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1.
Curr Drug Deliv ; 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39136517

RESUMEN

Bacterial skin and soft tissue infections (SSTIs) are widespread microbic invasions of the skin and deeper tissues. Topical drug delivery systems are the most favored administration pathway when treating SSTIs. This is down to their minimal risk of inducing systemic adverse events, reduced development of bacterial resistance, and ease of application. However, they have several drawbacks, including the lack of control over the drug release profile, skin irritations, and the limited permeability of certain compounds through the skin. To address these limitations, several nanocarrier systems were developed, with nanoliposomes standing out as the leading delivery system for the topical management of SSTIs. Despite considerable research into liposomes over the past decade, there remains a gap in detailed knowledge about designing these carriers specifically for SSTIs. Consequently, there is a pressing need for comprehensive research that focuses on the use of nanoliposomes for SSTIs and offers an extensive understanding of both SSTIs and liposomal formulations. This review explores bacterial SSTIs, covering their epidemiology, classification, microbiology, and management. It emphasizes the contribution of liposome-based nanovesicles in enhancing the local administration of antibiotics and natural antibacterial compounds for SSTI management. It also delves into the effects of liposomal formulation changes on the disease therapeutic outcomes. Additionally, it provides a guide for aligning the characteristics of the liposomes with the infection types, depths, properties, and causative agents. This signifies a substantial leap forward in the domains of drug design, development, and delivery.

2.
ACS Omega ; 9(22): 23802-23821, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38854577

RESUMEN

An unprecedented and efficient three-component 1,3-dipolar cycloaddition reaction using (E)-2-(benzo[d]thiazol-2-yl)-3-(aryl)acrylonitriles 4a-g and an in situ generated azomethine ylide 3 from isatin and N-methylglycine is described. The reaction exhibits exclusive regioselectivity, resulting in the formation of 3'-(benzo[d]thiazol-2-yl)-1'-methyl-2-oxo-4'-(aryl)spiro[indoline-3,2'-pyrrolidine]-3'-carbonitriles regioisomers through exo/endo approaches. The diastereoselectivity of the reaction is highly dependent on the substitution pattern of the phenyl ring in dipolarophiles 4a-g, leading to the formation of exo-/endo-cycloadducts in varying ratios. To understand the stereoselectivity, the transition state structures were optimized using the TS guess geometry with the QST3-based method. The reaction mechanism and regioselectivity were elucidated by evaluating global and local electrophilicity and nucleophilicity descriptors at the B3LYP/cc-pVTZ level of theory, along with considerations based on the HSAB principle. The analysis of global electron density transfer (GEDT) showed that the reactions are polar and electron density fluxes from azomethine ylide 3 toward dipolarophile 4a-g. It was found from the molecular electrostatic potential map (MESP) that at the more favorable transition state, approach of reactants locates the oppositely charged regions over each other resulting in attractive forces between the two fragments. The computational results are consistent with the experimental observations, confirming that the reactions proceed through an asynchronous one-step mechanism.

3.
Int J Breast Cancer ; 2024: 6373900, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38919805

RESUMEN

Background: The role of BRAF in breast cancer pathogenesis is still unclear. To address this knowledge gap, this study is aimed at evaluating the impact of BRAF gene expression and copy number alterations (CNAs) on clinicopathologic characteristics and survival in patients with breast cancer. Methods: The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset was obtained from the cBioPortal public domain. Tumoral BRAF mRNA expression and CNAs along with demographic and tumor data for patients with breast cancer were retrieved. The association of BRAF expression and CNAs with breast cancer clinicopathologic characteristics was analyzed. The impact of BRAF mRNA expression on the overall survival of patients was assessed using Kaplan-Meier survival analysis. Results: BRAF gene mRNA log intensity expression was positively correlated with tumor size and the Nottingham Prognostic Index (NPI) (p < 0.001). Alternatively, BRAF gene expression was negatively correlated with the age at diagnosis (p = 0.003). The average BRAF mRNA expression was significantly higher in premenopausal patients, patients with high tumor grade, hormone receptor-negative status, and non-luminal tumors compared to postmenopausal patients, patients with low-grade, hormone receptor-positive, and luminal disease. BRAF gain and high-level amplification copy numbers were significantly associated with higher NPI scores and larger tumor sizes compared to neutral copy number status. Survival analysis revealed no discernible differences in overall survival for patients with low and high BRAF mRNA expression. Conclusion: High BRAF mRNA expression as well as the gain and high-level amplification copy numbers were associated with advanced tumor characteristics and unfavorable prognostic factors in breast cancer. BRAF could be an appealing target for the treatment of premenopausal patients with hormone receptor-negative breast cancer.

4.
Cureus ; 16(2): e54553, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38516489

RESUMEN

Introduction The experience of pain is a complex phenomenon. A patient in the acute postsurgical pain setting may feel a constant bombardment of nociceptive input from the surgical site; this in turn influences psychological factors that determine the overall emotional experience of pain, which is significant. The aim of our study was to investigate the severity of pain in postsurgical patients three days after surgery using the 100 mm visual analog scale (VAS). Methods This was a cross-sectional assessment of postoperative pain. Participants were patients between 18 and 64 years of age who had undergone a surgical procedure (laparoscopic or open surgery), three days prior to the data collection and who were admitted or discharged postoperatively at the Al Salmaniya Complex, Manama, Bahrain. Participants were asked demographic questions about whether they had laparoscopic or open surgeries and completed self-reporting scales. Patient Health Questionnaire-9 (PHQ-9) was utilized to screen for both the presence and severity of depression; Generalized Anxiety Disorder 7-item (GAD-7) was administered to screen for anxiety; the Insomnia Severity Index (ISI) was used to evaluate insomnia; and the VAS was used to evaluate pain.  Results Sixty-seven patients were recruited, with a mean age of 61.53 years (SD = 7.37). Twenty-nine (43%) were females, 38 (57%) were males, 36 (54%) underwent elective surgery, 31 (46%) underwent emergency surgery, 31 (46%) underwent laparoscopic surgery, and 36 (54%) underwent open surgery. The average score on the Brief Pain Inventory Short Form (BPISF) was 8.12 (SD = 1.16), indicating a moderate level of pain. Twenty-six (43%) patients had moderate-severe insomnia, 21 participants (31%) had no insomnia, 17 participants (25%) had subthreshold insomnia, 28 (42%) had moderate depression, five (7%) had moderate-severe depression, and 34 (51%) had severe depression. Eighteen participants (27%) had mild anxiety, 46 (69%) had moderate anxiety, and 3 (4%) had severe anxiety. Six of the participants (9%) reported moderate pain, while 61 participants (91%) reported severe pain.

5.
ACS Omega ; 8(19): 17195-17208, 2023 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-37214694

RESUMEN

Benzothiazepines are pharmacologically active compounds, frequently utilized as a precursor for acquiring versatile molecules with several bioactivities including anti-inflammatory, anti-human immunodeficiency virus (anti-HIV), analgesic, antitumor, antimicrobial, and antitubercular. In this study, the 2,4-diphenyl-2,3-dihydro-1,5-benzothiazepine scaffold was selected for their in vitro, docking, and druglikeness studies to evaluate their inhibitory potential against mushroom tyrosinase. All synthesized analogues, 1-14, exhibited moderate to good IC50 values ranging from 1.21 to 70.65 µM. The synthesized benzothiazepine derivatives were potent tyrosinase inhibitors, which outperformed the reference kojic acid (IC50 = 16.69 µM). The kinetic analysis revealed that compound 2 (2-(3,4-dimethoxyphenyl)-4-(p-tolyl)-2,3-dihydrobenzo[b][1,4]thiazepine) was a mixed-type tyrosinase inhibitor with a Ki value of 1.01 µM. Molecular modeling studies against tyrosinase protein (PDB ID: 2Y9X) were conducted to recognize the binding modes of these analogues. The utilization of molecular dynamic (MD) simulations enabled the assessment of the protein-ligand complex's dynamic behavior, stability, and binding affinity for the compounds. These simulations ultimately led to the identification of compound 2 as a potential inhibitor of tyrosinase. Additionally, a druglikeness study was conducted, which supported the promising potential of the new analogues as novel antityrosinase agents. The in silico studies were consistent with the in vitro results, showing that these ligands had good binding scores against tyrosinase and interacted with the core residues of the target protein. Gaussian 09 was used for the geometry optimization of all complexes.

6.
Micromachines (Basel) ; 14(5)2023 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-37241604

RESUMEN

Following the seminal discovery of Richard Feynman, several micromachines have been made that are capable of several applications, such as solar energy harvesting, remediation of environmental pollution, etc. Here we have synthesized a nanohybrid combining TiO2 nanoparticle and light harvesting robust organic molecule RK1 (2-cyano-3-(4-(7-(5-(4-(diphenylamino)phenyl)-4-octylthiophen-2-yl)benzo[c][1,2,5] thiadiazol-4-yl)phenyl) acrylic acid) as a model micromachine having solar light harvesting ability potential for application in photocatalysis, preparation of solar active devices, etc. Detailed structural characterization, including High Resolution Transmission Electronic Microscopy (HRTEM) and Fourier-transform infrared spectroscopy (FTIR), has been performed on the nanohybrid. We have studied the excited-state ultrafast dynamics of the efficient push-pull dye RK1 in solution, on mesoporous semiconductor nanoparticles, and in insulator nanoparticles by streak camera (resolution of the order of 500 fs). The dynamics of such photosensitizers in polar solvents have been reported, and it has been observed that completely different dynamics occur when they are attached to the surface of the semiconductor/insulator nanosurface. A femtosecond-resolved fast electron transfer has been reported when photosensitizer RK1 has been attached to the surface of the semiconductor nanoparticle, which in turn plays a crucial role in the development of an efficient light harvesting material. The generation of reactive oxygen species as a result of femtosecond-resolved photoinduced electron injection in the aqueous medium is also investigated in order to explore the possibility of redox-active micromachines, which are found to be crucial for efficient and enhanced photocatalysis.

7.
Int J Mol Sci ; 24(5)2023 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-36902433

RESUMEN

Norovirus (HNoV) is a leading cause of gastroenteritis globally, and there are currently no treatment options or vaccines available to combat it. RNA-dependent RNA polymerase (RdRp), one of the viral proteins that direct viral replication, is a feasible target for therapeutic development. Despite the discovery of a small number of HNoV RdRp inhibitors, the majority of them have been found to possess a little effect on viral replication, owing to low cell penetrability and drug-likeness. Therefore, antiviral agents that target RdRp are in high demand. For this purpose, we used in silico screening of a library of 473 natural compounds targeting the RdRp active site. The top two compounds, ZINC66112069 and ZINC69481850, were chosen based on their binding energy (BE), physicochemical and drug-likeness properties, and molecular interactions. ZINC66112069 and ZINC69481850 interacted with key residues of RdRp with BEs of -9.7, and -9.4 kcal/mol, respectively, while the positive control had a BE of -9.0 kcal/mol with RdRp. In addition, hits interacted with key residues of RdRp and shared several residues with the PPNDS, the positive control. Furthermore, the docked complexes showed good stability during the molecular dynamic simulation of 100 ns. ZINC66112069 and ZINC69481850 could be proven as potential inhibitors of the HNoV RdRp in future antiviral medication development investigations.


Asunto(s)
Gastroenteritis , Norovirus , Humanos , Simulación de Dinámica Molecular , Unión Proteica , ARN Polimerasa Dependiente del ARN/metabolismo , Antivirales/farmacología , Simulación del Acoplamiento Molecular
8.
Pharmaceuticals (Basel) ; 16(3)2023 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-36986433

RESUMEN

Indole-tethered chromene derivatives were synthesised in a one-pot multicomponent reaction using N-alkyl-1H-indole-3-carbaldehydes, 5,5-dimethylcyclohexane-1,3-dione, and malononitrile, catalysed by DBU at 60-65 °C in a short reaction time. The benefits of the methodology include non-toxicity, an uncomplicated set-up procedure, a faster reaction time, and high yields. Moreover, the anticancer properties of the synthesised compounds were tested against selected cancer cell lines. The derivatives 4c and 4d displayed very good cytotoxic activity, with IC50 values ranging from 7.9 to 9.1 µM. Molecular docking revealed the potent derivatives have good binding affinity towards tubulin protein, better than the control, and the molecular dynamic simulations further demonstrated the stability of ligand-receptor interactions. Moreover, the derivatives followed all the drug-likeness filters.

9.
Artículo en Inglés | MEDLINE | ID: mdl-36674105

RESUMEN

Personal health records (PHR) systems are designed to ensure that individuals have access and control over their health information and to support them in being active participants rather than passive ones in their healthcare process. Yet, PHR systems have not yet been widely adopted or used by consumers despite their benefits. For these advantages to be realized, adoption of the system is necessary. In this study, we examined how self-determination of health management influences individuals' intention to implement a PHR system, i.e., their ability to actively manage their health. Using an extended technology acceptance model (TAM), the researchers developed and empirically tested a model explaining public adoption of PHRs. In total, 389 Saudi Arabian respondents were surveyed in a quantitative cross-sectional design. The hypotheses were analysed using structural equation modelling-partial least squares (SEM-PLS4). Results indicate that PHR system usage was influenced by three major factors: perceived ease of use (PEOU), perceived usefulness (PU), and security towards intention to use. PHR PEOU and PHR intention to use were also found to be moderated by privacy, whereas usability positively moderated PHR PEOU and PHR intention to use and negatively moderated PHR PU and PHR intention to use. For the first time, this study examined the use of personal health records in Saudi Arabia, including the extension of the TAM model as well as development of a context-driven model that examines the relationship between privacy, security, usability, and the use of PHRs. Furthermore, this study fills a gap in the literature regarding the moderating effects of privacy influence on PEOU and intention to use. Further, the moderating effects of usability on the relationship between PEOU, PU, and intention to use. Study findings are expected to assist government agencies, health policymakers, and health organizations around the world, including Saudi Arabia, in understanding the adoption of personal health records.


Asunto(s)
Registros de Salud Personal , Privacidad , Humanos , Estudios Transversales , Arabia Saudita , Tecnología
10.
Artículo en Inglés | MEDLINE | ID: mdl-36293773

RESUMEN

Musculoskeletal pain and disorders (MSDs) constitute a well-recognised occupational hazard to the dental community. Fortunately, they are preventable. Dental office ergonomics plays a key role in addressing these musculoskeletal challenges. An ergonomic improvement project based on Kotter's eight-step change model management theory was implemented within a dental practice. The project provided valuable evidence-based ergonomic interventions to prevent or reduce MSDs. The task force motivated staff to engage in strategies and interventions to enact an ergonomic vision. This case study represents an action plan to guide this ergonomic change. The key results of this project were an evidence-based ergonomics health promotional brochure, reduced sick leave attributable to MSDs, and workplace ergonomic checkpoints. The ergonomic change model represents an ongoing process where innovative trends and evaluative methods can be supported. Research limitations and practical implications were acknowledged.


Asunto(s)
Enfermedades Musculoesqueléticas , Enfermedades Profesionales , Humanos , Enfermedades Musculoesqueléticas/prevención & control , Enfermedades Profesionales/prevención & control , Gestión del Cambio , Ergonomía/métodos , Lugar de Trabajo
11.
ACS Omega ; 7(34): 30215-30232, 2022 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-36061741

RESUMEN

In the present study, a series of 2,3-dihydro-1,5-benzothiazepine derivatives 1B-14B has been synthesized sand characterized by various spectroscopic techniques. The enzyme inhibitory activities of the target analogues were assessed using in vitro and in vivo mechanism-based assays. The tested compounds 1B-14B exhibited in vitro inhibitory potential against α-glucosidase with IC50 = 2.62 ± 0.16 to 10.11 ± 0.32 µM as compared to the standard drug acarbose (IC50 = 37.38 ± 1.37 µM). Kinetic studies of the most active derivatives 2B and 3B illustrated competitive inhibitions. Based on the α-glucosidase inhibitory effect, the compounds 2B, 3B, 6B, 7B, 12B, 13B, and 14B were chosen in vivo for further evaluation of antidiabetic activity in streptozotocin-induced diabetic Wistar rats. All these evaluated compounds demonstrated significant antidiabetic activity and were found to be nontoxic in nature. Moreover, the molecular docking study was performed to elucidate the binding interactions of most active analogues with the various sites of the α-glucosidase enzyme (PDB ID 3AJ7). Additionally, quantitative structure-activity relationship (QSAR) studies were performed based on the α-glucosidase inhibitory assay. The value of correlation coefficient (r) 0.9553 shows that there was a good correlation between the 1B-14B structures and selected properties. There is a correlation between the experimental and theoretical results. Thus, these novel compounds could serve as potential candidates to become leads for the development of new drugs provoking an anti-hyperglycemic effect.

12.
Front Chem ; 10: 978668, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36118312

RESUMEN

Enzyme function can be altered via modification of its amino acid residues, side chains and large-scale domain modifications. Herein, we have addressed the role of residue modification in catalytic activity and molecular recognition of an enzyme alpha-chymotrypsin (CHT) in presence of a covalent cross-linker formalin. Enzyme assay reveals reduced catalytic activity upon increased formalin concentration. Polarization gated anisotropy studies of a fluorophore 8-Anilino-1-naphthalenesulfonic acid (ANS) in CHT show a dip rise pattern in presence of formalin which is consistent with the generation of multiple ANS binding sites in the enzyme owing to modifications of its local amino acid residues. Molecular docking study on amino acid residue modifications in CHT also indicate towards the formation of multiple ANS binding site. The docking model also predicted no change in binding behavior for the substrate Ala-Ala-Phe-7-amido-4-methylcoumarin (AMC) at the active site upon formalin induced amino acid cross-linking.

13.
RSC Adv ; 12(32): 20728-20734, 2022 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-35919133

RESUMEN

In the past few years, metal sulfide nanoparticles (NPs) have achieved enormous interest due to their photo and electrochemical properties, which can compete with the existing metal oxide NPs. However, there are fewer reports on the synthesis and the mechanism of surface functionalization of these NPs to achieve intrinsic optical properties. Here, we demonstrate a novel method for the synthesis and the surface modification of manganese sulfide (MnS) NPs to achieve intrinsic photoluminescence and special electrochemical properties. The MnS NPs were characterized using electron microscopy and optical spectroscopic methods. Fourier-transform infrared spectroscopy (FTIR) demonstrated the attachment of citrate on the surface of MnS NPs. The surface modification of insoluble as-prepared MnS NPs by citrate makes them soluble in water. The UV-vis absorption spectra show distinct d-d and ligand to metal charge transfer (LMCT) bands of the citrate-MnS NP nanohybrid. The citrate-MnS NPs exhibited strong photoluminescence. They generated a huge amount of ROS at neutral/acidic pH without any photo-activation which was shown to degrade bilirubin. In addition, the higher ROS generation at pH 5 and pH 7 was exploited to evaluate their anti-bacterial efficacy against Staphylococcus hominis (S. hominis). These observations could pave the path for the designing and development of new-age surface-functionalized metal sulfide NPs for the benefit of human health.

14.
RSC Adv ; 12(31): 19764-19855, 2022 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-35919585

RESUMEN

Heterocycles are the key structures in organic chemistry owing to their immense applications in the biological, chemical, and pharmaceutical fields. Heterocyclic compounds perform various noteworthy functions in nature, medication, innovation etc. Most frequently, pure nitrogen heterocycles or various positional combinations of nitrogen, oxygen, and sulfur atoms in five or six-membered rings can be found. Inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes is a popular strategy for the management of numerous mental diseases. In this context, cholinesterase inhibitors are utilized to relieve the symptoms of neurological illnesses like dementia and Alzheimer's disease (AD). The present review focuses on various heterocyclic scaffolds and their role in designing and developing new potential AChE and BChE inhibitors to treat AD. Moreover, a detailed structure-activity relationship (SAR) has been established for the future discovery of novel drugs for the treatment of AD. Most of the heterocyclic motifs have been used in the design of new potent cholinesterase inhibitors. In this regard, this review is an endeavor to summarize the biological and chemical studies over the past decade (2010-2022) describing the pursuit of new N, O and S containing heterocycles which can offer a rich supply of promising AChE and BChE inhibitory activities.

15.
J Magn Reson ; 342: 107272, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35917767

RESUMEN

Nuclear magnetic resonance (NMR) spectroscopy routinely characterizes the unique spin systems of molecules using a combination of chemical shift and J-coupling interactions for the 1H and 13C nuclei. However, at Earth's magnetic field, chemical shifts are unresolvable and the ability to characterize structure relies solely on the J-couplings. Fortuitously, the J-couplings at Earth's field provides the same spin system information as high field, but only requires detection of the 1H nucleus. We report the first identification of the multiple natural abundance 1H-13C spin systems on organic molecules detected at Earth's magnetic field. The results clearly demonstrate the feasibility of Earth's field NMR to characterize small organic molecules without costly enrichment strategies.


Asunto(s)
Campos Magnéticos , Espectroscopía de Resonancia Magnética/métodos
16.
Oncol Nurs Forum ; 49(4): 307-314, 2022 06 17.
Artículo en Inglés | MEDLINE | ID: mdl-35788735

RESUMEN

OBJECTIVES: To determine the relative predictive validity of personality and spirituality for mental health and salivary alpha-amylase (sAA) in breast cancer (BC) survivors. SAMPLE & SETTING: 23 BC survivors participated in a single-group, cross-sectional study. METHODS & VARIABLES: Predictor variables included personality and spiritual variables. Outcome variables included subjective physical and mental health outcomes and sAA, a neuroimmune biomarker. RESULTS: Hierarchical regressions indicated that (a) conscientiousness and forgiveness independently predict 38% and 11% of variance in mental health scores, respectively; and (b) conscientiousness and forgiveness independently predict 15% and 24% of the variance in sAA, respectively. Consistent with psychoneuroimmunology theory, personality and spiritual variables independently influence subjective mental health and neuroimmune activity in BC survivors. IMPLICATIONS FOR NURSING: Nurses should be aware of BC survivors' personality characteristics and spiritual dispositions so that distinct interventions can be offered to promote mental health and reduce stress-related neuroimmune inflammation.


Asunto(s)
Neoplasias de la Mama , Supervivientes de Cáncer , alfa-Amilasas Salivales , Femenino , Humanos , Estudios Transversales , Salud Mental , Personalidad , Espiritualidad , Sobrevivientes
17.
Artículo en Inglés | MEDLINE | ID: mdl-35742560

RESUMEN

The pandemic's context is rife with numerous dangerous threats and high fear levels, influencing human decision-making. Such characteristics are identified by investigating the acceptance of exposure detection apps from the technology acceptance model (TAM) perspective. This study purposed a model to investigate protection technology acceptance, specifically exposure detection apps in the context of COVID-19. Quantitative study approach and a cross-section design targeted 586 participants from Saudi Arabia. As the study model is complex, the study hypotheses were analysed using the structural equation modelling-partial least squares (SEM-PLS3) approach. The findings support the entire model hypothesis except the link between social media awareness and exposure detection apps' intention. Mediation of COVID-19 anxiety and influence was confirmed as well. The current paper contributes to the technologies acceptance domain by developing a context-driven model comprising the major pandemic characteristics that lead to various patterns of technology acceptance. This study also fills the literature gap regarding mediating effects of social influence and COVID-19 anxiety in the relationship between trust in government and exposure detection apps implementation, and between COVID-19 anxiety and exposure detection apps implementation, respectively. The results may assist government agencies, health policymakers, and health organisations in the wide world and specifically Saudi Arabia, in their attempts to contain the COVID-19 pandemic spread.


Asunto(s)
COVID-19 , Aplicaciones Móviles , Medios de Comunicación Sociales , COVID-19/epidemiología , Humanos , Intención , Pandemias , Arabia Saudita/epidemiología
18.
Conserv Physiol ; 10(1): coac009, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35492406

RESUMEN

Conservation translocations-the intentional movement of animals to restore populations-have increased over the past 30 years to halt and reverse species declines and losses. However, there are many challenges translocated animals face that should be considered for restoration programs to be successful. Understanding how long it takes for translocated animals to acclimate to these challenges and their new landscape is a critical component of post-release population management. Physiological measures such as hormone responses are increasingly used to assess animal responses and acclimation to disturbances including translocation. We determined the physiological acclimation period of elk (Cervus canadensis) translocated to the Missouri Ozarks, USA, as part of a restoration effort. From 2011 to 2013, we translocated 108 GPS-radio-collared elk from Kentucky, USA, to Missouri, USA, and collected faecal samples for glucocorticoid metabolite extraction to use as an indicator of physiological acclimation. We modelled the response of population-wide faecal glucocorticoid metabolites (fGCMs) across the initial 9 years of the restoration in response to days following release and additional site-specific covariates. Presence of white-tailed deer (Odocoileus virginianus) hunts and monthly precipitation levels were positively and negatively associated with fGCM levels, respectively. Concurrent with influences from site-specific conditions on the release landscape, fGCM levels declined following release. We identified a breakpoint in fGCM decline at ~42 days following translocation releases suggesting elk acclimated physiologically relatively quickly compared to other species. The fast physiological acclimation by Missouri elk suggests effective use of temporary post-release management efforts. Determining how quickly animals acclimate following translocations allows researchers to tailor post-release management plans to each species' needs, thus maximizing the success of future translocation efforts while minimizing costs.

19.
Artículo en Inglés | MEDLINE | ID: mdl-34803400

RESUMEN

PURPOSE: Tumor expression of programmed death-ligand 1 (PD-L1) is associated with evasion of immune response in several types of malignancies and such expression may render patients eligible for PD-L1 inhibitors. The use of immune checkpoint blockade therapy has been recently approved for the treatment of breast cancer. However, PD-L1 expression data are lacking among Jordanian breast cancer patients. In this study, the tumor PD-L1 expression was characterized in breast cancer patients to assess their eligibility for immune checkpoint blockade therapy. The study also aimed to explore the association between tumoral PD-L1 expression and the clinicopathologic characteristics and the prognostic factors in patients with breast cancer. PATIENTS AND METHODS: Tissue samples were available from 153 female patients with primary invasive breast cancer. Immunohistochemistry was performed on paraffin-embedded tumor sections that were stained with a PD-L1 antibody. Expression of tumor PD-L1 was correlated with demographics, clinicopathologic characteristics, and prognosis. RESULTS: The mean age at diagnosis was 54.2±12.8 years (median 52, interquartile range 45-65). The percentage of PD-L1-positive tumors was 26.1%. PD-L1 expression on tumor cells significantly and positively correlated with tumor size (rho=0.174, p=0.032). PD-L1 positivity was significantly associated with the grade of carcinoma (p=0.001), HER2-positivity (p=0.015), and lymphovascular invasion (p=0.036). PD-L1 intensity was significantly associated with tumor stage (p=0.046). No significant associations were observed for the PD-L1 expression status or intensity with patient menopausal status, hormone receptor expression, and molecular subtypes. PD-L1 expression significantly correlated with a worse prognosis of breast cancer patients at the time of diagnosis (rho=0.230, p=0.005). CONCLUSION: Tumor PD-L1 expression was associated with advanced clinicopathologic features and worse prognosis in this cohort of Jordanian breast cancer patients. Future studies are needed to better understand the impact of PD-L1 blockade therapy on treatment outcomes in eligible breast cancer patients in Jordan.

20.
Optom Vis Sci ; 98(5): 450-455, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33967253

RESUMEN

SIGNIFICANCE: Ocular surface squamous neoplasias are superficial tumors of the cornea and conjunctiva that can be sight threatening if neglected. Therefore, accurate noninvasive diagnostic modalities are needed. PURPOSE: The purpose of this case series was to describe the hallmark features of ocular surface squamous neoplasia on high-resolution optical coherence tomography (HR-OCT) imaging and its use in the evaluation and management of superficial ocular tumors. CASE SERIES: Five eyes of four patients with ocular surface squamous neoplasia are described. Whereas two eyes displayed the classic clinical features of ocular surface squamous neoplasia, three of the five eyes had more subtle atypical features. However, all shared features on HR-OCT of epithelial thickening and hyperreflectivity with abrupt transitions between normal and abnormal tissue, classic features of ocular surface squamous neoplasia. All lesions ultimately underwent incisional or excisional biopsy and were confirmed to be ocular surface squamous neoplasia on histopathology. CONCLUSIONS: Ocular surface squamous neoplasia may present as a classic tumor but can also have subtle features or masquerade. Accurate methods to diagnose and manage patients with ocular surface squamous neoplasia are necessary. With recent advancements in technology, HR-OCT has been demonstrated to accurately identify ocular surface squamous neoplasia with the repeatable optical findings of (1) epithelial thickening, (2) epithelial hyperreflectivity, and (3) abrupt transition zone between normal and abnormal tissue. This case series demonstrates how HR-OCT can help provide an optical biopsy to guide appropriate diagnosis and management of this neoplastic lesion.


Asunto(s)
Neoplasias de la Conjuntiva/diagnóstico por imagen , Enfermedades de la Córnea/diagnóstico por imagen , Lesiones Intraepiteliales Escamosas/diagnóstico por imagen , Tomografía de Coherencia Óptica , Anciano , Antibióticos Antineoplásicos/uso terapéutico , Antimetabolitos Antineoplásicos/uso terapéutico , Antineoplásicos/uso terapéutico , Biopsia , Neoplasias de la Conjuntiva/tratamiento farmacológico , Neoplasias de la Conjuntiva/patología , Enfermedades de la Córnea/tratamiento farmacológico , Enfermedades de la Córnea/patología , Pruebas Diagnósticas de Rutina , Fluorouracilo/uso terapéutico , Humanos , Interferones/uso terapéutico , Masculino , Persona de Mediana Edad , Mitomicina/uso terapéutico , Estudios Retrospectivos , Lesiones Intraepiteliales Escamosas/tratamiento farmacológico , Lesiones Intraepiteliales Escamosas/patología
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