High prevalence of dysfunctional uterine bleeding in candidates for metabolic/bariatric surgery: increased endometrial cancer risk?

BACKGROUND: Endometrial cancer (EC) is the strongest obesity-associated malignancy and the fastest-growing cancer in young women. Early identification of EC and other endometrial pathology (malignant and nonmalignant) in women with severe obesity may improve treatment options and uterine preservation. Screening for endometrial pathology using abnormal or postmenopausal uterine bleeding (APUB) as a surrogate in women pursuing metabolic/bariatric surgery may be clinically beneficial, but data supporting this effort are limited. OBJECTIVE: To develop and institute a screening program for APUB as a surrogate for endometrial pathology in bariatric surgery candidates. SETTING: Two, academic metabolic/bariatric surgery programs in Louisiana, United States. METHODS: The Modified SAMANTA is a 10-item questionnaire that was implemented to identify patients with APUB, specifically combining tools designed to identify anovulatory/postmenopausal and heavy menstrual bleeding. Demographic (age, race), body mass index, and questionnaire data were analyzed with respect to positive screening using data from March 2021 through May 2023. RESULTS: Of 1371 eligible women presenting for surgical evaluation, 664 (48.4%) positive screens were identified and referred for gynecologic evaluation to rule out endometrial hyperplasia/cancer or other endometrial pathology. The likelihood of positive screening for APUB was associated with increasing BMI (P = .001) and Black/African American race (P = .003), as well as increasing SAMANTA score (P < .001). In contrast, risk of positive screening was negatively associated with increasing age (P < .001). CONCLUSIONS: Women presenting for metabolic/bariatric surgery have a high prevalence of APUB and, given this dysfunctional bleeding and concurrent obesity, are at greater risk for underlying EC. Potential risk factors for APUB, given their associations with screening positive, include increased body mass index, younger age, and Black/African American race. Standardized screening with appropriate gynecologic referral should be a routine part of the overall evaluation for women with severe obesity.

Anthracycline-induced cardiovascular toxicity: validation of the Heart Failure Association and International Cardio-Oncology Society risk score.

BACKGROUND AND AIMS: Baseline cardiovascular toxicity risk stratification is critical in cardio-oncology. The Heart Failure Association (HFA) and International Cardio-Oncology Society (ICOS) score aims to assess this risk but lacks real-life validation. This study validates the HFA-ICOS score for anthracycline-induced cardiovascular toxicity. METHODS: Anthracycline-treated patients in the CARDIOTOX registry (NCT02039622) were stratified by the HFA-ICOS score. The primary endpoint was symptomatic or moderate to severe asymptomatic cancer therapy-related cardiac dysfunction (CTRCD), with all-cause mortality and cardiovascular mortality as secondary endpoints. RESULTS: The analysis included 1066 patients (mean age 54 ± 14 years; 81.9% women; 24.5% ≥65 years). According to the HFA-ICOS criteria, 571 patients (53.6%) were classified as low risk, 333 (31.2%) as moderate risk, 152 (14.3%) as high risk, and 10 (0.9%) as very high risk. Median follow-up was 54.8 months (interquartile range 24.6-81.8). A total of 197 patients (18.4%) died, and 718 (67.3%) developed CTRCD (symptomatic: n = 45; moderate to severe asymptomatic: n = 24; and mild asymptomatic: n = 649). Incidence rates of symptomatic or moderate to severe symptomatic CTRCD and all-cause mortality significantly increased with HFA-ICOS score [hazard ratio 28.74, 95% confidence interval (CI) 9.33-88.5; P < .001, and hazard ratio 7.43, 95% CI 3.21-17.2; P < .001) for very high-risk patients. The predictive model demonstrated good calibration (Brier score 0.04, 95% CI 0.03-0.05) and discrimination (area under the curve 0.78, 95% CI 0.70-0.82; Uno's C-statistic 0.78, 95% CI 0.71-0.84) for predicting symptomatic or severe/moderate asymptomatic CTRCD at 12 months. CONCLUSIONS: The HFA-ICOS score effectively categorizes patients by cardiovascular toxicity risk and demonstrates strong predictive ability for high-risk anthracycline-related cardiovascular toxicity and all-cause mortality.

Chiari malformation type III and its viability. Case report and literature review.

Chiari malformation type III is a rare congenital anomaly. It consists of the posterior fossa contents herniation through an occipital or high cervical encephalocele sac. Although it has traditionally been associated with a high mortality rate, the absence of certain poor prognostic factors and appropriate medical and surgical treatment allow these children to survive and have a remarkable initial functional improvement. Surgical goals are defect repair, preservation of viable brain tissue, adequate skin coverage and hydrocephalus management. Despite all of this, the tendency of these newborns is to maintain a significant disability and if they present poor prognostic criteria, they usually demise within a short period of time. We report the case of a newborn with Chiari malformation type III diagnosed during pregnancy. After characterizing the anomaly with a postnatal MRI, the encephalocele was excised and multi-layer closure was performed. The patient progressively developed hydrocephalus during the postoperative period and required ventriculoperitoneal shunt placement. After an initial uneventful course, our patient suffered several episodes of respiratory disturbances. The child became ventilator dependent and palliative care was established in agreement with the parents after ruling out shunt malfunction.

Serodiversity, antibiotic resistance, and virulence genes of Vibrio parahaemolyticus in oysters collected in coastal areas of northwestern Mexico between 2012 and 2020.

This study aimed to determine the prevalence of V. parahaemolyticus in oysters from the northwestern coast of Mexico and to identify the serotypes, virulence factors, and antibiotic resistance of the strains. Oyster samples were collected from 2012 to 2020 from the northwest coast of Mexico; biochemical and molecular methods were used to identify V. parahaemolyticus from oysters; antiserum reaction to determine V. parahaemolyticus serotypes, and PCR assays were performed to identify pathogenic (tdh and/or trh) or pandemic (toxRS/new, and/or orf8) strains and antibiotic resistance testing. A total of 441 oyster samples were collected and tested for V. parahaemolyticus. Forty-seven percent of oyster samples were positive for V. parahaemolyticus. Ten different O serogroups and 72 serovars were identified, predominantly serotype O1:KUT with 22.2% and OUT:KUT with 17.3%. Twenty new serotypes that had not been previously reported in our region were identified. We detected 4.3% of pathogenic clones but no pandemic strains. About 73.5% of strains were resistant to at least one antibiotic, mainly ampicillin and ciprofloxacin; 25% were multi-drug resistant. In conclusion, the pathogenic strains in oysters and antibiotic resistance are of public health concern, as the potential for outbreaks throughout northwestern Mexico is well established.

Probabilistic prediction and context tree identification in the Goalkeeper game.

In this article we address two related issues on the learning of probabilistic sequences of events. First, which features make the sequence of events generated by a stochastic chain more difficult to predict. Second, how to model the procedures employed by different learners to identify the structure of sequences of events. Playing the role of a goalkeeper in a video game, participants were told to predict step by step the successive directions-left, center or right-to which the penalty kicker would send the ball. The sequence of kicks was driven by a stochastic chain with memory of variable length. Results showed that at least three features play a role in the first issue: (1) the shape of the context tree summarizing the dependencies between present and past directions; (2) the entropy of the stochastic chain used to generate the sequences of events; (3) the existence or not of a deterministic periodic sequence underlying the sequences of events. Moreover, evidence suggests that best learners rely less on their own past choices to identify the structure of the sequences of events.

Brain Endurance Training Improves and Maintains Chest Press and Squat Jump Performance When Fatigued.

ABSTRACT: Díaz-García, J, López-Gajardo, MÁ, Parraca, JA, Batalla, N, López-Rodríguez, R, and Ring, C. Brain endurance training improves and maintains chest press and squat jump performance when fatigued. J Strength Cond Res XX(X): 000-000, 2024-Mental fatigue can impair resistance exercise performance. Brain endurance training (BET)-the addition of demanding cognitive tasks to standard exercise training-improves endurance exercise performance more than standard training. Although BET has yet to be evaluated with resistance exercise, it is expected to improve performance, particularly when the performer feels mentally fatigued. The study employed a pretest (week 0), midtest (week 3), posttest (week 6), and follow-up (week 9) design, with subjects randomized to BET (n = 46) or control (exercise training) (n = 45) groups. In testing sessions, subjects performed chest press and squat jump exercises to failure before (feeling fresh) and after (feeling tired) a 30-minute cognitively demanding Stroop task. Training comprised 5 BET or control training sessions per week for 6 weeks. In each training session, subjects completed 4 sets of each exercise to failure, with each exercise set preceded by a 3-minute cognitive task (BET) or rest (control). Exercise performance (number of repetitions to failure) and mental fatigue markers were assessed. In pretesting, exercise performance did not differ between the groups. In midtesting and posttesting, BET performed more chest press and squat jump repetitions when fatigued by the 30-minute Stroop than control. The mental fatigue elicited by the Stroop task gradually declined with training in BET compared with control. In conclusion, BET enhanced resistance exercise performance compared with standard training when tested subsequent to a mentally fatiguing cognitive task. These benefits were maintained weeks after training ended. Brain endurance training is an effective method to mitigate the deleterious effects of mental fatigue on resistance exercise performance.

Clinical Characteristics of Hospitalized Patients With COVID-19 and Their Association With the Progression to Critical Illness and Death: A Single-Center Retrospective Study From Northwestern Mexico.

OBJECTIVE: The objective of this study was to associate the epidemiological and clinical characteristics of patients hospitalized for COVID-19 with the progression to critical illness and death in northwestern Mexico. METHODS: From March to October 2020, we collected the demographic and clinical characteristics of 464 hospitalized patients from northwestern Mexico. RESULTS: Sixty-four percent (295/464) of the patients became critically ill. Age, occupation, steroid and antibiotic use at previous hospitalization, and underlying diseases (hypertension, obesity, and chronic kidney disease) were associated with critical illness or death (p: < 0.05). No symptoms were associated with critical illness. However, the parameters such as the heart rate, respiratory rate, oxygen saturation, and diastolic pressure and the laboratory parameters such as the glucose, creatinine, white line cells, hemoglobin, D-dimer, and C-reactive protein, among others, were associated with critical illness (p: < 0.05). Finally, advanced age, previous hospital treatment, and the presence of one or more underlying diseases were associated with critical illness and death (p: < 0.02). CONCLUSIONS: Several epidemiological (e.g., age and occupation) and clinical factors (e.g., previous treatment, underlying diseases, and vital signs and laboratory parameters) were associated with critical illness and death in patients hospitalized with COVID-19. These data provide us with possible markers to avoid critical illness or death from COVID-19 in our region.

Right Bundle Branch Block Predicts Appropriate Implantable Cardioverter Defibrillator Therapies in Patients with Non-Ischemic Dilated Cardiomyopathy and a Prophylactic Implantable Cardioverter Defibrillator.

Background: The benefit of prophylactic implantable cardioverter defibrillators (ICDs) in patients with severe systolic dysfunction of non-ischemic origin is still unclear, and the identification of patients at risk for sudden cardiac death remains a major challenge. Aims/Methods: We retrospectively reviewed all consecutive patients with non-ischemic dilated cardiomyopathy (NICM) who underwent prophylactic ICD implantation between 2008 and 2020 in two tertiary centers. Our main goal was to identify the predictors of appropriate ICD therapies (anti-tachycardia pacing [ATP] and/or shocks) in this cohort of patients. Results: A total of 224 patients were included. After a median follow-up of 51 months, 61 patients (27.2%) required appropriate ICD therapies. Patients with appropriate ICD therapies were more frequently men (87% vs. 69%, p = 0.006), of younger age (59 years, (53-65) vs. 64 years, (57-70); p = 0.02), showed more right bundle branch blocks (RBBBs) (15% vs. 4%, p = 0.007) and less left bundle branch blocks (LBBBs) (26% vs. 47%, p = 0.005) in the ECG, and had higher left ventricular end-diastolic (100 mL/m2, (90-117) vs. 86, (71-110); p = 0.011) and systolic volumes (72 mL/m2, (59-87) vs. 61, (47-81), p = 0.05). In a multivariate competing-risks regression analysis, RBBB (HR 2.26, CI 95% 1.02-4.98, p = 0.043) was identified as an independent predictor of appropriate ICD therapies. Conclusion: RBBBs may help to identify patients with NICM at high risk of ventricular arrhythmias and requiring ICD intervention.

Retrospective study of germline variants in patients with hereditary melanoma study criteria in a real clinical practice setting.

INTRODUCTION: Five to twelve percent of melanomas show aggregation of melanomas or other related tumors within the same family or individual. Genes such as CDKN2A, or BAP1, among others, have been involved in this condition. MATERIAL AND METHODS: Retrospective descriptive study that includes patients from Cruces University Hospital (2016-2023) who met any of the following criteria: presence of two or more melanomas (1), or a melanoma and a pancreatic cancer (2) in the same individual; presence of a melanoma in an individual and one or more first- or second-degree relatives with melanoma or pancreatic cancer (3); first- or second-degree relationship with an individual with a known deleterious variant in genes related to melanoma predisposition (4); or incidental discovery of deleterious variants in genes related to predisposition to melanoma, within hereditary cancer panels carried out for reasons other than melanoma (5). RESULTS: 59 families were included (69 patients; 63.8% women), of which 8.5% (13% of patients) presented pathogenic/likely pathogenic variants (PV/LPV) in CDKN2A (6% of families and patients, excluding criteria 4 and 5), and 1.7% of families (1.4% of patients) presented PV/LPV in BAP1, BRCA2 and TERF2IP. DISCUSSION AND CONCLUSIONS: The frequencies of PV/LPV in CDKN2A are similar to those previously described. This study could contribute to the knowledge of the characteristics of patients who meet genetic study criteria for hereditary melanoma, in a setting of real clinical practice.

A Metric Based on the Efficient Determination Criterion.

This paper extends the concept of metrics based on the Bayesian information criterion (BIC), to achieve strongly consistent estimation of partition Markov models (PMMs). We introduce a set of metrics drawn from the family of model selection criteria known as efficient determination criteria (EDC). This generalization extends the range of options available in BIC for penalizing the number of model parameters. We formally specify the relationship that determines how EDC works when selecting a model based on a threshold associated with the metric. Furthermore, we improve the penalty options within EDC, identifying the penalty ln(ln(n)) as a viable choice that maintains the strongly consistent estimation of a PMM. To demonstrate the utility of these new metrics, we apply them to the modeling of three DNA sequences of dengue virus type 3, endemic in Brazil in 2023.

Internalization of PEI-based complexes in transient transfection of HEK293 cells is triggered by coalescence of membrane heparan sulfate proteoglycans like Glypican-4.

Polymer-cationic mediated gene delivery is a well-stablished strategy of transient gene expression (TGE) in mammalian cell cultures. Nonetheless, its industrial implementation is hindered by the phenomenon known as cell density effect (CDE) that limits the cell density at which cultures can be efficiently transfected. The rise in personalized medicine and multiple cell and gene therapy approaches based on TGE, make more relevant to understand how to circumvent the CDE. A rational study upon DNA/PEI complex formation, stability and delivery during transfection of HEK293 cell cultures has been conducted, providing insights on the mechanisms for polyplexes uptake at low cell density and disruption at high cell density. DNA/PEI polyplexes were physiochemically characterized by coupling X-ray spectroscopy, confocal microscopy, cryo-transmission electron microscopy (TEM) and nuclear magnetic resonance (NMR). Our results showed that the ionic strength of polyplexes significantly increased upon their addition to exhausted media. This was reverted by depleting extracellular vesicles (EVs) from the media. The increase in ionic strength led to polyplex aggregation and prevented efficient cell transfection which could be counterbalanced by implementing a simple media replacement (MR) step before transfection. Inhibiting and labeling specific cell-surface proteoglycans (PGs) species revealed different roles of PGs in polyplexes uptake. Importantly, the polyplexes uptake process seemed to be triggered by a coalescence phenomenon of HSPG like glypican-4 around polyplex entry points. Ultimately, this study provides new insights into PEI-based cell transfection methodologies, enabling to enhance transient transfection and mitigate the cell density effect (CDE).

Clinical impact of remote heart failure management using the multiparameter ICD HeartLogic alert.

INTRODUCTION AND OBJECTIVES: The multiparametric implantable cardioverter-defibrillator HeartLogic index has proven to be a sensitive and timely predictor of impending heart failure (HF) decompensation. We evaluated the impact of a standardized follow-up protocol implemented by nursing staff and based on remote management of alerts. METHODS: The algorithm was activated in HF patients at 19 Spanish centers. Transmitted data were analyzed remotely, and patients were contacted by telephone if alerts were issued. Clinical actions were implemented remotely or through outpatient visits. The primary endpoint consisted of HF hospitalizations or death. Secondary endpoints were HF outpatient visits. We compared the 12-month periods before and after the adoption of the protocol. RESULTS: We analyzed 392 patients (aged 69±10 years, 76% male, 50% ischemic cardiomyopathy) with implantable cardioverter-defibrillators (20%) or cardiac resynchronization therapy defibrillators (80%). The primary endpoint occurred 151 times in 86 (22%) patients during the 12 months before the adoption of the protocol, and 69 times in 45 (11%) patients (P<.001) during the 12 months after its adoption. The mean number of hospitalizations per patient was 0.39±0.89 pre- and 0.18±0.57 postadoption (P<.001). There were 185 outpatient visits for HF in 96 (24%) patients before adoption and 64 in 48 (12%) patients after adoption (P<.001). The mean number of visits per patient was 0.47±1.11 pre- and 0.16±0.51 postadoption (P<.001). CONCLUSIONS: A standardized follow-up protocol based on remote management of HeartLogic alerts enabled effective remote management of HF patients. After its adoption, we observed a significant reduction in HF hospitalizations and outpatient visits.

Landscape features influencing gene flow and connectivity of an endangered passerine.

Dispersal of individuals and gene flow are crucial aspects to maintain genetic diversity and viability of populations, especially in the case of threatened species. Landscape composition and structure may facilitate or limit individual movement within and among populations. We used a landscape genetics approach to assess the connectivity patterns of the threatened Dupont's lark (Chersophilus duponti subsp. duponti), considering their genetic patterns and the landscape features associated with its gene flow in Spain. We analysed the genetic relatedness based on 11 species-specific polymorphic microsatellites on 416 Dupont's lark individuals sampled across peninsular Spain between 2017 and 2019, covering most of the European distribution of the species. To assess the relationship between the landscape composition and the species gene flow, we estimated genetic distance at the individual level (Dps). Next, we built a set of environmental surfaces from two time periods (years 1990 and 2018), based on factors such as land use and topography, influencing individuals' movement. We then obtained resistance surfaces from an optimization process on landscape variables. Landscape genetics analyses were done for single and composite surface models for each year separately. Our findings from both time points show that scatter or mosaic-structured vegetation composed by low agricultural and tree cover and high presence of sclerophyllous shrubs favoured Dupont's lark dispersal, while dense and continuous tree cover, as well as areas of intensive agriculture, were limiting factors. Our results suggest the importance of steppe habitat patches for the species' establishment and dispersal. In addition, our results provide key information to develop conservation measures, including conserving and restoring steppe habitats as scattered and/or mosaic-structured vegetation that could warrant the connectivity and persistence of Dupont's lark populations.

Production and Physicochemical Characterization of the Gel Obtained in the Fermentation Process of Blue Corn Flour (Zea mays L.) with Colletotrichum gloeosporioides.

Food gels are viscoelastic substances used in various gelled products manufactured around the world. Polysaccharides are the most common food gelling agents. The aim of this work was the production and characterization of a gel produced in a blue corn flour fermentation process, where different proportions were used of blue corn (Zea mays L.) flour and Czapek Dox culture medium (90 mL of culture medium with 10 g of blue corn flour, 80 mL of culture medium with 20 g of blue corn flour, and 70 mL of culture medium with 30 g of blue corn flour) and were fermented for three different durations (20, 25, and 30 days) with the Colletotrichum gloeosporioides fungus. A characterization of the gel was carried out studying the rheological properties, proximal analysis, toxicological analysis, microscopic structure, and molecular characterization, in addition to a solubility test with three different organic solvents (ethanol, hexane, and ethyl acetate, in addition to water). The results obtained showed in the rheological analysis that the gel could have resistance to high temperatures and a reversible behavior. The gel is soluble in polar solvents (ethanol and water). The main chemical components of the gel are carbohydrates, especially polysaccharides, and it was confirmed by FT-IR spectroscopy that the gel may be composed of pectin.

High frequency oscillations in human memory and cognition: a neurophysiological substrate of engrams?

Despite advances in understanding the cellular and molecular processes underlying memory and cognition, and recent successful modulation of cognitive performance in brain disorders, the neurophysiological mechanisms remain underexplored. High frequency oscillations beyond the classic electroencephalogram spectrum have emerged as a potential neural correlate of fundamental cognitive processes. High frequency oscillations are detected in the human mesial temporal lobe and neocortical intracranial recordings spanning gamma/epsilon (60-150 Hz), ripple (80-250 Hz) and higher frequency ranges. Separate from other non-oscillatory activities, these brief electrophysiological oscillations of distinct duration, frequency and amplitude are thought to be generated by coordinated spiking of neuronal ensembles within volumes as small as a single cortical column. Although the exact origins, mechanisms, and physiological roles in health and disease remain elusive, they have been associated with human memory consolidation and cognitive processing. Recent studies suggest their involvement in encoding and recall of episodic memory with a possible role in the formation and reactivation of memory traces. High frequency oscillations are detected during encoding, throughout maintenance, and right before recall of remembered items, meeting a basic definition for an engram activity. The temporal coordination of high frequency oscillations reactivated across cortical and subcortical neural networks is ideally suited for integrating multimodal memory representations, which can be replayed and consolidated during states of wakefulness and sleep. High frequency oscillations have been shown to reflect coordinated bursts of neuronal assembly firing and offer a promising substrate for tracking and modulation of the hypothetical electrophysiological engram.

Sucrose supplements modulate the Pseudomonas chlororaphis-Arabidopsis thaliana interaction via decreasing the production of phenazines and enhancing the root auxin response.

Management of the plant microbiome may help support food needs for the human population. Bacteria influence plants through enhancing nutrient uptake, metabolism, photosynthesis, biomass production and/or reinforcing immunity. However, information into how these microbes behave under different growth conditions is missing. In this work, we tested how carbon supplements modulate the interaction of Pseudomonas chlororaphis with Arabidopsis thaliana. P. chlororaphis streaks strongly repressed primary root growth, lateral root formation and ultimately, biomass production. Noteworthy, increasing sucrose availability into the media from 0 to 2.4% restored plant growth and promoted lateral root formation in bacterized seedlings. This effect could not be observed by supplementing sucrose to leaves only, indicating that the interaction was strongly modulated by bacterial access to sugar. Total phenazine content decreased in the bacteria grown in high (2.4%) sucrose medium, and conversely, the expression of phzH and pslA genes were diminished by sugar supply. Pyocyanin antagonized the promoting effects of sucrose in lateral root formation and biomass production in inoculated seedlings, indicating that this virulence factor accounts for growth repression during the plant-bacterial interaction. Defence reporter transgenes PR-1::GUS and LOX2::GUS were induced in leaves, while the expression of the auxin-inducible, synthetic reporter gene DR5::GUS was enhanced in the roots of bacterized seedlings at low and high sucrose treatments, which suggests that growth/defence trade-offs in plants are critically modulated by P. chlororaphis. Collectively, our data suggest that bacterial carbon nutrition controls the outcome of the relation with plants.

Habitat type modulates sharp body mass oscillations in cyclic common vole populations.

Cyclic rodent populations exhibit pronounced changes in body mass associated with the population cycle phase, long-known as Chitty effect. Although Chitty effect is a common epiphenomenon in both America and Europe, there is still incomplete evidence about the generality of these patterns across the entire range of most species. Moreover, despite decades of research, the underlying factors driving Chitty effect remains poorly understood. Here, we examined the influence of intrinsic and extrinsic factors that may underlie observed patterns in vole size variation in the Iberian common vole Microtus arvalis asturianus. We weighed and measured 2816 adult voles that were captured during 6 trapping periods. Vole numbers and body mass showed strong period- and phase-related variation both in females and males, demonstrating marked Chitty effect in the studied population. Body mass of adult males correlated with body length, evidencing that heavier males are also structurally larger. Statistical models showed that probability of occurrence of large-sized vole (> 37 g) was significantly more likely in reproductive males, during increase and peak phases, and it was modulated by habitat, with crop fields and field margins between crops showing an increased likelihood. We suggest an effect of the habitat on vole body mass mediated by predation.

Unravelling the essential elements for recombinant adeno-associated virus (rAAV) production in animal cell-based platforms.

Recombinant adeno-associated viruses (rAAVs) stand at the forefront of gene therapy applications, holding immense significance for their safe and efficient gene delivery capabilities. The constantly increasing and unmet demand for rAAVs underscores the need for a more comprehensive understanding of AAV biology and its impact on rAAV production. In this literature review, we delved into AAV biology and rAAV manufacturing bioprocesses, unravelling the functions and essentiality of proteins involved in rAAV production. We discuss the interconnections between these proteins and how they affect the choice of rAAV production platform. By addressing existing inconsistencies, literature gaps and limitations, this review aims to define a minimal set of genes that are essential for rAAV production, providing the potential to advance rAAV biomanufacturing, with a focus on minimizing the genetic load within rAAV-producing cells.

Hydrogen peroxide modulates the expression of the target of rapamycin (TOR) and cell division in Arabidopsis thaliana.

Hydrogen peroxide (H2O2) is naturally produced by plant cells during normal development and serves as a messenger that regulates cell metabolism. Despite its importance, the relationship between hydrogen peroxide and the target of rapamycin (TOR) pathway, as well as its impact on cell division, has been poorly analyzed. In this study, we explore the interaction of H2O2 with TOR, a serine/threonine protein kinase that plays a central role in controlling cell growth, size, and metabolism in Arabidopsis thaliana. By applying two concentrations of H2O2 exogenously (0.5 and 1 mM), we could correlate developmental traits, such as primary root growth, lateral root formation, and fresh weight, with the expression of the cell cycle gene CYCB1;1, as well as TOR expression. When assessing the expression of the ribosome biogenesis-related gene RPS27B, an increase of 94.34% was noted following exposure to 1 mM H2O2 treatment. This increase was suppressed by the TOR inhibitor torin 2. The elimination of H2O2 accumulation with ascorbic acid (AA) resulted in decreased cell division as well as TOR expression. The potential molecular mechanisms associated with the effects of H2O2 on the cell cycle and TOR expression in roots are discussed in the context of the results.