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OBJECTIVE: Individuals with psychosis are at elevated risk of adverse sexual and reproductive health (SRH) outcomes, and not receiving adequate SRH care. SRH is important for youth, yet little is known about SRH care access and experiences among those with early psychosis. This study explored SRH care experiences among women and nonbinary individuals with early psychosis. METHOD: We conducted semistructured qualitative interviews with 19 service users (cisgender and transgender women, nonbinary individuals) receiving care in 2 early psychosis programs in Ontario, Canada. We also conducted semistructured interviews and focus groups with 36 clinicians providing SRH or mental health care to this population. Participants were asked about SRH care access/provision experiences and the interplay with psychosis. Using a social interactionist orientation, a thematic analysis described and explained service user and clinician perspectives regarding SRH care. RESULTS: Amongst both service users and clinician groups, common themes developed: (a) diversity of settings: SRH services are accessed in a large range of spaces across the health care system, (b) barriers in nonpsychiatric SRH care settings: psychosis impacts the ability to engage with existing SRH services, (c) invisibility of SRH in psychiatric settings: SRH is rarely addressed in psychiatric care, (d) variability of informal SRH-related conversations and supports, and cutting across all of the above themes, (e) intersecting social and cultural factors impacted SRH services access. CONCLUSIONS: SRH is important for health and wellbeing; improvements are urgently needed across the healthcare system and within early psychosis programs to meet this population's multifaceted SRH needs.
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Trastornos Psicóticos , Salud Reproductiva , Adolescente , Humanos , Femenino , Conducta Sexual , Accesibilidad a los Servicios de Salud , Trastornos Psicóticos/terapia , OntarioRESUMEN
SUMMARY: Antimicrobials are lifesaving medicines, but their misuse drives antimicrobial resistance. Schools, as educational hubs wield transformative potential in fostering responsible antimicrobial behavior among students and the broader community. An online campaign targeted Delhi schools, training teachers as master trainers who, in turn, educated 359,940 students. Significant pre- to post-test score improvements were observed among teachers (6.98-8.14; P < 0.01) and students (5.20-6.56; P < 0.01). The campaign received excellent feedback (85%), with 966 students participating in the "IDEAthon" competition. While a single session improved knowledge, continuous engagement and activities are imperative for sustained behavioral change in antibiotic usage.
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Antibacterianos , Humanos , India , Instituciones Académicas , Programas de Optimización del Uso de los Antimicrobianos/organización & administración , Farmacorresistencia Microbiana , Promoción de la Salud/métodos , Servicios de Salud Escolar/organización & administración , Conocimientos, Actitudes y Práctica en SaludRESUMEN
BACKGROUND: Metallic nanoparticles from different natural sources exhibit superior therapeutic options as compared to the conventional methods. Selaginella species have attracted special attention of researchers worldwide due to the presence of bioactive molecules such as flavonoids, biflavonoids, triterpenes, steroids, saponins, tannins and other secondary metabolites that exhibit antimicrobial, antiplasmodial, anticancer and anti-inflammatory activities. Environment friendly green synthesised silver nanoparticles from Selaginella species provide viable, safe and efficient treatment against different fungal pathogens. OBJECTIVE: This systematic review aims to summarise the literature pertaining to superior antifungal ability of green synthesised silver nanoparticles using plant extracts of Selaginella spp. in comparison to both aqueous and ethanolic raw plant extracts by electronically collecting articles from databases. METHODS: The recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis were taken into consideration while preparing this review. The titles and abstracts of the collected data were stored in Endnote20 based on the inclusion and exclusion criteria. The search strategy included literature from established sources like PubMed, Google Scholar and Retrieval System Online using subject descriptors. RESULTS: The search yielded 60 articles with unique hits. After removal of duplications, 46 articles were identified, 40 were assessed and only seven articles were chosen and included in this review based on our eligibility criteria. CONCLUSION: The physicochemical and preliminary phytochemical investigations of Selaginella suggest higher drug potency of nanoparticles synthesised from plant extract against different diseases as compared to aqueous and ethanolic plant extracts. The study holds great promise as the synthesis of nanoparticles involves low energy consumption, minimal technology and least toxic effects.
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Antiinfecciosos , Nanopartículas del Metal , Selaginellaceae , Humanos , Nanopartículas del Metal/química , Selaginellaceae/química , Plata/farmacología , Plata/química , Antiinfecciosos/farmacología , Antiinfecciosos/química , Extractos Vegetales/farmacología , Extractos Vegetales/químicaRESUMEN
Avian pathogenic Escherichia coli (APEC) is the causative agent of avian colibacillosis, which causes significant economic losses to the poultry industry. The growing resistance of bacteria to antibiotics is a major global public health concern. However, there is limited data on the efficacy of phage therapy in effectively controlling and treating APEC infections. In this study, a novel lytic Escherichia phage, vB_EcoS_PJ16, was isolated from poultry farm wastewater and characterized in both in vitro and in vivo conditions. Transmission electron microscopy analysis revealed the presence of an icosahedral head and a long non-contractile tail, classifying the phage under the Caudoviricetes class. Host range determination showed that Escherichia phage vB_EcoS_PJ16 exhibited lytic activity against multiple strains of pathogenic E. coli, while no significant signs of lysis for Klebsiella pneumoniae, Salmonella Typhimurium, Listeria monocytogenes, and Staphylococcus aureus. Biophysical characterization revealed that the isolated phage was sturdy, as it remained viable for up to 300 days at temperatures of 30 °C, 37 °C, and 42 °C and for up to 24 h at pH 5 to 11, with only minor changes in titer. Kinetic analysis at multiplicity of infection (MOI) 0.1 showed a latency period of about 20 min and a burst size of 26.5 phage particles per infected cell for phage vB_EcoS_PJ16. Whole genome sequencing unveiled that the phage vB_EcoS_PJ16 genome consists of a double-stranded linear DNA molecule with 57,756 bp and a GC content of 43.58%. The Escherichia phage vB_EcoS_PJ16 genome consisted of 98 predicted putative ORFs, with no transfer RNA identified in the genome. Among these 98 genes, 34 genes were predicted to have known functions. A significant reduction in APEC viability was observed at MOI 100 during in vitro bacterial challenge tests conducted at different MOIs (0.01, 1, and 100). In vivo oral evaluation of the isolated phage to limit E. coli infections in day-old chicks indicated a decrease in mortality within both the therapeutic (20%) and prophylactic (30%) groups, when compared to the control group. The findings of this study contribute to our current knowledge of Escherichia phages and suggest a potentially effective role of phages in the therapeutic and prophylactic control of antibiotic-resistant APEC strains.
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In this study, 306 rectal swabs from diarrheal pigs of various ages (0-3 weeks, 3-6 weeks, and >6 weeks) were collected from 54 piggery units in different climatic zones in Haryana state, India. These samples were tested for the presence of porcine astrovirus (PAstV), porcine rotavirus group A (PRV-A), and classical swine fever virus (CSFV) by reverse transcription polymerase chain reaction (RT-PCR), and porcine circovirus 2 (PCV-2) by polymerase chain reaction (PCR). Out of the 306 samples tested, 153 (50%), 108 (35.3%), 32 (10.6%), and three (0.9%) tested positive for PAstV, PCV-2, PRV-A, and CSFV, respectively. A single infection was detected in 135 samples, while mixed infections were found in 77 samples: 70 with two viruses and seven samples with more than two. PAstV was detected most frequently (55.31%) in pigs aged 3-6 weeks. PCV-2 was more predominant in pigs aged 0-3 weeks (36.53%), whereas PRV-A was more common in pigs aged 3-6 weeks (11.3%). CSFV was observed in the age group of 0-3 weeks (1.92%). Phylogenetic analysis revealed the circulation of lineages 2 and 4 of PAstV in this region. Thus, it can be concluded that one or more than one virus is circulating in piggery units in Haryana, India.
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Circovirus , Virus de la Fiebre Porcina Clásica , Coinfección , Mamastrovirus , Rotavirus , Porcinos , Animales , Coinfección/epidemiología , Coinfección/veterinaria , Filogenia , Mamastrovirus/genética , Rotavirus/genética , India/epidemiologíaRESUMEN
DNA barcoding is a powerful taxonomic tool to identify and discover species. DNA barcoding utilizes one or more standardized short DNA regions for taxon identification. With the emergence of new sequencing techniques, such as Next-generation sequencing (NGS), ONT MinION nanopore sequencing, and Pac Bio sequencing, DNA barcoding has become more accurate, fast, and reliable. Rapid species identification by DNA barcodes has been used in a variety of fields, including forensic science, control of the food supply chain, and disease understanding. The Consortium for Barcode of Life (CBOL) presents various working groups to identify the universal barcode gene, such as COI in metazoans; rbcL, matK, and ITS in plants; ITS in fungi; 16S rRNA gene in bacteria and archaea, and creating a reference DNA barcode library. In this article, an attempt has been made to analyze the various proposed DNA barcode for different organisms, strengths & limitations, recent advancements in DNA barcoding, and methods to speed up the DNA barcode reference library construction. This study concludes that constructing a reference library with high species coverage would be a major step toward identifying species by DNA barcodes. This can be achieved in a short period of time by using advanced sequencing and data analysis methods.
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Código de Barras del ADN Taxonómico , ADN , Código de Barras del ADN Taxonómico/métodos , ARN Ribosómico 16S/genética , Plantas/genética , Archaea/genéticaRESUMEN
Antimicrobial resistance (AMR) is a burgeoning challenge of global priority, warranting immediate action to prevent the explosion of multidrug-resistant (MDR) pathogens. Indiscriminate antimicrobial use is the most important driver for AMR. AMR has led to depletion of the antibiotic pipeline and developing new antibiotics is extremely challenging due to technical and financial issues and also resistance emerges as soon any new antibiotic is introduced. At present, preserving the power of existing antibiotics by prudent use and curtailing spread of pathogens by infection prevention and control (biosecurity) in both humans and animals are the best available options to defer AMR crisis. Meanwhile, to reduce dependence on antibiotics, other alternatives such as vaccines, antibodies, pattern recognition receptors, probiotics, bacteriophages, peptides, phytochemicals, metals, and antimicrobial enzymes are being explored. This review provides an overview of various promising, potential and under investigative strategies as alternatives to antibiotics.
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Antiinfecciosos , Bacteriófagos , Animales , Humanos , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana , MetalesRESUMEN
Heavy metal pollutants in the environment are increasing exponentially due to various anthropogenic factors including mining, industrial and agricultural wastes. Living organisms exposed to heavy metals above a certain threshold level induces deleterious effects in these organisms. To live in such severe environments, microbes have developed a range of tolerance mechanisms which include upregulation of stress-responsive genes and/or antioxidant enzymes to detoxify the metal stress. Single cell eukaryotic microorganisms, i.e., ciliates, are highly sensitive to environmental pollutants mainly due to the absence of cell wall, which make them suitable candidates for conducting ecotoxicological studies. Therefore, the present investigation describes the effects of heavy metals (cadmium and copper) on freshwater ciliate, Euplotes aediculatus. The activities of antioxidant enzymes, i.e., catalase and glutathione peroxidase in E. aediculatus were determined under heavy metal exposure. Besides, the expression of stress-responsive genes, namely, heat-shock protein 70 (hsp70) and catalase (cat), has also been determined in this freshwater ciliate species under metal stress. The present study showed that the enzyme activity and the expression of these genes increased with an increase in the heavy metal concentration and with the duration of metal exposure. Also, these stress-responsive genes were sequenced and characterized to comprehend their role in cell rescue.
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Euplotes , Metales Pesados , Contaminantes Químicos del Agua , Cadmio/metabolismo , Catalasa/genética , Catalasa/metabolismo , Euplotes/genética , Euplotes/metabolismo , Agua Dulce , Metales Pesados/metabolismo , Metales Pesados/toxicidad , Estrés Oxidativo , Contaminantes Químicos del Agua/análisisRESUMEN
OBJECTIVE: Despite the importance of radiology in the diagnosis and management of patients, studies suggest that medical graduates exhibit a minimal level of radiology knowledge. This study aimed to assess the satisfaction of Kuwait's medical students with the radiology teaching and their confidence in their knowledge regarding basic radiological principles, as well as their views and suggestions for adequate teaching time and pattern of radiology teaching at the undergraduate level. SUBJECTS AND METHODS: This cross-sectional study was conducted among medical students in Kuwait University. The study employed a questionnaire, which aimed to assess the students' perception of the current radiological teaching approach. Ethical approval was obtained, and descriptive analysis was conducted using SPSS. RESULTS: Ninety-one percent of the 451 participants believed that the radiologist is an important part of the medical team. Ninety-seven percent of them believed that having a grasp of general radiological concepts is essential for clinical practice. More than half of the participants (55%) believed that the amount of radiology teaching they receive is inadequate. Most students claimed to lack the radiological skills that a competent doctor should own, such as reading X-rays, CTs, and MRIs. Most students chose hospital-based and problem-based learning sessions as their most desired methods for radiology learning. CONCLUSION: Radiology is an essential part of modern medicine. Adequate exposure to radiological techniques and adequate time to radiological teaching must be allocated to students during their undergraduate medical curriculum to improve the proper management of patients.
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Educación de Pregrado en Medicina , Radiología , Estudiantes de Medicina , Humanos , Estudios Transversales , Curriculum , Radiología/educaciónRESUMEN
During February 2020 to October 2020, four outbreaks of theileriosis in small ruminants were recorded with overall morbidity, mortality and case fatality rates of 27.95%, 17.46% and 62.5%, respectively. The disease was characterized by high fever (up to 106°F), superficial lymphadenopathy, anaemia, anorexia, lethargy, respiratory distress and death. The presence of pleomorphic intra-erythrocytic piroplasms of Theileria species in Giemsa's stained blood smears was a common finding in all the episodes. Significant haematological alterations including high total leucocyte count and low haemoglobin and packed cell volume were characteristic. Necropsy findings of the icteric liver, enlarged spleen, pulmonary oedema and abomasal ulcerations were observed in three flocks. Smear-positive blood samples from all the episodes were screened by PCR using 18S rRNA gene-specific primer sets for T. lestoquardi, T. luwenshuni, T. uilenbergi and T. ovis. T. lestoquardi which was detected in all four flocks, while there was co-infection of T. ovis in two flocks. Phylogenetic analysis revealed that T. ovis and T. lestoquardi identified in this study had 100% and ~ 99.86% homology, respectively, with the published sequences used for comparison. This is the first confirmed report of outbreaks of malignant ovine theileriosis in the Haryana state of India which caused high morbidity, mortality and case fatality among sheep and goats. Further studies on theilerioses in small ruminants are required to understand epidemiology better.
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Enfermedades de los Bovinos , Enfermedades de las Cabras , Enfermedades de las Ovejas , Theileria , Theileriosis , Bovinos , Ovinos , Animales , Theileriosis/epidemiología , Cabras , Filogenia , Enfermedades de las Ovejas/epidemiología , Theileria/genética , Brotes de Enfermedades/veterinaria , Enfermedades de los Bovinos/epidemiología , Enfermedades de las Cabras/epidemiologíaRESUMEN
Orf is an acute, highly contagious, and economically important viral disease of small ruminants. In this study, six orf suspected outbreaks among goats and sheep were investigated from Haryana state and adjoining areas of Rajasthan state during the year 2021. The disease was diagnosed on the basis of clinical signs and molecular identification. The causative agent of the disease, orf virus (ORFV), was confirmed using polymerase chain reaction (PCR) targeting immunodominant envelope antigen (B2L) gene and confirmed by sequencing. The morbidity in goats ranged from 8.75 to 100%, whereas in sheep, it ranged from 0 to 8%. The higher mortality was observed among flocks with mixed infections of orf and peste des petits (PPR) or orf and haemonchosis as compared to other outbreaks. The phylogenetic analysis of sequenced PCR products clustered the current study strains in the same clad with Indian as well as strains from other countries with nucleotide identity more than 99%, signifying a close genetic relationship. The study highlighted the circulation of strains of a single cluster among sheep and goats in Haryana and adjoining areas. Prompt diagnosis of the disease is highly important for facilitating the implementation of control measures to minimize the losses suffered by small and marginal farmers in this region. Further detailed studies are required to delineate the molecular details of ORFV for better understanding the dynamics and molecular epidemiology of strains circulating in the country and for designing the effective vaccines against the disease which are currently lacking in the country.
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Enfermedades de las Cabras , Virus del Orf , Peste de los Pequeños Rumiantes , Virus de la Peste de los Pequeños Rumiantes , Enfermedades de las Ovejas , Animales , Brotes de Enfermedades/veterinaria , Enfermedades de las Cabras/diagnóstico , Enfermedades de las Cabras/epidemiología , Cabras , India/epidemiología , Virus del Orf/genética , Peste de los Pequeños Rumiantes/diagnóstico , Peste de los Pequeños Rumiantes/epidemiología , Virus de la Peste de los Pequeños Rumiantes/genética , Filogenia , Ovinos , Enfermedades de las Ovejas/epidemiologíaRESUMEN
A rigorous exploration of microbial diversity has revealed its presence on Earth, deep oceans, and vast space. The presence of microbial life in diverse environmental conditions, ranging from moderate to extreme temperature, pH, salinity, oxygen, radiations, and altitudes, has provided the necessary impetus to search for them by extending the limits of their habitats. Microbiology started as a distinct science in the mid-nineteenth century and has provided inputs for the betterment of mankind during the last 150 years. As beneficial microbes are assets and pathogens are detrimental, studying both have its own merits. Scientists are nowadays working on illustrating the microbial dynamics in Earth's subsurface, deep sea, and polar regions. In addition to studying the role of microbes in the environment, the microbe-host interactions in humans, animals and plants are also unearthing newer insights that can help us to improve the health of the host by modulating the microbiota. Microbes have the potential to remediate persistent organic pollutants. Antimicrobial resistance which is a serious concern can also be tackled only after monitoring the spread of resistant microbes using disciplines of genomics and metagenomics The cognizance of microbiology has reached the top of the world. Space Missions are now looking for signs of life on the planets (specifically Mars), the Moon and beyond them. Among the most potent pieces of evidence to support the existence of life is to look for microbial, plant, and animal fossils. There is also an urgent need to deliberate and communicate these findings to layman and policymakers that would help them to take an adequate decision for better health and the environment around us. Here, we present a glimpse of recent advancements by scientists from around the world, exploring and exploiting microbial diversity.
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Soil quality is the competence of soil to perform necessary functions that are able to maintain animal and plant productivity of the soil. Soil consists of various physical, chemical, and biological parameters, and all these parameters are involved in the critical functioning of soil. There is a need for continuous assessment of soil quality as soil is a complex and dynamic constituent of Earth's biosphere that is continuously changing by natural and anthropogenic disturbances. Any perturbations in the soil cause disturbances in the physical (soil texture, bulk density, etc.), chemical (pH, salinity, organic carbon, etc.), and biological (microbes and enzymes) parameters. These physical, chemical, and biological parameters can serve as indicators for soil quality assessment. However, soil quality assessment cannot be possible by evaluating only one parameter out of physical, chemical, or biological. So, there is an emergent need to establish a minimum dataset (MDS) which shall include physical, chemical, and biological parameters to assess the quality of the given soil. This review attempts to describe various physical, chemical, and biological parameters, combinations of which can be used in the establishment of MDS.
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Monitoreo del Ambiente , Suelo , Animales , Carbono/análisis , Plantas , SalinidadRESUMEN
Among various infectious diseases of poultry, diseases of the respiratory tract are responsible for considerable economic losses. The present study was conducted to evaluate some of the risk factors, which included locations of farm, ventilation facilities, number of farms in 1 km2 area, agro-climatic zone, and age of flock in relation to respiratory problem in Haryana, India. One hundred poultry flocks with respiratory problems were identified and selected for conducting the survey. The "ODK Collect" app installed on a smartphone was used to capture coordinates of the farms. The collected data was accessed through http://odkproject-iirs.appspot.com/ . The location of farms was mapped with the help of QGIS. All the three parameters, viz., morbidity, mortality (p < 0.001), and case fatality rate (CFR) (p = 0.045), were significantly higher in birds of age 0-2 weeks. Natural ventilation was the most common facility observed in the present study (51/100). Maximum morbidity and mortality were observed in small flocks (< 10,000), whereas maximum CFR was observed in medium-sized flocks (> 10,000-30,000), and there was a significant difference in morbidity, mortality, and CFR. Further, there was a significant difference between agro-climatic zones with respect to morbidity and mortality (p < 0.001). It can be concluded that age, flock size, and agro-climatic conditions have an impact on intensity of diseases especially respiratory diseases. Therefore, special precautions should be taken for young flock. Flock size should be adequate, and such management practices should be adopted that are suitable for particular climatic conditions.
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Enfermedades de las Aves de Corral , Aves de Corral , Enfermedades Respiratorias/veterinaria , Crianza de Animales Domésticos , Animales , Pollos , Granjas , Sistemas de Información Geográfica , India/epidemiología , Enfermedades de las Aves de Corral/epidemiología , Enfermedades Respiratorias/epidemiologíaRESUMEN
Ciliates are highly divergent unicellular eukaryotic organisms with nuclear dualism and a highly specialized ciliary pattern. They inhabit all biotopes and play crucial roles in regulating microbial food webs as they prey on bacteria, protists and even on microscopic animals. Nevertheless, subtle morphological differences and tiny sizes hinder proper species identification for many ciliates. In the present review, an attempt has been made to elaborate the various approaches used by modern day ciliate taxonomists for species identification. The different approaches involved in taxonomic characterization of ciliates such as classical (using live-cell observations, staining techniques, etc.), molecular (involving various marker genes) and statistical (delimitation of cryptic species) methods have been reviewed. Ecological and behavioural aspects in species identification have also been discussed. In present-day taxonomy, it is important to use a 'total evidence' approach in identifying ciliates, relying on both classical and molecular information whenever possible. This integrative approach will help in the mergence of classical methods with modern-day tools for comprehensive species description in future.
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Cilióforos/clasificación , Filogenia , Animales , Núcleo Celular , Cilióforos/citología , Código de Barras del ADN Taxonómico , ADN Espaciador Ribosómico/genética , Genes de ARNr , Marcadores Genéticos , Microscopía , Microscopía Fluorescente , Análisis de Secuencia de ADN , Coloración y EtiquetadoRESUMEN
Ciliated protists have attracted wide interest among researchers from the Indian subcontinent in the last few years. An International Symposium on Ciliate Biology (ISCB) 2018 was held on 04-06 April 2018 at the India Habitat Centre, New Delhi, India. The symposium represented a synergy with International Research Coordination Network for Biodiversity of Ciliates (IRCN-BC), an affiliate society of International Society of Protistologists (ISOP). The symposium provided a platform for Indian and International delegates to exchange knowledge, present their latest research findings, and establish collaborations as well as creating a networking opportunity for undergraduate and postgraduate students. Nine foreign delegates from 5 countries and 300 Indian delegates actively participated in the event which included 22 oral and 57 poster presentations.
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BACKGROUND: There are conflicting reports on the role of hydroxyurea (HU) in the pathogenesis of avascular necrosis of the femoral head (AVNFH) in patients with sickle cell disease (SCD). PROCEDURE: The present study is a prospective cohort study of Kuwaiti children with SCD who were treated with HU. They had magnetic resonance imaging of the hips before starting HU and at regular intervals during a follow-up period, ranging from 1 to 15 years. RESULTS: There were 40 patients (18 SS, 19 Sß0-thalassemia, and three SD genotypes), aged 6-20 years. Pre-HU, 11 (27.5%) had varying grades of AVNFH, while post HU, the prevalence was 32.5%. Two patients developed new lesions during the study, while five (45.5%) that had lesions pre-HU remained static, another five (45.5%) progressed, and one (9%) improved radiologically. The older patients who had been on HU the longest were more likely to deteriorate. The only hematological parameter that was consistently associated with AVNFH was the reticulocyte count. CONCLUSIONS: The frequency and rate of progression of AVNFH in this study is much less than that previously reported for our patients not treated with HU. There is no evidence that HU therapy is a risk factor for AVNFH. It may, in fact, prevent new lesions and deter the progression of existing AVNFH.
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Anemia de Células Falciformes/tratamiento farmacológico , Antidrepanocíticos/efectos adversos , Necrosis de la Cabeza Femoral/epidemiología , Hidroxiurea/efectos adversos , Adolescente , Niño , Femenino , Necrosis de la Cabeza Femoral/inducido químicamente , Humanos , Imagen por Resonancia Magnética , Masculino , Prevalencia , Estudios Prospectivos , Adulto JovenRESUMEN
Response of heavy metals namely cadmium (Cd) and copper (Cu) on the expression of stress responsive genes in the fresh water ciliate, Tetmemena sp. (single cell eukaryote) was studied. Stress responsive genes include heat shock protein genes and genes involved in antioxidant defence system. Quantitative real time PCR (qRT-PCR) was employed to evaluate the effects of Cd and Cu on the expression of cytosolic hsp70 and Mn-sod genes. Increase in the expression of these genes was observed after exposure with the heavy metals. The macronuclear cytosolic hsp70 and Mn-sod (SOD2) genes were also sequenced and characterized using various bioinformatics tools. In antioxidant defence system, the superoxide dismutase (SOD) family is a first line antioxidant enzyme group involved in catalysing reactive oxygen species (ROS) to hydrogen peroxide and molecular oxygen. Influence of Cd and Cu on the activity of SOD has already been reported by our group. Therefore, the enzymatic activities of antioxidant enzymes, catalase (CAT) and glutathione peroxidase (GPx) were studied in the presence of Cd and Cu and there was significant increase in activity of these enzymes in concentration dependent manner. This study suggests that cytosolic hsp70, Mn-sod and the antioxidant enzymes such as CAT and GPx can be used as effective molecular biomarkers for heavy metal toxicity and Tetmemena sp. can be used as potential model for understanding the molecular response to heavy metal contamination in aquatic ecosystems.
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Cilióforos/metabolismo , Proteínas HSP70 de Choque Térmico/metabolismo , Superóxido Dismutasa/metabolismo , Antioxidantes/metabolismo , Antioxidantes/fisiología , Cadmio/efectos adversos , Cadmio/farmacología , Catalasa/análisis , Catalasa/metabolismo , Cilióforos/genética , Cobre/efectos adversos , Cobre/farmacología , Ecosistema , Agua Dulce , Regulación Bacteriana de la Expresión Génica/genética , Glutatión Peroxidasa/análisis , Glutatión Peroxidasa/metabolismo , Proteínas HSP70 de Choque Térmico/genética , Metales Pesados/efectos adversos , Estrés Oxidativo/efectos de los fármacos , Estrés Fisiológico/genética , Superóxido Dismutasa/genética , Contaminantes Químicos del Agua/toxicidadRESUMEN
RATIONALE: Lengthy, multidrug, toxic, and low-efficacy regimens limit management of pulmonary nontuberculous mycobacterial disease. OBJECTIVES: In this phase II study, we investigated the efficacy and safety of liposomal amikacin for inhalation (LAI) in treatment-refractory pulmonary nontuberculous mycobacterial (Mycobacterium avium complex [MAC] or Mycobacterium abscessus) disease. METHODS: During the double-blind phase, patients were randomly assigned to LAI (590 mg) or placebo once daily added to their multidrug regimen for 84 days. Both groups could receive open-label LAI for 84 additional days. The primary endpoint was change from baseline to Day 84 on a semiquantitative mycobacterial growth scale. Other endpoints included sputum conversion, 6-minute-walk distance, and adverse events. MEASUREMENTS AND MAIN RESULTS: The modified intention-to-treat population included 89 (LAI = 44; placebo = 45) patients. The average age of the sample was 59 years; 88% were female; 92% were white; and 80 and 59 patients completed study drug dosing during the double-blind and open-label phases, respectively. The primary endpoint was not achieved (P = 0.072); however, a greater proportion of the LAI group demonstrated at least one negative sputum culture (14 [32%] of 44 vs. 4 [9%] of 45; P = 0.006) and improvement in 6-minute-walk test (+20.6 m vs. -25.0 m; P = 0.017) at Day 84. A treatment effect was seen predominantly in patients without cystic fibrosis with MAC and was sustained 1 year after LAI. Most adverse events were respiratory, and in some patients it led to drug discontinuation. CONCLUSIONS: Although the primary endpoint was not reached, LAI added to a multidrug regimen produced improvements in sputum conversion and 6-minute-walk distance versus placebo with limited systemic toxicity in patients with refractory MAC lung disease. Further research in this area is needed. Clinical trial registered with www.clinicaltrials.gov (NCT01315236).
Asunto(s)
Amicacina/uso terapéutico , Antibacterianos/uso terapéutico , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Micobacterias no Tuberculosas/efectos de los fármacos , Administración por Inhalación , Amicacina/administración & dosificación , Antibacterianos/administración & dosificación , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Importance: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with poor prognosis. Approved therapies do not halt disease progression. Objective: To determine the effect of recombinant human pentraxin 2 vs placebo on change from baseline to week 28 in mean forced vital capacity (FVC) percentage of predicted value. Design, Setting, and Participants: Phase 2, randomized, double-blind, placebo-controlled trial conducted at 18 sites in 7 countries of eligible patients with IPF (N = 117; aged 40-80 years; FVC ≥50% and ≤90% predicted; ratio of forced expiratory volume in the first second/FVC >0.70; diffusing capacity for carbon monoxide [Dlco] ≥25% and ≤90% predicted; and distance of ≥150 m on the 6-minute walk test). Study period was August 2015-May 2017. Interventions: Patients were randomized to receive either recombinant human pentraxin 2 (10 mg/kg intravenous every 4 weeks, n = 77) or placebo (n = 39) for 24 weeks, and stratified by concurrent IPF treatment status. Main Outcomes and Measures: The primary end point was the least-squares mean change in FVC percentage of predicted value from baseline to week 28 (minimal clinically important difference, decline of 2%-6%). Secondary end points included mean change in lung volumes (total, normal, and interstitial lung abnormalities) on high-resolution computed tomography (HRCT) and 6-minute walk distance (minimal clinically important difference, 24-45 m). Results: Of 117 randomized patients, 116 received at least 1 dose of study drug (mean age, 68.6 years; 81.0% men; mean time since IPF diagnosis, 3.8 years), and 111 (95.7%) completed the study. The least-squares mean change in FVC percentage of predicted value from baseline to week 28 in patients treated with recombinant human pentraxin 2 was -2.5 vs -4.8 for those in the placebo group (difference, +2.3 [90% CI, 1.1 to 3.5]; P = .001). No significant treatment differences were observed in total lung volume (difference, 93.5 mL [90% CI, -27.7 to 214.7]), quantitative parenchymal features on HRCT (normal lung volume difference, -1.2% [90% CI, -4.4 to 1.9]; interstitial lung abnormalities difference, 1.1% [90% CI, -2.2 to 4.3]), or measurement of Dlco (difference, -0.4 [90% CI, -2.6 to 1.7]). The change in 6-minute walk distance was -0.5 m for patients treated with recombinant human pentraxin 2 vs -31.8 m for those in the placebo group (difference, +31.3 m [90% CI, 17.4 to 45.1]; P < .001). The most common adverse events in the recombinant human pentraxin 2 vs placebo group were cough (18% vs 5%), fatigue (17% vs 10%), and nasopharyngitis (16% vs 23%). Conclusions and Relevance: In this preliminary study, recombinant human pentraxin 2 vs placebo resulted in a slower decline in lung function over 28 weeks for patients with idiopathic pulmonary fibrosis. Further research should more fully assess efficacy and safety. Trial Registration: clinicaltrials.gov Identifier: NCT02550873.