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PurposeThe purpose of this paper is to create a “go-to-guide” of best practices in the creation of asynchronous courses. Due to the global pandemic, millions of students around the world transitioned from in-class instruction to online programs, which ranged from completely synchronous classrooms to completely asynchronous classrooms. Students were forced to learn how to engage within an online classroom environment with minimal notice and instructors were abruptly thrusted into a different operational environment, with many required to construct educational ecosystems in an unfamiliar and digitized interface. This led to several actions and the utilization of a multitude of different teaching techniques, many of which were poorly implemented.Design/methodology/approachKey words, “Asynchronous learning”, “Learning”, “Feedback”, “Online Instruction”, and “Classroom Design” were searched in online data bases (Google Scholar, PubMed, EBSCO and Data Base of Open Access Journals). These then were read by the authorial team and authoritative papers were selected by the team based on the frequency of utilization by other papers in the field and the utility of these papers for the design of asynchronous courses.FindingsThis paper explores asynchronous learning from the perspective of how instructional science and learning science can be applied to create the best classroom for both pupil and instructor.Originality/valueIt looks to provide a go-to-guide for best practices in asynchronous learning and the development of K-12 classrooms, graduate and medical school classrooms and finally continuous medical education classrooms. Finally, this guide looks to facilitate the development of master instructors through statements on how to properly provide feedback to students.

Pulmonary sclerosing pneumocytoma (PSP) is a rare and interesting pulmonary tumour that presents a diagnostic challenge to the surgeon due to its bland symptomatology, indolent course, non-specific radiological features and ambiguous histopathological findings, which could lead to errors in management and prognostication. Herein, we present a series of 4 patients with PSP who were managed in our institution over a period of 8 years and briefly discuss relevant literature.

Pulmonary mucormycosis (PM) is a rare disease. Literature about the surgical management of PM in India is sparse. Recently, there has been a surge in the number of cases of mucormycosis in association with the coronavirus disease 2019 (COVID-19) pandemic, igniting the interest in PM. Hence, we endeavoured to analyse our surgical experience in treating PM prior to the pandemic, in a tertiary care centre, to provide insight into this disease. Data of 10 adult patients with isolated PM, who underwent surgery between the years 2009 and 2020, and maintained in our departmental database, were retrieved and analysed.

Background: The ‘Sepsis Six’ bundle was promoted as a more deliverable tool outside of the critical care settings, but there is very little data available on the progress and change of sepsis care outside the critical care environment in the UK. Our aim was to compare the yearly prevalence, outcome and the Sepsis Six bundle compliance in patients at risk of mortality from sepsis in non-intensive care environments. Methods: Patients with a National Early Warning Score (NEWS) of 3 or above and suspected or proven infection were enrolled into four yearly 24-hour point prevalence studies, carried out in fourteen hospitals across Wales from 2016-2019. Results: Out of the 26,947 patients screened 1,651 fulfilled inclusion criteria and were recruited. The full ‘Sepsis Six’ care bundle was completed on 223 (14.0%) occasions, with no significant difference between the years. On 190 (11.5%) occasions none of the bundle elements were completed. There was no significant correlation between bundle element compliance, NEWS or year of study. One hundred and seventy (10.7%) patients were seen by critical care outreach; the ‘Sepsis Six’ bundle was completed significantly more often in this group (54/170, 32.0%) than for patients who were not reviewed by critical care outreach (168/1385, 11.6%; pConclusions: Our data suggests that despite efforts to increase sepsis awareness within the NHS, there is poor compliance with the sepsis care bundles and no change in the high mortality over the study period. Further research is needed to determine which time-sensitive ward-based interventions can reduce mortality in patients with sepsis and how can these results be embedded to routine clinical practice.Trial registration: Defining Sepsis on the Wards ISRCTN 86502304 https://doi.org/10.1186/ISRCTN86502304 prospectively registered 09/05/2016

Extracellular matrix (ECM) scaffolds that provide a conducive environment for normal cellular growth, differentiation and angiogenesis are important components of tissue engineered grafts for long term viability. ECM has shown to be an effective scaffold for the repair and reconstitution of several tissues, including blood vessels, skin graft, Dural repair, soft tissue grafts, hernia repair, myocardial repair, urinary tract structures, ophthalmic reconstruction and nerve tissue regeneration. These ECM scaffolds are completely degraded in vivo and induce a host cellular response that supports constructive remodeling rather than scar tissue formation. Several naturally occurring scaffold materials have been investigated, including small intestinal submucosa (SIS), acellular dermis (Allo Derm) bladder acellular matrix graft (UBM), amniotic membrane tissue (anthromatrix, ambiodry, amniograft), cadaveric fascia (Tutoplast) and porcine pericardium (IO patch). Common features of ECM-associated tissue remodeling include extensive angiogenesis, recruitment of circulating progenitor cells, rapid scaffold degradation and constructive remodeling of damaged or missing tissues. The sources, the methods of procurement and processing, and the effects of these naturally occurring, materials on angiogenesis and tissue deposition are reviewed.

BackgroundWe are in the midst of a pandemic caused by the novel SARS-Cov-2 virus. A large percentage of the patients are asymptomatic and hospitals around the world are struggling to restart routine services. We report the results of a universal testing protocol of all patients who underwent orthopaedic surgery in the month of July 2020 in a large orthopaedic speciality hospital in Bangalore, India.MethodsA retrospective study of all patients who underwent orthopaedic surgery in the month of July 2020 at a tertiary care orthopaedic speciality hospital in Bangalore, India. All patients underwent nasopharyngeal swab test before surgery. A questionnaire was used to assess the patient before the RT-PCR nasopharyngeal swab test. Data regarding imaging, investigations and follow up was recorded.ResultsIn the month of July 2020, 168 patients underwent routine nasopharyngeal RT-PCR swab test for COVID-19 prior to planned orthopaedic surgical procedure (Both trauma and elective cases). 16 of the RT-PCR tests were positive. However vascular cases and absolute emergencies were done without a RT - PCR test with PPE and all universal precautions. 11 patients underwent emergency surgery without a RT-PCR test. All 16 cases who were positive were asymptomatic. The asymptomatic positive rate was 9.52%. Of the 11 patients who underwent emergency surgery without a RT-PCR test, only one patient had a positive test post-operatively.ConclusionsRoutine nasopharyngeal RT-PCR testing revealed a high rate of asymptomatic cases. If the RT-PCR test is positive, it is best to defer the case till the test returns negative. All precautions must be taken while performing emergency surgeries. Our algorithm in managing patients has proven to be effective and can be replicated with ease to continue operating and taking care of orthopaedic patients during this pandemic.

Taking Venezuela’s complaint against the United States at the World Trade Organisation (“WTO”) as the inflection point, this Article will explore whether a characterisation of cryptocurrencies as a ‘currency’ (similar to a fiat currency) would ensure that cryptocurrencies are not covered by WTO disciplines on goods and services. Despite customary international law principles such as ius cudendae monetae and the persuasive argument that a ‘currency’ is neither a good or service – the Article answers this question in the negative. It will divide issues that can arise during such a WTO dispute into three categories: threshold, substantive and compliance issues. Threshold issues would involve interpretative challenges to determine whether the General Agreement on Trade in Services (“GATS”) and General Agreement on Tariffs and Trade (“GATT”) regulate cryptocurrencies. Since the GATS Schedule of Commitments has historically been interpreted in a technologically neutral manner, identifying cryptocurrencies as a ‘service’ may not prove to be insurmountable. However, the claim that cryptocurrencies are barter goods that will be subject to disciplines of the GATT deserves critical scrutiny – more so because the GATT regulates tangible products and contains specific provisions relating to balance-of-payments. The Article also undertakes a theoretical analysis of the heterodoxical nature of the cryptocurrency to evaluate whether it can be classified as a ‘security’ within the meaning of the GATS’ Annex on Financial Services. These threshold issues are, however, the tip of the iceberg. Once a WTO Panel commences its analysis, the substantive issues for consideration would involve determining whether a unique product such as cryptocurrencies has a ‘like product’ in the respondent Member’s market. Further, the Panel’s analysis would involve a consideration relating to ‘general exceptions’ under Article XIV, GATS or Article XX, GATT which would entail an examination of whether the measure was necessary to achieve, amongst other regulatory objectives, either compliance with domestic regulations or the maintenance of public order. If the measure adversely impacting cryptocurrencies is determined to be WTO-inconsistent, issues of compliance and suspension of concessions are imminent. WTO Panels have historically estimated the . quantum of suspensions of concessions by determining the trade volumes affected by the WTO-inconsistent measure and factoring it for a future time period. The decentralised nature of the distributed ledger technology underlying cryptocurrencies complicates any country-specific quantification of the impact on trade volumes of cryptocurrencies affected by the WTO inconsistent measure. Accordingly, determining suspensions of concessions in relation to cryptocurrencies would require significant judicial innovation by the arbitrator. Adjudicating Cryptocurrencies at the WTO: Potential Threshold and Substantive Issues.

Taking Venezuela’s complaint against the United States at the World Trade Organisation (“WTO”) as the inflection point, this article will explore whether a characterisation of cryptocurrencies as a ‘currency’ (similar to fiat currency) would ensure that cryptocurrencies are not covered by WTO disciplines on goods and services. Despite customary international law principles such as ius cudendae monetae and the persuasive argument that a ‘currency’ is neither a good or service - the article answers this question in the negative. In doing so, the article builds on the author’s blog post which was the first to analyse Venezuela’s complaint. It will divide issues that can arise during such a WTO dispute into three categories: threshold, substantive and compliance issues. Threshold issues would involve interpretative challenges to determine whether the General Agreement on Trade in Services (“GATS”) and General Agreement on Tariffs and Trade (“GATT”) regulate cryptocurrencies. Since the GATS Schedule of Commitments has historically been interpreted in a technologically neutral manner, identifying cryptocurrencies as a ‘service’ may not prove to be insurmountable. However, Howden’s claim that cryptocurrencies are barter goods that will be subject to disciplines of the GATT deserves critical scrutiny – more so because the GATT regulates tangible products and it also contains specific provisions relating to balance-of-payments. The article also undertakes a theoretical analysis of the heterodoxical nature of the cryptocurrency to evaluate whether it can be classified as a ‘security’ within the meaning of the GATS’ Annex on Financial Services. These threshold issues are, however, the tip of the iceberg. Once a WTO Panel commences its analysis, the substantive issues for consideration would involve determining whether a unique product such as cryptocurrencies has a ‘like product’ in the respondent member’s market. Further, the Panel’s analysis would involve a consideration relating to ‘general exceptions’ under Article XIV, GATS or Article XX, GATT which would entail an examination of whether the measure was necessary to achieve, amongst other regulatory objectives, either compliance with domestic regulations or the maintenance of public order. If the measure adversely impacting cryptocurrencies is determined to be WTO-inconsistent, issues of compliance and suspension of concessions are imminent. WTO Panels have historically estimated the quantum of suspensions of concessions by determining the trade volumes affected by the WTO-inconsistent measure and factoring it for a future time period. The decentralised nature of the distributed ledger technology underlying cryptocurrencies complicates any country-specific quantification of the impact on trade volumes of cryptocurrencies affected by the WTO inconsistent measure. Accordingly, determining suspensions of concessions in relation to cryptocurrencies would require significant judicial innovation by the arbitrator. The institutional perils of subjecting cryptocurrencies to WTO's disciplines highlighted in the article necessitate collective action by the WTO members to arrive at a normative framework to regulate cryptocurrencies at the WTO. The article concludes by arguing that the ongoing e-commerce negotiations between 76 member states at the WTO would be the most suitable forum for formulating such global rules. This is a Working Paper prepared for presentation at the conference on "International Economic Law in the Era of Distributed Ledger Technology" at the University of Turin, Italy on April 9, 2019. The full paper would soon be published in a leading journal.

Background: We are in the midst of a pandemic caused by the novel SARS-Cov-2 virus. A large percentage of the patients are asymptomatic and hospitals around the world are struggling to restart routine services. We report the results of a universal testing protocol of all patients who underwent orthopaedic surgery in the month of July 2020 in a large orthopaedic speciality hospital in Bangalore, India. Methods: A retrospective study of all patients who underwent orthopaedic surgery in the month of July 2020 at a tertiary care orthopaedic speciality hospital in Bangalore, India. All patients underwent nasopharyngeal swab test before surgery. A questionnaire was used to assess the patient before the RT-PCR nasopharyngeal swab test. Data regarding imaging, investigations and follow up was recorded. Results: In the month of July 2020, 168 patients underwent routine nasopharyngeal RT-PCR swab test for COVID-19 prior to planned orthopaedic surgical procedure (Both trauma and elective cases). 16 of the RT-PCR tests were positive. However vascular cases and absolute emergencies were done without a RT-PCR test with PPE and all universal precautions. 11 patients underwent emergency surgery without a RT-PCR test. All 16 cases who were positive were asymptomatic. The asymptomatic positive rate was 9.52%. Of the 11 patients who underwent emergency surgery without a RT-PCR test, only one patient had a positive test post-operatively. Conclusions: Routine nasopharyngeal RT-PCR testing revealed a high rate of asymptomatic cases. If the RT-PCR test is positive, it is best to defer the case till the test returns negative. All precautions must be taken while performing emergency surgeries. Our algorithm in managing patients has proven to be effective and can be replicated with ease to continue operating and taking care of orthopaedic patients during this pandemic.

Background: The Trauma Expectation Factor Trauma Outcomes Measure (TEFTOM) questionnaire is a self-administered, patient-rated outcome measurement questionnaire designed to measure both ‘expectation’ and ‘outcome’ in orthopaedic trauma patients using two subsets of 10 items. We aimed to validate this instrument in a culturally diverse cohort of patients recruited from Asian and European regions. Methods: A total of 193 adult patients with surgically treated AO Foundation/Orthopaedic Trauma Association types 43 and 44 ankle malleolar and distal tibia fractures were recruited with 158 followed up till 1 year. Expectations were assessed prior to surgery, at 2 weeks and after 6 months using the trauma expectation factor (TEF) score. Outcomes were evaluated at 2 weeks, 6 and 12 months using the trauma outcome measure (TOM), American Academy of Orthopaedic Surgeons (AAOS), foot and ankle outcome score (FAOS) and short form-36 (SF-36) questionnaires. Psychometric properties of TEFTOM were assessed. Results: TEF and TOM demonstrated good internal consistency (Cronbach’s α > 0.87) and reliability at all time points (intra-class correlation coefficients > 0.90). TOM showed strong correlations ( R 2 ≥ 0.60) with the AAOS foot and ankle score, all FAOS subscales, except ‘symptoms’ and SF-36 physical functioning, role physical, bodily pain, social functioning and the physical component summary at 6 and 12 months. Effect sizes for TOM were 2.30 and 0.74 from 2 weeks to 6 months and from 6 months to 12 months, respectively. The baseline patient TEF was predictive for the 1-year TOM score. Conclusions: TEFTOM demonstrated good psychometric properties in this cohort of patients with ankle fractures. The TEF ‘expectation’ score was predictive of the TOM ‘outcome’ score. We recommend researchers and clinicians to utilize TEFTOM when patient expectation measurement is concerned for orthopaedic trauma patients.

Background: The treatment of anterior cruciate ligament (ACL) injury consists of arthroscopic ACL reconstruction with patellar tendon or hamstring graft. Satisfactory results have been reported so far in the younger age group. Dilemma arises regarding the suitability of ACL reconstruction in the patients aged 50 years and above. This retrospective analyses the outcome of ACL reconstruction in patients aged 50 years and above at the time of presentation. Materials and Methods: 55 patients aged 50 years and above presented to our institution with symptomatic ACL tear and were managed with arthroscopic reconstruction with patellar tendon/hamstring graft. 22 patients underwent ACL reconstruction with bone- patellar tendon-bone graft and the remaining 33 with a hamstring graft. Evaluation of functional outcome was performed using International Knee Documentation Committee (IKDC) and Lysholm scoring in the preoperative period, at the end of 1 year and at the final followup. Radiographic evaluation was performed using the Kellgren–Lawrence grading system. Results: The mean preoperative IKDC score was 39.7 ± 3.3. At the end of 1-year following the operation, the mean IKDC score was 73.6 ± 4.9 and at the final followup was 67.8 ± 7.7. The mean preoperative Lysholm score was 40.4 ± 10.3. At the end of 1-year following the intervention, the mean Lysholm score was 89.7 ± 2.1 and at final followup was 85.3 ± 2.5. Overall, 14 out of 42 patients who underwent radiographic assessment showed progression of osteoarthritis changes at the final followup after the intervention. Conclusion: In our study, there was a statistically significant improvement in the IKDC and Lysholm scores following the intervention. There was a slight deterioration in the scores at the final followup but the overall rate of satisfaction was still high and most of the patients were able to do their routine chores and light exercises suitable for their age group. Around one-third of patients show progression of radiographic changes in the postoperative period and this requires long term evaluation.

Background & objectives: Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 Χ 10 [8] autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy. Methods: In this phase III prospective, multicentric trial 250 patients with AMI were included and randomized into stem cell therapy (SCT) and non SCT groups. All patients were followed up for six months. Patients with AMI having left ventricular ejection fraction (LVEF) of 20-50 per cent were included and were randomized to receive intracoronary stem cell infusion after successfully completing percutaneous coronary intervention (PCI). Results: On intention-to-treat analysis the infusion of MNCs had no positive impact on LVEF improvement of ≥ 5 per cent. The improvement in LVEF after six months was 5.17 ± 8.90 per cent in non SCT group and 4.82 ± 10.32 per cent in SCT group. The adverse effects were comparable in both the groups. On post hoc analysis it was noted that the cell dose had a positive impact when infused in the dose of ≥ 5 X 10 [8] (n=71). This benefit was noted upto three weeks post AMI. There were 38 trial deviates in the SCT group which was a limitation of the study. Interpretation & conclusions:Infusion of stem cells was found to have no benefit in ST elevation AMI. However, the procedure was safe. A possible benefit was seen when the predefined cell dose was administered which was noted upto three weeks post AMI, but this was not significant and needs confirmation by larger trials.

The purpose of this study was to evaluate the efficacy of the enhanced PS femoral component design released in 2008 by DePuy. The patellar clunk syndrome has been reported in a significant number of patients following total knee arthroplasty. Design modifications of the implant have been made to reduce the incidence of the patellar clunk, especially in the posterior substituted designs.130 total knee replacements performed using the enhanced PS femoral components were followed-up with clinical and radiographic evaluations.Patellar clunk was seen in 3 of the 130 knees (2%). This is much less than the incidence of patellar clunk reported until now.Removal of the sharp ridge in the intercondylar groove in the newer implant seems to have been effective in reducing the incidence of the patellar clunk. It also indicates that the sharp ridge was the most probable cause of the clunk.

An essay based on the theme - "Digital Creativity: Culture Reimagined”. This was WIPO's theme for the 2016 World Intellectual Property Day.

Wild indigenous small mammals including 83 rodents (bandicoot and black rats, and house mice) and a shrew captured from multiple sites in Vellore, south India, were tested for serological and molecular evidence of hantavirus infection. Indirect immunofluorescence assay (IFA) using Hantaan virus (HTNV) antigen indicated hantavirus-reactive antibodies in 16 (19.3%) of 83 rodents (bandicoot and black rats). Western blot (WB) using Thailand virus (THAIV) antigen confirmed hantavirus-reactive antibodies in nine of the 16 HTNV IFA-positive rodents. Reverse transcription polymerase chain reaction (RT-PCR) of lung and kidney tissue of captured mammals resulted in the detection of partial S segment sequence in a bandicoot rat. This study complements our earlier reports on hantavirus epidemiology in south India and documents first laboratory evidence for rodent-associated hantaviruses in south India.

Mountain economies are undergoing transformation from traditional agrarian to more industrial or service-oriented economies. Such changes invariably have socioeconomic impacts on nearby communities and lead to fragmentation and rural depopulation. Sikkim, a small state of India in the Eastern Himalayas, has recently embarked on a program of hydroelectricity project construction. This study examined community perceptions of the environmental and socioeconomic impacts of these projects in 3 rural areas and considers implications for future sustainable livelihoods. While benefits such as employment have accrued to the rural community from these economic development projects, changes in land use and in people's occupations may have adverse impacts on their future livelihoods. We argue that there is a need to support new types of land-based economic activities on abandoned agricultural lands, reclaim degraded lands, and introduce new products and production methods.

A safe and effective non-surgical method of termination of pregnancy is yet to be discovered. During the first 12 weeks of pregnancy, dilatation and curettage and vacuum suction are the methods of choice. Analysis of 3000 cases is done based on age, parity, religion, educational status, duration of pregnancy, methods of termination, complication, sterlization etc. Dilatation and evacuation as a single stage procedure was undertaken in 555 cases whereas in 2351 cases two-stage procedure using laminaria test was adopted. Vacuum suction is definitely an advance over the standard procedure of dilatation and curettage and 89 cases underwent this. Four hundred and eighty five patients had tubectomy along with termination and others were advised to have some other contraceptive measure. Important complications were haemorrhage, perforation, incomplete evacuation and post-operative pyrexia. The risk and complications of termination rises rapidly after 12 weeks of pregnancy so that there is a plea for dealing with a request for abortion as early as possible.

Objectives: The aim of this report was to study the effect of chronic stretch reversal on the electrophysiological characteristics of the atria in humans.Background: Atrial stretch is an important ...

The clinical presentation of hantavirus infections in India is unclear. We report here a case of hantavirus infection in a 46 year old quarry worker presenting with fever, abdominal pain, jaundice, thrombocytopenia and renal dysfunction. Seroconversion and rising anti-hantavirus IgG titers were taken as evidence of hantavirus infection. Clinicians should consider hantavirus infections in the differential diagnosis of acute febrile illness along with scrub typhus, leptospirosis and dengue.

Cardiovascular calcification, the formation of calcium phosphate deposits in cardiovascular tissue, is a common endstage phenomenon affecting a wide variety of bioprostheses. The purpose of the present paper is to study the possibility that some antiplatelet drugs (aspirin and persantine) and certain vitamins (vitamin C, vitamin B6, and vitamin E) and their combinations might prevent the mineralization of glutaraldehyde treated bovine pericardium (GABP) by modifying the pericardial surface. In this experimental protocol, we used Golomb and Wagner's (1991) in vitro model for studying GABP calcification and a diffusion cell with 2 compartments for evaluating the diffusion of calcium across the GABP. The results showed that a combination of aspirin and vitamins (0.5 mg% aspirin, 1.5 mg% vitamin C, 4 mg% vitamin B6, and 2 mg% vitamin E) in a metastable calcium phosphate solution not only reduced the transport of calcium ions through GABP, but along with the combinations of 0.5 mg% aspirin and 5 mg% persantine also produced significant reductions in GABP calcification. The exact mechanism of these changes in the calcification of GABP are still unknown. From these in vitro findings, it appears that a combined vitamin therapy with low doses of aspirin may be beneficial for platelet suppression and thereby prevent thrombosis. In addition, the vitamins may modify calcium transport and interfere with the adsorption at the surface, thus reducing GABP calcification. However, an important question that remains unanswered is whether this inhibitory effect would continue if the antiplatelet drugs and vitamins were discontinued. For the answer, more in vivo studies are needed to develop applications.

Micro catheter tubes were prepared from poly (carbonate urethane) (PCU, Bionate) and poly (ether urethane) (PEU, Pellethane) and their stability was investigated in vitro under applied strain. The tubes were stretched to an elongation of 200% or 300% and exposed to hydrogen peroxide/cobalt chloride (H(2)O(2)/CoCl(2)) solution for specific periods of time (up to 10 months). The samples were observed for surface degradation via scanning electron microscopy, the bulk erosion via the weight difference, and the changes in molecular weight using gel permeation chromatography. The 200% and 300% strained Pellethane tubes kept in H(2)O(2)/CoCl(2) solution for 1 month showed substantial cracking of the surface layer with pitting and have degraded completely within 45 to 60 days (from scanning electron microscopy). Bionate tubes treated in similar conditions for a 10-month period exhibited minute surface erosion in the depth of 0.25-1 microm and showed no evidence of major cracking or pitting. The gel permeation chromatography analysis of 300% strained catheters indicated that the degradation of Bionate tubes was negligible. The 10-month samples had shown approximately 18% reduction in their number average molecular weight (M(n)) and about 8% reduction in weight average molecular weight (M(w)). The Pellethane studied in similar conditions had indicated approximately 72% reduction in M(n) and about approximately 50% reduction in M(w) for 1 month. Overall, the Bionate underwent less degradation and the degradated surface layer was much thinner than Pellethane. These in vitro results are valuable in designing the in vivo studies for using Bionate tube as a long-term implant.

Aims To characterize the atrial remodelling in mitral stenosis (MS). Methods and results Twenty-four patients with severe MS undergoing commissurotomy and 24 controls were studied. Electrophysiological evaluation was performed in 12 patients in each group by positioning multi-electrode catheters in both atria to determine the following: effective refractory period (ERP) at 10 sites at 600 and 450 ms; conduction time; conduction delay at the crista terminalis (CT); and vulnerability for atrial fibrillation (AF). P-wave duration (PWD) was determined on the surface ECG. In the remaining 12 patients in each group, electroanatomic maps of both atria were created to determine conduction velocity and identify regions of low voltage and electrical silence. Patients with MS had larger left atria (LA) ( P < 0.0001); prolonged PWD ( P = 0.0007); prolonged ERP in both LA ( P < 0.0001) and right atria (RA) ( P < 0.0001); reduced conduction velocity in the LA ( P = 0.009) and RA ( P < 0.0001); greater number ( P < 0.0001) and duration ( P < 0.0001) of bipoles along the CT with delayed conduction; lower atrial voltage in the LA ( P < 0.0001) and RA ( P < 0.0001); and more frequent electrical scar ( P = 0.001) compared with controls. Five of twelve with MS and none of the controls developed AF with extra-stimulus ( P = 0.02). Conclusion Atrial remodelling in MS is characterized by LA enlargement, loss of myocardium, and scarring associated with widespread and site-specific conduction abnormalities and no change or an increase in ERP. These abnormalities were associated with a heightened inducibility of AF.

The development of suitable three-dimensional matrices for the maintenance of cellular viability and differentiation is critical for applications in tissue engineering and cell biology. To this end, gel matrices of different proportions of alginate/elastin/polyethylene glycol (Alg/Ela/PEG) were prepared and examined. The composite matrix membranes were evaluated for their porous scaffold using SEM, enzymatic degradation and water content. An equal blend of Alg/Ela with a ratio of Alg/Ela: PEG (7:3) was selected for fabricating Alg/Ela/PEG scaffolds for this study. The Alg/Ela/PEG membranes fabricated at 20 degrees C and - 20 degrees C had a mean surface pore size of 35-45 microm. However, their ultrastructures had shown bigger pore structures (60-75 microm) compared to their surface. It is interesting to note that the membranes of Alg/Ela/PEG prepared at 20 degrees C had larger ultrastructural pores than that of membranes prepared at -20 degrees C. Further, the SEM studies revealed that in the absence of PEG the composite membranes of Alg/Ela formed with less porous structures. The water content of membranes prepared at 20 degrees C was higher with Alg/Ela/PEG (61.6 +/- 4.8%), compared to Alg/Ela (49.9 +/- 0.3%). The enzymatic degradation and water content studies also revealed that the membranes fabricated at - 20 degrees C had high water uptake and low enzymatic degradation, as that of the membranes prepared at 20 degreees C. In other words the larger pore structured membranes had less water content and high degradation profile. This study proposes that this novel composite matrix produces a hierarchical structure that is useful for generating tissue scaffolds for repairing the failing cardiac muscles. However, more detailed investigations with cytocompatibility studies are needed to find applications.

The development of injectable microparticles for protein delivery is a major challenge. We demonstrated the possibility of entrapping human serum albumin (HSA) and thrombin (Thr) in poly(ethylene glycol) (PEG)-coated, monodisperse, biodegradable microspheres with a mean diameter of about 10 μm. In our earlier studies, diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) analysis was used to characterize the surface of PEG-coated, taxol-loaded poly(lactic acid) (PLA) microspheres. An analysis by DRIFTS revealed that PEG was incorporated well on the PLA microsphere surface. An emulsion of protein (in water) and PLA dissolved in an acetone–dichloromethane (or acetone–chloroform) mixture were poured into an aqueous solution of PEG [or poly(vinyl alcohol) (PVA)] with stirring with a high-speed homogenizer for the formation of microparticles. HSA recovery in microspheres ranged from 13 to 40%, depending on the solvent and emulsification systems used for the preparation. PLA dissolved in a dichloromethane/acetone system and albumin loaded via a PEG emulsification solution (PLA–PEG–HSA) showed maximum drug recovery (39.5%) and drug content (9.9%). Scanning electron microscopy revealed that PEG-coated microspheres had less surface micropores than PVA-based preparations. The drug-release behavior of microspheres suspended in phosphate-buffered saline exhibited a biphasic pattern. An initial burst release (30%) followed by a constant slow release for 20 days was observed for HSA and Thr from PLA–PEG microspheres. PEG-coated PLA microspheres show great potential for protein-based drug delivery. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 1285–1295, 2002

In this study, a spray coating technique was used to prepare poly(lactic acid) (PLA) tubes. To improve the flexibility of these devices, an elastomeric polymer, poly(ethylene vinyl acetate) (PEVAc), was added to the PLA. The PLA/PEVAc tubes were further surface modified with elastin and laminin via carbodiimide and glutaraldehyde treatment. This study evaluated the surface graft matrix components (elastin and laminin) on PLA/PEVAc tubes as a method for regenerating biointeractive materials for nerve growth and tissue engineering.

Heparin remains the gold-standard inhibitor of the process involved in the vascular response to injury. Continued anticoagulation is achieved by subcutaneous administration of low-molecular-weight heparin (LMW Hep) or with an orally active anticoagulant such as warfarin. An oral heparin would avoid the inconvenience of subcutaneous injections and adverse events associated with warfarin. A mild chitosan/PEG/calcium alginate microencapsulation process, as applied to encapsulation of biological macromolecules such as heparin and LMW Hep was investigated. Heparin and LMW Hep entrapped alginate beads were further surface/enteric coated with chitosan and cellulose acetate phthalate (CAP) via carbodiimide (EDC) functionalities. It was observed that approximately 70% of the content is being released into Tris-HCl buffer, pH 7.4 within the initial 6 hours and no significant release of LMW Hep was observed from enteric coated microspheres (12%) during treatment with 0.1 M HCl, pH 1.0 for 4 hours. But acid treated capsules had released almost all the entrapped LMW Hep into Tris-HCl, pH 7.4 media within 6 hours. From scanning electron microscopic and swelling studies, it appeared that the surface coatings (via chitosan and CAP) had modified the alginate microspheres and subsequently the drug release. The released heparin and LMW Hep had shown their anticoagulant functions. These results established the feasibility of modifying the formulation in order to obtain the desired controlled release of bioactive agent (LMW Hep), for a convenient pH dependent delivery system.

It is widely recognized that the technological and institutional integration of voice and data telecommunications beginning in the 1980s triggered what some people are calling the "e-revolution"of ...

The development of injectable microspheres for sustained drug delivery to the arterial wall is a major challenge. We demonstrated the possibility of entrapping an antiproliferative agent, taxol, in poly(ethylene glycol) (PEG)-coated biodegradable poly(lactic acid) (PLA) microspheres with a mean diameter of 2-6 microm. A solution of taxol and PLA dissolved in an acetone/dichloromethane mixture was poured into an aqueous solution of PEG [or poly(vinyl alcohol) (PVA] with stirring with a high-speed homogenizer for the formation of microspheres. Taxol recovery in PLA-PEG microspheres was higher (61.2 +/- 2.3%) than with PVA-based (41.6 +/- 1.8%) preparations. An analysis by diffuse reflectance infrared Fourier transform spectroscopy revealed that PEG was incorporated well on the PLA microsphere surface. Scanning electron microscopy revealed that the PEG-coated PLA microspheres were spherical in shape and had a smooth surface texture like those of PVA-based preparations. The amount of drug release was much higher initially (25-30%); this was followed by a constant slow-release profile for a 30-day period of study. This PEG-coated PLA microsphere formulation may have potential for the targeted delivery of antiproliferative agents to treat restenosis.

Smooth muscle cell proliferation plays a major role in the genesis of restenosis after angioplasty or vascular injury. Local delivery of agents capable of modulating vascular responses have the potential to prevent restenosis. However, the development of injectable microspheres for maintaining high tissue levels of drugs at the site of vascular injury is a major challenge. We demonstrated the possibility of entrapping an antiproliferative agent, colchicine, in polyethylene glycol (PEG)-coated biodegradable microspheres composed of poly(lactic acid)/poly(epsilon-caprolactone) blends, with a mean diameter of 3-6 microm. A solution of colchicine and blends of polylactic acid (PLA)/polycaprolactone (PCL) dissolved in acetone-dichloromethane mixture was poured into an aqueous solution of PEG (or polyvinyl alcohol) with stirring by a high-speed homogenizer to form microspheres. Colchicine recovery in microspheres ranged from 30-50% depending on the emulsification system and the ratio of polymer blends used for the preparations. Scanning electron microscopy revealed that the PLA/PCL microspheres were spherical in shape and had a smooth surface texture. Results of in vitro release studies showed that it is possible to control the colchicine release by choosing the appropriate particle size, loading, and PLA/PCL composition. Water permeability through the PLA membrane was greater, when compared with PCL blends. The amount of drug release also was much higher (58.3%) in PLA compared with PCL (39.3%) microspheres, for 30 days. Therefore, we concluded that the drug release from the microspheres followed a diffusion mechanism where bulk erosion and surface deposition were negligible. These PEG-coated PLA/PCL microspheres may have potential for targeting antiproliferative agents for prolonged periods to treat restenosis.

The strength, resorption rates, and biocompatibility of collagenous biomaterials are profoundly influenced by the method of cross-linking. The in vitro and in vivo calcification and enzymatic degradation of bovine pericardia (BP) after a series of surface modifications were studied as a function of exposure time. Collagenase degradations of modified BP were monitored by scanning electron microscopy and tensile strength measurements. Bovine pericardium was modified by a combination of different tissue fixatives such as glutaraldehyde (GA), carbodiimide (EDC), diisocyanate (HMDIC), and polyethylene glycol (PEG). GA-PEG-EDC-PEG and GA-PEG-HMDIC-PEG combination treated BP retained maximum stability in collagenase digestion compared to GATBP In vitro calcification studies and in vivo rat subcutaneous implantations of modified pericardium have shown substantial reduction in the calcification of double cross-linked BP with PEG modification. Further, the biocompatibility aspects of pericardial tissues were established by platelet adhesion and octane contact angle. It seems that cross-links involving amino and carboxyl residues may provide new ways of controlling biodegradation and calcification.