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1.
Child Abuse Negl ; 155: 106964, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39116553

RESUMO

BACKGROUND: While child welfare scholarship has paid much attention to workforce well-being such as burnout, secondary traumatic stress (STS), and compassion satisfaction, few studies have investigated how these outcomes influence utilization of casework skills. OBJECTIVES: This study aimed to understand the relationship between child welfare workforce well-being and use of casework skills. Specifically, we examined associations between burnout, STS, and compassion satisfaction and casework skills including parent/youth engagement, safety and risk assessment/case planning, and relative/kin connections. PARTICIPANTS AND SETTING: Participants comprised 786 child welfare direct service workers and supervisors in a Midwestern state. METHOD: Using a repeated cross-sectional design, data were collected via online surveys. Multivariate regression tested relationships between measures of well-being and casework skills. RESULTS: First, higher compassion satisfaction was positively associated (p = 0.000, f2 = 0.14) while higher burnout (p = 0.000, f2 = 0.04) and STS (p = 0.002, f2 = 0.01) were negatively associated with use of engagement skills. Similarly, higher compassion satisfaction was positively associated (p = 0.000, f2 = 0.18) and higher burnout (p = 0.000, f2 = 0.06) and STS (p = 0.001, f2 = 0.02) were negatively associated with use of assessment/case planning skills. Lastly, compassion satisfaction (p = 0.000, f2 = 0.06) was positively associated and burnout was negatively associated (p = 0.000, f2 = 0.02) with relative/kin connections. CONCLUSION: Child welfare workforce well-being may influence use of casework skills. More research is needed to understand how positive workforce well-being impacts service delivery and, ultimately, child and family outcomes.

2.
Brain ; 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39101580

RESUMO

Genetics and other data modalities indicate that microglia play a critical role in Alzheimer's disease (AD) progression, but details of microglia's disease-driving influence are poorly understood. Microglial cells can be parsed into subtypes based on their histologic appearance. One microglia subtype, termed dystrophic microglia, is characterised structurally by fragmented processes and cytoplasmic decay, and their presence has been associated with ageing and neurodegeneration. Recent studies suggest that the interaction between tau proteins and amyloid-ß might induce dystrophic changes in microglia, potentially linking amyloid-ß and tau pathologies to their effects on these microglia. We developed a study of human brains to test the hypothesis that dystrophic microglia are involved in AD progression. We speculated that if their presence is unique to AD neuropathologic change (ADNC), they would be substantially more common in ADNC than in neurodegenerative diseases characterised by other proteinopathies, e.g., α-synuclein or TDP-43 pathology. Our analyses used histologically stained sections from five human brain regions of 64 individuals across six disease states, from healthy controls to advanced AD stages, including comparative conditions such as Lewy Body Disease (LBD) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). Using stereological sampling and digital pathology, we assessed ramified, hypertrophic, and dystrophic microglia populations. We found a significant increase in dystrophic microglia in areas early affected by ADNC, suggesting a disease-specific role in neuropathology. Mediation analysis and structural equation modelling suggest dystrophic microglia may impact the regional spread of ADNC. In the mediation model, tau was found to be the initiating factor leading to the development of dystrophic microglia, which then was associated with the spread of amyloid-ß and tau. These results suggest that a loss of microglia's protective role could contribute to the spread of ADNC and indicate that further research into preserving microglial function may be warranted.

3.
Microbiol Spectr ; : e0084324, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39162552

RESUMO

The microbiome of wild animals is believed to be co-evolved with host species, which may play an important role in host physiology. It has been hypothesized that the rigorous hygienic practices in combination with antibiotics and diets with simplified formulas used in the modern swine industry may negatively affect the establishment and development of the gut microbiome. In this study, we evaluated the fecal microbiome of 90 domestic pigs sampled from nine farms in Canada and 39 wild pigs sampled from three different locations on two continents (North America and Europe) using 16S rRNA gene amplicon sequencing. Surprisingly, the gut microbiome in domestic pigs exhibited higher alpha-diversity indices than wild pigs (P < 0.0001). The wild pig microbiome showed a lower Firmicutes-to-Bacteroidetes ratio and a higher presence of bacterial phyla Elusimicrobiota, Verrucomicrobiota, Cyanobacteria, and Fibrobacterota when compared to their domestic counterparts. At the genus level, the wild pig microbiome had enriched genera that were known for fiber degradation and short-chain fatty acid production. Interestingly, the phylum Fusobacteriota was only observed in domestic pigs. We identified 31 ASVs that were commonly found in the pig gut microbiome, regardless of host sources, which could be recognized as members of the core gut microbiome. Interestingly, we found five ASVs missing in domestic pigs that were prevalent in wild ones, whereas domestic pigs harbored 59 ASVs that were completely absent in wild pigs. The present study sheds light on the impact of domestication on the pig gut microbiome, including the gain of new genera, which might provide the basis to identify novel targets to manipulate the pig gut microbiome for improved health. IMPORTANCE: The microbiome of pigs plays a crucial role in shaping host physiology and health. This study sought to identify if domestication and current rearing practices have resulted in a loss of co-evolved bacterial species by comparing the microbiome of wild boar and conventionally raised pigs. It provides a comparison of domestic and wild pigs with the largest sample sizes and is the first to examine wild boars from multiple sites and continents. We were able to identify core microbiome members that were shared between wild and domestic populations, and on the contrary to expectation, few microbes were identified to be lost from wild boar. Nevertheless, the microbiome of wild boars had a lower abundance of important pathogenic genera and was distinct from domestic pigs. The differences in the microbial composition may identify an opportunity to shift the microbial community of domestic pigs towards that of wild boar with the intent to reduce pathogen load.

5.
Ear Nose Throat J ; : 1455613241272451, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39192625

RESUMO

Objectives: The presence of a catheter required for contrast infusion during sialography obscures imaging of the distal duct. Static imaging via cone beam computed tomography and magnetic resonance sialography fails to address changes that occur dynamically to the anatomy of the flexible salivary ductal system. We aim to identify dynamic changes to the parotid gland by introducing a novel approach to analyze the full extent of Stensen's duct based on dynamic infusion digital sialography. Methods: Retrospective chart review of a single-center consecutive series of 409 parotid sialograms performed between April 2008 and June 2023 permitted selection of a contemporary series including seven normal sialograms and seven sialograms with stricture(s). Dynamic (fluoroscopic) infusion (iopamidol/gadolinium) sialograms were assessed through blinded review by two radiologists employing the institution's picture archiving and communication (PACS) system (©2023 Koninklijke Philips N.V., Amsterdam, Netherlands). Measurements determined changes, in two dimensions, to the angle of the masseteric bend and duct length while the catheter was in place (repose), during catheter withdrawal (stretch), and during recoil after withdrawal. Differences in median lengths and angles of Stensen's duct between the three time points were compared using Wilcoxon matched-pairs signed rank and Mann-Whitney tests. Results: Fourteen patients [median age (IQR), 55 years (24.7); 10 women] were evaluated. The median angle of the masseteric bend was 117.7° in repose versus 155.4° during catheter withdrawal (P < .001, n = 14). The median distance measured from the Stensen's duct orifice to the first major ductal bifurcation was 81.5 mm (IQR = 12.3) in repose. The median percent increase in length from repose to stretch was 6.3% (P < .001, n = 14). Conclusions: Dynamic infusion digital sialography with fluoroscopic recording during catheter removal permits assessment of the distal duct unobstructed by the presence of a catheter. The technique also identifies the dynamic nature and varying length and angulation of Stensen's duct.

6.
Mol Ecol ; 33(17): e17489, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39148259

RESUMO

Globalization has led to the frequent movement of species out of their native habitat. Some of these species become highly invasive and capable of profoundly altering invaded ecosystems. Feral swine (Sus scrofa × domesticus) are recognized as being among the most destructive invasive species, with populations established on all continents except Antarctica. Within the United States (US), feral swine are responsible for extensive crop damage, the destruction of native ecosystems, and the spread of disease. Purposeful human-mediated movement of feral swine has contributed to their rapid range expansion over the past 30 years. Patterns of deliberate introduction of feral swine have not been well described as populations may be established or augmented through small, undocumented releases. By leveraging an extensive genomic database of 18,789 samples genotyped at 35,141 single nucleotide polymorphisms (SNPs), we used deep neural networks to identify translocated feral swine across the contiguous US. We classified 20% (3364/16,774) of sampled animals as having been translocated and described general patterns of translocation using measures of centrality in a network analysis. These findings unveil extensive movement of feral swine well beyond their dispersal capabilities, including individuals with predicted origins >1000 km away from their sampling locations. Our study provides insight into the patterns of human-mediated movement of feral swine across the US and from Canada to the northern areas of the US. Further, our study validates the use of neural networks for studying the spread of invasive species.


Assuntos
Espécies Introduzidas , Redes Neurais de Computação , Polimorfismo de Nucleotídeo Único , Animais , Estados Unidos , Suínos/genética , Sus scrofa/genética , Genótipo , Ecossistema , Animais Selvagens/genética , Genética Populacional
7.
Neurotrauma Rep ; 5(1): 770-786, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39184175

RESUMO

The increasing incidence of traumatic brain injury (TBI) among older adults, particularly mild injuries from falls, underscores the need to investigate age-related outcomes and potential sex differences in response to TBI. Although previous research has defined an aging-TBI signature (heightened glial responses and cognitive impairment) in open-skull moderate-to-severe TBI models, it is unknown whether this signature is also present in mild closed-head injuries (CHIs). This study explores the influences of age and sex on recovery in a mouse CHI model induced by an electromagnetic impactor device in 4-month-old and 18-month-old C57BL/6 mice. We assessed the righting reflex, body weight, behavior (radial arm water maze and active avoidance), and inflammation (GFAP, IBA1, CD45) in the neocortex, corpus callosum, and hippocampus. We observed that aged female mice exhibited more severe TBI-induced cognitive deficits. In addition, a more pronounced reactive neuroinflammatory response with age was noted within white matter regions. Conversely, gray matter regions in aged animals either showed no enhanced pathological changes in response to injury or the aged mice displayed hyporesponsive glia and signs of dystrophic glial degeneration that were not evident in their younger counterparts following CHI. These findings suggest that aging influences CHI outcomes, partially reflecting the aging-TBI signature seen in more severe injuries in white matter, while a distinct aging and mild-TBI signature was identified in gray matter. The heightened vulnerability of females to the combined effects of age and mild CHI establishes a foundation for further investigation into the mechanisms underlying the sexually dimorphic response in aging females.

9.
Mol Ecol ; : e17500, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39188095

RESUMO

Disentangling the roles of structural landscape factors and animal movement behaviour can present challenges for practitioners managing landscapes to maintain functional connectivity and achieve conservation goals. We used a landscape genetics approach to combine robust demographic, behavioural and genetic datasets with spatially explicit simulations to evaluate the effects of anthropogenic barriers (dams, culverts) and natural landscape resistance (gradient, elevation) affecting dispersal behaviour, genetic connectivity and genetic structure in a resident population of Westslope Cutthroat Trout (Oncorhynchus clarkii lewisi). Analyses based on 10 years of sampling effort revealed a pattern of restricted dispersal, and population genetics identified discrete population clusters between distal tributaries and the mainstem stream and no structure within the mainstem stream. Demogenetic simulations demonstrated that, for this population, the effects of existing anthropogenic barriers on population structure are redundant with effects of restricted dispersal associated with the underlying environmental resistance. Our approach provides an example of how extensive field sampling combined with landscape genetics can be incorporated into spatially explicit simulation modelling to explore how, together, movement ecology and landscape resistance can be used to inform decisions around restoration and connectivity.

10.
J Antimicrob Chemother ; 79(8): 1990-1997, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946294

RESUMO

BACKGROUND: Successful use of carbapenems in combination with cefazolin or oxacillin for treatment of MSSA bacteraemia has been described; however, comparative data to standard treatment approaches are lacking. METHODS: This was a multicentre, retrospective study of adult patients with MSSA bacteraemia for >48 h. Standard treatment was considered monotherapy with cefazolin, oxacillin or nafcillin. Combination therapy was defined as the addition of ertapenem or meropenem to standard treatment for at least 24 h. The primary outcome was duration of bacteraemia defined as time from administration of an antibiotic with in vitro activity to first negative blood culture. Time to blood culture sterilization was compared through risk-set matching with aid of a propensity score. RESULTS: Overall, 238 patients were included; 66% (157/238) received standard treatment and 34% (81/238) received combination therapy. The median (IQR) time to carbapenem initiation was 4.7 (3.63-6.5) days. Patients who received combination therapy were younger (P = 0.012), more likely to have endocarditis (P = 0.034) and had longer median duration of bacteraemia (P < 0.001). After applying risk-set matching, patients who received combination therapy experienced faster time to blood culture sterilization compared with control patients [HR = 1.618 (95% CI; 1.119-2.339) P = 0.011]. Using a paired hazard model, 90 day mortality rates were not statistically different among patients who received combination therapy versus matched controls [HR = 1.267 (95% CI; 0.610-2.678), P = 0.608]. DISCUSSION: Carbapenem combination therapy resulted in faster time to blood culture sterilization, but no differences in overall mortality rates. Randomized trials are critical to determine the utility of carbapenem combination therapy.


Assuntos
Antibacterianos , Bacteriemia , Carbapenêmicos , Quimioterapia Combinada , Padrão de Cuidado , Infecções Estafilocócicas , Staphylococcus aureus , Humanos , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Idoso , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/mortalidade , Carbapenêmicos/uso terapêutico , Carbapenêmicos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Resultado do Tratamento , Adulto
11.
J Antimicrob Chemother ; 79(8): 2017-2021, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38958234

RESUMO

OBJECTIVES: To investigate clinical outcomes of patients with Pseudomonas endocarditis and identify factors associated with treatment failure. METHODS: Adult patients meeting definitive Duke's criteria for Pseudomonas endocarditis at 11 hospitals were identified between May 2000 and February 2024. Failure was defined as death or microbiological failure by day 42. First-line therapy consisted of cefepime, piperacillin/tazobactam, ceftazidime or ceftolozane/tazobactam alone or in combination. RESULTS: Forty-eight patients met inclusion criteria; 29% were persons who inject drugs and 13% were organ transplant recipients. Pseudomonas aeruginosa was the causative species in 98% of cases. Patients who experienced 42 day cure were more likely to be initially managed with first-line ß-lactam agents compared with those who experienced clinical failure (97% versus 62%, P = 0.004). Treatment with first-line ß-lactams was associated with shorter time to treatment initiation and a lower likelihood of infection due to MDR Pseudomonas spp. In the univariate model, patients who experienced 90 day mortality were more likely to have prosthetic valve endocarditis (57% versus 24%, P = 0.02), an intracardiac complication (36% versus 9%, P = 0.04) and a higher median (IQR) Pitt bacteraemia score [2.5 (2-3.8) versus 1 (0-2), P = 0.048]. Combination therapy did not improve clinical outcomes but did increase the rate of adverse effects resulting in drug discontinuation compared with monotherapy, (21% versus 0%, P = 0.08). CONCLUSIONS: This is the largest study of Pseudomonas endocarditis to date. We identified improved clinical outcomes when cefepime, piperacillin/tazobactam, ceftazidime or ceftolozane/tazobactam were used for initial treatment. We did not identify a clinical benefit for combination treatment.


Assuntos
Antibacterianos , Endocardite Bacteriana , Infecções por Pseudomonas , Pseudomonas aeruginosa , Humanos , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Endocardite Bacteriana/tratamento farmacológico , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/mortalidade , Adulto , Idoso , Pseudomonas aeruginosa/efeitos dos fármacos , Resultado do Tratamento , Tazobactam/uso terapêutico , Estudos Retrospectivos , Falha de Tratamento , Combinação Piperacilina e Tazobactam/uso terapêutico , Cefalosporinas
13.
Plast Reconstr Surg ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39046832

RESUMO

PURPOSE: To evaluate whether the sequence of osteotomies influences the accuracy of maxillary positioning in patients with cleft palate ± cleft lip undergoing bimaxillary orthognathic surgery (OGS). METHODS: This was a prospective study of patients with Veau 2-4 clefts who underwent bimaxillary OGS at tertiary-care children's hospital over a 3-year period. The primary predictor variable was the sequence of osteotomies (maxilla-first versus mandible-first). The primary outcome of interest was the concordance between the planned and achieved maxillary position, as assessed using linear and angular measurements. Secondary study predictors were demographic and surgical variables. Differences between groups were compared using non-parametric independent samples tests for continuous measures (data reported as median and interquartile range, IQR) and chi-squared tests for categorical measures. For all analyses, p≤ 0.05 was considered significant. RESULTS: Subjects who underwent maxilla-first (n=15) and mandible-first (n=16) operations were comparable with regard to age, gender, cleft type, skeletal classification, segmental maxillary osteotomy, and magnitude of maxillary movement (p ≥ 0.09). The planned sagittal and vertical positions of the maxilla were similarly accurate between the two groups (p ≥ 0.68). Angular accuracy was also comparable (p ≥ 0.56) between the study groups. CONCLUSION: In patients with CP ± CL undergoing bimaxillary orthognathic surgery, use of mandible-first sequencing, when compared to maxilla-first sequencing, does not impact accuracy of maxillary positioning in the immediate post-operative period in well-selected patients.

14.
J Neurosurg Spine ; : 1-10, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38996394

RESUMO

OBJECTIVE: Second cervical vertebrae (C2) fractures are a common traumatic spinal injury in the elderly population. Surgical fusion and nonoperative bracing are two primary treatments for cervical instability, but the former is often withheld in the elderly due to concerns for poor postoperative outcomes arising from patient frailty. This study sought to evaluate the in-hospital differences in mortality, outcomes, and discharge disposition in elderly patients with C2 fractures undergoing surgical intervention compared with conservative therapy. METHODS: The National Trauma Data Bank was queried from 2017 to 2019 for all patients aged ≥ 65 years with C2 fractures undergoing either surgical stabilization or conservative therapy. Propensity score matching was performed using k-nearest neighbors with replacement based on patient demographics, comorbidities, insurance type, injury severity, and fracture type. Group differences were compared using Student t-tests and Pearson's chi-square tests with Benjamini-Hochberg multiple comparisons correction. Subgroup analyses were performed in the 65-74, 75-79, and 80+ year age subgroups. RESULTS: Six thousand forty-nine patients were identified, of whom 2156 underwent surgery and 3893 received conservative treatment. Following matching, the surgery group had significantly lower mortality rates (5.52% vs 9.6%, p < 0.001), a longer mean hospital length of stay (LOS; 12.64 vs 7.49 days p < 0.001), and slightly higher rates of several complications (< 3% difference), as well as lower rates of discharge home (14.56% vs 23.52%, p < 0.001) and to hospice (1.07% vs 2.09%, p = 0.02) and a higher rate of discharge to intermediate care (68.83% vs 48.28%, p < 0.001). Similar trends in mortality and LOS were noted in all 3 subgroups. CONCLUSIONS: In elderly patients with C2 fractures, surgical stabilization confers a small survival advantage with a slightly higher in-hospital complication rate compared to conservative therapy. The increased rate of discharge to rehabilitation may represent better long-term prognosis following surgery. The increased risk of short-term complications is present but relatively small, thus surgery should not be withheld in patients with good long-term prognosis.

15.
Metabolites ; 14(7)2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39057703

RESUMO

This prospective study in Hong Kong aimed at identifying prognostic metabolomic and immunologic biomarkers for Coronavirus Disease 2019 (COVID-19). We examined 327 patients, mean age 55 (19-89) years, in whom 33.6% were infected with Omicron and 66.4% were infected with earlier variants. The effect size of disease severity on metabolome outweighed others including age, gender, peak C-reactive protein (CRP), vitamin D and peak viral levels. Sixty-five metabolites demonstrated strong associations and the majority (54, 83.1%) were downregulated in severe disease (z score: -3.30 to -8.61). Ten cytokines/chemokines demonstrated strong associations (p < 0.001), and all were upregulated in severe disease. Multiple pairs of metabolomic/immunologic biomarkers showed significant correlations. Fourteen metabolites had the area under the receiver operating characteristic curve (AUC) > 0.8, suggesting a high predictive value. Three metabolites carried high sensitivity for severe disease: triglycerides in medium high-density lipoprotein (MHDL) (sensitivity: 0.94), free cholesterol-to-total lipids ratio in very small very-low-density lipoprotein (VLDL) (0.93), cholesteryl esters-to-total lipids ratio in chylomicrons and extremely large VLDL (0.92);whereas metabolites with the highest specificity were creatinine (specificity: 0.94), phospholipids in large VLDL (0.94) and triglycerides-to-total lipids ratio in large VLDL (0.93). Five cytokines/chemokines, namely, interleukin (IL)-6, IL-18, IL-10, macrophage inflammatory protein (MIP)-1b and tumour necrosis factor (TNF)-a, had AUC > 0.8. In conclusion, we demonstrated a tight interaction and prognostic potential of metabolomic and immunologic biomarkers enabling an outcome-based patient stratification.

16.
Artigo em Inglês | MEDLINE | ID: mdl-38988331

RESUMO

Background: Minimally invasive surgical interventions for metastatic invasion of the pelvis have become more prevalent and varied. Our group hypothesized that the use of percutaneous photodynamic nails (PDNs) would result in decreased pain, improved functional outcomes and level of ambulation, and decreased use of opioid pain medication. Methods: We performed a retrospective chart review of patients with metastatic pelvic bone disease undergoing stabilization with PDNs (IlluminOss Medical) at 2 institutions. Functional outcome measures assessed include the Combined Pain and Ambulatory Function (CPAF), Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function, and PROMIS Global Health-Physical. Pain was assessed using a visual analog scale (VAS). Outcomes were assessed preoperatively and at 6 weeks, 3 months, 6 months, and 1 year following surgery. Results: A total of 39 patients treated with PDNs were included. No cases of surgical site infection or implant failure were identified. The median pain VAS score decreased from 8 preoperatively to 0 at the 6-week time point (p < 0.0001). The median CPAF score improved from 5.5 points preoperatively to 7 points at the 3-month mark (p = 0.0132). A significant improvement in physical function was seen at 6 months in the PROMIS Physical Function (p = 0.02) and at both 6 months (p = 0.01) and 1 year (p < 0.01) for the PROMIS Global Health-Physical. The rate of patients prescribed opioid analgesia dropped from 100% preoperatively to 20% at 6 months following surgery (p < 0.001). By 6 weeks, all patients were fully weight-bearing and able to walk independently with or without assistive devices. Conclusions: Percutaneous stabilization of metastatic periacetabular defects using PDNs is a safe and effective palliative procedure that has been shown to improve patient mobility and provide early pain relief. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

17.
Acta Neuropathol Commun ; 12(1): 114, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38997773

RESUMO

BACKGROUND: TAR DNA-Binding Protein 43 (TDP-43) pathological inclusions are a distinctive feature in dozens of neurodegenerative pathologies, including limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). Prior investigations identified vascular-associated TDP-43-positive micro-lesions, known as "Lin bodies," located on or near the brain capillaries of some individuals with LATE-NC. This study aimed to investigate the relationship between the accumulation of Lin bodies and glial cells in LATE-NC and the potential co-localization with ferritin, a protein associated with iron storage. Using multiplexed immunohistochemistry and digital pathology tools, we conducted pathological analyses to investigate the relationship between Lin bodies and glial markers (GFAP for astrocytes, IBA1 for microglia) and ferritin. Analyses were conducted on post-mortem brain tissues collected from individuals with pathologically confirmed Alzheimer's disease neuropathological changes (ADNC) and LATE-NC. RESULTS: As shown previously, there was a robust association between Lin bodies and GFAP-positive astrocyte processes. Moreover, we also observed Lin bodies frequently co-localizing with ferritin, suggesting a potential link to compromised vascular integrity. Subsequent analyses demonstrated increased astrocytosis near Lin body-positive vessels compared to those without Lin bodies, particularly in ADNC cases. These results suggest that the accumulation of Lin bodies may elicit an increased glial response, particularly among astrocytes, possibly related to impaired vascular integrity. CONCLUSIONS: Lin bodies are associated with a local reactive glial response. The strong association of Lin bodies with ferritin suggests that the loss of vascular integrity may be either a cause or a consequence of the pTDP-43 pathology. The reactive glia surrounding the affected vessels could further compromise vascular function.


Assuntos
Encéfalo , Proteínas de Ligação a DNA , Ferritinas , Humanos , Masculino , Feminino , Proteínas de Ligação a DNA/metabolismo , Idoso , Idoso de 80 Anos ou mais , Encéfalo/patologia , Encéfalo/metabolismo , Ferritinas/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Corpos de Inclusão/patologia , Corpos de Inclusão/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Astrócitos/patologia , Astrócitos/metabolismo , Proteinopatias TDP-43/patologia , Proteinopatias TDP-43/metabolismo , Neuroglia/patologia , Neuroglia/metabolismo , Pessoa de Meia-Idade , Demência
18.
JAMA Netw Open ; 7(7): e2420853, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38985472

RESUMO

Importance: Telehealth services expanded rapidly during the COVID-19 public health emergency (PHE). Objective: To evaluate changes in availability of telehealth services at outpatient mental health treatment facilities (MHTFs) throughout the US during and after the COVID-19 PHE. Design, Setting, and Participants: In this cohort study, callers posing as prospective clients contacted a random sample of 1404 MHTFs drawn from the Substance Abuse and Mental Health Services Administration's Behavioral Health Treatment Locator from December 2022 to March 2023 (wave 1 [W1]; during PHE). From September to November 2023 (wave 2 [W2]; after PHE), callers recontacted W1 participants. Analyses were conducted in January 2024. Main Outcomes and Measures: Callers inquired whether MHTFs offered telehealth (yes vs no), and, if yes, whether they offered (1) audio-only telehealth (vs audio and video); (2) telehealth for therapy, medication management, and/or diagnostic services; and (3) telehealth for comorbid alcohol use disorder (AUD). Sustainers (offered telehealth in both waves), late adopters (did not offer telehealth in W1 but did in W2), nonadopters (did not offer telehealth in W1 or W2), and discontinuers (offered telehealth in W1 but not W2) were all compared. Results: During W2, 1001 MHTFs (86.1%) were successfully recontacted. A total of 713 (71.2%) were located in a metropolitan county, 151 (15.1%) were publicly operated, and 935 (93.4%) accepted Medicaid as payment. The percentage offering telehealth declined from 799 (81.6%) to 765 (79.0%) (odds ratio [OR], 0.84; 95% CI, 0.72-1.00; P < .05). Among MHTFs offering telehealth, a smaller percentage in W2 offered audio-only telehealth (369 [49.3%] vs 244 [34.1%]; OR, 0.53; 95% CI, 0.44-0.64; P < .001) and telehealth for comorbid AUD (559 [76.3%] vs 457 [66.5%]; OR, 0.62; 95% CI, 0.50-0.76; P < .001) compared with W1. In W2, MHTFs were more likely to report telehealth was only available under certain conditions for therapy (141 facilities [18.0%] vs 276 [36.4%]; OR, 2.62; 95% CI, 1.10-3.26; P < .001) and medication management (216 facilities [28.0%] vs 304 [41.3%]; OR, 1.81; 95% CI, 1.48-2.21; P < .001). A total of 684 MHTFs (72.0%) constituted sustainers, 94 (9.9%) were discontinuers, 106 (11.2%) were nonadopters, and 66 (7.0%) were late adopters. Compared with sustainers, discontinuers were less likely to be private for-profit (adjusted OR [aOR], 0.28; 95% CI, 0.11-0.68) or private not-for-profit (aOR, 0.26; 95% CI, 0.14-0.48) after adjustment for facility and area characteristics. Conclusions and Relevance: Based on this longitudinal cohort study of 1001 MHTFs, telehealth availability has declined since the PHE end with respect to scope and modality of services, suggesting targeted policies may be necessary to sustain telehealth access.


Assuntos
COVID-19 , Acessibilidade aos Serviços de Saúde , Serviços de Saúde Mental , SARS-CoV-2 , Telemedicina , Humanos , COVID-19/epidemiologia , COVID-19/terapia , Telemedicina/estatística & dados numéricos , Masculino , Feminino , Serviços de Saúde Mental/organização & administração , Serviços de Saúde Mental/estatística & dados numéricos , Estados Unidos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Adulto , Pessoa de Meia-Idade , Transtornos Mentais/terapia , Transtornos Mentais/epidemiologia , Pandemias , Saúde Pública/métodos , Estudos de Coortes
19.
J Antimicrob Chemother ; 79(8): 1877-1884, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38831614

RESUMO

BACKGROUND: Candidaemia is associated with poor outcomes including high mortality rates. Controversy remains regarding whether fluconazole or an echinocandin is the optimal choice for initial candidaemia treatment, particularly among high-risk patients such as the immunocompromised or critically ill. OBJECTIVES: To understand optimal initial treatment of candidaemia. METHODS: We conducted a retrospective study of immunocompromised or ICU adult patients with candidaemia from 2010 to 2014. Patients who received ≥3 consecutive days of initial treatment with fluconazole or micafungin were included. The primary outcome was complete response at day 14, defined as clinical improvement and blood culture sterilization. Secondary outcomes included microbiological and clinical success, survival and recurrent candidaemia. RESULTS: A total of 197 patients were included; 76 received fluconazole and 121 received micafungin. There was no difference in complete response between the fluconazole and micafungin groups (ICU: 38% versus 40%, P = 0.87; immunocompromised: 57% versus 59%, P = 0.80). Secondary outcomes including survival were also similar. In multivariable analysis, among ICU patients, Pitt bacteraemia score < 4 (P = 0.002) and time to antifungal (P = 0.037) were associated with meeting the primary outcome; white blood cell count > 11 cells × 103/µL on day 0 (P < 0.001) and Candida isolated from a non-blood site (P = 0.025) were associated with not meeting the primary outcome. Among immunocompromised patients, white blood cells > 11 × 103/µL (P = 0.003) and Candida isolated from a non-blood site (P = 0.026) were associated with not meeting the primary outcome. CONCLUSIONS: These data suggest that among ICU or immunocompromised patients, severity of illness rather than initial antifungal choice drove clinical outcomes.


Assuntos
Antifúngicos , Candidemia , Estado Terminal , Equinocandinas , Fluconazol , Hospedeiro Imunocomprometido , Micafungina , Humanos , Micafungina/uso terapêutico , Micafungina/administração & dosagem , Antifúngicos/uso terapêutico , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Resultado do Tratamento , Candidemia/tratamento farmacológico , Candidemia/mortalidade , Idoso , Fluconazol/uso terapêutico , Fluconazol/administração & dosagem , Equinocandinas/uso terapêutico , Equinocandinas/administração & dosagem , Adulto , Lipopeptídeos/uso terapêutico , Lipopeptídeos/administração & dosagem , Análise de Sobrevida
20.
Adv Mater ; 36(35): e2401344, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38838094

RESUMO

This is a report on a pilot study that tests the feasibility of assembling photonic metamaterials (PMs) using light gradient forces. Following a strategy that works like modular construction, light gradient forces, produced by a tightly focused, 1D standing wave optical trap, time-multiplexed across a 2D lattice are used to assemble voxels consisting of prefabricated, monodispersed nanoparticles (NPs) with radii ranging from 30 to 500 nm into 3D structures on a hydrogel scaffold. Hundreds of NPs can be manipulated concurrently into a complex heterogeneous voxel this way, and then the process can be repeated by stitching together voxels to form a metamaterial of any size, shape, and constituency although imperfectly. Imperfections introduce random phase shifts and amplitude variations that can have an adverse effect on the band structure. Regardless, PMs are created this way using two different dielectric NPs, polystyrene and rutile, and then the near-infrared performance for each is analyzed with angle-, wavelength-, and polarization-dependent reflection spectroscopy. The cross-polarized spectra show evidence of a resonance peak. Interestingly, whereas the line shape from the polystyrene array is symmetric, the rutile array is not, which may be indicative of Fano resonance. So, even with the structural defects, reflection spectroscopy reveals a resonance.

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