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AIM: To explore the views and experiences of nurse academics about their professional work life. DESIGN: A qualitative exploratory interview study. METHODS: Data were collected during 2018/2019 using a semi-structured interview method with 19 experienced academic nurses from a range of academic levels in Australia. All interviews were audio recorded, transcribed verbatim and thematically analysed using a narrative approach. Ethics approval was granted by the relevant University Human Research Ethics Committee. RESULTS: Participants provided detailed insights into the type of daily job stressors they faced. They shared narratives about their personal job experiences and how, at times, they chose to remain silent to maintain a cordial working relationship with some of their senior colleagues and leaders. The main themes were identified included a lack of work-life balance, incivility towards staff, increasing workloads and inequitable distribution, lack of recognition, negative workplace culture, lack of awareness of the importance of political astuteness and lack of leadership skills. CONCLUSION: To ensure a sustainable academic nursing workforce and provide a clearer understanding of job stress and what contributes to faculty decision to leave, areas of priority and strategies that needed attention were identified. These included effective mentoring of less-experienced staff and leadership styles that promote greater inclusiveness, being heard, valued and recognized, improved work-life balance and the need to have a sense of belonging. IMPACT: The study explored the job experiences of nurse academics and identified occupational stressors that directly influenced their daily work life. The findings have global implications for the recruitment and sustainability of nurse academics. This also impacts on their professional and work-life balance.
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Recursos Humanos de Enfermagem , Estresse Ocupacional , Humanos , Satisfação no Emprego , Liderança , Pesquisa Qualitativa , Local de TrabalhoRESUMO
Diabetes and Obesity are major health problems worldwide. Obesity and Diabetes are interrelated. Visceral adiposity is well correlated with insulin resistance, metabolic syndrome and cardiovascular diseases. Visceral Adiposity Index (VAI) is calculated using anthropometric and laboratory data and Visceral Fat is measured radiologically here. Following study evaluated the correlation between them. AIM: To study correlation of visceral adiposity index with visceral fat in obese patients with and without type 2 Diabetes Mellitus. MATERIAL: Study Design: An observational cross sectional comparative study was conducted which included total 60 obese patients with BMI ≥ 25 kg/m2, of them 30 had type 2 diabetes mellitus (DM) and 30 were non diabetic (NDM). All were aged >40 years with no history of malignancy or any abdominal surgery. MATERIAL AND METHODS: Patients fulfilling inclusion criteria were included in the study after taking informed written consent. Physical examination and anthropometric measurements were done. Blood investigations included Lipid Profile [Total Cholesterol (TC), Serum Triglycerides (TG), High Density Lipoprotein Cholesterol (HDL), Low density Lipoprotein Cholesterol (LDL)], HBA1c, Fasting Blood Glucose (FBS) and Post-Prandial Blood Glucose (PPBS). Liver Kidney Space (LKS) measured by ultrasonography was taken as a parameter for Visceral Fat (VF). VAI was calculated using the necessary formula. OBSERVATION AND RESULTS: Mean VAI in DM group was 2.71±1.18 and in NDM group was 2.39±0.58. Mean VF(LKS) in DM group was 4.19±0.27 mm and in NDM group was 4.03±0.29 mm. VAI was significantly higher in females. There was significant correlation (p<0.05) of VAI with VF(LKS) in whole population, in DM group and in NDM group. No significant difference was seen in both DM and NDM in terms of VAI and VF(LKS). LKS was significantly correlated (p<0.05) with Weight, BMI, Waist circumference, FBS, TC, TG, HDL, LDL in whole population, DM and NDM group, with PPBS and HBA1c in whole population and in DM group and with height in NDM group. There was significant correlation (p<0.05) between VAI with PPBS and HBA1c in DM group. CONCLUSION: VAI and VF(LKS) were well correlated in whole population as well as in both DM and NDM group individually but there was no significant difference between DM and NDM groups. We need large population multicentric study for better assessment and its use in clinical practise.
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Diabetes Mellitus Tipo 2 , Gordura Intra-Abdominal , Adiposidade , Glicemia/metabolismo , Índice de Massa Corporal , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Obesidade/complicações , Obesidade Abdominal/epidemiologiaRESUMO
Purine breakdown produces uric acid (UA) as a by-product. Serum UA levels have been reported to be higher in hypoxic people, including Chronic Obstructive Pulmonary Disease (COPD) patients. Serum UA has been suggested as a marker for impaired oxidative metabolism, and it is also thought to play a role in the prognosis and evaluation of respiratory disorders such as COPD. AIM: To compare serum uric acid levels in patients with stable Chronic Obstructive Pulmonary Disease and in patients with acute exacerbation (AE). MATERIAL: Study Design: An observational cross sectional comparative study was conducted which included 25 stable COPD patients and 25 patients with AE of COPD, all of them aged more than 40 years. Serum UA levels were measured and compared between the two groups. MATERIAL AND METHODS: Patients fulfilling inclusion criteria were included in the study after taking informed written consent. Blood sample was taken in plain vial and sent to Biochemistry lab for serum UA analysis. The analysis of serum UA was done using system reagent on Beckman Coulter AU Analyser. Complete blood count, blood urea, serum creatinine, arterial blood gas and oxygen saturation were also measured. OBSERVATION AND RESULTS: The mean serum UA in the Stable group was 6.19 mg/dL and in AE group was 7.45 mg/ dL. There was a statistically significant difference between the 2 groups in terms of serum UA levels with a p value of 0.021 and the mean serum UA level being highest in the AE group. In this study, statistically significant difference was also found between Stable and AE group in terms of mMRC grading of dyspnea (p< 0.001), Pack years (p< 0.001), pH (p=0.009), pO2 (p< 0.001) and pCO2 (p< 0.001). There was no statistically significant difference between Stable and AE group in terms of age, gender, total leucocyte count, blood urea, serum creatinine and HCO3 Conclusion: Serum UA may be a useful parameter in assessing disease severity and hypoxemia in known COPD patients and may be helpful in early intensive management. Increased serum UA levels denote poor state and bad prognosis. Since serum UA is a simple, inexpensive and readily available routine laboratory test, it can be used in risk stratification in patients with COPD and can help in early management of patients with COPD.
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Doença Pulmonar Obstrutiva Crônica , Ácido Úrico , Creatinina , Estudos Transversais , Humanos , Hipóxia , UreiaRESUMO
Various new clinical signs and symptoms, such as dysfunction of smell (anosmia) and taste (dysgeusia) have emerged ever since the coronavirus disease 2019 (COVID-19) pandemic begun. The objective of this study was to identify the clinical presentation and factors associated with 'new loss/change of smell (anosmia) or taste (dysgeusia)' at admission in patients positive by real time polymerase chain reaction for SARS-CoV-2 infection. All adult COVID-19 patients with new onset anosmia or dysgeusia at admission were included in study group. Equal number of age and gender matched COVID-19 patients without anosmia or dysgeusia at admission were included in the control group. A total of 261 COVID-19 patients were admitted during the study period of which 55 (21%) had anosmia and or dysgeusia. The mean (SD) age was 36 (13) years and majority were males (58%, n = 32). Comorbidity was present in 38% of cases (n = 21). Anosmia and dysgeusia were noted in more than 1/5th of the cases. Anosmia (96%, n = 53) was more common than dysgeusia (75%, n = 41). Presence of both ansomia and dysgeusia was noted in 71% of patients (n = 39). On comparing the cases with the controls, on univariate analysis, fever (higher in cases), rhinitis (lower in cases), thrombocytopenia, elevated creatinine and bilirubin (all higher in cases) were significantly associated with anosmia or dysgeusia. On multivariate analysis, only rhinitis (odds ratio [OR]: 0.28; 95% confidence interval [CI]: 0.09-0.83; p = .02) thrombocytopenia (OR: 0.99; 95% CI: 0.99-0.99; p = .01) and elevated creatinine (OR: 7.6; 95% CI: 1.5-37.6; p = .01) remained significant. In this retrospective study of COVID-19 patients, we found anosmia and dysgeusia in more than 1/5th of the cases. Absence of rhinitis, low platelet counts and elevated creatinine were associated with anosmia or dysgeusia in these patients.
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Anosmia/epidemiologia , COVID-19/epidemiologia , Disgeusia/epidemiologia , Adulto , Anosmia/sangue , Anosmia/fisiopatologia , Anosmia/virologia , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/fisiopatologia , Estudos de Casos e Controles , Disgeusia/sangue , Disgeusia/fisiopatologia , Disgeusia/virologia , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Pandemias , Contagem de Plaquetas , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Rinite/epidemiologia , Rinite/etiologia , SARS-CoV-2/isolamento & purificação , Trombocitopenia/epidemiologia , Trombocitopenia/etiologiaRESUMO
AIM: To better understand occupational stress faced by nurse academics. METHODS: A mixed-methods systematic review, following the Joanna Briggs Institute [JBI], (Joanna Briggs Institute Reviewers' Manual: 2014 edition, 2014) process. Studies were assessed for quality and risk of bias by using standardised critical appraisal instruments from the Joanna Briggs Institute. In addition, processes and reporting were checked against the Equator guidelines. See Appendix S1. RESULTS: The review revealed that nursing academics do experience occupational stress, including burnout. Occupational stress for academic nurses is associated with various factors including work-life balance, workload issues, resources and support, and adapting to change. However, much of the literature focuses on nurses during the initial transition from clinical to academic environment, with rather less focus on established mid-to-late career nurse academics. DISCUSSION: Occupational stress and burnout are evident in the university academic workforce, adversely affecting the well-being of academic nurses, and the long-term sustainability of the academic nursing workforce. While there is considerable literature focusing on the novice academic nurse, particularly during the transition period, rather less is known about occupational stress among academic nurses across the career trajectory. Various strategies to deal with the negative consequences of occupational stress are identified, including (a) quality mentors for novice and younger nursing academics; (b) training in resilience building for novice academics; (c) supporting collegial relationships and reducing bullying; (d) assistance for professional development and research; (e) better support and resources to overcome increasing workloads; and (f) greater work-related empowerment to enhance job satisfaction. CONCLUSION: There is a need for a broader whole-of-career research focus to more fully identify, explore and mitigate the occupational stressors that negatively affect the academic nurse workforce. RELEVANCE TO CLINICAL PRACTICE: A strong and resilient academic nurse workforce is essential for the sustainability of the profession. Organisations should review their work practices and provide greater work-related empowerment to reduce occupational stressors among nursing academics.
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Esgotamento Profissional/psicologia , Docentes de Enfermagem/psicologia , Centros Médicos Acadêmicos , Humanos , Satisfação no Emprego , Mentores , Equilíbrio Trabalho-Vida , Carga de Trabalho/psicologiaRESUMO
As antibiotic resistance increases, there is a need for new therapies to treat infection, particularly in cystic fibrosis (CF), where Pseudomonas aeruginosa is a ubiquitous pathogen associated with increased morbidity and mortality. Bacteriophages are an attractive alternative treatment, as they are specific to the target bacteria and have no documented side effects. The efficacy of phage cocktails was established in vitro. Two P. aeruginosa strains were taken forward into an acute murine infection model with bacteriophage administered either prophylactically, simultaneously, or postinfection. The infective burden and inflammation in bronchoalveolar lavage fluid (BALF) were assessed at various times. With low infective doses, both control mice and those undergoing simultaneous phage treatment cleared P. aeruginosa infection at 48 h, but there were fewer neutrophils in BALF of phage-treated mice (median, 73.2 × 10(4)/ml [range, 35.2 to 102.1 × 10(4)/ml] versus 174 × 10(4)/ml [112.1 to 266.8 × 10(4)/ml], P < 0.01 for the clinical strain; median, 122.1 × 10(4)/ml [105.4 to 187.4 × 10(4)/ml] versus 206 × 10(4)/ml [160.1 to 331.6 × 10(4)/ml], P < 0.01 for PAO1). With higher infective doses of PAO1, all phage-treated mice cleared P. aeruginosa infection at 24 h, whereas infection persisted in all control mice (median, 1,305 CFU/ml [range, 190 to 4,700 CFU/ml], P < 0.01). Bacteriophage also reduced CFU/ml in BALF when administered postinfection (24 h) and both CFU/ml and inflammatory cells in BALF when administered prophylactically. A reduction in soluble inflammatory cytokine levels in BALF was also demonstrated under different conditions. Bacteriophages are efficacious in reducing both the bacterial load and inflammation in a murine model of P. aeruginosa lung infection. This study provides proof of concept for future clinical trials in patients with CF.
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Carga Bacteriana/efeitos dos fármacos , Bacteriófagos/crescimento & desenvolvimento , Pulmão/microbiologia , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/virologia , Animais , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/microbiologia , Modelos Animais de Doenças , Feminino , Inflamação/tratamento farmacológico , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/imunologia , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/imunologiaRESUMO
This article will present the findings of a research study that investigated the extent to which mental health nurses employed within rural and metropolitan areas of Australia are affected by burnout, using the Maslach Burnout Inventory (MBI) and a demographic questionnaire. The study also examined whether the Maslach Burnout Inventory (MBI) was a valid measure of mental health burnout within the Australian context and culture or alternatively, in what ways it needed to be refined? A cross-sectional study of mental health nurses (n = 319) from the states of New South Wales, Victoria, Queensland and Western Australia was undertaken. The 22-item Maslach Burnout Inventory (MBI) was used to measure burnout and a demographic questionnaire utilising a cluster sampling, cross-sectional design survey method, was used to gather the data. The study found that gender and level of qualification were the two major factors that showed any significance, where males experienced a higher level of depersonalisation on the frequency and intensity sub-scale scores of the MBI and that the more qualified a nurse, the greater the level of depersonalisation they experienced. These results were true for participants in both rural and metropolitan settings within Australia. Age was the third most influencing factor in terms of emotional exhaustion, where younger participants (under 30) reported higher levels of emotional exhaustion. Younger male mental health nurses experienced higher levels of depersonalisation.
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Esgotamento Profissional , Enfermagem Psiquiátrica , Serviços de Saúde Rural , Serviços Urbanos de Saúde , Adulto , Austrália , Estudos Transversais , Feminino , Humanos , Satisfação no Emprego , Masculino , Inquéritos e QuestionáriosRESUMO
The response to mRNA vaccines needs to be sufficient for immune cell activation and recruitment, but moderate enough to ensure efficacious antigen expression. The choice of the cap structure and use of N1-methylpseudouridine (m1Ψ) instead of uridine, which have been shown to reduce RNA sensing by the cellular innate immune system, has led to improved efficacy of mRNA vaccine platforms. Understanding how RNA modifications influence the cell intrinsic immune response may help in the development of more effective mRNA vaccines. In the current study, we compared mRNA vaccines in mice against influenza virus using three different mRNA formats: uridine-containing mRNA (D1-uRNA), m1Ψ-modified mRNA (D1-modRNA), and D1-modRNA with a cap1 structure (cC1-modRNA). D1-uRNA vaccine induced a significantly different gene expression profile to the modified mRNA vaccines, with an up-regulation of Stat1 and RnaseL, and increased systemic inflammation. This result correlated with significantly reduced antigen-specific antibody responses and reduced protection against influenza virus infection compared with D1-modRNA and cC1-modRNA. Incorporation of m1Ψ alone without cap1 improved antibodies, but both modifications were required for the optimum response. Therefore, the incorporation of m1Ψ and cap1 alters protective immunity from mRNA vaccines by altering the innate immune response to the vaccine material.
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People from culturally and linguistically diverse (CALD) backgrounds hold attitudes, values and beliefs surrounding health, illness and mental health issues that are not fully in harmony with Western approaches to health care. In particular, mental health services do not adequately meet the specific needs of CALD communities, a situation that is a violation of sound health care access and rights. A number of damning government reports highlight the inadequacies of the system. CALD groups that experience mental illness have the problem of dual vulnerabilities. They are disadvantaged on at least two fronts: The marginalization and stigmatization associated with mental illness and the access and utilization of services. This paper reviews the context of mental health service delivery in Australia. There is agreement that the needs of these people are only marginally being met at best despite individual and collective efforts to address the issue.
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Diversidade Cultural , Linguística , Transtornos Mentais/psicologia , Populações Vulneráveis , HumanosRESUMO
Vermicomposting of textile mill sludge (TMS) with cow dung (CD) and tea waste (TW) as amendments was done in seven different combinations using Eisenia fetida for 90 days. Results revealed that pH decreased from 7.68-8.63 to 7.09-7.59. TOC content and C/N ratio reductions were in range of 15.71-20.08% and 39.33-50.05%, respectively (P < 0.05). The macronutrients in the form of TN, TP, and TK increased 0.38-0.64, 1.07-2.27, and 0.56-1.98 times respectively after end of bioconversion process (P < 0.05), among increases in ash content and EC. The biomass and cocoon production of E. fetida increased significantly (P < 0.05), while high mortality rate of earthworms was observed in treatments containing 50% or more TMS content. The bacterial population beneficial for degradation of organic matter increased significantly over initial substrates (0th day) (P < 0.05). Increased humification index in end-product indicated better maturity of vermicompost as observed in treatments containing higher proportions of amendments. The addition of amendments favored earthworm activity which significantly decreased the heavy metal concentration (Fe, Cu, Pb, Zn) in the end-product. The study concluded that sustainable utilization of TMS could be achieved for cleaner and enriched vermicompost production by addition of amendments CD and TW in proportions of 50% and above.
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Oligoquetos , Animais , Bovinos , Feminino , Esterco , Oligoquetos/metabolismo , Esgotos/química , Solo/química , Chá , TêxteisRESUMO
BACKGROUND: The COVID-19 pandemic led to wide adoption of telehealth in primary care. The impact of telehealth on subsequent follow-up visit volume is mixed. This study examines the association of newly expanded telehealth with short-interval follow-up visits during the COVID-19 pandemic in an academic primary care practice. METHODS: Scheduling data were used to compare rates of 0 to 60-day follow-up visits after telehealth and in-person visits before and after onset of the COVID-19 pandemic. RESULTS: Compared with in-person visits, telehealth visits were associated with significantly higher rates of total short-interval follow-ups and higher rates of first short-interval follow-ups occurring in 0 to 15 days. DISCUSSION: Higher rates of short-interval follow-up may be due to inefficiencies created by rapid expansion of telehealth including suboptimal scheduling algorithms, pandemic-related safety considerations, and discomfort with the visit modality. Short-interval follow-ups have potential negative impacts on practice access, patient-centered outcomes, and sustainability of telehealth in primary care. CONCLUSION: Newly expanded telehealth visits conducted in the year after the onset of the COVID-19 pandemic resulted in higher rates and sooner first occurrence of short-interval follow-up visits. Future research should identify optimal scheduling processes for telehealth visits to minimize short-interval follow-ups.
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COVID-19 , Telemedicina , COVID-19/epidemiologia , Seguimentos , Humanos , Pandemias , Telemedicina/métodosRESUMO
Gene therapy for cystic fibrosis (CF) is making encouraging progress into clinical trials. However, further improvements in transduction efficiency are desired. To develop a novel gene transfer vector that is improved and truly effective for CF gene therapy, a simian immunodeficiency virus (SIV) was pseudotyped with envelope proteins from Sendai virus (SeV), which is known to efficiently transduce unconditioned airway epithelial cells from the apical side. This novel vector was evaluated in mice in vivo and in vitro directed toward CF gene therapy. Here, we show that (i) we can produce relevant titers of an SIV vector pseudotyped with SeV envelope proteins for in vivo use, (ii) this vector can transduce the respiratory epithelium of the murine nose in vivo at levels that may be relevant for clinical benefit in CF, (iii) this can be achieved in a single formulation, and without the need for preconditioning, (iv) expression can last for 15 months, (v) readministration is feasible, (vi) the vector can transduce human air-liquid interface (ALI) cultures, and (vii) functional CF transmembrane conductance regulator (CFTR) chloride channels can be generated in vitro. Our data suggest that this lentiviral vector may provide a step change in airway transduction efficiency relevant to a clinical programme of gene therapy for CF.
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Fibrose Cística/terapia , Terapia Genética , Vetores Genéticos , Lentivirus/genética , Vírus Sendai/genética , Proteínas do Envelope Viral/genética , Animais , Diferenciação Celular , Linhagem Celular , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Transdução GenéticaRESUMO
BACKGROUND: The evidence suggests that heavy workloads, pressure to publish, lack of recognition and job insecurity has led to increased job stress among nurse academics. Lack of proper mentoring, reorientation and transition into an academic role are contributory factors towards the lack of retention and recruitment among nurse academics. Internationally, the sustainability of the nurse academic workforce is an area of great concern. The experiences of nurse academics have not been extensively investigated. OBJECTIVES: To explore the work experiences of nurse academics. DESIGN: Qualitative Exploratory study. Data were analysed using thematic analysis. PARTICIPANTS: A purposive sample of nurse academics (n = 19), recruited from all states and territories of Australia, lecturer to professor level and work experiences from 2 to 30 years. METHODS: Data were collected using semi-structured face to face and telephone interviews. Data were transcribed verbatim and thematically analysed based upon Braun & Clark's model. The study is reported in accordance with the COREQ guidelines. Ethical approval was granted by the relevant University Human Research Ethics Committee. RESULTS: Four main themes were identified (a) Helping students achieve, finding satisfaction through student engagement, (b) working with challenging students, (c) increased workloads, lack of support and resources and (d) difficulty with retention of newly appointed staff. CONCLUSIONS: Although the findings highlighted the interactions with nursing students were a positive experience, many of the participants raised great concern about the challenging, difficult, academically weak, rude, and manipulative students. The growing workload increased non-academic administrative work, and the inability to sustain newly appointed staff were areas of great concern. Doing more with less and not being recognized were pertinent factors that needed to be addressed.
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Estudantes de Enfermagem , Humanos , Mentores , Pesquisa Qualitativa , Recursos Humanos , Carga de TrabalhoRESUMO
An advanced operational configuration of anoxic-aerobic moving bed biofilm reactors (AMOMOX process) was experimentally demonstrated to achieve simultaneous sludge yield minimization, pollution and nitrogen removal. The AMOMOX experimentation witnessed considerable variation in process parameters while feed operation changed from synthetic wastewater to real tannery influent. The strict maintenance of operational strategies resulted prominent removal of TCOD, SCOD, ammonia nitrogen and total nitrogen higher upto 93.5%, 94.8%, 95.2% and 88.7% respectively. The nourishment of filamentous microbiota and purposeful promotion of cell-lysis effectively sustained sludge yield restriction. Here, the sludge yield (Yobs) lowering upto 0.51 gVSS/gCOD ultimately turned an overall sludge minimization of 46.8% compared with a parallel-run conventional activated sludge treatment. The observations were further supported by sophisticated instrumental imaging, thermogravimetric analysis and batch digestion test of the sludge pool. The experimental Yobs and corresponding solids retention showed consensus with the reported correlation model and, thus, a modified correlation was tested.
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Poluentes Ambientais , Purificação da Água , Biofilmes , Reatores Biológicos , Desnitrificação , Nitrogênio , Esgotos , Eliminação de Resíduos LíquidosRESUMO
The commercial application of liquid-state Pickering emulsions in food systems remains a major challenge. In this study, we developed a spray-dried Pickering emulsion powder using chitosan as a Pickering emulsifier and alginate as a coating material. The functionality of the powder was evaluated in terms of its oxidative stability, pH-responsiveness, mucoadhesivity, and lipid digestibility. The Pickering emulsion powder was oxidatively more stable than the conventional emulsion powder stabilized by gum Arabic. The powder exhibited pH-responsiveness, whereby it remained intact in acidic pH, but dissolved to release the emulsion in 'Pickering form' at near-neutral pH. The Pickering emulsion powder was also mucoadhesive and could be digested by lipase in a controlled manner. These findings suggested that the multi-functional Pickering emulsion powder could be a potential delivery system for applications in the food industry.
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Alginatos/química , Quitosana/química , Emulsificantes/química , Liberação Controlada de Fármacos , Emulsões/química , Indústria Alimentícia , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Oxirredução , Tamanho da PartículaRESUMO
A clinical program to assess whether lipid GL67A-mediated gene transfer can ameliorate cystic fibrosis (CF) lung disease is currently being undertaken by the UK CF Gene Therapy Consortium. We have evaluated GL67A gene transfer to the murine nasal epithelium of wild-type and CF knockout mice to assess this tissue as a test site for gene transfer agents. The plasmids used were regulated by either (1) the commonly used short-acting cytomegalovirus promoter/enhancer or (2) the ubiquitin C promoter. In a study of approximately 400 mice with CF, vector-specific CF transmembrane conductance regulator (CFTR) mRNA was detected in nasal epithelial cells of 82% of mice treated with a cytomegalovirus-plasmid (pCF1-CFTR), and 62% of mice treated with an ubiquitin C-plasmid. We then assessed whether CFTR gene transfer corrected a panel of CFTR-specific endpoint assays in the murine nose, including ion transport, periciliary liquid height, and ex vivo bacterial adherence. Importantly, even with the comparatively large number of animals assessed, the CFTR function studies were only powered to detect changes of more than 50% toward wild-type values. Within this limitation, no significant correction of the CF phenotype was detected. At the current levels of gene transfer efficiency achievable with nonviral vectors, the murine nose is of limited value as a stepping stone to human trials.
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Técnicas de Transferência de Genes , Nariz/patologia , Animais , Aderência Bacteriana , Fibrose Cística/genética , Citomegalovirus/genética , Elementos Facilitadores Genéticos , Feminino , Terapia Genética/métodos , Lipossomos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mutação , Plasmídeos/metabolismo , Regiões Promotoras GenéticasRESUMO
The aim of the study was to assess if low-frequency ultrasound (US), in the range of 30-35 kHz, increases non-viral gene transfer to the mouse lung. US is greatly attenuated in the lung due to large energy losses at the air/tissue interfaces. The advantages of low-frequency US, compared with high-frequency US are: (i) increased cavitation (responsible for the formation of transient pores in the cell membrane) and (ii) reduced energy losses during lung penetration. Cationic lipid GL67/plasmid DNA (pDNA), polyethylenimine (PEI)/pDNA and naked pDNA were delivered via intranasal instillation and the animals were then exposed to US (sonoporation) at 0.07 or 0.1 MPa for 10 min. Under these conditions, US did not enhance GL67 or PEI-mediated transfection. It did, however, increase naked pDNA gene transfer by approximately 4 folds. Importantly, this was achieved in the absence of microbubbles, which are crucial for the commonly used high-frequency (1 MHz) sonoporation but may not be able to withstand nebulization in a clinically relevant setup. Lung hemorrhage was also assessed and shown to increase with US pressure in a dose-dependent manner. We have thus, established that low-frequency US can enhance lung gene transfer with naked pDNA and this enhancement is more effective than the previously reported 1 MHz US.
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Pulmão/virologia , Polietilenoimina/química , Transfecção/métodos , Animais , Técnicas de Transferência de Genes , Pulmão/química , Camundongos , Transfecção/estatística & dados numéricos , UltrassomRESUMO
OBJECTIVES: To identify the factors associated with intestinal parasitosis in rural and urban school children of Kashmir. METHODS: Single fresh stool samples from rural and urban school children in three age groups: a) 5 to < 8 years, b) 8 to < 11 years and c) 11-14 years were taken. Various demographic characteristics considered were source of drinking water, type of toilet used and social classes as per the Kuppuswamy social scale. Personal hygiene was assessed by the visiting physician based on length of nails, hair and frequency of bathing. Stool samples were analyzed for detection of motile forms of E. histolytica and microscopic examination under low power detected eggs of intestinal helminths. Concentration methods were used if egg count was low. RESULTS: 274 stool samples from rural school children and 240 samples were taken from urban school children respectively. 214 (46.7%) students had stool tests positive for parasitosis. Ascariasis was the most prevalent parasitosis (28%) followed by Giardiasis (7%), Trichuriasis( 5%) and Taeniasis( 4%). There was higher prevalence of parasitosis among rural orphanage children compared to urban orphanage students (76% vs. 48% p < or = 0.05). Highest prevalence of 70% was seen in the age group 8-11years. Students using river/stream water had higher rates of parasitosis compared to those who were using tap water. 202 students were found to have poor personal hygiene and parasitosis was higher in them compared to students with good personal hygiene (p < 0.05). CONCLUSION: Poor environmental sanitation, personal hygiene, type of toilet and water used were associated with recurrent intestinal infestation besides socio economic status. Regular deworming programmes need to be adopted at school level especially in 8-11 years old children to check the surge of intestinal parasites and their subsequent morbidities.
Assuntos
Enteropatias Parasitárias/epidemiologia , Adolescente , Criança , Pré-Escolar , Métodos Epidemiológicos , Fezes/parasitologia , Feminino , Humanos , Higiene , Índia/epidemiologia , Masculino , Valor Preditivo dos Testes , Prevalência , Fatores de RiscoRESUMO
BACKGROUND: The seroconversion is a significant health concern in patients with end-stage renal disease undergoing hemodialysis particularly in high endemic zones of HBV and HCV. PATIENTS AND METHODS: This prospective study was conducted from January 2009 to April 2018 at Sheri Kashmir Institute of Medical Sciences, Srinagar, Kashmir. A cohort of 459 end-stage renal disease patients on hemodialysis was enrolled from four dialysis centres and followed in a longitudinal manner. Their seroconversion rates, risk factors were studied. Positive patients were treated and followed up. RESULTS: This study demonstrated HBV seroconversion rate of 7.4 % (n = 34) and HCV seroconversion rate of 10% (n = 46) in a cohort of 459 patients on hemodialysis attending four dialysis centres of Kashmir. Patients with diabetes mellitus outnumbered in seroconversion rates of (43.75%) followed by patients with glomerulonephritis (23.75%). Of 15 patients who had undergone renal transplantation 10 (66.67%), patients had seroconversion on hemodialysis which was statistically significant (P < 0.001). Patients who were dialysed at multiple HD centres had significant seroconversion than those who followed up at a single center. Seroconversion was associated with longer duration of dialysis (80.30 ± 30.92 vs 61 ± 9.41months, P < 0.000). HBV vaccination of the ESRD patient on hemodialysis was significantly protective against seroconversion (P = 0.000). CONCLUSIONS: Hepatitis B vaccination, stringent precautions in all dialysis centres could help to reduce the high seroconversion rates which have a high financial burden on ESRD patients. Intense health education to both patients and medical staff will be beneficial to lower the seroconversion rates.
RESUMO
Current influenza vaccines manufactured using eggs have considerable limitations, both in terms of scale up production and the potential impact passaging through eggs can have on the antigenicity of the vaccine virus strains. Alternative methods of manufacture are required, particularly in the context of an emerging pandemic strain. Here we explore the production of recombinant influenza haemagglutinin using the ciliated protozoan Tetrahymena thermophila. For the first time we were able to produce haemagglutinin from both seasonal influenza A and B strains. This ciliate derived material was immunogenic, inducing an antibody response in both mice and non-human primates. Mice immunized with ciliate derived haemagglutinin were protected against challenge with homologous influenza A or B viruses. The antigen could also be combined with submicron particles containing a Nod2 ligand, significantly boosting the immune response and reducing the dose of antigen required. Thus, we show that Tetrahymena can be used as a manufacturing platform for viral vaccine antigens.