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El síndrome compartimental agudo requiere de la descompresión quirúrgica, mediante fasciotomía, esta técnica debe ser urgente y será clave para evitar la instauración de graves secuelas. El posterior abordaje de estas heridas de difícil y lenta cicatrización suponen un reto para los profesionales de la salud y un problema para la salud pública debido a los altos costes y elevada morbilidad. La terapia de presión negativa (TPN) o cura por vacío (VAC, "vacuum assisted closure") es un tratamiento no invasivo que consigue la curación de las heridas favoreciendo la vascularización, la aparición del tejido de granulación y eliminación del exceso de exudado[AU]

Acute compartment syndrome requires surgical decompression by fasciotomy, this technique must be urgent and will be key to avoid the establishment of serious sequels. The subsequent approach to these wounds, which are difficult and slow to heal, is a challenge for health professionals and a problem for public health due to high costs and high morbidity. Negative pressure therapy (NPWT) or vacuum assisted closure (VAC) is a non-invasive treatment that achieves wound healing by promoting vascularization, the appearance of granulation tissue and elimination of excess exudate[AU]

A síndrome compartimental aguda requer descompressão cirúrgica, por fasciotomia, esta técnica deve ser urgente e será fundamental para evitar o estabelecimento de sequelas graves. O tratamento subsequente destas feridas difíceis e de cicatrização lenta é um desafio para os profissionais de saúde e um problema desaúde pública devido aos elevados custos e à elevada morbilidade. A terapia por pressão negativa (NPWT) ou o encerramento assistido por vácuo (VAC) é um tratamento não invasivo que permite a cicatrização de feridas através da promoção da vascularização, do aparecimento de tecido de granulação e da remoção do excesso de exsudado[AU]

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Abstract Background Tuberous sclerosis complex (TSC) is a multisystem neurocutaneous syndrome with variable phenotypes. Recent updates of TSC diagnostic criteria reaffirmed the defined genetic diagnostic criterion as the finding of a pathogenic DNA alteration in either TSC1 or TSC2 genes. It also slightly modified definite clinical diagnostic criteria. TSC-associated skin lesions in infancy are important clinical signs to select individuals with possible TSC for a closer clinical follow-up and genetic testing. Objective To raise awareness of the updated TSC diagnosis criteria; to assess the frequency of skin lesions in TSC patients as well as the first dermatological presentation; and to associate the findings with either TSC1 or TSC2 mutations. Methods Observational cross-sectional study. Clinical and genetic data were retrospectively collected from 37 TSC patients from a Brazilian University Hospital. Patients with skin signs were examined and prospectively assessed for 12 months. Results The earliest cutaneous lesions were hypomelanotic macules, which together with angiofibromas were the most frequent dermatological lesions. The total pathogenic DNA alteration ratio between TSC2 and TSC1 genes was 8:1. The frequency of a TSC2 pathogenic variant was 10-fold greater in the presence of ungual fibromas. Study limitations Small sample and a limited number of patients with TSC1 pathogenic variants. Conclusion Clinicians should be knowledgeable about TSC updated diagnostic criteria. Patients need to be followed up by a multidisciplinary team and treated accordingly. Early detection of cutaneous lesions is important for TSC diagnosis. A significant association between TSC2 gene pathogenic alterations and ungual fibromas is described.

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The genus Corynebacterium is the largest genera among corynebacteria and has a range of species widely spread in ecological niches, some with epidemic potential and capable of causing fatal diseases. In recent years, due to the reclassifications and discoveries of new potentially toxin-producing species, microbiological identification and epidemiological control have been compromised, becoming possible only with sequencing techniques. Two bacterial strains isolated from a cat were identified by MALDI-TOF mass spectrometry as Corynebacterium diphtheriae and sent to the collaborating center of the Brazilian Ministry of Health for molecular identification and determination of toxigenicity potential, which were initially performed by multiplex PCR method. In addition, the antimicrobial susceptibility profile was determined according to BrCAST. Finally, for the final identification at the species level and effective epidemiological monitoring, the sequencing of the 16S rRNA and rpoB housekeeping genes was carried out. The isolates were identified as nontoxigenic C. diphtheriae strains by mPCR. Both strains were found susceptible to all antimicrobial agents. Although the identification at the species level was not possible through similarity analysis of  S rRNA and rpoB housekeeping genes, the phylogenetic analysis showed that the isolates belonged to the species Corynebacterium rouxii with a high value of reliability. This is the first report of the isolation of C. rouxii in Latin America. Molecular identification, whether by the MALDI-TOF mass spectrometry or PCR techniques, does not discriminate C. rouxii from C. diphtheriae, requiring gene sequencing and phylogenetic analysis for correct identification at the species level.

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BACKGROUND: Dopaminergic neurons from the substantia nigra pars compacta (SNc) have a higher susceptibility to aging-related degeneration, compared to midbrain dopaminergic cells present in the ventral tegmental area (VTA); the death of dopamine neurons in the SNc results in Parkinson´s disease (PD). In addition to increased loss by aging, dopaminergic neurons from the SNc are more prone to cell death when exposed to genetic or environmental factors, that either interfere with mitochondrial function, or cause an increase of oxidative stress. The oxidation of dopamine is a contributing source of reactive oxygen species (ROS), but this production is not enough to explain the differences in susceptibility to degeneration between SNc and VTA neurons. AIM OF REVIEW: In this review we aim to highlight the intrinsic differences between SNc and VTA dopamine neurons, in terms of gene expression, calcium oscillations, bioenergetics, and ROS responses. Also, to describe the changes in the pentose phosphate pathway and the induction of apoptosis in SNc neurons during aging, as related to the development of PD. KEY SCIENTIFIC CONCEPTS OF REVIEW: Recent work showed that neurons from the SNc possess intrinsic characteristics that result in metabolic differences, related to their intricate morphology, that render them more susceptible to degeneration. In particular, these neurons have an elevated basal energy metabolism, that is required to fulfill the demands of the constant firing of action potentials, but at the same time, is associated to higher ROS production, compared to VTA cells. Finally, we discuss how mutations related to PD affect metabolic pathways, and the related mechanisms, as revealed by metabolomics.

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Motor competence (MC) is conceptually defined as a multidimensional latent construct that covers the proficient performance in motor skills and its underlying mechanisms This study aimed to statistically provide arguments that MC is a network of interconnected constructs, such as FMS, coordination, and its underlying mechanisms, which are responsible for preschoolers' proficiency in motor tasks. Participated 102 preschoolers (65 girls, M age = 4.22 ± 0.19) who were assessed for the Test of Gross Motor Development - 2nd edition, the Motor Competence Assessment, and the Supine-to-Stand. Data were explored using Exploratory Graph Analysis, using the EGAnet package in RStudio. A four-dimensional structure (61.2% of interactions) comprising tasks of the different protocols was underlined, in which all the nodes presented stable and adequate indexes (≥0.65; TEFI = -2.67). Four dimensions of MC were highlighted, namely Dimension 1, which combined movements for locomotor patterns; Dimension 2, comprising three process-oriented measures of object control skills to project objects; Dimension 3, which comprised of skills which require body coordination to displace body through space; and Dimension 4, composed by object control skills evaluated through product-oriented measures. For a better understanding of MC, the assessment of these different aspects that comprises MC should be considered.

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MAIN CONCLUSION: This study provides evidence about the relationship between Target of Rapamycin (TOR) kinase and the signal molecule nitric oxide (NO) in plants. We showed that sucrose (SUC)-mediated TOR activation of root apical meristem (RAM) requires NO and that NO, in turn, participates in the regulation of TOR signaling. Nitric oxide (NO) constitutes a signal molecule that regulates important target proteins related to growth and development and also contributes to metabolic reprogramming that occurs under adverse conditions. Taking into account the important role of NO and its relationship with Target of Rapamycin (TOR) signaling in animals, we wondered about the putative link between both pathways in plants. With this aim, we studied a TOR-dependent process which is the reactivation of the root apical meristem (RAM) in Arabidopsis thaliana. We used pharmacological and genetic tools to evaluate the relationship between NO and TOR on the sugar induction of RAM, using SNP as NO donor, cPTIO as NO scavenger and the nitrate reductase (NR) mutant nia2. The results showed that sucrose (SUC)-mediated TOR activation of the RAM requires NO and that NO, in turn, participates in the regulation of TOR signaling. Interestingly, TOR activation induced by sugar increased the NO levels. We also observed that NO could mediate the repression of SnRK1 activity by SUC. By computational prediction we found putative S-nitrosylation sites in the TOR complex proteins and the catalytic subunit of SnRK1, SnRK1.1. The present work demonstrates for the first time a link between NO and TOR revealing the complex interplay between the two pathways in plants.

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BACKGROUND: In Chile demand for specialist care following exposure to interpersonal violence (IPV) in youth far exceeds capacity. Group interventions may improve access to care for youth. OBJECTIVE: To evaluate the effectiveness and acceptability of two low-intensity group interventions: Trama Focused Cognitive Behavioral Therapy (TF-CBT); Interpersonal Psychotherapy (IPT); and treatment as usual, Art therapy-based support (ATBS). Outcomes measured were post-traumatic stress symptoms, depression, interpersonal functioning and affect regulation. PARTICIPANTS AND SETTING: Participants were 67 Chilean youth aged 13-17 years, victims of IPV on a waiting list to receive specialist individual intervention. METHODS: Using a randomised controlled trial design, participants were randomly assigned to one of the interventions. Self-report measures were completed at 5 timepoints between baseline and follow up eight weeks after intervention ended. Dropout rates and attendance were also analysed. RESULTS: TF-CBT showed significant decreases for PTSD (d = 0.91) and depression (d = 0.77) symptoms, sustained at follow-up with affect regulation problems also showing significant decrease from baseline (d = 0.43). IPT showed significant decreases in PTSD symptoms (d = 0.64) and affect regulation problems (d = 0.66), both sustained at follow-up. ATBS showed statistically significant decrease for PTSD (d = 0.79) and interpersonal problems (d = 0.65) but only change in PTSD was sustained at follow-up. There were no significant differences in dropout or attendance between the interventions. CONCLUSION: Group interventions provide a viable and effective first-phase option for reducing psychological distress in IPV-exposed youth in high-demand contexts. Effectiveness may be further improved through the more active involvement of parents and carers.

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PURPOSE: The interplay between myopia and glaucoma has gained attention, with escalating myopia demonstrating a significant association with increased POAG rates, particularly in patients with severe myopia. This systematic review aimed to comprehensively analyze the relationship between myopia and glaucoma, focusing on the structural and functional implications, risk factors, and assessment modalities. Optical coherence tomography (OCT) played a crucial role in this study, particularly in highly myopic populations. METHODS: This study's rigor is underscored by using the PRISMA guidelines, which ensured a meticulous search strategy was employed across multiple databases from 2012 to 2024. The inclusion criteria included individuals aged 18 years or older with high myopia, defined as a spherical equivalent of less than -6.0 diopters or an axial length > 26.0 mm, diagnosed with chronic glaucoma. Various study designs were incorporated, including randomized controlled trials, prospective cohort studies, and observational studies. Quality assessment was performed using the Jadad Scale, and statistical analyses were performed to summarize the study characteristics and outcomes. RESULTS: Of the 350 initial articles, 15 met the inclusion criteria. OCT assessments revealed structural changes such as thinning of the retinal nerve fiber layer preceding functional losses. Meta-analyses demonstrated a heightened risk of POAG with increasing myopia severity, showing a significant nonlinear relationship. This meta-analysis of six studies involving 3040 patients revealed a relationship between myopia and glaucoma (OR = 12.0, 95% CI 10.1-4.7, P < 0.00001). CONCLUSION: This comprehensive analysis consolidates the evidence of the relationship between myopia and glaucoma, emphasizing the pivotal role of OCT and other imaging modalities in early detection and monitoring.

Glaucoma is a significant cause of permanent blindness worldwide. This causes damage to the visual nerve that worsens over time. The primary way to treat open-angle glaucoma and its many causes is to lower eye pressure. Further research is being conducted to determine the relationship between nearsightedness and glaucoma. Increased nearsightedness is significantly linked to higher rates of glaucoma, especially in people with severe nearsightedness. This review aimed to examine the link between myopia and glaucoma in greater depth, focusing on structural and functional effects, risk factors, and assessment methods, especially optical coherence tomography (OCT), in very nearsighted people. We conducted a thorough search of several databases between 2012 and 2024. Individuals aged 18 years or older with myopia greater than six diopters or an axial length greater than 26 mm and a diagnosis of chronic glaucoma were eligible. Randomized controlled trials, prospective cohort studies, and observational studies were some of the methods used in this study. The quality of the work and statistical methods were used to summarize the features and results of the study. Of the 350 articles initially published, only 15 met the inclusion criteria. These studies mostly used different optical tomography tests to detect structural changes, such as ocular nerve fiber layer damage, before functional loss. According to meta-analyses, the risk of chronic glaucoma increases as myopia worsens, indicating a solid nonlinear relationship. Myopia and glaucoma are linked, demonstrating the importance of thorough evaluation. Severe myopia is strongly associated with damage to the visual nerve. Over the past few years, optical tomography has become a vital imaging tool for identifying early damage to the optic nerve. However, further research is needed on the sex-related tendencies of glaucoma patients. This study provides data that reveal a link between nearsightedness and glaucoma, highlighting the importance of optical tomography and other imaging techniques for early detection and monitoring. To better manage glaucoma in highly myopic individuals, we need to understand how the severity of myopia, changes in structure, and changes in function affect each other.

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Three dinuclear zinc(II) acetate complexes of the general formula [Zn{Ln}(AcO)]2, namely, di-µ-acetato-κ4O:O'-bis[({2-[(pyridin-2-ylmethylidene)amino]phenyl}sulfanido-κ3N,N',S)zinc(II)], [Zn2(C12H9N2S)2(C2H3O2)2] (n = 1), 4, µ-acetato-1:2κ2O:O'-acetato-2κO-[µ-(2-{[1-(pyridin-2-yl)ethylidene]amino}phenyl)sulfanido-1κS:2κ3N,N',S][(2-{[1-(pyridin-2-yl)ethylidene]amino}phenyl)sulfanido-1κ3N,N',S]dizinc(II), [Zn2(C13H11N2S)2(C2H3O2)2] (n = 2), 5, and µ-acetato-1:2κ2O:O'-acetato-2κO-[µ-(2-{[phenyl(pyridin-2-yl)methylidene]amino}phenyl)sulfanido-1κS:2κ3N,N',S][(2-{[phenyl(pyridin-2-yl)methylidene]amino}phenyl)sulfanido-1κ3N,N',S]dizinc(II)-bis(2-aminophenyl) disulfide (2/1), [Zn2(C18H13N2S)2(C2H3O2)2]·0.5C12H12N2S2 (n = 3), 6·0.5(2-APS)2, were obtained from the reaction of 2-R-(pyridin-2-yl)benzothiazoline precursors (R = H, 1; R = Me, 2; R = Ph, 3) with zinc acetate dihydrate in a 1:1 ratio. All the complexes crystallized as dinuclear species and complex 6 cocrystallized with one molecule of bis(2-aminophenyl) disulfide (2-APS)2. The anionic Schiff base ligands {Ln}- displayed a κ2N,κS-tridentate coordination mode with the formation of two five-membered chelate rings. In 4, 5 and 6·0.5(2-APS)2, both ZnII ions are pentacoordinated and the coordination sphere of 4 was different with respect to those in 5 and 6·0.5(2-APS)2. For 4, the X-ray diffraction study showed a dinuclear complex containing two bridging acetate ligands linked to both ZnII ions. For 5 and 6·0.5(2-APS)2, the dinuclear complexes displayed one bridging acetate ligand linked to both ZnII ions, where the first ZnII ion includes a dative bond with one S atom from an adjacent anionic Schiff base {Ln}-, while the second ZnII ion is coordinated to one terminal acetate ligand. In each dinuclear complex, the geometry is the same for both ZnII metal centres. The local geometry of the ZnII cation in 4 is halfway between trigonal bipyramidal and square pyramidal local geometries; in 5 and 6, the local geometries are described as distorted square pyramidal. Hirshfeld surface analysis of 5 and 6 showed the predominance of H...H interactions, as well as the contribution of C-H...C, C-H...O and C-H...S noncovalent interactions to the cohesion of the crystalline network of the ZnII complexes.

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Most commercial anticancer nanomedicines are administered intravenously. This route is fast and precise as the drug enters directly into the systemic circulation, without undergoing absorption processes. When nanoparticles come into direct contact with the blood, however, they interact with physiological components that can induce colloidal destabilization and/or changes in their original biochemical identity, compromising their ability to selectively accumulate at target sites. In this way, these systems usually lack active targeting, offering limited therapeutic effectiveness. In the literature, there is a paucity of in-depth studies in complex environments to evaluate nanoparticle stability, protein corona formation, hemolytic activity, and targeting capabilities. To address this issue, fluorescent silica nanoparticles (SiO2NPs) are here functionalized with zwitterionic (kinetic stabilizer) and folate groups (targeting agent) to provide selective interaction with tumor cell lines in biological media. The stability of these dually functionalized SiO2NPs is preserved in unprocessed human plasma while yielding a decrease in the number of adsorbed proteins. Experiments in murine blood further proved that these nanoparticles are not hemolytic. Remarkably, the functionalized SiO2NPs are more internalized by tumor cells than their healthy counterparts. Investigations of this nature play a crucial role in garnering results with greater reliability, allowing the development of nanoparticle-based pharmaceutical drugs that exhibit heightened efficacy and reduced toxicity for medical purposes.

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Acinetobacter baumannii emerged as one of the most important pathogens for the development of new antimicrobials due to the worldwide detection of isolates resistant to all commercial antibiotics, especially in nosocomial infections. Biofilm formation enhances A. baumannii survival by impairing antimicrobial action, being an important target for new antimicrobials. Fluopsin C (FlpC) is an organocupric secondary metabolite with broad-spectrum antimicrobial activity. This study aimed to evaluate the antibiofilm activity of FlpC in established biofilms of extensively drug-resistant A. baumannii (XDRAb) and the effects of its combination with polymyxin B (PolB) on planktonic cells. XDRAb susceptibility profiles were determined by Vitek 2 Compact, disk diffusion, and broth microdilution. FlpC and PolB interaction was assessed using the microdilution checkerboard method and time-kill kinetics. Biofilms of XDRAb characterization and removal by FlpC exposure were assessed by biomass staining with crystal violet. Confocal Laser Scanning Microscopy was used to determine the temporal removal of the biofilms using DAPI, and cell viability using live/dead staining. The minimum inhibitory concentration (MIC) of FlpC on XDRAb was 3.5 µg mL-1. Combining FlpC + PolB culminated in an additive effect, increasing bacterial susceptibility to both antibiotics. FlpC-treated 24 h biofilms reached a major biomass removal of 92.40 ± 3.38% (isolate 230) using 7.0 µg mL-1 FlpC. Biomass removal occurred significantly over time through the dispersion of the extracellular matrix and decreasing cell number and viability. This is the first report of FlpC's activity on XDRAb and the compound showed a promissory response on planktonic and sessile cells, making it a candidate for the development of a new antimicrobial product.

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Sequence-type 5 (ST5) of methicillin-resistant Staphylococcus aureus (MRSA), harboring the staphylococcal chromosomal cassette mec type IV (SCCmecIV), was first detected in Portugal. It emerged as a significant cause of healthcare-associated (HA) infection in pediatric units and was hence named the pediatric clone. Another ST5 lineage, which carries SCCmecII, also prevailed in the USA and Japan for multiple years. More recently, another MRSA lineage, ST105-SCCmecII, part of the evolution of clonal complex 5 (CC5) MRSA, has emerged as the cause of hospital-acquired bloodstream infection outbreaks in countries including Portugal, the USA, and Brazil. This article reviews studies on the epidemiology and evolution of these newly emerging pathogens. To this end, a search of PUBMED from inception to 2024 was performed to find articles reporting the occurrence of ST105 MRSA in epidemiologic studies. A second search was performed to find studies on MRSA, CC5, ST5, and SCCmecII. A search of PUBMED from 1999 to 2024 was also performed to identify studies on the genomics and evolution of ST5, CC5, and ST105 MRSA. Further studies were identified by analyzing the references of the previously selected articles from PUBMED. Most articles on ST105 MRSA were included in this review. Only articles written in English were included. Furthermore, only studies that used a reliable genotyping method (e.g., whole genome sequencing, or MLST) to classify the CC5 lineages were selected. The quality and selection of articles were based on the consensus assessment of the three authors in independent evaluations. In conclusion, ST105-SCCmecII is an emerging MRSA in several countries, being the second/third most important CC5 lineage, with a relatively high frequency in bloodstream infections. Of concern is the increased mortality from BSI in patients older than 15 years and the higher prevalence of ST105-SCCmecII in the blood of patients older than 60 years reported in some studies.

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Approximately 80% of breast cancer (BC) cases are estrogen receptor positive (ER+) and sensitive to hormone treatment; Tamoxifen is a prodrug, and its main plasmatic active metabolites are 4-hydroxytamoxifen (4-OH Tam) and endoxifen. Despite the effectiveness of tamoxifen therapy, resistance can be developed. An increment in eukaryotic initiation factor-4A complex (eIF4A) activity can result in tamoxifen-resistant tumor cells. For this work, we developed a cell variant resistant to 4-OH Tam and endoxifen, denominated MCF-7Var E; then, the aim of this research was to reverse the acquired resistance of this variant to tamoxifen metabolites by incorporating the natural compound auraptene. Combination treatments of tamoxifen derivatives and auraptene successfully sensitized the chemoresistant MCF-7Var E. Our data suggest a dual regulation of eIF4A and ER by auraptene. Joint treatments of 4-OH Tam and endoxifen with auraptene identified a novel focus for chemoresistance disruption. Synergy was observed using the auraptene molecule and tamoxifen-derived metabolites, which induced a sensitization in MCF-7Var E cells and ERα parental cells that was not observed in triple-negative breast cancer cells (TNBC). Our results suggest a synergistic effect between auraptene and tamoxifen metabolites in a resistant ER+ breast cancer model, which could represent the first step to achieving a pharmacologic strategy.

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BACKGROUND: Noncommunicable diseases (NCDs) predominantly affect adults, but pathophysiological changes begin decades earlier, as a continuum, with initial events apparent in adolescence. Hence, early identification and intervention are crucial for the prevention and management of NCDs. We investigated the complex network of socioeconomic, behavioral, and metabolic factors associated with the presence of NCD in Brazilian adolescents. METHODS: We conducted a cross-sectional study nested within the São Luís segment of the Ribeirão Preto, Pelotas, and São Luís (RPS) cohort's consortium, focusing on 18-19-year-olds (n = 2515). Data were collected prospectively, from which we constructed a complex network with NCD-related factors/indicators as nodes and their co-occurrences as edges. General and sex-based models analyzed: socioeconomic status, behavioral (smoking, alcohol, and other drugs use, unhealthy diet, poor sleep, physical inactivity), and metabolic factors (overweight/obesity, elevated blood pressure, poor lipid profile). We also looked for NCDs in adolescence like asthma, abnormal spirometry, depression, suicide risk, and poor oral health. The network was characterized by degree, betweenness, eigenvector, local transitivity, Shannon entropy, and cluster coefficient. RESULTS: The adolescents had an average age of 18.3 years, 52.3% were female and 47.7% male. 99.8% of them have a diet rich in free sugars, 15% are overweight/obese and 72.3% had an elevated TyG index. High free sugar emerged as the central hub, followed by high TyG index (an early marker of insulin resistance) and low socioeconomic class. In males, low fiber intake and a high triglycerides/HDL ratio highlighted cardiometabolic concerns; in females, sedentary behavior and poor sleep marked metabolic and psychological challenges, along with caries in both sexes. CONCLUSIONS: Our findings provide insights into central health challenges during adolescence, such as high free sugars, insulin resistance, and low socioeconomic indicators, suggesting that interventions targeted at these central hubs could have a significant impact on their NCD network.

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Household water treatment (HWT) is recommended when safe drinking water is limited. To understand determinants of HWT adoption, we conducted a cross-sectional survey with 650 households across different regions in Haiti. Data were collected on 71 demographic and psychosocial factors and 2 outcomes (self-reported and confirmed HWT use). Data were transformed into 169 possible determinants of adoption across nine categories. We assessed determinants using logistic regression and, as machine learning methods are increasingly used, random forest analyses. Overall, 376 (58%) respondents self-reported treating or purchasing water, and 123 (19%) respondents had residual chlorine in stored household water. Both logistic regression and machine learning analyses had high accuracy (area under the receiver operating characteristic curve (AUC): 0.77-0.82), and the strongest determinants in models were in the demographics and socioeconomics, risk belief, and WASH practice categories. Determinants that can be influenced inform HWT promotion in Haiti. It is recommended to increase access to HWT products, provide cash and education on water treatment to emergency-impacted populations, and focus future surveys on known determinants of adoption. We found both regression and machine learning methods need informed, thoughtful, and trained analysts to ensure meaningful results and discuss the benefits/drawbacks of analysis methods herein.

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Among the myriad of neurodegenerative diseases, mitochondrial dysfunction represents a nexus regarding their pathogenic processes, in which Parkinson's disease (PD) is notable for inherent vulnerability of the dopaminergic pathway to energy deficits and oxidative stress. Underlying this dysfunction, the occurrence of defects in complex I (CI) derived from molecular alterations in its subunits has been described in the literature. However, the mechanistic understanding of the processes mediating the occurrence of mitochondrial dysfunction mediated by CI deficiency in PD remains uncertain and subject to some inconsistencies. Therefore, this review analyzed existing evidence that may explain the relationship between molecular alterations in the core subunits of CI, recognized for their direct contribution to its enzymatic performance, and the pathogenesis of PD. As a result, we discussed 47 genetic variants in the 14 core subunits of CI, which, despite some discordant results, were predominantly associated with varying degrees of deficiency in complex enzymatic activity, as well as defects in supercomplex biogenesis and CI itself. Finally, we hypothesized about the relationship of the described alterations with the pathogenesis of PD and offered some suggestions that may aid in the design of future studies aimed at elucidating the relationship between such alterations and PD.

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This study presents extended Immunity Agent-Based Model (IABM) simulations to evaluate vaccination strategies in controlling the spread of infectious diseases. The application of IABM in the analysis of vaccination configurations is innovative, as a vaccinated individual can be infected depending on how their immune system acts against the invading pathogen, without a pre-established infection rate. Analysis at the microscopic level demonstrates the impact of vaccination on individual immune responses and infection outcomes, providing a more realistic representation of how the humoral response caused by vaccination affects the individual's immune defense. At the macroscopic level, the effects of different population-wide vaccination strategies are explored, including random vaccination, targeted vaccination of specific demographic groups, and spatially focused vaccination. The results indicate that increased vaccination rates are correlated with decreased infection and mortality rates, highlighting the importance of achieving herd immunity. Furthermore, strategies focused on vulnerable populations or densely populated regions prove to be more effective in reducing disease transmission compared to randomly distributed vaccination. The results presented in this work show that vaccination strategies focused on highly crowded regions are more efficient in controlling epidemics and outbreaks. Results suggest that applying vaccination only in the densest region resulted in the suppression of infection in that region, with less intense viral spread in areas with lower population densities. Strategies focused on specific regions, in addition to being more efficient in reducing the number of infected and dead people, reduce costs related to transportation, storage, and distribution of doses compared to the random vaccination strategy. Considering that, despite scientific efforts to consolidate the use of mass vaccination, the accessibility, affordability, and acceptability of vaccines are problems that persist, investing in the study of strategies that mitigate such issues is crucial in the development and application of government policies that make immunization systems more efficient and robust.

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(1) Background: Insect pathogenic fungi of the genus Metarhizium are under study and in application as highly solicited, more eco-system friendly substitutes for chemical insecticides in many countries and in different agricultural contexts. In Cuba and Florida, Metarhizium strains have previously been isolated from economically important coffee and sugar cane pests. (2) Methods: Unambiguous species delineation within the Metarhizium anisopliae species complex is methodologically challenging. Recently, a species-discriminating PCR approach has been developed based on ribosomal intergenic spacer (rIGS) sequences that covered the prominent four "PARB" species within the complex. This approach is combined here with further genetic markers and is extended to a further species. (3) Results: Metarhizium isolates from Cuba, found to be more naturally associated with the coffee berry borer, Hypothenemus hampei, were morphologically, microscopically and molecular taxonomically characterized. Multilocus sequence analysis based on 5TEF, MzIGS3 and rIGS markers delineated these weevil-associated strains from all previously established Metarhizium species. (4) Conclusions: The isolates under study represent a new fungal taxon proposed to be designated Metarhizium caribense. The rIGS-based species-discriminating diagnostic PCR is a suitable tool for the identification of new Metarhizium species and can be productively combined to approaches using further genetic markers.

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The sand fly of the genus Bichromomyia (Galati, 1995) includes 3 subspecies considered vectors of Leishmania, which share high morphological similarity. Through information from the Cytochrome Oxidase Subunit I (COI) gene, we provide complementary evidence to support that Bichromomyia olmeca olmeca, and Bichromomyia olmeca bicolor, should be raised to nominal species status. We recovered specimens of Bi. o. olmeca from Quintana Roo, Tabasco, and Oaxaca, Mexico, supply 17 new COI sequences, and also incorporate GenBank sequences for other Bichromomyia species. After a Maximum Likelihood (ML) analysis, all Bichromomyia species clustered with a bootstrap of 100%, although sequences of Bichromomyia flaviscutellata were divided into 2 clusters with an interspecific range distance of 11.16% between them, which confirm cryptic species in Brazil. The genetic distance of Bi. o. olmeca compared to related subspecies ranged between 12.59% and 14.64%. A total of 29 haplotypes (Hd = 0.987; π = 0.08783; S = 136) were recovered from the Bichromomyia sequences. Results of the TC network were consistent with the ML analysis, supporting that subspecies of Bichromomyia are genetically distinct and deserve being raised to valid species category: Bichromomyia olmeca (Vargas & Díaz-Nájera) and Bichromomyia bicolor (Fairchild & Theodor).

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Peptides have emerged as promising therapeutic agents. However, their potential is hindered by hemotoxicity. Understanding the hemotoxicity of peptides is crucial for developing safe and effective peptide-based therapeutics. Here, we employed chemical space complex networks (CSNs) to unravel the hemotoxicity tapestry of peptides. CSNs are powerful tools for visualizing and analyzing the relationships between peptides based on their physicochemical properties and structural features. We constructed CSNs from the StarPepDB database, encompassing 2004 hemolytic peptides, and explored the impact of seven different (dis)similarity measures on network topology and cluster (communities) distribution. Our findings revealed that each CSN extracts orthogonal information, enhancing the motif discovery and enrichment process. We identified 12 consensus hemolytic motifs, whose amino acid composition unveiled a high abundance of lysine, leucine, and valine residues, while aspartic acid, methionine, histidine, asparagine and glutamine were depleted. Additionally, physicochemical properties were used to characterize clusters/communities of hemolytic peptides. To predict hemolytic activity directly from peptide sequences, we constructed multi-query similarity searching models (MQSSMs), which outperformed cutting-edge machine learning (ML)-based models, demonstrating robust hemotoxicity prediction capabilities. Overall, this novel in silico approach uses complex network science as its central strategy to develop robust model classifiers, to characterize the chemical space and to discover new motifs from hemolytic peptides. This will help to enhance the design/selection of peptides with potential therapeutic activity and low toxicity.