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1.
Nat Commun ; 15(1): 4820, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844479

RESUMO

Chondrocyte differentiation controls skeleton development and stature. Here we provide a comprehensive map of chondrocyte-specific enhancers and show that they provide a mechanistic framework through which non-coding genetic variants can influence skeletal development and human stature. Working with fetal chondrocytes isolated from mice bearing a Col2a1 fluorescent regulatory sensor, we identify 780 genes and 2'704 putative enhancers specifically active in chondrocytes using a combination of RNA-seq, ATAC-seq and H3K27ac ChIP-seq. Most of these enhancers (74%) show pan-chondrogenic activity, with smaller populations being restricted to limb (18%) or trunk (8%) chondrocytes only. Notably, genetic variations overlapping these enhancers better explain height differences than those overlapping non-chondrogenic enhancers. Finally, targeted deletions of identified enhancers at the Fgfr3, Col2a1, Hhip and, Nkx3-2 loci confirm their role in regulating cognate genes. This enhancer map provides a framework for understanding how genes and non-coding variations influence bone development and diseases.


Assuntos
Condrócitos , Condrogênese , Elementos Facilitadores Genéticos , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos , Animais , Elementos Facilitadores Genéticos/genética , Humanos , Condrócitos/metabolismo , Condrócitos/citologia , Camundongos , Condrogênese/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Desenvolvimento Ósseo/genética , Extremidades/embriologia , Masculino , Diferenciação Celular/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Feminino
2.
Int Wound J ; 21(6): e14907, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38822706

RESUMO

Recent randomised controlled trials (RCTs) have investigated the analgesic activity of sesame oil among patients with limb trauma; nevertheless, their findings are inconsistent. Hence, this review aimed to clarify the impact of topical administration of sesame oil on acute pain of adult outpatients with minor limb trauma. The online databases (e.g., Scopus, PubMed, Web of Science) were searched up to 31 January 2024. The RCTs were included if they compared the effect of applying standard treatments plus topical sesame oil to administering standard treatments alone or with a placebo/sham treatment. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) and the Cochrane Collaboration's risk of bias tool were applied to address the evidence quality and the study's methodological rigour, respectively. Four RCTs had the inclusion criteria, and their findings were pooled in a meta-analysis employing a random-effects approach. According to the pooled analysis, the reduction in mean change of the pain score from baseline to the second/third intervention day was significantly higher in favour of clients who received standard care plus daily massage of the trauma site with sesame oil compared to those who received a control condition (weighted mean difference: -1.10; 95% confidence interval [-1.62, -0.57]; p < 0.001). However, the evidence quality was moderate, and only two studies had good methodological rigour. Hence, more high-quality studies are needed to make a solid evidence-based conclusion about the favourable consequence of topical sesame oil on alleviating acute traumatic limb pain.


Assuntos
Administração Tópica , Ensaios Clínicos Controlados Aleatórios como Assunto , Óleo de Gergelim , Humanos , Óleo de Gergelim/uso terapêutico , Óleo de Gergelim/administração & dosagem , Manejo da Dor/métodos , Manejo da Dor/normas , Adulto , Feminino , Masculino , Analgésicos/administração & dosagem , Analgésicos/uso terapêutico , Medição da Dor/métodos , Pessoa de Meia-Idade , Extremidades/lesões
3.
Cell Mol Biol (Noisy-le-grand) ; 70(6): 61-65, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836683

RESUMO

This experiment aimed to explore the influence mechanism of external fixator on open fracture. A total of 128 patients with open tibiofibular fractures were included in this study. The patients were randomly divided into external fixator group (n=64) and control group (n=64) according to the order of admission. Double-blind controlled observation was used. The levels of osteocalcin (BGP), ß-CTX, P1 NP, BALP, including haptoglobin (Hp), ceruloplasmin (CER), serum adrenocorticotropic hormone (ACTH), cortisol (COR), C-reactive protein (CRP), white blood cell (WBC) and interleukin-6 (IL-6) were recorded in different groups. The postoperative VAS score and quality of life were recorded. Log-rank was used to analyze the difference in postoperative adverse reaction rates among different groups. External fixation stent treatment increased BGP, PINP, and BALP expression and decreased ß-CTX, Hp, CER, ACTH, COR, CRP, WBC, and IL-6 levels. Patients in the external fixation stent group had significantly lower VAS score quality of life scores and incidence of adverse events than the control group. External fixation stents protect open fracture patients by promoting bone metabolism.


Assuntos
Osso e Ossos , Proteína C-Reativa , Fixadores Externos , Osteocalcina , Qualidade de Vida , Humanos , Masculino , Feminino , Adulto , Osteocalcina/sangue , Osteocalcina/metabolismo , Pessoa de Meia-Idade , Osso e Ossos/metabolismo , Proteína C-Reativa/metabolismo , Fraturas Expostas/cirurgia , Fraturas Expostas/metabolismo , Interleucina-6/sangue , Interleucina-6/metabolismo , Pró-Colágeno/sangue , Pró-Colágeno/metabolismo , Método Duplo-Cego , Colágeno Tipo I/metabolismo , Colágeno Tipo I/sangue , Hormônio Adrenocorticotrópico/sangue , Hormônio Adrenocorticotrópico/metabolismo , Fragmentos de Peptídeos/sangue , Extremidades/cirurgia , Extremidades/lesões , Peptídeos , Hidrocortisona/sangue
4.
Yakugaku Zasshi ; 144(6): 685-690, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38825477

RESUMO

Docetaxel (DTX) is a key drug used in perioperative chemotherapy for breast cancer. Edema is a known adverse effect of DTX, but its effect on health-related QOL (HRQOL) is unclear. In this study, we evaluated the effects of edema caused by administration of DTX on HRQOL in patients with early-stage breast cancer. We prospectively investigated patients diagnosed with early-stage breast cancer (stage I-III) who received 4 cycles of DTX as preoperative or postoperative chemotherapy between September 2021 and December 2022 at Yamanashi Prefectural Central Hospital. The circumference of each extremity was measured at each administration of DTX, and limb edema was evaluated by Common Terminology Criteria for Adverse Events version 5.0. HRQOL was evaluated using SF-12 version 2, which has a range of 0-100 (national standard, 50), and compared between the presence and absence of grade 2 or higher edema and between before and after administration of DTX. Twenty patients met the eligibility criteria and were included in the study. There was no difference in the HRQOL score according to whether grade 2 limb edema was present. The median HRQOL summary scores before and after administration of DTX were 51.1 and 50.8 (p=0.763), respectively, for mental health, 52.6 and 49.4 (p=0.005) for physical health, and 38.9 and 37.5 (p=1.000) for role/social health. We found no direct effect of DTX-induced limb edema on HRQOL in patients with early-stage breast cancer. However, HRQOL summary scores indicated that administration of DTX reduced physical health in these patients.


Assuntos
Neoplasias da Mama , Docetaxel , Edema , Qualidade de Vida , Humanos , Docetaxel/efeitos adversos , Docetaxel/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Edema/induzido quimicamente , Edema/etiologia , Idoso , Estadiamento de Neoplasias , Adulto , Extremidades , Antineoplásicos/efeitos adversos , Assistência Perioperatória
6.
Arthropod Struct Dev ; 80: 101360, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38704965

RESUMO

Mate choice and male-male combat over successful mating often cause disproportionate exaggeration of male trait relative to body size. However, the exaggeration is often not the only trait involved with male-male combat and mate choice: suites of co-expressed traits may function together as a coordinated unit. When this occurs, dimorphism may be expected for these additional, non-exaggerated, structures. S. femorata males have disproportionately large hind-legs used in male-male combat over females. During the fights, fore- and mid-legs are used to keep males in positions where advantageous for leverage. Because use of the exaggerated hind-legs is coordinated with the other legs, they will coevolve as a functional unit. Here, we show that 1) S. femorata has sexual size differences in all three legs; 2) males show positive allometry in the relative sizes of all three legs; and 3) microstructures of tarsi on the fore- and mid-legs are also sexually dimorphic. Despite these differences in the tarsal microstructure, 4) adhesion forces of the tarsi had no sexual difference in flat surface. The microstructure would be specialized on attaching elytra surface. These results suggest that the three pairs of legs function together during fighting behavior, with hind-legs employed primarily for fighting, and the fore- and mid-legs functioning to grip females, keeping males positioned on the back of the female during combat.


Assuntos
Besouros , Extremidades , Caracteres Sexuais , Animais , Besouros/anatomia & histologia , Besouros/fisiologia , Masculino , Extremidades/anatomia & histologia , Feminino , Microscopia Eletrônica de Varredura , Comportamento Sexual Animal
7.
OMICS ; 28(6): 291-302, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38808529

RESUMO

The axolotl (Ambystoma mexicanum) is renowned for its remarkable regenerative capabilities, which are not diminished by the transition from a neotenic to a metamorphic state. This study explored the microbiome dynamics in axolotl limb regeneration by examining the microbial communities present in neotenic and metamorphic axolotls at two critical stages of limb regeneration: pre-amputation and during blastema formation. Utilizing 16S rRNA amplicon sequencing, we investigated the variations in microbiome profiles associated with different developmental and regenerative states. Our findings reveal a distinct separation in the microbiome profiles of neotenic and metamorphic samples, with a clear demarcation in microbial composition at both the phylum and genus levels. In neotenic 0DPA samples, Proteobacteria and Firmicutes were the most abundant, whereas in neotenic 7DPA samples, Proteobacteria and Bacteroidetes dominated. Conversely, metamorphic samples displayed a higher abundance of Firmicutes and Bacteroidetes at 0DPA and Proteobacteria and Firmicutes at 7DPA. Alpha and beta diversity analyses, along with dendrogram construction, demonstrated significant variations within and between the sample groups, suggesting a strong influence of both developmental stage and regenerative state on the microbiome. Notably, Flavobacterium and Undibacterium emerged as distinctive microbial entities in neotenic 7DPA samples, highlighting potential key players in the microbial ecology of regeneration. These findings suggest that the axolotl's microbiome is dynamically responsive to blastema formation, and they underscore the potential influence of microbial communities on the regeneration process. This study lays the groundwork for future research into the mechanisms by which the microbiome may modulate regenerative capacity.


Assuntos
Ambystoma mexicanum , Extremidades , Microbiota , RNA Ribossômico 16S , Regeneração , Animais , Microbiota/genética , Ambystoma mexicanum/microbiologia , Ambystoma mexicanum/fisiologia , RNA Ribossômico 16S/genética , Extremidades/microbiologia , Filogenia
9.
PLoS One ; 19(5): e0298959, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38739667

RESUMO

Informal caregivers play a significant role in providing care for older, often vulnerable, patients, and supporting them as they live with chronic diseases. Due to the rising prevalence of older vascular patients and their use of healthcare, the role of their informal caregivers will become more important. However, little is known about the experiences of informal caregivers of patients with critical limb-threatening ischemia and the impact of informal care on different aspects of these caregivers' lives. In addition, literature does not describe the burden this role brings with it, or lack thereof. Therefore a qualitative study using a phenomenological approach, specifically interpretive phenomenological analysis, was used to gain insight into the experiences of the primary informal caregivers of patients with chronic limb-threatening ischemia. Data were collected via semi-structured interviews and focus groups discussions. Fifteen primary informal caregivers of patients with critical limb-threatening ischemia under the care of the vascular surgeon at a tertiary teaching hospital in the Netherlands were included. Data analysis yielded three themes: the perceived identity of this group of caregivers; the varying intensity of informal care; and the collaboration between informal carers, their care recipients and the professional care provider within the vascular surgery department. In contrast to carers of other chronic diseases, the shifting intensity of care that informal caregivers of critical limb-threatening ischemia patients experience seems to prevent long-term overload. Adapting to that fluctuating situation requires flexibility from healthcare providers within the vascular surgery department. In addition, professionals need to involve informal caregivers in the patient's decision-making process and recognize their role in that process.


Assuntos
Cuidadores , Isquemia , Pesquisa Qualitativa , Humanos , Cuidadores/psicologia , Masculino , Feminino , Isquemia/psicologia , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Adulto , Países Baixos , Extremidades/irrigação sanguínea
10.
Biol Lett ; 20(5): 20240097, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38773927

RESUMO

Ostracod crustaceans originated at least 500 Ma ago. Their tiny bivalved shells represent the most species-abundant fossil arthropods, and ostracods are omnipresent in a wide array of freshwater and marine environments today and in the past. Derima paparme gen. et sp. nov. from the Herefordshire Silurian Lagerstätte (~430 Ma) in the Welsh Borderland, UK, is one of only a handful of exceptionally preserved ostracods (with soft parts as well as the shell) known from the Palaeozoic. A male specimen provides the first evidence of the appendages of Binodicopina, a major group of Palaeozoic ostracods comprising some 135 Ordovician to Permian genera. The appendage morphology of D. paparme, but not its shell, indicates that binodicopes belong to Podocopa. The discovery that the soft-part morphology of binodicopes allies them with podocopes affirms that using the shell alone is an unreliable basis for classifying certain fossil ostracods, and knowledge of soft-part morphology is critical for the task. Current assignment of many fossil ostracods to higher taxa, and therefore the evolutionary history of the group, may require reconsideration.


Assuntos
Evolução Biológica , Crustáceos , Fósseis , Animais , Crustáceos/anatomia & histologia , Crustáceos/classificação , Fósseis/anatomia & histologia , Masculino , Extremidades/anatomia & histologia , Exoesqueleto/anatomia & histologia
11.
Radiat Oncol ; 19(1): 56, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745333

RESUMO

BACKGROUND: Oncologic surgical resection is the standard of care for extremity and truncal soft tissue sarcoma (STS), often accompanied by the addition of pre- or postoperative radiation therapy (RT). Preoperative RT may decrease the risk of joint stiffness and fibrosis at the cost of higher rates of wound complications. Hypofractionated, preoperative RT has been shown to provide acceptable outcomes in prospective trials. Proton beam therapy (PBT) provides the means to decrease dose to surrounding organs at risk, such as the skin, bone, soft tissues, and adjacent joint(s), and has not yet been studied in patients with extremity and truncal sarcoma. METHODS: Our study titled "PROspective phase II trial of preoperative hypofractionated protoN therapy for extremity and Truncal soft tissue sarcOma (PRONTO)" is a non-randomized, prospective phase II trial evaluating the safety and efficacy of preoperative, hypofractionated PBT for patients with STS of the extremity and trunk planned for surgical resection. Adult patients with Eastern Cooperative Group Performance Status ≤ 2 with resectable extremity and truncal STS will be included, with the aim to accrue 40 patients. Treatment will consist of 30 Gy radiobiological equivalent of PBT in 5 fractions delivered every other day, followed by surgical resection 2-12 weeks later. The primary outcome is rate of major wound complications as defined according to the National Cancer Institute of Canada Sarcoma2 (NCIC-SR2) Multicenter Trial. Secondary objectives include rate of late grade ≥ 2 toxicity, local recurrence-free survival and distant metastasis-free survival at 1- and 2-years, functional outcomes, quality of life, and pathologic response. DISCUSSION: PRONTO represents the first trial evaluating the use of hypofractionated PBT for STS. We aim to prove the safety and efficacy of this approach and to compare our results to historical outcomes established by previous trials. Given the low number of proton centers and limited availability, the short course of PBT may provide the opportunity to treat patients who would otherwise be limited when treating with daily RT over several weeks. We hope that this trial will lead to increased referral patterns, offer benefits towards patient convenience and clinic workflow efficiency, and provide evidence supporting the use of PBT in this setting. TRIAL REGISTRATION: NCT05917301 (registered 23/6/2023).


Assuntos
Extremidades , Terapia com Prótons , Hipofracionamento da Dose de Radiação , Sarcoma , Humanos , Terapia com Prótons/métodos , Sarcoma/radioterapia , Sarcoma/patologia , Estudos Prospectivos , Adulto , Feminino , Masculino , Neoplasias de Tecidos Moles/radioterapia , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/cirurgia , Cuidados Pré-Operatórios , Tronco
12.
Zoology (Jena) ; 164: 126160, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38574691

RESUMO

Squamates exhibit evident diversity in their limb morphology. Gekkotans are a particularly diverse group in this respect. The appearance of toepads in gekkotans usually cooccurs with the reduction or loss of claws. The gecko Tarentola (Phyllodactylidae) shows a unique combination of features among geckos, with toepads, hyperphalangy, and dimorphism of claw expression (claws are retained on digits III and IV, but lost (manus) or strongly reduced (pes) on the remaining digits). Despite being a candidate model for studying embryonic skeletal development of the autopodium, no studies have investigated the autopodial development of the gecko Tarentola in detail. Here, we aim to follow up the development of the autopodial skeleton in T. annularis and T. mauritanica using acid-free double staining. The results indicate that the terminal phalanges of claw-bearing digits III and IV ossify earlier than in the remaining digits. This confirms the differential ossification as a result of claw regression in Tarentola. The strongly reduced second phalanges of digits IV in both the fore- and hindlimbs are the last ossifying phalanges. Such late ossification may precede the evolutionary loss of this phalanx. If this is correct, the autopodia of Tarentola would be an interesting example of both the hyperphalangy in digit I and the process of phalanx loss in digit IV. Delay in ossification of the miniaturised phalanx probably represents an example of paedomorphosis.


Assuntos
Lagartos , Animais , Lagartos/anatomia & histologia , Lagartos/embriologia , Extremidades/anatomia & histologia , Osteogênese
13.
Dev Biol ; 512: 1-10, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38657748

RESUMO

Precise regulation of gene expression is of utmost importance during cell fate specification. DNA methylation is a key epigenetic mechanism that plays a significant role in the regulation of cell fate by recruiting repression proteins or inhibiting the binding of transcription factors to DNA to regulate gene expression. Limb development is a well-established model for understanding cell fate decisions, and the formation of skeletal elements is coordinated through a sequence of events that control chondrogenesis spatiotemporally. It has been established that epigenetic control participates in cartilage maturation. However, further investigation is required to determine its role in the earliest stages of chondrocyte differentiation. This study investigates how the DNA methylation environment affects cell fate divergence during the early chondrogenic events. Our research has shown for the first time that inhibiting DNA methylation in interdigital tissue with 5-azacytidine results in the formation of an ectopic digit. This discovery suggested that DNA methylation dynamics could regulate the fate of cells between chondrogenesis and cell death during autopod development. Our in vitro findings indicate that DNA methylation at the early stages of chondrogenesis is integral in regulating condensation by controlling cell adhesion and proapoptotic genes. As a result, the dynamics of methylation and demethylation are crucial in governing chondrogenesis and cell death during different stages of limb chondrogenesis.


Assuntos
Diferenciação Celular , Condrócitos , Condrogênese , Metilação de DNA , Extremidades , Metilação de DNA/genética , Condrogênese/genética , Animais , Extremidades/embriologia , Diferenciação Celular/genética , Condrócitos/metabolismo , Condrócitos/citologia , Azacitidina/farmacologia , Regulação da Expressão Gênica no Desenvolvimento , Embrião de Galinha , Epigênese Genética , Apoptose/genética
14.
Dev Growth Differ ; 66(4): 285-296, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38600055

RESUMO

The northern house gecko Hemidactylus flaviviridis exhibits appendage-specific responses to injuries. The autotomized tail regenerates, whereas the severed limb fails to regrow. Many site-specific cellular processes influence tail regeneration. Herein, we analyzed the epithelial-mesenchymal transition contrast in the lizard's amputated appendages (tail and limb). Morphological observations in the healing frame indicated the formation of regeneration blastema in the tail and scar formation in limb. Histology of the tail showed that epithelial cells closer to mesenchyme appeared less columnar and loosely packed, with little intercellular matrix. Whereas in the limb, the columnar epithelial cells remained tightly packed. Collagen deposition was seen in the limb at the intersection of wound epithelium and mesenchyme, favoring scarring by blocking the epithelial-mesenchymal transition. Markers for epithelial-mesenchymal transition were assessed at transcript and protein levels. The regenerating tail showed upregulation of N-cadherin, vimentin, and PCNA, favoring epithelial-mesenchymal transition, cell migration, and proliferation, respectively. In contrast, the scarring limb showed persistently elevated levels of E-cadherin and EpCAM, indicating retention of epithelial characteristics. An attempt was made to screen the resident epithelial stem cell population in both appendages to check their potential role in the epithelial-mesenchymal transition (EMT), hence the differential wound healing. Upregulation in transcript and protein levels of Nanog and Sox2 was observed in the regenerating tail. Fluorescence-activated cell sorting (FACS) provided supporting evidence that the epithelial stem cell population in tail remained significantly higher than in limb. Thus, this study focuses on the mechanistic role of the epithelial-mesenchymal transition in wound healing, highlighting the molecular details of regeneration and scarring events.


Assuntos
Transição Epitelial-Mesenquimal , Extremidades , Lagartos , Regeneração , Cauda , Animais , Lagartos/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Extremidades/fisiologia , Regeneração/fisiologia , Amputação Cirúrgica
15.
Curr Biol ; 34(10): 2066-2076.e3, 2024 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-38657610

RESUMO

Flies groom in response to competing mechanosensory cues in an anterior-to-posterior order using specific legs. From behavior screens, we identified a pair of cholinergic command-like neurons, Mago-no-Te (MGT), whose optogenetic activation elicits thoracic grooming by the back legs. Thoracic grooming is typically composed of body sweeps and leg rubs in alternation, but clonal analysis coupled with amputation experiments revealed that MGT activation only commands the body sweeps: initiation of leg rubbing requires contact between the leg and thorax. With new electron microscopy (EM) connectome data for the ventral nerve cord (VNC), we uncovered a circuit-based explanation for why stimulation of posterior thoracic mechanosensory bristles initiates cleaning by the back legs. Our previous work showed that flies weigh mechanosensory inputs across the body to select which part to groom, but we did not know why the thorax was always cleaned last. Here, the connectome for the VNC enabled us to identify a pair of GABAergic inhibitory neurons, UMGT1, that receives diverse sensory inputs and synapses onto both MGT and components of its downstream circuits. Optogenetic activation of UMGT1 suppresses thoracic cleaning, representing a mechanism by which mechanosensory stimuli on other body parts could take precedence in the grooming hierarchy. We also anatomically mapped the pre-motor circuit downstream of MGT, including inhibitory feedback connections that may enable rhythmicity and coordination of limb movement during thoracic grooming. The combination of behavioral screens and connectome analysis allowed us to identify a neural circuit connecting sensory-to-motor neurons that contributes to thoracic grooming.


Assuntos
Drosophila melanogaster , Asseio Animal , Animais , Asseio Animal/fisiologia , Drosophila melanogaster/fisiologia , Extremidades/fisiologia , Conectoma , Optogenética , Mecanorreceptores/fisiologia , Mecanotransdução Celular
16.
Semin Thromb Hemost ; 50(5): 760-772, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38688305

RESUMO

Ischemic limb injury can be broadly classified into arterial (absent pulses) and venous/microvascular (detectable pulses); the latter can be divided into two overlapping disorders-venous limb gangrene (VLG) and symmetrical peripheral gangrene (SPG). Both VLG and SPG feature predominant acral (distal) extremity ischemic necrosis, although in some instances, concomitant nonacral ischemia/skin necrosis occurs. Historically, for coagulopathic disorders with prominent nonacral ischemic necrosis, clinician-scientists implicated depletion of natural anticoagulants, especially involving the protein C (PC) system. This historical review traces the recognition of natural anticoagulant depletion as a key feature of nonacral ischemic syndromes, such as classic warfarin-induced skin necrosis, neonatal purpura fulminans (PF), and meningococcemia-associated PF. However, only after several decades was it recognized that natural anticoagulant depletion is also a key feature of predominantly acral ischemic microthrombosis syndromes-VLG and SPG-even when accompanying nonacral thrombosis is not present. These acquired acral limb ischemic syndromes typically involve the triad of (a) disseminated intravascular coagulation, (b) natural anticoagulant depletion, and (c) a localizing explanation for microthrombosis occurring in one or more limbs, either deep vein thrombosis (helping to explain VLG) or circulatory shock (helping to explain SPG). In most cases of VLG or SPG there are one or more events that exacerbate natural anticoagulant depletion, such as warfarin therapy (e.g., warfarin-associated VLG complicating heparin-induced thrombocytopenia or cancer hypercoagulability) or acute ischemic hepatitis ("shock liver") as a proximate factor predisposing to severe depletion of hepatically synthesized natural anticoagulants (PC, antithrombin) in the setting of circulatory shock.


Assuntos
Necrose , Humanos , Trombose/etiologia , Trombose/história , Isquemia , Extremidades/irrigação sanguínea , História do Século XX
17.
Sci Rep ; 14(1): 8012, 2024 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580704

RESUMO

The objective of human pose estimation (HPE) derived from deep learning aims to accurately estimate and predict the human body posture in images or videos via the utilization of deep neural networks. However, the accuracy of real-time HPE tasks is still to be improved due to factors such as partial occlusion of body parts and limited receptive field of the model. To alleviate the accuracy loss caused by these issues, this paper proposes a real-time HPE model called CCAM - Person based on the YOLOv8 framework. Specifically, we have improved the backbone and neck of the YOLOv8x-pose real-time HPE model to alleviate the feature loss and receptive field constraints. Secondly, we introduce the context coordinate attention module (CCAM) to augment the model's focus on salient features, reduce background noise interference, alleviate key point regression failure caused by limb occlusion, and improve the accuracy of pose estimation. Our approach attains competitive results on multiple metrics of two open-source datasets, MS COCO 2017 and CrowdPose. Compared with the baseline model YOLOv8x-pose, CCAM-Person improves the average precision by 2.8% and 3.5% on the two datasets, respectively.


Assuntos
Benchmarking , Extremidades , Humanos , Redes Neurais de Computação , Postura , Gravação de Videoteipe
18.
Perfusion ; 39(1_suppl): 23S-38S, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38651584

RESUMO

Limb ischaemia is a clinically relevant complication of venoarterial extracorporeal membrane oxygenation (VA ECMO) with femoral artery cannulation. No selective distal perfusion or other advanced techniques were used in the past to maintain adequate distal limb perfusion. A more recent trend is the shift from the reactive or emergency management to the pro-active or prophylactic placement of a distal perfusion cannula to avoid or reduce limb ischaemia-related complications. Multiple alternative cannulation techniques to the distal perfusion cannula have been developed to maintain distal limb perfusion, including end-to-side grafting, external or endovascular femoro-femoral bypass, retrograde limb perfusion (e.g., via the posterior tibial, dorsalis pedis or anterior tibial artery), and, more recently, use of a bidirectional cannula. Venous congestion has also been recognized as a potential contributing factor to limb ischaemia development and specific techniques have been described with facilitated venous drainage or bilateral cannulation being the most recent, to reduce or avoid venous stasis as a contributor to impaired limb perfusion. Advances in monitoring techniques, such as near-infrared spectroscopy and duplex ultrasound analysis, have been applied to improve decision-making regarding both the monitoring and management of limb ischaemia. This narrative review describes the evolution of techniques used for distal limb perfusion during peripheral VA ECMO.


Assuntos
Oxigenação por Membrana Extracorpórea , Artéria Femoral , Humanos , Oxigenação por Membrana Extracorpórea/métodos , Perfusão/métodos , Cateterismo/métodos , Isquemia/prevenção & controle , Isquemia/etiologia , Adulto , Cateterismo Periférico/métodos , Cateterismo Periférico/efeitos adversos , Extremidades/irrigação sanguínea
19.
Ann Med ; 56(1): 2338248, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38590164

RESUMO

BACKGROUND/OBJECTIVE(S): Chronic obstructive pulmonary disease (COPD) can precipitate a deterioration of an individual's physical performance and overall health. Evidence suggests that, along with pulmonary functions, several other factors are related to the significant impairment of walking performance in individuals with COPD. This study compared the depressive symptoms, health status, upper and lower extremity functions, and peak oxygen uptake (VO2peak) in a group of individuals with COPD based on walking performance using a cutoff distance of 350 m in the six-minute walking test (6MWT). The study also investigated the associations between these factors and walking performance. MATERIALS AND METHODS: Participants performed the 6MWT according to the guidelines and were classified into high (>350 m; n = 40) or low (<350 m; n = 30) walking performance groups according to distance. The forced expiratory volume (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio were recorded. Participants completed the Patient Health Questionnaire-9 (PHQ-9), St. George's Respiratory Questionnaire (SGRQ), and the Upper and Lower Extremity Functional Index (UEFI/LEFI). Predicted VO2peak was measured using the Duke Activity Status Index (DASI). RESULTS: Seventy participants with a mean age of 63 ± 11 years (20% female) were enrolled in this study. Patients with high walking performance demonstrated significantly better health status than those with low walking performance (SGRQ: 49 ± 25 vs. 56 ± 21, p = 0.03). Participants with low walking performance had lower predicted VO2peak compared to their higher performing counterparts (p = 0.002). The overall model was significant (F(8, 61) = 7.48, p = 0.0006), with PHQ-9, SGRQ, UEFI/LEFI, VO2peak, and FEV1/FVC explaining approximately 49.5% of the variance in the 6MWT distance. CONCLUSION: This study shed light on the association of depressive symptoms, health status, extremity function, and VO2peak with walking performance, providing valuable insights that may impact the management and care of individuals with COPD.


COPD is a global health issue that significantly impairs physical performance, particularly walking.Depressive symptoms, health status, extremity function, and predicted peak oxygen uptake can predict walking performance in patients with COPD, offering insight into potential interventions.


Assuntos
Depressão , Doença Pulmonar Obstrutiva Crônica , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Nível de Saúde , Volume Expiratório Forçado , Extremidades , Caminhada , Desempenho Físico Funcional , Qualidade de Vida
20.
Am J Crit Care ; 33(3): 226-233, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38688844

RESUMO

BACKGROUND: It remains poorly understood why only some hemodynamically unstable patients who receive aggressive treatment with vasopressor medications develop limb necrosis. OBJECTIVE: To determine the incidence of limb necrosis and the factors associated with it following high-dose vasopressor therapy. METHODS: A retrospective case-control medical records review was performed of patients aged 18 to 89 years who received vasopressor therapy between 2012 and 2021 in a single academic medical center. The study population was stratified by the development of limb necrosis following vasopressor use. Patients who experienced necrosis were compared with age- and sex-matched controls who did not experience necrosis. Demographic information, comorbidities, and medication details were recorded. RESULTS: The incidence of limb necrosis following vasopressor administration was 0.25%. Neither baseline demographics nor medical comorbidities differed significantly between groups. Necrosis was present in the same limb as the arterial catheter most often for femoral catheters. The vasopressor dose administered was significantly higher in the necrosis group than in the control group for ephedrine (P = .02) but not for the other agents. The duration of therapy was significantly longer in the necrosis group than in the control group for norepinephrine (P = .001), epinephrine (P = .04), and ephedrine (P = .01). The duration of vasopressin administration did not differ significantly between groups. CONCLUSION: The findings of this study suggest that medication-specific factors, rather than patient and disease characteristics, should guide clinical management of necrosis in the setting of vasopressor administration.


Assuntos
Necrose , Vasoconstritores , Humanos , Vasoconstritores/efeitos adversos , Vasoconstritores/administração & dosagem , Vasoconstritores/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Necrose/induzido quimicamente , Adulto , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Adolescente , Norepinefrina/efeitos adversos , Norepinefrina/administração & dosagem , Norepinefrina/uso terapêutico , Adulto Jovem , Extremidades , Incidência , Epinefrina/administração & dosagem , Epinefrina/efeitos adversos , Epinefrina/uso terapêutico , Fatores de Risco
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