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1.
Proc Natl Acad Sci U S A ; 119(35): e2123267119, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-35994660

RESUMO

The pregnant uterus is an immunologically rich organ, with dynamic changes in the inflammatory milieu and immune cell function underlying key stages of pregnancy. Recent studies have implicated dysregulated expression of the interleukin-1 (IL-1) family cytokine, IL-33, and its receptor, ST2, in poor pregnancy outcomes in women, including recurrent pregnancy loss, preeclampsia, and preterm labor. How IL-33 supports pregnancy progression in vivo is not well understood. Here, we demonstrate that maternal IL-33 signaling critically regulates uterine tissue remodeling and immune cell function during early pregnancy in mice. IL-33-deficient dams exhibit defects in implantation chamber formation and decidualization, and abnormal vascular remodeling during early pregnancy. These defects coincide with delays in early embryogenesis, increased resorptions, and impaired fetal and placental growth by late pregnancy. At a cellular level, myometrial fibroblasts, and decidual endothelial and stromal cells, are the main IL-33+ cell types in the uterus during decidualization and early placentation, whereas ST2 is expressed by uterine immune populations associated with type 2 immune responses, including ILC2s, Tregs, CD4+ T cells, M2- and cDC2-like myeloid cells, and mast cells. Early pregnancy defects in IL-33-deficient dams are associated with impaired type 2 cytokine responses by uterine lymphocytes and fewer Arginase-1+ macrophages in the uterine microenvironment. Collectively, our data highlight a regulatory network, involving crosstalk between IL-33-producing nonimmune cells and ST2+ immune cells at the maternal-fetal interface, that critically supports pregnancy progression in mice. This work has the potential to advance our understanding of how IL-33 signaling may support optimal pregnancy outcomes in women.


Assuntos
Interleucina-33 , Placenta , Placentação , Útero , Animais , Decídua/irrigação sanguínea , Decídua/citologia , Decídua/crescimento & desenvolvimento , Decídua/imunologia , Feminino , Feto/imunologia , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Interleucina-33/deficiência , Interleucina-33/imunologia , Linfócitos/imunologia , Linfócitos/metabolismo , Camundongos , Placenta/imunologia , Placenta/metabolismo , Gravidez , Útero/irrigação sanguínea , Útero/crescimento & desenvolvimento , Útero/imunologia , Útero/metabolismo
2.
Eur Heart J ; 45(13): 1146-1155, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37935833

RESUMO

BACKGROUND AND AIMS: Haemodynamic instability is associated with peri-operative myocardial injury, particularly in patients receiving renin-angiotensin system (RAS) inhibitors (angiotensin-converting-enzyme inhibitors/angiotensin II receptor blockers). Whether stopping RAS inhibitors to minimise hypotension, or continuing RAS inhibitors to avoid hypertension, reduces peri-operative myocardial injury remains unclear. METHODS: From 31 July 2017 to 1 October 2021, patients aged ≥60 years undergoing elective non-cardiac surgery were randomly assigned to either discontinue or continue RAS inhibitors prescribed for existing medical conditions in six UK centres. Renin-angiotensin system inhibitors were withheld for different durations (2-3 days) before surgery, according to their pharmacokinetic profile. The primary outcome, masked to investigators, clinicians, and patients, was myocardial injury [plasma high-sensitivity troponin-T (hs-TnT) ≥ 15 ng/L within 48 h after surgery, or ≥5 ng/L increase when pre-operative hs-TnT ≥15 ng/L]. Pre-specified adverse haemodynamic events occurring within 48 h of surgery included acute hypertension (>180 mmHg) and hypotension requiring vasoactive therapy. RESULTS: Two hundred and sixty-two participants were randomized to continue (n = 132) or stop (n = 130) RAS inhibitors. Myocardial injury occurred in 58 (48.3%) patients randomized to discontinue, compared with 50 (41.3%) patients who continued, RAS inhibitors [odds ratio (for continuing): 0.77; 95% confidence interval (CI) 0.45-1.31]. Hypertensive adverse events were more frequent when RAS inhibitors were stopped [16 (12.4%)], compared with 7 (5.3%) who continued RAS inhibitors [odds ratio (for continuing): 0.4; 95% CI 0.16-1.00]. Hypotension rates were similar when RAS inhibitors were stopped [12 (9.3%)] or continued [11 (8.4%)]. CONCLUSIONS: Discontinuing RAS inhibitors before non-cardiac surgery did not reduce myocardial injury, and could increase the risk of clinically significant acute hypertension. These findings require confirmation in future studies.


Assuntos
Hipertensão , Hipotensão , Humanos , Sistema Renina-Angiotensina , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão/induzido quimicamente , Hipotensão/induzido quimicamente , Hipotensão/prevenção & controle , Hipotensão/tratamento farmacológico , Antagonistas de Receptores de Angiotensina/efeitos adversos
3.
Br J Anaesth ; 132(5): 857-866, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38341283

RESUMO

BACKGROUND: Patients with elevated preoperative plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP >100 pg ml-1) experience more complications after noncardiac surgery. Individuals prescribed renin-angiotensin system (RAS) inhibitors for cardiometabolic disease are at particular risk of perioperative myocardial injury and complications. We hypothesised that stopping RAS inhibitors before surgery increases the risk of perioperative myocardial injury, depending on preoperative risk stratified by plasma NT-proBNP concentrations. METHODS: In a preplanned analysis of a phase 2a trial in six UK centres, patients ≥60 yr old undergoing elective noncardiac surgery were randomly assigned either to stop or continue RAS inhibitors before surgery. The pharmacokinetic profile of individual RAS inhibitors determined for how long they were stopped before surgery. The primary outcome, masked to investigators, clinicians, and patients, was myocardial injury (plasma high-sensitivity troponin-T ≥15 ng L-1 or a ≥5 ng L-1 increase, when preoperative high-sensitivity troponin-T ≥15 ng L-1) within 48 h after surgery. The co-exposures of interest were preoperative plasma NT-proBNP (< or >100 pg ml -1) and stopping or continuing RAS inhibitors. RESULTS: Of 241 participants, 101 (41.9%; mean age 71 [7] yr; 48% females) had preoperative NT-proBNP >100 pg ml -1 (median 339 [160-833] pg ml-1), of whom 9/101 (8.9%) had a formal diagnosis of cardiac failure. Myocardial injury occurred in 63/101 (62.4%) subjects with NT-proBNP >100 pg ml-1, compared with 45/140 (32.1%) subjects with NT-proBNP <100 pg ml -1 {odds ratio (OR) 3.50 (95% confidence interval [CI] 2.05-5.99); P<0.0001}. For subjects with preoperative NT-proBNP <100 pg ml-1, 30/75 (40%) who stopped RAS inhibitors had myocardial injury, compared with 15/65 (23.1%) who continued RAS inhibitors (OR for stopping 2.22 [95% CI 1.06-4.65]; P=0.03). For preoperative NT-proBNP >100 pg ml-1, myocardial injury rates were similar regardless of stopping (62.2%) or continuing (62.5%) RAS inhibitors (OR for stopping 0.98 [95% CI 0.44-2.22]). CONCLUSIONS: Stopping renin-angiotensin system inhibitors in lower-risk patients (preoperative NT-proBNP <100 pg ml -1) increased the likelihood of myocardial injury before noncardiac surgery.


Assuntos
Traumatismos Cardíacos , Peptídeo Natriurético Encefálico , Feminino , Humanos , Idoso , Masculino , Troponina T , Sistema Renina-Angiotensina , Biomarcadores , Fragmentos de Peptídeos
4.
Development ; 146(9)2019 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-30952667

RESUMO

Arl/ARF GTPases regulate ciliary trafficking, but their tissue-specific functions are unclear. Here, we demonstrate that ciliary GTPase Arl3 is required for mitotic spindle orientation of mouse basal stem cells during skin development. Arl3 loss diminished cell divisions within the plane of the epithelium, leading to increased perpendicular divisions, expansion of progenitor cells and loss of epithelial integrity. These observations suggest that an Arl3-dependent mechanism maintains cell division polarity along the tissue axis, and disruption of planar spindle orientation has detrimental consequences for epidermal architecture. Defects in planar cell polarity (PCP) can disrupt spindle positioning during tissue morphogenesis. Upon Arl3 loss, the PCP signaling molecules Celsr1 and Vangl2 failed to maintain planar polarized distributions, resulting in defective hair follicle angling, a hallmark of disrupted PCP. In the absence of Celsr1 polarity, frizzled 6 lost its asymmetrical distribution and abnormally segregated to the apical cortex of basal cells. We propose that Arl3 regulates polarized endosomal trafficking of PCP components to compartmentalized membrane domains. Cell-cell communication via ciliary GTPase signaling directs mitotic spindle orientation and PCP signaling, processes that are crucial for the maintenance of epithelial architecture.


Assuntos
Fatores de Ribosilação do ADP/metabolismo , Fuso Acromático/metabolismo , Fatores de Ribosilação do ADP/genética , Animais , Western Blotting , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Polaridade Celular/genética , Polaridade Celular/fisiologia , Células Cultivadas , Receptores Frizzled/genética , Receptores Frizzled/metabolismo , Técnicas In Vitro , Queratinócitos/metabolismo , Lentivirus/genética , Camundongos , Mitose/genética , Mitose/fisiologia , Morfogênese/genética , Morfogênese/fisiologia , Reação em Cadeia da Polimerase , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
5.
Langmuir ; 38(21): 6531-6538, 2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35579436

RESUMO

External surface engineering of metal-organic framework nanoparticles (MOF NPs) is emerging as an important design strategy, leading to optimized chemical and colloidal stability. To date, most of the MOF surface modifications have been performed either by physical adsorption or chemical association of small molecules or (preformed) polymers. However, most of the currently employed approaches cannot precisely control the polymer density, and dynamic modifications at the surfaces on demand have been a challenging task. Here, we introduce a general approach based on covalent modification employing alkoxyamines as a versatile tool to modify the outer surface of MOF nanoparticles (NPs). The alkoxyamines serve as initiators to grow polymers from the MOF surface via nitroxide-mediated polymerization (NMP) and allow dynamic attachment of small molecules via a nitroxide exchange reaction (NER). The successful surface modification and successive surface polymerization are confirmed via time-of-flight secondary ion mass spectrometry (ToF-SIMS), size exclusion chromatography (SEC), and nuclear magnetic resonance (NMR) spectroscopy. The functionalized MOF NPs exhibit high suspension stability and good dispersibility while retaining their chemical integrity and crystalline structure. In addition, electron paramagnetic resonance spectroscopy (EPR) studies prove the dynamic exchange of two different nitroxide species via NER and further allow us to quantify the surface modification with high sensitivity. Our results demonstrate that alkoxyamines serve as a versatile tool to dynamically modify the surface of MOF NPs with high precision, allowing us to tailor their properties for a wide range of potential applications, such as drug delivery or mixed matrix membranes.

6.
Int J Mol Sci ; 23(11)2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35682660

RESUMO

Uterine leiomyosarcoma (uLMS) is a rare and aggressive cancer with few effective therapeutics. The Notch signaling pathway is evolutionarily conserved with oncogenic properties, but it has not been well studied in uLMS. The purpose of our study was to determine expression of Notch family genes and proteins and to investigate the therapeutic effect of γ-secretase inhibitors (GSIs), indirect inhibitors of Notch signaling, in uLMS. We determined expression of Notch genes and proteins in benign uterine smooth muscle tissue, fibroids, and uLMS samples by immunostaining and in two uLMS cell lines, SK-UT-1B (uterine primary) and SK-LMS-1 (vulvar metastasis) by RT-PCR, Western blot and immunostaining. We exposed our cell lines to GSIs, DAPT and MK-0752, and measured expression of HES1, a downstream effector of Notch. Notch proteins were differentially expressed in uLMS. Expression of NOTCH3 and NOTCH4 was higher in uLMS samples than in benign uterine smooth muscle and fibroids. Expression of NOTCH4 was higher in SK-LMS-1 compared to SK-UT-1B. Exposure of SK-UT-1B and SK-LMS-1 to DAPT and MK-0752 decreased expression of HES1 and decreased uLMS cell viability in a dose- and time-dependent manner that was unique to each GSI. Our findings suggest that GSIs are potential therapeutics for uLMS, albeit with limited efficacy.


Assuntos
Leiomioma , Leiomiossarcoma , Neoplasias Pélvicas , Neoplasias Uterinas , Feminino , Inibidores e Moduladores de Secretases gama , Humanos , Leiomiossarcoma/tratamento farmacológico , Leiomiossarcoma/genética , Leiomiossarcoma/metabolismo , Inibidores da Agregação Plaquetária/uso terapêutico , Receptores Notch , Transdução de Sinais , Neoplasias Uterinas/patologia
7.
Reproduction ; 161(6): 681-696, 2021 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-33784241

RESUMO

In the first trimester of human pregnancy, low oxygen tension or hypoxia is essential for proper placentation and placenta function. Low oxygen levels and activation of signaling pathways have been implicated as critical mediators in the promotion of trophoblast differentiation, migration, and invasion with inappropriate changes in oxygen tension and aberrant Notch signaling both individually reported as causative to abnormal placentation. Despite crosstalk between hypoxia and Notch signaling in multiple cell types, the relationship between hypoxia and Notch in first trimester trophoblast function is not understood. To determine how a low oxygen environment impacts Notch signaling and cellular motility, we utilized the human first trimester trophoblast cell line, HTR-8/SVneo. Gene set enrichment and ontology analyses identified pathways involved in angiogenesis, Notch and cellular migration as upregulated in HTR-8/SVneo cells exposed to hypoxic conditions. DAPT, a γ-secretase inhibitor that inhibits Notch activation, was used to interrogate the crosstalk between Notch and hypoxia pathways in HTR-8/SVneo cells. We found that hypoxia requires Notch activation to mediate HTR-8/SVneo cell migration, but not invasion. To determine if our in vitro findings were associated with preeclampsia, we analyzed the second trimester chorionic villous sampling (CVS) samples and third trimester placentas. We found a significant decrease in expression of migration and invasion genes in CVS from preeclamptic pregnancies and significantly lower levels of JAG1 in placentas from pregnancies with early-onset preeclampsia with severe features. Our data support a role for Notch in mediating hypoxia-induced trophoblast migration, which may contribute to preeclampsia development.


Assuntos
Movimento Celular , Hipóxia/fisiopatologia , Proteína Jagged-1/metabolismo , Placenta/patologia , Pré-Eclâmpsia/patologia , Receptores Notch/metabolismo , Trofoblastos/patologia , Adulto , Feminino , Humanos , Proteína Jagged-1/genética , Placenta/metabolismo , Pré-Eclâmpsia/etiologia , Pré-Eclâmpsia/metabolismo , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Receptores Notch/genética , Transdução de Sinais , Trofoblastos/metabolismo
8.
Acc Chem Res ; 52(6): 1598-1610, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-30977634

RESUMO

The integration of a porous crystalline framework with soft polymers to create novel biomaterials has tremendous potential yet remains very challenging to date. Metal-organic framework (MOF)-templated polymers (MTPs) have emerged as persistent modular materials that can be tailored for desired biofunctions. These represent a novel class of hierarchically structured assemblies that combine the advantages of MOFs (precisely controlled structure, enormous diversity in framework topology, and high porosity) with the intrinsic behaviors of polymers (soft texture, flexibility, biocompatibility, and improved stability under physiological conditions). Transformation of surface-anchored MOFs (SURMOFs) via orthogonal covalent cross-linking yields surface-anchored polymeric gels (SURGELs) that open up exciting new opportunities to create soft nanoporous materials. SURGELs overcome the main drawbacks of SURMOFs, such as their limited stability under physiological conditions and their potential to release toxic metal ions, a substantial problem for applications in life sciences. MOF (SURMOF)-templated polymerization processes control the synthesis on a molecular level. Additionally, the morphology of the original MOF crystal template is replicated in the final network polymers. The MOF-templated polymerization can be induced by light, a catalyst, or temperature using several types of reactions, including thiol-ene, metal-free alkyne-azide click reactions, and Glaser-Hay coupling. In the case of photoinduced reactions, the cross-linking process can be locally confined, allowing control of the macroscopic patterning of the resulting network polymer. The use of layer-by-layer (lbl) techniques in the SURMOF synthesis serves the purpose of precise, layer-selective incorporation of functionalities via the combination of the postsynthetic modification and heteroepitaxy strategies. Transforming the functionalized SURMOF into a SURGEL allows the fabrication of polymers with desired bioactive functions at the internal or external surfaces. This Account highlights our ongoing research and inspiring progress in transforming SURMOFs into persistent, modular nanoporous materials tailored with biofunctions. Using cell culture studies, we present various aspects of SURGEL materials, such as the ability to deliver bioactive molecules to adhering cells on SURGEL surfaces, applications to advanced drug delivery systems, the ability to tune cell adhesion via surface modification, and the development of porphyrin-based SURGEL thin films with antimicrobial properties. Then we critically examine the challenges and limitations of current systems and discuss future research directions and new approaches for advancing MOF-templated biocompatible materials, emphasizing the need to include responsive and adaptive functionalities into the system. We emphasize that the hierarchical structure, ranging from the molecular to the macroscopic scale, allows for optimization of the material properties across all length scales relevant for cell-material interactions.


Assuntos
Materiais Biocompatíveis/química , Portadores de Fármacos/química , Géis/química , Estruturas Metalorgânicas/química , Nanoestruturas/química , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/toxicidade , Portadores de Fármacos/síntese química , Portadores de Fármacos/toxicidade , Escherichia coli/efeitos dos fármacos , Géis/síntese química , Géis/toxicidade , Estruturas Metalorgânicas/síntese química , Estruturas Metalorgânicas/toxicidade , Nanoestruturas/toxicidade , Polimerização , Porfirinas/síntese química , Porfirinas/química , Porfirinas/farmacologia , Propriedades de Superfície
9.
Langmuir ; 36(36): 10657-10673, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32787055

RESUMO

This feature article describes recent trends and advances in structuring network polymers using a coordination-driven metal-organic framework (MOF)-based template approach to demonstrate the concept of crystal-controlled polymerization in confined nanospaces, forming tailored architectures ranging from simple linear one-dimensional macromolecules to tunable three-dimensional cross-linked network polymers and interwoven molecular architectures. MOF-templated network polymers combine the characteristics and advantages of crystalline MOFs (high porosity, structural regularity, and designability) with the intrinsic behaviors of soft polymers (flexibility, processability, stability, or biocompatibility) with widespread application possibilities and tunable properties. The article ends with a summary of the remaining challenges to be addressed, and future research opportunities in this field are discussed.

10.
Int J Mol Sci ; 21(18)2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32899448

RESUMO

Maternal spiral arteries and newly formed decidual capillaries support embryonic development prior to placentation. Previous studies demonstrated that Notch signaling is active in endothelial cells of both decidual capillaries and spiral arteries, however the role of Notch signaling in physiologic decidual angiogenesis and maintenance of the decidual vasculature in early mouse pregnancy has not yet been fully elucidated. We used the Cdh5-CreERT2;Jagged1(Jag1)flox/flox (Jag1∆EC) mouse model to delete Notch ligand, Jag1, in maternal endothelial cells during post-implantation, pre-placentation mouse pregnancy. Loss of endothelial Jag1 leads to increased expression of Notch effectors, Hey2 and Nrarp, and increased endothelial Notch signaling activity in areas of the decidua with remodeling angiogenesis. This correlated with an increase in Dll4 expression in capillary endothelial cells, but not spiral artery endothelial cells. Consistent with increased Dll4/Notch signaling, we observed decreased VEGFR2 expression and endothelial cell proliferation in angiogenic decidual capillaries. Despite aberrant Dll4 expression and Notch activation in Jag1∆EC mutants, pregnancies were maintained and the decidual vasculature was not altered up to embryonic day 7.5. Thus, Jag1 functions in the newly formed decidual capillaries as an antagonist of endothelial Dll4/Notch signaling during angiogenesis, but Jag1 signaling is not necessary for early uterine angiogenesis.


Assuntos
Proteína Jagged-1/metabolismo , Neovascularização Patológica/metabolismo , Neovascularização Fisiológica/fisiologia , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Proliferação de Células , Decídua/metabolismo , Implantação do Embrião/fisiologia , Desenvolvimento Embrionário , Endométrio/metabolismo , Células Endoteliais/metabolismo , Feminino , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteína Jagged-1/fisiologia , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Morfogênese , Placentação , Gravidez , Receptores Notch/metabolismo , Transdução de Sinais , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
11.
Artigo em Inglês | MEDLINE | ID: mdl-28095116

RESUMO

This review summarizes recent advances on design strategies for shape-controlled anisotropic gold nanoparticles. Detailed chemical mechanism has been discussed to understand the anisotropic growth. The effect of various chemical parameters and surface facets for the formation of different shaped anisotropic nanoparticles have been addressed.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Nanotecnologia/métodos , Anisotropia
12.
Zootaxa ; 3973(3): 401-24, 2015 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-26249869

RESUMO

The Indian species of the genus Oligosita Walker, 1851 (Hymenoptera: Trichogrammatidae) are revised. One new species, Oligosita aseta Begum & Anis, sp. nov., is described based on specimens collected from Kerala, India. A key to the 16 Indian species of the genus is also given.


Assuntos
Himenópteros/classificação , Distribuição Animal , Estruturas Animais/anatomia & histologia , Estruturas Animais/crescimento & desenvolvimento , Animais , Tamanho Corporal , Feminino , Himenópteros/anatomia & histologia , Himenópteros/crescimento & desenvolvimento , Índia , Masculino , Tamanho do Órgão
13.
Chemistry ; 20(29): 8862-6, 2014 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-24939723

RESUMO

The development of water-mediated proton-conducting materials operating above 100 °C remains challenging because the extended structures of existing materials usually deteriorate at high temperatures. A new triazolyl phosphonate metal-organic framework (MOF) [La3L4(H2O)6]Cl⋅x H2O (1, L(2-) = 4-(4H-1,2,4-triazol-4-yl)phenyl phosphonate) with highly hydrophilic 1D channels was synthesized hydrothermally. Compound 1 is an example of a phosphonate MOF with large regular pores with 1.9 nm in diameter. It forms a water-stable, porous structure that can be reversibly hydrated and dehydrated. The proton-conducting properties of 1 were investigated by impedance spectroscopy. Magic-angle spinning (MAS) and pulse field gradient (PFG) NMR spectroscopies confirm the dynamic nature of the incorporated water molecules. The diffusivities, determined by PFG NMR and IR microscopy, were found to be close to that of liquid water. This porous framework accomplishes the challenges of water stability and proton conduction even at 110 °C. The conductivity in 1 is proposed to occur by the vehicle mechanism.

14.
OTJR (Thorofare N J) ; 44(2): 205-217, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37942615

RESUMO

This research aimed to describe the process of occupational participation among persons with spinal cord injury (SCI) discharged from the only SCI rehabilitation hospital in Bangladesh. We analyzed seven participants' interview transcripts and observations using the trajectory equifinality model. Study participants demonstrated the following occupational participation trajectories: (a) employing a strategy or difficulty in occupational participation; (b) performing solidarity or experiencing deprivation; (c) creating identity or divergence; and (d) being included in or excluded from everyday life. There are four pathways: (I) discouraging conditions that minimized daily performance; (II) reinforcing obligatory connections to optimization of daily performance; (III) reciprocity to facilitate social activities; and (IV) manipulating mastery in occupational participation. Occupational therapists can consider the trajectory phases and pathways of occupational participation when facilitating the inclusion of service users after discharge from the hospital.


Experience of Occupational Participation Among Persons With Spinal Cord Injury: Life Story Analysis With Trajectory Equifinality Model (TEM)Persons with spinal cord injury (SCI) in Bangladesh demonstrated inadequate skills in community integration because of limited access to health care follow-ups and unfavorable sociocultural conditions. This research focuses on occupational participation experiences among seven persons with SCI living in the community. We used trajectory equifinality model (TEM) to analyze semi-structured interview and observation data to understand human experiences in an irreversible timeline from a starting point to an endpoint. Data analysis revealed a conceptualization of four periods of occupational participation and four common types of non-linear pathways. Participants optimized shared occupational participation and used mastery over occupations to minimize the experience of occupational deprivation. These findings could assist in developing independent peer-led occupation-based health care programs with few skilled occupational therapists and limited financial resources. These 3 years of interviews and follow-up reports with participants who were selected purposively do not necessarily reflect how actual participation unfolded over time.


Assuntos
Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/reabilitação , Emprego , Terapeutas Ocupacionais
15.
Cells ; 12(7)2023 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-37048068

RESUMO

Leptomeningeal disease occurs when cancer cells migrate into the ventricles of the brain and spinal cord and then colonize the meninges of the central nervous system. The triple-negative subtype of breast cancer often progresses toward leptomeningeal disease and has a poor prognosis because of limited treatment options. This is due, in part, to a lack of animal models with which to study leptomeningeal disease. Here, we developed a translucent zebrafish casper (roy-/-; nacre-/-) xenograft model of leptomeningeal disease in which fluorescent labeled MDA-MB-231 human triple-negative breast cancer cells are microinjected into the ventricles of zebrafish embryos and then tracked and measured using fluorescent microscopy and multimodal plate reader technology. We then used these techniques to measure tumor area, cell proliferation, and cell death in samples treated with the breast cancer drug doxorubicin and a vehicle control. We monitored MDA-MB-231 cell localization and tumor area, and showed that samples treated with doxorubicin exhibited decreased tumor area and proliferation and increased apoptosis compared to control samples.


Assuntos
Antineoplásicos , Neoplasias de Mama Triplo Negativas , Animais , Humanos , Neoplasias de Mama Triplo Negativas/patologia , Peixe-Zebra , Apoptose , Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico
16.
Occup Ther Int ; 2022: 2705104, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35359429

RESUMO

Purpose: This study explored how community-dwelling persons with spinal cord injury (SCI) and their primary caregivers execute self-management strategies in daily activities. These strategies were mapped to a preexisting self-management framework. Methods: Photoelicitation focus group discussions were conducted among 14 adults with SCI and their primary caregivers (in two groups). Moreover, a constant comparative framework was used to analyze the data. Results: This study identified nine groups of self-management strategies, some of which could not be categorized under the three main self-management components generally accepted in the literature. Accordingly, a new component is proposed based off of this analysis, entitled management of social complexities, which includes crucial strategies such as (1) relocating to another environment, (2) behaving in an assertive manner, and (3) advocating for social change. Conclusion: The results show that self-management, traditionally described as medical, emotional, and role management, should also include the management of social complexities. The identified strategies could be considered in the development of self-management enhancement programs in lower-middle-income countries.


Assuntos
Terapia Ocupacional , Autogestão , Traumatismos da Medula Espinal , Adulto , Bangladesh , Cuidadores , Grupos Focais , Humanos
17.
BJA Open ; 3: 100032, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37588576

RESUMO

Background: Anaemia is associated with complications and death after surgery. Perioperative red-cell transfusion triggers are not well defined in patients having oncological surgery, or with cardiovascular disease. Methods: We carried out a prospective multicentre cohort study and a clinician survey of UK transfusion practice in adult patients undergoing surgery for abdominal malignancy. The primary outcome was red cell transfusion. Secondary outcomes were transfusion trigger haemoglobin, incidence of complications, length of hospital stay, and acute hospital mortality. Results: In this prospective cohort study, data were collected on 412 patients undergoing surgery for intrabdominal malignancy in 14 NHS hospitals. Twenty-two (5.2%) patients received preoperative, 42 (10.2%) intraoperative, and 52 (12.2%) postoperative red blood cell transfusion. The mean postoperative transfusion trigger was 75.3 g L-1, and the mean number of units of red blood cells transfused was 1.5 (standard deviation, 1.1). Seventeen (4.0%) patients had a documented postoperative troponin elevation. Five (1.2%) patients died within 30 days of surgery. In the survey, 117 clinicians submitted complete responses, of whom 62 (53%) indicated that a transfusion threshold of 70 g L-1 was appropriate: however, this decreased to six (5.1%) if there was evidence of recent cardiac ischaemia. There were 100 (86%) respondents who indicated equipoise for a trial of restrictive vs liberal transfusion, decreasing to 56% if there was coexisting cardiovascular disease. Conclusions: Many patients having oncological surgery receive red cell transfusion, the majority being given postoperatively. Restrictive transfusion practice is generally followed; however, variability exists especially in cardiovascular disease. Equipoise exists for a study of transfusion thresholds in this group.

18.
Adv Mater ; 34(37): e2201761, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35555829

RESUMO

Molecular structuring of soft matter with precise arrangements over multiple hierarchical levels, especially on polymer surfaces, and enabling their post-synthetic modulation has tremendous potential for application in molecular engineering and interfacial science. Here, recent research and developments in design strategies for structurally controlled polymer surfaces via cyclophane-based chemical vapor deposition (CVD) polymerization with precise control over chemical functionalities and post-CVD fabrication via orthogonal surface functionalization that facilitates the formation of designable biointerfaces are summarized. Particular discussion about innovative approaches for the templated synthesis of shape-controlled CVD polymers, ranging from 1D to 3D architecture, including inside confined nanochannels, nanofibers/nanowires synthesis into an anisotropic media such as liquid crystals, and CVD polymer nanohelices via hierarchical chirality transfer across multiple length scales is provided. Aiming at multifunctional polymer surfaces via CVD copolymerization of multiple precursors, the structural and functional design of the fundamental [2.2]paracyclophane (PCP) precursor molecules, that is, functional CVD monomer chemistry is also described. Technologically advanced and innovative surface deposition techniques toward topological micro- and nanostructuring, including microcontact printing, photopatterning, photomask, and lithographic techniques such as dip-pen nanolithography, showcasing research from the authors' laboratories as well as other's relevant important findings in this evolving field are highlighted that have introduced new programmable CVD polymerization capabilities. Perspectives, current limitations, and future considerations are provided.

19.
Front Psychol ; 13: 887848, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35668959

RESUMO

The China-Pakistan Economic Corridor (CPEC) vision and mission are to improve the people's living standards of Pakistan and China through bilateral investments, trade, cultural exchanges, and economic activities. To achieve this envisioned dream, Pakistan established the China-Pakistan Economic Corridor Authority (CPECA) to further its completion, but Covid-19 slowed it down. This situation compelled the digitalization of CPEC. This article reviews the best practices and success stories of various digitalization and e-governance programs and, in this light, advises the implementation of the Ajman Digital Governance (ADG) model as a theoretical framework for CPEC digitalization. This article concludes that the Pakistani government needs to transform CPEC digitalization by setting up the CPEC Digitalization and Transformation Center (DTC) at the CPECA office to attract more investors and businesses.

20.
Heliyon ; 8(3): e09111, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35309400

RESUMO

Purpose: Considering the severity of the global outbreak of coronavirus (COVID-19) on the whole of humanity, particularly in this case on the physical and mental health of students, this study strives to explore the role of financial worries, employment anxiety and COVID-19 knowledge on depression and mental health among students in Bangladesh. Design/methodology/approach: In the study, a deductive reasoning approach was employed, together with a self-administered questionnaire survey. Questionnaires were sent to the respondents via different social media and by email by creating a Google form link. We finally received 387 responses students aged over 18 years who had internet access in order to complete the survey. To analyze the data, structural equation modeling via AMOS was used. Findings: The results showed that employment anxiety, financial worry, and knowledge on COVID-19 positively influence depression, and finally depression negatively influences the mental health of the students. Thus, our findings supported all of the proposed hypotheses. Originality/value: The research enriches the existing literature pool by contributing empirical substantiation on the role of employment anxiety, financial worries and knowledge of COVID-19 in depression, and the impact of depression on mental health.

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