Enhancing the production of L-proline in recombinant Escherichia coli BL21 by metabolic engineering.

L-proline is widely used in the fields of food, medicine and agriculture, and is also an important raw material for the synthesis of trans-4-hydroxy-L-proline. In this study, enhancing the production of L-proline by metabolic engineering was investigated. Three genes, proB, proA and proC, were introduced into Escherichia coli BL21 by molecular biology technology to increase the metabolic flow of L-proline from glucose. The genes putP and proP related to the proline transfer were knocked out by CRISPR/Cas9 gene editing technology to weaken the feedback inhibition of proB to increase the production of L-proline. The fermentation curves of the engineered strain at different glucose concentrations were determined, and a glucose concentration of 10 g/L was chosen to expand the batch culture to 1 L shake flask. Ultimately, through these efforts, the titer of L-proline reached 832.19 mg/L in intermittent glucose addition fermentation in a 1 L shake flask.

Bidirectional effects of the tryptophan metabolite indole-3-acetaldehyde on colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) has a high incidence and mortality. Recent studies have shown that indole derivatives involved in gut microbiota metabolism can impact the tumorigenesis, progression, and metastasis of CRC. AIM: To investigate the effect of indole-3-acetaldehyde (IAAD) on CRC. METHODS: The effect of IAAD was evaluated in a syngeneic mouse model of CRC and CRC cell lines (HCT116 and DLD-1). Cell proliferation was assessed by Ki-67 fluorescence staining and cytotoxicity tests. Cell apoptosis was analysed by flow cytometry after staining with Annexin V-fluorescein isothiocyanate and propidium iodide. Invasiveness was investigated using the transwell assay. Western blotting and real-time fluorescence quantitative polymerase chain reaction were performed to evaluate the expression of epithelial-mesenchymal transition related genes and aryl hydrocarbon receptor (AhR) downstream genes. The PharmMapper, SEA, and SWISS databases were used to screen for potential target proteins of IAAD, and the core proteins were identified through the String database. RESULTS: IAAD reduced tumorigenesis in a syngeneic mouse model. In CRC cell lines HCT116 and DLD1, IAAD exhibited cytotoxicity starting at 24 h of treatment, while it reduced Ki67 expression in the nucleus. The results of flow cytometry showed that IAAD induced apoptosis in HCT116 cells but had no effect on DLD1 cells, which may be related to the activation of AhR. IAAD can also increase the invasiveness and epithelial-mesenchymal transition of HCT116 and DLD1 cells. At low concentrations (< 12.5 µmol/L), IAAD only exhibited cytotoxic effects without promoting cell invasion. In addition, predictions based on online databases, protein-protein interaction analysis, and molecular docking showed that IAAD can bind to matrix metalloproteinase-9 (MMP9), angiotensin converting enzyme (ACE), poly(ADP-ribose) polymerase-1 (PARP1), matrix metalloproteinase-2 (MMP2), and myeloperoxidase (MPO). CONCLUSION: Indole-3-aldehyde can induce cell apoptosis and inhibit cell proliferation to prevent the occurrence of CRC; however, at high concentrations (≥ 25 µmol/L), it can also promote epithelial-mesenchymal transition and invasion in CRC cells. IAAD activates AhR and directly binds MMP9, ACE, PARP1, MMP2, and MPO, which partly reveals why it has a bidirectional effect.

Five-blade scratcher for treating severe rhinophyma: A retrospective study.

BACKGROUND: Rhinophyma, a late-stage subtype of rosacea, is characterized by excessive sebaceous glands and connective tissue proliferation. Patients may experience respiratory disturbances and psychological distress that significantly affect their quality of life when excessive nasal hyperplasia obstructs the external nasal valves. Surgery is the treatment of choice for rhinophyma. However, excessive bleeding, scarring, pigmentation, and high recurrence rates frequently characterize current surgical methods. AIM: To evaluate the clinical effectiveness and recurrence rates after treating severe rhinophyma with the five-blade scratcher. METHODS: This study retrospectively analyzed the clinical records of 28 patients with severe rhinophyma rosacea. The Global Flushing Severity Score (GFSS), Clinician Erythema Assessment (CEA), Rhinophyma Severity Index (RHISI), Glasgow Benefit Inventory (GBI), and satisfaction scores were used to assess the recovery of patients at 6 months and 5 years, with the recurrence rate calculated at 5 years postoperatively. In addition, the levels of pro-inflammatory factors (TNF-α, IL-1ß, and IL-6) in the serum of patients before and after surgery were detected by ELISA. RESULTS: The GFSS, CEA, and RHISI scores at 6 months and 5 years postoperatively were significantly lower than those preoperatively (P < 0.001 for both periods). Five-blade scratcher treatment greatly benefits patients as demonstrated by the GBI and patient satisfaction. A small number of patients (7/28, 25%) reported recurrence after surgical treatment for rhinophyma in our department that was not more serious than before treatment. The expression of pro-inflammatory factors (TNF-α, IL-1ß, and IL-6) in the patient's serum was significantly reduced after surgery of five-blade scratcher. CONCLUSION: The five-blade scratcher treatment demonstrates notable advantages, including simplicity, safety, efficacy, and cost-effectiveness, coupled with reduced bleeding, minimized scarring, lower recurrence rates, reduced the level of pro-inflammatory factors and improved patient satisfaction. Consequently, this therapeutic modality exhibits a viable option for individuals afflicted with severe rhinophyma.

Risk of severe dengue during secondary infection: A population-based cohort study in Taiwan.

BACKGROUND: Dengue poses a significant public health concern. Secondary dengue infections with different dengue virus (DENV) serotypes have been linked to an increased risk of severe dengue. This study aimed to assess the risk of severe dengue during secondary infection in Taiwan. METHODS: A retrospective cohort study was conducted using Taiwan's National Health Insurance Research Database to identify dengue cases with secondary dengue infection born after 1944 from 2014 to 2015. Ten matched patients with primary infection were selected as controls using propensity score matching for each secondary dengue infection case. The odds ratio (OR) for severe dengue in secondary versus primary infections was calculated using conditional logistic regression. RESULTS: This study included 357 cases with secondary dengue infection and 3570 matched controls. The risk of severe dengue was found to be 7.8% in individuals with secondary infection, compared to 3.8% in those with primary dengue infection. Secondary infection significantly increased the risk of severe dengue (OR 2.13, 95% CI: 1.40-3.25, P = 0.0004). Notably, a significant association between secondary infection and severe dengue was observed only when the interval between the first and secondary infection was greater than two years (OR 3.19, 95% CI 2.04-5.00, P < 0.0001). CONCLUSION: Secondary dengue infection significantly increases the risk of severe disease in Taiwan, particularly when the interval between infections is over two years. Healthcare professionals should maintain heightened vigilance for individuals with a history of previous dengue infection, particularly if their initial diagnosis was more than two years prior.

[Interaction Effects of Vegetation and Soil Factors on Microbial Communities in Alpine Steppe Under Degradation].

To clarify the regulating effect of vegetation and soil factors on microbial communities in the alpine steppe under degradation on the Qinghai-Xizang Plateau, the alpine steppe in the Sanjiangyuan area of the Qinghai-Tibet Plateau was chosen. We analyzed the differences in vegetation and soil factors in different stages of degradation （non-degradation, moderate degradation, and severe degradation） and detected the variations in microbial community characteristics in the alpine steppe under different degradation stages using high-throughput sequencing technology. Eventually, redundancy analysis （RDA） and multiple regression matrixes （MRM） based on the similarity or dissimilarity matrix were used to identify key environmental factors regulating microbial （bacterial and fungal） community changes under degradation. The results showed that the degradation of the alpine steppe significantly changed the community coverage, height, biomass, and important value of graminae； significantly reduced the contents of soil organic matter, total nitrogen, total phosphorus, and silt； and increased the soil bulk density and sand content. Degradation did not change the composition of bacteria and fungi, but their composition proportions changed and also resulted in the loss of microbial richness （Chao1 index and Richness index） but did not significantly change the microbial diversity （Shannon index）. With the occurrence of degradation, the vegetation characteristics, soil physicochemical properties, and microbial diversity showed a consistent change trend. Combined with the characteristics of the network topology changes （the number of nodes and clustering coefficient significantly decreased）, it was found that degradation of the alpine steppe led to the decline of interspecies interactions, decentralization of network, and homogenization of microorganisms, but the cooperation relations among the species were maintained （positive correlation connections accounted for more than 90% in all degradation stages）. Under the alpine steppe degradation, the vegetation-soil interaction had the greatest effect on soil bacterial community, whereas soil physicochemical properties had the greatest influence on soil fungal community. Specifically, vegetation community height, biomass, and soil bulk density were the mutual factors regulating soil microorganisms, whereas the vegetation Simpson index, important value of graminae, soil total phosphorus, total potassium, and silt content were the unique factors affecting the soil bacterial community, and soil pH and total nitrogen content were the particular factors affecting the soil fungal community.

Effect of Pretreatments on the Chemical, Bioactive and Physicochemical Properties of Cinnamomum camphora Seed Kernel Extracts.

Cinnamomum camphora seed kernels (CCSKs) are rich in phytochemicals, especially plant extracts. Phytochemicals play a vital role in therapy due to their strong antioxidant and anti-inflammatory activities. Extracts from CCSK can be obtained through multiple steps, including pretreatment, extraction and purification, and the purpose of pretreatment is to separate the oil from other substances in CCSKs. However, C. camphora seed kernel extracts (CKEs) were usually considered as by-products and discarded, and their potential bioactive values were underestimated. Additionally, little has been known about the effect of pretreatment on CKE. This study aimed to investigate the effects of pretreatment methods (including the solvent extraction method, cold pressing method, aqueous extraction method and sub-critical fluid extraction method) on the extraction yields, phytochemical profiles, volatile compounds and antioxidant capacities of different CKE samples. The results showed that the CKE samples were rich in phenolic compounds (15.28-20.29%) and alkaloids (24.44-27.41%). The extraction yield, bioactive substances content and in vitro antioxidant capacity of CKE pretreated by the sub-critical fluid extraction method (CKE-SCFE) were better than CKEs obtained by other methods. CKE pretreated by the solvent extraction method (CKE-SE) showed the best lipid emulsion protective capacity. Moreover, the volatile substances composition of the CKE samples was greatly influenced by the pretreatment method. The results provided a fundamental basis for evaluating the quality and nutritional value of CKE and increasing the economic value of by-products derived from CCSK.

Intensive Versus Moderate Statin-Based Therapies in Patients With Mild Ischemic Stroke: A Prospective Multicenter Cohort Study.

BACKGROUND: Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive statin-based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high-dose and moderate-dose statins for patients who had experienced mild ischemic stroke during the acute period. METHODS AND RESULTS: This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high-intensity and moderate-intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow-up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high-intensity statin and moderate-intensity statin groups (3 months: adjusted hazard ratio [HR], 1.12 [95% CI, 0.85-1.49]; P=0.424; 12 months: adjusted HR, 1.08 [95% CI, 0.86-1.34]; P=0.519). High-intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 [95% CI, 1.00-3.25]; P=0.048; 12 months: adjusted HR, 1.86 [95% CI, 1.10-3.16]; P=0.021). The results from the propensity score-matched analyses were consistent with those from the Cox proportional hazards analysis. CONCLUSIONS: Compared with moderate-intensity statin therapy, high-dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage. REGISTRATION: URL: www.chictr.org.cn/. Unique Identifier: ChiCTR1900025214.

Effects of different afforestation years on soil moisture and nutrient content in Maxian Mountain of the Loess Plateau.

In the area of "returning farmland to forest" on the Loess Plateau in China, it is difficult to cultivate artificially planted trees into forests. In the current study, abandoned cultivated land after 10 years of natural restoration served as controls (CK), while the treatments included afforestation periods of 2, 4, 6, 8, and 10 years. Soil samples were collected from various depths: 0-20, 20-40, 40-60, 60-80, to 80-100 cm. The findings revealed that with increasing years of artificial afforestation, soil pH gradually increased, and soil moisture content rose in the 0-20 cm layer while declining in deeper layers (20-100 cm) in the Maxian Mountain region of the Loess Plateau. Moreover, the total carbon, nitrogen, phosphorus, and potassium content initially increased and then decreased with the duration of artificial afforestation, reaching peak values after 8 years. Contents of organic matter, ammonium nitrogen, nitrate nitrogen, available phosphorus, and available potassium in the same soil layer increased with each year of afforestation. However, upon reaching 10 years of artificial afforestation, the effective nutrient content in the 60-80 and 80-100 cm soil layers exhibited a decrease. The values of Integrated Fertility Index (IFI) in different afforestation years were ranked as follows: 8 years > 6 years > 10 years > 4 years > 2 year, but all of them were significantly smaller than those of natural restoration plot CK (P < 0.05). Overall, soil fertility in the Maxian Mountain area of the Loess Plateau increases with each additional year of artificial afforestation. However, when the artificial afforestation period is 10 years, soil fertility decreases and marking a shift from enhancement to decline beyond this duration.

A Deep Dynamic Causal Learning Model to Study Changes in Dynamic Effective Connectivity during Brain Development.

OBJECTIVE: Brain dynamic effective connectivity (dEC), characterizes the information transmission patterns between brain regions that change over time, which provides insight into the biological mechanism underlying brain development. However, most existing methods predominantly capture fixed or temporally invariant EC, leaving dEC largely unexplored. METHODS: Herein we propose a deep dynamic causal learning model specifically designed to capture dEC. It includes a dynamic causal learner to detect time-varying causal relationships from spatio-temporal data, and a dynamic causal discriminator to validate these findings by comparing original and reconstructed data. RESULTS: Our model outperforms established baselines in the accuracy of identifying dynamic causalities when tested on the simulated data. When applied to the Philadelphia Neurodevelopmental Cohort, the model uncovers distinct patterns in dEC networks across different age groups. Specifically, the evolution process of brain dEC networks in young adults is more stable than in children, and significant differences in information transfer patterns exist between them. CONCLUSION: This study highlights the brain's developmental trajectory, where networks transition from undifferentiated to specialized structures with age, in accordance with the improvement of an individual's cognitive and information processing capability. SIGNIFICANCE: The proposed model consists of the identification and verification of dynamic causality, utilizing the spatio-temporal fusing information from fMRI. As a result, it can accurately detect dEC and characterize its evolution over age.

Non-contact elasticity contrast imaging using photon counting.

Significance: Tissues' biomechanical properties, such as elasticity, are related to tissue health. Optical coherence elastography produces images of tissues based on their elasticity, but its performance is constrained by the laser power used, working distance, and excitation methods. Aim: We develop a new method to reconstruct the elasticity contrast image over a long working distance, with only low-intensity illumination, and by non-contact acoustic wave excitation. Approach: We combine single-photon vibrometry and quantum parametric mode sorting (QPMS) to measure the oscillating backscattered signals at a single-photon level and derive the phantoms' relative elasticity. Results: We test our system on tissue-mimicking phantoms consisting of contrast sections with different concentrations and thus stiffness. Our results show that as the driving acoustic frequency is swept, the phantoms' vibrational responses are mapped onto the photon-counting histograms from which their mechanical properties-including elasticity-can be derived. Through lateral and longitudinal laser scanning at a fixed frequency, a contrast image based on samples' elasticity can be reliably reconstructed upon photon level signals. Conclusions: We demonstrated the reliability of QPMS-based elasticity contrast imaging of agar phantoms in a long working distance, low-intensity environment. This technique has the potential for in-depth images of real biological tissue and provides a new approach to elastography research and applications.

Several major herb pairs containing Coptidis rhizoma: a review of key traditional uses, constituents and compatibility effects.

Herb compatibility is the soul of traditional Chinese Medicine prescriptions. Coptidis rhizoma (CR) (Coptis chinensis Franch., Coptis deltoidea C.Y.Cheng et Hsiao, or Coptis teeta Wall.; family Ranunculaceae), is a well-known herb. The bitter and cold nature of CR can irritate the spleen and stomach, and certain ingredients in CR may trigger allergic reactions. Herb combinations can help alleviate the side effects caused by CR. Through data analysis and literature research, there are many herbs combined with CR have a high frequency, but only a few are currently used as formulae in clinical practice. The results showed that these six herb pairs are usually widely studied or used as prescriptions in the clinic. This paper describes the six herb pairs from the key traditional uses, changes in bioactive constituents, and compatibility effects, especially with Euodiae fructus (family Rutaceae), Scutellariae radix (family Lamiaceae), Magnoliae Officinalis cortex (family Magnoliaceae), Glycyrrhizae radix et rhizoma (family Fabaceae), Ginseng radix et rhizoma (family Araliaceae), and Aucklandiae radix (family Asteraceae), and found that herbs are more effective when used in combination. Therefore, it is feasible to establish some methods to study herb pairs comprehensively from different perspectives. This paper aims to provide the latest and most comprehensive information on the six herb pairs and summarize the pattern of CR compatibility effects. It aims to attract more attention, and further experimental studies will be conducted to investigate and evaluate the effects of herb pairs containing CR. These data can also provide valuable references for researchers and also provide more possibilities for future applications in clinical practice and new drug development.

Mechanism and treatment of secondary glaucoma after corneal transplantation: a review.

Corneal transplantation is a common treatment for corneal diseases. Secondary glaucoma after corneal transplantation is the second leading cause of failure of keratoplasty. This article reviews the mechanism and treatment of secondary glaucoma after corneal transplantation.

Serum Mac-2 binding protein glycosylation isomer dynamics in patients achieving sustained virologic response for hepatitis C virus.

BACKGROUND AND AIM: Understanding the dynamics of serum Mac-2 binding protein glycosylation isomer (M2BPGi) remains pivotal for hepatitis C virus (HCV) patients' post-sustained virologic response (SVR12) through direct-acting antivirals (DAAs). METHODS: We compared areas under receiver operating characteristic curves (AUROCs) of M2BPGi, FIB-4, and APRI and assess M2BPGi cutoff levels in predicting fibrosis stages of ≥F3 and F4 utilizing transient elastography in 638 patients. Variations in M2BPGi levels from pretreatment to SVR12 and their association with pretreatment alanine transaminase (ALT) levels and fibrosis stage were investigated. RESULTS: The AUROCs of M2BPGi were comparable to FIB-4 in predicting ≥F3 (0.914 vs 0.902, P = 0.48) and F4 (0.947 vs 0.915, P = 0.05) but were superior to APRI in predicting ≥F3 (0.914 vs 0.851, P = 0.001) and F4 (0.947 vs 0.857, P < 0.001). Using M2BPGi cutoff values of 2.83 and 3.98, fibrosis stages of ≥F3 and F4 were confirmed with a positive likelihood ratio ≥10. The median M2BPGi change was -0.55. Patients with ALT levels ≥5 times ULN or ≥F3 demonstrated more pronounced median decreases in M2BPGi level compared to those with ALT levels 2-5 times ULN and <2 times ULN (-0.97 vs -0.68 and -0.44; P < 0.001) or with < F3 (-1.52 vs -0.44; P < 0.001). CONCLUSIONS: Serum M2BPGi is a reliable marker for advanced hepatic fibrosis. Following viral clearance, there is a notable M2BPGi decrease, with the extent of reduction influenced by ALT levels and fibrosis stage.

A novel marine-derived anti-acute kidney injury agent targeting peroxiredoxin 1 and its nanodelivery strategy based on ADME optimization.

Insufficient therapeutic strategies for acute kidney injury (AKI) necessitate precision therapy targeting its pathogenesis. This study reveals the new mechanism of the marine-derived anti-AKI agent, piericidin glycoside S14, targeting peroxiredoxin 1 (PRDX1). By binding to Cys83 of PRDX1 and augmenting its peroxidase activity, S14 alleviates kidney injury efficiently in Prdx1-overexpression (Prdx1-OE) mice. Besides, S14 also increases PRDX1 nuclear translocation and directly activates the Nrf2/HO-1/NQO1 pathway to inhibit ROS production. Due to the limited druggability of S14 with low bioavailability (2.6%) and poor renal distribution, a pH-sensitive kidney-targeting dodecanamine-chitosan nanoparticle system is constructed to load S14 for precise treatment of AKI. l-Serine conjugation to chitosan imparts specificity to kidney injury molecule-1 (Kim-1)-overexpressed cells. The developed S14-nanodrug exhibits higher therapeutic efficiency by improving the in vivo behavior of S14 significantly. By encapsulation with micelles, the AUC0‒t , half-life time, and renal distribution of S14 increase 2.5-, 1.8-, and 3.1-fold, respectively. The main factors contributing to the improved druggability of S14 nanodrugs include the lower metabolic elimination rate and UDP-glycosyltransferase (UGT)-mediated biotransformation. In summary, this study identifies a new therapeutic target for the marine-derived anti-AKI agent while enhancing its ADME properties and druggability through nanotechnology, thereby driving advancements in marine drug development for AKI.

Using large language model (LLM) to identify high-burden informal caregivers in long-term care.

BACKGROUND: The rising global elderly population increases the demand for caregiving, yet traditional methods may not fully assess the challenges faced by vital informal caregivers. OBJECTIVE: To investigate the efficacy of Large Language Model (LLM) in detecting overburdened informal caregivers, benchmarking against rule-based and machine learning methods. METHODS: 1,791 eligible informal caregivers from Southern Taiwan and utilized their textual case summary reports for the LLM. We also employed structured questionnaire results for machine learning models. Furthermore, we leveraged the visualization of the LLM's attention mechanisms to enhance our understanding of the model's interpretative capabilities. RESULTS: The LLM achieved an Area Under the Receiver Operating Characteristic (AUROC) curve of 0.84 and an Area Under the Precision-Recall Curve (AUPRC) of 0.70, marking an 8% and 14% improvement over traditional methods. The visualization of the attention mechanism accurately reflected the evaluations of human experts, concentrating on descriptions of high-burden descriptions and the relationships between caregivers and recipients. CONCLUSION: This research demonstrates the notable capability of LLM to accurately identify high-burden caregivers in Long-term Care (LTC) settings. Compared to traditional approaches, LLM offers an opportunity for the future of LTC research and policymaking.

Estimating Octanol-Water Partition Coefficients of Novel Brominated Flame Retardants by Reversed-Phase High-Performance Liquid Chromatography and Computational Models.

Legacy brominated flame retardants, including polybrominated diphenyl ethers (PBDEs), have been classified as persistent organic pollutants and replaced with novel brominated flame retardants (NBFRs). The octanol-water partition coefficients (log KOW) of NBFRs have been computationally estimated, but the log KOW values provided by these methods can differ by 1 to 3 orders of magnitude. Given the importance of this parameter in fate and toxicity models, we indirectly measured the log KOW values of eight NBFRs by their capacity factor (k') on a reversed-phase high-performance liquid chromatography (HPLC) C18 column by isocratic elution and compared these measured values with those estimated by nine computational models. Log KOW values were obtained for the NBFRs 1,2-bis(2,4,6-tribromophenoxy) ethane, pentabromobenzene, pentabromoethylbenzene, pentabromotoluene, 2-ethylhexyl 2,3,4,5-tetrabromobenzoate, allyl 2,4,6-tribromophenylether, 2,3-dibromopropyl-2,4,6-tribromophenyl ether, and bis(2-ethylhexyl) tetrabromophthalate. A training set of phthalates, polychlorinated biphenyls, PBDEs, and halogenated benzenes were chosen to obtain the log k'-log KOW calibration for the NBFRs. The computational models KowWIN, XLogP3, EAS-E Suite, COSMOtherm, DirectML, and Abraham polyparameter linear free energy relationships all predicted the log KOW values of the calibration compounds to within 1 order of magnitude without significant bias. The median of these models predicted log KOW values for the calibration compounds that were close to those known in the literature with root mean square error (RMSE) = 0.224 and for the NBFRs that were close to those measured by HPLC (RMSE = 0.334). Environ Toxicol Chem 2024;00:1-10. © 2024 SETAC.

Effects of endogenous testosterone on oscillatory activity during verbal working memory in youth.

Testosterone levels sharply rise during the transition from childhood to adolescence and these changes are known to be associated with changes in human brain structure. During this same developmental window, there are also robust changes in the neural oscillatory dynamics serving verbal working memory processing. Surprisingly, whereas many studies have investigated the effects of chronological age on the neural oscillations supporting verbal working memory, none have probed the impact of endogenous testosterone levels during this developmental period. Using a sample of 89 youth aged 6-14 years-old, we collected salivary testosterone samples and recorded magnetoencephalography during a modified Sternberg verbal working memory task. Significant oscillatory responses were identified and imaged using a beamforming approach and the resulting maps were subjected to whole-brain ANCOVAs examining the effects of testosterone and sex, controlling for age, during verbal working memory encoding and maintenance. Our primary results indicated robust testosterone-related effects in theta (4-7 Hz) and alpha (8-14 Hz) oscillatory activity, controlling for age. During encoding, females exhibited weaker theta oscillations than males in right cerebellar cortices and stronger alpha oscillations in left temporal cortices. During maintenance, youth with greater testosterone exhibited weaker alpha oscillations in right parahippocampal and cerebellar cortices, as well as regions across the left-lateralized language network. These results extend the existing literature on the development of verbal working memory processing by showing region and sex-specific effects of testosterone, and are the first results to link endogenous testosterone levels to the neural oscillatory activity serving verbal working memory, above and beyond the effects of chronological age.

Psychosocial Characteristics by Pain Presence and Limitations Among Older Adults.

PURPOSE: To compare psychosocial outcomes of older adults according to pain experience. METHOD: Using cross-sectional 2021 data from the National Health and Aging Trends Study, we examined psychosocial characteristics in older adults (N = 3,376) divided into three groups: no pain, pain without activity limitations, and activity-limiting pain. RESULTS: In multiple regression models, older adults with activity-limiting pain compared to those without pain had significantly higher depression, anxiety, and fear of falling, as well as reduced positive affect, self-realization, self-efficacy, resilience, and social participation. Older adults with non-activity-limiting pain had significantly higher social participation than those without pain, but no differences in self-realization, self-efficacy, or resilience. CONCLUSION: Pain is strongly associated with all psychosocial outcomes, especially in older adults with activity-limiting pain. Future research should examine the impact of self-realization, self-efficacy, resilience, and social participation on activity limitations. [Journal of Gerontological Nursing, 50(7), 27-34.].

Risks of anxiety disorders, depressive disorders, and sleep disorders in patients with dengue fever: A nationwide, population-based cohort study.

BACKGROUND: Dengue virus (DENV) infection, a common mosquito-borne disease, has been linked to several mental disorders like depression and anxiety. However, the temporal risk of these disorders after DENV infection is not well studied. METHODS: This population-based cohort study encompassed 45,334 recently lab-confirmed dengue patients in Taiwan spanning 2002 to 2015, matched at a 1:5 ratio with non-dengue individuals based on age, gender, and residence (n = 226,670). Employing subdistribution hazard regression analysis, we assessed the immediate (<3 months), intermediate (3-12 months), and prolonged (>12 months) risks of anxiety disorders, depressive disorders, and sleep disorders post DENV infection. Corrections for multiple comparisons were carried out using the Benjamini-Hochberg procedure. RESULTS: A significant increase in depressive disorder risk across all timeframes post-infection was observed (<3 months [aSHR 1.90, 95% CI 1.20-2.99], 3-12 months [aSHR 1.68, 95% CI 1.32-2.14], and >12 months [aSHR 1.14, 95% CI 1.03-1.25]). Sleep disorder risk was higher only during 3-12 months (aSHR 1.55, 95% CI 1.18-2.04). No elevated anxiety disorder risk was found. Subgroup analysis of hospitalized dengue patients showed increased risk of anxiety disorders within 3 months (aSHR 2.14, 95% CI 1.19-3.85) and persistent risk of depressive disorders across all periods. Hospitalized dengue patients also had elevated sleep disorder risk within the first year. CONCLUSION: Dengue patients exhibited significantly elevated risks of depressive disorders in both the short and long term. However, dengue's impact on sleep disorders and anxiety seems to be short-lived. Further research is essential to elucidate the underlying mechanisms.