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BackgroundUnderstanding the perception and concerns of people about COVID-19 vaccine in developing and populous country like India will help in understanding demand for the vaccine and further tailoring out public health information and education activities before the launch of the vaccine. The study was carried out to assess the present state of knowledge people have about the probable vaccine for COVID-19, to know the preferences of respondents about this vaccine and to learn the expectations and apprehensions of people about features of this prospective COVID-19 vaccine residing in the capital city of India.MethodsThis cross-sectional study was conducted amongst the residents of Delhi, India from July-October 2020. Both offline and online interview method was used to collect date from 513 participants representing various occupational strata. Data was collected on socio demographic variable, vaccine acceptance and concerns regarding COVID-19 vaccine.ResultsAmong the study population 79.5% said they will take the vaccine while 8.8% said they were not going to take the vaccine and remaining 11.7% had not yet decided about it. Most of them(78.8%),believed that vaccine would be available to public next year but at the same time half(50.1%) of them believe that it may not be in sufficient amount for everyone to get. More than 50% were willing to pay for the vaccine and 72% felt vaccine should first be given to health workers and high risk group.ConclusionThe following study has helped to understand the percentage of people who are hesitant to take the vaccine and also the concerns regarding the vaccine. Also since half of the population is willing to pay for the vaccine, a strategical approach considering the various economical classes of people could be applied in a developing country like India.

Background: Understanding the perception and concerns of people about COVID-19 vaccine in developing and populous country like India will help in understanding demand for the vaccine and further tailoring out public health information and education activities. The study was carried out to assess the present state of knowledge people have about the probable vaccine for COVID-19, to know the preferences of respondents about this vaccine and to learn the expectations and apprehensions of people about features of this prospective COVID-19 vaccine residing in the capital city of India. Methods: This cross-sectional study was conducted amongst the residents of Delhi, India from July to October 2020. Both offline and online interview method was used to collect date from 513 participants representing various occupational strata. Data were collected on sociodemographic variable, vaccine acceptance and concerns regarding COVID-19 vaccine. Results: Among the study population, 79.5% said they will take the vaccine while 8.8% said they were not going to take the vaccine and remaining 11.7% had not yet decided about it. More than 50% were willing to pay for the vaccine and 72% felt vaccine should first be given to health workers and high-risk group. Conclusion: The following study has helped to understand the percentage of people who are hesitant to take the vaccine and also the concerns regarding the vaccine. Also since half of the population is willing to pay for the vaccine, a strategic approach considering the various economical classes of people could be applied in a developing country like India.

A feature of healthy human walking gait is a clearly defined heel-strike at initial contact, known as heel-to-toe gait. However, a common consequence of ageing is the deterioration of this heel first gait toward a flat foot, or “shuffling” gait. This leads to a shortened stride length, slowed gait speed, and an increased fall risk. Shuffling gait is normally treated by physiotherapy, however, therapist time is limited and training is restricted to a clinical environment. Gait rehabilitation could be expedited with the use of a device that distinguishes between heel-to-toe and shuffling gait and gives feedback to the user. This paper describes the design and validation of a device to achieve this. The device is innovative in that it both analyses the kinematics of the foot in real time and uses this information to classify the step quality in a manner that agrees with the subjective judgement of a physiotherapist. The device comprises a sensing module and a biofeedback module. The sensing module is a six axis inertial measurement unit that is strapped to the patient's foot. Raw data are streamed wirelessly to the biofeedback module (a smartphone), which runs an algorithm to detect step quality on the basis of angular velocity of the foot, and gives binary feedback to the user. Results from a validation study on the target population demonstrate very good classification performance, with an accuracy of 84.1% when compared with physiotherapist labels. The sensitivity is 92.4% at an operating point of 75% specificity, and the area under the ROC curve is 0.937. This performance should be more than adequate for clinical use and opens the door for investigations to determine how it can be used most effectively.

Azo prodrugs of aminosalicylates viz: 5-aminosalicylic acid and 4-aminosalicylic acid were synthesised using phenols as colon- targeting carriers for management of inflammatory bowel disease. The structures were confirmed by spectral and elemental analysis. These azo- linked prodrugs showed increased hydrophilicity which prevented their absorption from the upper GIT thus delivering them intact to the colon. They were also seen to be stable in stomach and intestinal homogenates, showing minimal release. Activation of prodrugs was faster in cecal matter showing upto 96-98% release with prolonged half lives. Amongst the azo series; 5-Aβ and 4-Ares significantly attenuated the symptoms of colitis induced by TNBS but their overall efficacy was less than SLZ. Safety assessment revealed absence of any abnormalities in hepatic and pancreas morphology with significantly low ulcerogenic propensity.

Novel carrier-linked azo prodrugs of 4 and 5-aminosalicylic acids (4-ASA and 5-ASA respectively) using the same drugs as carriers in different permutations and combinations were designed for targeting colon affected with inflammatory bowel disease (IBD). Improved hydrophilic nature of the prodrugs assisted in minimizing their absorption in upper GIT and efficient delivery of the active drugs to colon as evidenced from their stability in aqueous buffers (pH 1.2 and 7.4) and upper GIT homogenates with 68-91% release on incubation with rat cecal matter. Amongst the series, 4A4AAZ (prodrug of 4-ASA with 4-ASA) at a dose of 53 mg/Kg was found to be the most promising candidate as it substantially alleviated the quantifying markers of colonic inflammation in TNBS-induced experimental colitis in Wistar rats. Moreover it displayed significantly lower GI toxicity (at ten times higher dose). 5-ASA- induced pancreatitis and sulfapyridine-induced adverse effects on liver that are characteristic of sulfasalazine were not observed with 4A4AAZ. It could be explored further as a potential candidate for IBD patients intolerant to pancreatitis induced by oral administration of 5-ASA.

Sterically hindered esters or esters of drugs with macromolecular carriers like dextran and cyclodextrin find wide applicability in colon-targeted delivery. We report here synthesis, in vitro release kinetics of macromolecular prodrug of 4-aminosalicylic acid (4-ASA) with β-cyclodextrin and its extensive pharmacological evaluation in 2, 4, 6- trinitrobenzenesulphonic acid - induced colitis in rats. Formyl 4-ASA was conjugated with β-cyclodextrin by CDI coupling followed by deprotection of the final product which was then characterized by IR, 1H-NMR and LC-MS. In vitro stability and release were studied in buffers (pH 1.2 and 7.4), stomach/small intestinal homogenates and rat cecal/fecal matters. The prodrug resisted pH-dependent hydrolysis. In stomach and small intestinal homogenates 20-23% release was observed (t1/2: 1278 and 1103 min respectively) while 68% and 92% release was furnished in rat cecal and fecal matters (t1/2: 341 and 245 min respectively). Mitigating effect of 4-AβCyd on colitis was moderate when compared with sulfasalazine or 4/5-ASA administered rectally, but it was comparable to that of aminosalicylates administered orally, suggesting incomplete delivery of 4-ASA to colon due to partial hydrolysis of 4-AβCyd in the upper GIT. The histological assessment of pancreas and liver of the prodrug-treated group showed no pathological changes indicating its better safety profile than that of sulfasalazine or oral 5-ASA. The prodrug brought about significant lowering in ulcer index compared to aminosalicylates suggesting significant improvement in gastro-protective effect than oral aminosalicylates.

Sterically hindered esters or esters of drugs with macromolecular carriers like dextran and cyclodextrin find wide applicability in colon-targeted delivery. We report here synthesis, in vitro release kinetics of macromolecular prodrug of 4-aminosalicylic acid (4-ASA) with β-cyclodextrin and its extensive pharmacological evaluation in 2, 4, 6- trinitrobenzenesulphonic acid - induced colitis in rats. Formyl 4-ASA was conjugated with β-cyclodextrin by CDI coupling followed by deprotection of the final product which was then characterized by IR, 1H-NMR and LC-MS. In vitro stability and release were studied in buffers (pH 1.2 and 7.4), stomach/small intestinal homogenates and rat cecal/fecal matters. The prodrug resisted pH-dependent hydrolysis. In stomach and small intestinal homogenates 20-23% release was observed (t1/2: 1278 and 1103 min respectively) while 68% and 92% release was furnished in rat cecal and fecal matters (t1/2: 341 and 245 min respectively). Mitigating effect of 4-AβCyd on colitis was moderate when compared with sulfasalazine or 4/5-ASA administered rectally, but it was comparable to that of aminosalicylates administered orally, suggesting incomplete delivery of 4-ASA to colon due to partial hydrolysis of 4-AβCyd in the upper GIT. The histological assessment of pancreas and liver of the prodrug-treated group showed no pathological changes indicating its better safety profile than that of sulfasalazine or oral 5-ASA. The prodrug brought about significant lowering in ulcer index compared to aminosalicylates suggesting significant improvement in gastro-protective effect than oral aminosalicylates.

Fifty-six serum posaconazole trough levels were measured in 17 cardiothoracic transplant recipients. Initial levels were ≤0.5, 0.51 to 0.99, and ≥1 μg/ml for 47, 29, and 24% of patients, respectively. Median trough levels associated with therapeutic success were higher than those associated with failure (1.55 versus 0.34 μg/ml; P = 0.006). Patients with levels consistently >0.5 μg/ml were more likely to have successful outcome ( P = 0.055). Age ≥65 years, oral administration, and absence of proton pump inhibitors were associated with higher levels of posaconazole ( P = 0.006, 0.006, and 0.001, respectively).

Even though sulfasalazine is drug of choice for treatment of ulcerative colitis (UC), 5-aminosalicylicacid (5-ASA)-induced pancreatitis and sulfapyridine-induced hepatitis are well documented in the literature. 4-aminosalicylic acid (4-ASA) is a promising but unexplored alternative, offering a lower risk of pancreatitis than 5-ASA. According to recent reports, a nutritional supplement of glucosamine could be useful in UC by suppressing activation of intestinal epithelial cells. Considering these findings, amide conjugates of aminosalicylates with D-glucosamine were synthesized by DCC coupling. In vitro release was studied in aqueous buffers, tissue homogenates of stomach/small intestine and rat cecal/fecal matter while therapeutic efficacy was evaluated in trinitrobenzenesulphonic acid (TNBS)-induced experimental colitis. The ameliorating effect of 5-ASA prodrug on the course of TNBS- induced colitis was comparable, while that for 4-ASA prodrug was moderate compared to sulfasalazine. Combination co-drug therapy of aminosalicylates with D-glucosamine offers an innovative and attractive platform that could be explored further for the safer management of UC.

Background Skin cancer, in particular squamous cell carcinoma (SCC), is the most common malignancy after solid-organ transplantation. SCC has been reported in immunosuppressed patients receiving voriconazole, but the agent has not been shown to be a risk factor. Universal voriconazole prophylaxis and alemtuzumab induction are standard in our lung transplant program. Methods We performed a retrospective, case–control study (matched 1:3) among lung transplant recipients at our center from 2003 to 2008. Results SCC was diagnosed in 3.1% (17 of 543) of patients at a median follow-up of 36 months. Median time to development of SCC was 19 months post-transplant. Risk factors for SCC by univariate analysis included older age ( p = 0.02), residence in locations with high levels of sun exposure ( p = 0.0001), single-lung transplant ( p = 0.02) and duration ( p = 0.03) and cumulative dose ( p = 0.03) of voriconazole. Duration of voriconazole (hazard ratio [HR] = 2.1; p = 0.04) and residence in locations with high sun exposure (HR = 3.8; p = 0.0004) were independent risk factors by multivariate analysis. SCC lesions were located on the head and neck in 94% of cases, and 53% had multiple lesions. All patients were treated with surgery. At least one independent lesion developed subsequently in 47% of patients. Local spread and distant metastases each occurred in 7% of cases. There were no deaths among the cases. Conclusions Voriconazole exposure is a risk factor for SCC after lung transplantation, particularly among older patients living in areas with high sun exposure. Voriconazole should be used cautiously in these patients.

Introduction. Little is known about the incidence or significance of mold infections in the explanted lungs of lung transplant recipients. Method. We reviewed the histopathology of the explanted lungs from 304 patients who underwent lung transplantation at our institution from 2005 to 2007 and received alemtuzumab induction therapy and posttransplant voriconazole prophylaxis. Results. Invasive mold infections were present in the explanted lungs of 5% (14 of 304) of patients, including chronic necrotizing pneumonias (n=7), mycetomas (n=4), and invasive fungal pneumonias (n=3). Only 21% (3 of 14) received immunosuppressive therapy within 1 year before lung transplantation, suggesting that lung damage itself predisposed patients to mold infections. The risk of mold infection was higher in patients with cystic fibrosis (11%, 4 of 35) than other underlying lung diseases (4%, 10 of 269). Pulmonary mold infections were not diagnosed or suspected in 57% (8 of 14) of patients. Despite secondary voriconazole prophylaxis, fungal infections developed in 43% (6 of 14) of patients with mold infections of the explanted lungs compared with 14% (42 of 290) of patients without mold infections (P=0.01). Three patients developed invasive fungal infections while on voriconazole prophylaxis and three developed fungal infections more than 8 months after the discontinuation of voriconazole. The mortality attributable to invasive fungal infections among patients with mold infections of the explanted lungs was 29% (4 of 14). Conclusion. Invasive mold infections in the explanted lungs are often not recognized before lung transplantation and are associated with poor outcomes.

The objective of the present work was to investigate the targeting potential of L-glutamine utilizing concept-based mutual prodrug design for the delivery of meselamine to colon. Meselamine was linked with L-glutamine through azo linkage and was subjected to in vitro stability studies in aqueous buffers of varied pH range and rat fecal matter. 84.7% release of meselamine was achieved in rat fecal matter with a half-life of 153.5 min, following first order kinetics. Experimental colitis was induced in rats by TNBS to evaluate the therapeutic efficacy of the carrier system and mitigating effect of the conjugate on the colonic inflammation. The results for quantifying parameters like clinical activity score rate, colon to body weight ratio, myeloperoxidase activity and histopathological studies suggest that L-glutamine could be developed as a promising carrier for targeting meselamine to colon for the management of inflammatory bowel disease.

Mesalazine is widely used systemically or topically to achieve and maintain remission in inflammatory bowel disease. Latentiated derivatives of mesalazine having L-histidine and L-tyrosine covalently linked via an amide linkage were designed, developed and screened in 2, 4, 6-trini-trobenzenesulphonic acid-induced experimental colitis in rats. Incubation of prodrugs with tissue homogenates of stomach and small intestine of rats furnished 4-8% and 9-12% release respectively over a 10-h period. Their colon-specific activation was confirmed from their release profile on incubation with rat fecal and cecal material at 37°C in anaerobic conditions (5% CO2). 79-98% release of mesalazine was observed in rat fecal matter while almost complete release of mesalazine (99%) was observed in rat cecal matter over a 10-h period. The half-lives of mesalazine prodrugs ranged between 236-295 min following zero order kinetics. The improving effect of latentiated derivatives on the symptoms of colitis induced by 2, 4, 6-trinitrobenzenesulphonic acid is comparable to sulfasalazine. Amongst the reported prodrugs, potential of SSDGV2 (latentiated derivative of mesalazine with L-histidine) can be explored further as a promising candidate for the safer management of inflammatory bowel disease.

Summary Simvastatin is a selective HMG-CoA reductase inhibitor and ezetimibe has lipid-lowering activity. Both are potential anti-lipidemic agents used in combination to reduce the amount of cholesterol and triglycerides in systemic circulation. This paper describes a simple, precise, and accurate HPTLC method for simultaneous estimation of the compounds as the bulk drugs and in the tablet dosage form. Chromatographic separation was performed on aluminium-backed silica gel 60 F254 plates with 8:2 (v/v) toluene-2-propanol as mobile phase. The separated spots were densitometrically evaluated at 240 nm. The drugs were satisfactorily resolved with RF values 0.48 ± 0.01 and 0.53 ± 0.01 for simvastatin and ezetimibe, respectively. The accuracy and reliability of the method were assessed by determination of validation data for linearity (0.4–2.0 μg per spot for both simvastatin and ezetimibe), precision (intra-day RSD 0.51–1.04%, inter-day RSD 0.34–1.11% for simvastatin; intra-day RSD 0.47–0.61%, inter-day RSD 0...

Mutual azo prodrug of 5-aminosalicylic acid with L-tryptophan was synthesized by coupling L-tryptophan with salicylic acid, for targeted drug delivery to the inflamed gut tissue in inflammatory bowel disease. The structure of synthesized prodrug was confirmed by elemental analysis, IR and NMR spectroscopy. In vitro kinetic studies in HCl buffer (pH 1.2) showed negligible release of 5-aminosalicylic acid, whereas in phosphate buffer (pH 7.4) 18% release was observed over a period of 7 h. In rat fecal matter, 87.9% of 5-aminosalicylic acid was released with a half-life of 143.6 min, following first order kinetics. The azo conjugate was evaluated for its ulcerogenic potential by Rainsford's cold stress method. The ameliorating effect of the azo conjugate and therapeutic efficacy of the carrier system was evaluated in trinitrobenzenesulfonic acid-induced experimental colitis model. The synthesized prodrug was found to be equally effective in mitigating the colitis in rats as that of sulfasalazine without the ulcerogenicity of 5-amino-salicylic acid.

Mutual azo prodrug of 5-aminosalicylic acid with d-phenylalanine was synthesized by coupling D-phenylalanine with salicylic acid, for targeted drug delivery to the inflamed gut tissue in inflammatory bowel disease. The structure of synthesized prodrug was confirmed by elemental analysis, IR and NMR spectroscopy. In vitro kinetic studies in HCl buffer (pH 1.2) showed negligible release of 5-aminosalicylic acid, whereas in phosphate buffer (pH 7.4) only 15% release was observed over a period of 7h. In rat fecal matter the release of 5-aminosalicylic acid was almost complete (85%), with a half-life of 160.1 min, following first order kinetics. The azo conjugate was evaluated for its ulcerogenic potential by Rainsford's cold stress method. Therapeutic efficacy of the carrier system and the mitigating effect of the azo conjugate were evaluated in trinitrobenzenesulfonic acid-induced experimental colitis model. The synthesized prodrug was found to be equally effective in mitigating the colitis in rats as that of sulfasalazine without the ulcerogenicity of 5-aminosalicylic acid.

A feature of healthy gait is a clearly defined heel strike upon initial contact of the foot with the ground. However, a common consequence of ageing is deterioration of the heel first nature of gait towards a shuffling gait (flat foot at contact). Physiotherapy can be effective in correcting this but is costly and labour intensive. Gait rehabilitation could be accelerated with home exercise, guided by a biofeedback device that distinguishes between heel first and shuffling gait. This paper describes an algorithm that distinguishes between heel-to-toe gait and shuffling gait on the basis of angular velocity of the foot, using an inertial measurement unit. Measurements were made of normal and abnormal gait and used to develop an algorithm that distinguishes between good and bad steps. Results demonstrate very good algorithm performance, with a classification accuracy at the accuracy-optimal threshold of 92.7% when compared with physiotherapist labels. The sensitivity and specificity at this threshold are 84.4% and 97.5% respectively. These performance metrics suggest that this algorithm is usable in a biofeedback device.

In a prospective study, enhanced external counterpulsation (EECP) was performed for 1 hour each day for 35 days in 47 patients, mean age 61 +/- 8 years, with prior coronary revascularization who had chronic refractory angina pectoris despite antianginal drugs and who were not candidates for further coronary revascularization. Compared with baseline values, EECP significantly improved anginal symptoms, dyspnea on exertion, and quality of life after 35 days of treatment (P < 0.001) and at 1-year follow up (P < 0.001). Compared with the baseline value of 653 +/- 249 feet, EECP significantly improved the 6-minute walking distance to 1025 +/- 234 feet after 35 days of treatment (P < 0.001) and to 1040 +/- 221 feet at 1-year follow up (P < 0.001). However, EECP did not significantly affect left ventricular ejection fraction, left ventricular end-diastolic and end-systolic dimensions, left ventricular end-diastolic and end-systolic volumes, E/A ratio, isovolumic relaxation time, and deceleration time measured by two2-dimensional and Doppler echocardiography.

OBJECTIVES: Falls increase morbidity and mortality among nursing home residents and have varied causes and risk factors. The purpose of this study was to assess whether falls in nursing home residents were more prevalent at particular times of the day. DESIGN/PARTICIPANTS: This study was a retrospective chart review for falls in a skilled nursing facility in New York from January to June, 2007. RESULTS: There were 220 falls during the 6-month period. Most falls (66%) occurred in the resident's room and almost half (48%) resulted in an injury. Falls during the evening were likely to result in a more serious injury than daytime falls (P = .03). A statistically significant higher percentage of falls (27%) occurred between 4 pm and 8 pm (compared with expected number in a 4-hour period, P < .001). Among the 3 nursing shifts, the lowest percentage of falls occurred during the 11 pm to 7 am night shift (16%). CONCLUSION: This study reveals a variation in the prevalence of falls in the nursing home based on time of day that is different from the pattern of falls in the hospital setting. More research is needed to evaluate possible causes of this temporal pattern of falls in the nursing home. Perhaps these data can be used to implement specific interventions at times when falls are more common to reduce the risk of falls. Language: en

Background. The sensitivity of blood cultures for diagnosing invasive candidiasis (IC) is poor. Methods. We performed a validated Candida real-time polymerase chain reaction (PCR) and the Fungitell 1,3-b-D-glucan (BDG) assay on blood samples collected from prospectively identified patients with IC (n 5 55) and hospitalized controls (n 5 73). Patients with IC had candidemia (n 5 17), deep-seated candidiasis (n 5 33), or both (n 55). Controls had mucosal candidiasis (n 55), Candida colonization (n 5 48), or no known Candida colonization (n 5 20). Results. PCR using plasma or sera was more sensitive than whole blood for diagnosing IC (P 5 .008). Plasma or sera PCR was more sensitive than BDG in diagnosing IC (80% vs 56%; P 5 .03), with comparable specificity (70% vs 73%; P 5 .31). The tests were similar in diagnosing candidemia (59% vs 68%; P 5 .77), but PCR was more sensitive for deep-seated candidiasis (89% vs 53%; P 5 .004). PCR and BDG were more sensitive than blood cultures among patients with deep-seated candidiasis (88% and 62% vs 17%; P 5 .0005 and .003, respectively). PCR and culture identified the same Candida species in 82% of patients. The sensitivity of blood cultures combined with PCR or BDG among patients with IC was 98% and 79%, respectively. Conclusions. Candida PCR and, to a lesser extent, BDG testing significantly enhanced the ability of blood cultures to diagnose IC.

BACKGROUND Early diagnosis and treatment of invasive pulmonary aspergillosis (IPA) improves outcome. METHODS We compared the performance of publicly available pan-Aspergillus, Aspergillus fumigatus-, and Aspergillus terreus-specific real-time polymerase chain reaction (PCR) assays with the Platelia galactomannan (GM) assay in 150 bronchoalveolar lavage (BAL) samples from lung transplant recipients (16 proven/probable IPA, 26 Aspergillus colonization, 11 non-Aspergillus mold colonization, and 97 negative controls). RESULTS The sensitivity and specificity of pan-Aspergillus PCR (optimal quantification cycle [Cq], ≤35.0 by receiver operating characteristic analysis) and GM (≥.5) for diagnosing IPA were 100% (95% confidence interval, 79%-100%) and 88% (79%-92%), and 93% (68%-100%) and 89% (82%-93%), respectively. The sensitivity and specificity of A. fumigatus-specific PCR were 85% (55%-89%) and 96% (91%-98%), respectively. A. terreus-specific PCR was positive for the 1 patient with IPA due to this species; specificity was 99% (148 of 149 samples). Aspergillus PCR identified 1 patient with IPA not diagnosed by GM. For BAL samples associated with Aspergillus colonization, the specificity of GM (92%) was higher than that of pan-Aspergillus PCR (50%; P = .003). Among negative control samples, the specificity of pan-Aspergillus PCR (97%) was higher than that of BAL GM (88%; P = .03). Positive results for both BAL PCR and GM testing improved the specificity to 97% with minimal detriment to sensitivity (93%). CONCLUSIONS A recently developed pan-Aspergillus PCR assay and GM testing of BAL fluid may facilitate the diagnosis of IPA after lung transplantation. A. fumigatus- and A. terreus-specific real-time PCR assays may be useful in rapidly identifying the most common cause of IPA and a species that is intrinsically resistant to amphotericin B, respectively.

Background An age limit of 65 years has been suggested for lung transplantation (LTx). Methods We conducted a retrospective study of LTx recipients at our institution and compared survival rates among patients aged 65 years. We identified common complications and risk factors for death among patients aged ≥ 60 years. Results Between January 2006 and May 2008, 126 of 268 (47%) of LTx recipients were aged >60 years, among whom 36% were 60 to 65 and 64% were >65 years. There were no differences in survival among patients aged 65 years. Among older patients, the major complications were infections (78%), rejection (36%), thromboembolism (21%), bone fractures (12%), malignancies (10%), and drug toxicity (10%). Rejection was more common among patients who were aged 60 to 65, and malignancies and drug toxicity were more common among patients >65 years. Other complications did not differ by age group. Infections accounted for 69% of deaths within 12 months, and infection-related deaths did not differ among the groups. Major infections were the strongest independent risk factors for death (hazard ratio, 4.37), followed by cytomegalovirus mismatch (hazard ratio, 3.69) and pre-transplant coronary artery disease (hazard ratio, 2.43). Conclusions Survival rates among LTx recipients were similar regardless of age, but specific complications among older patients differed by age. Selection for LTx should not be based strictly on an age cutoff, but rather individualized according to general health status and other risk factors. Further research on risk factors affecting outcomes, pharmacokinetics and dynamics, quality of life, and mechanisms of untoward events is needed among older LTx recipients.

Earlier colon was considered as a black-box, acting as a site for production and temporary storage of excreta and responsible for absorption of electrolytes and water. But, with the discovery of sulfasalazine as colon-specific prodrug, the promising and challenging issue of treating local pathologies was presented with colon as an organ of significance for target-specific delivery of drugs. The need and desirable attributes of colon-specific drug delivery systems have been well recognized, extensively explored and documented in the literature. The success of a colon-specific prodrug depends on its rational design and understanding the demands of the organ to be targeted and the delivery system to be developed. The present review mainly focuses on anatomy/physiology of colon, colonic microbiota, enzymatic set up of colon, pathophysiology of local diseases of colon, factors, obstacles and rationale for designing colon specific drug delivery system, various targets, potential drug candidates and novel colon-targeting carriers along with varied linkages that could be explored, merits and demerits of this design and recent trends in this field. Brief review of methodologies for characterization and in vitro/in vivo release studies is presented. The available animal models with quantifying parameters for evaluating colon-targeting potential and effectiveness of the colon-specific prodrugs for inflammatory bowel disease is also included in this review.

Valganciclovir prophylaxis is advocated for lung transplant recipients, but its efficacy is unknown.Retrospective review was done of 109 donor-positive/recipient-negative lung transplant patients who received alemtuzumab induction and valganciclovir for cytomegalovirus prophylaxis.Median duration of follow-up after transplant was 27 months. Valganciclovir dose reductions (900 mg/day or renal-equivalent) were required for 18 patients (17%) due to toxicity, most commonly for neutropenia (n = 15) or gastrointestinal symptoms (n = 2). Of the 109 patients, 34 (31%) had no CMV infections, 45 (41%) had asymptomatic viremia, and 30 (27%) had CMV disease. CMV disease developed off prophylaxis in 10 patients (18%) at a median of 8.7 months after transplant and 2 months after valganciclovir discontinuation. Breakthrough disease occurred during prophylaxis in 10 patients (9%) at a median of 6.7 months. Patients with asymptomatic viremia or no CMV infection received prophylaxis for median 8.6 and 8.7 months, respectively. Risk factors for CMV disease by univariate analysis were increased age (p = 0.01), single-lung transplant (p = 0.03), chronic obstructive pulmonary disease (p = 0.05), reduced-dose valganciclovir (p = 0.001), and less than 6 months of prophylaxis (p = 0.005). By multivariate analysis, advanced age (p = 0.01) and reduced-dose valganciclovir (p = 0.0006) were independent risk factors for CMV disease. CMV disease developed in 4 patients (4%) due to ganciclovir-resistant viruses. CMV-attributable mortality was 5% (5 of 109), including 100% (4 of 4) with ganciclovir-resistant disease.Valganciclovir prophylaxis among donor-positive/recipient-negative lung transplant recipients delayed but did not eliminate CMV disease or CMV-related deaths and was limited by toxicity and ganciclovir-resistance. Our experience suggests that valganciclovir at reduced-doses or for less than 6 months is sub-optimal in preventing CMV disease.

We investigated in 51 consecutive outpatients with symptomatic congestive heart failure caused by abnormal left ventricular (LV) ejection fraction treated with furosemide or torsemide (10% also with metolazone), beta blockers, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, 55% with spironolactone, and 18% with digoxin, the effects of doubling the dose of furosemide, torsemide, and metolazone on symptoms, weight, 6-minute walk distance, and echocardiographic measurements of LV systolic and diastolic function at 24 ± 6 days follow-up. At follow-up, the weight decreased from 70 ± 6 kg to 65 ± 6 kg (P < 0.001), the New York Heart Association functional class decreased from 2.9 ± 0.4 to 2.1 ± 0.2 (P < 0.001), the Minnesota With Heart Failure Questionnaire score decreased from 43 ± 7 to 28 ± 8 (P < 0.001), the 6-minute walk distance increased from 270 ± 46 m to 318 ± 44 m (P < 0.001), and there was no significant change in LV ejection fraction, LV end-diastolic dimension, LV end-systolic dimension, left atrial dimension, pulmonary artery systolic pressure, peak mitral early/ atrial ratio, mitral deceleration time, and velocity time interval. In conclusion, doubling the dose of diuretics in outpatients with symptomatic congestive heart failure caused a significant loss of weight and a significant improvement in symptoms and 6-minute walk distance but did not change LV systolic and diastolic function.

Colon-specific mutual azo prodrugs of 5-aminosalicylic acid with essential amino acids were synthesized for the management of inflammatory bowel disease. The structures were confirmed by elemental and spectral analyses. 85-88% release of 5-aminosalicylic acid was achieved in rat fecal matter with half-lives ranging from 140 to 160 min, following first order kinetics. The prodrugs exhibited comparable ameliorating effect as that of sulfasalazine on trinitrobenzenesulfonic acid-induced experimental colitis in rats with a better safety profile.

Mutual amide prodrugs of 4-aminosalicylic acid with d -phenylalanine and l -tryptophan were synthesized for targeted drug delivery to the inflamed gut tissue in inflammatory bowel disease. Stability studies in aqueous buffers (pH 1.2 and 7.4) showed that the synthesized prodrugs were stable in both the buffers over a period of 10 h. In rat fecal matter the release of 4-aminosalicylic acid from the prodrugs was in the range of 86–91% over a period of 20 h, with half-lives ranging between 343 and 412 min following first order kinetics. Targeting potential of the carrier system and the ameliorating effect of the amide conjugates were evaluated in trinitrobenzenesulfonic acid-induced experimental colitis model in rats. The prodrugs were assessed for their probable damaging effects on pancreas and liver with the help of histopathological analysis and for their ulcerogenic potential by Rainsford's cold stress method. They were found to have improved safety profile than sulfasalazine, oral 4- and 5-aminosalicylic acid with similar pharmacological spectrum and advantages of sulfasalazine.

Mutual azo prodrug of 5-aminosalicylic acid with l-tyrosine was synthesized by coupling l-tyrosine with salicylic acid, for targeted drug delivery to the inflamed gut tissue in inflammatory bowel disease. The structure was confirmed by elemental analysis, IR and NMR spectroscopy. In vitro kinetic studies in rat fecal matter showed 87.18% release of 5-aminosalicylic acid with a half-life of 140.28min, following first order kinetics. Therapeutic efficacy of the carrier system and the mitigating effect of the azo conjugate were evaluated in trinitrobenzenesulfonic acid-induced experimental colitis model. Myeloperoxidase activity was determined by the method of Krawisz et al. The synthesized prodrug was found to produce comparable mitigating effect as that of sulfasalazine on colitis in rats.

This study aimed to quantify resistant starch (RS) beta-glucans (BG) and fructo-oligosaccharides (FOS) in Indian and Canadian wheat varieties and in chapaties made from these; and to assess the effects of soy flour on the levels of these components and its effects on the sensory and functional properties of the wheat-soy chapaties. Seven wheat varieties (Indian / Canadian) were milled into flour; supplemented with 0 % (control), 10 %, 20 % or 30 % defatted soy flour and made into chapaties. Flours and chapaties (freeze-dried, pulverized) were assayed for BG, FOS, RS and simple sugars (glucose / sucrose). Sensory evaluation was carried out by (9 point) hedonic rating of chapaties by 20 untrained Indian panelists. Flour water-holding capacity and water absorption indices (WAI) were determined. RS content of flours ranged from 7.1 g/100 g to 12.6 g/100g, but decreased when made into chapaties, (< 1 g/100 g), and decreased further with soy flour addition. BG content in flours ranged from 0.8 g/100 g to 1.4 g/100 g, while FOS content ranged from 1.3 g/100 g to 2.3 g/100 g. Minimal changes were observed in BG and FOS content when made into chapaties. Simple sugars were minimal in flours and chapaties. WAI of wheat flour was increased with addition of soy bean flour. Addition of up to 30 % soybean flour elevated the sensory acceptability of chapaties. While there is a decrease in RS with chapati making, the levels of BG and FOS are largely unchanged with processing. Master of Science

The hepatoprotective activity of the ethanol extract of the leaf of Ptrospermum acerifolium was investigated in rats for carbon tetrachloride induced hepatotoxicity. Hepatotoxicity was induced in male Wistar rats by intraperitoneal injection of carbon tetrachloride (0.1 ml/kg/d p.o. for 14 d). Ethanol extract of P. acerifolium leaves were administered to the experimental rats (25 mg/kg/d p.o. for 14d). The Hepatoprotective effect of these extracts was evaluated by liver function biochemical parameters (total bilirubin, serum protein, alanine aminotransaminase, asparatate aminotransaminase and alkaline phosphates activites) and histopathological studies of liver. In ethanol extract-treated animals, the toxicity effect of carbon tetrachloride was controlled significantly by restoration of the levels of serum bilirubin and enzymes as compared to the normal and standard drug silymarin-treated groups. Histology of liver sections of the animals treated with the extracts showed the presence of normal hepatic cords, absence of necrosis and fatty infiltration which further evidence the hepatoprotective activity.

Pictorial art, sculpture and architecture have served to interpret and record aspects of human activities over thousands of years. Over a much shorter period, musicians have prepared scores in notation according to which their music can be performed and depictions of scores can be found in some pictorial art, for example, in Indian Ragmala paintings (1600-1900). There has been considerable interest among Occidental artists during past decades to find relationships between painting and music [1-5] and composers have used visual art as a source of inspiration, for example, there is the piano suite 'Pictures from an Exhibition' by Mussorgsky. Possible correlations and relationships between music and visual artistic presentations have been of particular concern to those working with kinetic art [6]. As an architect and artist I have been attracted to textures of materials used decoratively in non-figurative murals for buildings. While such murals may visually please viewers, I find that many of them convey little, if any, meaning to them. It, therefore, occurred to me that such murals might be used to present musical scores in a special code based on the standard Occidental notation that viewers might learn to interpret more easily and to enjoy. I came to this idea because I sing, play the sitar and can reproduce a tune on a piano. I am interested in the classical Indian raga and in other types of Oriental music. My experience of Occidental music is rather limited.