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Long-term outcome and 'health-related quality of life' (HRQoL) following hospitalisation for COVID-19-related severe acute respiratory infection (SARI) is limited. OBJECTIVE: To assess the impact of HRQoL in patients hospitalised with COVID-19-related SARI at 1 year post discharge, focusing on the potential impact of age, frailty, and disease severity. METHOD: Routinely collected outcome data on 1207 patients admitted with confirmed COVID-19 related SARI across all three secondary care sites in our NHS trust over 3 months were assessed in this retrospective cohort study. Of those surviving 1 year, we prospectively collected 36-item short form (SF-36) HRQoL questionnaires, comparing three age groups (<49, 49-69, and the over 69-year-olds), the relative impact of frailty (using the Clinical Frailty Score; CFS), and disease severity (using National Early Warning Score; NEWS) on HRQoL domains. RESULTS: Overall mortality was 46.5% in admitted patients. In our SF-36 cohort (n=169), there was a significant reduction in all HRQoL domains versus normative data; the most significant reductions were in the physical component (p<0.001) across all ages and the emotional component (p<0.01) in the 49-69 year age group, with age having no additional impact on HRQoL. However, there was a significant correlation between physical well-being versus CFS (the correlation coefficient=-0.37, p<0.05), though not NEWS, with no gender difference observed. CONCLUSION: There was a significant reduction in all SF-36 domains at 1 year. Poor CFS at admission was associated with a significant and prolonged impact on physical parameters at 1 year. Age had little impact on the severity of HRQoL, except in the domains of physical functioning and the overall physical component.
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COVID-19 , Fragilidad , Humanos , Calidad de Vida/psicología , Estudios Retrospectivos , Alta del Paciente , Fragilidad/complicaciones , COVID-19/complicaciones , Cuidados Posteriores , Hospitalización , Gravedad del PacienteRESUMEN
Diabetes mellitus is the main cause of diabetic retinopathy, the most common cause of blindness worldwide. In order to slow down or prevent vision loss and degeneration, early detection and treatment are essential. For the purpose of detecting and classifying diabetic retinopathy on fundus retina images, numerous artificial intelligence-based algorithms have been put forth by the scientific community. Due to its real-time relevance to everyone's lives, smart healthcare is attracting a lot of interest. With the convergence of IoT, this attention has increased. The leading cause of blindness among persons in their working years is diabetic eye disease. Millions of people live in the most populous Asian nations, including China and India, and the number of diabetics among them is on the rise. To provide medical screening and diagnosis for this rising population of diabetes patients, skilled clinicians faced significant challenges. Our objective is to use deep learning techniques to automatically detect blind spots in eyes and determine how serious they may be. We suggest an enhanced convolutional neural network (ECNN) utilizing a genetic algorithm in this paper. The ECNN technique's accuracy results are compared to those of existing approaches like the K-nearest neighbor approach, convolutional neural network, and support vector machine with the genetic algorithm.
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Aprendizaje Profundo , Diabetes Mellitus , Retinopatía Diabética , Algoritmos , Inteligencia Artificial , Ceguera , Retinopatía Diabética/diagnóstico , Diagnóstico Precoz , Humanos , Aprendizaje AutomáticoRESUMEN
We are describing eleven autologous hematopoietic stem cell transplants (ASCT) that were performed in 2016 at three different transplant centers in Bangladesh. Indications for those patients were multiple myeloma (MM) (n=4), diffuse large B cell lymphoma (DLBCL) (n=2), Hodgkin's lymphoma (HD) (n=2), peripheral T cell lymphoma (PTCL) (n=1), acute myeloid leukemia (AML) (n=1), and acute promyelocytic leukemia (APL) (n=1). All autologous stem cell products were cryo-preserved and transfused back to patients freshly thawed at 37â. All were in second remission (CR2) except for the PTCL patient, who was in first remission (CR1). The bone marrow transplant (BMT) program was first initiated in Bangladesh in March 2014 at the Dhaka Medical College Hospital (DMCH), the country's largest and the leading government-run public hospital, in collaboration with the Massachusetts General Hospital in Boston, USA. Subsequently, two more centers, Apollo Hospitals Dhaka and the Combined Military Hospital (CMH), started transplant programs in 2016. Seven out of eleven ASCT were performed at the DMCH center, with two at Apollo Hospitals and two at CMH Dhaka. The median age for all patients was 39 (range 18-67) and the Male: Female ratio was 9: 2. The average time to neutrophil and platelet engraftment was day 9 (range 8-12) and day 12 (range 9-15), respectively. Major early complications were neutropenic fever, mucositis, and infection. There was no transplant related mortality (TRM) within the first 100 days. Over a median follow up of 2 years, overall survival is 82.0% and progression free survival is 63.6%.
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PURPOSE: Treatment of malignant and nonmalignant hematologic diseases with hematopoietic stem-cell transplantation (HSCT) was first described almost 60 years ago, and its use has expanded significantly over the last 20 years. Whereas HSCT has become the standard of care for many patients in developed countries, the significant economic investment, infrastructure, and health care provider training that are required to provide such a service have prohibited it from being widely adopted, particularly in developing countries. METHODS: Over the past two decades, however, efforts to bring HSCT to the developing world have increased, and several institutions have described their efforts to establish such a program. We aim to provide an overview of the current challenges and applications of HSCT in developing countries as well as to describe our experience in developing an HSCT program at Dhaka Medical College and Hospital in Bangladesh via a partnership with health care providers at Massachusetts General Hospital. RESULTS AND CONCLUSION: We discuss key steps of the program, including the formation of a collaborative partnership, infrastructure development, human resource capacity building, and financial considerations.
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Atención a la Salud , Recursos en Salud , Trasplante de Células Madre Hematopoyéticas , Bangladesh/epidemiología , Trasplante de Médula Ósea/métodos , Instituciones Oncológicas , Atención a la Salud/métodos , Atención a la Salud/organización & administración , Países en Desarrollo , Recursos en Salud/economía , Recursos en Salud/estadística & datos numéricos , Fuerza Laboral en Salud , Trasplante de Células Madre Hematopoyéticas/métodos , Hospitales Universitarios , Humanos , Grupo de Atención al PacienteRESUMEN
BACKGROUND: The global burden from cancer is rising, especially as low-income countries like Bangladesh observe rapid aging. So far, there are no comprehensive descriptions reporting diagnosed cancer group that include hematological malignancies in Bangladesh. METHODS: This was a multi-center hospital-based retrospective descriptive study of over 5000 confirmed hematological cancer cases in between January 2008 to December 2012. Morphological typing was carried out using the "French American British" classification system. RESULTS: A total of 5013 patients aged between 2 to 90 years had been diagnosed with malignant hematological disorders. A 69.2% were males (n=3468) and 30.8% females (n=1545), with a male to female ratio of 2.2:1. The overall median age at diagnosis was 42 years. Acute myeloid leukemia was most frequent (28.3%) with a median age of 35 years, followed by chronic myeloid leukemia with 18.2% (median age 40 years), non-Hodgkin lymphoma (16.9%; median age 48 years), acute lymphoblastic leukemia (14.1%; median age 27 years), multiple myeloma (10.5%; median age 55 years), myelodysplastic syndromes (4.5%; median age 57 years) and Hodgkin's lymphoma (3.9%; median age 36 years). The least common was chronic lymphocytic leukemia (3.7%; median age 60 years). Below the age of 20 years, acute lymphoblastic leukemia was predominant (37.3%), followed by acute myeloid leukemia (34%). Chronic lymphocytic leukemia and multiple myeloma had mostly occurred among older patients, aged 50-over. CONCLUSIONS: For the first time, our study presents the pattern and distribution of diagnosed hematological cancers in Bangladesh. It shows differences in population distributions as compared to other settings with possibly a lower presence of non-Hodgkin lymphoma. There might be under-reporting of affected women. Further studies are necessary on the epidemiology, genetics and potential environmental risk factors within this rapidly aging country.
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Neoplasias Hematológicas/clasificación , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bangladesh , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Access to good-quality medicines in many countries is largely hindered by the rampant circulation of spurious/falsely labeled/falsified/counterfeit (SFFC) and substandard medicines. In 2006, the Ministry of Health of Cambodia, in collaboration with Kanazawa University, Japan, initiated a project to combat SFFC medicines. METHODS: To assess the quality of medicines and prevalence of SFFC medicines among selected products, a cross-sectional survey was carried out in Cambodia. Cefixime, omeprazole, co-trimoxazole, clarithromycin, and sildenafil were selected as candidate medicines. These medicines were purchased from private community drug outlets in the capital, Phnom Penh, and Svay Rieng and Kandal provinces through a stratified random sampling scheme in July 2010. RESULTS: In total, 325 medicine samples were collected from 111 drug outlets. Non-licensed outlets were more commonly encountered in rural than in urban areas (p < 0.01). Of all the samples, 93.5% were registered and 80% were foreign products. Samples without registration numbers were found more frequently among foreign-manufactured products than in domestic ones (p < 0.01). According to pharmacopeial analytical results, 14.5%, 4.6%, and 24.6% of the samples were unacceptable in quantity, content uniformity, and dissolution test, respectively. All the ultimately unacceptable samples in the content uniformity tests were of foreign origin. Following authenticity investigations conducted with the respective manufacturers and medicine regulatory authorities, an unregistered product of cefixime collected from a pharmacy was confirmed as an SFFC medicine. However, the sample was acceptable in quantity, content uniformity, and dissolution test. CONCLUSIONS: The results of this survey indicate that medicine counterfeiting is not limited to essential medicines in Cambodia: newer-generation medicines are also targeted. Concerted efforts by both domestic and foreign manufacturers, wholesalers, retailers, and regulatory authorities should help improve the quality of medicines.
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Cefixima/análisis , Claritromicina/análisis , Medicamentos Falsificados , Omeprazol/análisis , Piperazinas/análisis , Sulfonas/análisis , Combinación Trimetoprim y Sulfametoxazol/análisis , Cambodia , Etiquetado de Medicamentos , Medicamentos Esenciales/análisis , Fraude , Vigilancia en Salud Pública , Purinas/análisis , Control de Calidad , Citrato de SildenafilRESUMEN
Application of environmentally friendly enzymes to remove thin-film composite (TFC) reverse osmosis (RO) membrane biofoulants without changing the physico-chemical properties of the RO surface is a challenging and new concept. Eight enzymes from Novozyme A/S were tested using a commercially available biofouling-resistant TFC polyamide RO membrane (BW30, FilmTech Corporation, Dow Chemical Co.) without filtration in a rotating disk reactor system operated for 58 days. At the end of the operation, the accumulated biofoulants on the TFC RO surfaces were treated with the three best enzymes, Subtilisin protease and lipase; dextranase; and polygalacturonase (PG) based enzymes, at neutral pH (~7) and doses of 50, 100, and 150 ppm. Contact times were 18 and 36 h. Live/dead staining, epifluorescence microscopy measurements, and 5 µm thick cryo-sections of enzyme and physically treated biofouled membranes revealed that Subtilisin protease- and lipase-based enzymes at 100 ppm and 18 h contact time were optimal for removing most of the cells and proteins from the RO surface. Culturable cells inside the biofilm declined by more than five logs even at the lower dose (50 ppm) and shorter incubation period (18 h). Subtilisin protease- and lipase-based enzyme cleaning at 100 ppm and for 18 h contact time restored the hydrophobicity of the TFC RO surface to its virgin condition while physical cleaning alone resulted in a 50° increase in hydrophobicity. Moreover, at this optimum working condition, the Subtilisin protease- and lipase-based enzyme treatment of biofouled RO surface also restored the surface roughness measured with atomic force microscopy and the mass percentage of the chemical compositions on the TFC surface estimated with X-ray photoelectron spectroscopy to its virgin condition. This novel study will encourage the further development and application of enzymes to remove biofoulants on the RO surface without changing its surface properties.
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Incrustaciones Biológicas , Reactores Biológicos/microbiología , Descontaminación/métodos , Hidrolasas/química , Membranas Artificiales , Biopelículas , Recuento de Células , Dextranasa/química , Lipasa/química , Ósmosis , Péptido Hidrolasas/química , Poligalacturonasa/química , SolubilidadRESUMEN
BACKGROUND: The use of substandard and degraded medicines is a major public health problem in developing countries such as Cambodia. A collaborative study was conducted to evaluate the quality of amoxicillin-clavulanic acid preparations under tropical conditions in a developing country. METHODS: Amoxicillin-clavulanic acid tablets were obtained from outlets in Cambodia. Packaging condition, printed information, and other sources of information were examined. The samples were tested for quantity, content uniformity, and dissolution. Authenticity was verified with manufacturers and regulatory authorities. RESULTS: A total of 59 samples were collected from 48 medicine outlets. Most (93.2%) of the samples were of foreign origin. Using predetermined acceptance criteria, 12 samples (20.3%) were non-compliant. Eight (13.6%), 10 (16.9%), and 20 (33.9%) samples failed quantity, content uniformity, and dissolution tests, respectively. Samples that violated our observational acceptance criteria were significantly more likely to fail the quality tests (Fisher's exact test, p < 0.05). CONCLUSIONS: Improper packaging and storage conditions may reduce the quality of amoxicillin-clavulanic acid preparations at community pharmacies. Strict quality control measures are urgently needed to maintain the quality of amoxicillin-clavulanic acid in tropical countries.
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Combinación Amoxicilina-Clavulanato de Potasio/análisis , Antibacterianos/análisis , Cambodia , Embalaje de Medicamentos , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Control de Calidad , ComprimidosRESUMEN
The mitochondrial ATP binding cassette transporter ABCB6 has been associated with a broad range of physiological functions, including growth and development, therapy-related drug resistance, and the new blood group system Langereis. ABCB6 has been proposed to regulate heme synthesis by shuttling coproporphyrinogen III from the cytoplasm into the mitochondria. However, direct functional information of the transport complex is not known. To understand the role of ABCB6 in mitochondrial transport, we developed an in vitro system with pure and active protein. ABCB6 overexpressed in HEK293 cells was solubilized from mitochondrial membranes and purified to homogeneity. Purified ABCB6 showed a high binding affinity for MgATP (Kd = 0.18 µM) and an ATPase activity with a Km of 0.99 mM. Reconstitution of ABCB6 into liposomes allowed biochemical characterization of the ATPase including (i) substrate-stimulated ATPase activity, (ii) transport kinetics of its proposed endogenous substrate coproporphyrinogen III, and (iii) transport kinetics of substrates identified using a high throughput screening assay. Mutagenesis of the conserved lysine to alanine (K629A) in the Walker A motif abolished ATP hydrolysis and substrate transport. These results suggest a direct interaction between mitochondrial ABCB6 and its transport substrates that is critical for the activity of the transporter. Furthermore, the simple immunoaffinity purification of ABCB6 to near homogeneity and efficient reconstitution of ABCB6 into liposomes might provide the basis for future studies on the structure/function of ABCB6.
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Transportadoras de Casetes de Unión a ATP/aislamiento & purificación , Isoformas de Proteínas/aislamiento & purificación , Transportadoras de Casetes de Unión a ATP/química , Transportadoras de Casetes de Unión a ATP/metabolismo , Adenosina Trifosfato/metabolismo , Coproporfirinas/metabolismo , Células HEK293 , Humanos , Cinética , Lípidos de la Membrana/metabolismo , Mitocondrias/metabolismo , Unión Proteica , Conformación Proteica , Isoformas de Proteínas/química , Isoformas de Proteínas/metabolismoRESUMEN
Submerged biofilm systems, such as integrated fixed-film activated sludge (IFAS) and moving bed bioreactors (MBBRs), are increasingly being used for domestic wastewater treatment, often to improve nitrification. Little is known about whether and how biofilm attachment surface chemical properties affect treatment performance, although surface chemistry is known to affect attachment in other systems, and work with pure strains has suggested that attachment of nitrifying bacteria may be enhanced on high surface energy surfaces. The objective of this research was to systematically evaluate the effects of surface chemistry on biofilm quantity and rates of nitrification and estrogen removal. Biofilms were grown on four plastic attachment surfaces with a range of hydrophobicity and surface energy values (nylon, melamine, high-density-polyethylene [HDPE], and acetal polymeric plastic) by immersing them in a full scale nitrifying activated sludge wastewater treatment system, followed by batch test experiments. The attachment surface water contact angles ranged from 53° to 98° and surface energies ranged from 48.9 to 20.9 mJ/m(2). Attachment surface hydrophilicity and surface energy were positively correlated with total biomass attachment, with more than twice as much biomass on the highest surface energy, most hydrophilic surface (nylon) than on the lowest surface energy, least hydrophilic surface (acetal plastic). Absolute and specific nitrification rates were also correlated with hydrophilicity and surface energy (varying by factors of 5 and 2, respectively), as were absolute and specific removal first order rate constants of the hormones estrone (E1), ß-estradiol (E2) and 17α-ethynylestradiol (EE2). These results suggested that attachment surface chemistry may be a useful design parameter for improving biofilm performance for removal of ammonia and endocrine disrupting hormones from wastewater. Further research is required to verify these results at longer time scales and with typical media geometries.
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Adhesión Bacteriana , Biopelículas , Estrógenos/aislamiento & purificación , Nitrificación , Aguas Residuales/microbiología , Purificación del Agua/métodos , Purificación del Agua/normas , Amoníaco/aislamiento & purificación , Biodegradación Ambiental , Biomasa , Cinética , Nitrógeno/metabolismo , Plásticos , Propiedades de Superficie , Termodinámica , Contaminantes Químicos del Agua/aislamiento & purificaciónRESUMEN
This study evaluated the quality and authenticity of the anti-influenza agent oseltamivir acquired via the Internet in Japan. The brand name drugs Tamiflu and Antiflu were obtained via the Internet using a search engine. The authenticity and legitimacy of the medicines were verified with the samples' manufacturers and the regulatory authorities of the country of origin, respectively. In addition, quantitative and dissolution tests were carried out using high-performance liquid chromatography. No counterfeits were detected among the samples. Additionally, all samples passed qualitative and quantitative tests according to the US Pharmacopeia monograph. However, different sorts of mismanagement were observed in the distribution channels. Through the Internet, oseltamivir can be purchased in quantities larger than the permissible amount in Japan. Furthermore, maintenance of medicine quality cannot be guaranteed. In addition, insufficient information and lack of quality control in some samples may cause unwanted health problems in patients.
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The goal of this study was to quantify and demonstrate the dynamic effects of hydraulic retention time (HRT), organic carbon and various components of extracellular polymeric substances (EPS) produced by microorganisms on the performance of submersed hollow-fiber microfiltration (MF) membrane in a hybrid powdered activated carbon (PAC)-MF membrane bioreactor (MBR). The reactors were operated continuously for 45 days to treat surface (river) water before and after pretreatment using a biofiltration unit. The real-time levels of organic carbon and the major components of EPS including five different carbohydrates (D(+) glucose and D(+) mannose, D(+) galactose, N-acetyl-D-galactosamine and D-galactose, oligosaccharides and L(-) fucose), proteins, and polysaccharides were quantified in the influent water, foulants, and in the bulk phases of different reactors. The presence of PAC extended the filtration cycle and enhanced the organic carbon adsorption and removal more than two fold. Biological filtration improved the filtrate quality and decreased membrane fouling. However, HRT influenced the length of the filtration cycle and had less effect on organic carbon and EPS component removal and/or biodegradation. The abundance of carbohydrates in the foulants on MF surfaces was more than 40 times higher than in the bulk phase, which demonstrates that the accumulation of carbohydrates on membrane surfaces contributed to the increase in transmembrane pressure significantly and PAC was not a potential adsorbent of carbohydrates. The abundance of N-acetyl-d-galactosamine and d-galactose was the highest in the foulants on membranes receiving biofilter-treated river water. Most of the biological fouling compounds were produced inside the reactors due to biodegradation. PAC inside the reactor enhanced the biodegradation of polysaccharides up to 97% and that of proteins by more than 95%. This real-time extensive and novel study demonstrates that the PAC-MF hybrid MBR is a sustainable technology for treating river water.
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Incrustaciones Biológicas , Reactores Biológicos , Agua Dulce/química , Membranas Artificiales , Filtros Microporos/microbiología , Polímeros/química , Purificación del Agua/instrumentación , Adsorción , Incrustaciones Biológicas/prevención & control , Agua Dulce/microbiología , Sustancias Húmicas/análisis , Sustancias Húmicas/microbiología , Hidrología/métodos , Hidrólisis , Japón , Cinética , Ensayo de Materiales , Polímeros/metabolismo , Polisacáridos/análisis , Polisacáridos/química , Polisacáridos/metabolismo , Presión , Proteínas/análisis , Proteínas/química , Proteínas/metabolismo , Ríos , Propiedades de Superficie , Calidad del AguaRESUMEN
ABCB6 is a member of the adenosine triphosphate (ATP)-binding cassette family of transporter proteins that is increasingly recognized as a relevant physiological and therapeutic target. Evaluation of modulators of ABCB6 activity would pave the way toward a more complete understanding of the significance of this transport process in tumor cell growth, proliferation and therapy-related drug resistance. In addition, this effort would improve our understanding of the function of ABCB6 in normal physiology with respect to heme biosynthesis, and cellular adaptation to metabolic demand and stress responses. To search for modulators of ABCB6, we developed a novel cell-based approach that, in combination with flow cytometric high-throughput screening (HTS), can be used to identify functional modulators of ABCB6. Accumulation of protoporphyrin, a fluorescent molecule, in wild-type ABCB6 expressing K562 cells, forms the basis of the HTS assay. Screening the Prestwick Chemical Library employing the HTS assay identified four compounds, benzethonium chloride, verteporfin, tomatine hydrochloride and piperlongumine, that reduced ABCB6 mediated cellular porphyrin levels. Validation of the identified compounds employing the hemin-agarose affinity chromatography and mitochondrial transport assays demonstrated that three out of the four compounds were capable of inhibiting ABCB6 mediated hemin transport into isolated mitochondria. However, only verteporfin and tomatine hydrochloride inhibited ABCB6's ability to compete with hemin as an ABCB6 substrate. This assay is therefore sensitive, robust, and suitable for automation in a high-throughput environment as demonstrated by our identification of selective functional modulators of ABCB6. Application of this assay to other libraries of synthetic compounds and natural products is expected to identify novel modulators of ABCB6 activity.
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Transportadoras de Casetes de Unión a ATP/metabolismo , Citometría de Flujo/métodos , Ensayos Analíticos de Alto Rendimiento , Mitocondrias/efectos de los fármacos , Porfirinas/farmacología , Protoporfirinas/metabolismo , Tomatina/farmacología , Transportadoras de Casetes de Unión a ATP/antagonistas & inhibidores , Bencetonio/farmacología , Transporte Biológico/efectos de los fármacos , Cromatografía de Afinidad , Dioxolanos/farmacología , Hemina/análogos & derivados , Hemina/antagonistas & inhibidores , Hemina/metabolismo , Humanos , Células K562 , Mitocondrias/metabolismo , Modelos Moleculares , Protoporfirinas/antagonistas & inhibidores , Sefarosa/análogos & derivados , Bibliotecas de Moléculas Pequeñas , VerteporfinaRESUMEN
OBJECTIVE: To explore the circulation of anti-obesity medicines via the internet and their quality. DESIGN: Cross-sectional study. SETTING: Internet pharmacies and pharmaceutical suppliers accessible from Japan. PARTICIPANTS: Anti-obesity medicines were purchased using relevant keywords on Japanese Google search engine. Blogs and advertisement-only sites were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: The authenticity of the samples was investigated in collaboration with the manufacturers of the samples and medicine regulatory authorities. Quality of the samples was assessed by pharmacopoeial analyses using high-performance liquid chromatography. RESULTS: 82 samples were purchased from 36 internet sites. Approximately half of the sites did not mention a physical address, and 45% of the samples did not contain a package insert. A variety of custom declarations were made for the shipments of the samples: personal health items, supplement, medicines, general merchandise, tea and others. Among 82 samples, 52 samples were analysed to check their pharmacopoeial quality. Authenticity responses were received from only five of 20 manufacturing companies. According to the pharmacopoeial analyses and authenticity investigation, three of the samples were identified as counterfeits and did not contain any active ingredients. Two of these samples were confirmed as counterfeits by the manufacturer of the authentic products. The manufacturer of the other sample did not respond to our request for an authenticity check even after several communication attempts. These counterfeit cases have been reported at the rapid alert system of Western Pacific Region of the WHO. CONCLUSIONS: Many counterfeit and unapproved anti-obesity medicines may be easily bypassing regulatory checks during shipping and are widely circulated through the internet. Regulatory authorities should take measures to prevent these medicines from entering countries to safeguard their citizens.
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BACKGROUND: Recent investigations by the Ministry of Health of Cambodia suggest that counterfeit medicines have been introduced into the pharmaceutical market in tampered packaging. To further explore this possibility, an interview survey was conducted at the wholesaler level to investigate the medicinal supply chain in Cambodia. METHODS: Managing executives of 62 (83.8%) registered wholesalers of modern medicines in Cambodia were interviewed in 2009 on their knowledge of, perception on, and practices related to counterfeiting issues through a semi-structured questionnaire. RESULTS: According to our findings, 12.9% of the wholesalers had encountered counterfeit medicine. However, they demonstrated a variety of perceptions regarding this issue. A majority (59.7%) defined counterfeit medicines as medicines without registration, while other definitions included medicines that were fraudulently manufactured, medicines without a batch/lot number, those containing harmful ingredients or a reduced amount of active ingredients, and expired medicines. Additionally, 8.1% responded that they did not know what counterfeit medicines were.During procurement, 66.1% of the wholesalers consider whether the product is registered in Cambodia, while 64.5% consider the credibility and quality of the products and 61.3% consider the reputation of the manufacturers. When receiving a consignment, 80.6% of wholesalers check the intactness of medicines, 72.6% check the specification and amount of medicines, 71% check Cambodian registration, 56.5% check that the packaging is intact, 54.8% check batch and lot numbers, 48.4% check the dates of manufacture and expiration, and 9.7% check analytical certificates.Out of 62 wholesalers, 14.5% had received medicines that arrived without packages or were separated from their packaging and had to be repacked before distribution. Significant statistical association was found between wholesalers who received medicines separately from their packs/containers and who consider their belief on reliability of pharmaceutical products of certain manufacturing country during procurement (Chi-square: 12.951, P = 0.002). When wholesalers divide medicines from larger packs into smaller ones, 54.8% use packaging purchased from local markets. CONCLUSION: A number of wholesalers think counterfeit medicines are medicines without registration, and/or do not have any uniform ideas on the issue and what to do, when they find or suspect counterfeits. Furthermore, their strict adherence to anti-counterfeiting measures is urgently needed.
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Medicamentos Falsificados , Países en Desarrollo , Industria Farmacéutica , Fraude , Conocimientos, Actitudes y Práctica en Salud , Adulto , Cambodia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Investigación Cualitativa , Encuestas y CuestionariosRESUMEN
Traditional antimicrobials are increasingly suffering from the emergence of multidrug resistance among pathogenic microorganisms. To overcome these deficiencies, a range of novel approaches to control microbial infections are under investigation as potential alternative treatments. Multidrug efflux is a key target of these efforts. Efflux mechanisms are broadly recognized as major components of resistance to many classes of chemotherapeutic agents as well as antimicrobials. Efflux occurs due to the activity of membrane transporter proteins widely known as Multidrug Efflux Systems (MES). They are implicated in a variety of physiological roles other than efflux and identifying natural substrates and inhibitors is an active and expanding research discipline. One plausible alternative is the combination of conventional antimicrobial agents/antibiotics with small molecules that block MES known as multidrug efflux pump inhibitors (EPIs). An array of approaches in academic and industrial research settings, varying from high-throughput screening (HTS) ventures to bioassay guided purification and determination, have yielded a number of promising EPIs in a series of pathogenic systems. This synergistic discovery platform has been exploited in translational directions beyond the potentiation of conventional antimicrobial treatments. This venture attempts to highlight different tactical elements of this platform, identifying the need for highly informative and comprehensive EPI-discovery strategies. Advances in assay development genomics, proteomics as well as the accumulation of bioactivity and structural information regarding MES facilitates the basis for a new discovery era. This platform is expanding drastically. A combination of chemogenomics and chemoinformatics approaches will integrate data mining with virtual and physical HTS ventures and populate the chemical-biological interface with a plethora of novel chemotypes. This comprehensive step will expedite the preclinical development of lead EPIs.
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Antiinfecciosos/farmacología , Diseño de Fármacos , Proteínas de Transporte de Membrana/efectos de los fármacos , Antiinfecciosos/farmacocinética , Transporte Biológico/efectos de los fármacos , Farmacorresistencia Microbiana , Resistencia a Múltiples Medicamentos , Ensayos Analíticos de Alto Rendimiento/métodos , Humanos , Proteínas de Transporte de Membrana/metabolismoRESUMEN
Biofouling is a major reason for flux decline in the performance of membrane-based water and wastewater treatment plants. Initial biochemical characterization of biofilm formation potential and biofouling on two commercially available membrane surfaces from FilmTec Corporation were investigated without filtration in laboratory rotating disc reactor systems. These surfaces were polyamide aromatic thin-film reverse osmosis (RO) (BW30) and semi-aromatic nanofiltration (NF270) membranes. Membrane swatches were fixed on removable coupons and exposed to water with indigenous microorganisms supplemented with 1.5 mg l(-1) organic carbon under continuous flow. After biofilms formed, the membrane swatches were removed for analyses. Staining and epifluorescence microscopy revealed more cells on the RO than on the NF surface. Based on image analyses of 5-µm thick cryo-sections, the accumulation of hydrated biofoulants on the RO and NF surfaces exceeded 0.74 and 0.64 µm day(-1), respectively. As determined by contact angle the biofoulants increased the hydrophobicity up to 30° for RO and 4° for NF surfaces. The initial difference between virgin RO and NO hydrophobicities was â¼5°, which increased up to 25° after biofoulant formation. The initial roughness of RO and NF virgin surfaces (75.3 nm and 8.2 nm, respectively) increased to 48 nm and 39 nm after fouling. A wide range of changes of the chemical element mass percentages on membrane surfaces was observed with X-ray photoelectron spectroscopy. The initial chemical signature on the NF surface was better restored after cleaning than the RO membrane. All the data suggest that the semi-aromatic NF surface was more biofilm resistant than the aromatic RO surface. The morphology of the biofilm and the location of active and dead cell zones could be related to the membrane surface properties and general biofouling accumulation was associated with changes in the surface chemistry of the membranes, suggesting the validity of the combination of these novel approaches for initial assessment of membrane performance.
Asunto(s)
Biopelículas , Nylons/química , Contaminantes Químicos del Agua/aislamiento & purificación , Contaminantes del Agua/aislamiento & purificación , Purificación del Agua/métodos , Membranas Artificiales , Microscopía de Fuerza Atómica/métodos , Ósmosis , Espectroscopía de Fotoelectrones , Propiedades de Superficie , Microbiología del AguaRESUMEN
Biofilm-based systems, including integrated fixed-film activated sludge and moving bed bioreactors, are becoming increasingly popular for wastewater treatment, often with the goal of improving nitrification through the enrichment of ammonia and nitrite oxidizing bacteria. We have previously demonstrated the utility of self-assembled monolayers (SAMs) as tools for studying the initial attachment of bacteria to substrata systematically varying in physicochemical properties. In this work, we expanded these studies to bacteria of importance in wastewater treatment systems and we demonstrated attachment rates were better correlated with surface energy than with wettability (water contact angle). Toward the long-term goal of improving wastewater treatment performance through the strategic design of attachment substrata, the attachment rates of two autotrophic ammonia-oxidizing bacteria (Nitrosomonas europaea and Nitrosospira multiformis) and a heterotroph (Escherichia coli) were evaluated using SAMs with a range of wettabilities, surface energies, and functional properties (methyl, hydroxyl, carboxyl, trimethylamine, and amine terminated). Cell attachment rates were somewhat correlated with the water contact angles of the SAMs with polar terminal groups (hydroxyl, carboxyl, trimethylamine, and amine). Including all SAM surfaces, a better correlation was found for all bacteria between attachment rates and surface free energy, as determined using the Lewis Acid-Base approach. The ammonia-oxidizers had higher adhesion rates on the SAMs with higher surface energies than did the heterotroph. This work demonstrated the successful application of SAMs to determine the attachment surface preferences of bacteria important to wastewater treatment, and it provides guidance for a new area of research aimed at improving treatment performance through rational attachment surface design.