Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 220
Filtrar
1.
Ecol Evol ; 14(8): e70077, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39114162

RESUMEN

Tree regeneration shapes forest carbon dynamics by determining long-term forest composition and structure, which suggests that threats to natural regeneration may diminish the capacity of forests to replace live tree carbon transferred to the atmosphere or other pools through tree mortality. Yet, the potential implications of tree regeneration patterns for future carbon dynamics have been sparsely studied. We used forest inventory plots to investigate whether the composition of existing tree regeneration is consistent with aboveground carbon stock loss, replacement, or gain for forests across the northeastern and midwestern USA, leveraging a recently developed method to predict the likelihood of sapling recruitment from seedling abundance tallied within six seedling height classes. A comparison of carbon stock predictions from tree and seedling composition suggested that 29% of plots were poised to lose carbon based on seedling composition, 55% were poised for replacement of carbon stocks (<5 Mg ha-1 difference) and 16% were poised to gain carbon. Forests predicted to lose carbon tended to be on steeper slopes, at lower latitudes, and in rolling upland environments. Although plots predicted to gain and lose carbon had similar stand ages, carbon loss plots had greater current carbon stocks. Synthesis and applications. Our results demonstrate the utility of considering tree regeneration through the lens of carbon replacement to develop effective management strategies to secure long-term carbon storage and resilience in the context of global change. Forests poised to lose C due to climate change and other stressors could be prioritized for regeneration strategies that enhance long-term carbon resilience and stewardship.

2.
J Neural Eng ; 21(4)2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39029499

RESUMEN

Objective. Macrophages and astrocytes play a crucial role in the aftermath of a traumatic spinal cord injury (SCI). Infiltrating macrophages adopt a pro-inflammatory phenotype while resident astrocytes adopt a neurotoxic phenotype at the injury site, both of which contribute to neuronal death and inhibit axonal regeneration. The cytokine interleukin-4 (IL-4) has shown significant promise in preclinical models of SCI by alleviating the macrophage-mediated inflammation and promoting functional recovery. However, its effect on neurotoxic reactive astrocytes remains to be elucidated, which we explored in this study. We also studied the beneficial effects of a sustained release of IL-4 from an injectable biomaterial compared to bolus administration of IL-4.Approach. We fabricated a heparin-based coacervate capable of anchoring and releasing bioactive IL-4 and tested its efficacyin vitroandin vivo. Main results. We show that IL-4 coacervate is biocompatible and drives a robust anti-inflammatory macrophage phenotype in culture. We also show that IL-4 and IL-4 coacervate can alleviate the reactive neurotoxic phenotype of astrocytes in culture. Finally, using a murine model of contusion SCI, we show that IL-4 and IL-4 coacervate, injected intraspinally 2 d post-injury, can reduce macrophage-mediated inflammation, and alleviate neurotoxic astrocyte phenotype, acutely and chronically, while also promoting neuroprotection with significant improvements in hindlimb locomotor recovery. We observed that IL-4 coacervate can promote a more robust regenerative macrophage phenotypein vitro, as well as match its efficacyin vivo,compared to bolus IL-4.Significance. Our work shows the promise of coacervate as a great choice for local and prolonged delivery of cytokines like IL-4. We support this by showing that the coacervate can release bioactive IL-4, which acts on macrophages and astrocytes to promote a pro-regenerative environment following a SCI leading to robust neuroprotective and functional outcomes.


Asunto(s)
Astrocitos , Interleucina-4 , Recuperación de la Función , Traumatismos de la Médula Espinal , Animales , Femenino , Ratones , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Células Cultivadas , Preparaciones de Acción Retardada/administración & dosificación , Interleucina-4/administración & dosificación , Interleucina-4/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Fenotipo , Recuperación de la Función/efectos de los fármacos , Recuperación de la Función/fisiología , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/metabolismo
3.
N Engl J Med ; 391(1): 69-76, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38959484

Asunto(s)
Humanos , Masculino
4.
J Environ Manage ; 366: 121786, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38991338

RESUMEN

Conservationists spend considerable resources to create and enhance wildlife habitat. Monitoring how species respond to these efforts helps managers allocate limited resources. However, monitoring efforts often encounter logistical challenges that are exacerbated as geographic extent increases. We used autonomous recording units (ARUs) and automated acoustic classification to mitigate the challenges of assessing Eastern Whip-poor-will (Antrostomus vociferus) response to forest management across the eastern USA. We deployed 1263 ARUs in forests with varying degrees of management intensity. Recordings were processed using an automated classifier and the resulting detection data were used to assess occupancy. Whip-poor-wills were detected at 401 survey locations. Across our study region, whip-poor-will occupancy decreased with latitude and elevation. At the landscape scale, occupancy decreased with the amount of impervious cover, increased with herbaceous cover and oak and evergreen forests, and exhibited a quadratic relationship with the amount of shrub-scrub cover. At the site-level, occupancy was negatively associated with basal area and brambles (Rubus spp.) and exhibited a quadratic relationship with woody stem density. Implementation of practices that create and sustain a mosaic of forest age classes and a diverse range of canopy closure within oak (Quercus spp.) dominated landscapes will have the highest probability of hosting whip-poor-wills. The use of ARUs and a machine learning classifier helped overcome challenges associated with monitoring a nocturnal species with a short survey window across a large spatial extent. Future monitoring efforts that combine ARU-based protocols and mappable fine-resolution structural vegetation data would likely further advance our understanding of whip-poor-will response to forest management.


Asunto(s)
Conservación de los Recursos Naturales , Ecosistema , Bosques , Animales , Conservación de los Recursos Naturales/métodos
5.
Neurol Genet ; 10(3): e200160, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38841627

RESUMEN

Objectives: Facial-onset sensory and motor neuronopathy (FOSMN) is a rare neuromuscular disorder characterized by progressive facial sensory impairment followed by motor dysfunction in a rostro-caudal distribution. FOSMN is clinically and pathologically associated with amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). In contrast to ALS/FTD, the genetic profile of patients with FOSMN and the role of genetic testing are poorly defined. Methods: A 66-year-old woman was evaluated in our neuromuscular clinic for progressive facial pain, dysphagia, and dysarthria. Her diagnostic evaluation included brain and cervical MRI, nerve conduction studies and EMG, and an ALS/FTD next-generation sequencing panel. Results: The patient was diagnosed with FOSMN, and we identified a N390D variant in transactive response DNA-binding protein (TDP-43/TARDBP). This variant has never been reported in FOSMN but was previously reported in 2 cases of ALS, and a N390S variant was also previously reported in FOSMN. A review of the literature revealed that TARDBP mutations are overrepresented in patients with FOSMN compared with patients with ALS/FTD. By contrast, other common familial forms of ALS, including C9ORF72 or SOD1, are respectively absent or rare in FOSMN. Discussion: FOSMN is pathologically and genetically associated with TDP-43. Therefore, ALS genetic testing that includes specifically TARDBP should be considered in patients with FOSMN.

6.
Biomaterials ; 309: 122598, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38696943

RESUMEN

Current vascular grafts, primarily Gore-Tex® and Dacron®, don't integrate with the host and have low patency in small-diameter vessels (<6 mm). Biomaterials that possess appropriate viscoelasticity, compliance, and high biocompatibility are essential for their application in small blood vessels. We have developed metal ion crosslinked poly(propanediol-co-(hydroxyphenyl methylene)amino-propanediol sebacate) (M-PAS), a biodegradable elastomer with a wide range of mechanical properties. We call these materials metallo-elastomers. An initial test on Zn-, Fe-, and Cu-PAS grafts reveals that Cu-PAS is the most suitable because of its excellent elastic recoil and well-balanced polymer degradation/tissue regeneration rate. Here we report host remodeling of Cu-PAS vascular grafts in rats over one year. 76 % of the grafts remain patent and >90 % of the synthetic polymer is degraded by 12 months. Extensive cell infiltration leads to a positive host remodeling. The remodeled grafts feature a fully endothelialized lumen. Circumferentially organized smooth muscle cells, elastin fibers, and widespread mature collagen give the neoarteries mechanical properties similar to native arteries. Proteomic analysis further reveals the presence of important vascular proteins in the neoarteries. Evidence suggests that Cu-PAS is a promising material for engineering small blood vessels.


Asunto(s)
Prótesis Vascular , Arterias Carótidas , Elastómeros , Animales , Elastómeros/química , Ratas , Masculino , Materiales Biocompatibles/química , Ratas Sprague-Dawley , Polímeros/química , Ensayo de Materiales
7.
Muscle Nerve ; 70(2): 166-172, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38801022

RESUMEN

The immune-mediated necrotizing myopathies (IMNM) are autoimmune myositides clinically characterized by proximal predominant weakness and elevated creatine kinase (CK). They may be associated with autoantibodies (anti-HMGCR, anti-SRP), triggered by statin use (e.g., anti-HMGCR myopathy), associated with cancer, or may be idiopathic. Immunotherapy is required to improve strength and decrease the CK level, but no therapies are currently approved by the U.S. Food and Drug Administration for the treatment of IMNM. The optimal treatment strategy for IMNM is currently unknown and wide practice variation exists in the management of this condition. However, observational studies and expert opinion suggest that certain therapies may be more effective for the different serological subtypes of IMNM. HMGCR IMNM often responds favorably to intravenous immunoglobulin (IVIG) even as monotherapy. Signal recognition peptide and seronegative IMNM typically require combination immunotherapy, most often consisting of an oral immunosuppressant, corticosteroids, and IVIG or rituximab. Patients often remain on immunotherapy for years and relapse is common during tapering of immunotherapy. Further studies are needed to guide the optimal management of these patients.


Asunto(s)
Miositis , Humanos , Miositis/inmunología , Miositis/terapia , Miositis/tratamiento farmacológico , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/terapia , Enfermedades Autoinmunes/tratamiento farmacológico , Inmunoterapia/métodos , Autoanticuerpos/inmunología , Inmunoglobulinas Intravenosas/uso terapéutico , Enfermedades Musculares/inmunología , Enfermedades Musculares/terapia , Enfermedades Musculares/tratamiento farmacológico , Hidroximetilglutaril-CoA Reductasas/inmunología , Necrosis , Manejo de la Enfermedad
8.
Ecol Evol ; 14(4): e11126, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38571787

RESUMEN

Cold-air pooling is an important topoclimatic process that creates temperature inversions with the coldest air at the lowest elevations. Incomplete understanding of sub-canopy spatiotemporal cold-air pooling dynamics and associated ecological impacts hinders predictions and conservation actions related to climate change and cold-dependent species and functions. To determine if and how cold-air pooling influences forest composition, we characterized the frequency, strength, and temporal dynamics of cold-air pooling in the sub-canopy at local to regional scales in New England, USA. We established a network of 48 plots along elevational transects and continuously measured sub-canopy air temperatures for 6-10 months (depending on site). We then estimated overstory and understory community temperature preferences by surveying tree composition in each plot and combining these data with known species temperature preferences. We found that cold-air pooling was frequent (19-43% seasonal occurrences) and that sites with the most frequent inversions displayed inverted forest composition patterns across slopes with more cold-adapted species, namely conifers, at low instead of high elevations. We also observed both local and regional variability in cold-air pooling dynamics, revealing that while cold-air pooling is common, it is also spatially complex. Our study, which uniquely focused on broad spatial and temporal scales, has revealed some rarely reported cold-air pooling dynamics. For instance, we discovered frequent and strong temperature inversions that occurred across seasons and in some locations were most frequent during the daytime, likely affecting forest composition. Together, our results show that cold-air pooling is a fundamental ecological process that requires integration into modeling efforts predicting future forest vegetation patterns under climate change, as well as greater consideration for conservation strategies identifying potential climate refugia for cold-adapted species.

10.
Nurs Philos ; 25(1): e12466, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37828850

RESUMEN

Many older gay men experience diminished psychological well-being (PWB) due to unique circumstances including discrimination, living with HIV, and aging through the HIV/AIDS crisis. However, there remains ambiguity as to how older gay men define and understand PWB. Our team interviewed and analyzed the accounts of 26 older (50+) self-identifying English-speaking men living in southwestern British Columbia, Canada. We drew on tenets of constructivist grounded theory and intersectionality to account for unique contextual considerations and power relations. Semi-structured Zoom interviews were conducted from August-October 2022. Interview transcripts were compared to generate high-order conceptual findings underpinned by processes understood as central to PWB. Three PWB temporal processes highlighted interlocking social and contextual circumstances intersecting with power and maturation: (1) being emotionally balanced, (2) living gratitude (3) and fully embracing self-acceptance. Being emotionally balanced supported the affective and sustainable state of contentment, living gratitude drew from the wisdom of accrued experiences to cultivate a positive affective state inclusive to recognising social location privileges, whilst fully embracing self-acceptance redressed the harms of anti-gay discourses that men endured throughout their lives. The knowledge is relevant to service and resource development to deliver tailored PWB supports to older gay men.


Asunto(s)
Infecciones por VIH , Minorías Sexuales y de Género , Masculino , Humanos , Homosexualidad Masculina/psicología , Canadá , Bienestar Psicológico , Formación de Concepto
11.
Lancet Neurol ; 22(10): 900-911, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37739573

RESUMEN

BACKGROUND: Inclusion body myositis is the most common progressive muscle wasting disease in people older than 50 years, with no effective drug treatment. Arimoclomol is an oral co-inducer of the cellular heat shock response that was safe and well-tolerated in a pilot study of inclusion body myositis, reduced key pathological markers of inclusion body myositis in two in-vitro models representing degenerative and inflammatory components of this disease, and improved disease pathology and muscle function in mutant valosin-containing protein mice. In the current study, we aimed to assess the safety, tolerability, and efficacy of arimoclomol in people with inclusion body myositis. METHODS: This multicentre, randomised, double-blind, placebo-controlled study enrolled adults in specialist neuromuscular centres in the USA (11 centres) and UK (one centre). Eligible participants had a diagnosis of inclusion body myositis fulfilling the European Neuromuscular Centre research diagnostic criteria 2011. Participants were randomised (1:1) to receive either oral arimoclomol 400 mg or matching placebo three times daily (1200 mg/day) for 20 months. The randomisation sequence was computer generated centrally using a permuted block algorithm with randomisation numbers masked to participants and trial staff, including those assessing outcomes. The primary endpoint was the change from baseline to month 20 in the Inclusion Body Myositis Functional Rating Scale (IBMFRS) total score, assessed in all randomly assigned participants, except for those who were randomised in error and did not receive any study medication, and those who did not meet inclusion criteria. Safety analyses included all randomly assigned participants who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, number NCT02753530, and is completed. FINDINGS: Between Aug 16, 2017 and May 22, 2019, 152 participants with inclusion body myositis were randomly assigned to arimoclomol (n=74) or placebo (n=78). One participant was randomised in error (to arimoclomol) but not treated, and another (assigned to placebo) did not meet inclusion criteria. 150 participants (114 [76%] male and 36 [24%] female) were included in the efficacy analyses, 73 in the arimoclomol group and 77 in the placebo group. 126 completed the trial on treatment (56 [77%] and 70 [90%], respectively) and the most common reason for treatment discontinuation was adverse events. At month 20, mean IBMFRS change from baseline was not statistically significantly different between arimoclomol and placebo (-3·26, 95% CI -4·15 to -2·36 in the arimoclomol group vs -2·26, -3·11 to -1·41 in the placebo group; mean difference -0·99 [95% CI -2·23 to 0·24]; p=0·12). Adverse events leading to discontinuation occurred in 13 (18%) of 73 participants in the arimoclomol group and four (5%) of 78 participants in the placebo group. Serious adverse events occurred in 11 (15%) participants in the arimoclomol group and 18 (23%) in the placebo group. Elevated transaminases three times or more of the upper limit of normal occurred in five (7%) participants in the arimoclomol group and one (1%) in the placebo group. Tubulointerstitial nephritis was observed in one (1%) participant in the arimoclomol group and none in the placebo group. INTERPRETATION: Arimoclomol did not improve efficacy outcomes, relative to placebo, but had an acceptable safety profile in individuals with inclusion body myositis. This is one of the largest trials done in people with inclusion body myositis, providing data on disease progression that might be used for subsequent clinical trial design. FUNDING: US Food and Drug Administration Office of Orphan Products Development and Orphazyme.


Asunto(s)
Miositis por Cuerpos de Inclusión , Estados Unidos , Adulto , Humanos , Animales , Femenino , Masculino , Ratones , Miositis por Cuerpos de Inclusión/tratamiento farmacológico , Proyectos Piloto , Método Doble Ciego , Progresión de la Enfermedad
12.
Handb Clin Neurol ; 195: 287-300, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37562873

RESUMEN

In this chapter, we discuss the indications for muscle, nerve, and skin biopsies, the techniques and normal processing of biopsy specimens, normal histological appearance, and the commonest histopathological abnormalities of different myopathies and neuropathies.


Asunto(s)
Enfermedades Musculares , Enfermedades del Sistema Nervioso Periférico , Humanos , Enfermedades del Sistema Nervioso Periférico/patología , Piel/inervación , Biopsia/métodos
13.
J Homosex ; : 1-20, 2023 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-37192266

RESUMEN

Some older gay men (50+) experience diminished quality of life (QOL) due to historical and ongoing discrimination in addition to living through a collective trauma-the pre-HAART era of the HIV/AIDS epidemic-characterized by the absence of treatment and rampant discrimination targeting gay men. A growing body of literature, however, illustrates that older gay men demonstrate remarkable resilience but little is known about how QOL is conceptualized and how these conceptualizations are potentially shaped by pre-HAART experiences. The current study drew on constructivist grounded theory methods to examine how QOL is conceptualized in light of the sociohistorical relevance of pre-HAART. Twenty Canadian based gay men aged 50+ participated in semi-structured interviews via Zoom. Ultimately, QOL is understood as experiencing contentment, which is made possible by the development and implementation of three key processes: (1) developing and cultivating meaningful connections, (2) growing into and embracing identity, and (3) appreciating the capacity to do what brings joy. QOL for this group is greatly informed by a context of disadvantage, and the demonstrated resilience warrants further investigation to meaningfully support the overall well-being of older gay men.

14.
Neurol Genet ; 9(3): e200073, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37123986

RESUMEN

Background and Objectives: The existence of clinical anticipation, congenital form, and parent-of-origin effect in myotonic dystrophy type 2 (DM2) remains uncertain. Here, we aimed at investigating whether there is a parent-of-origin effect on the age at the first DM2-related clinical manifestation. Methods: We identified patients with genetically confirmed DM2 with known parental inheritance from (1) the electronic medical records of our institutions and (2) a systematic review of the literature following the PRISMA 2020 guidelines and recorded their age at and type of first disease-related symptom. We also interrogated the Myotonic Dystrophy Foundation Family Registry (MDFFR) for patients with DM2 who completed a survey including questions about parental inheritance and age at the first medical problem which they related to their DM2 diagnosis. Results: A total of 26 patients with DM2 from 18 families were identified at our institutions as having maternal (n = 14) or paternal (n = 12) inheritance of the disease, whereas our systematic review of the literature rendered a total of 61 patients with DM2 from 41 families reported by 24 eligible articles as having maternal (n = 40) or paternal (n = 21) inheritance of the disease. Both cohorts were combined for downstream analyses. Up to 61% and 58% of patients had muscle-related symptoms as the first disease manifestation in maternally and paternally inherited DM2 subgroups, respectively. Four patients developed hypotonia at birth and/or delayed motor milestones early in life, and 7 had nonmuscular presentations (2 had cardiac events within the second decade of life and 5 had cataracts), all of them with maternal inheritance. A maternal inheritance was associated with an earlier (within the first 3 decades of life) age at symptom onset relative to a paternal inheritance in this combined cohort, and this association was independent of the patient's sex (OR [95% CI] = 4.245 [1.429-13.820], p = 0.0117). However, this association was not observed in the MDFFR DM2 cohort (n = 127), possibly because age at onset was self-reported, and the information about the type of first symptom or medical problem that patients related to DM2 was lacking. Discussion: A maternal inheritance may increase the risk of an early DM2 onset and of cataracts and cardiovascular events as first DM2 manifestations.

15.
J Vitreoretin Dis ; 7(2): 165-170, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37006658

RESUMEN

Purpose: To report a case of bilateral occlusive retinal vasculitis in a patient with autoimmunity. Methods: A case was analyzed and a literature review performed. Results: A 55-year-old woman with autoimmune diagnoses of Isaacs syndrome and inclusion body myositis (IBM) reported decreased vision for 3 months. A fundus examination showed peripheral intraretinal hemorrhages in the right eye and an inferotemporal subhyaloid hemorrhage with adjacent intraretinal hemorrhages and preretinal fibrosis in the left eye. Fluorescein angiography showed temporal peripheral leakage and capillary dropout in both eyes, consistent with occlusive vasculitis. Scatter laser treatment to peripheral areas of retinal nonperfusion was followed by an intravitreal bevacizumab injection. Four months later, vision had stabilized at 20/15 in both eyes and the peripheral leakage had resolved. Conclusions: This patient developed retinal vasculitis associated with the rare autoimmune neuromuscular disorders of Isaacs syndrome and IBM. An extensive workup showed the most plausible mechanism for the vasculitis was autoimmunity with a history of previously elevated antibodies levels associated with the antiphospholipid syndrome.

16.
Rheumatology (Oxford) ; 62(11): 3672-3679, 2023 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-36929923

RESUMEN

OBJECTIVE: The ACR-EULAR Myositis Response Criteria (MRC) were developed as a composite measure using absolute percentage change in six core set measures (CSMs). We aimed to further validate the MRC by assessing the contribution of each CSM, frequency of strength vs extramuscular activity improvement, representation of patient-reported outcome measures (PROM), and frequency of CSM worsening. METHODS: Data from adult dermatomyositis/polymyositis patients in the rituximab (n = 147), etanercept (n = 14), and abatacept (n = 19) trials, and consensus patient profiles (n = 232) were evaluated. The Total Improvement Score (TIS), number of improving vs worsening CSMs, frequency of improvement with and without muscle-related CSMs, and contribution of PROM were evaluated by MRC category. Regression analysis was performed to assess contribution of each CSM to the MRC. RESULTS: Of 412 adults with dermatomyositis/polymyositis, there were 37%, 24%, 25%, and 14% with no, minimal, moderate, and major MRC improvement, respectively. The number of improving CSMs and absolute percentage change in all CSMs increased by improvement category. In minimal-moderate improvement, only physician-reported disease activity contributed significantly more than expected by MRC. Of patients with at least minimal improvement, 95% had improvement in muscle-related measures and a majority (84%) had improvement in PROM. Patients with minimal improvement had worsening in a median of 1 CSM, and most patients with moderate-major improvement had no worsening CSMs. Physician assessment of change generally agreed with MRC improvement categories. CONCLUSION: The ACR-EULAR MRC performs consistently across multiple studies, further supporting its use as an efficacy end point in future myositis therapeutic trials.


Asunto(s)
Dermatomiositis , Miositis , Polimiositis , Adulto , Humanos , Dermatomiositis/tratamiento farmacológico , Consenso , Resultado del Tratamiento , Polimiositis/tratamiento farmacológico , Miositis/tratamiento farmacológico
17.
Semin Neurol ; 43(2): 251-259, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37001556

RESUMEN

Accumulating evidence in the third year of the global pandemic suggests that coronavirus disease 2019 (COVID-19) can cause neuromuscular complications during or after the acute phase of infection. Direct viral infection and immune-mediated mechanisms have been hypothesized. Furthermore, in patients with underlying autoimmune neuromuscular diseases, COVID-19 infection may trigger a disease flare. COVID-19 vaccines appear to be safe and effective at preventing severe illness from COVID-19. Certain vaccines are associated with an increased risk of Guillain-Barré syndrome and possibly Bell's palsy, but the absolute incidence is low, and benefits likely outweigh the risks. Newer prophylactic therapies and treatments are also becoming available for patients who may not mount a sufficient response to vaccination or have contraindications. In this article, we discuss the current available evidence on neuromuscular complications of COVID-19 and clinical considerations regarding vaccination.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Síndrome de Guillain-Barré , Humanos , COVID-19/complicaciones , COVID-19/epidemiología , Vacunas contra la COVID-19/administración & dosificación , Síndrome de Guillain-Barré/epidemiología , Síndrome de Guillain-Barré/etiología , Pandemias/prevención & control , Vacunación/efectos adversos
18.
Lancet Rheumatol ; 5(2): e67-e76, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36923454

RESUMEN

Background: Immune-mediated necrotizing myopathy (IMNM) is an autoimmune myopathy characterised by proximal muscle weakness, high creatine kinase (CK) values, and autoantibodies recognizing 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) or the signal recognition particle (SRP). There are currently no approved therapies for IMNM and many patients experience active disease despite off-label treatment with intravenous immunoglobulin, glucocorticoids, and immunosuppressants. Detection of complement-activating anti-HMGCR and anti-SRP autoantibodies and the presence of complement deposition on the sarcolemma of non-necrotic myofibers led to the hypothesis that complement activation may be pathogenic in IMNM, therefore zilucoplan, a complement component 5 (C5) inhibitor, could be a potential therapy. Methods: IMNM01, a phase 2, multicenter, randomised, double-blind, placebo-controlled study (NCT04025632) at 15 sites (four countries) evaluated efficacy, safety, and tolerability of zilucoplan in adult participants with anti-HMGCR or anti-SRP autoantibody-positive IMNM. Participants were randomised 1:1 to receive daily subcutaneous zilucoplan (0·3mg/kg) or placebo for eight weeks; with optional enrolment in the study open-label extension. Primary efficacy endpoint was percent change from baseline to Week 8 in CK levels. Secondary endpoints included safety. Findings: Between 07 November 2019 and 07 January 2021, 27 participants (13 female and 14 male) received zilucoplan (n=12) or placebo (n=15) and completed the 8-week main study. At Week 8 there were no clinically relevant or statistically significant differences, despite target engagement based on mode of action, between treatment arms in mean percent change (standard deviation) of CK levels versus baseline (-9·86% [26·06] versus -20·72% [31·22] in zilucoplan [n=10] and placebo arms [n=14], p=0·46, respectively) and no clinically relevant improvement over time within the treatment arm. There were no unexpected adverse safety or tolerability findings. Treatment emergent adverse events (TEAEs) and serious TEAEs were reported in n=9 (75·0%) vs n=13 (86·7%) and n=0 (0%) and n=3 (20·0%) participants, respectively. The most frequent TEAEs were headache (n=4 in both groups [33·3% and 26·7%, respectively]) and nausea (n=3 in both groups [25·0% and 20·0%, respectively]). Interpretation: C5 inhibition does not appear to be an effective treatment modality for IMNM. Rather than driving myofiber necrosis, complement activation may be secondary to muscle injury. Funding: Study funded by Ra Pharmaceuticals (now part of UCB Pharma).

19.
Ecology ; 104(6): e4039, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36960918

RESUMEN

Following a disturbance, dispersal shapes community composition as well as ecosystem structure and function. For fungi, dispersal is often wind or mammal facilitated, but it is unclear whether these pathways are complementary or redundant in the taxa they disperse and the ecosystem functions they provide. Here, we compare the diversity and morphology of fungi dispersed by wind and three rodent species in recently harvested forests using a combination of microscopy and Illumina sequencing. We demonstrate that fungal communities dispersed by wind and small mammals differ in richness and composition. Most wind-dispersed fungi are wood saprotrophs, litter saprotrophs, and plant pathogens, whereas fungi dispersed in mammal scat are primarily mycorrhizal, soil saprotrophs, and unspecified saprotrophs. We note substantial dispersal of truffles and agaricoid mushrooms by small mammals, and dispersal of agaricoid mushrooms, crusts, and polypores by wind. In addition, we find mammal-dispersed spores are larger than wind-dispersed spores. Our findings suggest that wind- and small-mammal-facilitated dispersal are complementary processes and highlight the role of small mammals in dispersing mycorrhizal fungi, particularly following disturbances such as timber harvest.


Asunto(s)
Ecosistema , Micorrizas , Animales , Viento , Bosques , Mamíferos , Roedores , Microbiología del Suelo , Hongos , Suelo , Esporas Fúngicas
20.
SSM Qual Res Health ; 3: 100233, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36777813

RESUMEN

Pandemics are a component of human life, and have had great bearing on the trajectory of human evolution. Historically, the biomedical aspects of pandemics have been overrepresented, but there is growing recognition of the degree to which pandemics are socially and culturally embedded, highlighting how virus perception is socially and politically informed. Older (50+), gay men represent a population who have experienced two global pandemics in their lifespans: HIV/AIDS and COVID-19. Although governments and health officials largely failed gay men during the HIV/AIDS pandemic, gay men represent an important source of pandemic information and their experiences have much to offer health professionals and policymakers. As such, a small but growing body of literature has compared gay men's experiences amidst the two pandemics. The current study drew on constructivist grounded theory methods to examine how living through the HIV/AIDS pandemic has influenced older gay men's perspectives of COVID-19. Twenty Canadian-based gay men aged 50+ participated in semi-structured interviews via Zoom. Analysis revealed three key processes: (1) uncertainty and the familiarity of loss, (2) witnessing pandemic inequities, and, (3) navigating constantly evolving (mis)information. We highlight the utility of this knowledge to informing future pandemic planning and policies.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...