The Mediating Role of Cardiorespiratory Fitness in the Association between a Negative Lifestyle and Poor Mental Health in Chilean Schoolchildren.

BACKGROUND: A negative lifestyle has a reported relationship with psychological problems and deteriorated well-being. However, there is little information regarding the mediating role of cardiorespiratory fitness (CRF) in this relationship. OBJECTIVES: The objectives of the present study are twofold: first, to investigate the association between negative lifestyle, physical self-concept (PSC), and depression, and second, to assess the potential mediating role of CRF in this complex relationship. METHODS: This cross-sectional study included 612 schoolchildren aged between 9 and 14 years from the Araucanía region (southern Chile). CRF was measured using the Leger test, and lifestyle, depression, and PSC were measured using validated questionnaires. RESULTS: A negative lifestyle reported an inverse association with PSC (p < 0.001) and a positive association with depression levels (p < 0.001). The mediation analysis showed that CRF was positively related to PSC (p < 0.001) and inversely related to depression (p = 0.001); besides, the indirect effect CRF acted as a partial mediator in the association between a negative lifestyle and PSC (indirect effect = -1.15; SE = 0.01; 95% CI, -1.87, -0.55) and depression levels (indirect effect = 0.22; SE = 0.08; 95% CI, 0.08, 0.38). CONCLUSION: In conclusion, CRF in schoolchildren played a potential mediating role in the association between a negative lifestyle and depression and PSC.

Association between Active Commuting and Lifestyle Parameters with Mental Health Problems in Chilean Children and Adolescent.

BACKGROUND: Little is known about the association between active commuting (i.e., walking or cycling to school) with lifestyle parameters and mental health in youths. The objective of the present study was to investigate the association between mental health problems and symptoms of depression, anxiety, and stress with lifestyle (i.e., food habits, screen time, physical activity, and sleep quality), active commuting, and gender. METHODS: A total of 511 children and adolescents (boys, n = 249; girls, n = 262) aged 10 to 17 years participated in the study. Lifestyle parameters and mental health were evaluated using the Depression Anxiety and Stress Scale (DASS-21). RESULTS: Girls reported higher levels of anxiety (p = 0.001), depression (p = 0.001), and stress (p = 0.001). Mental health problems showed a positive association with gender (girls, ß = 3.06, p < 0.001) and a negative association with food habits (ß = -0.65, p = 0.019). Anxiety was positively associated with gender (ß = 7.88, p < 0.001) and negatively associated with food habits (ß = -0.23, p = 0.019). Gender (girls) and food habits were also associated with symptoms of depression (ß = 2.29, p < 0.001 and ß = -0.27, p = 0.005, respectively). Finally, active commuting was inversely associated with stress (ß = -1.24, p = 0.008), and stress was positively linked to gender (ß = 2.53, p < 0.001). CONCLUSIONS: Active commuting, lifestyle parameters, and gender were associated with mental health in children and adolescents. Moreover, girls reported higher levels of anxiety, symptoms of depression, and stress.

An inactivated SARS-CoV-2 vaccine based on a Vero cell culture-adapted high-titer virus confers cross-protection in small animals.

Rapidly waning immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires continued global access to affordable vaccines. Globally, inactivated SARS-CoV-2 vaccines have been widely used during the SARS-CoV-2 pandemic. In this proof-of-concept study we adapted an original-D614G SARS-CoV-2 virus to Vero cell culture as a strategy to enhance inactivated vaccine manufacturing productivity. A passage 60 (P60) virus showed enhanced fitness and 50-fold increased virus yield in a bioreactor compared to the original-D614G virus. It further remained susceptible to neutralization by plasma from SARS-CoV-2 vaccinated and convalescent individuals, suggesting exposure of relevant epitopes. Monovalent inactivated P60 and bivalent inactivated P60/omicron BA.1 vaccines induced neutralizing responses against original-D614G and BA.1 viruses in mice and hamsters, demonstrating that the P60 virus is a suitable vaccine antigen. Antibodies further cross-neutralized delta and BA.5 viruses. Importantly, the inactivated P60 vaccine protected hamsters against disease upon challenge with original-D614G or BA.1 virus, with minimal lung pathology and lower virus loads in the upper and lower airways. Antigenicity of the P60 virus was thus retained compared to the original virus despite the acquisition of cell culture adaptive mutations. Consequently, cell culture adaptation may be a useful approach to increase yields in inactivated vaccine antigen production.

Unveiling the Shadows: A Rare Encounter With Cardiac Tamponade Following Influenza B in a Young Female.

Influenza B infection, although primarily recognized for respiratory symptoms, can lead to rare but severe cardiac complications such as pericardial effusion and cardiac tamponade. We present a case of a 33-year-old female with morbid obesity who initially exhibited flu-like symptoms, was subsequently diagnosed with influenza B infection, and was discharged with symptomatic treatment. Despite initial discharge, she returned with worsening weakness, gastrointestinal symptoms, and shortness of breath. Imaging studies confirmed pericardial effusion with early signs of tamponade, necessitating an emergent intervention. The patient underwent subxiphoid pericardial window and fluid removal, followed by colchicine treatment to prevent recurrence. Our case highlights the importance of recognizing and promptly managing rare influenza-related complications, particularly in patients without significant comorbidities. It underscores the value of a proactive approach, utilizing point-of-care ultrasound and echocardiography for early diagnosis and intervention to mitigate mortality and morbidity risks associated with pericarditis and cardiac tamponade secondary to influenza B.

Sweet Cherry Plants Prioritize Their Response to Cope with Summer Drought, Overshadowing the Defense Response to Pseudomonas syringae pv. syringae.

Disease severity and drought due to climate change present significant challenges to orchard productivity. This study examines the effects of spring inoculation with Pseudomonas syringae pv. syringae (Pss) on sweet cherry plants, cvs. Bing and Santina with varying defense responses, assessing plant growth, physiological variables (water potential, gas exchange, and plant hydraulic conductance), and the levels of abscisic acid (ABA) and salicylic acid (SA) under two summer irrigation levels. Pss inoculation elicited a more pronounced response in 'Santina' compared to 'Bing' at 14 days post-inoculation (dpi), and those plants inoculated with Pss exhibited a slower leaf growth and reduced transpiration compared to control plants during 60 dpi. During differential irrigations, leaf area was reduced 14% and 44% in Pss inoculated plants of 'Bing' and 'Santina' respectively, under well-watered (WW) conditions, without changes in plant water status or gas exchange. Conversely, water-deficit (WD) conditions led to gas exchange limitations and a 43% decrease in plant biomass compared to that under WW conditions, with no differences between inoculation treatments. ABA levels were lower under WW than under WD at 90 dpi, while SA levels were significantly higher in Pss-inoculated plants under WW conditions. These findings underscore the influence on plant growth during summer in sweet cherry cultivars that showed a differential response to Pss inoculations and how the relationship between ABA and SA changes in plant drought level responses.

A global dataset for assessing nitrogen-related plant traits using drone imagery in major field crop species.

Enhancing rapid phenotyping for key plant traits, such as biomass and nitrogen content, is critical for effectively monitoring crop growth and maximizing yield. Studies have explored the relationship between vegetation indices (VIs) and plant traits using drone imagery. However, there is a gap in the literature regarding data availability, accessible datasets. Based on this context, we conducted a systematic review to retrieve relevant data worldwide on the state of the art in drone-based plant trait assessment. The final dataset consists of 41 peer-reviewed papers with 11,189 observations for 11 major crop species distributed across 13 countries. It focuses on the association of plant traits with VIs at different growth/phenological stages. This dataset provides foundational knowledge on the key VIs to focus for phenotyping key plant traits. In addition, future updates to this dataset may include new open datasets. Our goal is to continually update this dataset, encourage collaboration and data inclusion, and thereby facilitate a more rapid advance of phenotyping for critical plant traits to increase yield gains over time.

Methods of alignment in total knee arthroplasty, systematic review.

Introduction: Although total knee arthroplasty (TKA) is a very frequent surgery, one in five patients is not completely satisfied. Mechanical alignment (MA) is the most popular technique for implanting TKA. However, to improve clinical outcomes, new techniques that aim to rebuild the native alignment of the knee have been developed. Objective: The aim of this study is to perform a systematic review of the available clinical trials and observational studies comparing clinical and radiological outcomes of different methods of alignment (kinematic, anatomic, functional) to MA. Methods: A systematic review is performed comparing results of patient reported outcome measures (PROMs) questionnaires (WOMAC, OKS, KSS, KOOS, FJS), radiological angles (HKA, mLDFA, MPTA, JLOA, femoral rotation and tibial slope) and range of motion (ROM). Results: Kinematic and functional alignment show a slight tendency to obtain better PROMs compared to mechanical alignment. Complication rates were not significantly different between groups. Nevertheless, these results are not consistent in every study. Anatomic alignment showed no significant differences compared to mechanical alignment. Conclusion: Kinematic alignment is an equal or slightly better alternative than mechanical alignment for patients included in this study. However, the difference between methods does not seem to be enough to explain the high percentage of dissatisfied patients. Studies implementing lax inclusion and exclusion criteria would be needed to resemble conditions of patients assisted in daily surgical practice. It would be interesting to study patient's knee phenotypes, to notice if any method of alignment is significantly better for any constitutional deviation.

An International Consensus Survey among Pediatric Surgeons on the Role of Appendectomy in Malrotation.

Introduction: Ladd's procedure, originally described in 1936 for the treatment of malrotation, does not traditionally include appendectomy as a standard step. We conducted a multinational survey to investigate the current consensus on the role of appendectomy in Ladd's procedure. Methodology: An anonymous online survey was distributed to pediatric surgeons worldwide. The survey collected demographic data and explored surgical preferences related to the management of malrotation. Open-ended questions were used to assess the opinions regarding the necessity of appendectomy, decision-making factors, and complications associated with appendectomy during Ladd's procedure. Results: A total of 343 responses were received from 46 countries. Of the respondents, 319 (93%) were consultants and 24 (7%) were residents/trainees. When asked about the choice between open and laparoscopic Ladd's procedure, 292 (85%) preferred open surgery. Overall, 184 (53%) respondents favored appendectomy in both open and laparoscopic Ladd's procedure. Furthermore, 172 (50%) surgeons advocated for appendectomy in all malrotation cases, citing concerns about potential future appendicitis. While differences existed between all comparisons, none of them reached statistical significance. The factors influencing the decision to preserve the appendix included the risk of postoperative complications and the potential future use of the appendix as a surgical conduit. The surgical complications following appendectomy included surgical site infections in 14 (33%) patients, adhesive obstruction in 13 (31%) patients, intrabdominal abscesses in 10 (24%) patients, and fecal fistulas in 5 (12%) patients. Conclusion: The majority of surgeons aim to perform appendectomy in all malrotation cases, considering the potential risks and benefits of this approach. These findings offer valuable insights for clinical practice and may inform future guidelines and decision-making algorithms.

Nitric Oxide Mitigates the Deleterious Effects Caused by Infection of Pseudomonas syringae pv. syringae and Modulates the Carbon Assimilation Process in Sweet Cherry under Water Stress.

Bacterial canker is an important disease of sweet cherry plants mainly caused by Pseudomonas syringae pv. syringae (Pss). Water deficit profoundly impairs the yield of this crop. Nitric oxide (NO) is a molecule that plays an important role in the plant defense mechanisms. To evaluate the protection exerted by NO against Pss infection under normal or water-restricted conditions, sodium nitroprusside (SNP), a NO donor, was applied to sweet cherry plants cv. Lapins, before they were exposed to Pss infection under normal or water-restricted conditions throughout two seasons. Well-watered plants treated with exogenous NO presented a lower susceptibility to Pss. A lower susceptibility to Pss was also induced in plants by water stress and this effect was increased when water stress was accompanied by exogenous NO. The lower susceptibility to Pss induced either by exogenous NO or water stress was accompanied by a decrease in the internal bacterial population. In well-watered plants, exogenous NO increased the stomatal conductance and the net CO2 assimilation. In water-stressed plants, NO induced an increase in the leaf membranes stability and proline content, but not an increase in the CO2 assimilation or the stomatal conductance.

A PAK family kinase and the Hippo/Yorkie pathway modulate WNT signaling to functionally integrate body axes during regeneration.

Successful regeneration of missing tissues requires seamless integration of positional information along the body axes. Planarians, which regenerate from almost any injury, use conserved, developmentally important signaling pathways to pattern the body axes. However, the molecular mechanisms which facilitate cross talk between these signaling pathways to integrate positional information remain poorly understood. Here, we report a p21-activated kinase (smed-pak1) which functionally integrates the anterior-posterior (AP) and the medio-lateral (ML) axes. pak1 inhibits WNT/ß-catenin signaling along the AP axis and, functions synergistically with the ß-catenin-independent WNT signaling of the ML axis. Furthermore, this functional integration is dependent on warts and merlin-the components of the Hippo/Yorkie (YKI) pathway. Hippo/YKI pathway is a critical regulator of body size in flies and mice, but our data suggest the pathway regulates body axes patterning in planarians. Our study provides a signaling network integrating positional information which can mediate coordinated growth and patterning during planarian regeneration.

Drugst.One - a plug-and-play solution for online systems medicine and network-based drug repurposing.

In recent decades, the development of new drugs has become increasingly expensive and inefficient, and the molecular mechanisms of most pharmaceuticals remain poorly understood. In response, computational systems and network medicine tools have emerged to identify potential drug repurposing candidates. However, these tools often require complex installation and lack intuitive visual network mining capabilities. To tackle these challenges, we introduce Drugst.One, a platform that assists specialized computational medicine tools in becoming user-friendly, web-based utilities for drug repurposing. With just three lines of code, Drugst.One turns any systems biology software into an interactive web tool for modeling and analyzing complex protein-drug-disease networks. Demonstrating its broad adaptability, Drugst.One has been successfully integrated with 21 computational systems medicine tools. Available at https://drugst.one, Drugst.One has significant potential for streamlining the drug discovery process, allowing researchers to focus on essential aspects of pharmaceutical treatment research.

Healthy Lifestyle Related to Executive Functions in Chilean University Students: A Pilot Study.

BACKGROUND: A negative lifestyle is reported to be related to cognitive problems. However, there is little information about this in relation to university students. The objective of the present study was to investigate the association between executive functions (EFs) and lifestyle parameters (i.e., physical activity (PA), sleep duration, screen time (ST), and food habits) among Chilean university students. METHODS: This cross-sectional study included a total of 150 university students (94 females and 56 males, aged 21.28 ± 3.15 and 22.18 ± 2.90 years, respectively). Cognitive outcomes were measured using the CogniFit assessment battery. Lifestyle was measured through validated questionnaires. RESULTS: Across the total sample, attention exhibited a positive association with PA h/week (ß: 24.34 95% CI: 12.46 to 36.22, p = 0.001). Additionally, coordination was positively associated with PA h/week (ß: 15.06 95% CI: 0.62 to 29.50, p < 0.041). PA h/week was positively linked with reasoning (ß: 20.34 95% CI: 4.52 to 36.17, p = 0.012) and perception (ß: 13.81 95% CI: 4.14 to 23.49, p = 0.005). Moreover, PA h/week was significantly linked to memory (ß: 23.01 95% CI: 7.62 to 38.40, p = 0.004). In terms of the EFs, PA h/week showed a positive association with cognitive flexibility (ß: 45.60 95% CI: 23.22 to 67.69, p = 0.001). CONCLUSIONS: In conclusion, lifestyle (PA h/week) was positively associated with EFs. Therefore, an increase in PA levels among these students should be a target for community- and university-based interventions in order to promote cognitive development such as attention, coordination, reasoning, perception, memory, and cognitive flexibility.

An isolated bioinductive repair vs. sutured repair for full-thickness rotator cuff tears: 2-year results of a double blinded, randomized controlled trial.

BACKGROUND: Partial-thickness rotator cuff tears treated with an isolated bioinductive repair (IBR) in lieu of a completion-and-repair have shown complete healing. This treatment option is afforded by the remaining tendon's structural integrity, which is similar to that present in small/medium full-thickness tears (FTTs) when the rotator cable remains intact. This randomized controlled trial (RCT) investigated whether an IBR for small/medium FTTs resulted in superior healing and patient-reported outcomes (PROs) compared with a sutured repair. METHODS: This prospective, double blinded (patients and outcome assessors), single-center RCT enrolled patients ≥18 years with a small/medium (≤2.5cm) full thickness supraspinatus tear and intact rotator cable. Patients were randomized and blinded to arthroscopic transosseous-equivalent repair (control, n = 30) or IBR (n = 30). The primary outcome was tendon quality on biopsy at 6 months. Secondary outcomes were PROs (American Shoulder and Elbow Surgeons [ASES], Constant-Murley Shoulder [CMS], and pain visual analogue scale scores) and tendon thickness and healing measured via MRI at 6, 12, and 24 months; satisfaction at 12 and 24 months; and time to return to work. RESULTS: Baseline demographic, tear, and surgical characteristics were comparable between the groups (IBR: mean age, 54.2 years, 14 male; control: mean age, 56.4 years, 16 male). Measured via 6 month biopsy, highly organized, parallel bundles of collagen, without inflammation, were present in all IBR patients, whereas poorly organized, non-parallel collagen fibers were present in 24/30 (80%) of control patients (P < .0001), with 28/30 having minimal to mild inflammation. The increase in tendon thickness measured via MRI at 6 months from baseline was greater in the IBR group (2.0 mm) than in the control group (0.8 mm) (P < .0001). All IBR patients had 100% healing on MRI at 12 and 24 months. Compared with the control group, the IBR group had higher ASES and CMS scores at each evaluation, less pain at 6 and 12 months, and greater satisfaction at 12 and 24 months (P < .0003). The IBR group returned to work significantly faster (median 90 days [IQR, 25] vs. median 163.5 days [IQR, 24]; P < .0001) than the control group. CONCLUSION: Compared with a sutured repair, the IBR treatment resulted in superior tendon quality, patient outcomes, satisfaction, and return to work. The IBR enabled a robust healing response evident through MRI and biopsy evaluation, demonstrating superior tendon quality and healing.

Click synthesis of dendronized malonates for the preparation of amphiphilic dendro[60]fullerenes.

Fullerene C60 and its malonate derivatives, produced via the Bingel-Hirsch reaction, have displayed promising properties against various diseases. These molecules have great therapeutic potential, but their broad use has been limited due to poor aqueous solubility and toxicity caused by accumulation. In this study, we synthesized new malonates and malonamides attached to first- and second-generation polyester dendrons using click chemistry (CuAAC). These dendrons were then linked at C60 through the Bingel-Hirsch reaction, resulting in an amphiphilic system that retains the hydrophobic nature of C60. The dendronized malonate derivatives showed good reaction yields for the Bingel-Hirsch mono-adducts and were easier to work with than the corresponding malonamides. However, the malonamide derivatives, which were obtained through a multistep reaction sequence, showed moderate yields in the Bingel-Hirsch reaction. Surprisingly, removing acetonide protecting groups from dendritic architectures was more challenging than anticipated, likely due to product decomposition. Only the corresponding free malonate derivatives 25 and 26 were obtained, but in a low yield due to decomposition under the reaction conditions. Meanwhile, it was not possible to obtain the corresponding malonamide derivatives 27 and 28. Currently, efforts are being made to improve the production of the desired molecules and to design new synthesis routes that allow direct access to the desired poly-hydroxylated derivatives. These derivatives will be evaluated as multitarget ligands against Alzheimer's disease, through their use as inhibitors of amyloid ß-peptide aggregation, acetylcholinesterase modulators, and antioxidants.

Arsenic and mercury exposure in different insect trophic guilds from mercury mining areas in Mexico.

The exposure to arsenic and mercury in various insect trophic guilds from two mercury mining sites in Mexico was assessed. The two study sites were La Laja (LL) and La Soledad (LS) mines. Additionally, a reference site (LSR) was evaluated for LS. The terrestrial ecosystem was studied at LL, whereas both the terrestrial ecosystem and a stream called El Cedral (EC) were assessed at LS. The study sites are situated in the Biosphere Reserve Sierra Gorda (BRSG). Mercury vapor concentrations were measured with a portable analyzer, and concentrations of arsenic and mercury in environmental and biological samples were determined through atomic absorption spectrophotometry. Both pollutants were detected in all terrestrial ecosystem components (soil, air, leaves, flowers, and insects) from the two mines. The insect trophic guilds exposed included pollinivores, rhizophages, predators, coprophages, and necrophages. In LS, insects accumulated arsenic at levels 29 to 80 times higher than those found in specimens from LSR, and 10 to 46 times higher than those from LL. Similarly, mercury exposure in LS was 13 to 62 times higher than LSR, and 15 to 54 times higher than in LL. The analysis of insect exposure routes indicated potential exposure through air, soil, leaves, flowers, animal prey, carrion, and excrement. Water and sediment from EC exhibited high levels of arsenic and mercury compared to reference values, and predatory aquatic insects were exposed to both pollutants. In conclusion, insects from mercury mining sites in the BRSG are at risk.

Origins of Second Malignancies in Children and Mutational Footprint of Chemotherapy in Normal Tissues.

Pediatric cancers are rare diseases, and children without known germline predisposing conditions who develop a second malignancy during developmental ages are extremely rare. We present four such clinical cases and, through whole-genome and error-correcting ultra-deep duplex sequencing of tumor and normal samples, we explored the origin of the second malignancy in four children, uncovering different routes of development. The exposure to cytotoxic therapies was linked to the emergence of a secondary acute myeloid leukemia. A common somatic mutation acquired early during embryonic development was the driver of two solid malignancies in another child. In two cases, the two tumors developed from completely independent clones diverging during embryogenesis. Importantly, we demonstrate that platinum-based therapies contributed at least one order of magnitude more mutations per day of exposure than aging to normal tissues in these children. SIGNIFICANCE: Using whole-genome and error-correcting ultra-deep duplex sequencing, we uncover different origins for second neoplasms in four children. We also uncover the presence of platinum-related mutations across 10 normal tissues of exposed individuals, highlighting the impact that the use of cytotoxic therapies may have on cancer survivors. See related commentary by Pacyna and Nangalia, p. 900. This article is featured in Selected Articles from This Issue, p. 897.

Cytokine and T cell responses in post-chikungunya viral arthritis: A cross-sectional study.

OBJECTIVE: To define the relationship between chronic chikungunya post-viral arthritis disease severity, cytokine response and T cell subsets in order to identify potential targets for therapy. METHODS: Participants with chikungunya arthritis were recruited from Colombia from 2019-2021. Arthritis disease severity was quantified using the Disease Activity Score-28 and an Arthritis-Flare Questionnaire adapted for chikungunya arthritis. Plasma cytokine concentrations (interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ and tumor necrosis factor (TNF)) were measured using a Meso Scale Diagnostics assay. Peripheral blood T cell subsets were measured using flow cytometry. RESULTS: Among participants with chikungunya arthritis (N = 158), IL-2 levels and frequency of regulatory T cells (Tregs) were low. Increased arthritis disease activity was associated with higher levels of inflammatory cytokines (IL-6, TNF and CRP) and immunoregulatory cytokine IL-10 (p<0.05). Increased arthritis flare activity was associated with higher Treg frequencies (p<0.05) without affecting T effector (Teff) frequencies, Treg/Teff ratios and Treg subsets. Finally, elevated levels of IL-2 were correlated with increased Treg frequency, percent Tregs out of CD4+ T cells, and Treg subsets expressing immunosuppressive markers, while also correlating with an increased percent Teff out of live lymphocytes (p<0.05). CONCLUSION: Chikungunya arthritis is characterized by increased inflammatory cytokines and deficient IL-2 and Treg responses. Greater levels of IL-2 were associated with improved Treg numbers and immunosuppressive markers. Future research may consider targeting these pathways for therapy.

The mRNACalc webserver accounts for the N1-methylpseudouridine hypochromicity to enable precise nucleoside-modified mRNA quantification.

Nucleoside-modified messenger RNA (mRNA) technologies necessarily incorporate N1-methylpseudouridine into the mRNA molecules to prevent the over-stimulation of cytoplasmic RNA sensors. Despite this modification, mRNA concentrations remain mostly determined through the measurement of UV absorbance at 260 nm wavelength (A260). Herein, we report that the N1-methylpseudouridine absorbs approximately 40% less UV light at 260 nm than uridine, and its incorporation into mRNAs leads to the under-estimation of nucleoside-modified mRNA concentrations, with 5%-15% error, in an mRNA-sequence-dependent manner. We therefore examined the RNA quantification methods and developed the mRNACalc webserver. It accounts for the molar absorption coefficient of modified nucleotides at 260 nm wavelength, the RNA composition of the mRNA, and the A260 of the mRNA sample to enable accurate quantification of nucleoside-modified mRNAs.