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TDP-43 pathology is found in several neurodegenerative disorders, collectively referred to as "TDP-43 proteinopathies". Aggregates of TDP-43 are present in the brains and spinal cords of >97% of amyotrophic lateral sclerosis (ALS), and in brains of â¼50% of frontotemporal dementia (FTD) patients. While mutations in the TDP-43 gene (TARDBP) are usually associated with ALS, many clinical reports have linked these mutations to cognitive impairments and/or FTD, but also to other neurodegenerative disorders including Parkinsonism (PD) or progressive supranuclear palsy (PSP). TDP-43 is a ubiquitously expressed, highly conserved RNA-binding protein that is involved in many cellular processes, mainly RNA metabolism. To investigate systemic pathological mechanisms in TDP-43 proteinopathies, aiming to capture the pleiotropic effects of TDP-43 mutations, we have further characterised a mouse model carrying a point mutation (M323K) within the endogenous Tardbp gene. Homozygous mutant mice developed cognitive and behavioural deficits as early as 3 months of age. This was coupled with significant brain structural abnormalities, mainly in the cortex, hippocampus, and white matter fibres, together with progressive cortical interneuron degeneration and neuroinflammation. At the motor level, progressive phenotypes appeared around 6 months of age. Thus, cognitive phenotypes appeared to be of a developmental origin with a mild associated progressive neurodegeneration, while the motor and neuromuscular phenotypes seemed neurodegenerative, underlined by a progressive loss of upper and lower motor neurons as well as distal denervation. This is accompanied by progressive elevated TDP-43 protein and mRNA levels in cortex and spinal cord of homozygous mutant mice from 3 months of age, together with increased cytoplasmic TDP-43 mislocalisation in cortex, hippocampus, hypothalamus, and spinal cord at 12 months of age. In conclusion, we find that Tardbp M323K homozygous mutant mice model many aspects of human TDP-43 proteinopathies, evidencing a dual role for TDP-43 in brain morphogenesis as well as in the maintenance of the motor system, making them an ideal in vivo model system to study the complex biology of TDP-43.
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Esclerose Lateral Amiotrófica , Demência Frontotemporal , Proteinopatias TDP-43 , Animais , Pré-Escolar , Humanos , Camundongos , Esclerose Lateral Amiotrófica/metabolismo , Encéfalo/metabolismo , Cognição , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Demência Frontotemporal/genética , Demência Frontotemporal/patologia , Proteinopatias TDP-43/genética , Proteinopatias TDP-43/patologiaRESUMO
This study was conducted to determine the effect of acidophilus yoghurt (yoghurt fortified with Lactobacillus acidophilus) in comparison to traditional plain yoghurt (St. thermophilus and L. bulgaricus starter cultures) on the survival of three pathogenic Escherichia coli strains; Shiga toxigenic O157 (STx O157), non-toxigenic O157 (Non-STx O157) and Shiga toxigenic non-O157 (STx O145). After six days of refrigerated storage of laboratory-manufactured yoghurt inoculated with the three strains of E. coli separately, all were eliminated in acidophilus yoghurt, while their survival extended in the traditional yoghurt along the storage period (17 d). Reduction percentages of the tested strains in acidophilus yoghurt were 99.93, 99.93 and 99.86%, with log reduction of 3.176, 3.176, and 2.865 cfu/g for Stx O157, Non-Stx O157, and Stx O145 E. coli, respectively, in comparison to 91.67, 93.33 and 93.33%, with log reduction of 1.079, 1.176 and 1.176 cfu/g in traditional yoghurt. Statistical analysis showed a significant effect of acidophilus yoghurt in reducing the count of Stx E. coli O157 (P = 0.001), Non-Stx E. coli O157 (P < 0.01) and Stx E. coli O145 (P < 0.01) compared to the traditional yoghurt. These findings emphasize the potential use of acidophilus yoghurt as a biocontrol alternative method for eliminating pathogenic E. coli, as well as other similar applications in the dairy industry.
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Nontuberculous mycobacteria (NTM) compose a group of mycobacteria that do not belong to the Mycobacterium tuberculosis complex group. They are frequently isolated from environmental samples such as water, soil, and, to a lesser extent, food samples. Isolates of NTM represent a major health threat to humans worldwide, especially those who have asthma or are immunocompromised. Human disease is acquired from environmental exposures and through consumption of NTM-contaminated food. The most common clinical manifestation of NTM disease in human is lung disease, but lymphatic, skin and soft tissue, and disseminated disease are also important. The main objective of the current study was to profile the farm-level contamination of cow milk with NTM by examining milk filters and bulk tank milk samples. Five different NTM species were isolated in one dairy herd in Wisconsin, with confirmed 16S rRNA genotypes including Mycobacterium fortuitum, Mycobacterium avium ssp. hominissuis, Mycobacterium abscessus, Mycobacterium simiae, and Mycobacterium avium ssp. paratuberculosis (Mycobacterium paratuberculosis). In tank milk samples, M. fortuitum was the predominant species in 48% of the samples, whereas M. chelonae/abscessus and M. fortuitum were the only 2 species obtained from 77 and 23% of the examined filters, respectively. Surprisingly, M. avium ssp. hominissuis, M. paratuberculosis, and M. simiae were isolated from 16.7, 10.4, and 4% of the examined milk samples, respectively, but not from milk filters. Interestingly, NTM isolates from human clinical cases in Wisconsin clustered very closely with those from milk samples. These findings suggest that the problem of NTM contamination is underestimated in dairy herds and could contribute to human infections with NTM. Overall, the study validates the use of bulk tank samples rather than milk filters to assess contamination of milk with NTM. Nontuberculous mycobacteria represent one type of pathogens that extensively contaminate raw milk at the farm level. The significance of our research is in evaluating the existence of NTM at the farm level and identifying a simple approach to examine the potential milk contamination with NTM members using tank milk or milk filters from dairy operations. In addition, we attempted to examine the potential link between NTM isolates found in the farm to those circulating in humans in Wisconsin.
Assuntos
Leite/microbiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas/classificação , Micobactérias não Tuberculosas/genética , Animais , Bovinos , Feminino , Contaminação de Alimentos , Armazenamento de Alimentos , Genótipo , Humanos , Mycobacterium/isolamento & purificação , Infecções por Mycobacterium não Tuberculosas/veterinária , Mycobacterium avium subsp. paratuberculosis/genética , Micobactérias não Tuberculosas/isolamento & purificação , RNA Ribossômico 16S , WisconsinRESUMO
Heat shock proteins (Hsps) have long been candidates for ecological adaptation given their unequivocal role in mitigating cell damage from heat stress, but linking Hsps to heat tolerance has proven difficult given the complexity of thermal adaptation. Experimental evolution has been utilized to examine direct and correlated responses to selection for increased heat tolerance in Drosophila, often focusing on the major Hsp family Hsp70 and/or the master regulator HSF as a selection response, but rarely on other aspects of the heat shock complex. We examined Hsp70 and co-chaperone stv isoform transcript expression in Australian D. melanogaster lines selected for static heat tolerance, and observed a temporal and stv isoform specific, coordinated transcriptional selection response with Hsp70, suggesting that increased chaperone output accompanied increased heat tolerance. We hypothesize that the coordinated evolutionary response of Hsp70 and stv may have arisen as a correlated response resulting from a shared regulatory hierarchy. Our work highlights the complexity and specificity of the heat shock response in D. melanogaster. The selected lines examined also showed correlated responses for other measures of heat tolerance, and the coevolution of Hsp70 and stv provide new avenues to examine the common mechanisms underpinning direct and correlated phenotypic responses to selection for heat tolerance.
Assuntos
Coevolução Biológica , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Proteínas de Choque Térmico HSP70/metabolismo , Termotolerância/genética , Animais , Drosophila melanogaster/metabolismo , Feminino , Masculino , Seleção GenéticaRESUMO
Neurodegenerative disease encompasses a wide range of disorders afflicting the central and peripheral nervous systems and is a major unmet biomedical need of our time. There are very limited treatments, and no cures, for most of these diseases, including Alzheimer's Disease, Parkinson's Disease, Huntington Disease, and Motor Neuron Diseases. Mouse and other animal models provide hope by analysing them to understand pathogenic mechanisms, to identify drug targets, and to develop gene therapies and stem cell therapies. However, despite many decades of research, virtually no new treatments have reached the clinic. Increasingly, it is apparent that human heterogeneity within clinically defined neurodegenerative disorders, and between patients with the same genetic mutations, significantly impacts disease presentation and, potentially, therapeutic efficacy. Therefore, stratifying patients according to genetics, lifestyle, disease presentation, ethnicity, and other parameters may hold the key to bringing effective therapies from the bench to the clinic. Here, we discuss genetic and cellular humanised mouse models, and how they help in defining the genetic and environmental parameters associated with neurodegenerative disease, and so help in developing effective precision medicine strategies for future healthcare.
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Modelos Animais de Doenças , Doenças Neurodegenerativas/terapia , Medicina de Precisão , Animais , Quimera , Humanos , Camundongos , Camundongos Transgênicos , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/patologia , Doenças Neurodegenerativas/fisiopatologia , FenótipoRESUMO
Current research on metal-organic framework (MOF) luminescent sensing probes focuses on the design of three-dimensional bulk-sized MOFs that in return limits their up-close interactions with targeted guest molecules. In this work, we report a two-dimensional (2D) copper-based metal-organic framework, namely, AUBM-6, synthesized via solvothermal method from isonicotinic acid linker and copper(II) ion. The resulting 2D-layered MOF crystals were highly fluorescent in their exfoliated form and, therefore, explored for detecting several solvents, where a ratiometric selectivity was shown toward acetone. Metal ion sensing was also performed, by which fluorescent detection was observed to have the highest turn-off quenching efficiency toward Pd2+.
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Infection with Mycobacterium avium ssp. paratuberculosis (M. paratuberculosis) is a widespread problem in the United States and worldwide, and it constitutes a significant health problem for dairy animals with a potential effect on human health. Mycobacterium paratuberculosis is easily transmitted through consumption of contaminated milk; therefore, finding safe methods to reduce the mycobacterial load in milk and other dairy products is important to the dairy industry. The main objective of the current study was to investigate the effect of natural products, such as bacteriocins designated as "generally regarded as safe" (GRAS), on the survival of M. paratuberculosis in milk. Commercially synthesized bacteriocin (nisin) was used to examine its effect on the survival of laboratory and field isolates of M. paratuberculosis and in contaminated milk. Surprisingly, nisin had a higher minimum inhibitory concentration (MIC) against the laboratory strain (M. paratuberculosis K10), at 500 U/mL, than against field isolates (e.g., M. paratuberculosis 4B and JTC 1281), at 15 U/mL. In milk, growth of M. paratuberculosis was inhibited after treatment with levels of nisin that are permissible in human food at 4°C and 37°C. Using both fluorescent and scanning electron microscopy, we were able to identify defects in the bacterial cell walls of treated cultures. Our analysis indicated that nisin reduced membrane integrity by forming pores in the mycobacterial cell wall, thereby decreasing survival of M. paratuberculosis. Thus, nisin treatment of milk could be implemented as a control measure to reduce M. paratuberculosis secreted in milk from infected herds. Nisin could also be used to reduce M. paratuberculosis in colostrum given to calves from infected animals, improving biosecurity control in dairy herds affected by Johne's disease.
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Antibacterianos/farmacologia , Parede Celular/efeitos dos fármacos , Leite/microbiologia , Mycobacterium avium subsp. paratuberculosis/efeitos dos fármacos , Nisina/farmacologia , Animais , Bovinos , Colostro/microbiologia , Feminino , Mycobacterium avium subsp. paratuberculosis/isolamento & purificaçãoRESUMO
Metal-organic frameworks (MOFs) have emerged as an important class of hybrid organic-inorganic materials. One of the reasons they have gained remarkable attention is attributed to the possibility of altering them by postsynthetic modification, thereby providing access to new and novel advanced materials. MOFs have been applied in catalysis, gas storage, gas separation, chemical sensing, and drug delivery. However, their bactericidal use has rarely been explored. Herein, we developed a two-step process for the synthesis of zirconium-based MOFs metalated with silver cations as a potent antibacterial agent. The obtained products were thoroughly characterized by powder X-ray diffraction, scanning electron microscopy, UV-visible, IR, thermogravimetric, and Brunauer-Emmett-Teller analyses. Their potency was evaluated against E. coli with a reported minimal inhibitory concentration and minimal bactericidal concentration of as low as 6.5 µg/mL of silver content. Besides the novelty of the system, the advantage of this strategy is that the MOFs could be potentially regenerated and remetalated after each antibacterial test, unlike previously reported frameworks, which involved the destruction of the framework.
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Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Zircônio/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Tamanho da Partícula , Relação Estrutura-Atividade , Zircônio/químicaRESUMO
The current study aimed to investigate the protective effect of the cardenolide glycoside acovenoside A (AcoA) against doxorubicin-induced cardiotoxicity in mice. AcoA was isolated from the pericarps of Acokanthera oppositifolia to chemical homogeneity and characterized by means of one- and two-dimensional nuclear magnetic resonance spectroscopy. AcoA exhibited relatively low toxicity in mice (LD50 = 223.3 mg/kg bw). Repeated administration of doxorubicin induced cardiotoxicity manifested by reduced activity of myocardial membrane-bound ion pumps and elevated serum biomarkers of myocardial dysfunction, oxidative stress, and inflammation. Pretreatment of doxorubicin-exposed mice with AcoA (11.16 or 22.33 mg/kg bw, i.p.) for 2 weeks after 2 weeks of combined administration of AcoA and doxorubicin protected the animals dose dependently against doxorubicin-induced cardiotoxicity as indicated by normalization of the levels of different myocardial markers of oxidative stress (malondialdehyde, nitric oxide, total antioxidant capacity, and cardiac glutathione), serum myocardial diagnostic marker enzymes (serum cardiac troponin T, creatine kinase isoenzyme MB, aspartate aminotransferase, and lactate dehydrogenase), and inflammatory markers (c-reactive protein, tumor necrosis factor-α, and interleukin-6), as well as myocardial Na(+)/K(+)-ATPase activity. These effects were attributed to the negative impact of AcoA on transcription factors nuclear factor κB and interferon regulatory factor 3/7. Thus acovenoside A might act as a cardioprotective agent to prevent doxorubicin-induced cardiotoxicity.
Assuntos
Cardenolídeos/farmacologia , Cardiotônicos/farmacologia , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Doxorrubicina/efeitos adversos , Animais , Apocynaceae/química , Biocatálise , Biomarcadores/sangue , Cardenolídeos/química , Cardenolídeos/isolamento & purificação , Cardiotônicos/química , Cardiotônicos/isolamento & purificação , Cardiotoxicidade/metabolismo , Cardiotoxicidade/patologia , DNA Topoisomerases Tipo II/metabolismo , Fatores Reguladores de Interferon/metabolismo , Masculino , Camundongos , Membranas Mitocondriais/efeitos dos fármacos , Membranas Mitocondriais/enzimologia , Modelos Moleculares , Conformação Molecular , Miocárdio/metabolismo , Miocárdio/patologia , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
CONTEXT: Pecans are commonly used nuts with important health benefits such as anti-hyperglycemic and anti-hyperlipidemic effects. OBJECTIVE: A comparative investigation of the antihyperglycemic and total phenolic content of the leaves and shells of four pecan cultivars growing in Egypt was carried out. The selected cultivars (cv.) were Carya illinoinensis Wangneh. K. Koch. cv. Wichita, cv. WesternSchely, cv. Cherokee, and cv. Sioux family Juglandaceae. MATERIALS AND METHODS: Total phenolic and flavonoid contents of the leaves and shells of pecan cultivars were carried out using Folin-Ciocalteu's and aluminum chloride assays, respectively. Moreover, HPLC profiling of phenolic and flavonoid contents was carried out using RP-HPLC-UV. In addition, in vivo anti-hyperglycemic activity of the ethanolic extracts (125 mg/kg bw, p.o.) of C. illinoinensis cultivars was carried out using streptozotocin (STZ)-induced diabetes in Sprague-Dawley rats for 4 weeks. RESULTS AND DISCUSSION: Phenolic contents were higher in shells than leaves in all studied cultivars, while flavonoids were higher in leaves. Leaves and shells of cv. Sioux showed the highest phenolics (251.7 µg gallic acid equivalent (GAE)/g), and flavonoid contents (103.27 µg rutin equivalent (RE)/g and 210.67 µg quercetin equivalent (QE)/g), respectively. The HPLC profiling of C. illinoinensis cultivars resulted in the identification of eight flavonoids (five of these compounds are identified for the first time from pecan), and 15 phenolic acids (six are identified for the first time from pecan). Leaves of cv. Sioux revealed the most potent decrease in blood glucose and glycated hemoglobin (HbA1c%) (194.9 mg/dl and 6.52%, respectively), among other tested cultivars. Moreover, leaves of cv. Sioux significantly elevated serum total antioxidant capacity (TAC) and reduced glutathione (GSH) (0.33 mMol/l and 30.68 mg/dl, respectively), and significantly suppressed the markers of both lipid peroxidation (malondialdehyde, MDA) and protein oxidation (protein carbonyl, PC) (14.25 µmol/ml and 3.18 nmol/mg protein, respectively). CONCLUSION: Different pecan cultivars showed significant variation in its phenolic and flavonoid contents and consequently their antioxidant and anti-hyperglycemic effects.
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Carya , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Fenóis/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Diabetes Mellitus Experimental/metabolismo , Egito , Sequestradores de Radicais Livres/isolamento & purificação , Sequestradores de Radicais Livres/uso terapêutico , Hipoglicemiantes/isolamento & purificação , Masculino , Fenóis/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Ratos , Ratos Sprague-DawleyRESUMO
The association between parental burnout and perfectionism, and whether and to what extent it is mediated by self-compassion, in case of mothers of children with Specific Learning Disorder (SLD) were rarely investigated in the related literature. To fill the gap felt, the present study aimed at providing a model for self-compassion, parental burnout, and perfectionism. The participants were 305 mothers of children with SLD, from Hamedan province, Iran, who had been referred to the relevant treatment centers between 2020 and 2021. Selected through convenience sampling, they took part in the study by completing three questionnaires, i.e., Parental Burnout Assessment (Roskam et al., 2018), Multidimensional Perfectionism Scale (Hewitt & Flett, 1991), and Self-Compassion Scale (Neff, 2003). To fit the model, structural equation modelling was conducted in Amos v24 software. It was found that self-compassion mediates the negative relationship between parental burnout and perfectionism. It can be concluded that women during motherhood become emotionally vulnerable and are susceptible to face psychological challenges and such challenges can be exacerbated in the case of mothers of children with SLD or other learning disabilities.
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Empatia , Perfeccionismo , Humanos , Feminino , Adulto , Empatia/fisiologia , Irã (Geográfico) , Masculino , Transtorno de Aprendizagem Específico , Esgotamento Psicológico , Mães/psicologia , Criança , Inquéritos e Questionários , Estudantes/psicologia , Pais/psicologia , Pessoa de Meia-IdadeRESUMO
BACKGROUND: COVID-19 saw an increase in child mental health presentations internationally. Clinicians analogised the exponential increase in anorexia nervosa to a 'tsunami' or 'outbreak', raising parallel concerns regarding medical and psychological risks (Marsh in The Guardian, 2021; Leask in NZ Herald, 2021; Monteleone et al. in Eat Weight Disord 26(8):2443-2452, 2021) . It is unclear whether Ireland emulated this picture of increased referrals with increased medical compromise. AIMS: This paper examines both rates and clinical profiles of child eating disorder presentations in the Republic of Ireland (ROI), across different clinical settings. METHODS: Following ethical approval, retrospective chart reviews were conducted in a community eating disorder service and in two paediatric hospital settings. The time frame of the different studies ranged from January 2016 to December 2022. RESULTS: Community eating disorder services saw significantly higher referral rates post COVID-19 (3.78/month vs. 2.31/month, p = 0.02), with a shorter duration of illness (4.8 months vs. 7.4 months, p = 0.001), but no significant difference in ideal body weight % (IBW%) at referral (85.32% vs. 83.7%, p = 0.1). Both paediatric hospitals witnessed significantly increased referrals post-COVID-19 (hospital 1; 4.38/month vs. 1.93/month, p = 0.0001; hospital 2; 2.8/month vs. 0.92/month, p < 0.0001), but no significant difference in IBW% at assessment (hospital 1; 82.7% vs. 81.39%, p = 0.673; hospital 2; 81.5% vs. 83%, p = 0.563). There was no significant difference in clinical profile, management, or duration of hospital stay. CONCLUSIONS: This study supports the growing consensus of a pandemic specific increase in eating disorder referrals to both medical and psychiatry services. However, there was little to indicate a change in clinical profile or severity. Ongoing monitoring of referrals is necessary to ensure adequate service availability and expertise.
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COVID-19 , Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , COVID-19/epidemiologia , Irlanda/epidemiologia , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Estudos Retrospectivos , Criança , Feminino , Masculino , Adolescente , Encaminhamento e Consulta/estatística & dados numéricos , SARS-CoV-2RESUMO
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by significant metabolic disruptions, including weight loss and hypermetabolism in both patients and animal models. Leptin, an adipose-derived hormone, displays altered levels in ALS. Genetically reducing leptin levels (Lepob/+) to maintain body weight improved motor performance and extended survival in female SOD1G93A mice, although the exact molecular mechanisms behind these effects remain elusive. Here, we corroborated the sexual dimorphism in circulating leptin levels in ALS patients and in SOD1G93A mice. We reproduced a previous strategy to generate a genetically deficient leptin SOD1G93A mice (SOD1G93ALepob/+) and studied the transcriptomic profile in the subcutaneous adipose tissue and the spinal cord. We found that leptin deficiency reduced the inflammation pathways activated by the SOD1G93A mutation in the adipose tissue, but not in the spinal cord. These findings emphasize the importance of considering sex-specific approaches in metabolic therapies and highlight the role of leptin in the systemic modulation of ALS by regulating immune responses outside the central nervous system.
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Esclerose Lateral Amiotrófica , Animais , Feminino , Humanos , Masculino , Camundongos , Tecido Adiposo/metabolismo , Esclerose Lateral Amiotrófica/metabolismo , Modelos Animais de Doenças , Haploinsuficiência , Leptina/metabolismo , Camundongos Transgênicos , Medula Espinal/metabolismo , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismoRESUMO
Background: Smoking is a common problem in university students worldwide. Smoking is one of the most dangerous social phenomena and has a significant impact on public health. This study investigated the beliefs and attitudes of medical students toward smoking in Sudan. Methods: A cross-sectional study was conducted among medical students at Al Neelain University, Sudan, from March to June 2022 using a web-based questionnaire. The questionnaire consisted of eight items on demographic characteristics and 13 on the beliefs and attitudes toward smoking. Other data included smoking status, smoking habits, the number of cigarettes smoked per day, and smoking duration. Data analysis was performed descriptively, and chi-square test and logistic regression were conducted using SPSS version 24. Statistical significance was set at 0.05. Results: A total of 336 students participated in this study, and the smoking prevalence was 48.8% (41.1% in men and 7.7% in women). In total, 76.8% reported smoking daily at a rate of 5-10 cigarettes per day. In terms of students' beliefs about smoking, 86.8% disagreed with selling cigarettes at the university. Of the respondents, 68.4% did not approve smoking on campus. There was a relationship between smoking habits and the age group of 22-25 years, which was the highest smoking category among students (p-value = 0.01). Conclusion: The prevalence of cigarette smoking among medical students is disturbing, particularly as they are future doctors. There is a need to include plans to reduce smoking among students that can be incorporated into courses and special programs.
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Estudantes de Medicina , Produtos do Tabaco , Masculino , Humanos , Feminino , Adulto Jovem , Adulto , Estudos Transversais , Prevalência , Sudão/epidemiologia , Fumar/epidemiologiaRESUMO
Variants in the ubiquitously expressed DNA/RNA-binding protein FUS cause aggressive juvenile forms of amyotrophic lateral sclerosis (ALS). Most FUS mutation studies have focused on motor neuron degeneration; little is known about wider systemic or developmental effects. We studied pleiotropic phenotypes in a physiological knock-in mouse model carrying the pathogenic FUSDelta14 mutation in homozygosity. RNA sequencing of multiple organs aimed to identify pathways altered by the mutant protein in the systemic transcriptome, including metabolic tissues, given the link between ALS-frontotemporal dementia and altered metabolism. Few genes were commonly altered across all tissues, and most genes and pathways affected were generally tissue specific. Phenotypic assessment of mice revealed systemic metabolic alterations related to the pathway changes identified. Magnetic resonance imaging brain scans and histological characterisation revealed that homozygous FUSDelta14 brains were smaller than heterozygous and wild-type brains and displayed significant morphological alterations, including a thinner cortex, reduced neuronal number and increased gliosis, which correlated with early cognitive impairment and fatal seizures. These findings show that the disease aetiology of FUS variants can include both neurodevelopmental and systemic alterations.
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Esclerose Lateral Amiotrófica , Camundongos , Animais , Esclerose Lateral Amiotrófica/patologia , Sinais de Localização Nuclear/genética , Sinais de Localização Nuclear/metabolismo , Proteína FUS de Ligação a RNA/genética , Proteína FUS de Ligação a RNA/metabolismo , Mutação/genética , Neurônios/metabolismoRESUMO
Bergenin and 11-O-(4'-O-methyl galloyl)-bergenin, previously isolated from Crassula capitella extract, were used as starting materials for the synthesis of eight derivatives; four derivatives 2a-2d were synthesized from bergenin through the formation of ester derivatives and four alkyl derivatives 4a-4d were synthesized from 11-O-(4'-O-methyl galloyl)-bergenin. The structures of the synthesized analogues were confirmed upon 1 H and 13 C NMR spectroscopic elucidation. Antileishmanial and antitrypanosomal activities of the synthesized derivatives were evaluated, compounds 11-O-(3',5' di-benzyl, 4'-O-methyl galloyl)-8,10-di-O-benzyl-bergenin (4c) and 11-O-(3',5'di-4-chlorobenzyl,4'-O-methyl galloyl)-8,10di-O-4-chlorobenzyl bergenin (4d) showed potent antitrypanosomal activity with IC50 values of 0.52 and 0.5 µM, respectively and IC90 values of 0.66 µM against T. brucei compared with IC50 and IC90 values of 21.7 and 50.3 µM for the positive control difluoromethylornithine.
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Benzopiranos/farmacologia , Tripanossomicidas/farmacologia , Benzopiranos/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Concentração Inibidora 50 , Espectroscopia de Prótons por Ressonância Magnética , Relação Estrutura-Atividade , Tripanossomicidas/química , Trypanosoma brucei brucei/efeitos dos fármacosRESUMO
OBJECTIVES: To evaluate the effectiveness of adding a supervised physical therapy exercise program to photobiomodulation therapy (PBMT) in the treatment of cervicogenic somatosensory tinnitus (CST). METHODS: Forty patients suffering from CST with age 45-55 years were included in the study. They were assigned randomly into 2 groups, 20 per each. (Study group) Group (A) received a supervised physical therapy exercise program in addition to 20 minutes PBMT with a 650-nanometer wavelength and a 5 milliWatt power output, spot size of 1 cm2, and energy density of 6 Joules, 3 sessions per week for 8 consecutive weeks, plus traditional medical treatment. While (control group), group (B) received the same PBMT protocol, 3 sessions per week for 8 consecutive weeks in addition to the traditional medical treatment. Tinnitus visual analog scaling (VAS), tinnitus handicap inventory (THI), and cervical range of motion (ROM) were measured at baseline and after 8 weeks. RESULTS: Mixed MANOVA showed a statistically significant reduction in tinnitus VAS, THI, and a significant improvement in cervical ROM (flexion, extension, right bending, left bending, right rotation, and left rotation) in favor of Group A (P < .05). There was a significant decrease in posttreatment VAS treatment (P > .001) MD [-2.05(-2.68:-1.41)], and THI relative to pretreatment mean difference [-5.35(-8.51: -2.19)] and a significant increase in posttreatment neck ROM in Groups A and B relative to pretreatment neck ROM (P > .001). Flexion range posttreatment MD[3.65(1.64:5.65)], Extension MD [6.55(1.35:11.75)], right bending MD[3.8(2.51:5.08)], left bending MD[1.75(0.19:3.3)], right rotation MD [3.5(1.28:5.71)] and left rotation [2.75(0.67:4.82)]. CONCLUSIONS: Adding a supervised physical therapy exercise program to PBMT showed positive and beneficial effects in the treatment of CST using VAS, THI, and Cervical ROM assessment tools.
Assuntos
Terapia com Luz de Baixa Intensidade , Zumbido , Terapia por Exercício , Humanos , Pessoa de Meia-Idade , Modalidades de Fisioterapia , Amplitude de Movimento Articular , Zumbido/radioterapia , Resultado do TratamentoRESUMO
BACKGROUND: Cervicofacial burn (CB) is a unique type of burn, involving the lateral part of the face, neck and chest region with significant skin contractures. Temporomandibular joint (TJ) pain and orofacial myalgia (OM) are the major problems in physiotherapy context to treat. Laser is commonly used as an adjunct therapy in painful conditions. However, clinical studies are lacking in investigating the effects of gallium-arsenide (Ga-As) super pulsed laser therapy on temporomandibular joint pain and orofacial myalgia following healed cervicofacial burn patients. OBJECTIVE: To investigate the effects of clinical and functional efficacy of Ga-As super pulsed laser therapy on temporomandibular joint pain with orofacial myalgia following healed cervicofacial burn patients. METHODS: Through two block random sampling method, the eligible participants were randomized and allocated into active laser (Active-L; n = 18) and placebo laser (Placebo-L; n = 18) groups. The Active-L group received laser treatment and the Placebo-L group received placebo laser effect (inactive laser) with regular physiotherapy care for 3 times in a week for 4 weeks. Primary (pain intensity, pain threshold, pain frequency) and secondary (mouth opening, disability level and quality of life) measures were measured at baseline, after the end 4th week, 8th week and 6 month follow up. RESULTS: Baseline subjective and clinical attributes show homogenous presentation among the study groups (p > 0.05). After four weeks of treatment, and at the end of 6 months follow up, the pain intensity, 2.9 (CI 95% 2.80-3.00), pain threshold 19.2 (CI 95% -30.4 to -7.9), pain frequency 3.4 (CI 95% 3.14-3.65), mouth opening, -16.0 (CI 95%-16.5 to -15.4), disability level 11.3 (CI 95%11.14-11.45), and quality of life -31.7 (CI 95%-37.1 to -26.2) showed more improvement (p < 0.001) in Active-L group than Placebo-L group. CONCLUSION: The reports of this study proved that, four weeks active laser therapy with regular physiotherapy care has an ideal treatment protocol for temporomandibular joint pain with orofacial myalgia following healed cervicofacial burn. This study also provided a new knowledge for physiotherapists in the field of temporomandibular joint pain rehabilitation.
Assuntos
Queimaduras , Gálio , Transtornos da Articulação Temporomandibular , Artralgia , Queimaduras/complicações , Queimaduras/terapia , Gálio/uso terapêutico , Humanos , Mialgia/complicações , Mialgia/terapia , Qualidade de Vida , Transtornos da Articulação Temporomandibular/complicações , Transtornos da Articulação Temporomandibular/terapia , Resultado do TratamentoRESUMO
BACKGROUND: Inhalation injuries can cause problems with diaphragmatic mobility and pulmonary function, which are accompanied by significant morbidity and mortality. No previous studies have determined the outcomes of acupoint transcutaneous electrical stimulation (Acu-TENS) in the treatment of inhalation burn injuries. The current study is therefore aimed at evaluating the influences of Acu-TENS on pulmonary functions and diaphragmatic mobility in adult-male patients experiencing after burn inhalation injury. METHODS: This randomized controlled study was double blinded in an inpatient setting and was conducted between June 2018 and July 2019. Forty-male participants with inhalation-injury (20-40 yrs.) were randomly allocated into two study and control groups equal in numbers; the same pulmonary rehabilitation program plus early mobility exercise was conducted in both groups. The study group (group A) received additional Acu-TENS while shame Acu-TENS was carried out on the control group (group B). The intervention program continued for four weeks, three sessions a week for 45 min bilaterally on the bilateral Ding-Chuan points (Ex-B1). Spirometry was used to assess pulmonary functions, the 5-points-Likert scale was used to assess dyspnea, and ultrasonography was used to assess diaphragmatic mobility (DM), and evaluations were performed before and after interventions. RESULTS: At baseline assessment, no significant differences were detected between the two study groups (pË0.05). In the post-interventional program, a noteworthy difference was detected in all outcome measures in the two study groups (pË0.05), supporting group A. After 4 weeks of intervention, the mean (SD) for FVC, FEV1, and DM was 83.7 ± 4.34, 86.75 ± 4.59, and 5.93 ± 1.13 in group A, 79.65 ± 5.14, 83.1 ± 4.44, and 5.08 ± 1.15, in-group B. The mean difference for FVC, FEV1, and DM was 4.05 (1: 7.09), 3.65 (0.75: 6.54), and 0.85 (0.11: 1.57) between groups after treatment, respectively. CONCLUSION: Depending on the study findings, Acu-TENS on bilateral Ding-Chuan points could be considered an effective approach for improving pulmonary functions and diaphragmatic mobility in patients with inhalation injuries after thermal burn. Future studies with a larger sample size and longer duration on different types of burn injuries are recommended.
Assuntos
Queimaduras , Lesão Pulmonar , Estimulação Elétrica Nervosa Transcutânea , Adulto , Humanos , Masculino , Pontos de Acupuntura , Queimaduras/complicações , Queimaduras/terapia , Pulmão/diagnóstico por imagem , Método Duplo-CegoRESUMO
BACKGROUND: Burns to the thorax are at high risk for long-term pulmonary complications due to chest muscle contractures and chronic inflammation in both adolescents and young adults. Few studies have investigated the effects of arm cycling exercise in those individuals. For that reason, this study examined pulmonary function, functional capacity, and quality of life (QOL) in adolescents with thoracic burns subsequent to 2-month arm cycling exercise programme. METHODS: A single-blinded, two-month randomized prospective controlled study was carried out between July 2019 and March 2020 on thirty adolescents with chest burns aged 11-17 years. They were randomized into two equal groups (n = 15), traditional physiotherapy programme (control group), and arm cycling exercise plus traditonal physiotherapy (arm cycling exercise group) for 2 consecutive months. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), six-minute walk test (6MWT), and Pediatric Quality of Life Inventory (PedsQL) were measured in both groups at baseline and after 2-month after intervention. RESULTS: No statistical significance was detected at baseline between control and arm cycling exercise groups (FVC, p = 0.903, FEV1, p = 0.835, 6MWT, p = 0.817, and PedsQL, p = 0.612). 2 months after intervention showed statistical improvements in the arm cycling exercise group in all measures (FVC, p = 0.001, FEV1, p < 0.0001, 6MWT, p = 0.001, and PedsQL, p = 0.001) however, the control group showed statistical improvements in FVC, p = 0.044 and FEV1, p = 0.024 with non-statistically significant changes in 6MWT, p = 0.145 and PedsQL, p = 0.067. The arm cycling exercise group showed greater improvements than control group in the outcome measures (FVC, p = 0.034, FEV1, p < 0.017, 6MWT, p = 0.037, and PedsQL, p = 0.021). CONCLUSIONS: This prospective study clearly demonstrated positive and beneficial influences of two-month arm cycling exercise in the optimization of pulmonary functions, functional performance, and QOL in adolescents suffering from chest burns and thereby eliminating post-burn complications.