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1.
Eur J Obstet Gynecol Reprod Biol ; 299: 43-53, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38833773

ABSTRACT

OBJECTIVE: To compare the female sexual function between cervical cancer survivors and healthy women or with benign gynecological diseases. STUDY DESIGN: From January 1, 2010 to January 31, 2019, a case-control study was conducted to compare the female sexual function of 106 cervical cancer survivors from a tertiary hospital and 185 women admitted to a gynecological outpatient clinic from the same health area for a routine gynecological examination (n=46) or for a benign gynecological disorder (symptomatic, n=113; asymptomatic, n=26). We prospectively assessed the female sexual function using the Female Sexual Function Index (FSFI). For the contrastive analysis hypothesis, we employed R statistical software. RESULTS: Cervical cancer survivors reported lower sexual activity rates than controls, in general, did (47.12% vs. 88.65%, p=0.0001), and, particularly, compared with healthy and symptomatic controls (47.12% vs. 82.61%, p=0.003; 47.12% vs. 87.61%, p=0.0001, respectively). Sixty and fifty-eight hundredths percent of the cervical cancer survivors experienced female sexual dysfunction, mainly due to hypoactive sexual desire (93.27%). Female sexual dysfunction was diagnosed in 64.32% of the controls, with sexual arousal disorders being the most common diagnosis (44.86%). Compared with controls, cervical cancer survivors exhibited considerably lower FSFI total scores and in sexual desire and lubrication domains (p <0.000; p <0.0001; p=0.023). CONCLUSIONS: Cervical cancer survivors had worse female sexual function and less sexual activity than controls did, although scores in both groups were in range of FSD. Rates of female sexual dysfunction were similar across cervical cancer survivors and controls, with hypoactive sexual desire and sexual arousal disorders as the most common diagnoses, respectively.

2.
Org Lett ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38856097

ABSTRACT

In this study, the use of terminal cyclopropylsilyl alcohols in Prins cyclization is reported as a very efficient methodology for the preparation of polysubstituted tetrahydropyrans, in which three new stereogenic centers have been created in a single pot. The reaction is general for a wide variety of aldehydes (alkylic, vinylic, aromatic, or dialdehydes), different types of alcohols, and halogenation agents providing high yields and excellent diastereoselectivity 2,3,4,6-tetrasubstituted tetrahydropyranyl frameworks. Interestingly, diastereomeric alcohols provide the same tetrahydropyranyl derivatives, showing that the reaction mechanism proceeds through common intermediates.

3.
Biofabrication ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862006

ABSTRACT

There is increasing evidence that cancer progression is linked to tissue viscoelasticity, which challenges the commonly accepted notion that stiffness is the main mechanical hallmark of cancer. However, this new insight has not reached widespread clinical use, as most clinical trials focus on the application of tissue elasticity and stiffness in diagnostic, therapeutic, and surgical planning. Therefore, there is a need to advance the fundamental understanding of the effect of viscoelasticity on cancer progression, to develop novel mechanical biomarkers of clinical significance. Tissue viscoelasticity is largely determined by the extracellular matrix (ECM), which can be simulated in vitro using hydrogel-based platforms. Since the mechanical properties of hydrogels can be easily adjusted by changing parameters such as molecular weight and crosslinking type, they provide a platform to systematically study the relationship between ECM viscoelasticity and cancer progression. This review begins with an overview of cancer viscoelasticity, describing how tumor cells interact with biophysical signals in their environment, how they contribute to tumor viscoelasticity, and how this translates into cancer progression. Next, an overview of clinical trials focused on measuring biomechanical properties of tumors is presented, highlighting the biomechanical properties utilized for cancer diagnosis and monitoring. Finally, this review examines the use of biofabricated tumor models for studying the impact of ECM viscoelasticity on cancer behavior and progression and it explores potential avenues for future research on the production of more sophisticated and biomimetic tumor models, as well as their mechanical evaluation.

4.
BMJ Open ; 14(5): e084447, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38692730

ABSTRACT

BACKGROUND: Telemedicine, a method of healthcare service delivery bridging geographic distances between patients and providers, has gained prominence. This modality is particularly advantageous for outpatient consultations, addressing inherent barriers of travel time and cost. OBJECTIVE: We aim to describe economical outcomes towards the implementation of a multidisciplinary telemedicine service in a high-complexity hospital in Latin America, from the perspective of patients. DESIGN: A cross-sectional study was conducted, analysing the institutional data obtained over a period of 9 months, between April 2020 and December 2020. SETTING: A high-complexity teaching hospital located in Cali, Colombia. PARTICIPANTS: Individuals who received care via telemedicine. The population was categorised into three groups based on their place of residence: Cali, Valle del Cauca excluding Cali and Outside of Valle del Cauca. OUTCOME MEASURES: Travel distance, time, fuel and public round-trip cost savings, and potential loss of productivity were estimated from the patient's perspective. RESULTS: A total of 62 258 teleconsultations were analysed. Telemedicine led to a total distance savings of 4 514 903 km, and 132 886 hours. The estimated cost savings were US$680 822 for private transportation and US$1 087 821 for public transportation. Patients in the Outside of Valle del Cauca group experienced an estimated average time savings of 21.2 hours, translating to an average fuel savings of US$149.02 or an average savings of US$156.62 in public transportation costs. Areas with exclusive air access achieved a mean cost savings of US$362.9 per teleconsultation, specifically related to transportation costs. CONCLUSION: Telemedicine emerges as a powerful tool for achieving substantial travel savings for patients, especially in regions confronting geographical and socioeconomic obstacles. These findings underscore the potential of telemedicine to bridge healthcare accessibility gaps in low-income and middle-income countries, calling for further investment and expansion of telemedicine services in such areas.


Subject(s)
Hospitals, Teaching , Telemedicine , Humans , Colombia , Cross-Sectional Studies , Telemedicine/economics , Telemedicine/methods , Female , Male , Middle Aged , Adult , Aged , Cost Savings , Health Services Accessibility/economics , Adolescent , Young Adult , Travel/economics
5.
Int J Equity Health ; 23(1): 91, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38711128

ABSTRACT

Primary health care (PHC) has increased in global relevance as it has been demonstrated to be a useful strategy to promote community access to health services. Multilateral organizations and national governments have reached a consensus regarding the basic principles of PHC, but the application of these varies from country to country due to the particularities of local health systems.This article aims to review and summarize PHC strategies and the configuration of health networks in Latin American and Caribbean countries.The review was carried out using keywords in at least 9 databases. Papers in languages other than English, Portuguese, and Spanish were excluded, while non-refereed articles and regional gray literature were incorporated. As a result, 1,146 papers were identified. After three instances of analysis, 142 articles were selected for this investigation. Data were analyzed according to an analysis by theme.The evidence collected on health reforms in the region reflects the need to intensify care strategies supported by PHC and care networks. These must be resilient to changes in the population's needs and must be able to adapt to contexts of epidemiological accumulation.


Subject(s)
Primary Health Care , Humans , Latin America , Caribbean Region , Health Equity , Health Services Accessibility , Health Care Reform
6.
Eur J Obstet Gynecol Reprod Biol ; 297: 78-85, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38583275

ABSTRACT

OBJECTIVE: The impact of cervical cancer treatment on the quality of life of long-term survivors compared with the general female population is controversial, and no studies have been conducted comparing patients with benign gynecological diseases. The aim of this study was to compare the quality of life of cervical cancer survivors with that of healthy controls. STUDY DESIGN: A case-control study was conducted to compare the quality of life of 106 cervical cancer survivors from a tertiary hospital and 185 women admitted to a gynecological outpatient clinic from the same health area for a healthy woman check-up (n 46) or for a benign gynecological disorder (symptomatic, n 113; asymptomatic, n 26). To measure quality of life, self-administered questionnaires, such as the Functional Assessment Cancer Therapy-cervix and World Health Organization quality of life-brief version, were employed. Baseline scores were collected when patients first reported, and further evaluations were completed at 0-6, 7-12, 13-24, 25-60, and more than 60 months. For the contrastive analysis hypothesis, we employed R statistical software. RESULTS: Except for the environment domain at 0-6, 7-12, and 13-24 months (51.52 vs. 60.73, p < 0.0001; 52 vs. 60.73, p < 0.0001; 49.81 vs. 60.73, p < 0.0001, respectively), we found no statistically significant differences in the quality of life between cervical cancer survivors and controls. We did find differences in the physical health domain scores at 0-6 months (60.22 vs. 72.42, p = 0.039) and the social relationships domain scores at 13-24 months (54 vs. 71.42, p = 0.017) between cases and asymptomatic controls. CONCLUSION: Except for physical well-being, environment and social relationships, which were substantially better for controls, especially in the asymptomatic, long-term cervical cancer survivorsquality of life did not vary from that of controls.


Subject(s)
Cancer Survivors , Quality of Life , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/psychology , Uterine Cervical Neoplasms/therapy , Case-Control Studies , Middle Aged , Cancer Survivors/psychology , Adult , Genital Diseases, Female/psychology , Aged , Surveys and Questionnaires
7.
Methods Mol Biol ; 2777: 145-161, 2024.
Article in English | MEDLINE | ID: mdl-38478342

ABSTRACT

Cancer stem cells (CSCs) play a significant role in driving several tumor hallmarks. Their behavior and tumor progression are strictly related to the tumor microenvironment (TME). The dynamic interplay between CSCs and TME drives metastasis, chemoresistance, and disease relapse. In this chapter, we describe different techniques and protocols for isolating, culturing, and characterizing CSCs and we explain the methodology for the culture of multicellular spheroids comprising CSCs.


Subject(s)
Neoplasms , Spheroids, Cellular , Humans , Spheroids, Cellular/pathology , Neoplasms/pathology , Neoplastic Stem Cells/pathology , Tumor Microenvironment
8.
Lancet Reg Health Am ; 31: 100705, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38445021

ABSTRACT

Background: Reducing maternal mortality ratio (MMR) remains a paramount goal for low- and middle-income countries (LMICs), especially after COVID-19's devastating impact on maternal health indicators. We describe our experience implementing the Hospital Padrino Strategy (HPS), a collaborative model between a high-complexity hospital (Fundación Valle del Lili) and 43 medium- and low-complexity hospitals in one Colombian department (an administrative and territorial division) from 2021 to 2022, to sustain the trend towards reducing MMR. The study aimed to assess the effects of implementing HPS on both hospital performance and maternal health indicators in Valle del Cauca department (VCD). Methods: A mixed-methods study was conducted, comprising two phases. In the first phase, we investigated a cohort of hospitals through prospective follow-up to assess the outcomes of HPS implementation on hospital performance and maternal health indicators in VCD. In the second phase, qualitative data were collected through focus groups with 131 health workers from 33 hospitals to explore the implications of the HPS implementation on healthcare personnel. All data were obtained from records within the HPS implementation and from the Health Secretary of VCD. Findings: Evidence shows that in the context of HPS, 51 workshops involved 980 healthcare workers, covering the entire territory. Substantial improvements were observed in hospital conditions and healthcare personnel's technical competencies when providing obstetric care. Seven hundred eighty-five pregnant women with obstetric or perinatal emergencies received care through telehealth systems, with a progressive increase in technology adoption. Nine percent required Intensive Care Unit (ICU) admission, and none died. The MMR decreased from 78.8 in 2021 to 12.0 cases per 100,000 live births by 2022. Improvements in indicators and conducted training sessions instilled confidence and empowerment among the healthcare teams in the sponsored hospitals, as evidenced in focus groups derived from a sample of 131 healthcare workers from 33 hospitals. Interpretation: Implementing the Hospital Padrino Strategy led to a significant MMR reduction, and consolidated a model of social healthcare innovation replicable in LMICs. Funding: The Hospital Padrino Strategy was funded by the Fundación Valle del Lili and the Health Secretary of Valle del Cauca. Furthermore, this study received funding from a general grant for research from Tecnoquimicas S.A.

9.
Commun Biol ; 7(1): 253, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38429383

ABSTRACT

Flatfish undergo a remarkable metamorphosis from symmetrical pelagic larvae to fully asymmetrical benthic juveniles. The most distinctive features of this transformation is the migration of one eye. The molecular role of thyroid hormone in the metamorphosis process in flatfishes is well established. However, the regulatory network that facilitates eye movement remains enigmatic. This paper presents a morphological investigation of the metamorphic process in turbot eyes, using advanced imaging techniques and a global view of gene expression. The study covers migrant and non-migrant eyes and aims to identify the genes that are active during ocular migration. Our transcriptomic analysis shows a significant up-regulation of immune-related genes. The analysis of eye-specific genes reveals distinct patterns during the metamorphic process. Myosin is highlighted in the non-migrant eye, while ependymin is highlighted in the migrant eye, possibly involved in optic nerve regeneration. Furthermore, a potential association between the alx3 gene and cranial restructuring has been identified. Additionally, it confirmed simultaneous adaptation to low light in both eyes, as described by changes in opsins expression during the metamorphic process. The study also revealed that ocular migration activates systems asynchronously in both eyes, providing insight into multifaceted reorganization processes during metamorphosis of flatfish.


Subject(s)
Flatfishes , Animals , Flatfishes/genetics , Metamorphosis, Biological/genetics , Eye , Thyroid Hormones/genetics , Gene Expression Profiling
10.
RSC Adv ; 14(1): 707-711, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38173586

ABSTRACT

We herein present a selective methodology for the synthesis of disubstituted dihydropyrans by silyl-Prins cyclization of Z-vinylsilyl alcohols mediated by trimethylsilyl trifluoromethanesulfonate (TMSOTf). The reaction features broad substrate scope, short reaction times and ease of process scale-up. Moreover, to showcase the applicability of the proposed method, we also report a facile and linear synthesis of analogues of rhopaloic acid and natural doremox fragrance.

11.
Clin Res Cardiol ; 113(4): 546-560, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37436514

ABSTRACT

AIM: The aim of clinical practice guidelines for ST elevation myocardial infarction (STEMI) and non-ST elevation acute coronary syndrome (NSTE-ACS) is to assist healthcare professionals in clinical decision-making. We evaluated the type of studies supporting these guidelines and their recommendations. METHODS: All references and recommendations in the 2013 and 2014 ACC/AHA and 2017 and 2020 (ESC clinical guidelines for STEMI and NSTE-ACS were reviewed. References were classified into meta-analyses, randomised, non-randomised, and other types (e.g., position papers, reviews). Recommendations were classified according to class and their level of evidence (LOE). RESULTS: We retrieved 2128 non-duplicated references: 8.4% were meta-analyses, 26.2% randomised studies, 44.7% non-randomised studies, and 20.7% 'other' papers. Meta-analyses were based on randomised data in 78% of cases and used individual-patient data in 20.2%. Compared to non-randomised studies, randomised studies were more frequently multicentre (85.5% vs. 65.5%) and international (58.2% vs. 28.5%). The type of studies supporting recommendations varied as per the LOE of the recommendation. For LOE-A recommendations, the breakdown of supporting recommendations was: 18.5% meta-analyses, 56.6% randomised studies, 16.6% non-randomised studies and 8.3% 'other' papers; for LOE-B this breakdown was 9%, 39.8%, 38.2%, and 12.9%; and for LOE-C; 4.6%, 19.3%, 30.3%, and 45.9%. CONCLUSIONS: The references supporting the ACC/AHA and ESC guidelines on STEMI and NSTE-ACS consisted of non-randomised studies in ~ 45% of cases, with less than a third of the references consisting of meta-analyses and randomised studies. The type of studies supporting guideline recommendations varied widely by the LOE of the recommendation.


Subject(s)
Acute Coronary Syndrome , ST Elevation Myocardial Infarction , Humans , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/therapy , Societies, Medical , Clinical Decision-Making
12.
Eur Heart J Qual Care Clin Outcomes ; 10(2): 176-188, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-37296213

ABSTRACT

AIMS: The aim of this study was to describe the methodological features of the randomized controlled trials (RCTs) cited in American and European clinical practice guidelines (CPGs) for ST elevation myocardial infarction (STEMI) and non-ST elevation acute coronary syndrome (NSTE-ACS). METHODS AND RESULTS: Out of 2128 non-duplicated references cited in the 2013 and 2014 American College of Cardiology/American Heart Association and 2017 and 2020 European Society of Cardiology CPGs for STEMI and NSTE-ACS, we extracted data for 407 RCTs (19.1% of total references). The majority were multicenter studies (81.8%), evaluated pharmacological interventions (63.1%), had a 2-arm (82.6%), and superiority (90.4%) design. Most RCTs (60.2%) had an active comparator, and 46.2% were funded by industry. The median observed sample size was 1001 patients (84.2% of RCTs achieved ≥80% of the intended sample size). Most RCTs had a single primary outcome (90.9%), which was a composite in just over half (51.9%). Among the RCTs testing for superiority, 44.0% reported a P-value of ≥0.05 for the primary outcome and 61.9% observed a risk reduction of >15%. The observed treatment effect was lower-than-expected in 67.6% of RCTs, with 34.4% having at least a 20% lower-than-expected treatment effect. The calculated post hoc statistical power was ≥80% for 33.9% of cited RCTs. CONCLUSIONS: This analysis demonstrates that RCTs cited by CPGs can still have significant methodological issues and limitations, highlighting that a better understanding of the methodological aspects of RCTs is crucial in order to formulate recommendations relevant to clinical practice.


Subject(s)
Acute Coronary Syndrome , Cardiology , ST Elevation Myocardial Infarction , United States , Humans , Acute Coronary Syndrome/therapy , Randomized Controlled Trials as Topic , American Heart Association
13.
Oman J Ophthalmol ; 16(3): 415-420, 2023.
Article in English | MEDLINE | ID: mdl-38059089

ABSTRACT

Plateau iris syndrome (PIS) was first coined in 1958 to describe the iris configuration of a patient, 2 years later; the concept of plateau iris was published. In 1992, the anatomic aspects of plateau iris were studied using ultrasound biomicroscopy (UBM) determining it as a form of primary angle-closure glaucoma caused by a large or anteriorly positioned ciliary body that leads to mechanical obstruction of the trabecular meshwork, this condition is most often found in young patients. We aim to review the current literature and knowledge on the diagnosis and treatment options of PIS; the search was conducted in PubMed, LILACS, and BIREME internet search sites using keywords and snowball search strategy of articles published until 2022, focusing on PIS history, epidemiology, clinical diagnosis, UBM feature, and treatment.

14.
Int J Mol Sci ; 24(21)2023 Nov 06.
Article in English | MEDLINE | ID: mdl-37958993

ABSTRACT

Breast cancer (BC) is the most diagnosed cancer in women and the second most common cancer globally. Significant advances in BC research have led to improved early detection and effective therapies. One of the key challenges in BC is the presence of BC stem cells (BCSCs). This small subpopulation within the tumor possesses unique characteristics, including tumor-initiating capabilities, contributes to treatment resistance, and plays a role in cancer recurrence and metastasis. In recent years, microRNAs (miRNAs) have emerged as potential regulators of BCSCs, which can modulate gene expression and influence cellular processes like BCSCs' self-renewal, differentiation, and tumor-promoting pathways. Understanding the miRNA signatures of BCSCs holds great promise for improving BC diagnosis and prognosis. By targeting BCSCs and their associated miRNAs, researchers aim to develop more effective and personalized treatment strategies that may offer better outcomes for BC patients, minimizing tumor recurrence and metastasis. In conclusion, the investigation of miRNAs as regulators of BCSCs opens new directions for advancing BC research through the use of bioinformatics and the development of innovative therapeutic approaches. This review summarizes the most recent and innovative studies and clinical trials on the role of BCSCs miRNAs as potential tools for early diagnosis, prognosis, and resistance.


Subject(s)
Breast Neoplasms , MicroRNAs , Humans , Female , MicroRNAs/genetics , MicroRNAs/metabolism , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Signal Transduction , Neoplastic Stem Cells/metabolism , Cell Differentiation
15.
Eur J Contracept Reprod Health Care ; 28(6): 295-300, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37910020

ABSTRACT

OBJECTIVE: To describe the knowledge, attitudes, and perceptions of healthcare providers in a region in southwestern Colombia regarding the recommendation and use of long-acting reversible contraceptive (LARC) methods for adolescents. STUDY DESIGN: This was a cross-sectional study. An online exploratory survey was designed to assess healthcare providers' knowledge, attitudes, and perceptions of Valle del Cauca hospitals. For the development of this the questionnaire, a literature search and validation of the instrument's appearance were conducted. RESULTS: The survey was completed by 115 people. Knowledge: 62.6% and 33% of the participants did not consider themselves capable of correctly placing an intrauterine device (IUD) or a subdermal implant, respectively. However, 73.9% of the participants had adequate theoretical knowledge. Attitudes: 64.3% of the participants considered that adolescents can acquire contraceptive methods without limitations. Short-acting reversible methods were the least recommended. Perceptions: For IUDs, 40.8% and 16.5% of the participants imposed a minimum age and minimum parity requirement for their use, respectively. Side effects were the main reason for not recommending in health institutions with a lower level of complexity. CONCLUSION: Healthcare providers had positive attitudes and adequate theoretical knowledge concerning to the effectiveness of LARCs. The main areas for improvement were practical knowledge about the insertion and proper use of the devices, indications for referral to gynaecologists for the insertion procedure, and concerns about side effects.


Our research explores healthcare providers' knowledge, attitudes, and perceptions regarding long-acting reversible contraceptives for adolescents. While attitudes were positive, practical knowledge gaps on device, placement and referral indications emerged. Read the full findings to uncover more about LARCs in adolescent healthcare.


Subject(s)
Contraceptive Agents, Female , Intrauterine Devices , Pregnancy , Female , Humans , Adolescent , Health Knowledge, Attitudes, Practice , Cross-Sectional Studies , Contraception/methods , Health Personnel
16.
J Neuroeng Rehabil ; 20(1): 138, 2023 10 17.
Article in English | MEDLINE | ID: mdl-37848992

ABSTRACT

OBJECTIVE: We aim to determine a comprehensive set of requirements, perceptions, and expectations that people with spinal cord injury (SCI) and the clinicians in charge of their rehabilitation have regarding the use of wearable robots (WR) for gait rehabilitation. BACKGROUND: There are concerns due to the limited user acceptance of WR for gait rehabilitation. Developers need to emphasize understanding the needs and constraints of all stakeholders involved, including the real-life dynamics of rehabilitation centers. METHODS: 15 people with SCI, 9 without experience with WR and 6 with experience with these technologies, and 10 clinicians from 3 rehabilitation centers in Spain were interviewed. A directed content analysis approach was used. RESULTS: 78 codes grouped into 9 categories (physical results, usability, psychology-related codes, technical characteristics, activities, acquisition issues, context of use, development of the technologies and clinical rehabilitation context) were expressed by at least 20% of the users interviewed, of whom 16 were not found in the literature. The agreement percentage between each group and subgroup included in the study, calculated as the number of codes that more than 20% of both groups expressed, divided over the total amount of codes any of those two groups agreed on (≥ 20%), showed limited agreement between patients and clinicians (50.00%) and between both types of patients (55.77%). The limited accessibility and availability of lower limb exoskeletons for gait rehabilitation arose in most of the interviews. CONCLUSIONS: The limited agreement percentage between patients and clinicians indicates that including both types of users in the design process of these technologies is important, given that their requirements are complementary. Engaging users with prior technology experience is recommended, as they often exhibit strong internal consensus and articulate well-defined requirements. This study adds up the knowledge available in the literature and the new codes found in our data, which enlighten important aspects that ought to be addressed in the field to develop technologies that respond to users' needs, are usable and feasible to implement in their intended contexts. APPLICATION: The set of criteria summarized in our study will be useful to guide the design, development, and evaluation of WR for gait rehabilitation to meet user's needs and allow them to be implemented in their intended context of use.


Subject(s)
Exoskeleton Device , Spinal Cord Injuries , Wearable Electronic Devices , Humans , Spinal Cord Injuries/rehabilitation , Gait , Lower Extremity
17.
Cells ; 12(18)2023 09 08.
Article in English | MEDLINE | ID: mdl-37759464

ABSTRACT

The lack of optimal models to evaluate novel agents is delaying the development of effective immunotherapies against human breast cancer (BC). In this prospective open label study, we applied neoadjuvant intratumoral immunotherapy with empty cowpea mosaic virus-like particles (eCPMV) to 11 companion dogs diagnosed with canine mammary cancer (CMC), a spontaneous tumor resembling human BC. We found that two neoadjuvant intratumoral eCPMV injections resulted in tumor reduction in injected tumors in all patients and in noninjected tumors located in the ipsilateral and contralateral mammary chains of injected dogs. Tumor reduction was independent of clinical stage, tumor size, histopathologic grade, and tumor molecular subtype. RNA-seq-based analysis of injected tumors indicated a decrease in DNA replication activity and an increase in activated dendritic cell infiltration in the tumor microenvironment. Immunohistochemistry analysis demonstrated significant intratumoral increases in neutrophils, T and B lymphocytes, and plasma cells. eCPMV intratumoral immunotherapy demonstrated antitumor efficacy without any adverse effects. This novel immunotherapy has the potential for improving outcomes for human BC patients.


Subject(s)
Breast Neoplasms , Comovirus , Humans , Animals , Dogs , Female , Neoadjuvant Therapy , Prospective Studies , Breast Neoplasms/therapy , Immunotherapy , Tumor Microenvironment
18.
Int J Mol Sci ; 24(18)2023 Sep 13.
Article in English | MEDLINE | ID: mdl-37762335

ABSTRACT

Canine inflammatory mammary cancer (IMC) is a highly aggressive and lethal cancer in dogs serving as a valuable animal model for its human counterpart, inflammatory breast cancer (IBC), both lacking effective therapies. Intratumoral immunotherapy (IT-IT) with empty cowpea mosaic virus (eCPMV) nanoparticles has shown promising results, demonstrating a reduction in tumor size, longer survival rates, and improved quality of life. This study compares the transcriptomic profiles of tumor samples from female dogs with IMC receiving eCPMV IT-IT and medical therapy (MT) versus MT alone. Transcriptomic analyses, gene expression profiles, signaling pathways, and cell type profiling of immune cell populations in samples from four eCPMV-treated dogs with IMC and four dogs with IMC treated with MT were evaluated using NanoString Technologies using a canine immune-oncology panel. Comparative analyses revealed 34 differentially expressed genes between treated and untreated samples. Five genes (CXCL8, S100A9, CCL20, IL6, and PTGS2) involved in neutrophil recruitment and activation were upregulated in the treated samples, linked to the IL17-signaling pathway. Cell type profiling showed a significant increase in neutrophil populations in the tumor microenvironment after eCPMV treatment. These findings highlight the role of neutrophils in the anti-tumor response mediated by eCPMV IT-IT and suggest eCPMV as a novel therapeutic approach for IBC/IMC.


Subject(s)
Comovirus , Inflammatory Breast Neoplasms , Humans , Dogs , Animals , Female , Transcriptome , Neutrophils , Quality of Life , Gene Expression Profiling , Tumor Microenvironment
19.
Polymers (Basel) ; 15(14)2023 Jul 12.
Article in English | MEDLINE | ID: mdl-37514401

ABSTRACT

This work investigates the effect of dilution on the phase separation process of binary charged polysaccharide-surfactant mixtures formed by two cationic polysaccharides and up to four surfactants of different nature (anionic, zwitterionic, and neutral), as well as the potential impact of dilution-induced phase separation on the formation of conditioning deposits on charged surfaces, mimicking the negative charge and wettability of damaged hair fibers. The results obtained showed that the dilution behavior of model washing formulations (concentrated polysaccharide-surfactant mixtures) cannot be described in terms of a classical complex precipitation framework, as phase separation phenomena occur even when the aggregates are far from the equilibrium phase separation composition. Therefore, dilution-enhanced deposition cannot be predicted in terms of the worsening of colloidal stability due to the charge neutralization phenomena, as common phase separation and, hence, enhanced deposition occurs even for highly charged complexes.

20.
Mar Drugs ; 21(7)2023 Jul 13.
Article in English | MEDLINE | ID: mdl-37504932

ABSTRACT

In this perspective, we showcase the benefits of continuous flow chemistry and photochemistry and how these valuable tools have contributed to the synthesis of organic scaffolds from the marine environment. These technologies have not only facilitated previously described synthetic pathways, but also opened new opportunities in the preparation of novel organic molecules with remarkable pharmacological properties which can be used in drug discovery programs.


Subject(s)
Drug Discovery , Technology , Chemistry, Pharmaceutical
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