Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 296
Filtrar
1.
MicroPubl Biol ; 20242024.
Artigo em Inglês | MEDLINE | ID: mdl-38495586

RESUMO

Adeno-associated viruses (AAVs) are a popular tool in gene therapy approaches and have been engineered to specifically target different cells. There is interest in targeting endothelial cells (ECs) of the blood brain barrier and the AAV2 capsid variant BR1 has been found to transduce ECs with high selectivity in various mice models. However, this has not been tested in rat models. Here, we show that there is no EC transduction with systemic injection of the AAV-BR1-CAG-GFP virus in Sprague-Dawley rats (n=3), but instead transduction of brain parenchymal cells with neuronal morphology. These findings emphasize the importance of species-differences in use of AAVs.

2.
J Alzheimers Dis ; 98(2): 619-628, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38427481

RESUMO

Background: Person-centered care is considered beneficial for persons with dementia. Objective: To evaluate the impact of a person-centered knowledge translation intervention on the quality of healthcare and outcomes for persons with dementia. Methods: Over nine months, sub-acute hospital nursing, allied health, and medical staff (n = 90) participated in online and/or face-to-face person-centered education and were supported by senior nursing, allied health, and medical staff champions (n = 8) to implement person-centered healthcare. The quality of healthcare service, ward climate and care delivery were evaluated pre/post study intervention. In the week following hospital admission (Time 1) and week of discharge (Time 3), agitation incidence (co-primary outcome) was assessed in participants with dementia (n = 80). Participant delirium (co-primary outcome), accidents/injuries, psychotropic medicines, length of stay, readmission and discharge destination (secondary outcomes) were compared with a retrospective group (n = 77) matched on demographics, cognition and function in activities of daily living. Results: Improvements occurred post-intervention in service quality by 17.5% (p = 0.369, phi = 0.08), ward climate by 18.1% (p = 0.291, phi = 0.08), and care quality by 50% (p = 0.000, phi = 0.37). Participant agitation did not change from Time 1 to Time 3 (p = 0.223). Relative to the retrospective group, significant reductions occurred in participant delirium (p = 0.000, phi = 0.73), incidents/injuries (p = 0.000, phi = 0.99), psychotropic medicine use (p = 0.030, phi = 0.09), and hospital readmissions within 30 days (p = 0.002, phi = 0.25), but not in discharge to home (p = 0.171). Conclusions: When person-centered healthcare knowledge is translated through staff education and practice support, persons with dementia can experience improved healthcare services and clinical outcomes, while healthcare services can benefit through reductions in unplanned service use.


Assuntos
Delírio , Demência , Humanos , Demência/terapia , Atividades Cotidianas , Estudos Retrospectivos , Hospitais , Qualidade da Assistência à Saúde , Delírio/epidemiologia , Delírio/terapia , Assistência Centrada no Paciente
3.
Front Microbiol ; 15: 1342478, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38435692

RESUMO

Salmonella spp. is one of the most isolated microorganisms reported to be responsible for human foodborne diseases and death. Water constitutes a major reservoir where the Salmonella spp. can persist and go undetected when present in low numbers. In this study, we assessed the viability of 12 serotypes of Salmonella enterica subsp. enterica for 160 days in nuclease-free water at 4 and 25°C using flow cytometry and Tryptic Soy Agar (TSA) plate counts. The results show that all 12 serotypes remain viable after 160 days in distilled water using flow cytometry, whereas traditional plate counts failed to detect ten serotypes incubated at 25°C. Moreover, the findings demonstrate that 4°C constitutes a more favorable environment where Salmonella can remain viable for prolonged periods without nutrients. Under such conditions, however, Salmonella exhibits a higher susceptibility to all tested antibiotics and benzalkonium chloride (BZK). The pre-enrichment with Universal Pre-enrichment Broth (UP) and 1/10 × Tryptic Soy broth (1/10 × TSB) resuscitated all tested serotypes on TSA plates, nevertheless cell size decreased after 160 days. Furthermore, phenotype microarray (PM) analysis of S. Inverness and S. Enteritidis combined with principal component analysis (PCA) revealed an inter-individual variability in serotypes with their phenotype characteristics, and the impact of long-term storage at 4 and 25°C for 160 days in nuclease-free water. This study provides an insight to Salmonella spp. long-term survivability at different temperatures and highlights the need for powerful tools to detect this microorganism to reduce the risk of disease transmission of foodborne pathogens via nuclease-free water.

4.
Cereb Circ Cogn Behav ; 6: 100202, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38379937

RESUMO

Background: Cerebral small vessel disease (SVD) is a common neurological disorder contributing to stroke, dementia, and disability. No treatment options exist although clinical trials are ongoing. We aimed to understand what matters to people and families affected by SVD to inform future research. Methods: We thematically analysed unsolicited correspondences from members of the public addressed to members of the Edinburgh SVD Research Group on a variety of subjects related to SVD. We used inductive thematic codes, categorised under concerns, requests, emotions, and contributions, to form a grounded theory that categorised and ranked concerns raised. Results: 101 correspondents expressed 346 concerns between August 2015 and February 2021, mostly via email. 60 correspondents (59.4 %) disclosed a SVD diagnosis, 39 (38.6 %) disclosed a previous stroke or TIA, and 40 (39.6 %) were family of people living with SVD. Primary concerns related to cognitive problems (number of correspondents (n)=43 (42.6 %)), lack of support or information from healthcare services (n = 41 (40.6 %)), prognosis (n = 37 (36.6 %)), sensory disturbances (n = 27 (26.7 %)), functional problems (n = 24, (23.8 %)), impact on daily life (n = 24 (23.8 %)), and causes of SVD (n = 19 (18.8 %)). 57 correspondents (56.4 %) expressed support for research, 43 (42.6 %) expressed an eagerness to understand SVD, 35 (34.7 %) expressed helplessness, and 19 (18.8 %) expressed frustration. Conclusions: Cognitive decline was the main concern for people and families living with SVD who corresponded with the Edinburgh SVD research group. These findings also indicate a need for more accessible services and better information about SVD for patients and families.

5.
BMC Pediatr ; 23(Suppl 1): 646, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38413926

RESUMO

BACKGROUND: Health policymakers aiming to reduce under-5 mortality (U5M) often lack data regarding how successful interventions in other countries were implemented. The Exemplars in U5M Study identified countries that achieved significant reductions in amenable U5M. This case study in Peru used implementation research to explore the contextual factors and strategies that contributed to the successful implementation of key evidence-based interventions (EBIs). METHODS: This research utilized a hybrid implementation research framework and a mixed-methods approach to understand the factors associated with EBI implementation and the successful reduction of U5M between 2000-2015. A desk review of existing literature on EBIs and U5M in Peru was completed, and in-depth interviews were performed with key Peruvian informants to understand the implementation strategies employed and the contextual factors that facilitated or were barriers to success. For the purposes of this analysis, three EBIs were selected and evaluated: antenatal care visits (ANC), facility-based deliveries, and infant vaccination. RESULTS: Between 2000-2015, the percent of mothers attending at least four antenatal care visits rose from 69% to 96.9%, and the percent of facility-based deliveries increased from 56 to 91%. Three doses of the tetanus/diphtheria/pertussis vaccine, widely acknowledged as a key global health indicator, reached 90% by 2015. Key informants noted that economic growth, financial reforms, strong national commitment to reduce poverty in Peru, and national prioritization of maternal and child health, were important contextual factors that contributed to the successful reduction of U5M. They noted key strategies that helped achieve success during the implementation of EBIs, including utilization of data for decision-making, adaptation driven by cultural sensitivity to address gaps in coverage, and a focus on equity and anti-poverty initiatives with the participation of government, civil society, and political parties to assure continuity of policies. CONCLUSION: Several EBIs contributed to the successful reduction of U5M in Peru between 2000-2015. Strategies such as the focus on equity throughout the study period contributed to an increase in coverage of EBIs like ANC visits, facility-based deliveries and infant vaccination which worked to reduce U5M. Understanding how Peru successfully implemented programs that reduced preventable infant and child deaths could be useful to replicating this substantial public health success in other low- and middle-income countries.


Assuntos
Pobreza , Cuidado Pré-Natal , Lactente , Criança , Humanos , Gravidez , Feminino , Peru/epidemiologia , Saúde da Criança , Mães
6.
Appl Spectrosc ; 78(2): 159-174, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37960870

RESUMO

Much research has focused on attempting to understand the drivers of bone diagenesis. However, this sensitive process is easily influenced by various factors, particularly the condition of the remains (i.e., whether they have been subjected to trauma). Previous research demonstrates that trauma can influence soft tissue decomposition, yet to date, no studies have looked at how bone fractures could affect bone diagenesis. To address this gap, two short timescale studies were conducted to investigate the influence of bone fractures on the physicochemical composition of disarticulated, partially fleshed animal remains. Disarticulated porcine bones were either fractured using blunt force or sharp force whilst fresh (producing perimortem damage), at 60 days producing postmortem damage (postmortem interval (PMI)), or left intact and left outside for up to 180 days post-fracture/240 days PMI. Retrieved bone sections were then analyzed for physicochemical differences using non-destructive methods, i.e., scanning electron microscopy energy dispersive spectroscopy and Fourier transform infrared spectroscopy with attenuated total reflectance. It was hypothesized that differences would be found in the physicochemical composition between the bones with fractures and those without after undergoing diagenetic change. The bone fractures significantly affected the elemental composition of bone over time, but structural composition initially remained stable. It was also possible to distinguish between perimortem and postmortem fractures using these two analytical techniques due to physicochemical differences. This research shows bone fractures can significantly alter the physicochemical composition of the bone during the postmortem period and have the potential to facilitate more accurate PMI estimations in forensic contexts.


Assuntos
Fraturas Ósseas , Mudanças Depois da Morte , Suínos , Animais , Osso e Ossos , Microscopia Eletrônica de Varredura , Espectroscopia de Infravermelho com Transformada de Fourier
7.
PLoS Comput Biol ; 19(11): e1010845, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37976310

RESUMO

Electron microscopy (EM) images of axons and their ensheathing myelin from both the central and peripheral nervous system are used for assessing myelin formation, degeneration (demyelination) and regeneration (remyelination). The g-ratio is the gold standard measure of assessing myelin thickness and quality, and traditionally is determined from measurements made manually from EM images-a time-consuming endeavour with limited reproducibility. These measurements have also historically neglected the innermost uncompacted myelin sheath, known as the inner tongue. Nonetheless, the inner tongue has been shown to be important for myelin growth and some studies have reported that certain conditions can elicit its enlargement. Ignoring this fact may bias the standard g-ratio analysis, whereas quantifying the uncompacted myelin has the potential to provide novel insights in the myelin field. In this regard, we have developed AimSeg, a bioimage analysis tool for axon, inner tongue and myelin segmentation. Aided by machine learning classifiers trained on transmission EM (TEM) images of tissue undergoing remyelination, AimSeg can be used either as an automated workflow or as a user-assisted segmentation tool. Validation results on TEM data from both healthy and remyelinating samples show good performance in segmenting all three fibre components, with the assisted segmentation showing the potential for further improvement with minimal user intervention. This results in a considerable reduction in time for analysis compared with manual annotation. AimSeg could also be used to build larger, high quality ground truth datasets to train novel deep learning models. Implemented in Fiji, AimSeg can use machine learning classifiers trained in ilastik. This, combined with a user-friendly interface and the ability to quantify uncompacted myelin, makes AimSeg a unique tool to assess myelin growth.


Assuntos
Axônios , Bainha de Mielina , Bainha de Mielina/fisiologia , Reprodutibilidade dos Testes , Axônios/fisiologia , Microscopia Eletrônica , Aprendizado de Máquina
8.
Ecol Restor ; 41(2-3): 84-98, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37990651

RESUMO

As salt marsh habitats face challenges due to sea level rise, storm events, and coastal development, there is an effort to use nature-based approaches such as living shorelines to enhance salt marshes and provide coastal protection. A living shoreline restoration and seasonal monitoring was conducted between July 2016 and October 2018 at an eroding salt marsh on Martha's Vineyard, Massachusetts, Northeastern USA to assess changes in two essential ecosystem services: shoreline stabilization and nitrogen removal. Neither the living shoreline nor unaltered sites demonstrated significant sediment deposition at the marsh edge or on the marsh platform between 2017 and 2018. While we expected nitrogen removal via denitrification to improve at the living shoreline sites over time as abiotic and biotic conditions became more favorable, we found limited support for this hypothesis. We found higher rates of denitrification enzyme activity (DEA) at the living shoreline sites when compared to unaltered sites, but these rates did not increase over time. This study also provides a qualitative assessment of our living shoreline structural integrity through the years, particularly following storm events that greatly challenged our restoration efforts. We demonstrate that living shorelines fortified solely with natural materials may not be the most effective approach to maintain these ecosystem services for Northeastern USA salt marshes exposed to intense northeasterly storms. We suggest the restoration of salt marshes to improve major functions be a priority among managers and restoration practitioners. Initiatives promoting the use of nature-based restoration solution where environmental conditions permit should be encouraged.

9.
Glob Health Sci Pract ; 11(5)2023 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-37903587

RESUMO

In 2008, a cadre of professional midwives was introduced in Bangladesh. Since then, 120 midwifery educational programs have been established. There are 2,556 midwives serving at 667 government health facilities, and there are more midwives working in nongovernmental organizations and the private sector. This case study documents the process of establishing a midwifery profession with distinct midwifery expertise in Bangladesh and aims to guide other low- and middle-income countries in best practices and challenges. We describe the national administrative groundwork for the profession's launch, roll-out of an education program aligned with the International Confederation of Midwives, national deployment, enabling environments in deployment, and the professional association. Bangladesh's professional midwives' roles in humanitarian response and the COVID-19 pandemic are also discussed. The first and final authors were closely involved in supporting the government's establishment of the profession, and their direct experience is drawn upon to contextualize the topics. In addition, the authors conducted a desk review of documents that supported the profession's integration into the health system and documented its results. Both routine program data and existing research studies were reviewed. Outcomes show that midwives are deployed to 95% of government subdistrict hospitals. About 50% of these hospitals are fully staffed with 4 midwives, and within the hospitals, midwives are in charge of 90% of the maternity wards and attend 75%-85% of the births. Since the midwives' deployment, significant quality improvement for most World Health Organization indicators has been found, along with increases in service utilization. The experience of establishing a new midwifery profession in Bangladesh shows that it is possible for a lower middle-income country to introduce a globally standard midwifery profession, distinct from nursing, to improve quality sexual, reproductive, maternal, newborn, and adolescent health services in both humanitarian and development settings.


Assuntos
Serviços de Saúde Materna , Tocologia , Recém-Nascido , Adolescente , Humanos , Feminino , Gravidez , Tocologia/educação , Bangladesh , Pandemias , Programas Governamentais
10.
Reprod Health ; 20(1): 128, 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37644451

RESUMO

BACKGROUND: The COVID-19 pandemic disrupted maternal and newborn health services in Bangladesh, exacerbating the large gaps in service utilization that existed prior to the pandemic. As part of its response, Bangladesh initiated remote antenatal and postnatal care telemedicine services led by midwives in 36 sub-district hospitals across five of Bangladesh's 64 districts. Gender-based violence screening and referral were integrated into the service to address a reported rise in violence following the country's pandemic lockdown. METHODS: Mixed-methods implementation research was used to develop an intrinsic case study describing the design and implementation of the telemedicine program. Qualitative analysis comprised document review, key informant interviews, and focus group discussions. Quantitative analysis employed an interrupted time series analysis with segmented multi-variate regression to compare maternity care service use trends before and after implementation. Poisson regression analysis was used to examine the trend in number of gender-based violence remote screenings, sessions held, and cases identified. RESULTS: A statistically significant change in trend for onsite antenatal and postpartum care as well as women seeking care at the hospital as a result of postpartum hemorrhage arising in the community was observed following the introduction of telemedicine. Facility births and cases of eclampsia appropriately identified and managed also had significant increases. In addition, over 6917 women were screened for GBV, 223 received counseling and 34 referrals were made, showing a statistically significant increase in frequency over time following the implementation of the telemedicine program. Challenges included that not all midwives adopted GBV screening, some women were reluctant to discuss GBV, there was an unanticipated need to introduce a patient visit scheduling system in all intervention hospitals, and many women were not reachable by phone due to lack of access or network coverage. CONCLUSIONS: Maternal health and gender-based violence telemedicine led by midwives was an effective, low-cost intervention in Bangladesh for addressing pandemic and pre-pandemic gaps in service use. Other low and middle-income countries planning to implement remote maternal health interventions via midwives should consider whether a patient visit scheduling system needs to be introduced, as well as limitations around mobile phone access and connectivity. Future research should include care quality oversight and improvement, and a more well-informed strategy for facilitating effective GBV screening.


To support the continuation of sexual and reproductive health services following pandemic lockdowns, Bangladesh introduced a midwife-led telemedicine program. Through the program, midwives who were already employed within the health system delivered remote antenatal and postnatal care, including gender-based violence screening and referral. The program operated in 36 sub-district hospitals across five of Bangladesh's 64 districts. Intrinsic implementation research was used to develop a case study describing the design and implementation of the telemedicine program. Qualitative and quantitative methods comprised document review, key informant interviews, focus group discussions, and service use trends. Analysis of the data identified a statistically significant trend increase for most maternity care services. Although they did increase significantly over time, referrals for GBV were less than expected, which may have been related to some midwives not screening for GBV, and/or that many women were reluctant to discuss GBV. In addition, there was an unanticipated need to introduce a patient visit scheduling system in all intervention hospitals, and many women were not reachable by phone due to lack of access or network coverage. In spite of this, 6197 women were screened for GBV. Of those, 223 received counseling and 34 received referrals. Overall, telemedicine led by midwives was an effective, low-cost intervention for maternal health, and a step toward stronger GBV response in Bangladesh. Other low and middle-income countries planning to implement remote maternal health interventions via midwives should consider what is needed to facilitate comfort for both providers and women as related to GBV screening, as well as practical issues regarding introducing scheduling systems and limitations of mobile phone access and connectivity.


Assuntos
COVID-19 , Violência de Gênero , Serviços de Saúde Materna , Tocologia , Gravidez , Recém-Nascido , Feminino , Humanos , Bangladesh/epidemiologia , Pandemias , Saúde Materna , COVID-19/epidemiologia , COVID-19/prevenção & controle , Controle de Doenças Transmissíveis
13.
J Urol ; 210(1): 186-195, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37293725

RESUMO

PURPOSE: Urodynamics is the standard method of diagnosing bladder dysfunction, but involves catheters and retrograde bladder filling. With these artificial conditions, urodynamics cannot always reproduce patient complaints. We have developed a wireless, catheter-free intravesical pressure sensor, the UroMonitor, which enables catheter-free telemetric ambulatory bladder monitoring. The purpose of this study was twofold: to evaluate accuracy of UroMonitor pressure data, and assess safety and feasibility of use in humans. MATERIALS AND METHODS: Eleven adult female patients undergoing urodynamics for overactive bladder symptoms were enrolled. After baseline urodynamics, the UroMonitor was transurethrally inserted into the bladder and position was confirmed cystoscopically. A second urodynamics was then performed with the UroMonitor simultaneously transmitting bladder pressure. Following removal of urodynamics catheters, the UroMonitor transmitted bladder pressure during ambulation and voiding in private. Visual analogue pain scales (0-5) were used to assess patient discomfort. RESULTS: The UroMonitor did not significantly alter capacity, sensation, or flow during urodynamics. The UroMonitor was also easily inserted and removed in all subjects. The UroMonitor reproduced bladder pressure, capturing 98% (85/87) of voiding and nonvoiding urodynamic events. All subjects voided with only the UroMonitor in place with low post-void residual volume. Median ambulatory pain score with the UroMonitor was rated 0 (0-2). There were no post-procedural infections or changes to voiding behavior. CONCLUSIONS: The UroMonitor is the first device to enable catheter-free telemetric ambulatory bladder pressure monitoring in humans. The UroMonitor appears safe and well tolerated, does not impede lower urinary tract function, and can reliably identify bladder events compared to urodynamics.


Assuntos
Bexiga Urinária , Micção , Adulto , Humanos , Feminino , Cateteres Urinários/efeitos adversos , Urodinâmica , Sujeitos da Pesquisa
14.
Nat Commun ; 14(1): 3372, 2023 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-37291151

RESUMO

Failed regeneration of myelin around neuronal axons following central nervous system damage contributes to nerve dysfunction and clinical decline in various neurological conditions, for which there is an unmet therapeutic demand. Here, we show that interaction between glial cells - astrocytes and mature myelin-forming oligodendrocytes - is a determinant of remyelination. Using in vivo/ ex vivo/ in vitro rodent models, unbiased RNA sequencing, functional manipulation, and human brain lesion analyses, we discover that astrocytes support the survival of regenerating oligodendrocytes, via downregulation of the Nrf2 pathway associated with increased astrocytic cholesterol biosynthesis pathway activation. Remyelination fails following sustained astrocytic Nrf2 activation in focally-lesioned male mice yet is restored by either cholesterol biosynthesis/efflux stimulation, or Nrf2 inhibition using the existing therapeutic Luteolin. We identify that astrocyte-oligodendrocyte interaction regulates remyelination, and reveal a drug strategy for central nervous system regeneration centred on targeting this interaction.


Assuntos
Astrócitos , Fator 2 Relacionado a NF-E2 , Masculino , Camundongos , Animais , Humanos , Astrócitos/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Sistema Nervoso Central/metabolismo , Oligodendroglia/metabolismo , Bainha de Mielina/metabolismo , Regeneração Nervosa/fisiologia , Colesterol/metabolismo
15.
Acta Neuropathol Commun ; 11(1): 84, 2023 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-37217978

RESUMO

The myelinated white matter tracts of the central nervous system (CNS) are essential for fast transmission of electrical impulses and are often differentially affected in human neurodegenerative diseases across CNS region, age and sex. We hypothesize that this selective vulnerability is underpinned by physiological variation in white matter glia. Using single nucleus RNA sequencing of human post-mortem white matter samples from the brain, cerebellum and spinal cord and subsequent tissue-based validation we found substantial glial heterogeneity with tissue region: we identified region-specific oligodendrocyte precursor cells (OPCs) that retain developmental origin markers into adulthood, distinguishing them from mouse OPCs. Region-specific OPCs give rise to similar oligodendrocyte populations, however spinal cord oligodendrocytes exhibit markers such as SKAP2 which are associated with increased myelin production and we found a spinal cord selective population particularly equipped for producing long and thick myelin sheaths based on the expression of genes/proteins such as HCN2. Spinal cord microglia exhibit a more activated phenotype compared to brain microglia, suggesting that the spinal cord is a more pro-inflammatory environment, a difference that intensifies with age. Astrocyte gene expression correlates strongly with CNS region, however, astrocytes do not show a more activated state with region or age. Across all glia, sex differences are subtle but the consistent increased expression of protein-folding genes in male donors hints at pathways that may contribute to sex differences in disease susceptibility. These findings are essential to consider for understanding selective CNS pathologies and developing tailored therapeutic strategies.


Assuntos
Neuroglia , Substância Branca , Humanos , Feminino , Masculino , Camundongos , Animais , Neuroglia/metabolismo , Medula Espinal/patologia , Bainha de Mielina/metabolismo , Oligodendroglia/patologia
16.
Nat Commun ; 14(1): 1592, 2023 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-36949062

RESUMO

Neuroprotective, anti-inflammatory, and remyelinating properties of androgens are well-characterized in demyelinated male mice and men suffering from multiple sclerosis. However, androgen effects mediated by the androgen receptor (AR), have been only poorly studied in females who make low androgen levels. Here, we show a predominant microglial AR expression in demyelinated lesions from female mice and women with multiple sclerosis, but virtually undetectable AR expression in lesions from male animals and men with multiple sclerosis. In female mice, androgens and estrogens act in a synergistic way while androgens drive microglia response towards regeneration. Transcriptomic comparisons of demyelinated mouse spinal cords indicate that, regardless of the sex, androgens up-regulate genes related to neuronal function integrity and myelin production. Depending on the sex, androgens down-regulate genes related to the immune system in females and lipid catabolism in males. Thus, androgens are required for proper myelin regeneration in females and therapeutic approaches of demyelinating diseases need to consider male-female differences.


Assuntos
Androgênios , Esclerose Múltipla , Animais , Camundongos , Feminino , Masculino , Modelos Animais de Doenças , Bainha de Mielina/fisiologia , Esclerose Múltipla/genética , Esclerose Múltipla/patologia , Neurônios/patologia
17.
J Med Humanit ; 44(4): 463-480, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37000293

RESUMO

The authors conducted a baseline survey of baccalaureate and graduate degree health humanities programs in the United States and Canada. The object of the survey was to formally assess the current state of the field, to gauge what kind of resources individual programs are receiving, and to assess their self-identified needs to become or remain programmatically sustainable, including their views on the potential benefits of program accreditation. A 56-question baseline survey was sent to 111 institutions with baccalaureate programs and 20 institutions with graduate programs. Respondents were asked about three areas: (1) program administration (managing unit, paid director, faculty lines, paid staff, funding sources); (2) educational program (curricular structure, CIP code usage, completion rates); and (3) views on accreditation for the field. A clear majority of respondents agreed that some form of accreditation or consultation service could address resource and sustainability issues. Overall, the survey responses to staffing, curricular structure, and support suggest the need for developing a sustainable infrastructure for health humanities.


Assuntos
Acreditação , Ciências Humanas , Humanos , Estados Unidos , América do Norte , Inquéritos e Questionários , Canadá , Currículo
18.
Acta Neuropathol Commun ; 11(1): 49, 2023 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-36949514

RESUMO

Myelination of neuronal axons is a critical aspect of central nervous system development and function. However, the fundamental cellular and molecular mechanisms influencing human developmental myelination and its failure are not fully understood. Here, we used digital spatial transcriptomics of a rare bank of human developing white matter to uncover that a localized dysregulated innate immune response is associated with impeded myelination. We identified that poorly myelinating areas have a distinct signature of Type II interferon signalling in microglia/macrophages, relative to adjacent myelinating areas. This is associated with a surprising increase in mature oligodendrocytes, which fail to form myelin processes appropriately. We functionally link these findings by showing that conditioned media from interferon-stimulated microglia is sufficient to dysregulate myelin process formation by oligodendrocytes in culture. We identify the Type II interferon inducer, Osteopontin (SPP1), as being upregulated in poorly myelinating brains, indicating a potential biomarker. Our results reveal the importance of microglia-mature oligodendrocyte interaction and interferon signaling in regulating myelination of the developing human brain.


Assuntos
Microglia , Bainha de Mielina , Humanos , Bainha de Mielina/fisiologia , Oligodendroglia/fisiologia , Axônios/fisiologia , Encéfalo
19.
BJGP Open ; 7(2)2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36750374

RESUMO

BACKGROUND: During the COVID-19 pandemic, telehealth emerged as a means of safely providing primary healthcare (PHC) consultations. In Australia, changes to telehealth funding led to the reconsideration of the role of telehealth in the ongoing provision of PHC services. AIM: To investigate GPs', registered nurses' (RNs), nurse practitioners' (NPs), and allied health (AH) clinicians perceptions of the sustainability of telehealth in PHC post-pandemic. DESIGN & SETTING: Semi-structured interviews were undertaken with 33 purposively selected clinicians, including GPs (n = 13), RNs (n = 5), NPs (n = 9), and AH clinicians (n = 6) working in PHC settings across Australia. Participants were drawn from responders to a national survey of PHC providers (n = 217). METHOD: The thematic analysis approach reported by Braun and Clarke was used to analyse the interview data. RESULTS: Data analysis revealed that the perception of providers was represented by the following two themes: lessons learnt; and the sustainability of telehealth. Lessons learnt included the need for rapid adaptation to telehealth, use of technology, and the pandemic being a catalyst for long-term change. The sustainability of telehealth in PHC comprised four subthemes around challenges: the funding model, maintaining patient and provider safety, hybrid service models, and access to support. CONCLUSION: Providers required resilience and flexibility to adapt to telehealth. Funding models must reward providers from an outcome focus, rather than placing limits on telehealth's use. Hybrid approaches to service delivery will best meet the needs of the community but must be accompanied by support and education for PHC professionals.

20.
Sci Rep ; 13(1): 207, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36604529

RESUMO

This paper describes the fabrication of cicada-wing-inspired antimicrobial surfaces using Glancing Angle Deposition (GLAD). From the study of an annual cicada (Neotibicen Canicularis, also known as dog-day cicada) in North America, it is found that the cicada wing surfaces are composed of unique three-dimensional (3D) nanofeature arrays, which grant them extraordinary properties including antimicrobial (antifouling) and antireflective. However, the morphology of these 3D nanostructures imposes challenges in artificially synthesizing the structures by utilizing and scaling up the template area from nature. From the perspective of circumventing the difficulties of creating 3D nanofeature arrays with top-down nanofabrication techniques, this paper introduces a nanofabrication process that combines bottom-up steps: self-assembled nanospheres are used as the bases of the features, while sub-100 nm pillars are grown on top of the bases by GLAD. Scanning electron micrographs show the resemblance of the synthesized cicada wing mimicry samples to the actual cicada wings, both quantitatively and qualitatively. The synthetic mimicry samples are hydrophobic with a water contact angle of 125˚. Finally, the antimicrobial properties of the mimicries are validated by showing flat growth curves of Escherichia coli (E. coli) and by direct observation under scanning electron microscopy (SEM). The process is potentially suitable for large-area antimicrobial applications in food and biomedical industries.


Assuntos
Anti-Infecciosos , Hemípteros , Nanoestruturas , Animais , Anti-Infecciosos/farmacologia , Escherichia coli , Hemípteros/anatomia & histologia , Interações Hidrofóbicas e Hidrofílicas , Nanoestruturas/química , Propriedades de Superfície
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...