do óleo essencial também aumentou com a aplicação 15 mg L-1 de extrato de alga marinha e quando utilizado somente GA3. A utilização de extrato de alga marinha aumentou a concentração de patchoulol no óleo essencial.

Pogostemon cablin (Blanco) Benth., commonly known as patchouli, is an aromatic species used by the perfume industry due to its woody fragrance and the fixative characteristic of its essential oil. Factors affecting the content of the constituents of essential oils should be evaluated in order to obtain raw materials with better quality. The experiment was carried out in a greenhouse in a completely randomized 2x3 factorial arrangement and four replications, with two levels of gibberellin (0 and 200 mg L-1) and three levels of seaweed extract (0, 15 and 30 mg L-1). Plant regulators were applied thirty days after planting the seedlings; the experiment was evaluated forty-five days after the treatments. There was no significant difference in plant height; the 15 mg L-1 concentration of seaweed extract promoted an increase in the number of leaves in relation to the control; and the 30 mg L-1 concentration promoted a decrease. In relation to leaf area and leaf number, there was an inverse relationship for the seaweed extract levels, in which the treatment with higher a concentration of the regulator resulted in an increased leaf area, reducing the number of leaves. The essential oil content was higher after applying 15 mg L-1 of seaweed extract alone or combined with GA3. The yield of essential oil also increased by applying 15 mg L-1 of seaweed extract and when only GA3 was used. The use of seaweed extract increased the patchoulol concentration in the essential oil.

Total dissociative electron attachment cross sections of selected amino acids.

Total dissociative electron attachment cross sections are presented for the amino acids, glycine, alanine, proline, phenylalanine, and tryptophan, at energies below the first ionization energy. Cross section magnitudes were determined by observation of positive ion production and normalization to ionization cross sections calculated using the binary-encounter-Bethe method. The prominent 1.2 eV feature in the cross sections of the amino acids and the closely related HCOOH molecule is widely attributed to the attachment into the -COOH pi* orbital. The authors discuss evidence that direct attachment to the lowest sigma* orbital may instead be responsible. A close correlation between the energies of the core-excited anion states of glycine, alanine, and proline and the ionization energies of the neutral molecules is found. A prominent feature in the total dissociative electron attachment cross section of these compounds is absent in previous studies using mass analysis, suggesting that the missing fragment is energetic H-.

Total dissociative electron attachment cross sections for molecular constituents of DNA.

Total cross sections for the dissociative electron attachment process are presented for the DNA bases thymine, cytosine, and adenine and for three compounds used as surrogates for the ribose and phosphate groups, tetrahydrofuran, 3-hydroxytetrahydrofuran, and trimethylphosphate, respectively. Cross section magnitudes are obtained by observation of positive ion production and normalization to ionization cross sections calculated elsewhere using the binary-encounter-Bethe method. The average cross section of the three bases is 3-10 times smaller than the effective cross section per nucleotide reported for single strand breaks in surface-bound supercoiled DNA. Consequently, damage to the bases alone does not appear to account for the major portion of the strand breaks. The presence of an OH group on the ribose surrogate considerably enhances its cross section. Model compounds in which protonation or OH groups are used to terminate bonds may therefore display larger cross sections than in DNA itself.