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The COVID-19 restrictions have caused economic losses that affected food availability and accessibility, thereby compromising people’s lifestyles and putting the already existing poor households into severe food insecurity. As such, national government agencies and local government units in the Philippines provided emergency cash assistance and food aid as safety nets during the pandemic to help vulnerable households cope with the impending economic crisis and to improve food security in the country. This cross-sectional study assesses the association of social safety net programs with household food security (i.e., food secure, consistently food insecure, and newly food insecure) in Cavite province, Philippines. Findings show that being beneficiaries of the Pantawid Pamilyang Pilipino Program and the Social Amelioration Program are associated with being consistently and newly food insecure. Furthermore, households that obtained food from the community pantry, a volunteer-led movement during the height of the COVID-19 pandemic are also associated with food insecurity. On the other hand, the households that were provided with food packs, across different socioeconomic conditions, are not significantly associated with food insecurity. The study also affirms that households most vulnerable to food crises in the context of COVID-19 are those who are consistently food insecure and were already exposed to critical food and dietary deprivations before the onset of the pandemic. There is much to be done to improve the safety net programs in the country. The study results can add information and policy recommendations toward strengthening the services for vulnerable population groups to withstand short- and long-term food system disruptions and eventually build food-resilient households and communities. [ABSTRACT FROM AUTHOR]

Abstract Brazil is renowned for its extensive plant biodiversity, with emphasis on Cymbopogon, C. citratus and C. nardus, with broad antimicrobial potential. Candidemias caused by Candida albicans are highly prevalent in immunosuppressed individuals and are associated with infections by biofilms on medical devices. The aim of this study was to evaluate the antimicrobial potential of essential oils C. citratus and C. nardus against C. albicans in planktonic and biofilm forms. Essential oils were obtained by hydrodistillation and chemical composition evaluated by GC-FID and GC-MS. The minimum inhibitory concentration was determined by the broth microdilution method and the synergy effect of essential oils and amphotericin B were evaluated by the checkerboard test. Biofilm activity was determined by the XTT assay. Cytotoxicity assays performed with VERO cells and molecular docking were performed to predict the effect of oil interaction on the SAP-5 enzyme site. The results showed activity of essential oils against planktonic cells and biofilm of C. albicans. Furthermore, the oils had a synergistic effect, and low cytotoxicity. Molecular docking showed interaction between Cadinene, Caryophyllen oxide, Germacrene D with SAP-5. The results indicate that Cymbopogon spp. studied are anti-Candida, with potential for further application in therapy against infections caused by C. albicans.

Abstract Multiple sclerosis (MS) is a chronic, progressive, inflammatory disorder of the central nervous system. Relapsing–remitting MS (RRMS), the most common form of the disease, is characterized by transient neurological dysfunction with concurrent accumulation of disability. Over the past three decades, disease-modifying therapies (DMTs) capable of reducing the frequency of relapses and slowing disability worsening have been studied and approved for use in patients with RRMS. The first DMTs were interferon-betas (IFN-βs), which were approved in the 1990s. Among them was IFN-β-1a for subcutaneous (sc) injection (Rebif®), which was approved for the treatment of MS in Europe and Canada in 1998 and in the USA in 2002. Twenty years of clinical data and experience have supported the efficacy and safety of IFN-β-1a sc in the treatment of RRMS, including pivotal trials, real-world data, and extension studies lasting up to 15 years past initial treatment. Today, IFN-β-1a sc remains an important therapeutic option in clinical use, especially around pregnancy planning and lactation, and may also be considered for aging patients, in which MS activity declines and long-term immunosuppression associated with some alternative therapies is a concern. In addition, IFN-β-1a sc is used as a comparator in many clinical studies and provides a framework for research into the mechanisms by which MS begins and progresses.

The incorporation of geosynthetic reinforcements during the rehabilitation of flexible pavements has significantly increased due to the ability of geosynthetic reinforcements to minimize reflective cracks. However, the performance of the geosynthetic-reinforced asphalt depends on the interface bond strength between the geosynthetic and the adjacent asphalt layers. Tack coat is generally used to maintain adequate bonding between the geosynthetic-reinforced asphalt layers. This study focusses on evaluating the influence of interface bond strength on the fracture resistance of geosynthetic-reinforced asphalt utilizing a new testing approach. The fracture resistance of geosynthetic-reinforced asphalt specimens was evaluated via cross-shear testing device, while interface bond strength was evaluated using interface shear strength testing. A Performance Grade (PG) 64-22 binder was applied as a tack coat at the geosynthetic-asphalt interface at four different rates that are relative to the asphalt retention capacity of the geosynthetic reinforcement. A fiberglass geocomposite was used as geosynthetic reinforcement in this study. The results indicate a correlation between interface shear strength tests and cross-shear tests, suggesting that the optimum tack coat rate is 125% of the asphalt retention capacity of the geosynthetic reinforcement to improve the fracture resistance as well as the interface bond strength of geosynthetic-reinforced asphalt layers.

The factors influencing bonding between geosynthetics, and asphalt layers have been extensively investigated through monotonic interface shear tests. However, little is known about how the geosynthetic pavement interlayers behaves under cyclic shear loading. Dynamic shear testing is recognized as more appropriate to understand the performance of pavements under traffic loads. This paper presents the characterization of bond stiffness and shear fatigue life using dynamic interface shear tests on three different geosynthetic-reinforced asphalt interlayers, including a geogrid and two reinforcement geocomposites. Double-layered samples of 150 mm diameter were compacted in the laboratory using Marshall adapted method. The dynamic interlayer shear behavior was evaluated using cyclic Leutner device at a frequency of 5 Hz. The bitumen coating content and thickness of the fabric backing showed to most influence the shear fatigue life of geosynthetic interlayers. This research shows that distinct shear fatigue behaviors were obtained for the different types of geosynthetics.

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a tumour target currently used for the development of novel therapeutic modalities, such as antibody-drug conjugates, chimeric antigen receptor T-cell therapies, and others. Success of these new drugs depends on the selection of relevant indications based on ROR1 tumour prevalence, staining heterogeneity, and subcellular localization, among other parameters. We investigated ROR1 immunophenotype using validated antibody clones for immunohistochemistry (IHC) and flow cytometry (FC), analyzing 292 tumour specimens from 7 haematological malignancies and triple negative breast cancer (TNBC) as a reference solid tumour indication. ROR1 prevalence varied significantly across distinct tumour types, showing 100% of ROR1 positivity in all chronic lymphocytic leukaemia (n = 48) and hairy cell leukaemia (n = 14) specimens analyzed via FC with ranges between 1.1-99.8% and 0.8-62.1%, respectively. Samples analysed via IHC showed ROR1 membrane/cytoplasmic positivity in 44% of mantle cell lymphoma tumour samples (n = 27; H-score range: 10-285 in positive cases); 30% in TNBC (n = 46; H-score range: 1-200); 15% in diffuse large B-cell lymphoma (n = 45; H-score: 40-250); and 11% in follicular lymphoma (n = 34; H-score: 2-300). Finally, all acute myeloid leukaemia (n = 52) and most T-cell non-Hodgkin lymphoma (n = 31/32) tested samples were negative for ROR1 via IHC. In conclusion, ROR1 shows a heterogeneous tumour cell expression profile across multiple leukaemias and lymphomas, making it a tumour target that would require different patient selection strategies to develop novel therapeutic modalities., Competing Interests: This work was funded by Boehringer-Ingelheim GmbH, the employer of Manuel A. Silva, Lorenz Waldmeier and Yarúa Jaimes. Shuntae Williams, Sylvie Hauert, and Hytham Al-Masri are employed by Hematogenix. Benjamin Ovadia and Indu Gupta are employed by NeoGenomics. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Silva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Genetic variability significantly impacts metabolism, weight gain, and feeding behaviors, predisposing individuals to obesity. This study explored how variations in key genes related to obesity- FOXO3A (forkhead box O3), AMPK (protein kinase AMP-activated), and POMC (proopiomelanocortin)-are associated with extreme obesity (EOB). Methods: We conducted a case-control study with 251 EOB patients and 212 healthy controls with a body mass index (BMI) of less than 25 kg/m 2 . We genotyped 10 single nucleotide variants (SNVs) using TaqMan-based assays. Results: Four SNVs-rs1536057 in FOXO3A , rs103685 in AMPK , rs934778, and rs6545975 in POMC -were associated with an increased risk of EOB. The strongest association was observed with rs934778 ( POMC ), which had a maximum odds ratio (OR) of 5.26 (95% CI: 2.86-9.09). While these genetic variations are closely linked to EOB, they do not affect serum glucose, triglycerides, HDL, LDL, BMI, or waist circumference. Conclusions: These findings indicate that factors beyond traditional metabolic pathways, potentially related to feeding behavior or hormonal regulation, may also link these genetic variations to obesity. Further research in a larger sample is essential to validate these findings and explore their potential to guide clinical interventions and public health strategies., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Cinthia Vila Nova Santana et al.)

Objective: Individuals with chronic conditions have long-term needs which can be addressed by maintenance rehabilitation. The 2013 Jimmo v Sebelius settlement in the United States (US) clarified the Medicare coverage of maintenance rehabilitation as a skilled service, even when no improvement is expected. A scoping review was conducted to describe maintenance rehabilitation., Materials and Methods: A systematic search was performed across 9 databases. Maintenance rehabilitation was defined as services (e.g. occupational, physical, or speech language therapies), intended to maintain a person's condition and prevent decline. Studies focused on medical, or non-rehabilitative, interventions (e.g. opioid cessation or chemotherapy) were excluded. Of the 734 abstracts reviewed, 90 met inclusion criteria. Two reviewers extracted data and used descriptive statistics. An exploratory thematic analysis in a convenience sample contextualized the works., Results: Most works (90%) were peer-reviewed publications. The works represented 12,638 individuals, with predominant populations being cardiac (4,122 individuals) and pulmonary (2,324 individuals). Physical activity interventions were identified most frequently (87%). Outcome measures primarily focused on activities (49%) or body systems (42%). Thematic analysis suggests maintenance rehabilitation may support domains contributing to quality of life., Conclusions: While evidence exists for maintenance therapy, future research on intervention design will guide implementation by health systems.

The PPARG gene encodes a member of a nuclear receptor superfamily known as peroxisome proliferator-activated gamma (PPARγ). PPARγ plays an essential role in adipogenesis, stimulating the differentiation of preadipocytes into adipocytes. Loss-of-function pathogenic variants in PPARG reduce the activity of the PPARγ receptor and can lead to severe metabolic consequences associated with familial partial lipodystrophy type 3 (FPLD3). This review focuses on recent scientific data related to FPLD3, including the role of PPARγ in adipose tissue metabolism and the phenotypic and clinical consequences of loss-of-function variants in the PPARG gene. The clinical features of 41 PPARG pathogenic variants associated with FPLD3 patients were reviewed, highlighting the genetic and clinical heterogeneity observed among 91 patients. Most of them were female, and the average age at the onset and diagnosis of lipoatrophy was 21 years and 33 years, respectively. Considering the metabolic profile, hypertriglyceridemia (91.9% of cases), diabetes (77%), hypertension (59.5%), polycystic ovary syndrome (58.2% of women), and metabolic-dysfunction-associated fatty liver disease (87,5%). We also discuss the current treatment for FPLD3. This review provides new data concerning the genetic and clinical heterogeneity in FPLD3 and highlights the importance of further understanding the genetics of this rare disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Soares, da Silva, Campos and Lima.)

Objective: To examine, among persons discharged from inpatient rehabilitation for traumatic brain injury (TBI), the degree to which pre-TBI factors were associated with post-TBI hospitalization for psychiatric reasons. The authors hypothesized that pre-TBI psychiatric hospitalization and other pre-TBI mental health treatment would predict post-TBI psychiatric hospitalization following rehabilitation discharge, up to 5 years post-TBI., Setting: Five Veterans Affairs Polytrauma Rehabilitation Centers., Participants: Participants with nonmissing rehospitalization status and reason, who were followed at 1 year (N = 1006), 2 years (N = 985), and 5 years (N = 772) post-TBI., Design: A secondary analysis of the Veterans Affairs TBI Model Systems, a multicenter, longitudinal study of veterans and active-duty service members with a history of mild, moderate, or severe TBI previously admitted to comprehensive inpatient medical rehabilitation. This study examined participants cross-sectionally at 3 follow-up timepoints., Main Measures: Psychiatric Rehospitalization was classified according to Healthcare Cost and Utilization Project multilevel Clinical Classifications diagnosis terminology (Category 5)., Results: Rates of post-TBI psychiatric hospitalization at years 1, 2, and 5 were 4.3%, 4.7%, and 4.1%, respectively. While bivariate comparisons identified pre-TBI psychiatric hospitalization and pre-TBI mental health treatment as factors associated with psychiatric rehospitalization after TBI across all postinjury timepoints, these factors were statistically nonsignificant when examined in a multivariate model across all timepoints. In the multivariable analysis, pre-TBI psychiatric hospitalization was significantly associated with increased odds of post-TBI psychiatric hospitalization only at 1-year post-TBI (adjusted odds ratio = 2.65; 95% confidence interval, 1.07-6.55, P = .04). Posttraumatic amnesia duration was unrelated to psychiatric rehospitalization., Conclusions: Study findings suggest the limited utility of age, education, and pre-TBI substance use and mental health utilization in predicting post-TBI psychiatric hospitalization. Temporally closer social and behavior factors, particularly those that are potentially modifiable, should be considered in future research., (Copyright ©.)

Background and Objectives: As the aging population increases, the incidence of chronic subdural hematomas (cSDHs) is expected to rise. Surgical evacuation, though effective, sees up to 30% recurrence. Middle meningeal artery (MMA) embolization, particularly with n-butyl cyanoacrylate (n-BCA) glue diluted in D5W for distal penetration, has shown promise in reducing recurrences. Limited reports have investigated the safety and technical feasibility of n-BCA as a primary liquid embolic agent using the D5W push technique in cSDH. This series is the largest in the literature investigating the outcomes of this technique in cSDH., Methods: A multicenter retrospective database analysis was conducted on consecutive patients who underwent MMA embolization using n-BCA embolisate. Data collected included patient demographics, procedural information, angiographic data, and periprocedural complications., Results: The study included 269 patients with a median age of 76 years. Nearly half of the patients had previous surgeries, and 93 underwent contralateral embolization for bilateral cSDH. Successful MMA embolization with effective distal penetration was achieved in all cases. The complication rate was 2.2%. Significant improvements were noted at a 60-day follow-up, with a median reduction in cSDH diameter of 40.6% (P < .001) and 53% of patients showing neurological improvement. No recurrent cSDH or need for retreatment was observed in patients who underwent follow-up., Conclusion: MMA embolization using n-BCA with the D5W push technique is safe and technically feasible. It can be used adjunctively or as an alternative to surgery in patients with cSDH, resulting in decreased recurrence, high technical success, improved distal penetration, and low complication rates., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Oceanic oil spills present significant ecological risks that have the potential to contaminate extensive areas, including coastal regions. The occurrence of the 2019 oil spill event in Brazil resulted in over 3000 km of contaminated beaches and shorelines. While assessing the impact on benthic and beach ecosystems is relatively straightforward due to direct accessibility, evaluating the ecotoxicological effects of open ocean oil spills on the pelagic community is a complex task. Difficulties are associated with the logistical challenges of responding promptly and, in case of the Brazilian mysterious oil spill, to the subsurface propagation of the oil that impeded remote visual detection. An oceanographic expedition was conducted in order to detect and evaluate the impact of this oil spill event along the north-eastern Brazilian continental shelf. The pursuit of dissolved and dispersed oil compounds was accomplished by standard oceanographic methods including seawater polycyclic aromatic hydrocarbons (PAHs) analysis, biomass stable carbon isotope (δ 13 C), particulate organic carbon to particulate organic nitrogen (POC:PON) ratios, nutrient analysis and ecotoxicological bioassays using the naupliar phase of the copepod Tisbe biminiensis. Significant ecotoxicological effects, reducing naupliar development by 20-40 %, were indicated to be caused by the presence of dispersed oil in the open ocean. The heterogeneous distribution of oil droplets aggravated the direct detection and biochemical indicators for oil are presented and discussed. Our findings serve as a case study for identifying and tracing subsurface propagation of oil, demonstrating the feasibility of utilizing standard oceanographic and ecotoxicological methods to assess the impacts of oil spill events in the open ocean. Ultimately, it encourages the establishment of appropriate measures and responses regarding the liability and regulation of entities to be held accountable for oil spills in the marine environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Simarouba, a neotropical genus in the family Simaroubaceae, currently lacks comprehensive genomic data in existing databases. This study aims to fill this gap by providing genomic resources for three Simarouba species, S. amara, S. versicolor, and S. glauca. It also aims to perform comparative molecular evolutionary analyses in relation to other species within the order Sapindales. The analysis of these three Simarouba species revealed the presence of the typical quadripartite structure expected in plastomes. However, some pseudogenization events were identified in the psbC, infA, rpl22, and ycf1 genes. In particular, the CDS of the psbC gene in S. amara was reduced from 1422 bp to 584 bp due to a premature stop codon. Nucleotide diversity data pointed to gene and intergenic regions as promising candidates for species and family discrimination within the group, specifically matK, ycf1, ndhF, rpl32, petA-psbJ, and trnS-trnG. Selection signal analyses showed strong evidence for positive selection on the rpl23 gene. Phylogenetic analyses indicated that S. versicolor and S. glauca have a closer phylogenetic relationship than S. amara. We provide chloroplast genomes of three Simaruba species and use them to elucidate plastome evolution, highlight the presence of pseudogenization, and identify potential DNA barcode regions., (© 2024. The Author(s).)

Purpose: To compare texture-based analysis using convolutional neural networks (CNNs) against lung densitometry in detecting chest computed tomography (CT) image abnormalities., Material and Methods: A U-NET was used for lung segmentation, and an ensemble of 7 CNN architectures was trained for the classification of low-attenuation areas (LAAs; emphysema, cysts), normal-attenuation areas (NAAs; normal parenchyma), and high-attenuation areas (HAAs; ground-glass opacities, crazy paving/linear opacity, consolidation). Lung densitometry also computes (LAAs, ≤-950 HU), NAAs (-949 to -700 HU), and HAAs (-699 to -250 HU). CNN-based and densitometry-based severity indices (CNN and Dens, respectively) were calculated as (LAA+HAA)/(LAA+NAA+HAA) in 812 CT scans from 176 normal subjects, 343 patients with emphysema, and 293 patients with interstitial lung disease (ILD). The correlation between CNN-derived and densitometry-derived indices was analyzed, alongside a comparison of severity indices among patient subgroups with emphysema and ILD, using the Spearman correlation and ANOVA with Bonferroni correction., Results: CNN-derived and densitometry-derived severity indices (SIs) showed a strong correlation (ρ=0.90) and increased with disease severity. CNN-SIs differed from densitometry SIs, being lower for emphysema and higher for moderate to severe ILD cases. CNN estimations for normal attenuation areas were higher than those from densitometry across all groups, indicating a potential for more accurate characterization of lung abnormalities., Conclusions: CNN outputs align closely with densitometry in assessing lung abnormalities on CT scans, offering improved estimates of normal areas and better distinguishing similar abnormalities. However, this requires higher computing power., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Polyploid varieties have been suggested as an alternative approach to promote drought tolerance in citrus crops. In this study, we compared the responses of diploid and tetraploid Sunki 'Tropical' rootstocks to water deficit when grafted onto 'Valencia' sweet orange trees and subjected to water withholding in isolation or competition experiments under potted conditions. Our results revealed that, when grown in isolation, tetraploid rootstocks took longer to show drought symptoms, but this advantage disappeared when grown in competition under the same soil moisture conditions. The differences in drought responses were mainly associated with variations in endogenous leaf levels of abscisic acid (ABA), hydrogen peroxide (H₂O₂) and carbohydrates among treatments. Overall, tetraploids were more affected by drought in individual experiments, showing higher H₂O₂ production, and in competition experiments, rapidly increasing ABA production to regulate stomatal closure and reduce water loss through transpiration. Therefore, our results highlight the crucial importance of evaluating diploid and tetraploid rootstocks under the same soil moisture conditions to better simulate field conditions, providing important insights to improve selection strategies for more resilient citrus rootstocks., (© 2024 John Wiley & Sons Ltd.)

Objective: Our aim was to report time-loss match injuries in Portugal's "Divisão de Honra" (Portuguese first tier) in the 2022/2023 season, focusing on injury incidence, burden, anatomical region, and type, to assess their impact on athletes' health and availability to play., Methods: A prospective cohort study was conducted monitoring injuries via an online form filled in by each team's medical department, categorizing player position, as well as injury type, location, and severity. Incidence and burden were calculated per 1000 player-match-hours., Results: The overall injury incidence was 54.4 injuries per 1000 player-match-hours (95% CI 30.3-96.2). Forwards had higher injury incidence than backs. Lower limbs were the most affected locations-29 injuries/1000 h of exposure (95% CI 13.7-52.0). Sprain/ligaments injuries were the most common type of injury (14.4 injuries/1000 h (95% CI 3.7-30.0), followed by muscle injuries (8.1 injuries/1000 h 95% CI 4.9-11.5)., Discussion: Injury incidence was higher than what is reported in amateur competitions and lower than for professionals. Injury severity was similar to that in other studies. Our study suggests a lower injury burden than in other semi-professional and elite leagues. These findings highlight the need for targeted injury prevention strategies in the Portuguese Rugby Union to increase athletes' availability by decreasing injury incidence and/or burden. Further research with broader participation and training injury data is needed.

Background: Prompt diagnosis and treatment of vertebral artery dissection (VAD) is critical for preventing stroke. The use of emboli detection studies (EDS) using Doppler ultrasonography is an emerging method that has been proposed to predict stroke risk and guide subsequent treatment. Limited data exists on the predictive value of this emerging modality in the posterior circulation. This study aims to assess the predictive value of emboli detection studies (EDS) in forecasting inpatient stroke in VAD patients and identify associated risk factors. Patients were recruited between January 2009 and January 2018., Methods: We performed a retrospective analysis of 104 consecutive patients with VAD who underwent EDS at our institution. Patients underwent transcranial ultrasonography for detection of microemboli and were followed clinically and radiographically thereafter for evidence of stroke., Results: A total of 104 patients with spontaneous (58 %), traumatic (39 %) or iatrogenic (4 %) VAD were included in our analysis. Stroke occurred more frequently in patients with spontaneous VAD compared to traumatic VAD (p < 0.001). Microemboli were detected in 17 patients (16 %), including 18.3 % of spontaneous VAD, 12.5 % of traumatic VAD, and 25 % of iatrogenic VAD. 61 patients (59 %) suffered a posterior circulation stroke, however there was no significant association between detection of microemboli and stroke events (60 % of patients without microemboli vs. 53 % of patients with ≥ 1 HITS during EDS; p = 0.6). Similarly, no microemboli were detected in any of the patients who went on to develop a delayed stroke., Conclusions: In our single-institution retrospective analysis of patients with VAD, the detection of microemboli on EDS was not associated with stroke nor was it predictive of delayed stroke. Additionally, patients with spontaneous VAD may be at higher risk for stroke compared to traumatic VAD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Owing to its exposed nature, the skin can be injured by various factors, including by Staphylococcus aureus, which inhabits its innate microbiota. Treatment of infected wounds presents an important challenge, making it imperative to develop new treatment options. Plant-derived formulations, such as those containing Melaleuca alternifolia essential oil (MaEO), are used for wound treatment because of their healing, anti-inflammatory, and antimicrobial properties. This study presents a cream containing 2% MaEO (2% CMa) and evaluates its effects in an S. aureus-infected wound murine model. The 2% CMa was subjected to quality control testing and pH and analysis of density, organoleptic characteristics, and microbiological effects. The quality control parameters all revealed the good stability of the 2% CMa. The formulation strongly reduced the S. aureus ATCC 6538 colony-forming unit (CFU) count in an ex vivo porcine skin model. In the murine model, daily topical application of 2% CMa reduced the severity and size of S. aureus-infected wounds and the bacterial load. These effects may be due to the presence of terpinen-4-ol, which exhibits anti-inflammatory activity. Based on these findings, the formulation exhibits good quality and safety. We suggest the topical application of this formulation, which exhibited an antimicrobial effect, as an interesting treatment strategy for wound healing., (Copyright © 2024 Elsevier B.V. All rights reserved.)

DARPP-32 (dopamine and cAMP-regulated phosphoprotein Mr. 32 kDa) is a phosphoprotein that is modulated by multiple receptors integrating intracellular pathways and playing roles in various physiological functions. It is regulated by dopaminergic receptors through the cAMP/protein kinase A (PKA) pathway, which modulates the phosphorylation of threonine 34 (Thr34). When phosphorylated at Thr34, DARPP-32 becomes a potent protein phosphatase-1 (PP1) inhibitor. Since dopamine is involved in the development of GABAergic neurons and DARPP-32 is expressed in the developing brain, it is possible that DARPP-32 has a role in GABAergic neuronal development. We cloned the zebrafish darpp-32 gene (ppp1r1b) gene and observed that it is evolutionarily conserved in its inhibitory domain (Thr34 and surrounding residues) and the docking motif (residues 7-11 (KKIQF)). We also characterized darpp-32 protein expression throughout the 5 days post-fertilization (dpf) zebrafish larval brain by immunofluorescence and demonstrated that darpp-32 is mainly expressed in regions that receive dopaminergic projections (pallium, subpallium, preoptic region, and hypothalamus). We demonstrated that dopamine acutely suppressed darpp-32 activity by reducing the levels of p-darpp-32 in the 5dpf zebrafish larval brain. In addition, the knockdown of darpp-32 resulted in a decrease in the number of GABAergic neurons in the subpallium of the 5dpf larval brain, with a concomitant increase in the number of DAergic neurons. Finally, we demonstrated that darpp-32 downregulation during development reduced the motor behavior of 5dpf zebrafish larvae. Thus, our observations suggest that darpp-32 is an evolutionarily conserved regulator of dopamine receptor signaling and is required for the formation of GABAergic neurons in the developing telencephalon., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Few studies have examined long-term mortality following traumatic brain injury (TBI) in a military population. This is a secondary analysis of a prospective, longitudinal study that examines long-term mortality (up to 10 years) post-TBI, including analyses of life expectancy, causes of death, and risk factors for death in service members and veterans (SM/V) who survived the acute TBI and inpatient rehabilitation. Among 922 participants in the study, the mortality rate was 8.3% following discharge from inpatient rehabilitation. The mean age of death was 54.5 years, with death occurring on average 3.2 years after injury, and with an average 7-year life expectancy reduction. SM/V with TBI were nearly four times more likely to die compared with the U.S. general population. Leading causes of death were external causes of injury, circulatory disease, and respiratory disorders. Also notable were deaths due to late effects of TBI itself and suicide. Falls were a significant mechanism of injury for those who died. Those who died were also more likely to be older at injury, unemployed, non-active duty status, not currently married, and had longer post-traumatic amnesia, longer rehabilitation stays, worse independence and disability scores at rehabilitation discharge, and a history of mental health issues before injury. These findings indicate that higher disability and less social supportive infrastructure are associated with higher mortality. Our investigation into the vulnerabilities underlying premature mortality and into the major causes of death may help target future prevention, surveillance, and monitoring interventions.

Selenium (Se) is a nutrient whose daily intake is often below the recommended levels in people. Biofortification with Se is a method to increase this intake by raising the Se concentration in tomato fruits, an effect dependent on sources and modes of application. Additionally, Se application can promote the enhancement of other compounds in tomato fruits, altering their metabolism, which may increase the fruit's shelf life. This study aimed to determine how different strategies of applying a multi-nutrient fertilizer containing Se (SeMNF) can increase the Se content and other bioactive compounds and enhance the shelf life of tomato ( Solanum lycopersicum L.) fruits. Different foliar fertilization strategies involving the use of SeMNF were evaluated in field trials conducted on commercial tomato crops. Indeterminate-growth tomatoes were used, and different Se doses and application strategies were tested. Harvesting was conducted in three phases according to fruit ripening. Each harvested fruit was assessed for the Se content, macro and micronutrients, total phenolic compounds, vitamin C, antioxidant activity, carotenoids, pH, total titratable acidity, and total soluble solids in tomato fruits. Doses of 15 g ha -1 of Se, split into three applications, increased the Se content in the fruits at 1 and 2 harvests. The application of SeMNF at Se doses above 10 g of Se ha -1 increased firmness, days of ripening, and the nutritional quality of the tomatoes (higher contents of carotenoids (+39%), lycopene (+33%), antioxidant activity (+16%), total phenolic compounds (+38%), and vitamin C (+14%) in a dose-dependent effect of the application strategy used. These results contributed to an increase in the shelf life of tomatoes, consequently reducing food waste.

Chronic low-grade inflammation is a common feature of obesity and plays a crucial role in the progression of its complications. Vitamin D (VitD) plays an important role in modulating the immune response and regulating inflammation. Thus, this systematic review and meta-analysis aimed to evaluate the effects of isolated VitD supplementation on main inflammatory markers in overweight and obese individuals with no comorbidities and with VitD deficiency. We hypothesized that the increase in serum VitD concentrations after supplementation would significantly reduce the concentrations of inflammatory markers. The search was conducted in Medline/PubMed, SCOPUS, EMBASE, and Web of Science. Eleven randomized placebo-controlled studies were included in the final analysis, with a total of 504 participants and daily (1000-7000 international units) or bolus (100,000-200,000 international units) doses of VitD lasting from 2 to 26 weeks. The VitD supplementation did not influence C-reactive protein (mean difference [MD]: 0.01; 95% confidence interval [CI] -0.37, 0.39; P = .97), interleukin-6 (MD: -0.34; 95% CI -1.09, 0.42; P = .38), and tumor necrosis factor concentrations (MD: -0.02; 95% CI -0.23, 0.19; P = .85). In the analysis considering the studies with a significant increase in serum VitD concentrations, VitD supplementation also did not influence C-reactive protein (MD: -0.17; 95% CI -0.88, 0.54; P = .64), interleukin-6 (MD: -0.47; 95% CI -1.31, 0.37; P = .27), and tumor necrosis factor concentrations (MD: 0.01; 95% CI -1.34, 1.37; P = .98). This meta-analysis suggests that VitD supplementation does not significantly alter inflammatory markers in overweight and obese individuals., Competing Interests: Author Declarations The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Pediatric intracranial arteriovenous malformation (AVM) patients are commonly admitted to the emergency room (ER). Increasing patient utilization of the ER has been associated with healthcare disparities and a trend of decreased efficiency. The aim of this study was to evaluate the trends of pediatric AVM ER admissions over recent years and identify factors associated with health care resource utilization and outcomes., Methods: The 2016-2019 National Inpatient Sample was queried for patients under the age of 18 admitted with AVM. Cases of admission through the ER were identified. Demographic and severity factors associated with ER admission were explored using comparative and regression statistics., Results: Of 3875 pediatric patients with AVM admitted between 2016 and 2019, 1280 (33.0%) were admitted via the ER. Patients admitted via the ER were more likely to be in the lowest median income category (P < 0.001), on Medicaid insurance (P = 0.008), or in the South (P < 0.001) than patients admitted otherwise. There was increased severity and increased rates of intracranial hemorrhage (ICH) in patients admitted via the ER (P < 0.001). Finally, there were increasing trends in ER admissions and ICH throughout the years., Conclusions: ER admission of pediatric AVM patients with ICH is increasing and is associated with a distinct socioeconomic profile and increased healthcare resource utilization. These findings may reflect decreased access to more advanced diagnostic modalities, primary care, and other important resources. Identifying populations with barriers to care is likely an important component of policy aimed at decreasing the risk of severe disease presentation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Diabetes mellitus (DM) has a complex relationship with pancreatic cancer. This study examines the impact of preoperative DM, both recent-onset and pre-existing, on long-term outcomes following pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC)., Methods: Data were extracted from the Recurrence After Whipple's (RAW) study, a multi-centre cohort of PD for pancreatic head malignancy (2012-2015). Recurrence and five-year survival rates of patients with DM were compared to those without, and subgroup analysis performed to compare patients with recent-onset DM (less than one year) to patients with established DM., Results: Out of 758 patients included, 187 (24.7%) had DM, of whom, 47 of the 187 (25.1%) had recent-onset DM. There was no difference in the rate of postoperative pancreatic fistula (DM: 5.9% vs no DM 9.8%; p = 0.11), five-year survival (DM: 24.1% vs no DM: 22.9%; p = 0.77) or five-year recurrence (DM: 71.7% vs no DM: 67.4%; p = 0.32). There was also no difference between patients with recent-onset DM and patients with established DM in postoperative outcomes, recurrence, or survival., Conclusion: We found no difference in five-year recurrence and survival between diabetic patients and those without diabetes. Patients with pre-existing DM should be evaluated for PD on a comparable basis to non-diabetic patients., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. All rights reserved.)

A growing proportion of percutaneous procedures are performed in outpatient centers. The shift from hospitals to ambulatory surgery centers and office-based laboratories has been driven by a number of factors, including declining reimbursements, increased patient demand, and competition for hospital resources. This transition has been dominated by the interventional radiology, cardiology, and vascular surgery fields. Cerebral angiography, in contrast, is still performed almost exclusively in a hospital-based setting, despite sharing many features with other endovascular procedures commonly performed in outpatient centers. As interest grows in performing cerebral angiography in outpatient endovascular centers, much can be learned from the decades of experience that our interventional colleagues have in the outpatient setting. In this article we examine the outpatient experience of other interventional fields and apply key principles to evaluate the prospect of outpatient neurointervention. The literature suggests that cerebral angiography can feasibly be performed in an outpatient center in both private and academic settings, as some groups have begun to do. Outpatient endovascular centers have helped to improve the patient experience, liberate inpatient resources, and control costs in other interventional fields, and might offer neurointerventionalists an opportunity to do the same., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Arteriovenous malformations (AVMs) of the brain stem are very rare lesions accounting for 2% to 6% of the cerebral AVMs.1,2 They carry higher risk of hemorrhage3,4 and are associated with poor prognosis.5-7 This is a 27-year-old man who presented with intraventricular hemorrhage, hydrocephalus, and poor neurological status secondary to ruptured AVM. Deep branches from right triplicate superior cerebellar artery, left duplicate superior cerebellar artery, and right posterior cerebral artery were feeding the AVM. The drainage was directly to the vein of Galen. MRI brain showed the location of the AVM in the posterior midbrain area. The AVM was mostly exophytic to brain stem parenchyma which made it favorable for surgical resection.8 After cerebrospinal fluid diversion (initially with external ventricular drain that was then converted to ventriculoperitoneal shunt), the patient showed some neurological improvement over the next weeks. Thus, the decision was made to treat the AVM. The patient underwent preoperative embolization followed by an occipital interhemispheric transtentorial approach. This illustrative video outlines the steps and technical nuances of the right occipital interhemispheric transtentorial approach for microsurgical resection of this Spetzler-Martin grade 3 (S1, E1, V1)/supplementary Spetzler-Martin grade 2 (A2, B0, C0) AVM. Postoperative cerebral angiogram demonstrated no AVM residual. The patient was discharged to a rehabilitation institute and at 3 months of follow-up, he was alert and orientated to time, person, and place without focal deficits. The patient consented to the procedure and to the publication of his image. Institutional Review Board approval was deemed unnecessary., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Introduction and Aim: Type 3 Familial Partial Lipodystrophy (FPLD3) is a rare metabolic disease related to pathogenic PPARG gene variants. FPLD3 is characterized by a loss of fatty tissue in the upper and lower limbs, hips, and face. FPLD3 pathophysiology is usually associated with metabolic comorbidities such as type 2 diabetes, insulin resistance, hypertriglyceridemia, and liver dysfunction. Here, we clinically and molecularly characterized FPLD3 patients harboring novel PPARG pathogenic variants., Materials and Methods: Lipodystrophy-suspected patients were recruited by clinicians from an Endocrinology Reference Center. Clinical evaluation was performed, biological samples were collected for biochemical analysis, and DNA sequencing was performed to define the pathogenic variants associated with the lipodystrophic phenotype found in our clinically diagnosed FPLD subjects. Bioinformatics predictions were conducted to characterize the novel mutated PPARγ proteins., Results: We clinically described FPLD patients harboring two novel heterozygous PPARG variants in Brazil. Case 1 had the c.533T > C variant, which promotes the substitution of leucine to proline in position 178 (p.Leu178Pro), and cases 2 and 3 had the c.641 C > T variant, which results in the substitution of proline to leucine in the position 214 (p.Pro214Leu) at the PPARγ2 protein. These variants result in substantial conformational changes in the PPARγ2 protein., Conclusion: Two novel PPARG pathogenic variants related to FPLD3 were identified in a Brazilian FPLD cohort. These data will provide new epidemiologic data concerning FPLD3 and help understand the genotype-phenotype relationships related to the PPARG gene., (© 2024. The Author(s).)

Background: Postoperative pancreatic fistula serves as the principle cause for the morbidity and mortality observed after pancreatectomy. Continuous drain irrigation as a treatment strategy for infected pancreatic necrosis has previously been described; however, its role adter pancreatectomy has yet to be determined. The aim of this study was to determine whether continuous drain irrigation reduces postoperative pancreatic fistula., Methods: A meta-analysis of the pre-existing literature was performed. The primary end point was whether continuous drain irrigation reduced postoperative pancreatic fistula after pancreatectomy. The secondary end point evaluated its impact on postoperative morbidity, mortality, and length of stay., Results: Nine articles involving 782 patients were included. Continuous drain irrigation use was associated with a statistically significant reduction in postoperative pancreatic fistula rates (odds ratio [95% confidence interval] 0.40 [0.19-0.82], P = .01). Upon subgroup analysis, a significant reduction in clinically relevant postoperative pancreatic fistula was also noted (odds ratio 0.37 [0.20-0.66], P = .0008). A reduction in postoperative complications was also observed-delayed gastric emptying (0.45 [0.24-0.84], P = .01) and the need for re-operation (0.33 [0.11-0.96], P = .04). This reduction in postoperative complications translated into a reduced length of stay (mean difference -2.62 [-4.97 to -0.26], P = .03)., Conclusion: Continuous drain irrigation after pancreatectomy is a novel treatment strategy with a limited body of published evidence. After acknowledging the limitations of the data, initial analysis would suggest that it may serve as an effective risk mitigation strategy against postoperative pancreatic fistula. Further research in a prospective context utilizing patient risk stratification for fistula development is, however, required to define its role within clinical practice., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Long COVID presents with diverse symptoms after COVID-19. Different clusters of symptoms have been reported; however, their persistence beyond 2 years after COVID-19 remains unclear. In this cohort study, we prospectively evaluated individuals with previous severe COVID-19 presenting with long COVID at a two-year follow-up. We characterized the included patients and performed a cluster analysis of symptoms through multiple correspondence analysis and hierarchical clustering. A total of 199 patients with long COVID were included. The median age was 58 years (48-69), 56% were male, and the median follow-up time since the COVID-19 diagnosis was 26 months (IQR: 25, 27). Three symptom clusters were identified: Cluster 1 is characterized by fatigue, myalgia/arthralgia, a low prevalence of symptoms, and a lack of specific symptoms; Cluster 2 is defined by a high prevalence of fatigue, myalgia/arthralgia, and cardiorespiratory symptoms, including palpitations, shortness of breath, cough, and chest pain; and Cluster 3 is demonstrated a high prevalence of ageusia, anosmia, fatigue, and cardiorespiratory symptoms. Our study reinforces the concept of symptom clustering in long COVID, providing evidence that these clusters may persist beyond two years after a COVID-19 diagnosis. This highlights the chronic and debilitating nature of long COVID and the importance of developing strategies to mitigate symptoms in these patients.

Introduction: This study is the first multicentric report on the safety, efficacy, and technical performance of utilizing a large bore (0.081″ inner diameter) access catheter in neurovascular interventions., Methods: Data were retrospectively collected from seven sites in the United States for neurovascular procedures via large bore 0.081″ inner diameter access catheter (Benchmark BMX81, Penumbra, Inc.). The primary outcome was technical success, defined as the access catheter reaching its target vessel. Safety outcomes included periprocedural device-related and access site complications., Results: There were 90 consecutive patients included. The median age of the patients was 63 years (IQR: 53, 68); 53% were female. The most common interventions were aneurysm embolization (33.3%), carotid stenting (12.2%), and arteriovenous malformation embolization (11.1%). The transradial approach was most used (56.7%), followed by transfemoral (41.1%). Challenging anatomic variations included severe vessel tortuosity (8/90, 8.9%), type 2 aortic arch (7/90, 7.8%), type 3 aortic arch (2/90, 2.2%), bovine arch (2/90, 2.2%), and severe angle (<30°) between the subclavian artery and target vessel (1/90, 1.1%). Technical success was achieved in 98.9% of the cases (89/90), with six cases requiring a switch from radial to femoral (6.7%) and one case from femoral to radial (1.1%). There were no access site complications or complications related to the 0.081″ catheter. Two postprocedural complications occurred (2.2%), unrelated to the access catheter., Conclusion: The BMX™ 81 large-bore access catheters was safe and effective in both radial and femoral access across a wide range of neurovascular procedures, achieving high technical success without any access site or device-related complications., Competing Interests: Declaration of conflicting interestsThe author(s) have disclosed any potential conflicts of interest regarding the research, authorship, and publication of this article in the disclosure section.

Background: Neurological complications of bacterial endocarditis (BE) are common, including acute ischemic stroke (AIS). Although mechanical thrombectomy (MT) is effective for large vessel occlusion (LVO) stroke, data are limited on MT for LVOs in patients with endocarditis. We assess outcomes in patients treated with thrombectomy for LVOs with concurrent BE., Methods: The National Inpatient Sample (NIS) was used. The NIS was queried from October 2015-2019 for patients receiving MT for LVO of the middle cerebral artery. Odds ratios (OR) were calculated using a multivariate logistic regression model., Results: A total of 635 AIS with BE patients and 57 420 AIS only patients were identified undergoing MT. AIS with BE patients had a death rate of 26.8% versus 10.2% in the stroke alone cohort, and were also less likely to have a routine discharge (10.2% vs 20.9%, both P<0.0001). AIS with BE patients had higher odds of death (OR 3.94) and lower odds of routine discharge (OR 0.23). AIS with BE patients also had higher rates of post-treatment cerebral hemorrhage, 39.4% vs 23.7%, with an OR of 2.20 (P<0.0001 for both analyses). These patients also had higher odds of other complications, including hydrocephalus, respiratory failure, acute kidney injury, and sepsis., Conclusion: While MT can be used to treat endocarditis patients with LVOs, these patients have worse outcomes. Additional investigations should be undertaken to better understand their clinical course, and further develop treatments for endocarditis patients with stroke., Competing Interests: Competing interests: The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. Robert M Starke has consulting and teaching agreements with Penumbra, Abbott, Medtronic, InNeuroCo, and Cerenovus., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Fetal posterior communicating artery (PComA) is a variant of the cerebral vasculature.1 Woven endobridge (WEB) embolization carries a good safety profile as treatment for ruptured wide neck PComA aneurysms, without the need for antiplatelet therapy. However, the reported occlusion rates are not optimal.2 Flow diversion is suboptimal in treating aneurysms originating from fetal PComA.3 Here we present a case of a 78-year-old female patient with a history of ruptured right fetal PComA aneurysm with wide base. It was initially treated with WEB embolization at an outside hospital. After WEB implantation, the initial follow-up of cerebral angiogram (6 months later) demonstrated a neck recurrence measuring 6 × 3 mm. Approximately 1 year after the initial treatment, pipeline embolization was performed and patient was placed on antiplatelet therapy since. Follow-up images demonstrated a 6 mm × 4 mm persistent neck remnant. Her care was transferred to our institution. Cerebral angiogram obtained 36 months post-WEB implantation showed growth of the neck remnant measuring 9 × 8.5 mm. The WEB device was found to be folded in the aneurysmal fundus. Given this was a growing recurrent previously ruptured fetal PComA aneurysm with a pipeline stent in the internal carotid artery the decision was made to retreat with microsurgical clipping; carotid access at the neck was required for proximal control. We achieved complete aneurysm obliteration through a minimal invasive approach. The patient gave informed consent for surgery and video recording. Institutional Review Board approval was deemed unnecessary., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

This study evaluates the use of the crosswalk between the PTSD Checklist-Civilian (PCL-C) and PTSD Checklist for DSM-5 (PCL-5) designed by Moshier et al. (2019) in a sample of service members and veterans (SM/V; N = 298) who had sustained a traumatic brain injury (TBI) and were receiving inpatient rehabilitation. The PCL-C and PCL-5 were completed at the same time. Predicted PCL-5 scores for the sample were obtained according to the crosswalk developed by Moshier et al. We used three measures of agreement: intraclass correlation coefficient (ICC), mean difference between predicted and observed scores, and Cohen's κ to determine the performance of the crosswalk in this sample. Subgroups relevant to those who have sustained a TBI, such as TBI severity, were also examined. There was strong agreement between the predicted and observed PCL-5 scores (ICC = .95). The overall mean difference between predicted and observed PCL-5 scores was 0.07 and not statistically significant (SD = 8.29, p = .89). Significant mean differences between predicted and observed PCL-5 scores calculated between subgroups were seen in Black participants (MD = -4.09, SD = 8.41, p = .01) and those in the Year 5 follow-up group (MD = 1.77, SD = 7.14, p = .03). Cohen's κ across subgroups had a mean of κ = 0.76 (.57-1.0), suggesting that there was moderate to almost perfect diagnostic agreement. Our results suggest the crosswalk created by Moshier et al. can be applied to SM/V who have suffered a TBI. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Objective: Existing literature documents high rates of experienced violence in asylum seekers. Despite this high prevalence, experiences of traumatic stress are neither necessary nor sufficient grounds for claiming asylum, without documented experiences of persecution. The aim of the current study is to better understand the role of co-occurring pre-migratory social determinants, stigma, and trauma on the experiences of persecution among asylum seekers in the United States., Method: We conducted a retrospective file review of legal declarations submitted by 25 asylum seekers who participated in forensic mental health evaluations at a pro-bono asylum clinic. We coded de-identified data for co-occurring events of trauma, social determinants of health, and components of "discrimination" from the legal definition of persecution - conceptualizing persecution as stigma-driven infliction of violence. Data was analyzed using a tiered deductive and inductive reflexive thematic analysis., Results: Findings suggest pre-migratory social determinants included demographics, neighborhood, economic, environmental, and social and cultural level disparities across various grounds for seeking asylum, and experiences of stigma were associated with the specific acts of violence and harm., Conclusions: Our findings - specific to asylum seekers who have obtained legal representation and completed applications for asylum in the United States - describe the co-occurrence of social determinants, stigma and traumatic experiences among asylum seekers. To our knowledge, this study is the first of its kind to bridge the existing legal framework of asylum to a psychological construct incorporating trauma, stigma, and social determinants of health, lending support for the conceptualization of persecution as stigma-driven trauma., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Probiotic-containing foods are among the most appreciated functional foods; however, probiotic-based dairy products cannot be consumed by people who are lactose intolerant, allergic to milk, or vegetarian or vegan individuals. Thus, new non-dairy matrices have been tested for probiotics delivery. This study evaluated the growth and viability of Limosilactobacillus fermentum ATCC 23271 and Lacticaseibacillus rhamnosus ATCC 9595 in Pitanga juice (Eugenia uniflora L.). The effects of the fermentation on the antioxidant and anti-infective properties of the juice were also analyzed. The E. uniflora juice allowed lactobacilli growth without supplementation, reaching rates around 8.4 Log CFU/mL and producing organic acids (pH values < 4) after 72 h of fermentation. The strain remained viable after 35 days of refrigerated storage. Fermentation by these bacteria increases the antioxidant capacity of the juice. The central composite rotational design was employed to evaluate the effects of bacterial inoculum and pulp concentration on growth and organic acids production by L. fermentum ATCC 23271. The strain was viable and produced organic acids in all tested combinations. L. fermentum-fermented juice and its cell-free supernatant significantly increased the survival of Tenebrio molitor larvae infected by enteroaggregative Escherichia coli 042. The results obtained in this study provide more insights into the potential of Pitanga juice to develop a functional non-dairy probiotic beverage with antioxidant and anti-infective properties., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

The objective of this study was to assess the photolysis-mediated degradation of malathion in standard and commercial formulations, and to determine the toxicity of these degraded formulations. Degradation tests were carried out with 500 μg L -1 of malathion and repeated three times. The initial and residual toxicity was assessed by using Lactuca sativa seeds for phytotoxicity, Stegomyia aegypti larvae for acute toxicity, and Stegomyia aegypti mosquitoes (cultivated from the larval stage until emergence as mosquitoes) to evaluate the biochemical markers of sublethal concentrations. For the standard formulations the photolytic process efficiently reduced the initial concentration of malathion to levels below the regulatory limits however, the formation of byproducts was revealed by chromatography, which allowed for a more complete proposal of photolytic-mediated malathion degradation route. The degraded formulations inhibited the growth of L. sativa seeds, while only the untreated formulations showed larvicidal activity and mortality. Both formulations slightly inhibited acetylcholinesterase activity in S. aegypti mosquitoes, while the standard formulation decreased and the commercial formulation increased glutathione S-transferase activity. However, there were no significant differences for superoxide dismutase, esterase-α, esterase-β and lipid peroxidation. These findings indicate that in the absence of the target compound, the presence of byproducts can alter the enzymatic activity. In general, photolysis effectively degrade malathion lower than the legislation values; however, longer treatment times must be evaluated for the commercial formulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Antipsychotics (APs) have been increasingly prescribed for psychiatric disorders from schizophrenia to disruptive behavioral conditions. These drugs have been associated with considerable side effects, such as weight gain, and increasing evidence has also indicated that its use impacts gut microbiota (GM), although this connection is still little understood. To assess APs effects on the GM of patients starting or ongoing treatment, a systematic review was carried out in PubMed and Scopus databases. Twelve articles were considered eligible for the review, which investigated the effects of risperidone (5 studies), quetiapine (3), amilsupride (1), olanzapine (1), and unspecified atypical drugs (2). Eleven reported changes in GM in response to APs, and associations between the abundance of bacterial groups and different metabolic parameters were described by most of them. However, the studies were noticeably heterogeneous considering design, methods, and results. In this way, the effects of APs on GM composition and diversity were inconclusive. Despite the uncertain interactions, a more comprehensive understanding on how microbiota is affected by APs may help to optimize treatment, potentially minimizing side effects and improving adherence to treatment., Competing Interests: Declaration of competing interest On behalf of all authors, I do inform and assume the whole responsibility that there is no conflict of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Patients undergoing pancreaticoduodenectomy for distal cholangiocarcinoma (dCCA) often develop cancer recurrence. Establishing timing, patterns and risk factors for recurrence may help inform surveillance protocol strategies or select patients who could benefit from additional systemic or locoregional therapies. This multicentre retrospective cohort study aimed to determine timing, patterns, and predictive factors of recurrence following pancreaticoduodenectomy for dCCA., Materials and Methods: Patients who underwent pancreaticoduodenectomy for dCCA between June 2012 and May 2015 with five years of follow-up were included. The primary outcome was recurrence pattern (none, local-only, distant-only or mixed local/distant). Data were collected on comorbidities, investigations, operation details, complications, histology, adjuvant and palliative therapies, recurrence-free and overall survival. Univariable tests and regression analyses investigated factors associated with recurrence., Results: In the cohort of 198 patients, 129 (65%) developed recurrence: 30 (15%) developed local-only recurrence, 44 (22%) developed distant-only recurrence and 55 (28%) developed mixed pattern recurrence. The most common recurrence sites were local (49%), liver (24%) and lung (11%). 94% of patients who developed recurrence did so within three years of surgery. Predictors of recurrence on univariable analysis were cancer stage, R1 resection, lymph node metastases, perineural invasion, microvascular invasion and lymphatic invasion. Predictors of recurrence on multivariable analysis were female sex, venous resection, advancing histological stage and lymphatic invasion., Conclusion: Two thirds of patients have cancer recurrence following pancreaticoduodenectomy for dCCA, and most recur within three years of surgery. The commonest sites of recurrence are the pancreatic bed, liver and lung. Multiple histological features are associated with recurrence., (© 2024 Published by Elsevier Ltd.)

Trypanosoma cruzi, a flagellated protozoan, is the causative agent of Chagas disease. The parasite has developed various mechanisms to get through its intricate life cycle and adapt to different evolutionary phases. T. cruzi proliferates in the insect vector's digestive tract as an epimastigote form, encountering fluctuating nutrient availability and oxidative stress caused by the digestion of red blood cells from the mammalian host blood meal. To unravel how the parasite's metabolism adapts to these changing conditions, we conducted an analysis of the chemical species present in epimastigote forms. This involved comparing cultured parasites with those subjected to nutritional deficiency or oxidative stress using untargeted metabolomics. We looked at 21 samples: seven biological copies of parasites that were actively growing, seven samples that were put in a medium without nutrients for 3 h, and seven samples that were treated with glucose oxidase for 30 min to make H 2 O 2 continuously. Importantly, in all conditions, parasite viability was maintained when the samples were collected. Upon nutrient removal, we observed a substantial decrease in amino acids and carbohydrate metabolites, accompanied by the accumulation of fatty acids and steroids, with the predominance of inositol and sphingolipid metabolism, along with a simultaneous decrease in the levels of H 2 O 2 . In the presence of H 2 O 2 , a significant rise in components of the pentose pathway and specific amino acids such as methionine and serine occurred, along with pathways related to an increase in antioxidant species metabolism such as ribulose 5-phosphate and glyceric acid. Conversely, fatty acid and steroid levels decrease. We found no common increase in metabolites or lipids. In contrast, eight species (succinic acid, glutamic acid, valine, 2-hydroxyisocaproic acid, alanine, indolelactic acid, proline, and lanosterol) were consumed under both stresses. These findings underscore the rapid and distinct enrichment responses in amino acids, lipids, and carbohydrates required to cope with each different environmental condition. We concluded that T. cruzi presents a flexible metabolism that rapidly adapts to variable changes in the environment., (© 2024 John Wiley & Sons Ltd.)

Microorganisms with multiple ecological functions can be a useful biotechnological resource in integrated pest- and disease-management programs. This work aimed to investigate the potential endophytic and virulent effects of a strain of Purpureocillium lilacinum on organic cultivation in Brazil. Specifically, the strain's ability to establish itself as an endophyte in common bean, soybean, and sunflower plants when inoculated via seed was evaluated. Furthermore, its antifungal activity against phytopathogens and its pathogenicity and virulence against insects of the order Lepidoptera, Coleoptera, and Hemiptera were evaluated. Furthermore, the strain was evaluated for its biochemical and physiological characteristics. For virulence bioassays, the experiments were conducted under a factorial scheme (2 × 3), with the following factors: (a) fungal inoculation and control without inoculum and (b) types of inocula (blastospores, aerial conidia, and metabolites). The treatments were sprayed on insect species at different stages of development. In summary, it was found that the SBF054 strain endophytically colonized the common bean, with partial recovery from the root tissues of soybean and sunflower plants, 30 days after inoculation; suppressed 86% of Rhizoctonia solani mycelial growth in an in vitro assay; and controlled eggs, nymphs, and Euschistus heros adults. These multifunctional abilities are mainly attributed to the strain's mechanisms of producing metabolites, such as organic acids, soluble nutrients, and hydrolytic enzymes.

Objective: To investigate the effectiveness of botulinum toxin in the salivary glands of patients with neurological impairment and drooling and its impact on the quality of life., Materials and Methods: This systematic review was registered with the International Prospective Register of Systematic Reviews (CRD 42,023,435,242) and conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses. An electronic search was performed in the PubMed/MEDLINE, Embase, Scopus, Cochrane Library, and clinical trial databases until August 2023, no language restriction. Cohort studies and randomized clinical trials of patients diagnosed with drooling and neurological impairment who used botulinum toxin on the salivary gland were included, which evaluated subjective quality of life parameters. The risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist and Risk of Bias 2 tools. The certainty of the evidence was analyzed using the Grading of Recommendations Assessment, Development, and Evaluation approach., Results: Eight studies involving 317 patients were included. All studies, through subjective parameters, suggested the effectiveness of botulinum toxin in reducing drooling, resulting in an improvement in the quality of life. Three studies demonstrated improvements in swallowing and four in cases of respiratory diseases. Two clinical trials had a high risk of bias, whereas one had low risk. The five cohort studies that were evaluated had a high risk of bias. The certainty of the evidence was considered low., Conclusions: Based on the patient/caregivers' perception of improvement in drooling, dysphagia, and respiratory symptoms, it can be inferred that botulinum toxin application reduces subjective drooling in neurologically compromised patients. Its impact contributes to the general well-being and quality of life., Clinical Relevance: Injection of botulinum toxin into the salivary glands can be considered an alternative technique to surgical or medicinal approaches in reducing drooling. It is effective, less invasive and without significant side effects. It promotes a positive impact on the well-being and quality of life of neurological patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)