Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 66
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
J Neurosci ; 44(16)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38383497

RESUMO

Recent work suggests that indentations of the cerebral cortex, or sulci, may be uniquely vulnerable to atrophy in aging and Alzheimer's disease (AD) and that the posteromedial cortex (PMC) is particularly vulnerable to atrophy and pathology accumulation. However, these studies did not consider small, shallow, and variable tertiary sulci that are located in association cortices and are often associated with human-specific aspects of cognition. Here, we manually defined 4,362 PMC sulci in 432 hemispheres in 216 human participants (50.5% female) and found that these smaller putative tertiary sulci showed more age- and AD-related thinning than larger, more consistent sulci, with the strongest effects for two newly uncovered sulci. A model-based approach relating sulcal morphology to cognition identified that a subset of these sulci was most associated with memory and executive function scores in older adults. These findings lend support to the retrogenesis hypothesis linking brain development and aging and provide new neuroanatomical targets for future studies of aging and AD.


Assuntos
Doença de Alzheimer , Humanos , Feminino , Idoso , Masculino , Doença de Alzheimer/patologia , Córtex Cerebral/patologia , Envelhecimento/patologia , Cognição , Atrofia/patologia , Imageamento por Ressonância Magnética
2.
J Chem Phys ; 159(1)2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37409707

RESUMO

Electron transfer at electrode interfaces to molecules in solution or at the electrode surface plays a vital role in numerous technological processes. However, treating these processes requires a unified and accurate treatment of the fermionic states of the electrode and their coupling to the molecule being oxidized or reduced in the electrochemical processes and, in turn, the way the molecular energy levels are modulated by the bosonic nuclear modes of the molecule and solvent. Here we present a physically transparent quasiclassical scheme to treat these electrochemical electron transfer processes in the presence of molecular vibrations by using an appropriately chosen mapping of the fermionic variables. We demonstrate that this approach, which is exact in the limit of non-interacting fermions in the absence of coupling to vibrations, is able to accurately capture the electron transfer dynamics from the electrode even when the process is coupled to vibrational motions in the regimes of weak coupling. This approach, thus, provides a scalable strategy to explicitly treat electron transfer from electrode interfaces in condensed-phase molecular systems.

3.
Lancet ; 398(10307): 1217-1229, 2021 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-34534517

RESUMO

BACKGROUND: School-based COVID-19 contacts in England have been asked to self-isolate at home, missing key educational opportunities. We trialled daily testing of contacts as an alternative to assess whether this resulted in similar control of transmission, while allowing more school attendance. METHODS: We did an open-label, cluster-randomised, controlled trial in secondary schools and further education colleges in England. Schools were randomly assigned (1:1) to self-isolation of school-based COVID-19 contacts for 10 days (control) or to voluntary daily lateral flow device (LFD) testing for 7 days with LFD-negative contacts remaining at school (intervention). Randomisation was stratified according to school type and size, presence of a sixth form, presence of residential students, and proportion of students eligible for free school meals. Group assignment was not masked during procedures or analysis. Coprimary outcomes in all students and staff were COVID-19-related school absence and symptomatic PCR-confirmed COVID-19, adjusted for community case rates, to estimate within-school transmission (non-inferiority margin <50% relative increase). Analyses were done on an intention-to-treat basis using quasi-Poisson regression, also estimating complier average causal effects (CACE). This trial is registered with the ISRCTN registry, ISRCTN18100261. FINDINGS: Between March 18 and May 4, 2021, 204 schools were taken through the consent process, during which three decided not to participate further. 201 schools were randomly assigned (control group n=99, intervention group n=102) in the 10-week study (April 19-May 10, 2021), which continued until the pre-appointed stop date (June 27, 2021). 76 control group schools and 86 intervention group schools actively participated; additional national data allowed most non-participating schools to be included in analysis of coprimary outcomes. 2432 (42·4%) of 5763 intervention group contacts participated in daily contact testing. There were 657 symptomatic PCR-confirmed infections during 7 782 537 days-at-risk (59·1 per 100 000 per week) in the control group and 740 during 8 379 749 days-at-risk (61·8 per 100 000 per week) in the intervention group (intention-to-treat adjusted incidence rate ratio [aIRR] 0·96 [95% CI 0·75-1·22]; p=0·72; CACE aIRR 0·86 [0·55-1·34]). Among students and staff, there were 59 422 (1·62%) COVID-19-related absences during 3 659 017 person-school-days in the control group and 51 541 (1·34%) during 3 845 208 person-school-days in the intervention group (intention-to-treat aIRR 0·80 [95% CI 0·54-1·19]; p=0·27; CACE aIRR 0·61 [0·30-1·23]). INTERPRETATION: Daily contact testing of school-based contacts was non-inferior to self-isolation for control of COVID-19 transmission, with similar rates of symptomatic infections among students and staff with both approaches. Infection rates in school-based contacts were low, with very few school contacts testing positive. Daily contact testing should be considered for implementation as a safe alternative to home isolation following school-based exposures. FUNDING: UK Government Department of Health and Social Care.


Assuntos
Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , Controle de Doenças Transmissíveis/métodos , Quarentena/métodos , Instituições Acadêmicas , Adolescente , Adulto , Idoso , COVID-19/prevenção & controle , COVID-19/transmissão , Teste de Ácido Nucleico para COVID-19 , Teste para COVID-19/métodos , Criança , Pessoal de Educação , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Adulto Jovem
4.
Environ Microbiol ; 24(12): 5924-5935, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35799468

RESUMO

Endosymbiosis, an interaction between two species where one lives within the other, has evolved multiple times independently, but the underlying mechanisms remain unclear. Evolutionary theory suggests that for an endosymbiotic interaction to remain stable over time, births of both partners should be higher than their deaths in symbiosis and deaths of both partners should be higher than their births when living independently. However, experimentally measuring this can be difficult and conclusions tend to focus on the host. Using a ciliate-algal system (Paramecium bursaria host and Chlorella endosymbionts), we estimated the benefits and costs of endosymbiosis for both organisms using fitness measurements in different biotic environments to test under which environmental conditions the net effects of the interaction were positive for both partners. We found that the net effects of harbouring endosymbionts were positive for the ciliate hosts as it allowed them to survive in conditions of low-quality bacteria food. The algae benefitted by being endosymbiotic when predators such as the hosts were present, but the net effects were dependent on the total density of hosts, decreasing as hosts densities increased. Overall, we show that including context-dependency of endosymbiosis is essential in understanding how these interactions have evolved.


Assuntos
Chlorella , Cilióforos , Paramecium , Simbiose , Análise Custo-Benefício
5.
Bioorg Med Chem Lett ; 30(13): 127197, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32331932

RESUMO

A novel series of ethyl ketone based HDACs 1, 2, and 3 selective inhibitors have been identified with good enzymatic and cellular activity and high selectivity over HDACs 6 and 8. These inhibitors contain a spirobicyclic group in the amide region. Compound 13 stands out as a lead due to its good potency, high selectivity, and reasonable rat and dog PK. Compounds 33 and 34 show good potency and rat PK profiles as well.


Assuntos
Fármacos Anti-HIV/farmacologia , HIV-1/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Cetonas/farmacologia , Ativação Viral/efeitos dos fármacos , Latência Viral/efeitos dos fármacos , Animais , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/farmacocinética , Linhagem Celular Tumoral , Cães , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/farmacocinética , Humanos , Cetonas/síntese química , Cetonas/farmacocinética , Testes de Sensibilidade Microbiana , Ratos , Compostos de Espiro/síntese química , Compostos de Espiro/farmacocinética , Compostos de Espiro/farmacologia
6.
Bioorg Med Chem Lett ; 30(17): 127390, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32738973

RESUMO

Bruton's tyrosine kinase (BTK) is a Tec family kinase with a well-defined role in the B cell receptor (BCR) pathway. It has become an attractive kinase target for selective B cell inhibition, and for the treatment of B cell related diseases. Many BTK inhibitors have been discovered for the treatment of cancer and rheumatoid arthritis, including a series of BTK inhibitors based on 8-amino-imidazo[1,5-a]pyrazine we recently reported. The X-ray crystal structures of BTK with inhibitors were also published, which provided great help for the SAR design. Here we report our SAR work introducing ring constraints for the 3-position piperidine amides on the BTK inhibitors based on 8-amino-imidazo[1,5-a]pyrazine. This modification improved the potency in BTK inhibitions, as well as the PK profile and the off-target selectivity. The dose-dependent efficacy of two BTK inhibitors was observed in the rat collagen induced arthritis (CIA) model.


Assuntos
Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Imidazóis/química , Inibidores de Proteínas Quinases/química , Pirazinas/química , Tirosina Quinase da Agamaglobulinemia/metabolismo , Animais , Artrite Experimental/tratamento farmacológico , Sítios de Ligação , Compostos Bicíclicos com Pontes/química , Cristalografia por Raios X , Modelos Animais de Doenças , Cães , Relação Dose-Resposta a Droga , Meia-Vida , Humanos , Imidazóis/metabolismo , Imidazóis/uso terapêutico , Simulação de Dinâmica Molecular , Inibidores de Proteínas Quinases/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Pirazinas/metabolismo , Pirazinas/uso terapêutico , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Quinases da Família src/antagonistas & inibidores , Quinases da Família src/metabolismo
7.
Chem Res Toxicol ; 32(3): 474-483, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30701970

RESUMO

To prevent the accumulation of reactive oxygen species and limit associated damage to biological macromolecules, cells express a variety of oxidant-detoxifying enzymes, including peroxiredoxins. In Saccharomyces cerevisiae, the peroxiredoxin Tsa1 plays a key role in peroxide clearance and maintenance of genome stability. Five homodimers of Tsa1 can assemble into a toroid-shaped decamer, with the active sites in the enzyme being shared between individual dimers in the decamer. Here, we have examined whether two conserved aromatic residues at the decamer-building interface promote Tsa1 oligomerization, enzymatic activity, and biological function. When substituting either or both of these aromatic residues at the decamer-building interface with either alanine or leucine, we found that the Tsa1 decamer is destabilized, favoring dimeric species instead. These proteins exhibit varying abilities to rescue the phenotypes of oxidant sensitivity and genomic instability in yeast lacking Tsa1 and Tsa2, with the individual leucine substitutions at this interface partially complementing the deletion phenotypes. The ability of Tsa1 decamer interface variants to partially rescue peroxidase function in deletion strains is temperature-dependent and correlates with their relative rate of reactivity with hydrogen peroxide and their ability to interact with thioredoxin. Based on the combined results of in vitro and in vivo assays, our findings indicate that multiple steps in the catalytic cycle of Tsa1 may be impaired by introducing substitutions at its decamer-building interface, suggesting a multifaceted biological basis for its assembly into decamers.


Assuntos
Peroxidases/química , Peroxidases/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo , Dimerização , Modelos Moleculares , Software
8.
Angew Chem Int Ed Engl ; 58(29): 9948-9953, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31004389

RESUMO

The development of sensitive and chemically selective MRI contrast agents is imperative for the early detection and diagnosis of many diseases. Conventional responsive contrast agents used in 1 H MRI are impaired by the high abundance of protons in the body. 129 Xe hyperCEST NMR/MRI comprises a highly sensitive complement to traditional 1 H MRI because of its ability to report specific chemical environments. To date, the scope of responsive 129 Xe NMR contrast agents lacks breadth in the specific detection of small molecules, which are often important markers of disease. Herein, we report the synthesis and characterization of a rotaxane-based 129 Xe hyperCEST NMR contrast agent that can be turned on in response to H2 O2 , which is upregulated in several disease states. Added H2 O2 was detected by 129 Xe hyperCEST NMR spectroscopy in the low micromolar range, as well as H2 O2 produced by HEK 293T cells activated with tumor necrosis factor.


Assuntos
Peróxido de Hidrogênio/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Rotaxanos/uso terapêutico
9.
Bioorg Med Chem Lett ; 28(11): 2029-2034, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29748051

RESUMO

Compound 5 (SCH772984) was identified as a potent inhibitor of ERK1/2 with excellent selectivity against a panel of kinases (0/231 kinases tested @ 100 nM) and good cell proliferation activity, but suffered from poor PK (rat AUC PK @10 mpk = 0 µM h; F% = 0) which precluded further development. In an effort to identify novel ERK inhibitors with improved PK properties with respect to 5, a systematic exploration of sterics and composition at the 3-position of the pyrrolidine led to the discovery of a novel 3(S)-thiomethyl pyrrolidine analog 28 with vastly improved PK (rat AUC PK @10 mpk = 26 µM h; F% = 70).


Assuntos
Antineoplásicos/farmacologia , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Pirrolidinas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Modelos Moleculares , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Pirrolidinas/síntese química , Pirrolidinas/química , Ratos , Relação Estrutura-Atividade , Células Tumorais Cultivadas
10.
J Manipulative Physiol Ther ; 40(9): 625-634, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29229052

RESUMO

OBJECTIVE: The purpose of this study was to examine whether cerebral activation in response to noxious mechanical stimuli varies with thrust manipulation (TM) when compared with sham manipulation (SM) as measured by blood oxygenation level-dependent functional magnetic resonance imaging. METHODS: Twenty-four volunteers (67% female) with complaints of acute or subacute mechanical (nontraumatic) neck pain satisfied eligibility requirements and agreed to participate. Participants were randomized to receive TM to the thoracic spine or SM, and then underwent functional magnetic resonance scanning while receiving noxious stimuli before and after TM or SM. An 11-point numeric pain rating scale was administered pre- and postmanipulation for neck pain and to determine perceptions of pain intensity with respect to neck pain and mechanical stimuli. Blood oxygenation level-dependent functional magnetic resonance imaging recorded the cerebral hemodynamic response to the mechanical stimuli. RESULTS: Imaging revealed significant group differences, with those individuals in the manipulation group exhibiting increased areas of activation (postmanipulation) in the insular and somatosensory cortices and individuals in the sham group exhibiting greater areas of activation in the precentral gyrus, supplementary motor area, and cingulate cortices (P < .05). However, between-group differences on the numeric pain rating scale for mechanical stimuli and for self-reported neck pain were not statistically significant. CONCLUSIONS: This study provides preliminary level 2b evidence suggesting cortical responses in patients with nontraumatic neck pain may vary between thoracic TM and a sham comparator.


Assuntos
Circulação Cerebrovascular/fisiologia , Hemodinâmica/fisiologia , Imageamento por Ressonância Magnética/métodos , Manipulação da Coluna/métodos , Cervicalgia/terapia , Medição da Dor , Adulto , Feminino , Humanos , Cervicalgia/diagnóstico por imagem , Oxigênio/sangue , Percepção da Dor/fisiologia , Estudos Prospectivos , Valores de Referência , Índice de Gravidade de Doença
11.
Arch Phys Med Rehabil ; 96(11): 2041-7, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26254947

RESUMO

OBJECTIVE: To quantify resting lumbar erector myofascial stiffness in younger patients with ankylosing spondylitis (AS) and age-comparable healthy control subjects using a handheld mechanical impulse-based myotonometric device. DESIGN: A case-control study of 24 patients with AS and 24 age-comparable healthy control subjects. SETTING: University physical therapy department. PARTICIPANTS: Patients with AS (men: n=19; women: n=5; total: N=24) and healthy volunteers (men: n=19; women: n=5; total: N=24) without low back pain (age range, 18-46y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Lumbar myofascial stiffness. RESULTS: At the initial measurements, median stiffness (Nm) of the averaged right- and left-sided values was greater (P=.021) in 24 patients with AS than 24 control subjects (268.9 vs 238.9, respectively). Repeated measurements after a 10-minute prone resting period were also greater (P=.007) in patients with AS than control subjects (281.0 vs 241.4, respectively). The 48 averaged right- and left-sided values from baseline and 10-minute measurements were compared in each subject group. The patients with AS more frequently (P=.012) had stiffness values >250 Nm (35 [72.9%] vs 22 [45.8%] in control subjects). CONCLUSIONS: Lumbar myofascial stiffness was greater in 24 patients with AS than in the control subjects. A hypothesized biomechanical concept of increased resting lumbar myofascial stiffness in AS may be supported by this preliminary controlled study.


Assuntos
Fáscia/fisiopatologia , Região Lombossacral/fisiopatologia , Músculo Esquelético/fisiopatologia , Espondilite Anquilosante/fisiopatologia , Adolescente , Adulto , Estudos de Casos e Controles , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
Am J Primatol ; 77(10): 1122-34, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26179423

RESUMO

Monitoring of animal populations is essential for conservation management. Various techniques are available to assess spatiotemporal patterns of species distribution and abundance. Nest surveys are often used for monitoring great apes. Quickly developing technologies, including unmanned aerial vehicles (UAVs) can be used to complement these ground-based surveys, especially for covering large areas rapidly. Aerial surveys have been used successfully to detect the nests of orang-utans. It is unknown if such an approach is practical for African apes, which usually build their nests at lower heights, where they might be obscured by forest canopy. In this 2-month study, UAV-derived aerial imagery was used for two distinct purposes: testing the detectability of chimpanzee nests and identifying fruiting trees used by chimpanzees in Loango National Park (Gabon). Chimpanzee nest data were collected through two approaches: we located nests on the ground and then tried to detect them in UAV photos and vice versa. Ground surveys were conducted using line transects, reconnaissance trails, and opportunistic sampling during which we detected 116 individual nests in 28 nest groups. In complementary UAV images we detected 48% of the individual nests (68% of nest groups) in open coastal forests and 8% of individual nests (33% of nest groups) in closed canopy inland forests. The key factor for nest detectability in UAV imagery was canopy openness. Data on fruiting trees were collected from five line transects. In 122 UAV images 14 species of trees (N = 433) were identified, alongside 37 tree species (N = 205) in complementary ground surveys. Relative abundance of common tree species correlated between ground and UAV surveys. We conclude that UAVs have great potential as a rapid assessment tool for detecting chimpanzee presence in forest with open canopy and assessing fruit tree availability. UAVs may have limited applicability for nest detection in closed canopy forest.


Assuntos
Frutas , Comportamento de Nidação , Pan troglodytes/fisiologia , Tecnologia de Sensoriamento Remoto/métodos , Animais , Ecossistema , Florestas , Gabão , Árvores
13.
JBJS Case Connect ; 13(3)2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37616443

RESUMO

CASE: A 28-year-old woman with no medical history involved in a motor vehicle collision presented with deformity of the right leg and traumatic right heel pad avulsion. Radiographs demonstrated a right foot mid-tarsal fracture-dislocation, open cuboid, closed right tibia, and segmental fibula fractures. The heel pad was repaired using polydioxanone suture in a quilted technique with sterile buttons. At 1-year follow-up, the patient's heel pad was well-fixed with intact sensation and no pain. CONCLUSION: Repair of a heel pad avulsion using this novel technique is a versatile and cost-effective method that reduces concern for tissue necrosis associated with suture repair.


Assuntos
Fraturas Ósseas , Polidioxanona , Feminino , Adulto , Humanos , Calcanhar , , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Suturas
14.
J Spec Oper Med ; 23(2): 40-43, 2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37083895

RESUMO

INTRODUCTION: Although the instances of Special Operations Forces (SOF) medical providers treating pediatric pelvic fractures are rare, such fractures are notable injuries in terror attacks and are at high risk for morbidity and mortality for the patient as well as stress for the provider. Presently, guidelines for pediatric-sized pelvic stabilization device application are limited to measured pelvic circumference. This study aims to inform more practical sizing guidelines. METHODS: Subjects aged 1 year to 14 years were enrolled. Subject height, weight, pelvic circumference, and fit on the Broselow Pediatric Emergency Tape® (Armstrong Medical Industries), fit with the Pediatric PelvicBinder® (PelvicBinder), and fit with the small SAM Pelvic Sling® (SAM® Medical) were collected. The primary outcome was the proportion of subjects fitting each device. RESULTS: Sixty-five subjects were recruited; median age was 5 years (interquartile range, 1-8 years); 40 (62%) subjects were male. Ninety-one percent of subjects fit within the scale of the Broselow Tape (height <143-cm). One hundred percent of subjects with a height <143-cm had an appropriate fit with the Pediatric PelvicBinder (95% confidence level [CI], 91.8-100%), while 91.7% of subjects with a height >143-cm fit the SAM Pelvic Sling (95%CI, 61.5-99.8%). CONCLUSIONS: Providers should attempt to fit the Pediatric PelvicBinder for children >1 year old with suspected unstable pelvic fracture who fall on the Broselow Tape (<143-cm). The small SAM Pelvic Sling should be used for those taller than 143-cm.


Assuntos
Serviços Médicos de Emergência , Fraturas Ósseas , Ossos Pélvicos , Lactente , Criança , Humanos , Masculino , Pré-Escolar , Feminino , Fraturas Ósseas/terapia , Peso Corporal , Pelve
15.
Sci Rep ; 13(1): 11802, 2023 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-37479833

RESUMO

Ulcerative colitis (UC) is an idiopathic disease of the large intestine linked to high fat-high protein diets, a dysbiotic microbiome, and a metabolome linked to diet and/or aberrant circadian rhythms associated with poor sleeping patterns. Understanding diet-affected factors that negatively influence colonic health may offer new insights into how to prevent UC and enhance the efficacy of UC immunotherapy. In this preclinical study, we found that standard or high fiber diets in mice positively influenced their colonic health, whereas a high fat-high protein diet negatively influenced colonic health, consistent with clinical findings. Animals fed a high fat/high protein diet experienced obesity and a reduced colon length, illustrating a phenotype we suggest calling peinosis [hunger-like-condition; Greek, peina: hunger; osis: condition], as marked by a lack of nutrient energy remaining in fecal pellets. Notably, a high fat/high protein diet also led to signs of muscle weakness that could not be explained fully by weight gain. In contrast, mice on a high fiber diet ranked highest compared to other diets in terms of colon length and lack of muscle weakness. That said, mice on a high fiber diet were more prone to UC and toxic responses to immunotherapy, consistent with clinical observations. Recent studies have suggested that a standard diet may be needed to support the efficacy of immunotherapeutic drugs used to prevent and treat UC. Here we observed that protection against UC by Bin1 mAb, a passive UC immunotherapy that acts by coordinately enforcing intestinal barrier function, protecting enteric neurons, and normalizing the microbiome, was associated with increased colonic levels of healthful short-chain fatty acids (SCFA), particularly butyric acid and propionic acid, which help enforce intestinal barrier function. This work offers a preclinical platform to investigate how diet affects UC immunotherapy and the potential of dietary SCFA supplements to enhance it. Further, it suggests that the beneficial effects of passive immunotherapy by Bin1 mAb in UC treatment may be mediated to some extent by promoting increased levels of healthful SCFA.


Assuntos
Colite Ulcerativa , Animais , Camundongos , Colite Ulcerativa/terapia , Imunoterapia , Dieta Hiperlipídica/efeitos adversos , Proteínas Adaptadoras de Transdução de Sinal , Ácido Butírico , Proteínas do Tecido Nervoso , Proteínas Supressoras de Tumor
16.
Cureus ; 15(5): e39490, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37362497

RESUMO

Introduction Surgical site infections (SSI) following orthopedic procedures can cause significant morbidity and mortality, particularly in total joint arthroplasty. Biofilm formation in surgical wounds has made it difficult to prevent and treat these infections. SURGX® Antimicrobial Wound Gel (Next Science, Jacksonville, Florida, USA) was developed to disrupt biofilm formation but has not been evaluated in prophylactic use in total joint arthroplasty to prevent superficial SSI. Methods A retrospective chart review was performed at a single institution comparing the rate of SSI in patients undergoing primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). SSI data were collected from patients with standard postoperative dressings (Group A: Control) and patients with SURGX® applied as part of a standardized dressing following THA/TKA (Group B: Study). Rates of SSI were compared.  Results SURGX® was administered to 120 patients, including 91 TKAs and 29 THAs. The overall infection rate in this cohort was 2.5%. No superficial site infections developed. The control group constituted 566 patients, with 386 TKAs and 180 THAs. The infection rate was 1.24%, which included one superficial infection. Binary logistic regression did not show different odds of developing infections with the use of SURGX® (OR = 2.23, 95% CI: 0.54-9.13, p = 0.27). Conclusion In our small retrospective study, Next Science SURGX® Antimicrobial Wound Gel did not demonstrate a statistically significant difference in the rate of superficial SSI in total joint arthroplasty; however, Group B did not have any superficial SSI.

17.
bioRxiv ; 2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36798269

RESUMO

Recent studies identify a surprising coupling between evolutionarily new sulci and the functional organization of human posteromedial cortex (PMC). Yet, no study has compared this modern PMC sulcal patterning between humans and non-human hominoids. To fill this gap in knowledge, we first manually defined 918 sulci in 120 chimpanzee ( Pan Troglodytes ) hemispheres and 1619 sulci in 144 human hemispheres. We uncovered four new PMC sulci, and quantitatively identified species differences in incidence, depth, and surface area. Interestingly, some PMC sulci are more common in humans and others, in chimpanzees. Further, we found that the prominent marginal ramus of the cingulate sulcus differs significantly between species. Contrary to classic observations, the present results reveal that the surface anatomy of PMC substantially differs between humans and chimpanzees â€" findings which lay a foundation for better understanding the evolution of neuroanatomical-functional and neuroanatomical-behavioral relationships in this highly expanded region of the human cerebral cortex.

18.
Commun Biol ; 6(1): 586, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37264068

RESUMO

Recent studies identify a surprising coupling between evolutionarily new sulci and the functional organization of human posteromedial cortex (PMC). Yet, no study has compared this modern PMC sulcal patterning between humans and non-human hominoids. To fill this gap in knowledge, we first manually defined over 2500 PMC sulci in 120 chimpanzee (Pan Troglodytes) hemispheres and 144 human hemispheres. We uncovered four new sulci, and quantitatively identified species differences in sulcal incidence, depth, and surface area. Interestingly, some sulci are more common in humans and others, in chimpanzees. Further, we found that the prominent marginal ramus of the cingulate sulcus differs significantly between species. Contrary to classic observations, the present results reveal that the surface anatomy of PMC substantially differs between humans and chimpanzees-findings which lay a foundation for better understanding the evolution of neuroanatomical-functional and neuroanatomical-behavioral relationships in this highly expanded region of the human cerebral cortex.


Assuntos
Hominidae , Pan troglodytes , Animais , Humanos , Pan troglodytes/anatomia & histologia , Córtex Cerebral/anatomia & histologia
19.
Microbiome ; 10(1): 164, 2022 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-36195901

RESUMO

BACKGROUND: Tropical members of the sponge genus Ircinia possess highly complex microbiomes that perform a broad spectrum of chemical processes that influence host fitness. Despite the pervasive role of microbiomes in Ircinia biology, it is still unknown how they remain in stable association across tropical species. To address this question, we performed a comparative analysis of the microbiomes of 11 Ircinia species using whole-metagenomic shotgun sequencing data to investigate three aspects of bacterial symbiont genomes-the redundancy in metabolic pathways across taxa, the evolution of genes involved in pathogenesis, and the nature of selection acting on genes relevant to secondary metabolism. RESULTS: A total of 424 new, high-quality bacterial metagenome-assembled genomes (MAGs) were produced for 10 Caribbean Ircinia species, which were evaluated alongside 113 publicly available MAGs sourced from the Pacific species Ircinia ramosa. Evidence of redundancy was discovered in that the core genes of several primary metabolic pathways could be found in the genomes of multiple bacterial taxa. Across hosts, the metagenomes were depleted in genes relevant to pathogenicity and enriched in eukaryotic-like proteins (ELPs) that likely mimic the hosts' molecular patterning. Finally, clusters of steroid biosynthesis genes (CSGs), which appear to be under purifying selection and undergo horizontal gene transfer, were found to be a defining feature of Ircinia metagenomes. CONCLUSIONS: These results illustrate patterns of genome evolution within highly complex microbiomes that illuminate how associations with hosts are maintained. The metabolic redundancy within the microbiomes could help buffer the hosts from changes in the ambient chemical and physical regimes and from fluctuations in the population sizes of the individual microbial strains that make up the microbiome. Additionally, the enrichment of ELPs and depletion of LPS and cellular motility genes provide a model for how alternative strategies to virulence can evolve in microbiomes undergoing mixed-mode transmission that do not ultimately result in higher levels of damage (i.e., pathogenicity) to the host. Our last set of results provides evidence that sterol biosynthesis in Ircinia-associated bacteria is widespread and that these molecules are important for the survival of bacteria in highly complex Ircinia microbiomes. Video Abstract.


Assuntos
Lipopolissacarídeos , Microbiota , Bactérias/genética , Evolução Molecular , Metagenoma/genética , Metagenômica , Microbiota/genética , Filogenia , Esteroides , Esteróis
20.
Zootaxa ; 5072(4): 301-323, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-35390863

RESUMO

Seven Ircinia morphospecies were collected from three sites in the Caribbean (Bocas del Toro, Panama; the Mesoamerican Barrier Reef, Belize; and the Florida Keys, United States of America). Previous research used an integrative taxonomic framework (genome-wide SNP sampling and microbiome profiling) to delimit species boundaries among these Ircinia. Here, we present morphological descriptions for these species, six of which are new to science (Ircinia lowi sp. nov., Ircinia bocatorensis sp. nov., Ircinia radix sp. nov., Ircinia laeviconulosa sp. nov., Ircinia vansoesti sp. nov., Ircinia ruetzleri sp. nov.) in addition to one species conferre (Ircinia cf. reteplana Topsent, 1923).


Assuntos
Poríferos , Água , Animais , Região do Caribe
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA