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1.
J Cutan Pathol ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38698729

RESUMO

A neurofibroma with focal glomus-like body differentiation is an unusual phenomenon recently encountered in an excision specimen from the right lateral distal forearm of a 26-year-old man. Glomus cells are modified smooth muscle cells normally present in glomus-like bodies but can also be found in glomus tumors (GT) or lesions considered in the spectrum of GT, including myopericytoma, myofibroma, and angiolipoma. Neurofibromas are peripheral nerve sheath tumors derived from the neural crest cells. While both GT and its variants and neurofibroma are thought to be derived from different cell types, there is growing evidence that glomus cells have a neural crest origin. This is based on multiple theories, with some overlapping pathways, including neural crest cell differentiation, Schwann cell reprogramming, VEGF expression, and NF1 gene biallelic inactivation. This report adds to the growing evidence of possible neural crest origin for glomus cells and would help explain finding glomus-like bodies scattered through a neurofibroma.

2.
Protein J ; 43(3): 405-424, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38724751

RESUMO

As the demand for immunotherapy to treat and manage cancers, infectious diseases and other disorders grows, a comprehensive understanding of amino acids and their intricate role in antibody engineering has become a prime requirement. Naturally produced antibodies may not have the most suitable amino acids at the complementarity determining regions (CDR) and framework regions, for therapeutic purposes. Therefore, to enhance the binding affinity and therapeutic properties of an antibody, the specific impact of certain amino acids on the antibody's architecture must be thoroughly studied. In antibody engineering, it is crucial to identify the key amino acid residues that significantly contribute to improving antibody properties. Therapeutic antibodies with higher binding affinity and improved functionality can be achieved through modifications or substitutions with highly suitable amino acid residues. Here, we have indicated the frequency of amino acids and their association with the binding free energy in CDRs. The review also analyzes the experimental outcome of two studies that reveal the frequency of amino acids in CDRs and provides their significant correlation between the outcomes. Additionally, it discusses the various bond interactions within the antibody structure and antigen binding. A detailed understanding of these amino acid properties should assist in the analysis of antibody sequences and structures needed for designing and enhancing the overall performance of therapeutic antibodies.


Assuntos
Aminoácidos , Regiões Determinantes de Complementaridade , Engenharia de Proteínas , Aminoácidos/química , Regiões Determinantes de Complementaridade/química , Regiões Determinantes de Complementaridade/genética , Humanos , Engenharia de Proteínas/métodos , Anticorpos/química , Anticorpos/imunologia , Anticorpos/metabolismo , Afinidade de Anticorpos , Animais
3.
Artigo em Inglês | MEDLINE | ID: mdl-38673383

RESUMO

INTRODUCTION: Smoking in pregnancy is associated with negative health outcomes for both mothers and babies; e-cigarettes, which contain nicotine without hazardous tobacco, may offer an additional smoking cessation strategy for pregnant women. Although e-cigarettes are being increasingly offered within services, there is limited understanding about whether e-cigarettes can improve smoking cessation support for pregnant individuals. This study aimed to explore service users' experiences of using e-cigarettes as a tool for smoking cessation during pregnancy. METHODS: Semi-structured interviews were conducted with 14 women who had accepted one of two pilots and were analysed using inductive reflexive thematic analysis. The findings from each site were integrated to develop qualitative insight. RESULTS: Participants largely had positive perceptions of the free and easy-to-use e-cigarette, preferring it to nicotine replacement therapies. The desire to have a healthy pregnancy and baby and the inclusion of non-judgemental behavioural support facilitated motivation to quit. Many participants reduced or quit tobacco use, with positive social and health implications reported. However, numerous barriers to quitting were present and intentions about long-term quitting of combustible cigarettes and e-cigarettes were mixed and uncertain. CONCLUSIONS: Providing e-cigarettes within smoking cessation services was indicated to be a positive and effective strategy for pregnant women trying to quit tobacco. However, numerous barriers to quitting and staying quit remained, suggesting scope for further improvements to smoking cessation support for pregnant women.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Gestantes , Abandono do Hábito de Fumar , Humanos , Feminino , Abandono do Hábito de Fumar/métodos , Abandono do Hábito de Fumar/psicologia , Gravidez , Adulto , Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Reino Unido , Gestantes/psicologia , Adulto Jovem
4.
Artigo em Inglês | MEDLINE | ID: mdl-38541291

RESUMO

Smoking during pregnancy increases the risk of adverse maternal and foetal health outcomes, with effective smoking cessation support important. E-cigarette use in the general population has increased rapidly in recent years, with their use viewed as an alternate, additional offer to nicotine-replacement therapy and behavioural support. However, their use in pregnancy has limited investigation. This study aimed to understand how two e-cigarette pilots for pregnant women were delivered and implemented. Referrals to the general stop smoking in pregnancy service, as well as pilot enrolment, engagement and outcomes were recorded. Seven professionals involved in pilot 2 design, setup and/or delivery took part in semi-structured interviews informed by the Consolidated Framework for Implementation Research (CFIR). Transcripts were deductively coded into CFIR. In total, 124 of 296 women accessed at least one visit after being contacted and offered the e-cigarette pilot (Pilot 1: N = 99, Pilot 2: N = 25). In Pilot 2, 13 (of 25) reached 4 weeks, and common reasons for withdrawal by 12 weeks included relapse, loss of contact and no further support wanted. Forty-five (36.3%) validated quits were reported (Pilot 1: 32 of 99 (32.3%); Pilot 2: 13 of 25 (52%)). Facilitators included regular communication and the advisors physically taking e-cigarettes to home visits. Barriers included misalignment between the pilot and the standard treatment offer and availability of the staff resource. Enrolment to both pilots was demonstrated, with greater enrolment in one pilot and notable quit rates among women across both pilots. The perceived role of e-cigarettes for pregnant women varied, and a lack of staff resources explained some challenges. Adaptations may be needed during scale-up, including additional resources and the alignment of the e-cigarette provision to standard treatment.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Abandono do Hábito de Fumar , Feminino , Humanos , Gravidez , Dispositivos para o Abandono do Uso de Tabaco , Fumar/terapia , Reino Unido
5.
Cardiovasc Intervent Radiol ; 47(5): 556-566, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38548981

RESUMO

PURPOSE: Venous thromboembolism (VTE) is a major contributor to the mortality of cancer patients. Mechanical thrombectomy (MT) is an endovascular technique that physically removes a thrombus without thrombolytics. The purpose of this study was to evaluate safety, efficacy, and clinical outcomes following MT for lower extremity DVT in cancer patients. METHODS: This single-center, retrospective study evaluated outcomes following MT of lower extremity DVT in cancer patients from November 2019 to May 2023. The primary outcome measure was clinical success, defined as a decrease in Villalta score by at least 2 points following the intervention. Secondary outcomes included repeat intervention-free survival and overall survival. Technical success was defined as restoring venous flow with mild (< 10%) or no residual filling defect. RESULTS: In total, 90 patients and 113 procedures were included. Technical and clinical success was achieved in 81% and 87% of procedures performed. Repeat intervention-free survival at 1 month, 3 months, and 6 months post-procedure was 92%, 82%, and 77%, respectively. The complication rate was 2.7%. Pathologic analysis of the extracted thrombus revealed tumor thrombus in 18.4% (18/98) samples. Overall survival for the study cohort was 87% at 1 month, 74% at 3 months, and 62% at 6 months. Patients who were found to have tumor thrombi were noted to have a decreased overall survival compared to patients with non-tumor thrombi (P = 0.012). CONCLUSION: MT is safe and efficacious in reducing cancer patients' VTE-related symptoms. The high rate of tumor thrombus in thrombectomy specimens suggests this phenomenon is more common than suspected.


Assuntos
Neoplasias , Trombectomia , Trombose Venosa , Humanos , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/terapia , Neoplasias/complicações , Idoso , Trombectomia/métodos , Adulto , Resultado do Tratamento , Idoso de 80 Anos ou mais
6.
J Surg Case Rep ; 2024(3): rjae092, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38455981

RESUMO

Intra-aortic balloon pumps (IABPs) are used to mechanically temporize a failing heart by decreasing afterload while increasing coronary perfusion pressure of the heart while more definitive treatment is sought. We report a case of a 65-year-old male with nonischemic cardiomyopathy, atrial fibrillation, thyroiditis, and non-Hodgkin lymphoma who presented with worsening heart failure. He underwent a percutaneous placement of a left axillary IABP with seemingly no complications. Approximately 3 weeks post-placement, the patient was taken for a heart transplant when an intraoperative transesophageal echo showed that the IABP was in the aortic arch and ascending aorta, instead of its proper placement in the descending aorta. The patient's arterial line showed waveforms appropriate for an IABP patient, and the patient showed no signs indicative of improper placement. This erroneous placement carried the potential to affect the aortic valve function, injure the aortic intima and/or occlude the aortic arch vessels. .

7.
Clin Colorectal Cancer ; 23(1): 14-21.e1, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-37919185

RESUMO

BACKGROUND: Randomized clinical trials have defined the survival advantage with the addition of biologic drugs to chemotherapy in patients with metastatic colorectal cancer (mCRC). Under representation of Hispanics contributes to poorly defined outcomes in this group. We aim to determine whether the real-world benefit of biologics extends to Hispanics using a comparative effectiveness research approach. METHODS: This retrospective cohort study included all treatment centers contributing to SEER registry with available claims in the SEER-Medicare linked database (2001-2011) and 2 hospitals (2004-2016) catering to minorities. Metastatic CRC patients were classified as receiving chemotherapy or biochemotherapy (CT plus biologics; if initiated within 3 months of chemotherapy). The primary outcome was overall survival (OS) among the Hispanic patients calculated from time of administration of first dose of chemotherapy to death or last follow-up. A weighted Cox regression model was used to assess differences in survival. RESULTS: We identified 182 Hispanic patients with mCRC from the Patient Entitlement and Diagnosis Summary (PEDSF) file (n = 101) and hospital database (n = 81). Overall, 52% were women and 72% received biologics. The median OS was 11.3 and 17.0 months in chemotherapy and biochemotherapy group, respectively. Biochemotherapy offered a survival benefit compared with chemotherapy alone, with an average hazard rate reduction of 39% (95% CI 6%-60%, p = .0236) using inverse probability of treatment weighting (IPTW) based analysis. CONCLUSION: In this cohort of Hispanic patients with mCRC, biochemotherapy was associated with longer survival. Clinicians may offer biochemotherapy therapy to all patients regardless of race/ethnicity to maximize clinical benefit.


Assuntos
Produtos Biológicos , Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Idoso , Feminino , Humanos , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fatores Biológicos , Produtos Biológicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias Colorretais/patologia , Hispânico ou Latino , Medicare , Neoplasias Retais/tratamento farmacológico , Estudos Retrospectivos , Estados Unidos/epidemiologia
8.
Ophthalmic Surg Lasers Imaging Retina ; 54(12): 692-700, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38113360

RESUMO

BACKGROUND AND OBJECTIVE: Disorganization of retinal inner layers (DRIL) is a potential spectral-domain optical coherence tomography (SD-OCT) imaging biomarker with clinical utility in diabetic retinopathy (DR). PATIENTS AND METHODS: A cross-sectional study was conducted at a large academic center. The cohort was composed of 1,175 patients with type 2 diabetes with and without retinopathy on initial examination between September 2009 and January 2019 (n = 2,083 eyes). DR risk and progression factors were obtained from the medical record. Trained graders masked to patients' clinical histories evaluated SD-OCT scans for DRIL. RESULTS: Of 2,083 eyes, 28.1% (n = 585) demonstrated presence of DRIL with high interrater reliability (K = 0.88, 95% CI 0.86-0.90). DRIL was associated with worse visual acuity (VA) (P < 0.001) and DR severity (P < 0.0001). Insulin users had more severe DR (P < 0.0001). DR-related factors, race (Black, White) and sex (male) were significantly associated with DRIL (P < 0.05). CONCLUSIONS: DRIL was strongly associated with DR severity and worse VA, supporting its utility as an unfavorable prognostic indicator. [Ophthalmic Surg Lasers Imaging Retina 2023;54:692-700.].


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Edema Macular , Humanos , Masculino , Retinopatia Diabética/complicações , Tomografia de Coerência Óptica/métodos , Diabetes Mellitus Tipo 2/complicações , Estudos Transversais , Reprodutibilidade dos Testes , Edema Macular/diagnóstico , Estudos Retrospectivos , Angiofluoresceinografia/métodos , Retina
9.
Biomaterials ; 303: 122397, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37979513

RESUMO

Critical limb ischemia (CLI) occurs when blood flow is restricted through the arteries, resulting in ulcers, necrosis, and chronic wounds in the downstream extremities. The development of collateral arterioles (i.e. arteriogenesis), either by remodeling of pre-existing vascular networks or de novo growth of new vessels, can prevent or reverse ischemic damage, but it remains challenging to stimulate collateral arteriole development in a therapeutic context. Here, we show that a gelatin-based hydrogel, devoid of growth factors or encapsulated cells, promotes arteriogenesis and attenuates tissue damage in a murine CLI model. The gelatin hydrogel is functionalized with a peptide derived from the extracellular epitope of Type 1 cadherins. Mechanistically, these "GelCad" hydrogels promote arteriogenesis by recruiting smooth muscle cells to vessel structures in both ex vivo and in vivo assays. In a murine femoral artery ligation model of CLI, delivery of in situ crosslinking GelCad hydrogels was sufficient to restore limb perfusion and maintain tissue health for 14 days, whereas mice treated with gelatin hydrogels had extensive necrosis and autoamputated within 7 days. A small cohort of mice receiving the GelCad hydrogels were aged out to 5 months and exhibited no decline in tissue quality, indicating durability of the collateral arteriole networks. Overall, given the simplicity and off-the-shelf format of the GelCad hydrogel platform, we suggest it could have utility for CLI treatment and potentially other indications that would benefit from arteriole development.


Assuntos
Circulação Colateral , Neovascularização Fisiológica , Humanos , Camundongos , Animais , Idoso , Neovascularização Fisiológica/fisiologia , Circulação Colateral/fisiologia , Hidrogéis/uso terapêutico , Gelatina/uso terapêutico , Isquemia Crônica Crítica de Membro , Modelos Animais de Doenças , Artéria Femoral/metabolismo , Isquemia/tratamento farmacológico , Isquemia/metabolismo , Necrose , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Membro Posterior/metabolismo
10.
Artigo em Inglês | MEDLINE | ID: mdl-37707661

RESUMO

BACKGROUND: The burden of early onset colorectal cancer (EOCRC) falls disproportionately on minorities and individuals in specific geographic regions. While these disparities are likely multi-factorial, access to high-quality health care plays a significant role. We sought to determine if Medicaid expansion is associated with reducing racial disparities in EOCRC detection in Hispanics and non-Hispanic Blacks (NHB), compared to non-Hispanic Whites (NHW). METHODS: Analysis of data from National Cancer Database was undertaken to compare incidence of EOCRC among those aged 40-49 between Medicaid expansion states (ES) and non-expansion states (NES) by racial/ethnic groups. Data was classified by race (NHW, NHB, or Hispanic), state of residence (ES or NES), and time (pre- or post-expansion). The primary outcome was change in incidence rate of EOCRC among racial/ethnic groups, according to whether patients resided in Medicaid expansion or non-expansion states. RESULTS: Among Hispanics, the ES showed a significant increase in EOCRC incidence post expansion as compared to NES (p = 0.03). The rate of increase in annual incidence of EOCRC among Hispanics was 4.3% per year (pre-expansion) and 9.8% (post-expansion) for ES; and 6.4% (pre-expansion) and 1% (post-expansion) in NES. However, no difference was noted among NHB (p = 0.33) and NHW (p = 0.94). CONCLUSIONS: Medicaid expansion has improved detection rates of EOCRC in ES especially in Hispanic population. This is the first study to demonstrate the effect of Medicaid expansion on the incidence of EOCRC. Based on our study findings we suggest that racial and ethnic disparities should be considered in the earlier CRC screening debates.

11.
Exp Hematol Oncol ; 12(1): 60, 2023 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-37422676

RESUMO

Dysregulation of the innate immune system and inflammatory-related pathways has been implicated in hematopoietic defects in the bone marrow microenvironment and associated with aging, clonal hematopoiesis, myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML). As the innate immune system and its pathway regulators have been implicated in the pathogenesis of MDS/AML, novel approaches targeting these pathways have shown promising results. Variability in expression of Toll like receptors (TLRs), abnormal levels of MyD88 and subsequent activation of NF-κß, dysregulated IL1-receptor associated kinases (IRAK), alterations in TGF-ß and SMAD signaling, high levels of S100A8/A9 have all been implicated in pathogenesis of MDS/AML. In this review we not only discuss the interplay of various innate immune pathways in MDS pathogenesis but also focus on potential therapeutic targets from recent clinical trials including the use of monoclonal antibodies and small molecule inhibitors against these pathways.

12.
Cureus ; 15(4): e37860, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37213984

RESUMO

Pulmonary pleomorphic carcinoma (PPC) is a subtype of non-small cell lung cancer that is extremely rare and carries a poor prognosis due to its inadequate response to treatment. Patients that present with PPC often exhibit similar symptoms of other malignancies of the lung, making it hard for clinicians to distinguish between each type. However, cytology and gene mutation testing are two approaches that can aid physicians in an accurate and definitive diagnosis. We present a case of an 88-year-old male patient with a diagnosis of pulmonary pleomorphic carcinoma after experiencing recurrent sanguineous pleural effusions. The patient had no smoking history but did have a history of asbestos exposure and pulmonary fibrosis. The patient underwent thoracotomy with pleurodesis and analysis of the surgical pleural biopsy specimen stained positive for markers indicative of PPC. The pathology report was also consistent with the associated cell morphology. Lung cancer is the leading cause of mortality due to cancer in the United States, and exposure to certain substances contributes to the development of these poorly treatable lung malignancies. Smoking and asbestos exposure are well known to act synergistically with each other as risk factors in developing these lung malignancies. In addition to clinical suspicion, screening for these risk factors with laboratory values and imaging is important to diagnose these rare cases of lung malignancies.

13.
Dermatol Online J ; 29(1)2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-37040908

RESUMO

Pretibial myxedema, more generally thyroid dermopathy, results from mucopolysaccharide accumulation in the dermis, typically between the knee and dorsal foot. Thyroid dermopathy presents in Graves disease, but can occur in Hashimoto thyroiditis, primary hypothyroidism, and euthyroid patients. Treatment of thyroid eye disease with teprotumumab is established in the literature, with few case reports also showing improvement in pretibial myxedema. Reported is a 76-year-old man with thyroid eye disease and pretibial myxedema treated with teprotumumab; improvement was demonstrated in both conditions. He developed "muffled" hearing as an adverse effect, a complication not widely published in the dermatology literature. At 18 months post-treatment, his symptoms are stable without recurrence, but hypoacusis persists. Given the long-term efficacy and side-effects, dermatologists should recognize the potential benefits and risks of using teprotumumab for thyroid dermopathy. A baseline audiogram may be considered prior to therapy. Additionally, longitudinal data is needed to document the benefits and risks of this novel therapy.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Oftalmopatia de Graves , Dermatoses da Perna , Mixedema , Ototoxicidade , Masculino , Humanos , Idoso , Dermatoses da Perna/complicações , Ototoxicidade/complicações , Oftalmopatia de Graves/complicações , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/complicações
14.
Clin Hematol Int ; 5(2-3): 78-91, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36918485

RESUMO

Adult T-cell leukemia/lymphoma (ATLL) remains challenging to treat and has dismal outcome. Allogeneic stem-cell transplantation (allo-SCT) has promising results, but data remain scarce. In this single-center retrospective analysis of 100 patients with ATLL from north America (67 acute, 22 lymphomatous), 17 underwent allo-SCT and 5 autologous SCT (ASCT), with a median follow-up of 65 months. Post-transplant 3-years relapse incidence (RI) and non-relapse mortality (NRM) were 51% and 37%, respectively, and 3-year progression-free survival (PFS) and overall survival (OS) were 31% and 35%, respectively. ASCT 1-year RI was 80% compared to 30% in allo-SCT (p = 0.03). After adjusting for immortal-time bias, allo-SCT had significantly improved OS (HR = 0.4, p = 0.01). In exploratory multivariate analysis, patients achieving first complete response and Karnofsky score ≥ 90 had significantly better outcomes, as did Black patients, compared to Hispanics, who had worse outcome. In transplanted patients, 14 died within 2 years, 4 of which ASCT recipients. Our data are the largest ATLL transplant cohort presented to date outside of Japan and Europe. We show that allo-SCT, but not ASCT, is a valid option in select ATLL patients, and can induce long term survival, with 40% of patients alive after more than 5 years.

15.
Am J Dermatopathol ; 45(4): 250-253, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36806052

RESUMO

ABSTRACT: Primary cutaneous marginal zone lymphoma (PCMZL) is a low-grade malignant B-cell lymphoma that originates from the skin. It often presents as erythematous solitary or multiple papules, nodules, and/or plaques. It is one of the 3 main subtypes of primary cutaneous B-cell lymphomas. PCMZLs are believed to develop from chronic antigenic stimulation such as from tick-borne bacteria, vaccines, tattoo pigment, or other foreign body. In addition, cutaneous lymphoid hyperplasia, a documented precursor to malignant PCMZL, often presents in response to areas of chronic inflammation. Cutaneous lymphoid hyperplasia and PCMZL share several clinical and histological similarities that require clinicopathologic suspicion, immunohistochemical ancillary studies, and histopathologic analysis to accurately differentiate the 2 entities. Although gene rearrangement studies have historically been of limited value in the diagnosis of PCMZL, recent studies investigating molecular markers have identified the presence of multiple genetic abnormalities that have helped to better characterize the disease and aid in diagnosis. In addition, newer studies have found associations between PCMZL and gastrointestinal disorders, including Helicobacter pylori and inflammatory bowel disorders. In this article, we describe a case of a 56-year-old patient with a history of ulcerative colitis presenting with chronic reactive lymphoid hyperplasia that transformed to primary cutaneous marginal zone lymphoma.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Linfoma de Células B , Linfoma , Pseudolinfoma , Neoplasias Cutâneas , Humanos , Pessoa de Meia-Idade , Pseudolinfoma/patologia , Neoplasias Cutâneas/patologia , Hiperplasia , Linfoma de Células B/patologia , Linfoma de Zona Marginal Tipo Células B/patologia
16.
J Relig Health ; 62(2): 1223-1250, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35501521

RESUMO

Registered dietitians assess, diagnose and treat nutritional problems. Although integral to healthcare, their role in spiritual care is unknown. We conducted a systematic review of spiritual needs and spiritual care in nutrition and dietetic practice. Subject Headings and keywords were used to search Medline, CINAHL, PsycINFO and AMED for studies exploring spiritual care and nutrition or dietetic practice. From 1433 records, 13 studies were included. Medium quality evidence showed unmet spiritual needs among dietetic patients suffering from cancer, COPD, heart failure and diabetes. Unmet needs occurred in patients from a variety of ethnicities, religions and none. However, dietitians were only involved in spiritual care regarding nutrition and hydration at the end of life. Integrating spiritual screening and sign-posting within dietetic practice is prudent, but clinical trials are needed to evaluate its effectiveness.


Assuntos
Dietética , Terapias Espirituais , Humanos , Espiritualidade
17.
Hum Antibodies ; 31(4): 71-80, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38217590

RESUMO

Immunotherapy has become increasingly popular in recent years for treating a variety of diseases including inflammatory, neurological, oncological, and auto-immune disorders. The significant interest in antibody development is due to the high binding affinity and specificity of an antibody against a specific antigen. Recent advances in antibody engineering have provided a different view on how to engineer antibodies in silico for therapeutic and diagnostic applications. In order to improve the clinical utility of therapeutic antibodies, it is of paramount importance to understand the various molecular properties which impact antigen targeting and its potency. In antibody engineering, antibody numbering (AbN) systems play an important role to identify the complementarity determining regions (CDRs) and the framework regions (FR). Hence, it is crucial to accurately define and understand the CDR, FR and the crucial residues of heavy and light chains that aid in the binding of the antibody to the antigenic site. Detailed understanding of amino acids positions are useful for modifying the binding affinity, specificity, physicochemical features, and half-life of an antibody. In this review, we have summarized the different antibody numbering systems that are widely used in antibody engineering and highlighted their significance. Here, we have systematically explored and mentioned the various tools and servers that harness different AbN systems.


Assuntos
Anticorpos , Regiões Determinantes de Complementaridade , Humanos , Anticorpos/genética , Anticorpos/química , Regiões Determinantes de Complementaridade/química , Afinidade de Anticorpos , Sítios de Ligação de Anticorpos
18.
Cells ; 11(19)2022 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-36230914

RESUMO

Pancreatic cancer has a notoriously poor prognosis, exhibits persistent drug resistance, and lacks a cure. Unique features of the pancreatic tumor microenvironment exacerbate tumorigenesis, metastasis, and therapy resistance. Recent studies emphasize the importance of exploiting cells in the tumor microenvironment to thwart cancers. In this review, we summarize the hallmarks of the multifaceted pancreatic tumor microenvironment, notably pancreatic stellate cells, tumor-associated fibroblasts, macrophages, and neutrophils, in the regulation of chemo-, radio-, immuno-, and targeted therapy resistance in pancreatic cancer. The molecular insight will facilitate the development of novel therapeutics against pancreatic cancer.


Assuntos
Neoplasias Pancreáticas , Microambiente Tumoral , Humanos , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Células Estreladas do Pâncreas/patologia , Microambiente Tumoral/fisiologia , Neoplasias Pancreáticas
19.
Behav Brain Res ; 419: 113677, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34818568

RESUMO

In long-term spaceflight, astronauts will face unique cognitive loads and social challenges which will be complicated by communication delays with Earth. It is important to understand the central nervous system (CNS) effects of deep spaceflight and the associated unavoidable exposure to galactic cosmic radiation (GCR). Rodent studies show single- or simple-particle combination exposure alters CNS endpoints, including hippocampal-dependent behavior. An even better Earth-based simulation of GCR is now available, consisting of a 33-beam (33-GCR) exposure. However, the effect of whole-body 33-GCR exposure on rodent behavior is unknown, and no 33-GCR CNS countermeasures have been tested. Here astronaut-age-equivalent (6mo-old) C57BL/6J male mice were exposed to 33-GCR (75cGy, a Mars mission dose). Pre-/during/post-Sham or 33-GCR exposure, mice received a diet containing a 'vehicle' formulation alone or with the antioxidant/anti-inflammatory compound CDDO-EA as a potential countermeasure. Behavioral testing beginning 4mo post-irradiation suggested radiation and diet did not affect measures of exploration/anxiety-like behaviors (open field, elevated plus maze) or recognition of a novel object. However, in 3-Chamber Social Interaction (3-CSI), CDDO-EA/33-GCR mice failed to spend more time exploring a holder containing a novel mouse vs. a novel object (empty holder), suggesting sociability deficits. Also, Vehicle/33-GCR and CDDO-EA/Sham mice failed to discriminate between a novel stranger vs. familiarized stranger mouse, suggesting blunted preference for social novelty. CDDO-EA given pre-/during/post-irradiation did not attenuate the 33-GCR-induced blunting of preference for social novelty. Future elucidation of the mechanisms underlying 33-GCR-induced blunting of preference for social novelty will improve risk analysis for astronauts which may in-turn improve countermeasures.


Assuntos
Comportamento Animal , Disfunção Cognitiva , Radiação Cósmica/efeitos adversos , Ácido Oleanólico/análogos & derivados , Exposição à Radiação/efeitos adversos , Reconhecimento Psicológico , Comportamento Social , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/efeitos da radiação , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ácido Oleanólico/farmacologia , Reconhecimento Psicológico/efeitos dos fármacos , Reconhecimento Psicológico/efeitos da radiação
20.
J Immunol Methods ; 491: 112992, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33577777

RESUMO

Natural Killer (NK) cells are lymphocytes that are the first line of defense against malignantly transformed cells, virally infected cells and other stressed cell types. To study the cytolytic function of NK cells in vitro, a cytotoxicity assay is normally conducted against a target cancerous cell line. Current assay methods are typically performed in mixed 2D cocultures with destructive endpoints and low throughput, thereby limiting the scale, time-resolution, and relevance of the assay to in vivo conditions. Here, we evaluated a novel, non-invasive, quantitative image-based cytometry (qIBC) assay for detection of NK-mediated killing of target cells in 2D and 3D environments in vitro and compared its performance to two common flow cytometry- and fluorescence-based cytotoxicity assays. Similar to the other methods evaluated, the qIBC assay allowed for reproducible detection of target cell killing across a range of effector-to-target ratios with reduced variability. The qIBC assay also allowed for detection of NK cytolysis in 3D spheroids, which enabled scalable measurements of cell cytotoxicity in 3D models. Our findings suggest that quantitative image-based cytometry would be suitable for rapid, high-throughput screening of NK cytolysis in vitro, including in quasi-3D structures that model tissue environments in vivo.


Assuntos
Testes Imunológicos de Citotoxicidade/métodos , Citometria por Imagem/métodos , Células Matadoras Naturais/imunologia , Citometria de Fluxo , Humanos , Células K562 , Esferoides Celulares
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