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2.
J Am Dent Assoc ; 155(6): 515-525.e1, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38839239

ABSTRACT

BACKGROUND: Dental unit waterline (DWL) infection control is critical to infection prevention. Identifying challenges and barriers to its implementation is a first step toward understanding how to improve engagement. METHODS: A survey was distributed to dentists, dental hygienists, and dental assistants via the Qualtrics XM platform (Qualtrics). Responses were analyzed to quantify engagement in practices contrary to Centers for Disease Control and Prevention guidance and identify avenues to improve engagement. RESULTS: Although oral health care providers recognized DWL infection control was important, there was a lack of clarity about appropriate routine engagement (eg, what lines should be tested), what should be noted in practice infection control records, and steps to be taken in response to a failed test result (ie, ≥ 500 colony-forming units/mL), such as taking a chair out of service. CONCLUSIONS: Survey results showed there were considerable gaps in knowledge and practice that could lead to patient harm. Oral health care provider training may not prepare personnel adequately to engage in, let alone supervise, DWL infection control. DWL infection control, like other aspects of infection control, requires action informed via an understanding of what needs to be done. Although good intentions are appreciated, better approaches to DWL infection control information dissemination and strategies to engage dental assistants, dental hygienists, and dentists in best practices are needed. PRACTICAL IMPLICATIONS: Evolving standards of care, including infection control, should be reflected in the provision of dental treatment. Improvements in communicating and ensuring engagement in best practices are needed when it comes to DWL infection control.


Subject(s)
Infection Control, Dental , Humans , Infection Control, Dental/methods , Dental Hygienists , Surveys and Questionnaires , Dentists , Dental Equipment , Equipment Contamination/prevention & control , Health Knowledge, Attitudes, Practice , Dental Assistants
4.
Front Immunol ; 15: 1330796, 2024.
Article in English | MEDLINE | ID: mdl-38665909

ABSTRACT

Introduction: There is no useful method to discriminate between latent tuberculosis infection (LTBI) and active pulmonary tuberculosis (PTB). This study aimed to investigate the potential of cytokine profiles to discriminate between LTBI and active PTB using whole-blood stimulation with Mycobacterium tuberculosis (MTB) antigens, including latency-associated antigens. Materials and methods: Patients with active PTB, household contacts of active PTB patients and community exposure subjects were recruited in Manila, the Philippines. Peripheral blood was collected from the participants and used for whole-blood stimulation (WBS) with either the early secretory antigenic target and the 10-kDa culture filtrate protein (ESAT-6/CFP-10), Rv3879c or latency-associated MTB antigens, including mycobacterial DNA-binding protein 1 (MDP-1), α-crystallin (Acr) and heparin-binding hemagglutinin (HBHA). Multiple cytokine concentrations were analyzed using the Bio-Plex™ multiplex cytokine assay. Results: A total of 78 participants consisting of 15 active PTB patients, 48 household contacts and 15 community exposure subjects were eligible. The MDP-1-specific IFN-γ level in the active PTB group was significantly lower than that in the household contact group (p < 0.001) and the community exposure group (p < 0.001). The Acr-specific TNF-α and IL-10 levels in the active PTB group were significantly higher than those in the household contact (TNF-α; p = 0.001, IL-10; p = 0.001) and community exposure (TNF-α; p < 0.001, IL-10; p = 0.01) groups. However, there was no significant difference in the ESAT-6/CFP-10-specific IFN-γ levels among the groups. Conclusion: The patterns of cytokine profiles induced by latency-associated MTB antigens using WBS have the potential to discriminate between LTBI and active PTB. In particular, combinations of IFN-γ and MDP-1, TNF-α and Acr, and IL-10 and Acr are promising. This study provides the first demonstration of the utility of MDP-1-specific cytokine responses in WBS.


Subject(s)
Antigens, Bacterial , Cytokines , Latent Tuberculosis , Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Humans , Antigens, Bacterial/immunology , Antigens, Bacterial/blood , Male , Latent Tuberculosis/diagnosis , Latent Tuberculosis/immunology , Latent Tuberculosis/blood , Latent Tuberculosis/microbiology , Female , Mycobacterium tuberculosis/immunology , Philippines , Adult , Cytokines/blood , Middle Aged , Tuberculosis, Pulmonary/immunology , Tuberculosis, Pulmonary/blood , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/microbiology , Young Adult , Bacterial Proteins/immunology
5.
Geriatrics (Basel) ; 9(2)2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38667513

ABSTRACT

INTRODUCTION: We conducted a head-to-head comparison of step 2 (tramadol) and step 3 (oxycodone) of the WHO pain ladder in older adults with moderate to severe acute locomotor pain. MATERIALS AND METHODS: Multi-center prospective randomized study. Patients were 70 years or older, admitted to the acute geriatric ward of three hospitals, suffering from acute moderate to severe locomotor pain, and opioid-naive. Patients were randomized into two treatment groups: tramadol versus oxycodone. The Consort reporting guidelines were used. RESULTS: Forty-nine patients were included. Mean numeric rating scale (NRS) decreased significantly between day 0 and 2 of the inclusion in both groups. A sustained significant decrease in mean NRS was seen at day 7 in both groups. Nausea was significantly more prevalent in the tramadol group, with a trend towards a higher prevalence of delirium and falls and three serious adverse events in the same group. CONCLUSIONS: Opioid therapy may be considered as a short-term effective treatment for moderate to severe acute locomotor pain in older adults. Oxycodone may possibly be preferred for safety reasons. These results can have implications for geriatric practice, showing that opioids for treatment of acute moderate to severe locomotor pain in older patients are effective and safe if carefully monitored for side effects. Opioid therapy may be considered as a short-term treatment for moderate to severe acute locomotor pain in older adults, if carefully monitored for (side) effects, while oxycodone may possibly be preferred for safety reasons. These results can have implications for daily practice in geriatric, orthopedic, and orthogeriatric wards, as well as in terminal care, more precisely for the treatment of moderate to severe acute locomotor pain in older adults.

6.
J Proteome Res ; 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38686625

ABSTRACT

NPC intracellular cholesterol transporter 1 (NPC1) is a multipass, transmembrane glycoprotein mostly recognized for its key role in facilitating cholesterol efflux. Mutations in the NPC1 gene result in Niemann-Pick disease, type C (NPC), a fatal, lysosomal storage disease. Due to the progressively expanding implications of NPC1-related disorders, we investigated endogenous NPC1 protein-protein interactions in the mouse cortex and human-derived iPSCs neuronal models of the disease through coimmunoprecipitation-coupled with LC-MS based proteomics. The current study investigated protein-protein interactions specific to the wild-type and the most prevalent NPC1 mutation (NPC1I1061T) while filtering out any protein interactor identified in the Npc1-/- mouse model. Additionally, the results were matched across the two species to map the parallel interactome of wild-type and mutant NPC1I1061T. Most of the identified wild-type NPC1 interactors were related to cytoskeleton organization, synaptic vesicle activity, and translation. We found many putative NPC1 interactors not previously reported, including two SCAR/WAVE complex proteins that regulate ARP 2/3 complex actin nucleation and multiple membrane proteins important for neuronal activity at synapse. Moreover, we identified proteins important in trafficking specific to wild-type and mutant NPC1I1061T. Together, the findings are essential for a comprehensive understanding of NPC1 biological functions in addition to its classical role in sterol efflux.

7.
Nat Commun ; 15(1): 1215, 2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38331971

ABSTRACT

Tissue adhesives are promising alternatives to sutures and staples for joining tissues, sealing defects, and immobilizing devices. However, existing adhesives mostly take the forms of glues or hydrogels, which offer limited versatility. We report a direct-ink-write 3D printable tissue adhesive which can be used to fabricate bioadhesive patches and devices with programmable architectures, unlocking new potential for application-specific designs. The adhesive is conformable and stretchable, achieves robust adhesion with wet tissues within seconds, and exhibits favorable biocompatibility. In vivo rat trachea and colon defect models demonstrate the fluid-tight tissue sealing capability of the printed patches, which maintained adhesion over 4 weeks. Moreover, incorporation of a blood-repelling hydrophobic matrix enables the printed patches to seal actively bleeding tissues. Beyond wound closure, the 3D printable adhesive has broad applicability across various tissue-interfacing devices, highlighted through representative proof-of-concept designs. Together, this platform offers a promising strategy toward developing advanced tissue adhesive technologies.


Subject(s)
Tissue Adhesives , Rats , Animals , Tissue Adhesives/chemistry , Adhesives , Hydrogels/chemistry , Technology
8.
Proc Biol Sci ; 291(2017): 20231534, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38378154

ABSTRACT

In mesophotic coral ecosystems, reef-building corals and their photosynthetic symbionts can survive with less than 1% of surface irradiance. How depth-specialist corals rely upon autotrophically and heterotrophically derived energy sources across the mesophotic zone remains unclear. We analysed the stable carbon (δ13C) and nitrogen (δ15N) isotope values of a Leptoseris community from the 'Au'au Channel, Maui, Hawai'i (65-125 m) including four coral host species living symbiotically with three algal haplotypes. We characterized the isotope values of hosts and symbionts across species and depth to compare trophic strategies. Symbiont δ13C was consistently 0.5‰ higher than host δ13C at all depths. Mean colony host and symbiont δ15N differed by up to 3.7‰ at shallow depths and converged at deeper depths. These results suggest that both heterotrophy and autotrophy remained integral to colony survival across depth. The increasing similarity between host and symbiont δ15N at deeper depths suggests that nitrogen is more efficiently shared between mesophotic coral hosts and their algal symbionts to sustain autotrophy. Isotopic trends across depth did not generally vary by host species or algal haplotype, suggesting that photosynthesis remains essential to Leptoseris survival and growth despite low light availability in the mesophotic zone.


Subject(s)
Anthozoa , Animals , Ecosystem , Coral Reefs , Hawaii , Autotrophic Processes , Nitrogen , Isotopes
9.
Glob Adv Integr Med Health ; 13: 27536130241231736, 2024.
Article in English | MEDLINE | ID: mdl-38322150

ABSTRACT

Background: To improve the implementation of clinical trial interventions, there is a need to facilitate communication between key stakeholders and research teams. Community Advisory Boards (CAB) bring together a range of stakeholders not historically included in the research process to inform and work collaboratively with research teams. Objective: To describe our procedures and processes for (1) integration of a CAB into a pragmatic clinical trial of a telehealth-delivered group mindfulness program for persons with chronic low back pain (cLBP) within primary care, and (2) for the rapid uptake and implementation of CAB recommendations. Methods: The CAB we convened includes persons with cLBP who have undergone the mindfulness intervention, health care system leadership, advocacy groups, and mindfulness experts. The CAB members underwent a two hour initial training that introduced the research process and the CAB's role as research partners. The CAB met monthly for 1 hour. We used the Lighting Report method to summarize meetings and share feedback with the research team. Results: The recommendations of the CAB during the first year they met were divided into recruitment, informed consent, and survey recommendations. The study website also was overhauled based on recommendations, including a more engaging first page with rotating images of nature and testimonials. The language on the website was edited to be more concise and participant-friendly. The CAB recommended talking points to discuss with participants during screening or informed consent about the benefits of participating in research. Conclusion: We established a CAB that represented diverse perspectives, organizations, and experience with cLBP and mindfulness. The differing perspectives of the CAB resulted in recommendations that the research team itself would not have decided on their own. The Lightning Reports were also an effective way to efficiently communicate the CAB recommendations to the research team.

10.
J Am Dent Assoc ; 155(4): 280-293.e4, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38300176

ABSTRACT

BACKGROUND: The value of dental radiographs to oral health care decision making must be balanced with radiation safety to minimize patient exposure and occupational risk of oral health care providers. This review summarizes recommendations and regulatory guidance regarding dental radiography and cone-beam computed tomography. An expert panel presents recommendations on radiation safety, appropriate imaging practices, and reducing radiation exposure. TYPES OF STUDIES REVIEWED: A systematic search run in Ovid MEDLINE, Embase, and Cochrane Database of Systematic Reviews identified relevant topical systematic reviews, organizational guidelines, and regulatory reviews published in the peer-reviewed literature since 2010. A supplemental search of the gray literature (eg, technical reports, standards, and regulations) identified topical nonindexed publications. Inclusion criteria required relevance to primary oral health care (ie, general or pediatric dentistry). RESULTS: A total of 95 articles, guidance documents, and regulations met the inclusion criteria. Resources were characterized as applicable to all modalities, operator and occupational protection, dose reduction and optimization, and quality assurance and control. PRACTICAL IMPLICATIONS: Understanding factors affecting imaging safety and applying fundamental principles of radiation protection consistent with federal, state, and local requirements are essential for limiting patient ionizing radiation exposure, in conjunction with implementing optimal imaging procedures to support prudent use of dental radiographs and cone-beam computed tomographic imaging. The regulatory guidance and best practice recommendations summarized in this article should be followed by dentists and other oral health care providers.


Subject(s)
Cone-Beam Computed Tomography , Pediatric Dentistry , Child , Humans , Systematic Reviews as Topic , Cone-Beam Computed Tomography/methods , Radiography, Dental/methods , Radiation Dosage
11.
Ann Med ; 56(1): 2310132, 2024 12.
Article in English | MEDLINE | ID: mdl-38294956

ABSTRACT

Introduction: Adverse effects of opioids are common among older individuals, and undertreatment as well as overuse can be an issue. Epidemiological data on opioid use in older individuals are available, but scarce in hospitalized patients.Aims: The aim of this study is to examine the one-day prevalence of opioid use among older inpatients and identify the factors associated with both opioid use and dosage.Materials and methods: One-day cross-sectional study with data collected from geriatric units across 14 Belgian hospitals. The primary focus of the study is to assess the prevalence of opioid use and dosage, along with identifying associated factors. To achieve this, a multiple binary logistic regression model was fitted for opioid use, and a multiple linear regression model for opioid dose.Results: Opioids were used in 24.4% of 784 patients, of which 57.9% was treated with tramadol, 13.2% with oxycodone or morphine and 28.9% with transdermal buprenorphine or fentanyl. The odds for opioid use were 4.2 times higher in patients in orthogeriatric units compared to other patients (OR=4.2, 95% CI=2.50-7.05). The prevalence of opioid use was 34% higher in patients without dementia compared to patients with dementia (OR=0.66, 95% CI=0.46-0.95). The overall mean daily dosage was 14.07mg subcutaneous morphine equivalent. After adjustment for age, gender and dementia, dosage was only associated with type of opioid: the estimated mean opioid dose was 70% lower with tramadol (mean ratio=0,30,95% CI=0,23-0,39) and 67% lower with oxycodone and morphine (mean ratio=0,33, 95% CI=0,22-0,48) compared to transdermal buprenorphine and transdermal fentanyl.Conclusions: One in four patients received opioid treatment. It is not clear whether this reflects under- or overtreatment, but these results can serve as a benchmark for geriatric units to guide future pain management practices. The utilization of transdermal fentanyl and buprenorphine, resulting in higher doses of morphine equivalent, poses significant risks for side effects.


Subject(s)
Buprenorphine , Dementia , Tramadol , Humans , Aged , Analgesics, Opioid/adverse effects , Oxycodone/adverse effects , Tramadol/adverse effects , Cross-Sectional Studies , Belgium/epidemiology , Prevalence , Fentanyl/adverse effects , Morphine/adverse effects , Buprenorphine/adverse effects , Dementia/drug therapy , Dementia/epidemiology , Dementia/chemically induced
12.
Tree Physiol ; 44(1)2024 02 06.
Article in English | MEDLINE | ID: mdl-38070183

ABSTRACT

Stomatal density, stomatal length and carbon isotope composition can all provide insights into environmental controls on photosynthesis and transpiration. Stomatal measurements can be time-consuming; it is therefore wise to consider efficient sampling schemes. Knowing the variance partitioning at different measurement levels (i.e., among stands, plots, trees, leaves and within leaves) can aid in making informed decisions around where to focus sampling effort. In this study, we explored the effects of nitrogen (N), phosphorus (P) and calcium silicate (CaSiO3) addition on stomatal density, length and carbon isotope composition (δ13C) of sugar maple (Acer saccharum Marsh.) and yellow birch (Betula alleghaniensis Britton). We observed a positive but small (8%) increase in stomatal density with P addition and an increase in δ13C with N and CaSiO3 addition in sugar maple, but we did not observe effects of nutrient addition on these characteristics in yellow birch. Variability was highest within leaves and among trees for stomatal density and highest among stomata for stomatal length. To reduce variability and increase chances of detecting treatment differences in stomatal density and length, future protocols should consider pretreatment and repeated measurements of trees over time or measure more trees per plot, increase the number of leaf impressions or standardize their locations, measure more stomata per image and ensure consistent light availability.


Subject(s)
Acer , Betula , Betula/physiology , Acer/physiology , Carbon Isotopes , Trees/physiology , Fertilization , Plant Leaves/physiology
13.
CA Cancer J Clin ; 74(1): 50-81, 2024.
Article in English | MEDLINE | ID: mdl-37909877

ABSTRACT

Lung cancer is the leading cause of mortality and person-years of life lost from cancer among US men and women. Early detection has been shown to be associated with reduced lung cancer mortality. Our objective was to update the American Cancer Society (ACS) 2013 lung cancer screening (LCS) guideline for adults at high risk for lung cancer. The guideline is intended to provide guidance for screening to health care providers and their patients who are at high risk for lung cancer due to a history of smoking. The ACS Guideline Development Group (GDG) utilized a systematic review of the LCS literature commissioned for the US Preventive Services Task Force 2021 LCS recommendation update; a second systematic review of lung cancer risk associated with years since quitting smoking (YSQ); literature published since 2021; two Cancer Intervention and Surveillance Modeling Network-validated lung cancer models to assess the benefits and harms of screening; an epidemiologic and modeling analysis examining the effect of YSQ and aging on lung cancer risk; and an updated analysis of benefit-to-radiation-risk ratios from LCS and follow-up examinations. The GDG also examined disease burden data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program. Formulation of recommendations was based on the quality of the evidence and judgment (incorporating values and preferences) about the balance of benefits and harms. The GDG judged that the overall evidence was moderate and sufficient to support a strong recommendation for screening individuals who meet the eligibility criteria. LCS in men and women aged 50-80 years is associated with a reduction in lung cancer deaths across a range of study designs, and inferential evidence supports LCS for men and women older than 80 years who are in good health. The ACS recommends annual LCS with low-dose computed tomography for asymptomatic individuals aged 50-80 years who currently smoke or formerly smoked and have a ≥20 pack-year smoking history (strong recommendation, moderate quality of evidence). Before the decision is made to initiate LCS, individuals should engage in a shared decision-making discussion with a qualified health professional. For individuals who formerly smoked, the number of YSQ is not an eligibility criterion to begin or to stop screening. Individuals who currently smoke should receive counseling to quit and be connected to cessation resources. Individuals with comorbid conditions that substantially limit life expectancy should not be screened. These recommendations should be considered by health care providers and adults at high risk for lung cancer in discussions about LCS. If fully implemented, these recommendations have a high likelihood of significantly reducing death and suffering from lung cancer in the United States.


Subject(s)
Lung Neoplasms , Smoking , Female , Humans , Male , American Cancer Society , Early Detection of Cancer/methods , Lung Neoplasms/diagnosis , Lung Neoplasms/epidemiology , Mass Screening/methods , Risk Assessment , United States/epidemiology , Smoking/adverse effects , Smoking/epidemiology , Middle Aged , Aged , Aged, 80 and over , Systematic Reviews as Topic
14.
Diabetes Spectr ; 36(4): 364-372, 2023.
Article in English | MEDLINE | ID: mdl-38024218

ABSTRACT

Objective: Given the bidirectional relationship between type 2 diabetes and periodontal disease, this study sought to compile the available data regarding the relationship between home oral hygiene, specifically toothbrushing, and glycemic control and oral health in people with type 2 diabetes. Methods: A systematic scoping review was conducted using a combination of controlled vocabulary and keyword terms for type 2 diabetes and home oral care in PubMed and CINHAL. Publications from the past 20 years were considered for inclusion. Study data were summarized. Results: A total of 11 studies met our inclusion criteria. In all survey research identified, self-report of more frequent toothbrushing in people with type 2 diabetes was always found to be associated with self-report of better glycemic control and was often associated with better clinician-conducted measures oral health. In the interventional studies identified, health coaching about oral health was associated with improvements in glycemic control, and health coaching compared with health education was found to be associated with enhanced improvement in glycemic control and self-reported toothbrushing behavior. Conclusion: The available data suggest that improved engagement in toothbrushing behavior may be associated with improved oral health and better glycemic control in people with type 2 diabetes. Whether improvement in glycemic control is a direct result of change to the oral environment, succeeding with one behavior change stimulating engagement in other health behavior changes, a combination of the two, or something else cannot be determined from this review. Additional studies are needed to further explore the potential for oral health coaching to improve the well-being of people with type 2 diabetes.

15.
J Am Dent Assoc ; 154(10): 875, 2023 10.
Article in English | MEDLINE | ID: mdl-37642610
16.
J Clin Med ; 12(15)2023 Jul 28.
Article in English | MEDLINE | ID: mdl-37568385

ABSTRACT

It is not well established to what extent previous immunizations offer protection against infections with the SARS-CoV-2 Omicron variant in dialysis patients. We aimed to define the relevant humoral response in dialysis patients using a SARS-CoV-2 IgG chemiluminescence microparticle immunoassay (CMIA) compared to the activity of neutralizing antibodies assessed by a virus neutralization test. Next, we aimed to determine differences in humoral and cellular response levels over time among patients infected or not infected by the Omicron variant of SARS-CoV-2. Immunological parameters of cellular and humoral response to SARS-CoV-2 were analyzed at baseline and after 3 (T3), 6 (T6) and 14 months (T14). In this monocentric cohort study, we followed 110 dialysis patients (mean age 68.4 ± 13.7 years, 60.9% male) for a median of 545 days. We determined an anti-SARS-CoV-2 IgG level of 56.7 BAU/mL as an ideal cut-off value with a J-index of 90.7. Patients infected during the Omicron era had significantly lower (p < 0.001) mean antibody levels at T0 (3.5 vs. 111.2 BAU/mL), T3 (269.8 vs. 699.8 BAU/mL) and T6 (260.2 vs. 513.9 BAU/mL) than patients without Omicron infection. Patients who developed higher antibody levels at the time of the basic immunizations were less likely to become infected with SARS-CoV-2 during the Omicron era. There is a need to adjust the cut-off values for anti-SARS-CoV-2 IgG levels in dialysis patients.

17.
Sci Rep ; 13(1): 8957, 2023 06 02.
Article in English | MEDLINE | ID: mdl-37268692

ABSTRACT

Coral reefs are iconic examples of climate change impacts because climate-induced heat stress causes the breakdown of the coral-algal symbiosis leading to a spectacular loss of color, termed 'coral bleaching'. To examine the fine-scale dynamics of this process, we re-sampled 600 individually marked Montipora capitata colonies from across Kane'ohe Bay, Hawai'i and compared the algal symbiont composition before and after the 2019 bleaching event. The relative proportion of the heat-tolerant symbiont Durusdinium in corals increased in most parts of the bay following the bleaching event. Despite this widespread increase in abundance of Durusdinium, the overall algal symbiont community composition was largely unchanged, and hydrodynamically defined regions of the bay retained their distinct pre-bleaching compositions. We explain ~ 21% of the total variation, of which depth and temperature variability were the most significant environmental drivers of Symbiodiniaceae community composition by site regardless of bleaching intensity or change in relative proportion of Durusdinium. We hypothesize that the plasticity of symbiont composition in corals may be constrained to adaptively match the long-term environmental conditions surrounding the holobiont, despite an individual coral's stress and bleaching response.


Subject(s)
Anthozoa , Dinoflagellida , Animals , Anthozoa/physiology , Temperature , Coral Reefs , Heat-Shock Response , Dinoflagellida/physiology , Symbiosis , Hot Temperature
18.
J Gen Intern Med ; 38(11): 2621, 2023 08.
Article in English | MEDLINE | ID: mdl-37310642
19.
Front Pharmacol ; 14: 1190476, 2023.
Article in English | MEDLINE | ID: mdl-37180699

ABSTRACT

Introduction: Mechanical thrombectomy has improved treatment options and outcomes for acute ischemic stroke with large artery occlusion. However, as the time window of endovascular thrombectomy is extended there is an increasing need to develop immunocytoprotective therapies that can reduce inflammation in the penumbra and prevent reperfusion injury. We previously demonstrated, that by reducing neuroinflammation, KV1.3 inhibitors can improve outcomes not only in young male rodents but also in female and aged animals. To further explore the therapeutic potential of KV1.3 inhibitors for stroke therapy, we here directly compared a peptidic and a small molecule KV1.3 blocker and asked whether KV1.3 inhibition would still be beneficial when started at 72 hours after reperfusion. Methods: Transient middle cerebral artery occlusion (tMCAO, 90-min) was induced in male Wistar rats and neurological deficit assessed daily. On day-8 infarction was determined by T2-weighted MRI and inflammatory marker expression in the brain by quantitative PCR. Potential interactions with tissue plasminogen activator (tPA) were evaluated in-vitro with a chromogenic assay. Results: In a direct comparison with administration started at 2 hours after reperfusion, the small molecule PAP-1 significantly improved outcomes on day-8, while the peptide ShK-223 failed to reduce infarction and neurological deficits despite reducing inflammatory marker expression. PAP-1 still provided benefits when started 72 hours after reperfusion. PAP-1 does not reduce the proteolytic activity of tPA. Discussion: Our studies suggest that KV1.3 inhibition for immunocytoprotection after ischemic stroke has a wide therapeutic window for salvaging the inflammatory penumbra and requires brain-penetrant small molecules.

20.
Tree Physiol ; 43(7): 1118-1129, 2023 07 09.
Article in English | MEDLINE | ID: mdl-37040317

ABSTRACT

Few previous studies have described the patterns of leaf characteristics in response to nutrient availability and depth in the crown. Sugar maple has been studied for both sensitivity to light, as a shade-tolerant species, and sensitivity to soil nutrient availability, as a species in decline due to acid rain. To explore leaf characteristics from the top to bottom of the canopy, we collected leaves along a vertical gradient within mature sugar maple crowns in a full-factorial nitrogen (N) by phosphorus (P) addition experiment in three forest stands in central New Hampshire, USA. Thirty-two of the 44 leaf characteristics had significant relationships with depth in the crown, with the effect of depth in the crown strongest for leaf area, photosynthetic pigments and polyamines. Nitrogen addition had a strong impact on the concentration of foliar N, chlorophyll, carotenoids, alanine and glutamate. For several other elements and amino acids, N addition changed patterns with depth in the crown. Phosphorus addition increased foliar P and boron (B); it also caused a steeper increase of P and B with depth in the crown. Since most of these leaf characteristics play a direct or indirect role in photosynthesis, metabolic regulation or cell division, studies that ignore the vertical gradient may not accurately represent whole-canopy performance.


Subject(s)
Acer , Light , Acer/metabolism , Nitrogen/metabolism , Phosphorus/metabolism , Photosynthesis/physiology , Plant Leaves/physiology , Trees/physiology
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