Protective Effect of Indole-3-Aldehyde in Murine COVID-19-Associated Pulmonary Aspergillosis.

Aspergillus fumigatus is an environmental fungus recently included in the fungal high-priority pathogens by the World Health Organization. While immunodeficiency and/or pre-existing lung damage represent a well-recognized fertile ground for fungal growth, it is increasingly being recognized that severe viral infections may similarly favor A. fumigatus colonization and infection, as recently experienced in the Coronavirus disease 2019 (COVID-19) pandemic. Herein, in a murine model of COVID-19-associated pulmonary aspergillosis (CAPA), obtained by the concomitant exposure to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein and A. fumigatus conidia, we found that the microbial compound indole-3-aldehyde (3-IAld) was able to ameliorate CAPA by working at multiple levels during viral infection and fungal superinfection, including epithelial barrier protection, promotion of antiviral responses, and limiting viral replication. As a consequence, 3-IAld limited the pathogenic sequelae of fungal superinfection as revealed by the controlled fungal burden and restrained inflammatory pathology. These results point to indole compounds as potential agents to prevent CAPA.

Immune gene regulation is associated with age and environmental adversity in a nonhuman primate.

Phenotypic aging is ubiquitous across mammalian species, suggesting shared underlying mechanisms of aging. Aging is linked to molecular changes to DNA methylation and gene expression, and environmental factors, such as severe external challenges or adversities, can moderate these age-related changes. Yet, it remains unclear whether environmental adversities affect gene regulation via the same molecular pathways as chronological, or 'primary', aging. Investigating molecular aging in naturalistic animal populations can fill this gap by providing insight into shared molecular mechanisms of aging and the effects of a greater diversity of environmental adversities - particularly those that can be challenging to study in humans or laboratory organisms. Here, we characterised molecular aging - specifically, CpG methylation - in a sample of free-ranging rhesus macaques living off the coast of Puerto Rico (n samples = 571, n individuals = 499), which endured a major hurricane during our study. Age was associated with methylation at 78,661 sites (31% of all sites tested). Age-associated hypermethylation occurred more frequently in areas of active gene regulation, while hypomethylation was enriched in regions that show less activity in immune cells, suggesting these regions may become de-repressed in older individuals. Age-associated hypomethylation also co-occurred with increased chromatin accessibility while hypermethylation showed the opposite trend, hinting at a coordinated, multi-level loss of epigenetic stability during aging. We detected 32,048 CpG sites significantly associated with exposure to a hurricane, and these sites overlapped age-associated sites, most strongly in regulatory regions and most weakly in quiescent regions. Together, our results suggest that environmental adversity may contribute to aging-related molecular phenotypes in regions of active gene transcription, but that primary aging has specific signatures in non-regulatory regions.

No-load resistance training as a promising alternative to stop detraining period due to covid-19 lockdown in older adults - Case report.

Restrictions to control the COVID-19 pandemic have caused older adults to stop their usual activities, including physical exercises. The novel approach of isometric no-load resistance training (NLRT) can be an interesting alternative to conventional training to oppose the harmful effects of detraining. We described the design and preliminary evaluation of an eight-week, twice-weekly NLRT program for older adults returning to strength training programs after COVID-19 lockdown. An older woman (66 years, 61.9kg, 158.5cm) and an older man (66 years, 84.1kg, 166.5cm) who were engaged in conventional strength training programs before the first COVID-19 lockdown participated in this case study. We collected muscle thickness measures using a B-mode ultrasound imaging and maximum isometric torque using an isokinetic dynamometer. Our results revealed that NLRT seems to be a good alternative to increase muscle thickness of knee and elbow flexors and extensors muscles in older adults. However, NLRT effects were inconsistent for maximum torque.

Sustainable extraction of proteins from lime peels using ultrasound, deep eutectic solvents, and pressurized liquids, as a source of bioactive peptides.

The aim of this work was to develop, for the first time, sustainable strategies, based on the use of Ultrasound-Assisted Extraction, Natural Deep Eutectic Solvents, and Pressurized Liquid Extraction, to extract proteins from lime (Citrus x latifolia) peels and to evaluate their potential to release bioactive peptides. PLE showed the largest extraction of proteins (66-69%), which were hydrolysed using three different enzymes (Alcalase 2.4 L FG, Alcalase®PURE 2.4 L, and Thermolysin). The in vitro antioxidant and antihypertensive activities of released peptides were evaluated. Although all hydrolysates showed antioxidant and antihypertensive activity, the hydrolysate obtained with Thermolysin showed the most significant values. Since the Total Phenolic Content in all hydrolysates was low, peptides were likely the main contributors to these bioactivities. Hydrolysates were analyzed by UHPLC-QTOF-MS and a total of 98 different peptides were identified. Most of these peptides were rich in amino acids associated with antioxidant activity.

Comparative Analysis of High-Frequency and Low-Frequency Transcutaneous Electrical Stimulation of the Right Median Nerve in the Regression of Clinical and Neurophysiological Manifestations of Generalized Anxiety Disorder.

Background/Objectives: The anxiolytic effect of transcutaneous electrical nerve stimulation (TENS) is associated with the activation of endogenous inhibitory mechanisms in the central nervous system. Both low-frequency, high-amplitude TENS (LF-TENS) and high-frequency, low-amplitude TENS (HF-TENS) are capable of activating opioid, GABA, serotonin, muscarinic, and cannabinoid receptors. However, there has been no comparative analysis of the effectiveness of HF-TENS and LF-TENS in the treatment of GAD. The purpose of our research was to study the effectiveness of direct HF-TENS and LF-TENS of the right median nerve in the treatment of patients with GAD compared with sham TENS. Methods: The effectiveness of direct HF-TENS and LF-TENS of the right median nerve in the treatment of GAD was studied using Generalized Anxiety Disorder 7-item scale (GAD-7) and the Hamilton Anxiety Rating Scale (HAM-A). 40 patients underwent sham TENS, 40 patients passed HF-TENS (50 Hz-50 µs-sensory response) and 41 patients completed LF -TENS (1 Hz-200 µs-motor response) for 30 days daily. After completion of treatment, half of the patients received weekly maintenance therapy for 6 months. Electroencephalography was performed before and after treatment. Results: Our study showed that a significant reduction in the clinical symptoms of GAD as assessed by GAD-7 and HAM-A was observed after HF-TENS and LF-TENS by an average of 42.4%, and after sham stimulation only by 13.5% for at least 2 months after the end of treatment. However, LF-TENS turned out to be superior in effectiveness to HF-TENS by 51% and only on electroencephalography leads to an increase in PSD for the alpha rhythm in the occipital regions by 24% and a decrease in PSD for the beta I rhythm in the temporal and frontal regions by 28%. The prolonged effect of HF-TENS and LF-TENS was maintained without negative dynamics when TENS treatment was continued weekly throughout the entire six-month observation period. Conclusions: A prolonged anxiolytic effect of direct TENS of the right median nerve has been proven with greater regression of clinical and neurophysiological manifestations of GAD after LF-TENS compared to HF-TENS. Minimal side effects, low cost, safety, and simplicity of TENS procedures are appropriate as a home treatment modality.

A systems approach to multilingual language attitudes: A case study of Montréal, Québec, Canada.

Purpose: People are shaped holistically by dynamic and interrelated individual and social-ecological systems. This perspective has been discussed in the context of varied aspects of bilingual experiences, namely language acquisition and development. Here, we applied a Systems Framework of Bilingualism to language attitudes, which may be especially responsive to social-ecological influences. Methodology: One hundred twenty-three French-English bilingual adults (M age = 21.20, SD = 3.21) completed self-report questionnaires on demographic information and their attitudes toward languages. A subset of these bilinguals (n = 73) completed a social network survey. Data and analysis: We used language-tagged social network analysis and geospatial demographic analysis to examine the role of individual characteristics (i.e., first language), interpersonal language dynamics (i.e., person-to-person interactions), and ecological language dynamics (i.e., neighborhood language exposure). Findings and Conclusions: At an individual level, we found that bilinguals' language background (i.e., first language) predicted attitudes of solidarity toward a language (i.e., whether a language is associated with personal identity and belongingness). When considering sociolinguistic layers of influence, we found that bilinguals' social network and neighborhood-level language exposure jointly predicted their attitudes of solidarity toward a language, as well as their attitudes toward the protection of minority languages. Originality: While most studies have examined language experience in a unidimensional nature, the present study investigated multilingual language attitudes by considering multiple systems within a social-ecological framework. Implications: Taken together, the results suggest that several interrelated interpersonal and ecological systems are associated with language attitudes, which could have important implications for planning future language policies in multilingual societies such as Montréal.

Competing Risks Analysis of Kidney Transplant Waitlist Outcomes: Two Important Statistical Perspectives.

Modern competing risks analysis has 2 primary goals in clinical epidemiology as follows: (i) to maximize the clinician's knowledge of etiologic associations existing between potential predictor variables and various cause-specific outcomes via cause-specific hazard models, and (ii) to maximize the clinician's knowledge of noteworthy differences existing in cause-specific patient risk via cause-specific subdistribution hazard models (cumulative incidence functions [CIFs]). A perfect application exists in analyzing the following 4 distinct outcomes after listing for a deceased donor kidney transplant (DDKT): (i) receiving a DDKT, (ii) receiving a living donor kidney transplant (LDKT), (iii) waitlist removal due to patient mortality or a deteriorating medical condition, and (iv) waitlist removal due to other reasons. It is important to realize that obtaining a complete understanding of subdistribution hazard ratios (HRs) is simply not possible without first having knowledge of the multivariable relationships existing between the potential predictor variables and the cause-specific hazards (perspective #1), because the cause-specific hazards form the "building blocks" of CIFs. In addition, though we believe that a worthy and practical alternative to estimating the median waiting-time-to DDKT is to ask, "what is the conditional probability of the patient receiving a DDKT, given that he or she would not previously experience one of the competing events (known as the cause-specific conditional failure probability)," only an appropriate estimator of this conditional type of cumulative incidence should be used (perspective #2). One suggested estimator, the well-known "one minus Kaplan-Meier" approach (censoring competing events), simply does not represent any probability in the presence of competing risks and will almost always produce biased estimates (thus, it should never be used).

Optimizing the kidney donor pool: transplanting donor kidneys after partial nephrectomy of masses or cysts.

Background: A limiting factor in expanding the kidney donor pool is donor kidneys with renal tumors or cysts. Partial nephrectomy (PN) to remove these lesions prior to transplantation may help optimize organ usage without recurrence of malignancy or increased risk of complications. Methods: We retrospectively analyzed all recipients of a living or deceased donor graft between February 2009 and October 2022 in which a PN was performed prior to transplant due to the presence of one or more concerning growths. Donor and recipient demographics, perioperative data, donor allograft pathology, and recipient outcomes were obtained. Results: Thirty-six recipients received a graft in which a PN was performed to remove suspicious masses or cysts prior to transplant. Majority of pathologies turned out to be a simple renal cyst (65%), followed by renal cell carcinoma (15%), benign multilocular cystic renal neoplasm (7.5%), angiomyolipoma (5%), benign renal tissue (5%), and papillary adenoma (2.5%). No renal malignancy recurrences were observed during the study period (median follow-up: 67.2 months). Fourteen complications occurred among 11 patients (30.6% overall) during the first 6mo post-transplant. Mean eGFR (± standard error) at 36 months post-transplant was 51.9 ± 4.2 ml/min/1.73 m2 (N = 23). Three death-censored graft losses and four deaths with a functioning graft and were observed. Conclusion: PN of renal grafts with suspicious looking masses or cysts is a safe option to optimize organ usage and decrease the kidney non-use rate, with no observed recurrence of malignancy or increased risk of complications.

T-wave Peak-to-End Changes Quantified by Time-Warping Predicts Ventricular Fibrillation in a Porcine Myocardial Infarction Model.

BACKGROUND: The T-peak-to-T-end ( Tpe) interval has shown potential in predicting ventricular arrhythmic risk. It is an appealing index to be measured during ischemia since it is less influenced by ST-segment changes than the early part of the T wave. A time-warping-based index, derived from a spatially transformed PCA lead, [Formula: see text], quantifying changes in the Tpe morphology, has previously demonstrated utility in tracking repolarization changes induced by a 5-minute ischemia model in humans. The value of [Formula: see text] as a predictor of ventricular fibrillation (VF) episodes is assessed in a porcine model of myocardial ischemia with ischemia maintained for 40 minutes. METHODS: From 32 pigs undergoing a coronary occlusion, pre-occlusion and occlusion ECG recordings from 10 pigs suffering a VF episode after 10 min of occlusion (Delayed VF) and 16 that did not had any episode during the recording were analyzed. The [Formula: see text] series was measured by comparing Tpe morphologies at different stages of the occlusion relative to the peak-to-end morphology of a baseline T-wave. RESULTS: During baseline, [Formula: see text] remained stationary with an intra-recording median [IQR] value of 1.60 [1.33] ms. During artery occlusion, [Formula: see text] followed a well-marked gradual increasing trend as ischemia progressed, reaching a median of 14.58 [17.72] ms. [Formula: see text] averages were significantly higher ( ) in the VF group than in the Non-VF group at time intervals 0-5, 5-10, 10-15, 15-20, 20-25 min after occlusion onset and at 10-15, 5-10 and 5-0 minutes prior to VF episode, with median values of 12.5, 18.8, 26.8, 24.0, 31.0, 18.6, 25.0 and 28.8 vs 6.3, 7.6, 8.0, 7.8, 7.8, 8.5, 7.2 and 6.0 ms, respectively. The [Formula: see text] interval was also significantly higher in the VF group at all analyzed time periods, but with a lower significance level. Pigs with maximum [Formula: see text] ≥ 20.0 ms and [Formula: see text] ≥ 85.4 ms had significantly higher risk for VF occurring in the early 5-10 minutes interval, with 90.0%/75.0% and 80.0%/69.0% sensitivity/specificity, respectively. Univariate Cox analysis yielded hazard ratios of 12.5 for [Formula: see text] vs 5.5 for [Formula: see text]. CONCLUSIONS AND SIGNIFICANCE: The time-warping-based index, [Formula: see text], is a stronger VF predictor than [Formula: see text] during ischemia in a porcine model, advising for further clinical exploration studies in humans.

Comparative analysis of the processes involved in the loss of elaiophores in two species of the christianelloid clade (Malpighiaceae).

Alicia anisopetala and Callaeum psilophyllum are two closely related species that belong to the christianelloid clade of the family Malpighiaceae. Both species are pollinated by oil-collecting bees and exhibit variations at specimen and population level in the number of elaiophores per flower. These floral glands that secrete non-volatile oils constitute an ancestral trait for the family. There is evidence that the observed variations in the number of elaiophores can be the result of processes of connation or reduction associated with differences in their vascularization. In order to identify which process occurs in each species, we conducted an anatomical study in natural populations of both species distributed along a wide range of their geographical distributions in Argentina. We collected flowers of different individuals, counted the number of elaiophores per flower, carried out exomorphological observations, and used conventional histological techniques to examine the vascularization of these glands. The floral anatomy of both species does not show any modifications in other whorls related to the fusion or reduction of elaiophores. Our results indicate that the process of loss of elaiophores in A. anisopetala is caused by incomplete connation and in C. psilophyllum by reduction, suggesting that the processes that lead to the loss of elaiophores in Malpighiaceae are homoplastic and would not reflect phylogenetic signals.

Chemical defence of a centipede (Clinopodes flavidus).

Chemical substances are of utmost importance for the biotic interactions between animals and their predators/parasites; many of these semiochemicals are emitted for defence purposes. One of the most deterrent and toxic biogenic substances we know of is hydrogen cyanide, which can be stored by certain insects, millipedes, centipedes and arachnids in the form of stable and less volatile molecules. The aim of this study was to analyse the biology and chemistry of such a defence mechanism in a geophilomorph centipede (Chilopoda). The cyanogenic secretion of Clinopodes flavidus is discharged from the ventral glands, whose glandular units are located in the space between the cuticle and the trunk muscles and do not extend deep into the segment. In addition to hydrogen cyanide, the ventral secretion contains 2-methylpentanoic acid, benzaldehyde, benzoyl cyanide, 2-methyl branched C-9 carboxylic acid (tentatively identified as 2-methyloctanoic acid), methyl 2-phenylacetate, benzoic acid and mandelonitrile as well as four major proteins with a molecular weight of 150, 66.2, 59 and 55 kDa. The correlation between the presence of ventral glands and guarding with the female's ventral side facing away from the eggs and young indicates a functional link between these two traits. We hope that the specificity of the chemical composition of the ventral secretion could serve as a criterion for chemotaxonomy and that the analysis of more species will help to clarify the phylogenetic relationships within the Geophilomorpha.

Ethnic Aspects of Valproic Acid P-Oxidation.

The safety of the use of psychotropic drugs, widely used in neurological and psychiatric practice, is an urgent problem in personalized medicine. This narrative review demonstrated the variability in allelic frequencies of low-functioning and non-functional single nucleotide variants in genes encoding key isoenzymes of valproic acid P-oxidation in the liver across different ethnic/racial groups. The sensitivity and specificity of pharmacogenetic testing panels for predicting the rate of metabolism of valproic acid by P-oxidation can be increased by prioritizing the inclusion of the most common risk allele characteristic of a particular population (country).

A comprehensive study on Geranium robertianum L. antibacterial potential.

AIMS: The research aimed to optimize the ultrasound-assisted extraction of secondary metabolites and the antibacterial activity of the plant species Geranium robertianum. The phytochemical profiles of the optimized extracts, as well as their antibacterial and synergistic activity with an antibiotic and their potential mechanisms of action and cytotoxicity, were examined. METHODS AND RESULTS: Response Surface Methodology was used to optimize extraction conditions. Optimized ethanol and acetone extracts were tested via microdilution, checkerboard, time-kill kinetics, and cell membrane permeability methods. The extracts displayed broad antibacterial activity with minimum inhibitory concentrations ranging from 1.25 to 20 mg ml-1. In addition, the extract synergistically reacted with gentamicin against gentamicin-resistant strains of Escherichia coli and Staphylococcus aureus, enhancing the efficacy of the antibiotic up to 32-fold. The extracts demonstrated strain-dependent bactericidal activity in a 24-h time interval. They increase the permeability of the cell membrane, thus disrupting its normal functioning. The cytotoxic concentration (CC50) on human keratinocytes was 1771.24 ± 5.78 µg ml-1 for ethanol extract, and 958.01 ± 6.14 µg ml-1 for acetone extract. Kaempferol, ellagic acid, quercetin, and rutin were recognized as the main components in both extracts. CONCLUSIONS: The findings of this study indicate that the extracts of G. robertianum can be considered as potential natural antibacterial agents in the control of microorganisms.

Muscle Recruitment Strategies in a Redundant Task: Age Differences Through Network Analyses.

There are numerous studies comparing young and old adults in terms of muscle coordination in standard tasks (e.g., walking, reaching) and small variations of them. These tasks might hide differences: individuals would converge to similar behavior as they practice these throughout life. Also, we are unaware of studies that considered the muscle recruitment nested dynamics. For this reason, our study evaluated how young and old women coordinate and control the movement system while performing an unusual redundant motor control task through the network physiology approach. We acquired electromyographic signals from nine leg muscles of the dominant and non-dominant limbs during maximum voluntary isometric contractions (knee extension and flexion) and co-contraction bouts. Our results showed that young participants presented higher peak torque output, with similar EMG variability, compared to older participants. Considering firing rate frequencies, old and young women demonstrated different traits for network clustering and efficiency for the task. Age seems to affect muscle coordination at higher frequencies, even with a similar number of muscle synergies, indicating that younger women might have more integrated synergies than older women. The findings also point to differential muscle coordination adaptability.

5th Argentinean Meeting on Evolutionary Biology (RABE V): Report on the "Evo-Devo" Extended Symposium.

Evolutionary developmental biology (Evo-Devo) is flourishing in Latin America, particularly Argentina, where researchers are leveraging this integrative field to unlock the secrets of the region's remarkable biodiversity. A recent symposium held at the 5th Argentinean Meeting on Evolutionary Biology (RABE V) showcased a vibrant Evo-Devo community and the diversity of its research endeavors. The symposium included 3 plenary talks, 3 short talks, and 12 posters, and spanned a range of organisms and approaches. Interestingly, the symposium highlighted a prevalence of "top-down" Evo-Devo studies in the region, where researchers first analyze existing diversity and then propose potential developmental mechanisms. This approach, driven in part by financial constraints and the region's historical focus on natural history, presents a unique opportunity to bridge disciplines like comparative biology, paleontology, and botany. The symposium's success underscores the vital role of Evo-Devo in Latin America, not only for advancing our understanding of evolution but also for providing valuable tools to conserve and manage the region's irreplaceable biodiversity. As Evo-Devo continues to grow in Latin America, fostering collaboration and knowledge exchange within the region and beyond will be crucial for realizing the full potential of this transformative field.

Surgical modifications to the conventional kidney transplant technique - the miami transplant institute approach: a retrospective cohort study.

BACKGROUND: At our center, surgical modifications to the conventional kidney transplant technique were developed with two goals in mind: to minimize the risk of developing post-transplant urologic/vascular/other surgical complications, and to simultaneously eliminate the need for initial ureteral stent placement and surgical drainage. METHODS: Here, we describe these modifications along with(what we believe are) their advantages over the conventional technique: creating an abdominal flap for easier abdominal closure(reflecting the parietal peritoneum from the abdominal wall), mobilizing the bladder before transplant(creating more space for bladder dissection, allowing it to move upward during abdominal wall closure), minimizing the dissection of iliac vessels to only anterior lymphatic tissue(attempting to minimize the incidence of fluid collections), using plastic arterial vascular bulldog clamps(causing less trauma to the iliac artery), performing vascular anastomosis of the renal artery first(making it easier for the surgeon to perform this anastomoses), creating longer ureteral spatulation, and inclusion of bladder mucosa along with some detrusor muscle layer in performing the ureteral anastomosis(attempting to minimize the incidence of urologic complications). Of note, no initial ureteral stent placement or surgical drainage was used. We report our experience during the first 12mo post-transplant of a single transplant surgeon who used each of these modifications among 707 consecutive recipients of kidney-alone transplants at our center since 2014. RESULTS: During the first 12mo post-transplant, 2.3%(16/707) of patients developed a urologic complication; only 1.0%(7/707) required surgical repair of their original ureteroneocystostomy. Additionally, 2.7%(19/707) developed a vascular complication; 8.8%(62/707) developed some other type of surgical complication(wound complication, lymphocele development, or development of a peri-renal hematoma or peri-renal collection). These overall results were clearly advantageous when compared with other studies. CONCLUSION: We believe that this modified kidney transplant technique clearly helped in reducing post-transplant risks of developing urologic/vascular/other surgical complications. Importantly, these results were achieved without initial ureteral stent placement or surgical drainage.

The global diet quality score as an indicator of adequate nutrient intake and dietary quality - a nation-wide representative study.

BACKGROUND: The Global Diet Quality Score (GDQS) was developed to be a simple, timely and cost-effective tool to track, simultaneously, nutritional deficiency and non-communicable disease risks from diet in diverse settings. The objective was to investigate the performance of GDQS as an indicator of adequate nutrient intake and dietary quality in a national-representative sample of the Brazilian population. METHODS: Nationally-representative data from 44,744 men and non-pregnant and non-lactating women aging ≥ 10 years, from the Brazilian National Dietary Survey were used. Dietary data were collected through two 24-h recalls (24HR). The GDQS was calculated and compared to a proxy indicator of nutrient adequate intake (the Minimum Dietary Diversity for Women-MDD-W) and to an indicator of high-risk diet for non-communicable diseases (caloric contribution from ultra-processed foods-UPF). To estimate the odds for overall nutrient inadequacy across MDD-W and GDQS quintiles, a multiple logistic regression was applied, and the two metrics' performances were compared using Wald's post-test. RESULTS: The mean GDQS for Brazilians was 14.5 (0-49 possible range), and only 1% of the population had a low-risk diet (GDQS ≥ 23). The GDQS mean was higher in women, elderly individuals and in higher-income households. An inverse correlation was found between the GDQS and UPF (rho (95% CI) = -0.20(-0.21;-0.19)). The odds for nutrient inadequacy were lower as quintiles of GDQS and MDD-W were higher (p-trend < 0.001), and MDD-W had a slightly better performance than GDQS (p-diff < 0.001). Having a low-risk GDQS (≥ 23) lowered the odds for nutrient inadequacy by 74% (95% CI:63%-81%). CONCLUSION: The GDQS is a good indicator of overall nutrient adequacy, and correlates well with UPF in a nationally representative sample of Brazil. Future studies must investigate the relationship between the GDQS and clinical endpoints, strengthening the recommendation to use this metric to surveillance dietary risks.