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1.
Cell Rep ; 43(8): 114495, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39068661

RESUMO

The subthalamic nucleus (STN) is traditionally thought to restrict movement. Lesion or prolonged STN inhibition increases movement vigor and propensity, while optogenetic excitation has opposing effects. However, STN neurons often exhibit movement-related increases in firing. To address this paradox, STN activity was recorded and manipulated in head-fixed mice at rest and during self-initiated and self-paced treadmill locomotion. We found that (1) most STN neurons (type 1) exhibit locomotion-dependent increases in activity, with half firing preferentially during the propulsive phase of the contralateral locomotor cycle; (2) a minority of STN neurons exhibit dips in activity or are uncorrelated with movement; (3) brief optogenetic inhibition of the lateral STN (where type 1 neurons are concentrated) slows and prematurely terminates locomotion; and (4) in Q175 Huntington's disease mice, abnormally brief, low-velocity locomotion is associated with type 1 hypoactivity. Together, these data argue that movement-related increases in STN activity contribute to optimal locomotor performance.

2.
Acta Psychol (Amst) ; 248: 104423, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39068765

RESUMO

In this paper, we tested the idea that local changes in action demands (e.g., due to an invalid cue or trial-by-trial) result in frugal modifications of existing action plans via action-plan-modification operations. We implemented an experimental procedure making use of a cue that indicates the action requirements for an upcoming signal with a certain degree of reliability. Crucially, incongruent cue-stimulus pairs either require action-plan modification or "resetting" the prepared action plan and reselecting a new response from scratch. We systematically varied the proportion of valid cues over four experiments. There were four most basic response conditions: left button press, right button press, dual button presses, no action. Results support the concept of action-plan modification rather than reset-reselect: switching between a left and a right response was faster and less error-prone than any other type of switch, both between trials and between cue and signal. Thus, it appears that given two responses that can be conceived of as polar opposites (within the same single-action category), there is an action-plan-modification operation ("invert") that transforms one into the other at a comparatively low cost. Furthermore, we observed a mixed pattern of dual-action costs and benefits. This indicates that participants represented dual actions holistically, that is, not based on a conjunction of single-action plans as building blocks. In addition, switching from null actions to overt actions appeared to require very similar action-plan-modification operations as other types of switches - thus, null actions are apparently not coded as empty sets, but rather represent actions in their own right. Finally, we observed strikingly similar patterns of results for trial-by-trial changes in action demands and intra-trial cue-signal incongruency. This implies that the mere cue-based formulation of an action plan - which is not actually executed - is sufficient to produce action-switching-like effects.

3.
Complement Ther Clin Pract ; 57: 101888, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39068875

RESUMO

BACKGROUND: and Purpose: Pilates exercises have been recommended to improve postural balance and reduce the risk of falls in older adults. However, the certainty of these recommendations remains unclear. In this sense, our objective was to update the literature and verify the effects of Pilates on postural balance and the risk of falls in this population. METHODS: A systematic search was conducted across multiple databases, including PubMed, EMBASE, CENTRAL, CINAHL, Web of Science, SPORTDiscus, LILACS, and PEDro, on April 17, 2023. The methodological quality of the studies was assessed using the PEDro scale, and the certainty of evidence was evaluated using the GRADE system. Meta-analysis calculations were performed by standardized mean difference (SMD). RESULTS: A total of 39 studies, involving 1770 participants, were included in the systematic review. Only 14 studies exhibited satisfactory methodological quality. Evidence with very low to moderate certainty showed that Pilates was significantly superior to control groups on indicators of dynamic postural balance (SMD = 1.60 to 0.72), static postural balance (SMD = 0.37 to 0.25), and general state of balance (SMD = 0.76), but not to reduce the number and fear of falls. Furthermore, Pilates was comparable to other forms of exercise for these outcomes. CONCLUSIONS: Pilates can be recommended to enhance static and dynamic postural balance in older adults, but not to reduce the number of falls or the fear of falling. Given that no outcomes showed high certainty of evidence, future studies may alter these findings.

4.
Gene ; : 148797, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39068999

RESUMO

BACKGROUND: Strabismus is a complex oculomotor condition characterized by a misalignment of the visual axis. The genetics of strabismus are poorly defined although a few candidate genes have been identified, among which is the WNT2 gene. Our study was designed to assess the association of single nucleotide polymorphisms (SNPs) of WNT2 in Pakistani strabismus patients. METHODS: A total of six SNPs, three intronic and three in the 3́ untranslated region, were screened in the current study. Logistic regression was performed using a dominant, recessive and additive model to determine the association of SNPs with strabismus and its clinical subtypes: esotropia and exotropia. Furthermore, haplotype analysis was performed. RESULTS: Regression analysis revealed an association of rs2896218, rs3779550, rs2285544 and rs4730775 with strabismus under the dominant model. When analyzed separately, rs2896218 and rs2285544 were found to be associated with both esotropia and exotropia, while rs4730775 was significantly associated only with exotropia under the dominant model. Based on clinical parameters, rs2896218, rs2285544 and rs4730775 were also found to be associated with the group of strabismus patients who were diagnosed at birth, but not in the group of patients who were diagnosed later in life. Haplotype analysis revealed that the haplotype A T T (corresponding to rs2896218, rs3779550 and rs2285544) was significantly more prevalent in the strabismus group. CONCLUSION: Overall, the results of the present study suggest an association of WNT2 polymorphisms with strabismus and its subtypes in the Pakistani population, though further studies are needed to elucidate their role in strabismus etiology.

5.
J Hosp Infect ; 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39069006

RESUMO

BACKGROUND: Contact precautions (CP) are recommended when caring for patients with carbapenemase-producing Enterobacterales (CPE), carbapenemase-producing Pseudomonas aeruginosa (CPPA), and extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E). AIM: Our aim was to determine the interpretation of CP and associated infection prevention and control (IPC) measures in the non-ICU hospital setting for patients with CPE, CPPA or ESBL-E in 11 hospitals in the Southwest of the Netherlands. METHODS: A cross-sectional survey was developed to collect information on all implemented IPC measures, including use of personal protective equipment, IPC measures for visitors, cleaning and disinfection, precautions during outpatient care and follow-up strategies. All eleven hospitals were invited to participate between November 2020 and April 2021. FINDINGS: The survey was filled together with each hospital. All hospitals installed isolation precautions for patients with CPE and CPPA during inpatient care and day admissions, whereas ten hospitals (90.9%) applied isolation precautions for patients with ESBL-E. Gloves and gowns were always used during physical contact with the patient in isolation. Large variations were identified in IPC measures for visitors, cleaning and disinfection products used, and precautions during outpatient care. Four hospitals (36.4%) actively followed up on CPE or CPPA patients with the aim to declare them CPE- or CPPA-negative as timely as possible, and two hospitals (20.0%) actively followed up on ESBL-E patients. CONCLUSION: CP are interpreted differently between hospitals, leading to regional differences in IPC measures applied in clinical settings. Harmonizing infection-control policies between the hospitals could facilitate patient transfers and benefit collective efforts of preventing transmission of MDR-GNB.

6.
J Ethnopharmacol ; : 118615, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39069030

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Amomum villosum Lour. is a widely esteemed species of medicinal plant on a global scale. Its medicinal properties have been documented as early as the Tang Dynasty, particularly the fruit, which holds significant medicinal and culinary value. This plant is extensively found in tropical and subtropical regions across Asia. It possesses the properties of warming the middle and dispelling cold, regulating Qi to invigorate the spleen, harmonizing the stomach to alleviate vomiting, and nourishing deficiencies. In recent years, A. villosum has garnered global attention for its remarkable biological activity. Currently, numerous bioactive compounds have been successfully isolated and identified, showcasing a diverse array of pharmacological activities and medicinal benefits. AIM OF THE WORK: This review aims to provide a comprehensive analysis of the research advancements in the geographical distribution, botany, traditional applications, phytochemistry, pharmacological activity, quality control, clinical applications, and toxicology of A. villosum. Furthermore, a critical summary of the current research and future prospects of this plant is presented. MATERIALS AND METHODS: Obtain information about A. villosum from ancient literature, doctoral and master's theses, and scholarly databases including Google Scholar, Web of Science, PubMed, China National Knowledge Infrastructure (CNKI), ScienceDirect, plant directories, and clinical reports. RESULTS: At present, about 500 compounds have been isolated and identified from various organs of A. villosum, including monoterpenoids, sesquiterpenoids, diterpenoids, flavonoids, phenols, polysaccharides, and other components. Modern pharmacological studies have revealed that A. villosum exhibits exceptional biological activities in vitro and in vivo, such as anti-inflammatory, antioxidant, liver protection, anti-tumor, hypoglycemic, anti-microbial, regulating gastrointestinal activity, immune regulation, regulating flora, anti-obesity, estrogen, and more. Some of these activities have found extensive application in clinical practice. CONCLUSION: A. villosum, as a well-established medicinal herb, holds significant therapeutic potential and is also valued for its culinary applications. Currently, the research on the active components or crude extracts of A. villosum and their potential mechanisms of action remains limited. Furthermore, certain pharmacological activities require further elucidation for a comprehensive understanding of its internal mechanisms. Moreover, it is strongly recommended to prioritize research on pharmacokinetics and toxicity studies. These efforts will facilitate a thorough exploration of the potential of A. villosum and establish a robust foundation for its potential clinical applications.

7.
Clin Chest Med ; 45(3): 611-623, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39069325

RESUMO

This article is a comprehensive review of the latest knowledge and developments on pediatric asthma. It serves as a guide for general practitioners and subspecialists who treat asthma. The pathophysiology and critical features of asthma that should be addressed and the latest therapies available are discussed. The areas where further investigation is needed are also highlighted.


Assuntos
Antiasmáticos , Asma , Humanos , Asma/terapia , Asma/fisiopatologia , Asma/diagnóstico , Criança , Antiasmáticos/uso terapêutico
8.
Trends Cell Biol ; 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39069439

RESUMO

High-risk human papillomaviruses (HPVs) cause most cases of cervical cancer, a disease with an increasing impact worldwide. Recent studies have shown that the synthesis of viral oncoproteins is strongly subject to translational control. Thus, targeting the protein synthesis machinery might open novel avenues to develop innovative therapies aiming to improve patients' survival.

9.
ISA Trans ; 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39069453

RESUMO

The optimal control design of the boiler-turbine system is vital to ensure feasibility and high responsiveness over desired load variations. Using the traditional linear control techniques realization of this task is difficult, as the boiler-turbine mechanism has strong nonlinearities. Besides, environmental and economic concerns have replaced existing tracking control ones as the primary concerns of advanced power plants. Thus, this study proposes an optimal economic model predictive controller (EMPC) scheme for this unit on the basis of the input/output feedback linearization (IOFL) method. By employing the IOFL method, this unit is decoupled into a new linearized model that is utilized for developing the suggested optimal IOFL EMPC technique. The proposed control scheme is formulated in an economic quadratic programming form that considers the input-rate and input limits of the unit for optimal economic performance. In addition, an adaptive iterative algorithm is utilized for constraints mapping with guaranteeing a feasible solution in a finite number of steps without violation of original constraints over the entire predictive horizon. The outcomes of the simulation show that the suggested optimal IOFL EMPC scheme offers an improved dynamic and economic output performance over fuzzy hierarchical MPC, fuzzy EMPC, and nonlinear EMPC techniques during various load variations.

10.
BMC Infect Dis ; 24(1): 743, 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39069620

RESUMO

BACKGROUND: Cysticercosis is a zoonotic parasitic disease that poses a serious threat to public health. It is widely distributed and has a high incidence rate in China. Reports of disseminated cysticercosis worldwide are rare. This article presents a case of disseminated cysticercosis in the Guangxi Zhuang Autonomous Region of southwestern China. CASE PRESENTATION: The patient, a 46-year-old male belonging to the Miao ethnic group, hailed from a region in Guangxi Zhuang Autonomous Region known for its high incidence of cysticercosis. He had a habit of consuming raw pork and beef. With a history of recurrent consciousness disturbances and limb convulsions for five years, he presented with headaches and dizziness nine days prior. Comprehensive examinations were conducted on the patient. Ultimately, based on epidemiological history, imaging findings, pathogen testing, and pathological results, he was diagnosed with disseminated cysticercosis. Following anthelmintic treatment, the patient was discharged with clear consciousness, free from headaches, dizziness, nausea, vomiting, and seizures. The patient is currently under follow-up care. CONCLUSION: It is crucial to enhance public awareness, promote health education, and cultivate good hygiene habits, as these are essential measures in reducing the incidence of cysticercosis.


Assuntos
Cisticercose , Humanos , Masculino , Pessoa de Meia-Idade , China/epidemiologia , Cisticercose/epidemiologia , Cisticercose/tratamento farmacológico , Cisticercose/diagnóstico , Animais , Anti-Helmínticos/uso terapêutico
11.
Philos Trans A Math Phys Eng Sci ; 382(2278): 20230369, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39069760

RESUMO

The concept of metamaterial recently emerged as a new frontier of scientific research, encompassing physics, materials science and engineering. In a broad sense, a metamaterial indicates an engineered material with exotic properties not found in nature, obtained by appropriate architecture either at macro-scale or at micro-/nano-scales. The architecture of metamaterials can be tailored to open unforeseen opportunities for mechanical and acoustic applications, as demonstrated by an impressive and increasing number of studies. Building on this knowledge, this theme issue aims to gather cutting-edge theoretical, computational and experimental studies on elastic and acoustic metamaterials, with the purpose of offering a wide perspective on recent achievements and future challenges. This article is part of the theme issue 'Current developments in elastic and acoustic metamaterials science (Part 1)'.

12.
Games Health J ; 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39069879

RESUMO

Objective: The present study was conducted to evaluate the effects of video-based exercises added to conventional physiotherapy (CPT) on upper extremity functionality, selective motor control, and proprioception in individuals with unilateral cerebral palsy (UCP). Materials and Methods: Thirty patients with UCP were randomized into two groups: the intervention group (15 individuals with a mean age of 9.2 ± 3.8 years) and the control group (15 individuals with a mean age of 8.3 ± 4.1 years). The intervention group received 8 weeks of video-based exercises, and the control group received 8 weeks of conventional physiotherapy. Upper extremity functional abilities, upper extremity selective motor control, proprioception, and entertainment levels were evaluated before and after the intervention for all groups. Results: While a significant change was observed in the mean scores of the ABILHAND-Kids, Selective Control of the Upper Extremity Scale right-left scores, shoulder flexion, shoulder abduction, and elbow flexion proprioception angles after the video-based exercises in the intervention group (P < 0.05), a significant change was observed only in the 60-degree flexion angle in the control group (P = 0.001). In the comparison between the groups, there were significant differences in post-intervention value only in shoulder flexion and abduction angles, whereas there was no difference between the groups in elbow flexion angles (P > 0.05). Conclusion: Incorporating video-based exercises into the upper extremity rehabilitation processes of individuals with UCP is beneficial in terms of upper extremity functionality, selective motor control, and proprioception.

13.
J Clin Sleep Med ; 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39069967

RESUMO

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a highly prevalent disorder with serious health consequences but limited therapeutic options. For a subset of those with OSA, a key underlying mechanism is hypersensitive chemoreflex control of breathing. There is no approved therapy that targets this endotypic trait. Here we determine whether the P2X3 receptor antagonist gefapixant, which is predicted to attenuate hypersensitive carotid chemoreflexes, reduces OSA severity in patients with chemoreflex-dependent OSA. METHODS: In a randomized placebo-controlled cross-over study, 24 patients with moderate-to-severe OSA (aged 39-68 years, non-CPAP users) whose disorder was partially responsive to supplemental oxygen (chemoreflex-dependent OSA) were treated with gefapixant 180 mg (or placebo) administered as tablets taken orally before bedtime for 7 days and assessed via overnight polysomnography. The primary analysis examined whether gefapixant treatment resulted in a greater reduction in the apnea-hypopnea index (AHI) from baseline than placebo. RESULTS: Gefapixant did not lower the AHI significantly more than placebo; the estimated ratio of the AHI on gefapixant versus placebo was 0.92 [90% CI: 0.73, 1.17]. Notably, nocturnal hypoxemia was increased (ratio of total sleep time with SpO2 <90% on gefapixant versus placebo = 2.08 [90% CI: 1.53, 2.82]), consistent with reduced chemoreflex output. Commonly reported adverse events with gefapixant included ageusia, dysgeusia, oral hypoaesthesia, nausea, somnolence, and taste disorders. CONCLUSIONS: Gefapixant, while generally well tolerated, did not reduce OSA severity in patients with chemoreflex-dependent OSA. P2X3 receptor antagonism is unlikely to provide an avenue for therapeutic intervention in OSA. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Safety and Tolerability of Gefapixant (MK-7264) in Participants With Obstructive Sleep Apnea (MK-7264-039); URL: https://clinicaltrials.gov/study/NCT03882801; Identifier: NCT03882801.

14.
Psychol Res Behav Manag ; 17: 2757-2767, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39070067

RESUMO

Purpose: Psychosocial determinants influence healthcare workers' compliance with surgical site infection (SSI) preventive interventions. In order to design needs-based interventions promoting compliance, such determinants must first be assessed using valid and reliable questionnaire scales. To compare professional groups without bias, the scales must also be measurement-equivalent. We examine the validity/reliability and measurement equivalence of four scales using data from physicians and nurses from outside the university sector. Additionally, we explore associations with self-reported SSI preventive compliance. Participants and Methods: N = 90 physicians and N = 193 nurses (response rate: 31.5%) from nine general/visceral or orthopedic/trauma surgery departments in six non-university hospitals in Germany participated. A written questionnaire was used to assess the compliance with SSI preventive interventions and the determinants of compliance based on the Capability-Opportunity-Motivation-Behavior-Model. Psychometric testing involved single- and multiple-group confirmatory factor analyses, and explorative analyses used t-tests and multiple linear regression. Results: The scales assessing individual determinants of compliance (capability, motivation, and planning) were found to be reliable (each Cronbach's α ≥ 0.85) and valid (each Root-Mean-Square-Error of Approximation ≤ 0.065, each Comparative-Fit-Index = 0.95) and revealed measurement equivalence for physicians and nurses. The scale assessing external determinants (opportunity) did not demonstrate validity, reliability, or measurement equivalence. Group differences were found neither in compliance (p = 0.627) nor determinants (p = 0.192; p = 0.866; p = 0.964). Capability (ß = 0.301) and planning (ß = 0.201) showed associations with compliance for nurses only. Conclusion: The scales assessing motivation, capability, and planning regarding SSI preventive compliance provided reliable and valid scores for physicians and nurses in surgery. Measurement equivalence allows group comparisons of scale means to be interpreted without bias.

15.
Ann Glob Health ; 90(1): 46, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39070078

RESUMO

Background: Nurses play a pivotal role in combating antimicrobial resistance (AMR). However, the success of local and national AMR containment efforts hinges on the knowledge, attitude, and practice (KAP) of nursing staff and undergraduate students. Objectives: This study aims to explore the determinants of nurses' KAP regarding AMR, offering insights to control the emergence and spread of drug-resistant pathogens. Methods: This cross-sectional, multicenter survey involving Italian nurses, nursing students, and healthcare professionals was conducted administering an anonymous online questionnaire focusing on AMR. The median score of 12 was taken as the cutoff for "good KAP." The association between study variables and good KAP was assessed using chi-square or t-tests, followed by multivariable logistic regression analysis for statistically significant (p < 0.05) variables. Findings: Among 848 participants, 61.9% (n = 525) were students, and 39.6% (n = 336) scored as having "low KAP." High KAP was associated with being female and studying AMR independently. Conversely, living in southern Italy and receiving AMR training from pharmaceutical companies were associated with low KAP. Conclusions: Among Italian nurses, AMR awareness relies on those who have studied AMR as self-taught and is affected by gender and region. Italian universities lack in lectures on AMR management, and much needs to be done to improve awareness of antimicrobial stewardship among nonmedical health workers.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Estudantes de Enfermagem , Humanos , Estudos Transversais , Feminino , Itália , Masculino , Adulto , Adulto Jovem , Inquéritos e Questionários , Enfermeiras e Enfermeiros , Atitude do Pessoal de Saúde , Pessoa de Meia-Idade , Modelos Logísticos , Fatores Sexuais
16.
Front Sports Act Living ; 6: 1421881, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39070234

RESUMO

Introduction: Differences in motor control between the lower limbs may influence the risk of sports injury and recovery from rehabilitation. In this study, differences in the visual feedback ability of the left and right lower limbs were assessed using visual target tracking tasks. Methods: Thirty-four healthy young subjects (aged 20.4 ± 1.2 years) were asked to move their bodies back and forth while tracking a visual target displayed on a monitor in front of them for 30 s. The two target motions were sinusoidal (i.e., predictable patterns) and more complex (random) patterns. To assess the ability of the lower limbs to follow visual target tracking, antero-posterior CoP (right limb, CoPap-r; left limb, CoPap-l) and medio-lateral CoP (right limb, CoPml-r; left limb, CoPml-l) data were measured using a stabilometer. Tracking ability by visual feedback ability was calculated as the difference in displacement between the target signal and the trajectories of the right and left pressure centers as trapezoidal areas, and a smaller sum of area (SoA) over the entire measurement time was defined as a greater tracking ability. Results: Regarding the SoA in the anterior-posterior CoP, the mean SoA in the sinusoidal and random tasks was significantly lower in the CoP-r data than in the CoP-l data, indicating that the right lower limb had a more remarkable ability to follow visual target tracking. Regarding the SoA in the medial-lateral direction (CoP), the mean SoA in the sinusoidal and random tasks did not significantly differ between the two legs. Discussion: The right lower limb may have a tracking function activated by the target signal when responding to visual stimuli. Identifying the motor strategies of each lower limb in response to visual stimuli will not only help identify potential differences between each lower limb but also suggest the possibility of enhancing the role of each lower limb in balance control.

17.
Artigo em Inglês | MEDLINE | ID: mdl-39070230

RESUMO

Mosquito control, which is not always easily accomplished, is further complicated by the spread of invasive species. This is the case of Aedes koreicus, a mosquito native to East Asia, whose presence has been recorded in several European countries, including Italy. This mosquito found suitable ecological conditions in central Europe in general, and in northern Italy in particular, as shown by the ongoing expansion of its distribution. While basic knowledge on feeding habits of Ae. koreicus have already been acquired, information on its vectorial competence is scarce. Therefore, active monitoring on the presence of this mosquito, and the pre-planning of future control actions, are of paramount importance. Currently, there are no specific guidelines for controlling this mosquito, both in its native regions and in invaded countries. Here we present the first study on the efficacy of a bioinsecticide based on Bacillus thuringiensis on Ae. koreicus larvae, with a comparison with results obtained on the tiger mosquito Aedes albopictus. Our results proved that this bioinsecticide is effective on Ae. koreicus, both dissolved in water and incorporated into MosChito raft, a hydrogel-based matrix that has recently been developed for the delivery of insecticides to other mosquito species and suitable for safe and eco-compatible applications.

18.
Front Microbiol ; 15: 1425790, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39070265

RESUMO

Aflatoxins (AFs) are highly carcinogenic metabolites produced by Aspergillus species that can contaminate critical food staples, leading to significant health and economic risks. The cytochrome P450 monooxygenase AflG catalyzes an early step in AF biosynthesis, resulting in the conversion of averantin (AVN) to 5'-hydroxy-averantin. However, the molecular mechanism underlying the AflG-AVN interaction remains unclear. Here, we sought to understand the structural features of AflG in complex with AVN to enable the identification of inhibitors targeting the AflG binding pocket. To achieve this goal, we employed a comprehensive approach combining computational and experimental methods. Structural modeling and microsecond-scale molecular dynamics (MD) simulations yielded new insights into AflG architecture and unveiled unique ligand binding conformations of the AflG-AVN complex. High-throughput virtual screening of more than 1.3 million compounds pinpointed specific subsets with favorable predicted docking scores. The resulting compounds were ranked based on binding free energy calculations and evaluated with MD simulations and in vitro experiments with Aspergillus flavus. Our results revealed two compounds significantly inhibited AF biosynthesis. Comprehensive structural analysis elucidated the binding sites of competitive inhibitors and demonstrated their regulation of AflG dynamics. This structure-guided pipeline successfully enabled the identification of novel AflG inhibitors and provided novel molecular insights that will guide future efforts to develop effective therapeutics that prevent AF contamination.

19.
Cureus ; 16(6): e63365, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39070431

RESUMO

Background Multiple myeloma is a crippling cancer that puts a significant strain on patients and their families alike. The long and exhausting treatment journey with the disease is challenging not only for patients but also for healthcare systems. This exploratory study was conducted to look into these patients' experiences with their treatment and explore their recommendations and views to improve the Palestinian healthcare system, which can be viewed as an evolving healthcare system within a resource-limited and developing country. Methods The consolidated criteria for reporting qualitative research (COREQ) checklist was used for conducting this multicenter exploratory qualitative study. A total number of eight patients with multiple myeloma who received treatment in the Palestinian healthcare system participated in semi-structured in-depth interviews. The semi-structured in-depth interviews followed a set interview schedule. Thematic analysis of the data was done using the qualitative interpretive description approach. Results A total of 5.48 h (329 min) of total interview time was analyzed. Among the patients, 6 (75%) were males, 5 (63.5%) lived in urban areas, 5 (62.5%) reported satisfaction with their household income, 6 (75%) underwent bone marrow transplantation, and all of them (100%) had governmental insurance. The qualitative data that emerged after analysis were classified into three major themes and multiple sub-themes. The three major themes were: (1) treatment side effects, (2) factors affecting treatment experience, and (3) recommendations to improve healthcare service. Conclusion The results of this qualitative study offer insight into how people with multiple myeloma view the healthcare system in Palestine and shed light on the variable and challenging experiences with their treatment, side effects, and communication with healthcare providers within the context of a resource-limited and developing country. Future research should involve hemato-oncology doctors and benefit from their expertise in the field.

20.
Cureus ; 16(6): e63162, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39070449

RESUMO

Background Malaria is a vector-borne disease transmitted by female anopheline mosquitoes. It is also a multidimensional disease influenced by social factors such as poor environmental conditions and awareness gaps. India has witnessed a substantial reduction in malaria cases and has declared three regions as malaria-free, with Karnataka being one of the states. However, Karnataka witnesses significant population movement and migration, which influences the spread of malaria. Ramanagara, a district in Karnataka, reported zero indigenous cases over the past three years. Hence, we selected this district to evaluate outbreak preparedness to prevent the reintroduction of malaria. This choice underscores the district's significance as a valuable model for preventing the reintroduction of malaria. Methodology Baseline survey data on malaria cases and vector survey data were evaluated for the period spanning 2018 to 2022. The data were gathered from both the regional office and the Ramanagara district health office. In addition to the documenting system, because there was no regular submission of Form-P and Form-L of the Integrated Disease Surveillance Project and Integrated Health Information Platform from the private sector, to complete the missing data, a cross-sectional study was conducted among private sector practitioners and pharmacies in Ramanagara from April 2023 to June 2023. Data was collected via interviews using a malaria surveillance assessment toolkit sourced from the National Centre for Vector Borne Diseases Control and World Health Organization protocols to assess six core areas of malaria elimination. Data collected via interviews were compiled in MS Excel and analyzed using SPSS Statistics for Windows, version 26.0 (IBM Corp., Armonk, NY, USA). Results Malaria control measures in the selected district achieved >80% coverage with notable improvements in the National Health Mission-National Vector Borne Disease Control Programme fund utilization, logistics availability, and physical performance over the past five years. The Annual Parasite Index was <1 at 0.0061 in 2018 and 0.0017 in 2022. The annual blood examination rate was consistently >10 from 22.05 in 2018 to 24.36 in 2022. The primary vectors identified were Anopheles culicifacies and Anopheles stephensi. In 2018, there were six cases of Plasmodium vivax and one case of Plasmodium falciparum reported as imported cases. In 2021 and 2022, two cases of P. vivax were reported. Notably, there were no instances of mixed infections or indigenous cases documented from 2018 to 2022 Conclusions Although the level of outbreak preparedness in the region is satisfactory, the effectiveness of vector control measures appears to be lacking. Increased government funding is needed along with comprehensive training and workshops for healthcare workers. Adequate financial resources and enhanced skills among healthcare workers are crucial to reinforce the existing efforts to control vectors and prevent potential outbreaks effectively.

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