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This paper describes an application of genetic algorithms to the bus driver scheduling problem. The application of genetic algorithms extends the traditional approach of Set Coveting/Set Partitioning formulations, allowing the simultaneous consideration of several complex criteria. The genetic algorithm is integrated in a DSS but can be used as a very interactive tool or a stand-alone application. It incorporates the user's knowledge in a quite natural way and produces solutions that are almost directly implemented by the transport companies in their operational planning processes. Computational results with airline and bus crew scheduling problems from real world companies are presented and discussed. Keywords: genetic algorithms; bus driver scheduling problem; decision support systems

Dichloro(l-histidine)copper(II) crystal ([Cu(l-His)Cl 2 ] complex) was obtained by the slow evaporation method and characterized concerning its thermal stability, phase transformations, and electronic and vibrational properties. X-ray diffraction (XRPD) confirmed that this complex crystallizes with an orthorhombic structure ( P 2 1 2 1 2 1 space group). Thermal analyses (TG and DTA) demonstrate stability from ambient temperature up to 460 K, followed by a phase transition from the orthorhombic structure to the amorphous form around 465 K, as confirmed by temperature-dependent XRPD studies. The active modes in Fourier transform infrared (FT-IR) and Raman spectroscopy spectra were suitably assigned via density functional theory (DFT) calculations. Additionally, Hirshfeld surface analysis uncovered the prominence of Cl···H, O···H, and H···H interactions as the primary intermolecular forces within the crystal structure. The antimicrobial activity of the [Cu(l-His)Cl 2 ] complex was investigated, demonstrating significant efficacy against Gram-positive bacteria ( Staphylococcus aureus ), Gram-negative bacteria ( Pseudomonas aeruginosa ), and fungi ( Candida albicans ). The minimum inhibitory concentration and cell viability tests showed that the complex inhibits the growth of S. aureus bacteria at a concentration of 1.5 μM without causing damage to the human cell line. The pharmacokinetic parameters corroborate the other tested parameters and highlight the [Cu(l-His)Cl 2 ] complex as a promising alternative for future clinical trials and medicinal applications. The alignment of the pharmacokinetic parameters with other tested criteria highlights the potential of the [Cu(l-His)Cl 2 ] complex as a promising candidate for future clinical studies., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

As resistance to conventional antibiotics among bacteria continues to increase, researchers are increasingly focusing on alternative strategies for preventing and treating bacterial infections, one of which is microbiota modulation. The objective of this review is to analyze the scientific literature on the immunomodulatory effects of probiotics in bacterial infections. This is an integrative review of the literature based on systematic steps, with searches performed in the databases Medline, PubMed, Scopus, Embase, and ScienceDirect. The most prevalent bacterial genera used to evaluate infectious processes were Salmonella, Escherichia, Klebsiella, and Streptococcus. Lactobacillus was the most commonly used probiotic genus, with Lactobacillus delbrueckii subsp. bulgaricus is the most frequently used species. In most studies, prophylactic treatment with concentrations of probiotics equal to or greater than 8 log CFU/mL was chosen. However, there was considerable heterogeneity in terms of effective treatment duration, indicating that the results cannot be generalized across all studies. This review found that probiotics interact with the immune system through different mechanisms and have a positive effect on preventing different types of bacterial infections., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Sepsis treatment is a challenging condition due to its complexity, which involves host inflammatory responses to a severe and potentially fatal infection, associated with organ dysfunction. The aim of this study was to analyze the scientific literature on the immunomodulatory effects of glucans in a murine model of systemic infection induced by cecal ligation and puncture. This study comprises an integrative literature review based on systematic steps, with searches carried out in the PubMed, ScienceDirect, Scopus, Web of Science, and Embase databases. In most studies, the main type of glucan investigated was β -glucan, at 50 mg/kg, and a reduction of inflammatory responses was identified, minimizing the occurrence of tissue damage leading to increased animal survival. Based on the data obtained and discussed in this review, glucans represent a promising biotechnological alternative to modulate the immune response and could potentially be used in the clinical management of septic individuals., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Jesse P. M. Viana et al.)

Leishmaniasis is caused by protozoans of the genus Leishmania , and its treatment is highly toxic, leading to treatment discontinuation and the emergence of resistant strains. In this study, we assessed the leishmanicidal activity and chemical composition of red propolis collected from the Amazon-dominated region of northern Tocantins State, Brazil. The MTT assay was employed to determine the samples' activity against Leishmania amazonensis promastigotes and their cytotoxicity against RAW macrophages. Spectrophotometric assays were utilised to measure the concentrations of total phenolics and flavonoids, while high-performance liquid chromatography coupled to a mass spectrometer (LC-MS/MS) was used to determine the chemical composition. An in silico study was conducted to evaluate which compounds from Brazilian Amazon red propolis may correlate with this biological activity. Brazilian Amazon red propolis exhibited a high concentration of phenolic compounds and an inhibitory activity against L. amazonensis , with an IC 50 ranging from 23.37 to 36.10 µg/mL. Moreover, fractionation of the propolis yielded a fraction with enhanced bioactivity (16.11 µg/mL). Interestingly, neither the propolis nor its most active fraction showed cytotoxicity towards macrophages at concentrations up to 200 µg/mL. The red colour and the presence of isoflavonoid components (isoflavones, isoflavans, and pterocarpans) confirm that the substance is Brazilian red propolis. However, the absence of polyprenylated benzophenones suggests that this is a new variety of Brazilian red propolis. The in silico study performed with two of the main leishmanicidal drug targets using all compounds identified in Amazon red propolis reported that liquiritigenin was the compound that exhibited the best electronic interaction parameters, which was confirmed in an assay with promastigotes using a standard. The findings indicate that Amazon red propolis possesses leishmanicidal activity, low toxicity, and significant biotechnological potential.

Due to an increase in population, urban centers are currently seeing an increase in traffic, resulting in negative consequences such as pollution and congestion. Efforts have been made to promote a modal shift towards the use of more sustainable means of transport, such as walking and cycling, but several deterrents influence the citizens' perceptions of safety, security and comfort, discouraging their choice of active modes of transport. This study focuses on the importance of providing meaningful information to vulnerable road users (VRUs) to support their perceptions and objectives while moving within urban spaces through a novel concept of route planning. A broad survey of the needs and concerns of VRUs through interviews, focus groups and questionnaires, applied to the Portuguese population of the Metropolitan Area of Porto, led to the development of a new concept of route planners that show personalized routes according to the individual perceptions of each user. This concept is materialized in a route planner prototype that has been extensively tested by potential users. Subjective evaluation and feedback showed the usefulness of the concept and added value to a familiar product, leading to a satisfying experience for participants. This study shows that there is an opportunity to improve these tools to provide a higher degree of power and customization to users on route planning, which includes addressing mobility restrictions and personal perceptions of safety, security and comfort. The ultimate goal of this new approach is to persuade citizens to switch to more sustainable means of transport.

Background: Managing HIV infection as a chronic condition includes encouraging adoption of healthy behaviors and promotion of physical activity (PA). However, people living with HIV (PLH) are often under social and programmatic vulnerability that may compromise behavior change. Understanding such barriers is crucial for successful incorporation of PA in their comprehensive care., Methods and Findings: In this study, we describe PA, energy intake from diet, and anthropometry of a cohort of PLH starting antiretroviral therapy (ART) at a Brazilian reference clinic, report how PA was addressed in routine care and investigate association between PA, energy intake and psychosocial constructs that may facilitate PA (social support and self-efficacy for PA). Among 61 PLH (86.9% males, mean age = 32.5 years) anthropometry was normal, but 47.5% reported PA below recommendations. Despite presenting high social support scores, family encouragement for PA was low, and self-efficacy classified as medium. Chart reviews yielded infrequent reports concerning PA. After adjusting for gender and age, we found a negative association between energy intake from diet and self-efficacy, but none between PA and energy intake or between PA and psychosocial constructs., Conclusions: We conclude that patients in our cohort were insufficiently active when starting ART, and that PA was poorly addressed by caretakers in routine HIV care. Nevertheless, social support and self-efficacy scores suggest potential for behavioral change. Caregivers should therefore start considering patients' vulnerabilities and establishing strategies to help them overcome barriers to incorporate PA in their comprehensive care effectively., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Comprehensive care for people living with human immunodeficiency virus (HIV) (PLH) includes the promotion of healthier habits, including physical activity (PA). This study aimed to describe a multicomponent pragmatic trial protocol to assess the effect of PA in preventing body changes and metabolic disturbances, improving the quality of life of PLH starting antiretroviral therapy (ART) and present cohort characteristics., Methods: PLH undergoing ART for ≤4 months were recruited for a randomized trial. The intervention comprised three cardiorespiratory and/or strength training sessions per week at the clinic or in public spaces for 6 months under on-site or remote supervision, and educational sessions. Participants' PA levels, cardiorespiratory fitness, anthropometric measures, strength, flexibility, quality of life, and laboratory monitoring (blood glucose and lipids, CD4 counts) at baseline and post-intervention will be compared. The pragmatic design aims to enable the assessment of intervention effectiveness in real-life conditions., Results: At baseline, our cohort of 38 recently diagnosed patients (mean time since HIV diagnosis and duration of ART were 3 and 2.58 months, respectively) were predominantly male, young, with high schooling and good immune status (median CD4 count=498 cells/mm3). Twenty-two (57.9%) patients reported a PA below the World Health Organization recommendations. We found baseline normal anthropometric measures and metabolic parameters: below-average trunk flexion and elbow extension strength, poor handgrip strength and flexibility, and high quality of life scores in all except the physical domain., Conclusions: Understanding how effective PA is in preventing body changes and metabolic disturbances, and in improving the quality of PLH starting ART may help establish guidelines to better incorporate PA in HIV care.

Objective: To investigate the temporal trend of practicing physical exercise and sports during leisure time in adults in São Paulo between 2006 to 2016., Methods: Time series analysis study using the VIGITEL System. Adding up the number of people who participated each year, a total 21,357 people were studied. Analyzes of the physical exercises and sports practiced during leisure time (yes or no) stratified by sex, age and education were performed. The prevalences and the differences for all of the years were calculated using the Prains-Winster regression., Results: Practice of physical exercises or sports increased by 7.9 percentage points in the period (p = 0.003) (from 39.9% 95%CI 37.4 - 42.4 to 47.8% 95%CI 45.2 - 50.4). There was a significant increase for women (p = 0.011), for people between 18-24 years old (p = 0.001), 25-34 years old (p = 0.003), 45-54 years old (p = 0.003), and for people with up to eight years of schooling (p = 0.010). There was a decrease in walking and playing soccer and there was an increase in doing gymnastics., Conclusion: There was an increase in the practice of physical exercise and sports during leisure time in adults from São Paulo. These increases were observed mainly in women, in people between 18 and 34 years old, between 45 and 54 years old, and in people with up to eight years of schooling. These results are important, as they have shown an increase in general and in more vulnerable groups, and may be related to environmental changes and interventions that have occurred in the city in the last 15 years.

Objectives: Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that consists of applying a weak electric current over the scalp to modulate cortical excitability. tDCS has been extensively investigated in adults with psychiatric disorders. The aim of this study was to review the current literature regarding the use of tDCS in children and adolescents with psychiatric disorders., Methods: We searched MEDLINE and EMBASE databases for studies evaluating the safety and efficacy of tDCS in children and adolescents from age 0 to 18 years with psychiatric disorders., Results: We found six studies that evaluated patients with different psychiatric disorders, with diverse study designs and stimulation parameters, including three small randomized clinical trials (RCTs), one evaluating childhood-onset schizophrenia, one RCT with patients with autism spectrum disorders (ASD), and one study in attention-deficit/hyperactivity disorder (ADHD); three open-label studies, two evaluating patients with ASD, and one study of feasibility of the technique in children and adolescents with language disorders and diverse psychiatric disorders, including ASD, intellectual disability, and ADHD. We also found three studies of dosage considerations in the general pediatric population. The technique was well tolerated, with no reports of serious side effects., Conclusion: Preliminary research suggests that tDCS may be well tolerated and safe for children and adolescents with psychiatric and neurodevelopmental disorders. Nevertheless, because the literature regarding tDCS in child and adolescent psychiatry is scarce and there exist limited numbers of randomized controlled trials, it is not possible to draw definite conclusions. Future studies should investigate the technique with regard to specific psychiatric conditions in comparison with standard treatments. In addition, long-term efficacy and safety should be monitored.

Objective: The aim of this randomized, double-blind, controlled trial was to compare the computed and conventional inferior alveolar nerve block techniques in symmetrically positioned inferior third molars., Patients and Methods: Both computed and conventional anesthetic techniques were performed in 29 healthy patients (58 surgeries) aged between 18 and 40 years. The anesthetic of choice was 2% lidocaine with 1: 200,000 epinephrine. The Visual Analogue Scale assessed the pain variable after anesthetic infiltration. Patient satisfaction was evaluated using the Likert Scale. Heart and respiratory rates, mean time to perform technique, and the need for additional anesthesia were also evaluated., Results: Pain variable means were higher for the conventional technique as compared with computed, 3.45 ± 2.73 and 2.86 ± 1.96, respectively, but no statistically significant differences were found (P > 0.05). Patient satisfaction showed no statistically significant differences. The average computed technique runtime and the conventional were 3.85 and 1.61 minutes, respectively, showing statistically significant differences (P <0.001)., Conclusions: The computed anesthetic technique showed lower mean pain perception, but did not show statistically significant differences when contrasted to the conventional technique.

The aim of the present study was to compare hemodynamic changes using midazolam 7.5 mg and diazepam 10.0 mg during the surgical removal of symmetrically positioned third molars. A prospective, randomized, double-blind, clinical trial was carried out involving 120 patients divided into three groups: Group 1 (diazepam and placebo), Group 2 (midazolam and placebo), and Group 3 (diazepam and midazolam). Each subject underwent two surgeries on separate occasions under local anesthesia. The following parameters were assessed at five different times (T0, T1, T2, T3, and T4): systolic, diastolic, and mean blood pressure (SBP, DBP, and MBP, respectively); heart rate (HR); oxygen saturation (SpO(2)); rate pressure product (RPP); and pressure rate quotient (PRQ). Statistically significant differences were found regarding heart rate at T2 and T3 (p < 0.005) in Group 2, with a higher rate occurring during midazolam administration. Moreover, significant differences in rate pressure product were found at T2, T3, and T4 in this group, with higher values also occurring during midazolam administration. In Group 3, significant differences in diastolic blood pressure were found at T3 and T4, with higher values occurring during diazepam administration, whereas a higher heart rate occurred at T3 with midazolam. Midazolam 7.5 mg and diazepam 10.0 mg exert an influence on some hemodynamic parameters without perceptible clinical changes in healthy patients undergoing lower third molar surgery.

One potential obstacle limiting our ability to clarify ADHD etiology is the heterogeneity within the disorder, as well as in typical samples. In this study, we utilized a community detection approach on 106 children with and without ADHD (aged 7-12 years), in order to identify potential subgroups of participants based on the connectivity of the reward system. Children with ADHD were compared to typically developing children within each identified community, aiming to find the community-specific ADHD characteristics. Furthermore, to assess how the organization in subgroups relates to behavior, we evaluated delay-discounting gradient and impulsivity-related temperament traits within each community. We found that discrete subgroups were identified that characterized distinct connectivity profiles in the reward system. Importantly, which connections were atypical in ADHD relative to the control children were specific to the community membership. Our findings showed that children with ADHD and typically developing children could be classified into distinct subgroups according to brain functional connectivity. Results also suggested that the differentiation in "functional" subgroups is related to specific behavioral characteristics, in this case impulsivity. Thus, combining neuroimaging data and community detection might be a valuable approach to elucidate heterogeneity in ADHD etiology and examine ADHD neurobiology., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Recent studies using Magnetic Resonance Imaging (MRI) have proposed that the brain's white matter is organized as a rich club, whereby the most highly connected regions of the brain are also highly connected to each other. Here we use both functional and diffusion-weighted MRI in the human brain to investigate whether the rich club phenomena is present with functional connectivity, and how this organization relates to the structural phenomena. We also examine whether rich club regions serve to integrate information between distinct brain systems, and conclude with a brief investigation of the developmental trajectory of rich-club phenomena. In agreement with prior work, both adults and children showed robust structural rich club organization, comprising regions of the superior medial frontal/dACC, medial parietal/PCC, insula, and inferior temporal cortex. We also show that these regions were highly integrated across the brain's major networks. Functional brain networks were found to have rich club phenomena in a similar spatial layout, but a high level of segregation between systems. While no significant differences between adults and children were found structurally, adults showed significantly greater functional rich club organization. This difference appeared to be driven by a specific set of connections between superior parietal, insula, and supramarginal cortex. In sum, this work highlights the existence of both a structural and functional rich club in adult and child populations with some functional changes over development. It also offers a potential target in examining atypical network organization in common developmental brain disorders, such as ADHD and Autism.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent psychiatric disorder that has poor long-term outcomes and remains a major public health concern. Recent theories have proposed that ADHD arises from alterations in multiple neural pathways. Alterations in reward circuits are hypothesized as one core dysfunction, leading to altered processing of anticipated rewards. The nucleus accumbens (NAcc) is particularly important for reward processes; task-based fMRI studies have found atypical activation of this region while the participants performed a reward task. Understanding how reward circuits are involved with ADHD may be further enhanced by considering how the NAcc interacts with other brain regions. Here we used the technique of resting-state functional connectivity MRI (rs-fcMRI) to examine the alterations in the NAcc interactions and how they relate to impulsive decision making in ADHD. Using rs-fcMRI, this study: examined differences in functional connectivity of the NAcc between children with ADHD and control children; correlated the functional connectivity of NAcc with impulsivity, as measured by a delay discounting task; and combined these two initial segments to identify the atypical NAcc connections that were associated with impulsive decision making in ADHD. We found that functional connectivity of NAcc was atypical in children with ADHD and the ADHD-related increased connectivity between NAcc and the prefrontal cortex was associated with greater impulsivity (steeper delayed-reward discounting). These findings are consistent with the hypothesis that atypical signaling of the NAcc to the prefrontal cortex in ADHD may lead to excessive approach and failure in estimating future consequences; thus, leading to impulsive behavior., (Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.)

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder, often associated with other psychiatric comorbidities, functional impairments, and poor long-term outcomes. The objective of this selected review is to describe current advances and challenges in the diagnosis and treatment of ADHD. The disorder is associated with neurobiological underpinnings and is highly heterogeneous in various aspects, such as symptom profiles, cognitive impairments, and neurobiological and genetic features. The efficacy and safety of short-term pharmacological treatments across the life cycle is well studied, but further research investigating long-term treatment, impact of treatment in preschoolers, and non-pharmacological interventions is needed. Future research is also needed to better characterize the neurodevelopmental pathways of the disorder, linking clinical and neurobiological information, less investigated populations, and new interventions.

Introduction: Attention deficit hyperactivity disorder (ADHD) captures a heterogeneous group of children, who are characterized by a range of cognitive and behavioral symptoms. Previous resting-state functional connectivity MRI (rs-fcMRI) studies have sought to understand the neural correlates of ADHD by comparing connectivity measurements between those with and without the disorder, focusing primarily on cortical-striatal circuits mediated by the thalamus. To integrate the multiple phenotypic features associated with ADHD and help resolve its heterogeneity, it is helpful to determine how specific circuits relate to unique cognitive domains of the ADHD syndrome. Spatial working memory has been proposed as a key mechanism in the pathophysiology of ADHD., Methods: We correlated the rs-fcMRI of five thalamic regions of interest (ROIs) with spatial span working memory scores in a sample of 67 children aged 7-11 years [ADHD and typically developing children (TDC)]. In an independent dataset, we then examined group differences in thalamo-striatal functional connectivity between 70 ADHD and 89 TDC (7-11 years) from the ADHD-200 dataset. Thalamic ROIs were created based on previous methods that utilize known thalamo-cortical loops and rs-fcMRI to identify functional boundaries in the thalamus., Results/conclusion: Using these thalamic regions, we found atypical rs-fcMRI between specific thalamic groupings with the basal ganglia. To identify the thalamic connections that relate to spatial working memory in ADHD, only connections identified in both the correlational and comparative analyses were considered. Multiple connections between the thalamus and basal ganglia, particularly between medial and anterior dorsal thalamus and the putamen, were related to spatial working memory and also altered in ADHD. These thalamo-striatal disruptions may be one of multiple atypical neural and cognitive mechanisms that relate to the ADHD clinical phenotype.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a major public health concern. It has been suggested that the brain's default network may provide a crucial avenue for understanding the neurobiology of attention deficit/hyperactivity disorder. Evaluations of the default network have increased over recent years with the applied technique of resting-state functional connectivity magnetic resonance imaging (rs-fcMRI). These investigations have established that spontaneous activity in this network is highly correlated at rest in young adult populations. This coherence seems to be reduced in adults with ADHD. This is an intriguing finding, as coherence in spontaneous activity within the default network strengthens with age. Thus, the pathophysiology of ADHD might include delayed or disrupted maturation of the default network. If so, it is important to determine whether an altered developmental picture can be detected using rs-fcMRI in children with ADHD., Methods: This study used the typical developmental context provided previously by Fair et al. (2008) to examine coherence of brain activity within the default network using rs-fcMRI in children with (n = 23) and without attention deficit/hyperactivity disorder (n = 23)., Results: We found that functional connections previously shown as developmentally dynamic in the default network were atypical in children with attention deficit/hyperactivity disorder-consistent with perturbation or failure of the maturational processes., Conclusions: These findings are consistent with the hypothesis that atypical consolidation of this network over development plays a role in attention deficit/hyperactivity disorder., (Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Recent years have witnessed a surge of investigations examining functional brain organization using resting-state functional connectivity MRI (rs-fcMRI). To date, this method has been used to examine systems organization in typical and atypical developing populations. While the majority of these investigations have focused on cortical-cortical interactions, cortical-subcortical interactions also mature into adulthood. Innovative work by Zhang et al. (2008) in adults have identified methods that utilize rs-fcMRI and known thalamo-cortical topographic segregation to identify functional boundaries in the thalamus that are remarkably similar to known thalamic nuclear grouping. However, despite thalamic nuclei being well formed early in development, the developmental trajectory of functional thalamo-cortical relations remains unexplored. Thalamic maps generated by rs-fcMRI are based on functional relationships, and should modify with the dynamic thalamo-cortical changes that occur throughout maturation. To examine this possibility, we employed a strategy as previously described by Zhang et al. to a sample of healthy children, adolescents, and adults. We found strengthening functional connectivity of the cortex with dorsal/anterior subdivisions of the thalamus, with greater connectivity observed in adults versus children. Temporal lobe connectivity with ventral/midline/posterior subdivisions of the thalamus weakened with age. Changes in sensory and motor thalamo-cortical interactions were also identified but were limited. These findings are consistent with known anatomical and physiological cortical-subcortical changes over development. The methods and developmental context provided here will be important for understanding how cortical-subcortical interactions relate to models of typically developing behavior and developmental neuropsychiatric disorders.