The conformational phase diagram of neutral polymers in the presence of attractive crowders

Extensive coarse grained molecular dynamics simulations are performed to investigate the conformational phase diagram of a neutral polymer in the presence of attractive crowders. We show that, for low crowded densities, the polymer predominantly shows three phases as a function of both intra polymer and polymer-crowder interactions: (1) weak intra polymer and weak polymer-crowder attractive interactions induce extended or coil polymer conformations (phase E) (2) strong intra polymer and relatively weak polymer-crowder attractive interactions induce collapsed or globular conformations (phase CI) and (3) strong polymer-crowder attractive interactions, regardless of intra polymer interactions, induce a second collapsed or globular conformation that encloses bridging crowders (phase CB). The detailed phase diagram is obtained by determining the phase boundaries delineating the different phases based on an analysis of the radius of gyration as well as bridging crowders. The dependence of the phase diagram on strength of crowder-crowder attractive interactions and crowder density is clarified. We also show that when the crowder density is increased, a third collapsed phase of the polymer emerges for weak intra polymer attractive interactions. This crowder density induced compaction is shown to be enhanced by stronger crowder-crowder attraction and is different from the depletion induced collapse mechanism which is primarily driven by repulsive interactions. We also provide a unified explanation of the observed reentrant swollen/extended conformations of earlier simulations of weak and strongly self interacting polymers in terms of crowder-crowder attractive interactions

The conformational phase diagram of charged polymers in the presence of attractive bridging crowders

Using extensive molecular dynamics simulations, we obtain the conformational phase diagram of a charged polymer in the presence of oppositely charged counterions and neutral attractive crowders for monovalent, divalent and trivalent counterion valencies. We demonstrate that the charged polymer can exist in three phases: (1) an extended phase for low charge densities and weak polymer-crowder attractive interactions ($CE$), (2) a collapsed phase for high charge densities and weak polymer-crowder attractive interactions, primarily driven by counterion condensation ($CCI$), and (3) a collapsed phase for strong polymer-crowder attractive interactions, irrespective of the charge density, driven by crowders acting as bridges or crosslinks ($CCB$). Importantly, the simulations reveal that the interaction with crowders can induce collapse, despite the presence of strong repulsive electrostatic interactions, and can replace condensed counterions to facilitate a direct transition from the $CCI$ and $CE$ phases to the $CCB$ phase.Comment: 12 pages, 10 figure

A COMPLETE AND UPDATED REVIEW ON VARIOUS TYPES OF DRUG DELIVERY SYSTEMS

The World of medicine has gained considerable interest in the research area all over the World. Scientists constantly work on the three parameters ‘Quality, Safety, Efficacy’ of a pharmaceutical ingredient. Refine these parameters; they are continually developing different dosage forms. These unique types of dosage forms help to provide improved bioavailability and efficacy of a pharmaceutical ingredient. The role of dosage form is to improve the availability of the medicine to treat the symptoms and disease. This article focus on the different types of dosage forms, their advantages and some important facts related to that dosage forms

A radiological evaluation of loop length change in adjustable versus fixed loop femoral cortical fixation devices in arthroscopic anterior cruciate ligament reconstruction: a prospective study

Background: In anterior cruciate ligament reconstructions, fixed devices require over-drilling to flip the button whereas loops of adjustable devices can be adjusted intraoperatively, and they minimize over-drilling. But they can loosen rendering the reconstruction incompetent. Most studies comparing them are bio-mechanical studies. Our aim was to record and compare loop length change radiologically in adjustable versus fixed devices in clinical settings. Methods: 32 patients were divided into 2 groups of 16 patients each. Hamstring graft were prepared. It was loaded in the suspension device and the apex of the graft was marked using silicon vascular radio-opaque marker. In adjustable devices, lengthening was checked after cycling and re-tensioning was done intra-operatively. Post-surgery, digital X-ray of the knee was taken in true antero-posterior and lateral view. Distance between the centre point of the button and the centre-point of the radio-opaque inert silicon marker was recorded at immediate post-operative and at 6 weeks respectively and compared. Results: 15 patients in each group were incorporated. Intra-operatively, loop lengthening was seen in all 15 patients with adjustable loop and re-tensioning was done. 2 of the 15 cases showed evidence of radiological loop lengthening however in both cases the lengthening was less than 3 mm and thus was not significant. Conclusions: We in in vivo radiology based clinical study did not find any significant loop lengthening in patients with adjustable loop devices. Hence fixed and adjustable loop devices are comparable

Medicalization of sexuality and sexual health: A perspective review

Sexuality has become a medical issue in the context of aging due to a variety of aspects, such as growing life expectancy, an optimistic societal paradigm that indorses sexuality as significant for the superiority of life with age, and the medicalization of sexuality with the emergence of remedial medicines to extravagance sexual dysfunction. At any age, a reduction in the desire for sexual activity or inadequate performance of sexual intercourse is considered atypical and requires a medicinal treatment response. However, despite concerns that this is leading to an unhealthy obsession with sexuality from a medical perspective, this line of thinking is likely to continue. In this context, people can identify and take advantage of sexual problems. Sexual desire and performance are affected by normal physiological changes associated with aging in both genders. Medical experts must understand these changes to optimize sexual functioning in older patients. Sexual health can only be improved by addressing both sexual rights and enjoyment, even in the current politically charged context. Through legislation, programming, and lobbying, we may all work to enhance health, happiness, and quality of life by fostering more positive associations between sexual health, sexual rights, and sexual pleasure. This calls for not just a thorough understanding of the real-world consequences of these ideas' interconnectivity, but also conceptual, individual, and systemic approaches that properly acknowledge and alleviate the problems imposed on people's lives due to insufficient consideration of these links. This review describes the factors associated with aging and sexuality, the normalization and medicalization of sexual health, and unusual situations associated with aging, including institutionalized care and the prospects of elder abuse

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

Background: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Methods: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Findings: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). Interpretation: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. Funding: National Institute for Health Research Health Services and Delivery Research Programme