Association Between Greater Social Vulnerability and Delayed Glaucoma Surgery.

PURPOSE: Timing of surgical intervention in glaucoma is crucial to preserving sight. While ocular characteristics that increase surgical risk are known, the impact of neighborhood-level social risk factors such as the Social Vulnerability Index (SVI) and Area Deprivation Index (ADI) on time to glaucoma surgery is unknown. The objective of this study was to evaluate the association between SVI or ADI scores and the timing of glaucoma surgical intervention. DESIGN: Retrospective cohort study. METHODS: Adult subjects with open-angle glaucoma were identified from the Bascom Palmer Glaucoma Repository using International Classification of Disease-10 codes. Subject demographics, ocular characteristics, and standard automated perimetry (SAP) data were extracted. Geocoded data were obtained using subject residences and American Community Survey data. Univariable and multivariable time-to-event survival analyses using accelerated failure time (AFT) models were completed to evaluate whether geocoded SVI and ADI scores accelerated or delayed time to glaucoma surgery from initial glaucoma diagnosis in the electronic health record. RESULTS: A total of 10,553 eyes from 6,934 subjects were evaluated, of which 637 eyes (6.0%) from 568 subjects (8.2%) underwent glaucoma surgery. Mean age was 68.3±13.5 years, with 57.9% female, 21.5% Black, and 34.5% Hispanic subjects. Mean follow-up time was 5.0±2.1 years, with time to surgery of 3.2±1.9 years. Multivariable AFT models demonstrated that higher mean intraocular pressure (time ratio (TR) 0.27 per 5 mmHg higher; 95% CI: 0.23-0.31, p<0.001), faster SAP rate of progression (TR 0.74 per 0.5 dB/year faster; 95% CI: 0.69-0.78, p<0.001), moderate (TR 0.69; 95% CI: 0.56-0.85, p<0.001) or severe baseline severity (TR 0.39; 95% CI: 0.32-0.47, p<0.001), and thinner central corneal thickness (TR 0.85 per 50µm thinner; 95% CI: 0.77-0.95, p=0.003) all accelerated time to surgery. In contrast, overall SVI delayed surgery (TR 1.11 per 25% increase; 95% CI: 1.03-1.20, p=0.006). Specifically, SVI Themes 1 (TR 1.08; 95% CI: 1.01-1.17, p=0.037) and 4 (TR 1.11; 95% CI: 1.03-1.19, p=0.006) were significant. Patients from the most deprived neighborhoods (highest national ADI quartile) had a 68% increase in time to surgery compared to the least deprived quartile (TR 1.68; 95% CI: 1.20-2.36, p=0.002). CONCLUSIONS: Residence in areas with higher SVI or ADI scores was associated with delayed glaucoma surgery after controlling for demographic and ocular parameters. Awareness of such disparities can guide initiatives aimed at achieving parity in health outcomes.

Prolonged unemployment is associated with control loss and personal as well as social disengagement.

OBJECTIVE AND BACKGROUND: The need for control is a fundamental human motivation, that when deprived can lead to broad and substantial changes in human behavior. We aimed to assess the consequences of control deprivation in a real-life situation that poses a severe threat to personal control: a prolonged unemployment. METHOD: Using a sample N = 1055 of unemployed (n = 748) versus working (n = 307) individuals, we examined predictions derived from two models of reactions to control deprivation: control-regaining and disengagement/withdrawal. RESULTS AND CONCLUSIONS: We found that length unemployment is correlated with a psychological state strongly interfering with psychological as well as social functioning. While control-regaining models of responding to lack of control have received virtually no support from our findings, our results provide evidence that long-term unemployed individuals are more disengaged than working individuals. They are more apathetic, less likely to engage in control-regaining efforts and in active forms of construing one's own future.

Impact of chronic sleep deprivation on male reproductive health: Insights from testicular and epididymal responses in mice.

BACKGROUND: Sleep deprivation (SD) can cause damage to the male reproductive system. However, the duration required for such damage and the specific sequence and severity of damage to the testis and epididymis remain unclear. OBJECTIVE: To investigate the effects of different durations of SD on different parts of the testis and epididymis caput, corpus, and cauda. METHODS: Adult ICR mice were randomly assigned to five groups: the SD group (SD for 18 h/day for 1, 2, 3, or 4 weeks), the SD + Vit E group (supplemented with Vit E 50 mg/kg/d during 4 weeks of SD, the SD+NS group (saline supplementation during 4 weeks of SD), the SD + RS group (5 weeks of recovery sleep after 4 weeks of SD), and a normal sleep control (Ctrl) group. Following the interventions, sperm parameters, testicular and epididymal histopathology, inflammatory response, and oxidative stress markers were compared between the groups. RESULTS: Compared to the Ctrl group, the SD group showed a decrease in sperm motility and concentration from SD 2 W and SD 3 W, respectively. Decreases in sperm concentration and motility were more pronounced in the cauda compared to the caput and corpus. Pathological damage was less severe in the epididymis caput than in the corpus and cauda. After 4 weeks of SD, inflammation and oxidative stress increased in both testes and epididymis. Both sleep recovery and vitamin E supplementation showed significant improvements, though they did not fully reach the level of the Ctrl group. CONCLUSION: Chronic SD for more than 2 weeks causes varying degrees of damage to the testis, epididymis caput, corpus, and cauda in male mice. This damage is not fully reversible after 5 weeks of sleep recovery and antioxidant stress treatment. These findings help us to identify and prevent SD damage to the male reproduction at an early stage.

Neuroelectrophysiological alteration associated with cognitive flexibility after 24 h sleep deprivation in adolescents.

The cognitive neural mechanisms by which sleep deprivation affects cognitive flexibility are poorly understood. Therefore, the study investigated the neuroelectrophysiological basis of the effect of 24 h sleep deprivation on cognitive flexibility in adolescents. 72 participants (36 females, mean age ± SD=20.46 ± 2.385 years old) participated in the study and were randomly assigned to the sleep deprivation group and control group. They were instructed to complete a task switch paradigm, during which participants' behavioral and electroencephalographic data were recorded. Behaviorally, there were significant between-group differences in accuracy. The results of event-related potential showed that the P2, N2 and P3 components had significant group effects or interaction effects. At the time-frequency level, there were statistically significant differences between the delta and theta bands. These results suggested that 24 h sleep deprivation affected problem-solving effectiveness rather than efficiency, mainly because it systematically impaired cognitive processing associated with cognitive flexibility.

3,3',4,5'-Tetramethoxy-trans-stilbene and 3,4',5-trimethoxy-trans-stilbene prevent oxygen-glucose deprivation-induced injury in brain endothelial cell.

Blood-brain barrier (BBB) disruption is a major pathophysiological event of ischemic stroke. Brain microvascular endothelial cells are critical to maintain homeostasis between central nervous system and periphery. Resveratrol protects against ischemic stroke. 3,3',4,5'-tetramethoxy-trans-stilbene (3,3',4,5'-TMS) and 3,4',5-trimethoxy-trans-stilbene (3,4',5-TMS) are resveratrol derivatives with addition of methoxy groups, showing better pharmacokinetic performance. We aimed to explore their protective effects and underlying mechanisms. Oxygen-glucose deprivation (OGD) model was applied in bEnd.3 cell line, mouse brain microvascular endothelium to mimic ischemia. The cells were pre-treated with 3,3',4,5'-TMS or 3,4',5-TMS (1 and 5 µM, 24 h) and then subjected to 2-h OGD injury. Cell viability, levels of proinflammatory cytokines and reactive oxygen species (ROS), and protein expressions were measured by molecular assays and fluorescence staining. OGD injury triggered cell death, inflammatory responses, ROS production and nuclear factor-kappa B (NF-κB) signalling pathway. These impairments were remarkably attenuated by the two stilbenes, 3,3',4,5'-TMS and 3,4',5-TMS. They also alleviated endothelial barrier injuries through upregulating the expression of tight junction proteins. Moreover, 3,3',4,5'-TMS and 3,4',5-TMS activated 5' adenosine monophosphate-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS). Overall, 3,3',4,5'-TMS and 3,4',5-TMS exert protective effects against OGD damage through suppressing cell death, inflammatory responses, oxidative stress, as well as BBB disruption on bEnd.3 cells.

Modulating the Pronociceptive Effect of Sleep Deprivation: A Possible Role for Cholinergic Neurons in the Medial Habenula.

Sleep deprivation has been shown to exacerbate pain sensitivity and may contribute to the onset of chronic pain, yet the precise neural mechanisms underlying this association remain elusive. In our study, we explored the contribution of cholinergic neurons within the medial habenula (MHb) to hyperalgesia induced by sleep deprivation in rats. Our findings indicate that the activity of MHb cholinergic neurons diminishes during sleep deprivation and that chemogenetic stimulation of these neurons can mitigate the results. Interestingly, we did not find a direct response of MHb cholinergic neurons to pain stimulation. Further investigation identified the interpeduncular nucleus (IPN) and the paraventricular nucleus of the thalamus (PVT) as key players in the pro-nociceptive effect of sleep deprivation. Stimulating the pathways connecting the MHb to the IPN and PVT alleviated the hyperalgesia. These results underscore the important role of MHb cholinergic neurons in modulating pain sensitivity linked to sleep deprivation, highlighting potential neural targets for mitigating sleep deprivation-induced hyperalgesia.

Subclinical hypomanic experiences in young adults after sleep deprivation are independent of depressive disorders, chronotype or 5-HTTLPR polymorphism.

INTRODUCTION: The acute antidepressant effect of sleep deprivation (SD) in patients with depressive disorders has been studied for more than 60 years. However, hypomanic mood swings after partial or total SD have also been described in people without diagnosed mental disorders. Studying this phenomenon in the general population may yield insights about the mechanisms of therapeutic SD, mania and bipolar disorders. METHODS: A cross-sectional sample of young adults was recruited and classified into those who described having regularly occurring subclinical hypomanic experiences (ROHE) after SD and those who did not. History of psychiatric and physical illness, with screening for depression and mania, as well as alcohol or drug consumption, family history of depressive disorders or suicide, 5-HTTLPR polymorphism, and MEQ-SA chronotype were collected. RESULTS: A total of 251 participants were included; 39.0% indicated regularly having subclinical hypomanic experiences after SD. These experiences were not associated with depressive or mania screening, history of psychiatric illness, family history, 5-HTTLPR polymorphism, or MEQ-SA chronotype. CONCLUSIONS: ROHE after non-therapeutic SD seem to be a relatively common phenomenon in young adults, independent of depressive mood state. Our results suggest that therapeutic SD may depend on a physiological phenomenon of subclinical affective disturbance after SD that affects a part of the general population, independent of psychiatric diagnosis. Further studies could elucidate associated factors and contribute to our understanding of (hypo-)manic mood states.

The relationship between neighborhood economic deprivation and community-acquired pneumonia related admissions in Maryland.

Introduction: Community-acquired pneumonia (CAP) is a major health concern in the United States (US), with its incidence, severity, and outcomes influenced by social determinants of health, including socioeconomic status. The impact of neighborhood socioeconomic status, as measured by the Distressed Communities Index (DCI), on CAP-related admissions remains understudied in the literature. Objective: To determine the independent association between DCI and CAP-related admissions in Maryland. Methods: We conducted a retrospective study using the Maryland State Inpatient Database (SID) to collate data on CAP-related admissions from January 2018 to December 2020. The study included adults aged 18-85 years. We explored the independent association between community-level economic deprivation based on DCI quintiles and CAP-related admissions, adjusting for significant covariates. Results: In the study period, 61,467 cases of CAP-related admissions were identified. The patients were predominantly White (49.7%) and female (52.4%), with 48.6% being over 65 years old. A substantive association was found between the DCI and CAP-related admissions. Compared to prosperous neighborhoods, patients living in economically deprived communities had 43% increased odds of CAP-related admissions. Conclusion: Residents of the poorest neighborhoods in Maryland have the highest risk of CAP-related admissions, emphasizing the need to develop effective public health strategies beneficial to the at-risk patient population.

Human serum proteomics reveals a molecular signature after one night of sleep deprivation.

Study Objectives: Sleep deprivation is highly prevalent and caused by conditions such as night shift work or illnesses like obstructive sleep apnea. Compromised sleep affects cardiovascular-, immune-, and neuronal systems. Recently, we published human serum proteome changes after a simulated night shift. This pilot proteomic study aimed to further explore changes in human blood serum after 6 hours of sleep deprivation at night. Methods: Human blood serum samples from eight self-declared healthy females were analyzed using Orbitrap Eclipse mass spectrometry (MS-MS) and high-pressure liquid chromatography. We used a within-participant design, in which the samples were taken after 6 hours of sleep at night and after 6 hours of sleep deprivation the following night. Systems biological databases and bioinformatic software were used to analyze the data and comparative analysis were done with other published sleep-related proteomic datasets. Results: Out of 494 proteins, 66 were found to be differentially expressed proteins (DEPs) after 6 hours of sleep deprivation. Functional enrichment analysis revealed the associations of these DEPs with several biological functions related to the altered regulation of cellular processes such as platelet degranulation and blood coagulation, as well as associations with different curated gene sets. Conclusions: This study presents serum proteomic changes after 6 hours of sleep deprivation, supports previous findings showing that short sleep deprivation affects several biological processes, and reveals a molecular signature of proteins related to pathological conditions such as altered coagulation and platelet function, impaired lipid and immune function, and cell proliferation. Data are available via ProteomeXchange with identifier PXD045729. This paper is part of the Genetic and other molecular underpinnings of sleep, sleep disorders, and circadian rhythms including translational approaches Collection.

Cyclooxygenase-2 (COX-2)-dependent mechanisms mediate sleep responses to microbial and thermal stimuli.

Prostaglandins (PGs) play a crucial role in sleep regulation, yet the broader physiological context that leads to the activation of the prostaglandin-mediated sleep-promoting system remains elusive. In this study, we explored sleep-inducing mechanisms potentially involving PGs, including microbial, immune and thermal stimuli as well as homeostatic sleep responses induced by short-term sleep deprivation using cyclooxygenase-2 knockout (COX-2 KO) mice and their wild-type littermates (WT). Systemic administration of 0.4 µg lipopolysaccharide (LPS) induced increased non-rapid-eye movement sleep (NREMS) and fever in WT animals, these effects were completely absent in COX-2 KO mice. This finding underscores the essential role of COX-2-dependent prostaglandins in mediating sleep and febrile responses to LPS. In contrast, the sleep and fever responses induced by the pro-inflammatory cytokine tumor necrosis factor α, a proinflammatory cytokine which activates COX-2, were preserved in COX-2 KO animals, indicating that these effects are independent of COX-2-related signaling. Additionally, we examined the impact of ambient temperature on sleep. The sleep-promoting effects of moderate warm ambient temperature were suppressed in COX-2 KO animals, resulting in significantly reduced NREMS at ambient temperatures of 30 °C and 35 °C compared to WT mice. However, rapid-eye-movement sleep responses to moderately cold or warm temperatures did not differ between the two genotypes. Furthermore, 6 h of sleep deprivation induced rebound increases in sleep with no significant differences observed between COX-2 KO and WT mice. This suggests that while COX-2-derived prostaglandins are crucial for the somnogenic effects of increased ambient temperature, the homeostatic responses to sleep loss are COX-2-independent. Overall, the results highlight the critical role of COX-2-derived prostaglandins as mediators of the sleep-wake and thermoregulatory responses to various physiological challenges, including microbial, immune, and thermal stimuli. These findings emphasize the interconnected regulation of body temperature and sleep, with peripheral mechanisms emerging as key players in these integrative processes.

Androgen deprivation increases frontopolar cortical thickness in prostate cancer patients: an effect of early neurodegeneration?

Androgen deprivation therapy (ADT) has been associated with adverse effects on the brain. ADT leads to altered testosterone levels that may affect brain morphology as well as cognition. Considering the reliability of cortical thickness (CT) as a marker of cognitive and brain changes, e.g., in Alzheimer's disease, we assessed the impacts of ADT on CT and working memory. Thirty men with non-metastatic prostate cancer receiving ADT and 32 patients not receiving ADT (controls or CON), matched in age and years of education, participated in N-back task and quality-of-life (QoL) assessments as well as brain imaging at baseline and prospectively at 6 months. Imaging data were processed with published routines to estimate CT and the results of a group by time flexible factorial analysis were evaluated at a corrected threshold. ADT and CON did not differ in N-back performance or QoL across time points. Relative to CON, patients receiving ADT showed significantly higher frontopolar cortex (FPC) CT at 6-month follow-up vs. baseline. Follow-up vs. baseline FPC CT change correlated negatively with changes in 2-back correct response rate and in testosterone levels across all participants. In mediation analysis, FPC CT change mediated the association between testosterone level change and 2-back accuracy rate change. Increases in FPC CT following 6 months of ADT may reflect early neurodegenerative changes in response to androgen deprivation. While no significant impact on working memory or QoL was observed over 6 months, further research of longer duration of treatment is warranted to unravel the full spectrum of cognitive and neural consequences of ADT in prostate cancer patients.

Coffee and sleep: Benefits and risks.

Consuming coffee, a widely enjoyed beverage with caffeine, can impact the central nervous system and disturb sleep if taken too close to bedtime. Caffeine impacts sleep by slowing the onset, blocking adenosine receptors, lowering deep sleep levels, disrupting sleep patterns, and lessening rapid eye movement sleep. Although coffee can help with alertness in the morning, it may disturb sleep in the evening, particularly for individuals who are sensitive to caffeine. To enhance the quality of sleep, reduce the consumption of caffeine in the afternoon and evening, refrain from drinking caffeine before going to bed, and choose decaffeinated drinks instead. Variables such as personal reactions, ability to handle caffeine, and engagement with other compounds also influence the impact of coffee on sleep. Keeping track of how much caffeine you consume and your sleeping habits can assist in recognizing any disturbances and making needed changes. Furthermore, taking into account variables such as metabolism, age, and the timing of coffee consumption can assist in lessening the effects of coffee on sleep. In general, paying attention to the amount of caffeine consumed from different sources and consuming it at the right times can assist in preserving healthy sleep patterns even while enjoying coffee.

Unveiling Hidden Disparities: Evaluating US Multiple Listing Practices in Lung Transplantation.

BACKGROUND: Multiple listing (ML) is a practice utilized to increase the potential for transplant but is controversial due to concerns that it disproportionately benefits patients with greater access to healthcare resources. RESEARCH QUESTION: Is there disparity in ML practices based on social deprivation in the United States and does ML lead to quicker time to transplant? STUDY DESIGN AND METHODS: A retrospective cohort study of adult (>18 years old) lung transplant candidates listed for transplant (2005-2018) was conducted. Exclusion criteria included heart only or heart and lung transplant and patients relisted during the observation period. Data were obtained from the UNOS Standard Transplant Analysis and Research File. The first exposure of interest was social deprivation index (SDI) with a primary outcome of ML status, to assess disparities between ML and SL participants. The second exposure of interest was ML status with a primary outcome of time to transplant, to assess whether implementation of ML leads to quicker time to transplant. RESULTS: 35,890 subjects were included in the final analysis, of whom 791 (2.2%) were ML and 35,099 (97.8%) were SL. ML participants had lower median level of social deprivation (5 units, more often female (60.0% vs 42.3%), and had lower median LAS (35.3 vs 37.3). ML patients were more likely to be transplanted compared to SL patients (OR=1.42, 95%CI [1.17-1.73]), but there was a significantly quicker time to transplant only for whom ML was early (within 6 months of initial listing) (sHR=1.17, 95%CI [1.04-1.32]). INTERPRETATION: ML is an uncommon practice with disparities existing between ML and SL patients on the basis of several factors including social deprivation. ML patients are more likely to be transplanted, but only if they ML early in their transplant candidacy. With changing allocation guidelines, it is yet to be seen how ML will change with the implementation of continuous distribution.

Mechanisms, Consequences and Role of Interventions for Sleep Deprivation: Focus on Mild Cognitive Impairment and Alzheimer's Disease in Elderly.

Sleep is established as an essential physiological need that impacts physical, emotional, and cognitive functions profoundly. Physiologically, inadequate sleep weakens immune function, heightening susceptibility to infections and chronic illnesses such as obesity, diabetes, and cardiovascular diseases. Hormonal disruptions due to sleep loss further exacerbate metabolic dysregulation, contributing to weight gain and other health complications. Emotionally, sleep deprivation leads to mood disturbances, including increased irritability, heightened stress responses, and a greater likelihood of mood disorders like depression and anxiety. These effects are compounded by cognitive impairments such as reduced alertness, impaired memory consolidation, and compromised decision-making abilities, akin to the impairments caused by alcohol consumption. Motor skills and coordination also suffer, elevating the risk of accidents, particularly in high-stress environments. For older adults, sleep quality is closely linked to cognitive function and overall longevity. Optimal sleep patterns are associated with slower brain aging and improved health outcomes. However, sleep disorders exacerbate existing conditions such as epilepsy and asthma, necessitating interventions like cognitive behavioral therapy (CBT) and medications such as melatonin to mitigate their impact. Education emerges as a crucial tool in promoting healthier sleep habits across all age groups. Addressing misconceptions about sleep and integrating sleep health into public health policies are essential steps toward improving overall well-being. Additionally, lifestyle factors such as diet and physical activity play significant roles in regulating sleep patterns, further emphasizing the interconnectedness of sleep with broader health outcomes. In summary, the articles underscore the intricate mechanisms through which sleep influences physiological functions and advocate for comprehensive approaches to enhance sleep hygiene and mitigate the adverse effects of sleep deprivation on human health.

Effect of offline bullying on online unethical behavior among college students: the mediating roles of relative deprivation and anger rumination.

This research delves into the correlation between offline bullying and online unethical behavior among college students; and examines the potential mediating influences of anger rumination and perceived relative deprivation. The findings suggest that anger rumination, perceived relative deprivation, offline bullying, and online unethical behavior exhibit significant positive correlations with each other. Offline bullying is a strong predictor of online unethical behavior among college students, with the dual mediating effects of perceived relative deprivation and anger rumination on the relationship between offline bullying and online unethical behavior. This suggests that offline bullying directly influences college students' online unethical behavior and also influences it indirectly through anger rumination and perceived relative deprivation.

Impact of definitive radiotherapy on metabolic response measured with 68Ga-PSMA-PET/CT in patients with intermediate-risk prostate cancer.

PURPOSE: To assess the early metabolic response of the primary tumor using Gallium-68 (68Ga)-labeled-prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-PET/CT), as well as the relationship between PSMA change in the primary tumor and PSA response after definitive radiotherapy (RT), either alone or in combination with androgen deprivation therapy (ADT) in intermediate risk prostate cancer (IR-PCa) patients. METHODS: The clinical data of 71 IR-PCa patients treated with RT alone (36 patients, 50.7%) or RT and ADT (35 patients, 49.3%) were retrospectively analyzed. The difference between pre- and Posttreatment primary tumor PSMA expression and serum PSA values measured 4 months after completion of treatment were compared between treatment arms. Correlation between primary tumor metabolic response and serum PSA changes was analyzed. RESULTS: The median duration between pre- and Posttreatment 68Ga-PSMA-PET/CT for the entire patient population was 6.9 months (range, 5.6-8.4 months), and it was similar in both treatment arms. A decrease in primary tumor maximum standardized uptake value (SUVmax) was seen in 66 patients (93.0%), with a median value of 61.2%, which is significantly lower in patients undergoing RT alone than those undergoing RT and ADT (45.1 ± 30.6% vs. 59.1 ± 24.7%; p = 0.004). The complete metabolic response rate was significantly higher in patients undergoing RT and ADT than those treated with RT alone (40% vs. 0%; p < 0.001). Although moderate and positive correlation between pretreatment SUVmax and oosttreatment SUVmax was observed, there was no significant correlation between SUV change and PSA change. For patients treated with RT and ADT, posttreatment SUVmax was significantly lower and SUV change was significantly higher in patients with PSA nadir than in those without. CONCLUSIONS: Our preliminary results show that RT, with or without ADT, significantly reduces primary tumor SUVmax and serum PSA levels. Nonetheless, our findings indicate that early treatment response using 68Ga-PSMA-PET/CT is not feasible for those treated with RT alone, and it may only be useful in better distinguishing patients with and without PSA nadir for those who received both RT and ADT.

Relationship between persistence with topical antiglaucomatous prescription and patient socioeconomic status at a tertiary university hospital in Jerez de la Frontera (Spain).

INTRODUCTION: To study the relationship between socioeconomic status and persistence with topical antiglaucomatous medication. METHODS: A retrospective epidemiological observational cohort study was conducted with a sample of 1563 patients. The main dependent variable was persistence (medication possession ratio), the independent variable was socioeconomic status (deprivation index). Additional independent variables were used for multivariate analysis: individual health card index, sex, age, pharmacological group, number of eye drops, preservatives, diagnosis and concurrent medications. Bivariate statistical analysis was obtained using non-parametric tests. Logistic regression was used for multivariate analysis. The level of statistical significance was set at p < 0.05. RESULTS: We obtained data showing greater persistence in the groups with a higher socioeconomic level (deprivation index 1 and 2), with medication possession ratio values of 79.97 and 75.30, respectively) as opposed to the groups at lower socioeconomic levels (deprivation index 4 and 5, with medication possession ratio values of 73.75 and 69.85, respectively. Logistic regression corroborated this difference, reaching a significant value (no persistence in deprivation index group 5 versus 1) with OR = 1.62; 95%CI: 1.13-2.31. Additionally, lower persistence was detected in males, under 60 years of age, undergoing treatment with alpha-agonists, and in patients with ocular hypertension. DISCUSSION: Low socioeconomic status of the patient was significantly associated with decreased persistence with topical antiglaucomatous therapy.

Protective effects of a probiotic-fermented germinated grain complex on neurotransmitters and sleep quality in sleep-deprived mice.

Objective: To explore the effects of probiotic fermentation products of germinated grains on cognitive and sleep improvement in mice with sleep deprivation induced by chlorophenylalanine (PCPA), and to provide theoretical and experimental basis for the development of natural products to alleviate insomnia. Methods: ELISA and high-performance liquid chromatography (HPLC) were used to determine the contents of γ-aminobutyric acid and L-theanine in fermentation products. Open Field Test was used to analyze the changes of emotional behavior between groups before and after intervention. ELISA was used to analyze the changes of hypothalamic serotonin, GABA, glutamate, and serum interleukin 6. 16S rRNA sequencing was used to analyze the changes of intestinal flora before and after the intervention of compound fermentation products. LC-MS/MS was used to analyze the changes of intestinal SCFAs before and after the intervention. Results: The content of GABA and L-theanine in 7 L fermentation products was 12.555 µmol/L (1.295 mg/L) and 0.471 mg/mL by ELISA. Compared with the PCPA-induced Model group, the sleep duration of the KEY group was statistically significant (p < 0.0001). Compared with the PCPA-induced Model group, the number of crossing the central lattice in the KEY group was significantly increased, and the number of grooming was significantly reduced (all p < 0.05), suggesting that the anxiety behavior of the mice was improved. In addition, this study found that the compound fermentation products could significantly increase the content of neurotransmitters such as 5-HT, GABA and Glu in the hypothalamus of mice, reduce the content of inflammatory factors such as IL-6, IL-1ß and TNF-α in serum, regulate the structure of intestinal flora and increase the content of short-chain fatty acids. Conclusion: Probiotic fermentation products of germinated grains can significantly improve sleep deprivation in PCPA mice, which may be related to regulating the levels of neurotransmitters and inflammatory factors, improving the structure of intestinal flora, and increasing the content of short-chain fatty acids. This study provides new candidates and research directions for the development of natural drugs to alleviate insomnia.

Caffeine and modafinil modulate the effects of sleep deprivation on thalamic resting-state functional connectivity: A double-blind pilot study.

BACKGROUND: Studies have found that the use of clinically approved caffeine and modafinil can alleviate cognitive impairment due to sleep deprivation (SD) to some extent. However, the neural mechanisms by which these two cognitive enhancers work to counteract the effects of SD on cognitive impairment remain unclear. METHODS: A double-blind within-subjects experiment using resting-state functional magnetic resonance imaging (rs-fMRI) was designed. Participants underwent three 36-h SD trials, each of which involved taking 200 mg of caffeine, modafinil, or placebo at the 28th and 32 nd h of SD. Sixteen subregions of the thalamus were selected as the regions of interest and changes in functional connectivity (FC) between the thalamus and the other brain regions were explored after the participants took caffeine or modafinil. RESULTS: The subjective sleepiness of the participants increased with the duration of SD. compared with placebo, modafinil and caffeine had insignificant effects on wakefulness or sleepiness. However, in terms of neural FC, we found varying degrees of attenuation or enhancement of the FC between the thalamus and other regions. Taking caffeine during SD weakened the FC between the right rostral temporal thalamus (rTtha) subregion and the left lingual gyrus compared with placebo. Caffeine enhanced the FC between three subregions of the thalamus, namely the left sensory thalamus, the left rTtha, and the right lateral pre-frontal thalamus, and the right inferior temporal, left orbitofrontal, and right superior occipital gyris. Modafinil weakened the FC between the right posterior parietal thalamus and left middle temporal gyrus, and enhanced the FC between the left medial pre-frontal thalamus, left rTtha, and right occipital thalamus and left middle frontal gyrus. CONCLUSIONS: After 36 h of total SD, modafinil and caffeine administration enhanced or attenuated the time-domain correlations between various subregions of the thalamus and brain regions of the frontal and temporal lobes in healthy adults, compared with placebo. These results provide valuable evidence for further unraveling the neuropharmacological mechanisms of caffeine and modafinil, as well as important insights for exploring effective pharmacological intervention strategies against SD.