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Systematic review of microorganism disinfection performance by chemical and ultraviolet light water treatment methods.

Safe drinking water is critical for public health, yet microbial contamination remains a significant global challenge. We conducted a systematic review to update World Health Organization guidance on water disinfection technologies by synthesizing peer-reviewed literature from 1997 to 2021 on the performance of free chlorine, chlorine dioxide, ozone, and ultraviolet (UV) light against bacteria, viruses, and protozoa. Following PRISMA guidelines, we analyzed log10 reduction values (LRVs) and contact times (Ct) or fluence (for UV) from laboratory and field studies. We included studies from multiple databases and expert-recommended studies. Results show mean Cts for 2 LRV of non-opportunistic bacteria as 6.0 (free chlorine), 0.4 (chlorine dioxide), and 1.2 (ozone) mg/L*min, and a mean UV fluence of 8.2 mJ/cm² (all bacteria). Viruses required lower Cts, except for UV-resistant adenoviruses, while protozoa required higher Cts or fluences. Opportunistic bacteria required significantly higher Cts than non-opportunistic bacteria for free chlorine and chlorine dioxide. Temperature and pH effects were inconsistent, highlighting data variability and gaps in field studies. These findings support global guidance on water treatment and may be used alongside other context-specific data to understand the roles these technologies play in reducing waterborne exposures. We recommend standardized reporting from performance studies to enable straightforward synthesis of evidence.

Disinfection

Application of causal discovery of factors driving dissolved oxygen in estuarine environments.

Dissolved oxygen (DO) concentrations in estuarine bottom waters are a manifestation of multiple, interacting physical and biogeochemical processes, yet identifying their independent contributions remains challenging. Here, we analyze monthly water quality monitoring data from eight stations across Long Island Sound from 1994 to 2022 using a causal discovery framework (PCMCI+) and transformation of forcing variables. Our goal is to identify and isolate variables that causally influence bottom DO and improve predictive models by minimizing overfitting and multicollinearity. PCMCI+ reveals surface-layer temperature as the most important and consistent negative driver of bottom DO, followed by stratification. Wind events exhibit only brief relief by advection and mixing, while river discharge shows no direct causal link to DO, making it less influential than previously thought. Biogeochemical variables, including chlorophyll-a (Chl-a), nitrate and nitrite, and particulate carbon, influence DO through both contemporaneous and time-lagged pathways, often with signs that shift depending on the process. The derived models were evaluated by comparing skill scores, mean squared error, and Akaike Information Criterion. Both model types perform well, with coefficient of determination values exceeding 0.90 at multiple stations using only 3-5 predictors. Our analysis reveals that the best causal predictors are surface-layer temperature, stratification, Chl-a, and particle carbon. This approach provides a scalable framework for improving prediction models and understanding the mechanistic links that control the seasonal variability of DO in estuarine systems.

Estuaries

Glycerophospholipid remodeling under osmotic stress in grass carp gills.

Salinity fluctuations represent a pervasive environmental challenge for freshwater fishes, yet the cellular and metabolic programs governing early osmoregulatory responses remain understudied. Here, we investigated the time-dependent gill responses of juvenile grass carp (Ctenopharyngodon idella) subjected to an acute, sublethal salinity increase 9 parts per thousand (ppt). Histological and biochemical analyses revealed progressive gill lesions accompanied by elevated lactate dehydrogenase (LDH) activity and lipid peroxidation, indicating rapid tissue injury under osmotic stress. Integrative metabolomic and transcriptomic profiling uncovered pronounced temporal reprogramming, consistently highlighting glycerophospholipid metabolism as a central axis of response. In particular, phosphatidylcholine (PC) species exhibited dynamic remodeling, coupled with transcriptional enrichment of lipid turnover, membrane transport, and innate immune pathways. Network-based integration identified a PC-centered remodeling module characterized by accelerated PC headgroup turnover, disruption of the PLA2-LPCAT2 lyso-PC reacylation cycle, and enhanced ABC transporter-associated lipid and sterol export, reflected by cholesteryl sulfate accumulation and a shifted n-6 polyunsaturated fatty acid-derived oxylipin signature. Functional assays further demonstrated that PC and linoleic acid (LA) supplementation improved cell viability and alleviated oxidative stress and pro-inflammatory signaling in grass carp cells under salinity challenge. Collectively, these findings reveal phospholipid-centered membrane remodeling as an early, integrative mechanism linking osmotic stress to gill injury and immune activation in freshwater fish, providing insights into potential strategies of environmental stress adaptation.

Animals

Do vaccinated cases transmit measles? A systematic review and meta-analysis.

INTRODUCTION: We reviewed evidence on whether vaccinated individuals can transmit measles and conducted a meta-analysis to understand transmission characteristics. METHODS: We searched and extracted data from peer-reviewed and gray literature and included studies reporting measles transmission events from vaccinated individuals. We meta-analyzed the data to calculate the median number of transmissions from vaccinated cases by measles burden, number of doses, and time since first and last dose. RESULTS: We identified 11,911 peer-reviewed and 22 gray literature records and included 33 articles in our review. Seventy individuals who had received 1 or more doses of measles-containing vaccine transmitted measles virus, resulting in 237 secondary cases. Vaccinated transmitters in eliminated areas were older (median age of 19 years (IQR: 3, 21)) than those in non-eliminated areas (median age 16 years; IQR 13, 18) (p = 0.12). Additionally, 91% (30/33) of studies provided data on subsequent transmission generations, leading to 812 measles cases traced back to vaccinated individuals, with a median of 4 (IQR: 1, 10) cases per vaccinated transmitter. CONCLUSION: Measles transmissions from vaccinated cases, although relatively uncommon, must be considered in public health investigations, as such transmissions can contribute to outbreaks.

Adolescent

The impact of alcohol sale restrictions on unnatural deaths during the COVID-19 pandemic in Johannesburg, South Africa.

The COVID-19-related restrictions on the sale of alcohol in South Africa presented a unique opportunity to examine the association between alcohol availability and the prevalence of unnatural deaths. The study sample included all unnatural deaths investigated by the Johannesburg Forensic Pathology Services Medico-Legal Laboratory during the four COVID-19 alcohol restriction periods compared to the same time periods in the previous year when there were no restrictions. When alcohol sales were initially prohibited, there was a 54.2% decrease in cases of unnatural deaths (p&#x2009;<&#x2009;0.05), suggesting a link between alcohol use and the occurrence of such deaths. Over all four periods of alcohol sale bans, there was a total reduction of unnatural deaths by 26.4% with declining frequencies in all demographics. There were significant decreases (p&#x2009;<&#x2009;0.05) in the frequency of deaths in males, Black and Coloured individuals, and the 21-40 years age group. Deaths whose circumstances were a result of motor vehicle accidents, pedestrian vehicle accidents, and firearm discharges decreased significantly (p&#x2009;<&#x2009;0.05). The cause of death due to blunt forces trauma and gunshot wounds also significantly decreased (p&#x2009;<&#x2009;0.05). This study highlights the significant impact alcohol consumption has on mortality in South Africa.

Humans

The spatial and temporal distribution of Staphylococcus aureus along a tropical Hawaiian watershed.

Staphylococcus aureus is a leading cause of community-acquired skin and soft-tissue infections worldwide. One major route of exposure is recreating in marine waters, but knowledge is limited regarding the drivers of S. aureus in surface waters that discharge into marine environments. This study explores spatial and temporal distributions of S. aureus, including antimicrobial-resistant and virulence genes, using both culture-dependent and molecular techniques across a tropical Hawaiian watershed with a gradient of human influence. Negative binomial generalized linear mixed models revealed that the interaction between spatial and temporal factors was the strongest predictor of S. aureus and associated genes. Cultured S. aureus was highest at mid-watershed sites in summer, which included a popular swimming hole, suggesting human shedding as a significant source. Molecular detection of S. aureus (femA gene) yielded concentrations two orders of magnitude higher than cultured concentrations and peaked at estuarine sites with the greatest nutrients and water residence times. In the winter at upstream sites with no public access, staphylococci antibiotic-resistant (mecA) and S. aureus virulence gene (etb) were elevated, indicating highly pathogenic S. aureus strains in surface waters may originate from zoonotic sources. Our findings indicate that human and zoonotic sources contribute antibiotic-resistant and virulent S. aureus to watersheds, with streams facilitating environmental transmission to marine waters. This watershed-scale assessment enables the prediction of spatial and temporal conditions associated with elevated S. aureus concentrations, thereby reducing exposure and infections.

Staphylococcus aureus

Thrombus Metabolism-Based Molecular Subtyping for Prognostic Risk Stratification in Acute Ischemic Stroke: A Preliminary Study.

AIMS: To preliminarily characterize metabolic molecular subtypes of cerebral thromboemboli and evaluate their clinical significance in anterior circulation acute ischemic stroke due to large vessel occlusion (AIS-LVO). METHODS: Untargeted metabolomics was performed on thromboemboli retrieved from 36 patients with anterior circulation AIS-LVO using ultra-performance coupled liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Unsupervised hierarchical clustering was employed to identify distinct metabolic molecular subtypes, and their associations with stroke etiology, radiographic severity, and functional outcomes were analyzed. RESULTS: Two distinct thrombus metabolic molecular subtypes (C1 and C2) were identified based on 12 metabolites significantly associated with both short-term (7-day &#x2206;NIHSS) and long-term (90-day mRS) functional outcomes. The C1 subtype, predominantly cardioembolic, exhibited enhanced lipid metabolism, whereas the C2 subtype, primarily atherothrombotic, demonstrated increased folate metabolism. Patients with C1 thromboemboli presented more severe admission ischemic lesions (as indicated by ASPECTS) and experienced poorer short-term and long-term outcomes. A six-metabolite signature derived from LASSO regression was identified for exploratory discrimination of thrombus metabolic subtypes, etiological subtypes, and 90-day outcomes. CONCLUSION: This preliminary exploratory study identifies two metabolically distinct thrombus molecular subtypes with clinical implications in anterior circulation AIS-LVO, providing a novel basis for risk stratification and personalized secondary prevention and warrants further investigation.

Humans

Glucocorticoids and placental 11&#x3b2;HSD2 - A systematic review of human studies and animal models.

CONTEXT: Elevated prenatal glucocorticoid (GC) exposure is linked to adverse offspring outcomes. The placental enzyme 11&#x3b2;-hydroxysteroid-dehydrogenase-type-2 (11&#x3b2;HSD2) protects the fetus by converting maternal derived cortisol to inactive cortisone. Although in vitro studies suggest GC mediated upregulation of 11&#x3b2;HSD2, in vivo evidence remains inconclusive. METHODS: PubMed, Embase, and PsycInfo were searched in October 2024 for human and mammalian animal studies on endogenous or exogenous GCs during pregnancy and associations with placental 11&#x3b2;HSD2 (mRNA, protein, activity, gene methylation). Narrative synthesis was conducted due to heterogeneity precluding meta-analysis. RESULTS: Eighteen studies (eight human, ten animal populations) met inclusion criteria. Exogenous GC exposure was associated with modifications in placental 11&#x3b2;HSD2 expression in animal models, with effects varying by substance, timing, and species. Dexamethasone trended towards increased expression in rodents, whereas betamethasone increased expression in non-human primates but not rodents. Human studies on endogenous GCs showed inconsistent associations with 11&#x3b2;HSD2 changes. In asthmatic pregnancies, moderate inhaled GC-use maintained enzyme activity compared to untreated patients. No convincing sex-specific trend emerged. CONCLUSIONS: GC exposure alters placental 11&#x3b2;HSD2 in a substance- and species-specific way; translational relevance remains limited based on current literature. Future studies should employ technological advances and include GC-sensitive biomarkers to clarify mechanisms of maternal-fetal stress transmission.

Female

Simulating the effects of an alcohol minimum unit price policy on distilled spirits sales in 28 states of the USA.

BACKGROUND AND AIMS: Excessive alcohol use is a leading preventable chronic disease risk factor. Alcohol minimum unit pricing (MUP) policies are not used in the United States despite evidence of associations with reduced drinking and alcohol-related harms. To inform potential population-level chronic disease prevention strategies, we estimated effects of various hypothetical MUPs on alcohol sales. METHOD: Simulation based on observational time-series data. We used weekly off-premises product-specific alcohol retail sales and prices in 28 states of the United States for November 2022-November 2023 from NielsenIQ to estimate the own-price elasticity of spirits and cross-price elasticities of wine, beer and ready-to-drinks with respect to spirits. Using estimated elasticities, we simulated changes in total alcohol sales associated with hypothetical spirits MUPs ranging from $0.10 to $1.10 per standard drink (0.6 fluid ounces of alcohol). RESULTS: A hypothetical MUP of $0.80 per standard drink on spirits yielded the largest estimated decrease in alcohol sales (-1.7%) and would affect 5374 of 26&#x2009;249 spirits products. To reach the $0.80 MUP, the sales-weighted average price increase among affected products was $0.24 per drink. CONCLUSIONS: Minimum unit pricing policies on distilled spirits in the United States could shift purchasing behavior and help reduce alcohol-related harms.

alcohol policy

Molecular mechanisms of neuroendocrine regulation of molting in the Chinese mitten crab (Eriocheir sinensis): A transcriptomic analysis based on eyestalk ablation model.

Molting disability severely restricts the sustainable aquaculture of the Chinese mitten crab, yet the neuroendocrine mechanisms coordinating physiological responses remain poorly understood. Using unilateral eyestalk ablation to remove the primary source of molt-inhibiting hormone (MIH), we performed time-resolved transcriptomic profiling of the thoracic ganglion at 24&#xa0;h (early premolt) and 48&#xa0;h (ecdysis) post-ablation. We identified 2825 differentially expressed genes and uncovered a biphasic molecular response. At 24&#xa0;h, the thoracic ganglion activates pathways associated with neuromuscular adaptation, oxidative stress, and cardiac muscle contraction. Notably, the arachidonic acid metabolism pathway is selectively rewired: cytochrome P450 &#x3c9;-hydroxylases (CYP2J2, CYP4V2) are upregulated, while competing branches (epoxide hydrolase, cyclooxygenase) are suppressed, promoting local synthesis of the potent vasoconstrictor 20-HETE within the thoracic ganglion. This enzymatic switch provides a mechanistic link between MIH withdrawal and the local generation of elevated hemolymph pressure required for molting. By 48&#xa0;h, the transcriptional program shifts toward chitin-based extracellular matrix remodeling, glycosphingolipid biosynthesis, and synaptic reorganization. Collectively, our findings redefine the thoracic ganglion as an active neuroendocrine integrator that translates reduced MIH signaling into phased physiological outputs, revealing a "neuro-endocrine-hemolymph pressure" regulatory axis. This study provides novel molecular targets (e.g., CYP2J2, CHS1, UGCG) for mitigating molting disability in E. sinensis aquaculture.

Animals

Multisensory stimulation for promoting development and preventing morbidity in preterm infants.

RATIONALE: Multisensory stimulation is a structured, developmentally appropriate intervention that provides simultaneous or sequential stimulation of two or more senses (e.g. tactile, auditory, visual, or vestibular) in a controlled and non-stressful manner, with the aim of supporting early neurodevelopment in preterm infants. It has the potential to enhance physiological regulation in preterm infants by stabilizing key functions, such as respiratory patterns, heart rate, and oxygen saturation; reducing the need for respiratory support; and improving feeding performance and sleep regulation. Targeted multisensory interventions have also been associated with improved neurodevelopmental outcomes, including enhanced psychomotor development and visual function. OBJECTIVES: To assess the benefits and harms of multisensory stimulation compared to any single sensory intervention or standard care on major neurodevelopmental disability, mortality, and growth in preterm infants. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Emcare, CINAHL, Epistemonikos, two trial registries, and conference abstracts up to 28 November 2025. We checked reference lists of included trials, and systematic reviews on sensory interventions. ELIGIBILITY CRITERIA: We included 18 randomized controlled trials (RCTs) comparing multisensory stimulation in preterm infants with no intervention (placebo or standard care), and one RCT comparing multisensory stimulation with single-sense stimulation (tactile stimulation). OUTCOMES: Our critical outcomes were major neurodevelopmental disability at 18 to 24 months: cerebral palsy (CP), developmental delay, intellectual impairment, blindness, sensorineural deafness; death during initial hospitalization; and total weight gain (grams), assessed at discharge. When comparing multisensory stimulation with single-sense intervention, we also included weight gain during the intervention, an outcome added during the post-hoc analysis. Important outcomes were duration of hospital stay, of NICU stay, and of respiratory support; and time until full oral feeding. RISK OF BIAS: We used the Cochrane tool, RoB 2. SYNTHESIS METHODS: We conducted meta-analyses using fixed-effect models to calculate risk ratios (RR) for dichotomous data, and mean differences (MDs) for continuous data, each with its 95% confidence intervals (CIs). We assessed statistical heterogeneity by calculating the I2 statistic when we included more than two trials in a meta-analysis. We evaluated the certainty of evidence using GRADE. INCLUDED STUDIES: We included 19 trials (1554 newborn infants): 18 studies compared multisensory stimulation with standard care; one compared multisensory stimulation with single-sensory stimulation (tactile). In 10 studies, the primary aim was to assess the neurobehavioral outcomes of multisensory stimulation on preterm neo-nates. The other nine studies aimed to assess the impact of multisensory stimulation on weight gain during the intervention, weight gain until hospital discharge, length of neonatal intensive care unit (NICU) stay, length of hospital stay, time until full oral feeding, length of respiratory support, or a combination. In the abstract we report results for the critical outcomes only. We identified 13 ongoing studies. Four studies are awaiting assessment. SYNTHESIS OF RESULTS: Multisensory stimulation compared to standard care No studies reported on these major neurodevelopmental disabilities, assessed at 18 to 24 months' corrected age (CA): developmental delay, intellectual impairment, blindness, or sensorineural deafness. One study reported on rates of CP at 12 months of age. The evidence is very uncertain about the effect of multisensory stimulation on CP (RR 0.67, 95% CI 0.28 to 1.58; I&#xb2; not applicable; 1 study, 18 participants; very low-certainty evidence). The evidence suggests that multisensory stimulation may result in little to no difference in death during initial hospitalization (RR 0.97, 95% CI 0.54 to 1.73; I&#xb2; not applicable; 1 study, 395 participants; low-certainty evidence). Multisensory stimulation may increase total weight gain prior to discharge (MD 72.67, 95% CI 68.23 to 77.12; I&#xb2; = 0%; 3 studies, 474 participants; low-certainty evidence). Multisensory stimulation compared to single-sense (tactile) stimulation No studies reported on major neurodevelopmental disability, assessed at 18 to 24 months' CA, or death during initial hospitalization. The evidence is very uncertain about the effect of multisensory stimulation compared to tactile stimulation on weight gain during the intervention (MD -175.00, 95% CI -376.60 to 26.60; I&#xb2; not applicable; 1 study, 20 participants; very low-certainty evidence). The certainty of the evidence was low to very low across outcomes, primarily due to risk of bias, imprecision from small sample sizes and wide CIs, and in some cases, inconsistency. The evidence base was also limited by the lack of reporting of relevant outcomes and reliance on surrogate outcomes or shorter follow-up periods. AUTHORS' CONCLUSIONS: The available evidence on multisensory stimulation in preterm infants is limited and of low to very low certainty. No included studies reported on major neurodevelopmental disabilities at 18 to 24 months' CA, which represented a critical outcome for this review. Evidence regarding the effect of multisensory stimulation on CP is very uncertain, as it is based on a single small study reporting a surrogate outcome at 12 months. Multisensory stimulation may result in little to no difference in mortality during the initial hospitalization. It may increase total weight gain prior to discharge. However, the clinical significance of this finding is uncertain, particularly given the low certainty of the evidence and the multifactorial nature of growth in preterm infants. The evidence is very uncertain about the effect of multisensory stimulation compared to single-sense (tactile) stimulation on weight gain during the intervention. The only included study did not report major neurodevelopmental disabilities at 18 to 24 months' CA, mortality during the initial hospitalization, or total weight gain prior to discharge, which represented the critical outcomes for this review. Overall, the current evidence does not allow firm conclusions about the effectiveness of multisensory stimulation in promoting development or preventing morbidity in preterm infants. Future studies on multisensory stimulation should use more rigorous designs, larger samples, and report interventions using the template for intervention description and replication (TIDieR) checklist to ensure transparency. They should also report essential outcomes, such as neonatal death, major neurodevelopmental disabilities, length of hospital and NICU stay, time to full oral feeding, duration of respiratory support, and weight gain, to better assess the long&#x2011;term effects of multisensory stimulation in preterm infants. FUNDING: This Cochrane review had no dedicated funding. REGISTRATION: Protocol available via DOI: 10.1002/14651858.CD016073.

Humans

A Meta-analysis of the intervention effects of ball sports on children with autism Spectrum disorder.

PURPOSE: To evaluate the overall efficacy of ball sports interventions for children with autism spectrum disorder (ASD) and to explore potential moderators that may influence intervention outcomes. METHODS: Randomized controlled trials were retrieved from nine databases (e.g., CNKI, PubMed) from 2000 to April 2025. Meta-analysis was conducted using RevMan 5.4 and Stata 18.0, with subgroup analyses by age, duration, frequency, session length, and ball sport type. RESULTS: A total of 14 randomized controlled trials involving 406 children were ultimately included. Meta-analysis results indicated that ball sports had a significant overall intervention effect on children with ASD (SMD&#xa0;=&#xa0;-1.12, 95% CI: -1.56, -0.68, P&#xa0;<&#xa0;0.05), with significant improvements observed in social skills (SMD&#xa0;=&#xa0;-0.55), verbal communication (SMD&#xa0;=&#xa0;-0.85), and behavioral problems (SMD&#xa0;=&#xa0;-1.10). Subgroup analysis indicated that interventions involving mini-basketball or other ball sports with simple rules-conducted over a 12-week period, 3-5 times per week, for 30-60&#xa0;min per session-yielded better outcomes, with children aged 3-6&#xa0;years showing more consistent benefits. CONCLUSION: Ball-based interventions effectively alleviate core ASD symptoms. Structured moderate-intensity programs are recommended as adjunct therapies. Future studies should standardize protocols and examine long-term benefits.

Humans

Emergence of an optrA-positive Enterococcus faecalis ST699 lineage in animal-derived foods in Beijing, China.

Enterococci from animal-derived foods are key reservoirs for antimicrobial resistance (AMR) in the food chain. However, comparative genomic studies investigating the distribution of the oxazolidinone resistance gene optrA among food- and human-derived Enterococci remain limited. This study assessed linezolid-resistant Enterococci from retail meat and healthy humans in Beijing, China (2023-2024). Among 87 isolates, E. faecalis and E. faecium predominated. Food-derived isolates showed broader resistance profiles than human isolates. Fourteen optrA-positive strains were identified, accounting for 92.9% of food isolates. optrA frequently co-localized with erm(A), ant(9)-Ia, and fexA on Tn554-family transposons, suggesting a potentially transferable multidrug resistance module. Notably, an optrA-positive E. faecalis ST699 clone was identified for the first time in Chinese retail meat. This clone formed a distinct lineage and carried a complete Tn554-optrA island. A representative ST699 isolate exhibited enhanced fitness and virulence potential in the Galleria mellonella model. These findings highlight animal-derived foods as important reservoirs of linezolid-resistant Enterococci and provide genomic evidence consistent with their role as potential sources of optrA-mediated resistance. The emergence of a multidrug-resistant E. faecalis ST699 clone with enhanced fitness characteristics underscores the need for continued surveillance of foodborne antimicrobial resistance within the One Health framework.

Enterococcus faecalis

Management of neonates born to mothers with reactive serologic tests for syphilis.

PURPOSE OF REVIEW: The dramatic resurgence of maternal and congenital syphilis in the United States highlights the need for their optimal management as syphilis in pregnancy can result in substantial neonatal morbidity and mortality. This review summarizes current epidemiology and discusses guidance on the management of neonates born to mothers with reactive serologic tests for syphilis. RECENT FINDINGS: Timely communication with local health department professionals is essential for optimal management of mothers with reactive serologic tests for syphilis and their neonates. Knowledge of maternal syphilis treatment history by partnering with local jurisdictions can circumvent much of the incertitude surrounding neonatal management. All neonates born to mothers with reactive serologic tests for syphilis should be tested using a nontreponemal ('lipoidal antigen') test. However, a reactive test may only indicate maternal nontreponemal IgG antibodies that are transferred transplacentally to the fetus. Therefore, neonatal management depends on maternal history and treatment for syphilis as well as clinical, laboratory, and radiographic findings in the neonatal evaluation. Existing management algorithms are complex, highlighting the need for a more practical, yet safe, approach. SUMMARY: A neonatal management guideline is proposed that may simplify the management of neonates born to mothers with reactive serologic tests for syphilis while advocating for expanded use of single-dose benzathine penicillin G therapy.

Humans

Maternal age as a driver of genome instability: mechanisms linking aneuploidy, mutagenesis and mitochondrial dysfunction.

Advanced maternal age is a well-established risk factor for adverse reproductive outcomes due to increased rates of aneuploidy. However, emerging evidence indicates that the genetic consequences of maternal aging extend well beyond chromosome mis-segregation. Aging oocytes acquire a broad spectrum of genetic abnormalities, including maternally derived nuclear de novo mutations (DNMs) and mitochondrial DNA mutations, together with epigenetic dysregulation of DNA methylation and post-translational modification levels. These changes reflect the unique biology of the female germline in which oocytes remain arrested in meiotic prophase I for decades. Age-related deterioration of key processes, such as erosion of cohesion complexes, altered meiotic recombination, and weakened spindle assembly checkpoint surveillance collectively destabilize meiotic chromosome architecture, directly driving chromosome mis-segregation. At the same time, accumulation of endogenous DNA damage and declining DNA damage and repair processes increase the chances of transmitting lesions that can be converted into sequence-level mutations during the earliest embryonic divisions, when genome maintenance relies exclusively on maternal factors. High-resolution sequencing studies further demonstrate that maternal aging is associated with increased DNMs burden in both nuclear and mitochondrial DNA. Together, these findings support a model in which maternal aging is a driver of genome-wide instability that links aneuploidy and mutagenesis through shared defects in meiotic surveillance, declining DNA repair efficiency, and mitochondrial function. This framework positions delayed childbearing as a multifaceted genetic risk factor that extend beyond aneuploidy to include mutations and other genomic alterations that can impact intergenerational genetic risk.

Aneuploidy

Nonviral transposon&#x2011;engineered stem cells characterization: dose&#x2011;dependency between vector copy number and transgene expression.

Genetically engineered stem cells hold substantial promises for advancing regenerative medicine, yet ensuring their genomic safety remains a critical challenge. A key safety concern is vector copy number (VCN), which defines the number of integrated transgene copies per genome. Although ddPCR is used to assess VCN in virally transduced cells, its application in transposon&#x2011;engineered systems is limited. In this study, we extended VCN determination to non&#x2011;viral, transposon&#x2011;engineered stem cells. In alignment with FDA recommendations, the primary objective was to establish a robust and quantitative framework for interim VCN determination at the time of lot release. Specifically, we demonstrate that reliable interim VCN estimates increase in a dose&#x2011;dependent manner with increasing plasmid input. In addition, strong linear correlations between VCN and both EGFP median fluorescence intensity (MFI) and gene&#x2011;of&#x2011;interest (GOI) protein expression validate the accuracy of this framework. Furthermore, comparison of two distinct GOIs revealed gene&#x2011;specific differences in expression efficiency. Together, these findings validate a standardized VCN determination workflow that quantitatively links plasmid dose, genomic integration, and functional transgene expression. This workflow provides a systematic characterization of engineered cells, offering comprehensive information to support downstream risk&#x2011;based analyses to ensure the genomic safety and stability of the final cell product.

Transgenes

The combination of morphogenic regulators BABY BOOM and GRF-GIF improves maize transformation efficiency and promotes leaf regeneration.

Transformation is an indispensable tool for plant genetics and functional genomics. Although stable transformation in maize is no longer a major obstacle, there remains a need for accessible and efficient methods for academic laboratories. Here, we present the GGB&#xa0;system, a rapid and efficient approach optimized for immature embryo transformation in B104 and other maize lines. This system combines two distinct morphogenetic regulators, the wheat GRF4-GIF1 chimera and the maize BABY BOOM (BBM) transcription factor (hence the name "GGB") with a modified QuickCorn protocol, enabling regeneration of transformed maize plantlets in c. 2 months with an efficiency 7-fold higher than when compared to either morphogenic factor used in isolation. Expression of both regulators did not significantly affect development, eliminating the need to excise them after regeneration. However, transmission of the transgenic GGB construct through pollen was significantly reduced, potentially aiding transgenic line containment. We show that the GGB system is adaptable for CRISPR-Cas9 editing and reporter line generation. Furthermore, stable GGB transformants exhibited high leaf regeneration capacity via somatic embryogenesis. RNA-seq time-course profiling of GGB leaf cultures identified additional factors that could promote regeneration and led to the discovery of asparagine and trehalose as additional media components that significantly enhanced leaf regeneration.

Zea mays

The circadian clock proteins PRR modulate root hair development via the RHD6/RSL module in Arabidopsis.

Root hairs, derived from trichoblasts, are critical for plant growth and environmental adaptation. Although environmental cues are known to influence root hair development, how endogenous timing systems such as the circadian clock integrate into the core transcriptional network governing root hair formation remains unclear. Here, we show that the circadian clock-associated protein PSEUDO-RESPONSE REGULATOR5 (PRR5) physically interacts with ROOT HAIR DEFECTIVE6 (RHD6) and RHD6 LIKE1 (RSL1), two basic helix-loop-helix transcription factors essential for root hair initiation. Genetic analyses suggest that PRR proteins contribute to root hair development under long-day conditions in Arabidopsis thaliana. Simultaneous disruption of PRR5, PRR7, and PRR9 results in defective root hairs, whereas PRR5 overexpression markedly increases root hair density and length. Transcriptomic and RT-qPCR analyses reveal that PRRs enhance the expression of RHD6, RSL1, and multiple downstream root hair-responsive genes, while modulating their temporal expression patterns. Furthermore, PRR5-mediated root hair promotion requires RHD6/RSL1, and PRR proteins enhance RHD6-dependent activation of the RSL4 promoter. PRRs also contribute to root hair development under phosphate-deficient and salt-stress conditions. Together, these findings establish a molecular framework in which PRR proteins regulate the RHD6/RSL network to coordinate root hair development and environmental responses.

Arabidopsis