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Kaki Mudra is a yogic gesture that involves nasikagara drishti focusing on the nose tip without the eyes blinking and pursing the lips, which form beaks during inhalation, and exhaling slowly through the nose. However, there is a lack of evidence on the impact of kaki mudra on cardiovascular changes and autonomic function using pupillary light reflex (PLR).

Purpose: /Objective(S)A low-cost, prior knowledge-based individualized dose-constraint generator for organs-at-risk has been developed for prostate cancer radiation therapy (RT) planning. In this study, we aimed to evaluate the feasibility and improvements in organs-at-risk (OAR) doses in prostate cancer RT planning using this tool served on a web application. Materials And Methods: A set of previously treated prostate cancer cases planned and treated with generic constraints were replanned using individualized dose constraints derived from a library of cases with similar volumes of target, OAR, and overlap regions and served on the web-based application. The goal was to assess the reduction in mean dose, specified dose volumes (V59Gy, V56Gy, V53Gy, V47Gy, and V40Gy), and generalized equivalent uniform dose (gEUD) to the rectum and bladder. Planners and assessors were blinded to the initial achieved doses and penalties. Sample size estimation was based on improvement in V53Gy for the rectum and bladder with a paired evaluation. Results: Twenty-four patients were replanned. All the plans had a PTV D95 of at least 97% of the prescribed dose. The individualized OAR constraints could be met for 87.5% of patients for all dose levels. The mean dose, V59Gy, V53Gy, and V47Gy for the bladder was reduced by 7.5 Gy, 1.12%, 5.51%, and 10.53% respectively. Similarly for the rectum, the mean dose, V59Gy, V53Gy, V47Gy and was reduced by 5.5 Gy, 4.34%, 6.97%, and 11.61% respectively. All dose reductions were statistically significant. The gEUD of the bladder was reduced by 2.47 Gy (p

Abstract Background With recent emphasis placed on workplace based assessment (WBA) as a method of formative performance assessment, there is limited evidence in the current literature regarding the role of feedback in improving the effectiveness of WBA. The aim of this systematic review was to elucidate the impact of feedback on the effectiveness of WBA in postgraduate medical training. Methods Searches were conducted using the following bibliographic databases to identify original published studies related to WBA and the role of feedback: Medline (1950-December 2010), Embase (1980-December 2010) and Journals@Ovid (English language only, 1996-December 2010). Studies which attempted to evaluate the role of feedback in WBA involving postgraduate doctors were included. Results 15 identified studies met the inclusion criteria and minimum quality threshold. They were heterogeneous in methodological design. 7 studies focused on multi source feedback, 3 studies were based on mini-clinical evaluation exercise, 2 looked at procedural based assessment, one study looked at workplace based assessments in general and 2 studies looked at a combination of 3 to 6 workplace based assessments. 7 studies originated from the United Kingdom. Others were from Canada, the United States and New Zealand. Study populations were doctors in various grades of training from a wide range of specialties including general practice, general medicine, general surgery, dermatology, paediatrics and anaesthetics. All studies were prospective in design, and non-comparative descriptive or observational studies using a variety of methods including questionnaires, one to one interviews and focus groups. Conclusions The evidence base contains few high quality conclusive studies and more studies are required to provide further evidence for the effect of feedback from workplace based assessment on subsequent performance. There is, however, good evidence that if well implemented, feedback from workplace based assessments, particularly multisource feedback, leads to a perceived positive effect on practice.

Bioengineered 3D models that can mimic patient-specific pathologies in vitro are valuable tools for developing and validating anticancer therapeutics. In this study, microfibrillar matrices with unique structural and functional properties were fabricated as 3D spherical and disc-shaped scaffolds with highly interconnected pores and the potential of the newly developed scaffolds for developing prostate cancer model has been investigated. The newly developed scaffolds showed improved cell retention upon seeding with cancer cells compared to conventional electrospun scaffolds. They facilitated rapid growth and deposition of cancer-specific extracellular matrix through-the-thickness of the scaffold. Compared to the prostate cancer cells grown in 2D culture, the newly developed prostate cancer model showed increased resistance to the chemodrug Docetaxel regardless of the drug concentration or the treatment frequency. A significant reduction in the cell number was observed within one week after the drug treatment in the 2D culture for both PC3 and patient-derived cells. Interestingly, almost 20%-30% of the cancer cells in the newly developed 3D model survived the drug treatment, and the patient-derived cells were more resistant than the tested cell line PC3. The results from this study indicate the potential of the newly developed prostate cancer model for in vitro drug testing., (© 2023 IOP Publishing Ltd.)

Importance: Guidelines for cancer genetic testing based on family history may miss clinically actionable genetic changes with established implications for cancer screening or prevention., Objective: To determine the proportion and potential clinical implications of inherited variants detected using simultaneous sequencing of the tumor and normal tissue ("tumor-normal sequencing") compared with genetic test results based on current guidelines., Design, Setting, and Participants: From January 2014 until May 2016 at Memorial Sloan Kettering Cancer Center, 10 336 patients consented to tumor DNA sequencing. Since May 2015, 1040 of these patients with advanced cancer were referred by their oncologists for germline analysis of 76 cancer predisposition genes. Patients with clinically actionable inherited mutations whose genetic test results would not have been predicted by published decision rules were identified. Follow-up for potential clinical implications of mutation detection was through May 2017., Exposure: Tumor and germline sequencing compared with the predicted yield of targeted germline sequencing based on clinical guidelines., Main Outcomes and Measures: Proportion of clinically actionable germline mutations detected by universal tumor-normal sequencing that would not have been detected by guideline-directed testing., Results: Of 1040 patients, the median age was 58 years (interquartile range, 50.5-66 years), 65.3% were male, and 81.3% had stage IV disease at the time of genomic analysis, with prostate, renal, pancreatic, breast, and colon cancer as the most common diagnoses. Of the 1040 patients, 182 (17.5%; 95% CI, 15.3%-19.9%) had clinically actionable mutations conferring cancer susceptibility, including 149 with moderate- to high-penetrance mutations; 101 patients tested (9.7%; 95% CI, 8.1%-11.7%) would not have had these mutations detected using clinical guidelines, including 65 with moderate- to high-penetrance mutations. Frequency of inherited mutations was related to case mix, stage, and founder mutations. Germline findings led to discussion or initiation of change to targeted therapy in 38 patients tested (3.7%) and predictive testing in the families of 13 individuals (1.3%), including 6 for whom genetic evaluation would not have been initiated by guideline-based testing., Conclusions and Relevance: In this referral population with selected advanced cancers, universal sequencing of a broad panel of cancer-related genes in paired germline and tumor DNA samples was associated with increased detection of individuals with potentially clinically significant heritable mutations over the predicted yield of targeted germline testing based on current clinical guidelines. Knowledge of these additional mutations can help guide therapeutic and preventive interventions, but whether all of these interventions would improve outcomes for patients with cancer or their family members requires further study., Trial Registration: clinicaltrials.gov Identifier: NCT01775072.

Detailed studies on the solution conformation of polyene antibiotic, filipin III using circular dichroism (CD) and proton nuclear magnetic resonance techniques have been carried out. In dimethyl sulfoxide (DMSO), filipin III exhibits concentration dependent aggregation-monomeric at lower and oligomeric at higher concentrations of the antibiotic. At concentrations used for 1H NMR studies (6 x 10(-3)M) the molecule coexists as monomeric and oligomeric species. However, titration experiments indicated that, in a mixed solvent system of DMSO:methanol (2:3 v/v) the antibiotic exists only as a monomer. Complete 1H NMR assignments and the conformation of the monomer filipin III have been determined by the combined use of DQFCOSY and ROESY experiments in DMSO:methanol solvent system.

We report in this paper the aggregation properties of amphotericin-B (amp-B) in solution using CD and 1H-NMR techniques. Our results indicate that the preferred structure of amp-B in dimethylsulfoxide is a monomer at low concentrations (10(-4) M and below) and a stable dimer at higher concentrations (range 5.10(-3) M to 10(-2) M). In a DMSO/ethanol mixture (1:1 (v/v)), the antibiotic is monomeric, irrespective of the concentration within the range studied. We propose a head-to-tail model based on NMR data. An understanding of the head-to-tail dimer, is, we believe important, particularly in view of the recent report wherein it is proposed that the drug inserts into bilayers as head-to-tail oligomers.

The interactions between the polyene antibiotic amphotericin B with dipalmitoylphosphatidylcholine were investigated in vesicles (using circular dichroism) and in chloroform solution (using circular dichroism and 1H, 13C, and 31P nuclear magnetic resonance). The results show that amphotericin B readily aggregates in vesicles and that the extent of aggregation depends on the lipid:drug concentration ratio. Introduction of sterol molecules into the membrane hastens the process of aggregation of amphotericin B. In chloroform solutions amphotericin B strongly interacts with phospholipid molecules to form a stoichiometric complex. The results suggest that there are interactions between the conjugated heptene stretch of amphotericin B and the methylene groups of lipid acyl chains, while the sugar moiety interacts with the phosphate head group by the formation of a hydrogen bond. A model is proposed for the lipid-amphotericin B complex, in which amphotericin B interacts equally well with the two lipid acyl chains, forming a 1:1 complex.