Efficiency of letrozole loaded PLGA nanoparticles on sex reversal of Poecilia reticulata (Peters, 1859)

Males of Poecilia reticulata showed extreme diversity in color, particularly of their fins, while the females lack the bright colors and are largely whitish. Such extreme variability of color and finnage lead to demand of males in the markets. The aim of present work was to develop a new Letrozole (LTZ)-loaded PLGA nanoparticles for effective delivery of the masculinization drug, letrozole, as an alternative to commercially available masculinization agents. The LTZ-loaded PLGA NPs were prepared by solvent displacement technique. The particle size of LTZ-loaded PLGA NPs was analyzed using LICOMP particle size analyzer and was found to be in the range of 72 nm to 520 nm with average size of 221.5±63.3 nm. Zeta potential was estimated to be about 21.35 mV with loading efficiency of 43.63±4.63 %. In the present study, a series of experiments were carried out to induce masculinization using LTZ-loaded PLGA nanoparticles during the sex differentiation period. Guppy (P. reticulate) fry were treated with LTZ-loaded PLGA nanoparticles at dosages 5, 25, 50 and 100 ppm/kg diet for 10, 15 and 30 days. The gonopodium index and GSI showed increasing order in male and female respectively with dose of LTZ-loaded nanoparticles. The results indicated an increase in the proportion of males with dosage and duration of treatment. This has been done for the first time using nanotechnology efficiently which has shown an increase in the male population of Poecilia reticulata with lesser dose of nano-encapsulated Letrozole (LTZ)-loaded PLGA nanoparticles drug as compared with naked control Letrozole (LTZ) drug delivery

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Only spinal fixation as treatment of prolapsed cervical intervertebral disc in patients presenting with myelopathy

Aim: An alternative form of surgical treatment of prolapsed cervical intervertebral disc in patients presenting with symptoms related to myelopathy is discussed. The treatment involved fixation of the affected spinal segments and aimed at arthrodesis. No direct manipulation or handling of the disc was done. Materials and Methods: During the period August 2010 to June 2017, 16 patients presenting with symptoms attributed to myelopathy and diagnosed to have prolapsed cervical intervertebral disc were surgically treated by spinal stabilization. There were 11 males and 5 females and their ages ranged from 20 to 66 years (average: 40.6 years). Apart from clinical and radiological indicators, the number of spinal segments that were stabilized depended on direct observation of facetal morphology, alignment, and stability. Surgery involved distraction-fixation of facets using Goel facet spacer (8 patients), transarticular facetal fixation (5 patients) using screws or a combination of both facetal spacer, and transarticular screws (3 patients). Results: All patients had “remarkable” clinical improvement in the immediate postoperative period as assessed by visual analog scale, Goel's clinical grading, and Japanese Orthopedic Association scores. Follow-up ranged from 3 to 84 months (average: 50 months). The herniated disc regressed or disappeared at follow-up radiological assessment that ranged from 24 h to 3 months after surgery. Conclusions: Spinal segmental fixation aiming at arthrodesis with or without distraction of facets and without any direct surgical manipulation in the disc space or removal of the prolapsed portion of the disc can be considered in the armamentarium of the surgeon

Epidermolysis bullosa: Careful monitoring and no touch principle for anesthesia management

Epidermolysis bullosa (EB) is a rare genetic mechanobullous disorder, with excessive fragility of the skin and mucous membranes. Avoiding mechanical injury to the skin and mucous membranes is essential in the anesthetic management. Shearing forces applied to the skin result in bullae formation, while compressive forces to the skin are tolerated. The challenge is to use monitoring technology without damaging the epithelial surface. Difficult airway, positioning issues, nutritional deficiencies, poor immunity, and carcinogenic potential add to the comorbidities. We managed a child with EB undergoing syndactyly release. Ensuring maximal skin and mucous membrane protection, anesthesia in children with EB can be conducted with few sequelae

Brain Herniation in Neurofibromatosis with Dysplasia of Occipital Bone and Posterior Skull Base

A 22-year-old female, a known case of neurofibromatosis 1 (NF1), presented with a congenital swelling in the left occipital region. She had developed recent onset dysphagia and localized occipital headache. Neuroradiology revealed a left occipital meningoencephalocele and a left parapharyngeal meningocele. This was associated with ventriculomegaly. She was advised on cranioplasty along with duraplasty which she denied. She agreed to a lumbar-peritoneal shunt. She described a dramatic improvement in her symptoms following the lumbar-peritoneal shunt. Occipital dysplasias, though uncommon, have been reported in the literature. We review this case and its management and discuss relevant literature on occipital dysplasias in NF1

Enabling change in public health services: Insights from the implementation of nurse mentoring interventions to improve quality of obstetric and newborn care in two North Indian states

Background: Few studies have explicitly examined the implementation of change interventions in low- and middle-income country (LMIC) public health services. We contribute to implementation science by analyzing the implementation of an organizational change intervention in a large, hierarchical and bureaucratic public service in a LMIC health system. Methods: Using qualitative methods, we critically interrogate the implementation of an intervention to improve quality of obstetric and newborn services across 692 facilities in Uttar Pradesh and Bihar states of India to reveal how to go about making change happen in LMIC public health services. Results: We found that focusing the interventions on a discreet part of the health service (labour rooms) ensured minimal disruption of the status quo and created room for initiating change. Establishing and maintaining respectful, trusting relationships is critical, and it takes time and much effort to cultivate such relationships. Investing in doing so allows one to create a safe space for change; it helps thaw entrenched practices, behaviours and attitudes, thereby creating opportunities for change. Those at the frontline of change processes need to be enabled and supported to: lead by example, model and embody desirable behaviours, be empathetic and humble, and make the change process a positive and meaningful experience for all involved. They need discretionary space to tailor activities to local contexts and need support from higher levels of the organisation to exercise discretion. Conclusions: We conclude that making change happen in LMIC public health services, is possible, and is best approached as a flexible, incremental, localised, learning process. Smaller change interventions targeting discreet parts of the public health services, if appropriately contextualised, can set the stage for incremental system wide changes and improvements to be initiated. To succeed, change initiatives need to cultivate and foster support across all levels of the organisation.</p