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1.
J Hum Genet ; 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33879837

RESUMO

BACKGROUND: Wolfram syndrome (WFS) is characterized by deafness, diabetes mellitus, and diabetes insipidus along with optic atrophy. WFS has an autosomal recessive mode of inheritance and is due to variants in WFS1 and CISD2. METHODS: We evaluated the underlying molecular etiology of three affected members of a consanguineous family with hearing impairment, bicuspid aortic valve, diabetes mellitus and insipidus, clinodactyly, and gastrointestinal tract abnormalities via exome sequencing approach. We correlated clinical and imaging data with the genetic findings and their associated phenotypes. RESULTS: We identified a homozygous missense variant p.(Asn1097Lys) in CDK13, a gene previously associated with autosomal dominant congenital heart defects, dysmorphic facial features, clinodactyly, gastrointestinal tract abnormalities, intellectual developmental disorder, and seizures with variable phenotypic features. CONCLUSION: We report a homozygous variant in CDK13 and suggest that this gene causes an autosomal recessive disorder with hearing impairment, bicuspid aortic valve, diabetes mellitus and insipidus, clinodactyly, and gastrointestinal tract abnormalities.

2.
Biomed Res Int ; 2021: 5532864, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33880367

RESUMO

Bovine tuberculosis (bTB) is a widespread zoonotic infection targeting the livestock sector, especially in developing countries, and posing a risk to humans and animal populations. Its recent prevalence in river buffaloes has been estimated as higher as 33.7%. In emergent countries like Pakistan, there is likeliness of human-livestock interfaces extensively and lacking of effective preventive measures that illustrate the risk of spreading the infection at a remarkable rate. The river buffalo (Bubalus bubalis) is an upkeep host of Mycobacterium bovis and is responsible for disease transmission among buffaloes and other livestock species. In this study, potential molecular biomarkers in the Interferon-gamma gene (IFNg) were identified after genomic screening of river buffaloes. Unique genomic loci in river buffalo proved the novelty of the genomic structure of this phenomenal animal but also highlighted its significance in natural immunity against the Mycobacterium. A total of eight single nucleotide polymorphisms were identified in the coding region of IFNg. The SNPs in the exonic region were all transitions, i.e., the conversion of purines to purines. These SNPs were analyzed for Hardy Weinberg Equilibrium, chi2 test, gene diversity, and protein structural conformation. Pathway analysis in tuberculosis revealed that IFNg inhibits the antigen-presenting cells (APC) through JAK and STAT pathways. Network analysis of IFNg proteins in both species showed strong associations among the immunity-related proteins (interleukins, tissue necrosis factors) and receptors of interferons. The identified polymorphic sites might be novel-potentiated markers for the selection of animals with superior immune response against bTB and can be exploited as promising genomic sites for breeding the resistant animal herds to combat Mycobacterium infection in a long run.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33924056

RESUMO

This study examined individual-level determinants of self-reported changes in healthy (diet and physical activity) and addictive (alcohol use, smoking, and vaping) lifestyle behaviors during the initial COVID-19 lockdown period in the USA. A national online survey was administered between May and June 2020 that targeted a representative U.S. sample and yielded data from 1276 respondents, including 58% male and 50% racial/ethnic minorities. We used univariate and multivariable linear regression models to examine the associations of sociodemographic, mental health, and behavioral determinants with self-reported changes in lifestyle behaviors. Some study participants reported increases in healthy lifestyle behaviors since the pandemic (i.e., 36% increased healthy eating behaviors, and 33% increased physical activity). However, they also reported increases in addictive lifestyle behaviors including alcohol use (40%), tobacco use (41%), and vaping (46%). With regard to individual-level determinants, individuals who reported adhering to social distancing guidelines were also more likely to report increases in healthy lifestyle behaviors (ß = 0.12, 95% CI 0.04 to 0.21). Conversely, women (ß = -0.37, 95% CI -0.62 to -0.12), and unemployed individuals (ß = -0.33, 95% CI -0.64 to -0.02) were less likely to report increases in healthy lifestyle behaviors. In addition, individuals reporting anxiety were more likely to report increases in addictive behaviors (ß = 0.26, 95% CI 0.09 to 0.43). Taken together, these findings suggest that women and unemployed individuals may benefit from interventions targeting diet and physical activity, and that individuals reporting anxiety may benefit from interventions targeting smoking and alcohol cessation to address lifestyle changes during the pandemic.


Assuntos
Controle de Doenças Transmissíveis , Feminino , Humanos , Estilo de Vida , Masculino , Inquéritos e Questionários , Estados Unidos/epidemiologia
4.
BMC Infect Dis ; 21(1): 388, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33902477

RESUMO

BACKGROUND: One of the leading long-term complications of type 2 diabetes mellitus (T2DM) includes renal dysfunction and urinary tract infections (UTI) which are considered to be prevalent in uncontrolled diabetes. Moreover, physiological factors like age, gender, duration of diabetes, other diabetic complications like neuropathy, autonomic neuropathy and glycosuria are also considered as predisposing factors for increased prevalence of UTI in diabetes which can be symptomatic or asymptomatic. METHODS: This was a cross-sectional, multi-centre study including diabetic patients from 12 clinical sites spread across major cities of Pakistan. The inclusion criteria were adult Pakistani population of age between 18 to 75 years both genders and suffering from T2DM irrespective of duration. A detailed clinical history of the past 3 months was recorded and, biochemical investigations of blood samples were conducted. Urine culture analysis performed identified the type of pathogen present and was done only for asymptomatic patients. RESULTS: A total of 745 type 2 diabetic patients were initially screened, out of 545 patients considered for final analysis 501 (91.92%) were negative and the rest 44 (8.08%) had positive urine culture. Female gender had a significantly higher proportion of positive urine culture (77.27%, p-value< 0.001). Body mass index and mean age had insignificant distribution among the two groups of positive and negative urine culture, with age 40-59 years having higher proportion (70.45%) in the positive group. Escherichia coli was detected in most of the positive samples (52.3%). All bacterial samples were found resistant to Ciprofloxacin. CONCLUSION: Diabetic Pakistani muslim female patients are identified to be at high risk of suffering from asymptomatic UTI and age more than 40 years is an important risk factor. Escherichia coli was the most common causative organism among people living in this geographical area.


Assuntos
Infecções Assintomáticas/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/etiologia , Escherichia coli/isolamento & purificação , Islamismo , Infecções Urinárias/epidemiologia , Infecções Urinárias/etiologia , Adolescente , Adulto , Fatores Etários , Idoso , Estudos Transversais , Infecções por Escherichia coli/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia , Prevalência , Fatores de Risco , Fatores Sexuais , Urinálise , Infecções Urinárias/microbiologia , Infecções Urinárias/urina , Adulto Jovem
5.
J Pak Med Assoc ; 71(2(A)): 497-501, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33819236

RESUMO

OBJECTIVE: To identify the vaccination status and risk factors for mortality in children admitted with complications of measles. METHODS: The retrospective study was conducted at Children Hospital, Pakistan Institute of Medical Sciences, Islamabad, Pakistan, and comprised data of children admitted with complications of measles between 2013 and 2017. Information on vaccination history, complications of measles, anthropometry, hospital stay and outcome within 15 days of admission was retrieved from hospital records. Data was analysed using Stata 14. RESULTS: Of the 307 children admitted, 79(26%) were aged <9 months and were excluded. Of the remaining 228 subjects, 109(47.8) were unvaccinated. Risk factors significantly associated with mortality were an unvaccinated state of measles vaccine, being stunted, and encephalitis in comparison with pneumonia (p<0.05). A total of 39(17%) children died within 15 days of admission. CONCLUSIONS: Encephalitis, non-vaccination and under-nutrition were significantly associated with mortality in children with complications of measles.

6.
Sensors (Basel) ; 21(4)2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33669314

RESUMO

Containers virtually package a piece of software and share the host Operating System (OS) upon deployment. This makes them notably light weight and suitable for dynamic service deployment at the network edge and Internet of Things (IoT) devices for reduced latency and energy consumption. Data collection, computation, and now intelligence is included in variety of IoT devices which have very tight latency and energy consumption conditions. Recent studies satisfy latency condition through containerized services deployment on IoT devices and gateways. They fail to account for the limited energy and computing resources of these devices which limit the scalability and concurrent services deployment. This paper aims to establish guidelines and identify critical factors for containerized services deployment on resource constrained IoT devices. For this purpose, two container orchestration tools (i.e., Docker Swarm and Kubernetes) are tested and compared on a baseline IoT gateways testbed. Experiments use Deep Learning driven data analytics and Intrusion Detection System services, and evaluate the time it takes to prepare and deploy a container (creation time), Central Processing Unit (CPU) utilization for concurrent containers deployment, memory usage under different traffic loads, and energy consumption. The results indicate that container creation time and memory usage are decisive factors for containerized micro service architecture.

7.
Infect Genet Evol ; 91: 104801, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33676010

RESUMO

Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) has first emerged from China in December 2019 and causes coronavirus induced disease 19 (COVID-19). Since then researchers worldwide have been struggling to detect the possible pathogenesis of this disease. COVID-19 showed a wide range of clinical behavior from asymptomatic to severe acute respiratory disease syndrome. However, the etiology of susceptibility to severe lung injury is not yet fully understood. Angiotensin-converting enzyme1 (ACE1) convert angiotensin I into Angiotensin II that was further metabolized by ACE 2 (ACE2). The binding ACE2 receptor to SARS-CoV-2 facilitate its enter into the host cell. The interaction and imbalance between ACE1 and ACE2 play a crucial role in the pathogenesis of lung injury. Thus, the aim of this study was to investigate the association of ACE1 I/D polymorphism with severity of Covid-19. The study included RT-PCR confirmed 269 cases of Covid-19. All cases were genotyped for ACE1 I/D polymorphism using polymerase chain reaction and followed by statistical analysis (SPSS, version 15.0). We found that ACE1 DD genotype, frequency of D allele, older age (≥46 years), unmarried status, and presence of diabetes and hypertension were significantly higher in severe COVID-19 patient. ACE1 ID genotype was significantly independently associated with high socio-economic COVID-19 patients (OR: 2.48, 95% CI: 1.331-4.609). These data suggest that the ACE1 genotype may impact the incidence and clinical outcome of COVID-19 and serve as a predictive marker for COVID-19 risk and severity.

8.
Eur J Pharm Sci ; 161: 105817, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33757829

RESUMO

The study was aimed to improve the aqueous solubility of atorvastatin (AT) and ameliorate permeability of metformin (MT) in a combination formulation, improving their oral bioavailability. Several AT-MT loaded polyvinylpyrrolidone (PVP) and hyaluronic acid (HA) based nanoparticles were prepared through electrospraying method (ES-NPs), and tested for physicochemical, in vitro, and in vivo parameters. Among the trialed formulations, a sample consisting of AT, MT, PVP, and HA at the weight ratio of 1/6.25/3.75/15 furnished the most satisfying solubility and release rate results. It enhanced approximately 10.3-fold and 3.6-fold solubility of AT as compared with AT powder and marketed product (Lipilow) in phosphate buffer pH = 6.8, respectively. Whereas, permeation of MT was 1.60-fold and 1.47-fold improved as compared with MT powder and marketed product (Glucophage), respectively. As compared with Lipilow, AUC (0-∞) and Cmax of AT with ES-NPs in rats were improved to 3.6-fold and 3.2-fold, respectively. Similarly, as compared with Glucophage, AUC (0-∞) and Cmax of MT were improved to 2.3-fold and 1.8-fold, respectively. Thus, ES-NPs significantly enhanced the solubility of AT (a BCS class II drug) and permeability of MT (a BCS class III drug) and might be a promising drug delivery system for co-delivery of these drugs.

9.
Nucleic Acid Ther ; 31(2): 93-113, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33534646

RESUMO

The designation of starting materials (SMs) for pharmaceuticals has been a topic of great interest and debate since the first ICH quality guidance was published. The increase in the number and variety of commercialized oligonucleotides (antisense oligonucleotides-ASOs, small interfering RNAs-siRNAs, etc.) in recent years has reignited dialogue on this topic because of the unique complexity of the monomeric nucleotides and other contributory materials used to manufacture oligonucleotides. The SM working group in the European Pharma Oligonucleotide Consortium (EPOC) was formed to help establish simple, risk-based criteria to guide the justification of oligonucleotide SMs. This article provides a description of the common types of SMs, classes of SM impurities, and control strategies that will be helpful to maintain manufacturing consistency.

10.
Clin Ther ; 43(2): 320-335, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33581878

RESUMO

PURPOSE: Some classes of glucose-lowering medications, including sodium-glucose co-transporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1-receptor agonists (GLP1-RAs) have cardio-protective benefit, but it is unclear whether this influences prescribing in the United Kingdom (UK). This study aims to describe class-level prescribing in adults with type 2 diabetes mellitus (T2DM) by cardiovascular disease (CVD) history using the Clinical Practice Research Datalink (CPRD). METHODS: Four cross-sections of people with T2DM aged 18-90 and registered with their general practice for >1 year on 1st January 2017 (n = 166,012), 1st January 2018 (n = 155,290), 1st January 2019 (n = 152,602) and 31st December 2019 (n = 143,373) were identified. Age-standardised proportions for class use through time were calculated separately in those with and without CVD history and by total number of medications prescribed (one, two, three, four+). An analysis by UK country was also performed. FINDINGS: Around 31% of patients had CVD history at each cross-section. Metformin was the most common treatment (>70% of those with and without CVD had prescriptions across all treatment lines). Overall use of SGLT2is and GLP1-RAs was low, with slightly less use in patients with CVD (SGLT2i: 9.8% and 13.8% in those with and without CVD respectively; GLP1-RA: 4.3% and 4.9%, December 2019). Use of SGLT2is as part of dual therapy was low but rose throughout the study. In January 2017, estimated use was 8.0% (95% CI 6.9-9.1%) and 8.9% (8.6-9.3%) in those with and without CVD. By December 2019 this reached 18.3% (17.0-19.5%) and 21.2% (20.6-21.7%) for those with and without CVD respectively. SGLT2i use as triple therapy increased: 22.7% (21.0-24.4%) and 25.9% (25.2-26.6%) in January 2017 to 41.3% (39.5-43.0%) and 45.5% (44.7-46.3%) in December 2019. GLP1-RA use also increased, but observed usage remained lower than SGLT2 inhibitors. Insulin use remained stable throughout, with higher use observed in those with CVD (16% vs 9.7% Dec 2019). Time trends in England, Wales, Scotland and Northern Ireland were similar, although class prevalence varied. IMPLICATIONS: Although use of SGLT2is and GLP1-RAs has increased, overall usage remains low with slightly lower use in those with CVD history, suggesting there is opportunity to optimise use of these medicines in T2DM patients to manage CVD risk. Insulin use was substantially more prevalent in those with CVD despite no evidence of CVD benefit. Further investigation of factors influencing this finding may highlight strategies to improve patient access to the most appropriate treatments, including those with evidence of cardiovascular benefit.

11.
Anesth Analg ; 132(4): 1138-1145, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33617181

RESUMO

BACKGROUND: Epidural block are often used for analgesia after open nephrectomy surgery. Subcostal anterior quadratus lumborum block may be an alternative. We therefore tested the hypothesis that the continuous subcostal anterior quadratus lumborum block is noninferior to epidural block for analgesia in patients having open partial nephrectomies. METHODS: Adults having open partial nephrectomies were randomly allocated to epidural or unilateral subcostal anterior quadratus lumborum block. The joint primary outcomes were opioid consumption measured in morphine equivalents and pain measured on a numeric rating scale (0-10) from postanesthesia care unit (PACU) until 72 hours after surgery. The noninferiority deltas were 30% for opioid consumption and 1 point on a 0-10 scale for pain. Secondary outcomes included patient global assessment of pain management on the third postoperative day, the number of antiemetic medication doses through the third postoperative day, duration of PACU stay, and postoperative duration of hospitalization. RESULTS: Twenty-six patients were randomized to anterior quadratus lumborum block and 29 to epidural analgesia. Neither pain scores nor opioid consumption in the quadratus lumborum patients were noninferior to epidural analgesia. At 72 hours, mean ± standard deviation pain scores in subcoastal anterior quadratus lumborum block and epidural group were 4.7 ± 1.8 and 4.1 ± 1.7, with an estimated difference in pain scores of 0.62 (95% confidence interval [CI], 0.74-1.99; noninferiority P = .21). The median [Q1, Q3] opioid consumption was more than doubled in quadratus lumborum patients at 70 mg [43, 125] versus 30 mg [18, 75] in the epidural group with an estimated ratio of geometric means of 1.69 (95% CI, 0.66-4.33; noninferiority P = .80). Patient global assessment and duration of PACU and hospital stays did not differ significantly in the 2 groups. CONCLUSIONS: We were unable to show that subcostal anterior quadratus lumborum block are noninferior to epidural analgesia in terms of pain scores and opioid consumption for open partial nephrectomies. Effectiveness of novel blocks should be rigorously tested in specific surgical setting before widespread adoption.


Assuntos
Analgesia Epidural , Nefrectomia , Bloqueio Nervoso , Dor Pós-Operatória/prevenção & controle , Idoso , Analgesia Epidural/efeitos adversos , Analgésicos Opioides/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefrectomia/efeitos adversos , Bloqueio Nervoso/efeitos adversos , Ohio , Medição da Dor , Limiar da Dor/efeitos dos fármacos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
12.
Mater Sci Eng C Mater Biol Appl ; 121: 111851, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33579485

RESUMO

Ulcerative colitis (UC) is an idiopathic bowel disease involving chronic inflammation and ulcers in colon and implicates severe epithelial damage with disruption in colon homeostasis. Presently existing treatments possess serious concerns like off target effects and adverse reactions, drug inactivation, poor absorption and other complications resulting in poor bioavailability. In context of high risk of thrombotic events in UC patients, heparin can offer appreciable benefits in UC management due to its remarkable anti-coagulating properties, its ability to intervene inflammatory pathways and acceleration of wound healing process. However, oral administration of heparin being impractical due to harsh gastric acidic environment and heparin degradation, conventional heparin administration is done via intravenous route. Present study was designed to formulate, characterize and evaluate sustained release heparin formulation in mice model of experimental colitis. Heparin liposomes (HLp) were formulated by solvent evaporation and extrusion process and possessed hydrodynamic diameter of 242 ± 4.3 nm. Size, shape and surface morphology was confirmed by TEM, SEM and AFM micrographs while encapsulation efficiency and loading of heparin in optimized HLp were 59.61% and 12.27%, respectively. HLp enema administration ameliorated gross disease indices like body weight, colon length, stool consistency, fecal occult blood. Further, anti-inflammatory efficacy of HLp was established in histopathological analysis where HLp appreciably restored protective mucin layer, colon epithelial mucosal histoarchitecture and considerably attenuated mast cell infiltration in colon epithelia. Overall, results of this study indicate that HLp demonstrated an appreciable therapeutic efficacy in experimental colitis and these results are attributed to their ability to suppress inflammation.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33563161

RESUMO

BACKGROUND: Peganum harmala is traditionally used to manage rheumatoid arthritis (RA) and other inflammatory conditions. However, its use against RA has not been scientifically evaluated. The current study was designed to assess the anti-arthritic and anti-inflammatory activities of the methanolic extract of P. harmala leaves by in vitro and in vivo methods. METHODS: The in vitro assays were carried out to determine the effect of plant extract on inhibition of egg albumin denaturation and human red blood cell membrane (HRBC) stabilization. Moreover, 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity was performed to determine the antioxidant potential. In vivo anti-arthritic activity was performed by determining the curative effect against Complete Freund's adjuvant (0.1 ml). The plant extract was administered to rats orally at 200, 400 and 600 mg/kg/day for 21 days. RESULTS: The values of IC50 of plant extract in protein denaturation, stabilization of HRBC and DPPH assays were 77.54 mg/ml, 23.90 mg/ml and 58.09 µg/ml respectively. Moreover, the plant extract significantly attenuated the poly-arthritis and weight loss, anemia and paw edema. The plant extract restored the level of C-reactive protein, rheumatoid factor, alanine transaminase, aspartate transaminase and alkaline phosphatase in poly-arthritic rats. Moreover, the plant extract restored the immune organs weight in treated rats. Treatment with P. harmala also significantly subdued the oxidative stress by reinstating superoxide dismutase, reduced glutathione, catalase and malondialdehyde in poly-arthritic rats. The plant extract notably restored the prostaglandin-E2 and tumor necrosis factor (TNF)-α in the serum of poly-arthritic rats. CONCLUSION: It was concluded that P. harmala extract had potential antioxidant, anti-inflammatory and antiarthritic activities which primarily might be attributed to alkaloids, flavonoids and phenols.

14.
Mater Sci Eng C Mater Biol Appl ; 120: 111700, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33545859

RESUMO

Stroke remains the leading cause of morbidity and mortality. Stem cell-based therapy offers promising hope for survivors and their families. Despite the clinical translation of stem cell-based therapies in stroke patients for almost two decades, results of these randomized controlled trials are not very optimistic. In these lines, an amalgamation of nanocarriers based drug delivery with stem cells holds great promise in enhancing stroke recovery. In the present study, we treated oxygen-glucose deprivation (OGD) exposed dental pulp stem cells (DPSCs) and mesenchymal stem cells (MSCs) with sivelestat-loaded nanostructured lipid carriers (NLCs). Various physicochemical limitations associated with sivelestat drug applications and its recent inefficacy in the clinical trials necessitates the development of novel delivery approaches for sivelestat. Therefore, to improve its efficacy on the survival of DPSCs and MSCs cell types under OGD insult, the current NLCs were formulated and characterized. Resulting NLCs exhibited a hydrodynamic diameter of 160-180 nm by DLS technique and possessed good PDI values of 0.2-0.3. Their shape, size and surface morphology were corroborated with microscopic techniques like TEM, SEM, and AFM. FTIR and UV-Vis techniques confirmed nanocarrier's loading capacity, encapsulation efficiency of sivelestat, and drug release profile. Oxidative stress in DPSCs and MSCs was assessed by DHE and DCFDA staining, and cell viability was assessed by Trypan blue exclusion test and MTT assay. Results indicated that sivelestat-loaded NLCs protected the loss of cell membrane integrity and restored cell morphology. Furthermore, NLCs successfully defended human DPSCs and MSCs against OGD-induced oxidative and inflammatory stress. In conclusion, modulation of oxidative and inflammatory stress by treatment with sivelestat-loaded NLCs in DPSCs and MSCs provides a novel strategy to rescue stem cells during ischemic stroke.

15.
Carbohydr Polym ; 258: 117600, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33593531

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune disorder and serious cause of disability. Despite considerable advances in RA management, challenges like extensive drug metabolism and rapid clearance causes poor bioavailability. Core-shell nanocarriers for co-delivery of glycyrrhizic acid (GA) and budesonide against RA were developed. GA-loaded gelatin nanoparticles (NPs) were synthesized and coated with budesonide encapsulated aminocellulose-grafted polycaprolactone (PCL-AC). GA- and budesonide-loaded PCL-AC-gel NPs had diameter of 200-225 nm. Dual drug-loaded (DDL) NPs reduced joint swelling and erythema in rats while markedly ameliorating bone erosion evidenced by radiological analysis, suppressed collagen destruction, restored synovial tissue, bone and cartilage histoarchitecture with reduced inflammatory cells infiltration. NPs also reduced various inflammatory biomarkers such as TNF-α, IL-1ß, COX-2, iNOS. Results of this study suggest that dual NPs exerted superior therapeutic effects in RA compared to free drugs which may be attributed to slow and sustained drug release and NPs' ability to inhibit inflammatory mediators.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33477726

RESUMO

Plastic waste management has become a serious environmental and health concern owing to large amounts of plastic deposits globally. Recently, innovative and sustainable solutions have been introduced (e.g., bio-nanomaterial plastics) to overcome the growing environmental threats. Hence, green marketers need to develop effective advertising campaigns to enhance the usage of bio-nanomaterial plastics. Past literature has suggested that cultural value-laden advertising appeals can give sustainable behavioral cues to consumers. Hence, this research unfolds the underlying cultural dimensions between the value-laden eco-friendly advertising appeals and intention to use bio-nanomaterial plastics (henceforth IBP). The present study proposes a moderating model in which two dimensions presented in the Global Leadership and Organizational Behavior Effectiveness (henceforth GLOBE) framework interact with the individuals' perception of eco-friendly advertising appeals (henceforth IPEA) to drive bio-nanomaterial plastics usage. The model was tested by conducting an experimental study on a sample of 364 Pakistani consumers. Findings of structural equation modeling show a significant difference in the relationship between IPEA and IBP, which is moderated by the performance orientation (henceforth PO) and institutional collectivism (henceforth IC) dimensions with diverse intensity. These findings validate the effectiveness of PO and IC (as cultural dimensions) and eco-friendly advertisements that can potentially promote the consumption of bio-nanomaterials plastic.


Assuntos
Nanoestruturas , Gerenciamento de Resíduos , Publicidade , Humanos , Intenção , Plásticos
17.
BMC Public Health ; 21(1): 44, 2021 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407294

RESUMO

BACKGROUND: Inactivated Polio Vaccine (IPV) campaign was conducted in February 2019 in Karachi where needle-free injectors were introduced for the administration of the fractional dose of IPV (fIPV) on a large scale. This study aimed to determine the impact of needle-free injectors on vaccination coverage. METHODS: In four towns of Karachi, fIPV was given using needle-free injectors "PharmaJet Tropis ID". Whereas, in six towns full dose of IPV was administered to children of 4-59 months of age. Cluster surveys through rapid convenience assessment method were conducted after the completion of vaccination activity. RESULTS: A total of 33,815 households' data was analyzed. Among these, 27,650 (82.8%) children were vaccinated. In fIPV areas, 85.3% of children were vaccinated compared to 79.5% in full dose IPV areas. A comparison of reasons for unvaccinated showed that 1.6% of parents do not give importance to vaccination in fIPV areas compared to 4.2% in full IPV areas (p-value < 0.0001). More children were not vaccinated due to fear of injection 1.8% in full IPV areas compared to 0.7% in fIPV areas (p-value < 0.0001). The source of campaign information shows that more frequent mobile miking 3.1% was observed in fIPV areas compared to 0.4% in full IPV areas (p-value < 0.0001). CONCLUSIONS: Our analysis supports the fractional dose of IPV in mass campaigns to achieve good vaccination coverage especially using needle-free injectors "PharmaJet Tropis ID" and vigorous social mobilization activities are expedient in accomplishing high coverage.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33483931

RESUMO

Environmental degradation has severely affected the natural cycle of ecosystem. It's high time now and humans should execute strategies effectively to protect the further degradation. Initially, we need to understand the ways that might affect the environment. Thus, existing research is designed to explore the nonlinear association between financial development (FD) and carbon dioxide emissions (CO2) in the context of low-income countries by employing the yearly data of 1990-2016. The panel smooth transition regression model (PSTR) is applied, and the result confirmed that the nexus between the two variables are nonlinear. Moreover, it also shows that at a low regime, FD increases the CO2 emissions but as the economy of low-income states progress to the high regime, the association between the two variables becomes negative and significant. The study also confirms that FD can reduce CO2 emissions once it reaches a certain threshold point. Based on these findings, new insights are provided for the policymakers, and several policies are suggested to improve the environmental quality in low-income countries.

19.
Am J Case Rep ; 22: e929002, 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33493142

RESUMO

BACKGROUND Apixaban is one of the newer direct oral anticoagulants (DOACs) being used to manage venous thrombosis. Skin toxicities are recognized adverse effects of the new DOACs, but are rare and usually associated with vasculitis. This report is of a 78-year-old man admitted to the hospital with pulmonary thromboembolism, who developed severe and extensive skin necrosis of both forearms 7 days after treatment with apixaban. CASE REPORT A 78-year-old man was admitted for pulmonary embolism and congestive heart failure exacerbation. He was started on therapeutic enoxaparin and diuresis. Later on, enoxaparin was substituted with apixaban. Seven days after starting apixaban, he suddenly developed skin changes that developed into skin necrosis on both forearms and the abdominal wall. A skin biopsy was not performed due to the high risk of bleeding. Skin necrosis was diagnosed based on clinical findings. A review of clinical data and the patient's medication profile did not reveal any other possible etiology or culprit medication. Clinical presentation and lab values were not consistent with infections or autoimmune etiologies. Apixaban was discontinued as it was perceived to be the likely cause of skin necrosis. The skin changes gradually improved within 1 week with supportive wound care, and the patient did not require a skin graft. The patient was discharged safely with subcutaneous low-molecular-weight heparin therapy. CONCLUSIONS This report shows that skin toxicity can be associated with apixaban and that with the increasing use of these newer DOACs, clinicians should be aware of these potential adverse effects.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33442799

RESUMO

The current investigation examines causal relation between PPP investment in energy sector and CO2 emissions in selected developing countries by using non-parametric causality in quantiles and linear granger causality techniques. Range of the data is from January 1998 to December 2016. Although results obtained by linear granger causality test does not report any causal relation between PPP investment in energy and CO2 emissions, but findings from non-parametric test show that non-linear relationship exhibit between variables. The non-parametric outcomes indicate that PPP investment in non-renewable energy in the selected countries contribute to carbon emissions and thus degrade environment. And therefore, the need is to divert PPP investment to renewable energy where it is more effective. This investigation provides valuable information to policy-makers in developing countries to think out of box and address pressing environmental issues.

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