Miracle-dz/UniFAR-FTUs huggingface dataset:
Doughnut Rounds: A self-directed learning approach to teaching critical care in surgery

In light of medical students and residents becoming more knowledgeable and vocal in their evaluation of traditional clinical teaching methods, a number of innovative approaches have been tried in our program. We examined a self-directed learning approach to teaching critical care in surgery, known locally as 'Doughnut Rounds', which involve four to seven medical students and or residents during their surgical intensive care unit (SICU) rotation. They choose the reading material as a group and are expected to formulate 12 questions based on the week's readings. They pose these questions to their colleagues in a 'game show' format. In this scenario, the attending surgeon has only to bring the doughnuts and to act as a moderator during the session. Several weeks following the end of their three-month ICU rotation, 25 students were sent a questionnaire. It was designed to reflect their degree of satisfaction with Doughnut Rounds and their perception of the importance of various components of these teaching se.
In the linear quadratic model, the Poisson approximation and the Zaider-Minerbo formula agree on the ranking of tumor control probabilities, up to a critical cell birth rate

Abstract Purpose: To provide a rule for the agreement or disagreement of the Poisson approximation (PA) and the Zaider-Minerbo formula (ZM) on the ranking of treatment alternatives in terms of tumor control probability (TCP) in the linear quadratic model. Materials and methods: A general criterion involving a critical cell birth rate was formally derived. For demonstration, the criterion was applied to a distinct radiobiological model of fast growing head and neck tumors and a respective range of 22 conventional and nonconventional head and neck schedules. Results: There is a critical cell birth rate bcrit below which PA and ZM agree on which one out of two alternative treatment schemes with single-cell survival curves S′(t) and S′′(t) offers better TCP: For cell birth rates b above this critical cell birth rate, PA and ZM disagree if and only if b >bcrit > 0. In case of the exemplary head and neck schedules, out of 231 possible combinations, only 16 or 7% were found where PA and ZM disagreed. In all 231 cases the prediction of the criterion was numerically confirmed, and cell birth rates at crossovers between schedules matched the calculated critical cell birth rates. Conclusions: TCP estimated by PA and ZM almost never numerically coincide. Still, in many cases both formulas at least agree about which one out of two alternative fractionation schemes offers better TCP. In case of fast growing tumors featuring a high cell birth rate, however, ZM may suggest a re-evaluation of treatment options.
Increased radiotoxicity in two cancerous cell lines irradiated by low and high energy photons in the presence of thio-glucose bound gold nanoparticles

Abstract Purpose: Gold nanoparticles modified by thio-glucose are believed to increase the toxicity of radiotherapy in human malignant cells. We report the effect of thio-glucose bound gold nanoparticles (Glu-G nanoparticles), 16 nm in size, on two human lung (QU-DB) and breast (MCF7) cancer cell lines combined with kilo and megavoltage X-rays. Materials and methods: The shape and surface characteristics, the size distribution and light absorption spectrum of the prepared nanoparticles were measured by transmission electron microscopy, dynamic light scattering, and ultraviolet-visible spectrophotometry, respectively. The cell uptake was assayed using the atomic absorption spectrometry. Mitochondrial activity, colony formation, and comet assays were applied to assess and compare the enhanced radiotoxicity of 100 KV and 6 MV X-rays, when combined with Glu-G nanoparticles. Results: Glu-G nanoparticles had no significant toxicity for MCF7 and QU-DB cells up to 100 micromolar concentration. Compared to radiation alone, the intracellular uptake of Glu-G nanoparticles resulted in increased inhibition of cell proliferation by 64.1% and 38.7% for MCF7 cells, and 64.4% and 32.4% for QU-DB cells by 100 kVp and 6 MV X-rays, respectively. Comet assay confirmed an increase of DNA damage as a result of combination of 6 MV photons with Glu-G nanoparticles. Conclusion: Glu-G nanoparticles have remarkable potential for enhancing radiotoxicity of both low and high energy photons in MCF7 and QU-DB cells.
8‐Benzyltetrahydropyrazino[2,1‐f]purinediones: Water‐Soluble Tricyclic Xanthine Derivatives as Multitarget Drugs for Neurodegenerative Diseases

8‐Benzyl‐substituted tetrahydropyrazino[2,1‐f]purinediones were designed as tricyclic xanthine derivatives containing a basic nitrogen atom in the tetrahydropyrazine ring to improve water solubility. A library of 69 derivatives was prepared and evaluated in radioligand binding studies at adenosine receptor (AR) subtypes and for their ability to inhibit monoamine oxidases (MAO). Potent dual‐target‐directed A1/A2A adenosine receptor antagonists were identified. Several compounds showed triple‐target inhibition; one of the best compounds was 8‐(2,4‐dichloro‐5‐fluorobenzyl)‐1,3‐dimethyl‐6,7,8,9‐tetrahydropyrazino[2,1‐f]purine‐2,4(1H,3H)‐dione (72) (human AR: Ki A1 217 nM, A2A 233 nM; IC50 MAO‐B: 508 nM). Dichlorinated compound 36 [8‐(3,4‐dichlorobenzyl)‐1,3‐dimethyl‐6,7,8,9‐tetrahydropyrazino[2,1‐f]purine‐2,4(1H,3H)‐dione] was found to be the best triple‐target drug in rat (Ki A1 351 nM, A2A 322 nm; IC50 MAO‐B: 260 nM), and may serve as a useful tool for preclinical proof‐of‐principle studies. Compounds that act at multiple targets relevant for symptomatic as well as disease‐modifying treatment of neurodegenerative diseases are expected to show advantages over single‐target therapeutics.
The effect of radiation dose on the onset and progression of radiation-induced brain necrosis in the rat model

Abstract Purpose: To provide a comprehensive understanding of how the selection of radiation dose affects the temporal and spatial progression of radiation-induced necrosis in the rat model. Materials and methods: Necrosis was induced with a single fraction of radiation exposure, at doses ranging between 20 and 60 Gy, to the right hemisphere of 8-week-old Fischer rats from a linear accelerator. The development and progression of necrosis in the rats was monitored and quantified every other week with T1- and T2-weighted gadolinium contrast-enhanced MRI studies. Results: The time to onset of necrosis was found to be dose-dependent, but after the initial onset, the necrosis progression rate and total volume generated was constant across different doses ranging between 30 and 60 Gy. Radiation doses less than 30 Gy did not develop necrosis within 33 weeks after treatment, indicating a dose threshold existing between 20 and 30 Gy. Conclusion: The highest dose used in this study led to the shortest time to onset of radiation-induced necrosis, while producing comparable disease progression dynamics after the onset. Therefore, for the radiation-induced necrosis rat model using a linear accelerator, the most optimum results were generated from a dose of 60 Gy.
PREDICTIVE FACTORS FOR DEVELOPMENT OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Spectral-Domain Optical Coherence Tomography Study

Purpose: To investigate the risk factors predictive for the development of neovascular age-related macular degeneration (NVAMD) by means of spectral-domain optical coherence tomography. Methods: Retrospective study of 73 eyes graded Stage 2 and Stage 3 according to the AMD International Grading System with minimum follow-up of 24 months. Drusenoid pigment epithelial detachment, hyperreflective foci, external limiting membrane, inner ellipsoid band, and retinal pigment epithelium integrity were analyzed at baseline and last follow-up. Binary logistic regression model analyzed significant predictors of neovascular conversion. Results: The discontinuity of external limiting membrane, inner ellipsoid band, and retinal pigment epithelium bands were significantly more prevalent in the NVAMD group at baseline and last follow-up (P < 0.001). Hyperreflective foci represented the single most important predictor of neovascular conversion (Exp [B], 15.15; P = 0.005) as confirmed by Kaplan–Meier curve (P = 0.002). Drusenoid pigment epithelial detachment width was significantly greater in NVAMD group than control subjects at baseline and last follow-up (P < 0.001), and its delta value also resulted a significant neovascular predictor (Exp [B], 0.99; P = 0.04). Conclusion: Hyperreflective foci significantly increase the risk of NVAMD progression. The delta width of drusenoid pigment epithelial detachment also predicts disease progression, integrating the stratification of NVAMD progression risk.
A multi‐family group day treatment programme for adolescent eating disorder

We describe a new treatment for the outpatient management of disabling eating disorder in adolescents. The pilot programme has thus far treated 14 adolescents, half with anorexia nervosa and half with bulimia. Most of the young people had been previously admitted or the current referral was for admission. None of the patients has subsequently had to be taken into an inpatient service and the preliminary results suggest that the programme may be beneficial. The programme has elicited a very positive response from the patients and their families. For the professionals involved, the experience of participating in the multi-family group treatment has been unusual and powerful and the training opportunities provided by it seem rather unique. This has led us to make this preliminary communication. We describe the context and structure of the programme and give some details of the patients so far treated. Copyright © 2000 John Wiley & Sons, Ltd and Eating Disorders Association.
Radioprotective activity of curcumin-encapsulated liposomes against genotoxicity caused by Gamma Cobalt-60 irradiation in human blood cells

Abstract Purpose: While the radioprotective activity of curcumin against genotoxicity has been well established, its poor oral bioavailability has limited its successful clinical applications. Nanoscale formulations, including liposomes, have been demonstrated to improve curcumin bioavailability. The objective of the present work was (1) to prepare and characterize curcumin-encapsulated liposomes (i.e. size, colloidal stability, encapsulation efficiency, and payload), and (2) subsequently to evaluate their radioprotective activity against genotoxicity in human blood cells caused by Gamma Cobalt-60 irradiation. Materials and methods: The curcumin-encapsulated liposomes were prepared by lipid-film hydration method using commercial phosphatidylcholine (i.e. Phospholipon® 90G). The blood cells were obtained from healthy male donors (n = 3) under an approved ethics protocol. The cell uptake and the radioprotective activity of the curcumin-encapsulated liposomes were characterized by fluorescence microscopy and micronucleus assay, respectively. Results: Nanoscale curcumin-encapsulated liposomes exhibiting good physical characteristics and successful uptake by the human blood cells were successfully prepared. The radioprotective activity of the curcumin-encapsulated liposomes was found to be dependent on the curcumin concentration, where an optimal concentration existed (i.e. 30 μg/mL) independent of the irradiation dose, above which the radioprotective activity had become stagnant (i.e. no more reduction in the micronuclei frequency). Conclusions: The present results established for the first time the radioprotective activity of curcumin-encapsulated liposomes in human blood cells, which coupled by its well-established bioavailability, boded well for its potential application as a nanoscale delivery system of other radioprotective phytochemicals.
α‐Keto Phenylamides as P1′‐Extended Proteasome Inhibitors

The major challenge for proteasome inhibitor design lies in achieving high selectivity for, and activity against, the target, which requires specific interactions with the active site. Novel ligands aim to overcome off‐target‐related side effects such as peripheral neuropathy, which is frequently observed in cancer patients treated with the FDA‐approved proteasome inhibitors bortezomib (1) or carfilzomib (2). A systematic comparison of electrophilic headgroups recently identified the class of α‐keto amides as promising for next generation drug development. On the basis of crystallographic knowledge, we were able to develop a structure–activity relationship (SAR)‐based approach for rational ligand design using an electronic parameter (Hammett’s σ) and in silico molecular modeling. This resulted in the tripeptidic α‐keto phenylamide BSc4999 [(S)‐3‐(benzyloxycarbonyl‐(S)‐leucyl‐(S)‐leucylamino)‐5‐methyl‐2‐oxo‐N‐(2,4‐dimethylphenyl)hexanamide, 6 a], a highly potent (IC50=38 nM), cell‐permeable, and slowly reversible covalent inhibitor which targets both the primed and non‐primed sites of the proteasome’s substrate binding channel as a special criterion for selectivity. The improved inhibition potency and selectivity of this new α‐keto phenylamide makes it a promising candidate for targeting a wider range of tumor subtypes than commercially available proteasome inhibitors and presents a new candidate for future studies.
The influence of changing dose rate patterns from inhaled beta-gamma emitting radionuclide on lung cancer

Abstract Purpose: Dose and dose rate are both appropriate for estimating risk from internally deposited radioactive materials. We investigated the role of dose rate on lung cancer induction in Beagle dogs following a single inhalation of strontium-90 (90Sr), cerium-144 (144Ce), yttrium-91 (91Y), or yttrium-90 (90Y). As retention of the radionuclide is dependent on biological clearance and physical half-life a representative quantity to describe this complex changing dose rate is needed. Materials and methods: Data were obtained from Beagle dog experiments from the Inhalation Toxicology Research Institute. The authors selected the dose rate at the effective half-life of each radionuclide (DRef). Results: Dogs exposed to DRef (1–100 Gy/day) died within the first year after exposure from acute lung disease. Dogs exposed at lower DRef (0.1–10 Gy/day) died of lung cancer. As DRef decreased further (<0.1 Gy/day 90Sr, <0.5 Gy/day 144Ce, <0.9 Gy/day 91Y, <8 Gy/day 90Y), survival and lung cancer frequency were not significantly different from control dogs. Conclusion: Radiation exposures resulting from inhalation of beta-gamma emitting radionuclides that decay at different rates based on their effective half-life, leading to different rates of decrease in dose rate and cumulative dose, is less effective in causing cancer than acute low linear energy transfer exposures of the lung.
ACUTE RETINAL DAMAGE AFTER USING A TOXIC PERFLUORO-OCTANE FOR VITREO-RETINAL SURGERY

Purpose: To describe a series of retinal acute toxicity cases with severe visual loss after intraocular use of a toxic perfluoro-octane (PFO). The clinical presentation is described, and the likely causes are analyzed. New biological methods for testing safety of intraocular medical devices are proposed. Methods: Information regarding a series of eyes suffering acute severe events after intraocular use of a toxic PFO was analyzed. Four types of spectroscopy, nuclear magnetic resonance, and chromatography were used to identify the potential PFO contaminants. Cultures of human retinal pigment epithelial cells (ARPE-19) and porcine neuroretina were used to quantify the toxicity of the suspect PFO lots. Results: Of 117 cases of intraocular toxicity, 96 were considered clearly related to the use of PFO. Fifty-three cases had no light perception, and 97 had no measurable visual acuity. Retinal necrosis (n = 38) and vascular occlusion (n = 33) were the most characteristic findings. Two hydroxyl compounds, perfluorooctanoic acid and dodecafluoro-1-heptanol, and benzene derivatives were identified as the suspected toxic agents. While existing toxicity testing failed, we proposed new tests that demonstrated clear toxicity. Conclusion: Protocols to determine cytotoxicity of intraocular medical devices should be revised to assure safety. Acute toxic events should be reported to health authorities and scientific media.
T cell infiltrate and outcome following resection of intermediate-grade primary neuroendocrine tumours and liver metastases.

BACKGROUND Tumour-infiltrating lymphocytes (TILs) have been shown to predict survival in numerous malignancies. The importance of TILs in primary pancreatic neuroendocrine tumours (NETs) and NET liver metastases (NETLMs) has not been defined. METHODS We identified 87 patients with NETs and 39 with NETLMs who had undergone resection. Immunohistochemistry was performed to determine TIL counts. Recurrence-free survival (RFS) and overall survival (OS) were determined using the log-rank test. RESULTS The median follow-up time was 62 months in NET patients and 48 months in NETLM patients. Vascular invasion and histologic grade were the only independent predictors of outcome for NETs and NETLMs, respectively. Analysis of intermediate-grade NETs indicated that a dense T cell (CD3+) infiltrate was associated with a median RFS of 128 months compared with 61 months for those with low levels of intratumoral T cells (P= 0.05, univariate analysis). Examination of NETLMs revealed that a low level of infiltrating regulatory T cells (Treg, FoxP3+) was a predictor of prolonged survival (P < 0.01, univariate analysis). CONCLUSIONS A robust T cell infiltrate is associated with improved RFS following resection of intermediate-grade NETs, whereas the presence of more Treg correlated with shorter OS after treatment of NETLMs. Further study of the immune response to intermediate-grade NETs and NETLMs is warranted.
Audit of prescribing patterns of doctors for the management of acute respiratory infections in children

Background: Acute respiratory infections (ARI) account for 80% of all children reporting to outpatient departments (OPD). In most of the cases the cause of morbidity is a viral infection that does not require antibiotic treatment, but in spite of this, antibiotics are used much too frequently. The guidelines for the management of ARI have been developed by World Health Organization (WHO), but generally, the physicians do not follow the recommended guidelines. This study was conducted to audit the prescriptions of general practitioners, to determine their practices regarding ARI management and to provide recommendations to improve their practices in the area of identified needs. Methods: Practitioners working in District Bulleda (Turbat), Balochistan were surveyed and five of them were selected randomly using simple random sampling technique for this cross sectional study. They were informed about the objectives of the study and consent was obtained. Their prescriptions of cases of ARI management for one month were obtained. Results: The results of the study show that a total of 202 patients of ARI were seen by the 5 selected physicians of the district. It was seen that in 60% cases the chief complaints were recorded. Temperature was recorded in 48% case. Respiratory rate was recorded in 33% cases. The diagnosis was noted down in 44% cases. In 97% cases, antibiotics were prescribed and in 37.5% cases the dose was not according to recommendation. Conclusion: It is concluded that most physicians in Bulleda are not following the WHO recommended protocol of ARI management. Refresher courses and training programs for physicians are recommended. Use of electronic media may be helpful in increasing awareness both in the health care provider and health care recipient.
Modification of right hepatectomy results in improvement outcome: a retrospective comparative study.

OBJECTIVE To evaluate any change in the operative and survival outcomes in patients undergoing a right hepatectomy after adoption of the no-clamp technique using a radiofrequency dissecting sealer (TissueLink™) in liver resection. METHODS In all, 58 consecutive patients who underwent a right hepatectomy from July 2003 to December 2007 (Group 1) were compared with 66 consecutive patients who underwent a right hepatectomy from January 1999 to June 2003 (Group 2). In group 1, a liver transection was performed with a cavitron ultrasonic surgical aspirator (CUSA) and TissueLink™ without hilar clamping whereas in group 2, a liver transection was performed with CUSA and diathermy with routine continuous hilar clamping. RESULTS For the operative outcomes, there was significantly less blood loss (median 450 vs. 900 ml, P < 0.001) in group 1. The complication rate was also significantly lower in group 1 (22.4% vs. 47.0%, P = 0.004). In subgroup analysis for patients with hepatocellular carcinoma (HCC), the overall survival rate was significantly better in group 1; 1-, 3- and 5-year survival rates were 78%, 72% and 57% in group 1 vs. 72%, 44% and 39% in group 2, respectively (P = 0.048). CONCLUSIONS When compared with the retrospective cohort, a right hepatectomy utilizing TissueLink™ without hilar clamping was feasible with potential benefits in surgical outcomes.
SUBRETINAL HEMORRHAGE AFTER LENS-SPARING VITRECTOMY IN INFANTS BORN AT OR UNDER 24 WEEKS GESTATION

Purpose: To describe short term outcomes in a case series of infants with rapidly progressive retinopathy of prematurity (ROP) requiring laser and lens-sparing vitrectomies (LSV) at early postmenstrual ages (PMAs). Methods: Retrospective chart review of infants born at or under 24 0/7 weeks consecutively referred for management of severe ROP between August 2006 and January 2007. Results: Five female infants (mean gestational age 23 4/7 weeks, mean birthweight 514.4 g) required laser treatment bilaterally for zone 1 or posterior zone II ROP at 35–37 weeks PMA. LSV was performed for progressive stage 4 ROP in eight eyes at 37–39 weeks PMA (mean 38.2 weeks). Subretinal hemorrhage occurred after LSV in five eyes, with three developing subretinal fibrosis preventing complete retinal reattachment. Conclusion: Premature infants in this series had rapidly progressive ROP requiring laser and LSV at early PMAs. Subretinal hemorrhage occurred and may be related to the amount of laser necessary to treat large zones of avascular retina, and the early timing of vitrectomy when postoperative contracting preretinal vitreous no longer has the natural tamponading force of formed gel against it. Improved therapies for premature infants of very young gestational ages and large avascular zones are needed.