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1.
Clin Park Relat Disord ; 10: 100261, 2024.
Article in English | MEDLINE | ID: mdl-38952436

ABSTRACT

Background: People with a chronic condition such as Parkinson's disease (PD) struggle with acceptance and finding meaning in life. Consciousness coaching could be a valuable addition in addressing these issues. Objective: We aim to evaluate the user experiences and potential effectiveness of consciousness coaching for people with PD (PwPD). Methods: We performed a pilot randomized controlled trial including PwPD in Hoehn & Yahr stage 1-3. People with cognitive impairments, severe psychiatric disorders, or those who did not have a clear issue to address with consciousness coaching, were excluded. PwPD were randomly allocated to either receiving 6 months of consciousness coaching in addition to usual care or to usual care alone. To explore experiences we performed semi-structured qualitative interviews with all PwPD in the intervention group. Potential effects were explored using questionnaires on quality of life, activities of daily life, self-management and non-motor symptoms at baseline and after 6 months. Results: We included 39 PwPD, 19 participants in the intervention group and 20 in the control group. Based on the interviews, we identified a number of themes and codes. In general PwPD experienced consciousness coaching as confronting but supportive in reaching their goals and in taking more responsibility for their lives. Quantitatively, we did not find a difference between groups for any of the outcomes. Conclusions: Consciousness coaching was considered valuable by most participants in this study and may be an interesting addition to PD treatment. We did not find any effects of the intervention on PD symptoms or quality of life.

2.
Dement Neuropsychol ; 18: e20230098, 2024.
Article in English | MEDLINE | ID: mdl-38957727

ABSTRACT

The majority of people with dementia live in low or middle-income countries (LMICs) where resources that play a crucial role in brain health, such as quality education, are still not widely available. In Brazil, illiteracy remains a prevalent issue, especially in communities with lower socioeconomic status (SES). The PROAME study set out to explore basic education in illiterate adults as a means to improve cognitive reserve. Objective: This manuscript aims to explore the relationship between SES and learning, as well as cognitive outcomes, in an older illiterate population. Methods: This six-month clinical trial (NCT04473235) involved 108 participants, of which 77 concluded all assessments, enrolled in late-life basic education. SES assessments included Quality of Urban Living Index, Municipal Human Development Index and Household SES calculated for each participant. Cognitive assessments encompassed the Free and Cued Selective Reminding Test (FCSRT), a word list to assess reading, and the Beta III matrix. Results: The sample consisted primarily of women, with a mean age of 58.5. Participants improved their reading (p=0.01) and their FCSRT (p=0.003). Regarding episodic memory, women outperformed men (p=0.007) and younger participants improved more than their older counterparts (p=0.001). There was no association observed between SES and cognitive outcomes. Conclusion: Irrespective of SES, participants demonstrated positive outcomes after attending basic education. These findings highlight that late life education could be an important non-pharmacologic preventative measure, especially in LMICs.


A maioria das pessoas com demência vive em países de baixa/média renda, onde recursos essenciais para a saúde cerebral, como educação de qualidade, ainda não são amplamente acessíveis. No Brasil, o analfabetismo ainda é frequente, especialmente em comunidades de baixo nível socioeconômico. O estudo PROAME teve como objetivo explorar a educação básica tardia em pessoas analfabetas como ferramenta para o aumento da reserva cognitiva. Objetivo: Investigar a relação entre nível socioeconômico com aprendizado e com desempenho em testes cognitivos, em adultos analfabetos. Métodos: Este estudo clínico de seis meses (NCT04473235) contou com 108 participantes inscritos no projeto Educação para Jovens e Adultos (EJA), dos quais 77 completaram os testes. O nível socioeconômico de cada participante foi medido usando-se: o Índice de Qualidade de Vida Urbana, o Índice de Desenvolvimento Humano Municipal e o nível socioeconômico doméstico. Avaliações cognitivas incluíram: o Teste de Recordação Seletiva Livre e Guiada (TRSLG), uma lista de palavras para avaliar leitura e a matriz Beta III. Resultados: A amostra era predominantemente feminina, com idade média de 58,5. Os participantes melhoraram a leitura (p=0,01) e o TRSLG (p=0,003). Com relação à memoria episódica, as mulheres tiveram resultados superiores aos dos homens (p=0,007) e participantes mais jovens melhoraram mais que seus colegas mais velhos (p=0,001). Não foi observada nenhuma relação entre o nível socioeconômico e o desempenho cognitivo. Conclusão: Independentemente do nível socioeconômico, participantes obtiveram resultados positivos após frequentar a educação básica. Isso sugere que a educação tardia pode ser uma medida preventiva não farmacológica importante, especialmente em países de baixa/média renda.

3.
Vet Res Commun ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38954255

ABSTRACT

Due to events related to the urbanization process, specimens of Saimiri collinsi are often referred to veterinarians specializing in the treatment of wild animals. With these professionals and the oral health of this species in mind, we evaluated the skull and the exact location of the infraorbital, mentual and mandibular foramens, with the aim of supporting the anesthetic block for dental procedures in Saimiri collinsi. The infraorbital foramen was located in the maxillary bone and was arranged with one on each side, except in one individual, with a pair in each antimer. The mentual foramen was located in the diastema between the canine tooth and the lateral incisor. The mandibular foramen was located medially on the ramus of the mandible, close to the mandibular incisure. The distances between the foramina and the main reference points, were greater in females than in males (p < 0.05). For access purposes, in the foramens investigated we suggest using a Gingival Needle 30G 21 mm Short, positioned externally at 15º to the maxillary bone to access the infraorbital foramen. Externally, perpendicular to the chin, in the diastema between the lower lateral incisor tooth and the canine tooth, to approach the mentual foramen, and ventral to the edge of the mandibular body, at a 90º angle, to access the mandibular foramen.

4.
Vaccines (Basel) ; 12(6)2024 May 25.
Article in English | MEDLINE | ID: mdl-38932307

ABSTRACT

The yellow fever (YF) vaccine is one of the safest and most effective vaccines currently available. Still, its administration in people living with HIV (PLWH) is limited due to safety concerns and a lack of consensus regarding decreased immunogenicity and long-lasting protection for this population. The mechanisms associated with impaired YF vaccine immunogenicity in PLWH are not fully understood, but the general immune deregulation during HIV infection may play an important role. To assess if HIV infection impacts YF vaccine immunogenicity and if markers of immune deregulation could predict lower immunogenicity, we evaluated the association of YF neutralization antibody (NAb) titers with the pre-vaccination frequency of activated and exhausted T cells, levels of pro-inflammatory cytokines, and frequency of T cells, B cells, and monocyte subsets in PLWH and HIV-negative controls. We observed impaired YF vaccine immunogenicity in PLWH with lower titers of YF-NAbs 30 days after vaccination, mainly in individuals with CD4 count <350 cells/mm3. At the baseline, those individuals were characterized by having a higher frequency of activated and exhausted T cells and tissue-like memory B cells. Elevated levels of those markers were also observed in individuals with CD4 count between 500 and 350 cells/mm3. We observed a negative correlation between the pre-vaccination level of CD8+ T cell exhaustion and CD4+ T cell activation with YF-NAb titers at D365 and the pre-vaccination level of IP-10 with YF-NAb titers at D30 and D365. Our results emphasize the impact of immune activation, exhaustion, and inflammation in YF vaccine immunogenicity in PLWH.

5.
Antioxidants (Basel) ; 13(6)2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38929167

ABSTRACT

In the Azores archipelago (Portugal), forest operations and wood industry generate large amounts of Cryptomeria japonica biomass residues (CJBR), which can be used to produce valuable essential oils (EOs). In this study, we evaluated the chemical composition and antioxidant activities of EOs from Azorean C. japonica sawdust (CJS) and resin-rich bark (CJRRB). The CJS and CJRRB EOs, obtained via hydrodistillation, showed different yield values (0.27% vs. 0.80% v/w, dry weight) and also different chemical profiles, as assessed using GC/MS. A total of 64 and 85 components were identified in CJS and CJRRB EOs, representing 95.7% and 96.9% of the total composition, respectively. The major components in CJS EO were oxygenated sesquiterpenes (mainly α+ß-eudesmol, 1-epicubenol, and cubebol), while in CJRRB EO, the major components were monoterpene hydrocarbons, including α-pinene, δ-3-carene, and limonene (66.6% vs. 6.4% for oxygenated sesquiterpenes and 0% vs. 64% for monoterpene hydrocarbons, respectively). Antioxidant activity was estimated using (i) two radical-based assays, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity, and (ii) a lipid model assay, ß-carotene-linoleic acid bleaching activity (BCBA). Both CJS and CJRRB EOs exhibited concentration-dependent antioxidant activities, and their DPPH, ABTS, and BCBA EC50 values were 1107 vs. 1275 µg/mL, 260 vs. 498 µg/mL, and 1764 vs. 662 µg/mL, respectively. The results indicate that both EOs were able to exert antioxidant activity via different mechanisms of action. Therefore, Azorean CJS and CJRRB may be sustainable sources for antioxidant compounds. This study expands the chemical and biological knowledge of CJBR EOs and, consequently, adds more value to the C. japonica EO industry.

6.
Comput Struct Biotechnol J ; 23: 2375-2387, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38873646

ABSTRACT

Anti-CD19 CAR-T cell therapy represents a breakthrough in the treatment of B-cell malignancies, and it is expected that this therapy modality will soon cover a range of solid tumors as well. Therefore, a universal cheap and sensitive method to detect CAR expression is of foremost importance. One possibility is the use of epitope tags such as c-Myc, HA or FLAG tags attached to the CAR extracellular domain, however, it is important to determine whether these tags can influence binding of the CAR with its target molecule. Here, we conducted in-silico structural modelling of an FMC63-based anti-CD19 single-chain variable fragment (scFv) with and without a c-Myc peptide tag added to the N-terminus portion and performed molecular dynamics simulation of the scFv with the CD19 target. We show that the c-Myc tag presence in the N-terminus portion does not affect the scFv's structural equilibrium and grants more stability to the scFv. However, intermolecular interaction potential (IIP) analysis reveals that the tag can approximate the complementarity-determining regions (CDRs) present in the scFv and cause steric impediment, potentially disturbing interaction with the CD19 protein. We then tested this possibility with CAR-T cells generated from human donors in a Nalm-6 leukemia model, showing that CAR-T cells with the c-Myc tag have overall worse antitumor activity, which was also observed when the tag was added to the C-terminus position. Ultimately, our results suggest that tag addition is an important aspect of CAR design and can influence CAR-T cell function, therefore its use should be carefully considered.

7.
Nanomedicine (Lond) ; : 1-13, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38905147

ABSTRACT

Artificial intelligence has revolutionized many sectors with unparalleled predictive capabilities supported by machine learning (ML). So far, this tool has not been able to provide the same level of development in pharmaceutical nanotechnology. This review discusses the current data science methodologies related to polymeric drug-loaded nanoparticle production from an innovative multidisciplinary perspective while considering the strictest data science practices. Several methodological and data interpretation flaws were identified by analyzing the few qualified ML studies. Most issues lie in following appropriate analysis steps, such as cross-validation, balancing data, or testing alternative models. Thus, better-planned studies following the recommended data science analysis steps along with adequate numbers of experiments would change the current landscape, allowing the exploration of the full potential of ML.


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9.
Braz J Microbiol ; 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38896342

ABSTRACT

Osteomyelitis caused by non-Candida species is rare and often neglected, and current recommendations are based on primarily clinical experience and expert opinion. The objective of this study was to describe a case series of non-Candida fungal osteomyelitis. This retrospective study included 10 patients with non-Candida fungal osteomyelitis. Patients with osteomyelitis and microbiologically confirmed non-Candida species from bone fragment cultures were selected from the institution Infection Control Board database. Fusarium spp. were the most commonly isolated fungus from bone fragment cultures in five patients (50%). The majority did not present immunosuppression. The most common etiology was post-traumatic (n = 7, 70%), particularly open fractures. All patients were treated with antifungals associated with surgery. The antifungals used were itraconazole in five patients (50%), and voriconazole in another five patients (50%), with a median duration of antifungal therapy of four weeks (range: 3-25). There were no observed deaths within 30 days and one year. An antifungal approach combined with surgical treatment demonstrated favorable clinical outcomes, including low mortality rates and effective remission.

10.
Microsc Res Tech ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38934119

ABSTRACT

The species Cuniculus paca is highly subject to predation, whether natural or anthropogenic, and the ability of species to withstand different levels of depredation depends directly on their reproductive dynamics. However, there is little literature on the developmental biology of this species, and so the aim of this paper was to describe the fetal development of the urinary tract of C. paca through morphological analysis. Twelve specimens with estimated gestational ages of between 75 and 157 days were used, divided into 3 groups. We found the urinary tract in pelvic-abdominal topography with macroscopic differentiation between the organs already present in the first ages studied; in addition, the microscopic structural pattern changed little between the groups. This evidence reinforces the precocial development of these individuals. RESEARCH HIGHLIGHTS: With the results obtained for development of urinary tract in Cuniculus paca reinforces the precocial development of these individuals. The urinary tract had pelvic-abdominal topography with macroscopic differentiation between the organs already present in the first ages studied. The microscopic structural pattern changed little between the groups. At all analyzed fetal ages, the cortical region of kidney was characterized by the presence of glomeruli arranged throughout the region, formed by capillary plexuses surrounded by a glomerular capsule. In addition, the cortical region also presented convoluted tubules with cubic epithelial tissue cells and a brush border. The presence of a developed macula densa was observed next to the glomeruli, suggesting the initial formation of the fetal juxtaglomerular apparatus.

11.
Coron Artery Dis ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38829316

ABSTRACT

BACKGROUND: Evidence from randomized studies support complete over culprit-only revascularization for patients with acute coronary artery syndrome (ACS) and multivessel coronary artery diseases (MVD). Whether these findings extend to elderly patients, however, has not been thoroughly explored. METHODS: We conducted a systematic review and meta-analysis comparing clinical outcomes of elderly individuals (defined as age ≥75 years) with ACS and MVD submitted to complete vs partial-only percutaneous coronary intervention (PCI). PubMed, Embase, and Cochrane were searched. We computed pooled hazard ratios with 95% confidence intervals (CI) to preserve time time-to-event data. RESULTS: We included 7 studies, of which 2 were RCT and 5 were multivariable adjusted cohorts, comprising a total 10 147, of whom 43.8% underwent complete revascularization. As compared with partial-only PCI, complete revascularization was associated with a lower all-cause mortality (hazard ratio 0.71; 95% CI 0.60-0.85; P < 0.01), cardiovascular mortality (hazard ratio 0.64; 95% CI 0.52-0.79; P < 0.01), and recurrent myocardial infarction (hazard ratio 0.65; 95% CI 0.50-0.85; P < 0.01). There was no significant difference between groups regarding the risk of revascularizations (hazard ratio 0.80; 95% CI 0.53-1.20; P = 0.28). CONCLUSION: Among elderly patients with ACS and multivessel CAD, complete revascularization is associated with a lower risk of all-cause mortality, cardiovascular mortality, and recurrent myocardial infarction.

12.
Acta Trop ; 256: 107267, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38777256

ABSTRACT

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi (T. cruzi), is a neglected disease endemic to some Latin American countries, including Brazil. Soon after infection, individuals develop an acute phase, which in most cases is asymptomatic and may go undetected. However, when CD is detected early, notification in the Notifiable Diseases Information System (SINAN), is mandatory. This study aimed to evaluate the information registered in the SINAN database and to determine the epidemiological profile of acute CD in Northeast Brazil, an endemic region, from 2001 to 2021. According to this survey, 1,444 cases of acute CD were reported in the Northeastern region of Brazil during this period. During the first six years, referred to as period 1, 90.24% of the notifications were registered, while the number of notifications significantly decreased in the subsequent years, referred to as period 2. Most individuals diagnosed with acute CD were Afro-Brazilian adults. All known routes of infection by the parasite were reported. Vector-borne transmission was predominant during period 1 (73.29%) and oral transmission during period 2 (58.87%). All nine states in Northeast Brazil reported cases in both periods. A higher incidence of disease was reported in Rio Grande do Norte (RN) during period 1, and in Maranhão (MA) during period 2. Our results show that CD remains a significant public health challenge.


Subject(s)
Chagas Disease , Chagas Disease/epidemiology , Chagas Disease/transmission , Brazil/epidemiology , Humans , Male , Adult , Female , Middle Aged , Adolescent , Child , Child, Preschool , Young Adult , Disease Notification/statistics & numerical data , Infant , Aged , Incidence , Trypanosoma cruzi , Acute Disease/epidemiology , Infant, Newborn , Aged, 80 and over
13.
Res Vet Sci ; 174: 105308, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38788298

ABSTRACT

Myxosarcoma is a rare malignant mesenchymal neoplasm of soft tissues originating from fibroblasts. This report describes a case of bilateral myxosarcoma in a three-year-old cryptorchid dog. The animal was referred to the veterinary clinic because of the absence of testicles in the scrotum. Ultrasonography revealed two masses in the abdominal cavity with testicular echotexture. Exploratory laparotomy revealed the presence of cryptorchid testicles, and orchiectomy was recommended to treat the animal. Testicles were gray and reddish in color and enlarged with firm consistency. For histopathological analysis, testis fragments were fixed in 10% formalin and stained with hematoxylin and eosin and Alcian blue. Immunohistochemistry was performed using the following primary antibodies:1A4, HHF35, desmin, glial fibrillary acidic protein, CD31, S-100, vimentin, and Ki-67. Histopathological evaluation revealed the proliferation of fusiform and round cells associated with extensive areas of myxoid matrix. Neoplasms featured multinucleated giant cells, pleomorphism, karyomegaly, nuclear hyperchromasia, anisokaryosis, mitoses, and necrosis, with coarse chromatin and prominent nucleoli. Immunohistochemical analysis of vimentin- and the Alcian blue-positive cells confirmed the diagnosis of myxosarcoma. A high mitotic count and Ki-67 proliferative index suggests this myxosarcoma had a high degree of malignancy. To the best of our knowledge, this is the first case report of bilateral testicular myxosarcoma in a cryptorchid animal.


Subject(s)
Cryptorchidism , Dog Diseases , Myxosarcoma , Testicular Neoplasms , Male , Animals , Dogs , Dog Diseases/pathology , Dog Diseases/surgery , Testicular Neoplasms/veterinary , Testicular Neoplasms/pathology , Testicular Neoplasms/surgery , Myxosarcoma/veterinary , Myxosarcoma/pathology , Cryptorchidism/veterinary , Cryptorchidism/pathology , Orchiectomy/veterinary , Immunohistochemistry/veterinary
14.
Int J Mol Sci ; 25(10)2024 May 07.
Article in English | MEDLINE | ID: mdl-38791100

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is comprised of histopathological alterations such as pulmonary emphysema and peribronchial fibrosis. Matrix metalloproteinase 9 (MMP-9) is one of the key enzymes involved in both types of tissue remodeling during the development of lung damage. In recent studies, it was demonstrated that deflamin, a protein component extracted from Lupinus albus, markedly inhibits the catalytic activity of MMP-9 in experimental models of colon adenocarcinoma and ulcerative colitis. Therefore, in the present study, we investigated for the first time the biological effect of deflamin in a murine COPD model induced by chronic exposure to ozone. Ozone exposure was carried out in C57BL/6 mice twice a week for six weeks for 3 h each time, and the treated group was orally administered deflamin (20 mg/kg body weight) after each ozone exposure. The histological results showed that deflamin attenuated pulmonary emphysema and peribronchial fibrosis, as evidenced by H&E and Masson's trichrome staining. Furthermore, deflamin administration significantly decreased MMP-9 activity, as assessed by fluorogenic substrate assay and gelatin zymography. Interestingly, bioinformatic analysis reveals a plausible interaction between deflamin and MMP-9. Collectively, our findings demonstrate the therapeutic potential of deflamin in a COPD murine model, and suggest that the attenuation of the development of lung tissue damage occurs by deflamin-regulated MMP-9 catalytic activity.


Subject(s)
Disease Models, Animal , Matrix Metalloproteinase 9 , Ozone , Pulmonary Disease, Chronic Obstructive , Animals , Male , Mice , Lung/pathology , Lung/drug effects , Lung/metabolism , Matrix Metalloproteinase 9/metabolism , Mice, Inbred C57BL , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/pathology , Pulmonary Disease, Chronic Obstructive/chemically induced
15.
Front Public Health ; 12: 1376113, 2024.
Article in English | MEDLINE | ID: mdl-38807989

ABSTRACT

To optimize the efficient introduction and deployment of COVID-19 vaccines across the globe during the COVID-19 pandemic, in April 2021 WHO launched a new process and tools for countries to rapidly review the early phase of countries' COVID-19 vaccine introduction. This methodology is called the COVID-19 vaccination intra-action review, also known as mini COVID-19 vaccine post-introduction evaluation (mini-cPIE). As of November 2022, 46 mini-cPIEs had been conducted. In collaboration with Project ECHO, WHO convened and facilitated real-time experience sharing and peer-learning among countries following their mini-cPIEs through a virtual global real-time learning forum. This five-session clinic series was attended by 736 participants from 129 countries. Based on post-session feedback surveys, when asked about the utility of the sessions, half of the participants said that sessions led them to review national guidelines and protocols or make other changes to their health systems. The post-series survey sent following the end of the clinic series showed that at least eight countries subsequently conducted a mini-cPIE after participating in the clinics, and participants from at least nine countries indicated the experience shared by peer countries on the clinic largely benefited their COVID-19 vaccine introduction and deployment. In this article, we highlight the benefits and importance of creating a global experience-sharing forum for countries to connect and share pertinent learnings in real-time during an international public health emergency. Moving forward, it is critical to foster a culture of individual and collective learning within and between countries during public health emergencies, with WHO playing an important convening role.


Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , COVID-19/prevention & control , Global Health , SARS-CoV-2 , World Health Organization , Pandemics/prevention & control
16.
Invest Ophthalmol Vis Sci ; 65(5): 4, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38691089

ABSTRACT

Purpose: To investigate the adhesion of Acanthamoeba to scleral contact lens (ScCL) surface according to lens shape. Methods: Two strains of A. polyphaga (CDC:V062 and ATCC 30461) and one clinical Acanthamoeba isolate, were inoculated onto five contact lens (CL): one first-generation silicone hydrogel (SHCL; lotrafilcon B; adhesion control) containing plasma surface treatment; two ScCL (fluorosilicone acrylate) one containing surface treatment composed of plasma and the other containing plasma with Hydra-PEG, and two CL designed with a flat shape having the same material and surface treatments of the ScCL. Trophozoites that adhered to the lens's surfaces were counted by inverted optical light microscopy. Possible alterations of the lens surface that could predispose amoeba adhesion and Acanthamoeba attached to these lens surfaces were evaluated by scanning electron microscopy (SEM). Results: All strains revealed greater adhesion to the ScCL when compared with the flat lenses (P < 0.001). The clinical isolate and the ATCC 30461 had a higher adhesion (P < 0.001) when compared with the CDC:V062. A rough texture was observed on the surface of the lenses that have been examined by SEM. Also, SEM revealed that the isolates had a rounded appearance on the surface of the ScCL in contrast with an elongated appearance on the surface of the silicone hydrogel. Conclusions: The findings revealed that the curved shape of the ScCL favors amoeba adhesion.


Subject(s)
Acanthamoeba , Microscopy, Electron, Scanning , Acanthamoeba/physiology , Acanthamoeba/ultrastructure , Sclera , Humans , Contact Lenses, Hydrophilic/parasitology , Cell Adhesion/physiology , Contact Lenses/parasitology , Trophozoites/ultrastructure , Trophozoites/physiology , Hydrogels , Animals
17.
Spectrochim Acta A Mol Biomol Spectrosc ; 316: 124346, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-38692105

ABSTRACT

Considering the health relevance of Chagas' disease, recent research efforts have focused on developing more efficient drug delivery systems containing nifurtimox (NFX). This paper comprehensively investigates NFX through conformational analysis and spectroscopic characterization. Using a conformer-rotamer ensemble sampling tool (CREST-xtb), five distinct conformers of NFX were sampled within a 3.0 kcal mol-1 relative energy window. Subsequently, such structures were used as inputs for geometry optimization by density functional theory (DFT) at B3LYP-def2-TZVP level of theory. Notably, harmonic vibrational frequencies were calculated to establish an in-depth comparison with experimental results and existing literature for the NFX or similar molecules and functional groups, thereby achieving a widely reasoned assignment of the mid-infrared band absorptions for the first time. Moreover, UV-VIS spectra of NFX were obtained in several solvents, enabling the determination of the molar absorptivity coefficient for the two electronic transitions observed for NFX. Among the aprotic solvents, a bathochromic effect was observed in the function of the dielectric constants. Furthermore, a hypochromic effect was observed when the drug was dissolved in protic solvents. These findings offer crucial support for new drug delivery systems containing NFX while demonstrating the potential of spectrophotometric studies in establishing quality control assays for NFX drug products.


Subject(s)
Chagas Disease , Molecular Conformation , Nifurtimox , Chagas Disease/drug therapy , Nifurtimox/chemistry , Spectrophotometry, Ultraviolet , Trypanocidal Agents/chemistry , Models, Molecular , Density Functional Theory , Trypanosoma cruzi/drug effects , Solvents/chemistry
18.
J. Am. Coll. Cardiol ; 83(13 Suppl. A)Apr. 2024. tab.
Article in English | CONASS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1551803

ABSTRACT

BACKGROUND: Intracardiac echocardiography (ICE) has improved catheter ablation procedures, reducing reliance on fluoroscopy. Yet, the efficacy and safety of zero-fluoroscopy (ZF) procedures remain uncertain. METHODS: We conducted a systematic review and meta-analysis comparing ZF ablation procedures guided by ICE vs. conventional techniques regarding efficacy and safety outcomes. PubMed, Cochrane, and embase were searched. A random-effects model was used to calculate risk ratios (RRs), odds ratios (OR) and mean differences (MDs) with 95% confidence intervals (CI). RESULTS: We includedfourteen studies with 1,919 patients of whom 1,023 (58.72%) performed ZF ablation using ICE. We found a significant reduced ablation time (SMD -0.18; 95% CI -0.31;-0.04; p=0.009), procedure time (MD -7.54; 95% CI -14.68;-0.41; p=0.04), fluoroscopic time (MD -2.52; 95% CI -3.20;-1.84; p<0.001) in patients treated with ZF approach compared with NZF approach. However, there was no significant difference between the two groups in acute success rate (RR 1.00; 95% CI 0.99-1.01; p=0.85), long-term success rate (RR 0.99; 95% CI 0.93-1.05; p=0.77) and complications (RR 0.84, 95% CI: 0.48-1.46; p = 0.54). CONCLUSION: Our findings suggest that among patients undergoing arrhythmia ablation, fluoroscopy-free ICE-guided technique reduces procedure time and radiation exposure with comparable short and long-term success rates and complications.


Subject(s)
Fluoroscopy
19.
J. Am. Coll. Cardiol ; 83(13 Suppl. A)Apr. 2024. tab.
Article in English | CONASS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1551808

ABSTRACT

BACKGROUND: Randomized studies support complete over culprit-only revascularization for patients with acute coronary syndrome (ACS) However,whether these findings extend to elderly patients has not been thoroughly explored. METHODS: We conducted a systematic review and meta-analysis comparing clinical outcomes of elderly individuals (defined as age > 75 years) with ACS and multivessel coronary artery disease submitted to complete vs. culprit-only percutaneous coronary intervention (PCI). PubMed, Embase, and Cochrane were searched. We computed pooled hazard ratios (HRs) with 95% confidence intervals (CI) to preserve time-to-event data RESULTS: We included 7 studies, of which 2 were randomized controlled trials (RCTs), comprising 7,409 patients, of whom 3225 (43.5%) underwent complete revascularization. As compared with culprit lesion only PCI, complete revascularization was associated with a lower risk of all-cause mortality (HR 0.76; 95% CI 0.68-0.85; p<0.001), cardiovascular mortality (HR 0.67; 95% CI 0.54-0.82; p<0.001), and recurrent myocardial infarction (MI) (HR 0.65; 95% CI 0.50-0.85; p=0.002). There was no significant difference between the groups regarding the risk of recurrent revascularizations (HR 0.79; 95% CI 0.54-1.16; p=0.23). CONCLUSION: Among elderly patients with ACS and multivessel CAD, complete revascularization is associated with a lower risk of all-cause mortality, cardiovascular mortality, and recurrent MI.


Subject(s)
Humans , Aged , Aged, 80 and over , Angioplasty, Balloon, Coronary , Acute Coronary Syndrome , Myocardial Revascularization
20.
J. Am. Coll. Cardiol ; 83(13 Suppl. A)Apr. 2024. tab.
Article in English | CONASS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1551797

ABSTRACT

BACKGROUND: Reflex syncope reduces quality of life and leads to fall-related injuries, with no highly effective treatment. In this context, cardioneuroablation (CNA) presents as a promising therapy for these patients. METHODS: We searched PubMed, Embase and Cochrane Central for studies that evaluated safety and efficacy outcomes related to CNA procedures. Two reviewers independently performed study selection, data extraction and assessment of bias. Generalized linear mixed models was used. We performed a single-arm meta-analysis using R version 4.2.3. RESULTS: A total of 25 studies comprising 871 patients were included. The mean follow-up ranged from 8 to 40 months. Mean age ranged from 32.9 to 53.9 years and 541 (62.1%) were female. The ablation target was biatrial in 302 patients (34%), left atrium only in 433 (49%), and right atrium only in 136 (15%). The freedom from syncope was 94% (95% confidence interval (CI) 90.13-97.00; P<0.01). Left and right atrial CNA was associated with a significant higher freedom from syncope (96.03%; 95% CI 93.13-97.73) than left atrial ablation only (94.61%; 95% CI 82.88-98.45) and right ablation only (84.53%; 95% CI 74.30-91.18). Peri-procedural adverse event occurred on 1.4% (95% CI 0.44- 4.50). CONCLUSION: Our findings suggest that in patients with reflex syncope, CNA is a procedure associated with a significant reduction in syncope incidence and with low complication rates. Among the procedures used, both right and left ablation were more effective.


Subject(s)
Catheter Ablation
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