Early postnatal whisker deprivation cross-modally modulates prefrontal cortex myelination and leads to social novelty deficit.

Sensory experience affects not only the corresponding primary sensory cortex, but also synaptic and neural circuit functions in other brain regions in a cross-modal manner. However, it remains unclear whether oligodendrocyte (OL) generation and myelination can also undergo cross-modal modulation. Here, we report that while early life short-term whisker deprivation from birth significantly reduces in the number of mature of OLs and the degree of myelination in the primary somatosensory cortex(S1) at postnatal day 14 (P14), it also simultaneously affects the primary visual cortex (V1), but not the medial prefrontal cortex (mPFC) with a similar reduction. Interestingly, when mice were subjected to long-term early whisker deprivation from birth (P0) to P35, they exhibited dramatically impaired myelination and a deduced number of differentiated OLs in regions including the S1, V1, and mPFC, as detected at P60. Meanwhile, the process complexity of OL precursor cells (OPCs) was also rduced, as detected in the mPFC. However, when whisker deprivation occurred during the mid-late postnatal period (P35 to P50), myelination was unaffected in both V1 and mPFC brain regions at P60. In addition to impaired OL and myelin development in the mPFC, long-term early whisker-deprived mice also showed deficits in social novelty, accompanied by abnormal activation of c-Fos in the mPFC. Thus, our results reveal a novel form of cross-modal modulation of myelination by sensory experience that can lead to abnormalities in social behavioral, suggesting a possible similar mechanism underlying brain pathological conditions that suffer from both sensory and social behavioral deficits, such as autism spectrum disorders.

ALKBH5 deficiency attenuates oxygen-glucose deprivation-induced injury in mouse brain microvascular endothelial cells in an m6A dependent manner.

Structural and functional alterations in brain microvascular endothelial cells (BMECs) caused by oxygen-glucose deprivation (OGD) are involved in the pathogenesis of various brain disorders. AlkB homolog 5 (ALKBH5) is a primary m6A demethylase that regulates various cell processes, but its distinct roles in BMEC function remain to be clarified. In the present study, in mouse middle cerebral artery occlusion (MCAO) model, knockout of ALKBH5 reduced neurological deficits, infarct volumes and tissue apoptosis caused by ischemia/reperfusion injury. Evans blue leakage and decreased expression of the tight junction protein ZO-1 and Occludin were also attenuated by ALKBH5 knockout. During the exploration of the underlying mechanisms of the role of ALKBH5 in BMECs, we found that the expression of ALKBH5 was induced at both the mRNA and protein levels by hypoxia; however, its protein stability was impaired by OGD treatment. Knockdown of ALKBH5 expression increased total m6A levels and alleviated OGD-induced BMEC injury. At the same time, the selective ALKBH5 inhibitor Cpd 20m also exhibited a protective effect on cell injury. In contrast, overexpression of ALKBH5 increased the sensitivity of BMECs to OGD. Interestingly, the m6A sequencing data revealed that knockdown of ALKBH5altered the expression of many genes via m6A upregulation. The gene expression alterations were verified by real-time PCR. Taken together, our results suggest that ALKBH5, as well as its target genes, plays important roles in the regulation of brain microvascular endothelial cell function through its RNA demethylase activity.

Social Determinants of Health Impact Complications Following Free-Flap Reconstruction for Head and Neck Cancer.

OBJECTIVE: Head and neck cancers (HNCs) have increased in prevalence and often require free-flap reconstruction (FFR) after tumor ablation. Postoperative complications following FFR can be high, occurring in as many as 48% and 71% of cases. HNC patients also have many disparities in Social Determinants of Health (SDOH), but the potential impact of SDOH disparities on postoperative complications following FFR has not been formally assessed. STUDY DESIGN: Retrospective cohort review. SETTING: Academic Tertiary Care Institution in Northeast United States. METHODS: Patients that underwent head and neck FFR between January 2018 and December 2021 were analyzed to determine associations between quartiles of the national Area Deprivation Index (ADI), a proxy for SDOH disparity, and various medical and surgical postoperative complications. Associations were assessed using χ2 analysis. RESULTS: Two hundred four patients were included in the study, and 61 patients had 97 complications. Significant associations between higher national ADI quartile and incidence of several postoperative complications were identified, including any surgical complication (P = .0419), wound dehiscence (P = .0494), myocardial infarction (MI) (P = .0215), and sepsis (P = .0464). CONCLUSION: There are significant associations between SDOH disparities and postoperative surgical complications, wound dehiscence, MI, and sepsis following head and neck FFR. Addressing SDOH disparities in HNC is pivotal to enhance postoperative outcomes and promote holistic patient care.

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.

Patient Preferences for Attributes of Androgen Deprivation Therapies in Prostate Cancer: A Discrete Choice Experiment with Latent Class Analysis.

INTRODUCTION: Medical androgen deprivation therapy (ADT) options have expanded for patients with advanced prostate cancer (PC). Historically, ADT was primarily available in long-acting injectable formulations. In 2020, the first oral formulation was US Food and Drug Administration-approved for adults with advanced PC. This study's aim was to assess patient preferences for attributes of medical ADT, including mode of administration, side effects, impact on sexual interest, and out-of-pocket (OOP) costs, and to segment respondents into distinct groups based on their treatment choice patterns. METHODS: A cross-sectional survey was conducted among US residents aged > 40 years with PC, employing a discrete choice experiment to assess preferences for ADT attributes. For each choice task, respondents were asked to select the hypothetical treatment profile that they preferred out of two presented. Latent class analysis (LCA) was conducted to estimate attribute-level preference weights and calculate attribute relative importance for groups of respondents with similar treatment preferences. RESULTS: A total of 304 respondents completed the survey (mean age 64.4 years). LCA identified four preference groups, named according to the attribute each group considered most important: Sexual interest, Cost-sensitive, Favors daily pill, and Favors injection. Most respondents in the Sexual interest group were < 65 years, while the Cost-sensitive group was mostly ≥ 65 years. Favors daily pill had the highest proportion of ADT-naïve individuals. On average, respondents in these groups preferred an oral medication. Favors injection, which had the highest proportion of ADT-experienced individuals, preferred infrequent intramuscular injections, lower chance of post-ADT testosterone recovery, and lower OOP cost. CONCLUSION: Respondents differed in their preferences regarding ADT attributes, highlighting the need for patient involvement in their treatment decisions. Effective communication between healthcare providers and patients about the benefits and risks of available therapies should be encouraged to ensure that patients receive the PC treatment that best meets their needs.

Prostate cancers often depend on the male sex hormone, testosterone, to grow. Androgen deprivation therapy (ADT) is used to lower testosterone levels in patients with advanced prostate cancer. ADT options available to patients have different characteristics, including how they are taken (injection or pill), side effects, impact on sexual interest, and costs. Researchers wanted to understand which ADT characteristics were most important to groups of patients with similar preferences. To do this, they gave 304 patients a series of two hypothetical (meaning not real) examples of ADT options with different characteristics and asked them to choose the option that they preferred most. Researchers found that patients could be separated into four different groups based on their preferences for ADT characteristics. One group preferred an ADT that had the least impact on their interest in sex. These patients were mainly younger than 65 years old. A second group preferred a lower cost ADT. These patients were mainly 65 years or older. A third group preferred a pill that could be taken once a day by mouth. Most of these patients did not take ADT in the past. A fourth group preferred an ADT that was given in a physician's office as an injection every 6 months. These patients mainly had taken ADT in the past. This study shows that patients have different preferences for ADT treatment characteristics. It is important for doctors to discuss the different ADT options with patients to find the treatment that best meets their needs.

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.

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.

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.

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.

Implementation of fracture risk assessment in men with prostate cancer requiring long-term androgen deprivation therapy: a systematic scoping review using the i-PARIHS implementation framework.

PURPOSE: Androgen deprivation therapy (ADT) is a mainstay of treatment for prostate cancer (PCa) and is associated with increased risks of osteoporosis and fragility fractures. Despite international guidelines to mitigate fracture risk, osteoporosis is under-diagnosed and under-treated due to poor implementation. This scoping review aims to synthesise knowledge surrounding the implementation of guidelines to inform health service interventions to reduce fracture risk in men with PCa-taking ADT (PCa-ADT). METHOD: Four databases and additional literature were searched for studies published between January 2000 and January 2023. Studies that provided evidence influencing guidelines implementation were included. The i-PARIHS (Promoting Action on Research Implementation in Health Services) implementation framework was used to inform the narrative synthesis. RESULTS: Of the 1229 studies identified, 9 studies met the inclusion criteria. Overall, an improvement in fracture risk assessment was observed across heterogeneous study designs and outcome measures. Six studies were from Canada. Two studies involved family physicians or a community healthcare programme. Two studies incorporated patient or specialist surveys. One utilised an implementation framework. Implementation barriers included the lack of knowledge for both patients and clinicians, time constraints, unsupportive organisational structures, and challenges in transferring patient care from specialists to primary care. Effective strategies included education, novel care pathways using a multidisciplinary approach, incorporating a healthy bone prescription tool into routine care, point-of-care interventions, and bespoke clinics. CONCLUSION: There is an unmet need to provide evidence-based bone healthcare in men with PCa receiving ADT. This study highlights barriers and strategies in the implementation of fracture risk assessment for PCa-ADT patients. IMPLICATIONS FOR CANCER SURVIVORS: Primary care clinicians can play a significant role in the management of complications from long-term cancer treatment such as treatment-induced bone loss. Future studies should consult patients, families, specialists, and primary care clinicians in service re-design.

Form-deprivation myopia promotes sclera M2-type macrophages polarization in mice.

PURPOSE: To explore the phenotype of sclera macrophages in form-deprivation (FD) myopia mice and the effects of M2 macrophage in FD myopia development. METHODS: C57BL/6 mice were under 2 weeks of unilateral FD treatment. and they were separated into two groups, including an intraperitoneally injected(IP) vehicle group and Panobinostat (LBH589) (10 mg/kg per body weight) treatment group. All biometric parameters were measured before and after treatments, and the type and density of sclera macrophages were identified by immunofluorescence and RT-qPCR. In vitro, we analyzed the M2 macrophage and primary human sclera fibroblast (HSF) co-culture system by using the transcriptome sequencing method. Gene ontology (GO) and KEGG enrichment analyses were used to pinpoint the biological functions and pathways associated with the identified Differentially Expressed Genes (DEGs). The hub genes were investigated using the STRING database and Cytoscape software and were confirmed using RT-qPCR. RESULTS: We found that the M2-type sclera macrophage density and expression increased in FD-treated eyes. The results showed that LBH589 inhibited the M2 macrophage polarization, and reduced FDM development. GO and KEGG analyses revealed that the DEGs were predominantly involved in the synthesis and breakdown of the extracellular matrix (ECM), as well as in pathways related to ECM-receptor interaction and the PI3K-Akt signaling pathway. Five hub genes (FN-1, MMP-2, COL1A1, CD44, and IL6) were identified, and RT-qPCR validated the variation in expression levels among these genes. CONCLUSION: M2 macrophage polarization occurred in the sclera in FDM mice. Panobinostat-mediated inhibition of M2 macrophage polarization may decrease FDM progression, as M2 macrophages are crucial in controlling ECM remodeling by HSFs.

Neighborhood economic vulnerability as a predictor for patterns of care and outcomes for patients with uterine cancer.

OBJECTIVE: To quantify the effect of neighborhood socioeconomic vulnerability as it relates to racial disparity in uterine cancer treatment and survival. METHODS: Patients with a diagnosis of uterine cancer who underwent hysterectomy in New York State from 2004 to 2017 were included in this retrospective cohort study. Neighborhood socioeconomic vulnerability as quantified by the Area Deprivation Index was calculated. Primary outcome was guideline adherent treatment; secondary outcome was 5 year overall survival. RESULTS: A total of 34,356 patients were included in the final cohort. Residence within a vulnerable neighborhood was associated with a lower likelihood of receiving appropriate adjuvant chemotherapy (59.7% vs 75.7% with aRR = 0.81; 95% CI, 0.77-0.86) and timely surgery (63.7% vs. 74.5% with aRR = 0.85; 95% CI, 0.82-0.87). All-cause mortality was 24% higher for those who resided in vulnerable neighborhoods compared to affluent neighborhoods (aHR = 1.24; 95% CI, 1.16-1.32). The greatest Black/White racial disparity in 5 year overall survival was seen in the most affluent neighborhoods at 18.6%, with survival being 79.8% for White patients and 61.2% for Black patients (aHR 1.31; 95% CI 1.14-1.51). For patients with advanced stage disease, this disparity was driven by improved survival for White patients with increasing neighborhood affluence but no change in survival for Black patients. On adjusted analysis controlling for age, comorbidities, insurance, tumor histology, stage, and grade, the disparity remained widest in the most affluent neighborhoods in NYC (aHR = 1.59; 95%CI 1.26-1.2.01). CONCLUSIONS: Neighborhood socioeconomic vulnerability is associated with poor outcomes for patients with uterine cancer. The greatest Black/White survival disparities are in the wealthiest neighborhoods. Neighborhood affluence may not affect survival of Black patients with advanced stage endometrial cancer.

Neighborhood Deprivation and Crime on Asthma Exacerbations and Utilization in Mild Adult Asthma.

BACKGROUND: Social determinants of health (SDOH) have a significant impact on asthma outcomes, with factors such as income level and neighborhood environment playing crucial roles. OBJECTIVE: This study aimed to assess the impact of Neighborhood Deprivation Index (NDI) and Total Crime Index (TCI) on acute asthma exacerbation (AAE) and asthma-related Emergency Department and urgent care (ED/UC) visits in adults with mild asthma. METHODS: This retrospective cohort study utilized administrative data from Kaiser Permanente Southern California among 198,873 mild adult asthma patients between January 1, 2013, and December 31, 2018. Robust Poisson regression models, adjusted for age and sex, were employed to investigate the associations of NDI and TCI with AAE and asthma-related ED/UC visits. Data analysis included subgroup assessments by race and ethnicity and BMI categories to explore potential disparities in asthma outcomes. RESULTS: Among the cohort, 12,906 patients (6.5%) experienced AAE in one year, with Black patients having the highest AAE percentage (7.1%). Higher NDI quintiles were associated with increased AAE risk (aRRs: 1.11-1.27), with similar trends across BMI categories and race or ethnicity, except for Black patients. TCI showed weaker associations with AAE. Regarding ED/UC visits, 5.0% had such visits within one year. Higher NDI quintiles were associated with higher ED/UC visit risk (aRRs: 1.23-1.75), while TCI associations were weaker. CONCLUSION: Addressing socioeconomic disparities, as indicated by NDI, may be crucial in mitigating asthma exacerbations and reducing healthcare utilization, highlighting the importance of incorporating social determinants into asthma management strategies even in patients with mild asthma.

Neighborhood socioeconomic disadvantage does not predict need for manipulation under anesthesia or range of motion following total knee arthroplasty.

Background: Studies have linked socioeconomic factors including lower income and minority race with worse functional outcomes following total knee arthroplasty (TKA). Arthrofibrosis is a common complication following TKA, and manipulation under anesthesia (MUA) is an effective treatment option for arthrofibrosis. This study aimed to determine if neighborhood-level socioeconomic disadvantage predicts need for MUA and postoperative range of motion (ROM) among patients undergoing primary elective TKA. Methods: We performed a retrospective cohort study of primary TKAs performed at a single institution over a three-year duration. Area Deprivation Index (ADI) was used to determine each patient's level of socioeconomic disadvantage based on their home address. Patients were allocated into three groups based on ADI: least socioeconomic disadvantage (ADI 1-3), middle socioeconomic disadvantage (ADI 4-6), and most socioeconomic disadvantage (ADI 7-10). Demographic factors and comorbid conditions were recorded. Bivariate analysis was used to evaluate the relationship between degree of socioeconomic disadvantage and need for MUA and postoperative ROM. Results: In total, 600 patients were included and 26.7 % were categorized as most disadvantaged. In comparison to the middle and least disadvantaged groups, these patients were more likely to be Women (71.2 vs. 67.9 and 58.6 %; p = 0.027), younger (60.7 vs. 62.9 and 66.3 years; p < 0.001) and have higher BMI (34.9 vs. 33 and 31.7; p < 0.001) (most disadvantaged vs. middle and least). Analysis revealed no difference in rate of MUA (6.3 vs. 2.5 vs. 4 %; p = 0.179) or postoperative ROM (98 vs. 98 vs. 100°; p = 0.753) between the three groups (most, middle, and least disadvantaged, respectively). Conclusion: Neighborhood socioeconomic disadvantage does not predict rate of MUA or postoperative ROM following TKA. Patients residing in neighborhoods with higher ADI who underwent TKA were more likely to be younger, Women, and have higher BMI, consistent with previous literature. Our results support efforts to improve access to orthopaedic care, including TKA, to patients of all socioeconomic levels.

Socioeconomic area deprivation index is not associated with postoperative complications following revision total hip and knee joint arthroplasty.

Introduction: Revision hip and knee total joint arthroplasty (TJA) carries a high burden of postoperative complications, including surgical site infections (SSI), venous thromboembolism (VTE), reoperation, and readmission, which negatively affect postoperative outcomes and patient satisfaction. Socioeconomic area-level composite indices such as the area deprivation index (ADI) are increasingly important measures of social determinants of health (SDoH). This study aims to determine the potential association between ADI and SSI, VTE, reoperation, and readmission occurrence 90 days following revision TJA. Methods: 1047 consecutive revision TJA patients were retrospectively reviewed. Complications, including SSI, VTE, reoperation, and readmission, were combined into one dependent variable. ADI rankings were extracted using residential zip codes and categorized into quartiles. Univariate and multivariate logistic regressions were performed to analyze the association of ADI as an independent factor for complication following revision TJA. Results: Depression (p = 0.034) and high ASA score (p < 0.001) were associated with higher odds of a combined complication postoperatively on univariate logistic regression. ADI was not associated with the occurrence of any of the complications recorded following surgery (p = 0.092). ASA remained an independent risk factor for developing postoperative complications on multivariate analysis. Conclusion: An ASA score of 3 or higher was significantly associated with higher odds of developing postoperative complications. Our findings suggest that ADI alone may not be a sufficient tool for predicting postoperative outcomes following revision TJA, and other area-level indices should be further investigated as potential markers of social determinants of health.

Altered Functional Connectivity of the Thalamus Subregions Associated with Impaired Attention After Sleep Deprivation.

Objective: The thalamus plays a critical role in attentional maintenance. Previous studies have revealed the dysfunction of the thalamus in attention decline after acute sleep deprivation (SD). However, the functional connectivity (FC) between the thalamus subregions and cortical regions underlying attentional impairment after acute SD remains unclear. Here, we aimed to probe the relationship between attentional function and the altered thalamocortical FC after acute SD. Methods: In this study, 25 healthy participants with regular sleep conducted an attentional network test and received a resting-state fMRI scan before and after 24 hours of SD. Then, we analyzed the FC between the thalamus and cerebrum and relationships with attentional function in the enrolled subjects. Results: Our results showed that the participants showed a significantly lower alerting effect, a higher executive effect, and lower accuracy after acute SD. Compared to the rested wakefulness state, we observed decreased FCs between the "somatosensory" thalamic seed and left frontal pole, right frontal pole, left middle temporal gyrus (posterior division), and right middle temporal gyrus (posterior division). Furthermore, the reduced FC between the right middle temporal gyrus and "somatosensory" thalamic seed was negatively associated with the change in orienting effect of the participants. Conclusion: Our findings reveal that the disrupted FC between thalamus subregions and cortical regions may contribute to impaired attention after SD.

Melatonin modulates TLR4/MyD88/NF-κB signaling pathway to ameliorate cognitive impairment in sleep-deprived rats.

Sleep deprivation (SD) is commonplace in today's fast-paced society. SD is a severe public health problem globally since it may cause cognitive decline and even neurodegenerative disorders like Alzheimer's disease. Melatonin (MT) is a natural chemical secreted by the pineal gland with neuroprotective effects. The purpose of this study was to investigate the protective effect and mechanism of MT on chronic sleep deprivation-induced cognitive impairment. A 3-week modified multi-platform method was used to create the SD rat model. The Morris water maze test (MWM), Tissue staining (including Hematoxylin and Eosin (H & E) staining, Nissl staining, and immunofluorescence), Western blot, Enzyme-linked immunosorbent assay (ELISA), and Quantitative real-time polymerase chain reaction (qPCR) were used to investigate the protective effect and mechanism of MT in ameliorating cognitive impairment in SD rats. The results showed that MT (50 and 100 mg/kg) significantly improved cognitive function in rats, as evidenced by a shortening of escape latency and increased time of crossing the platform and time spent in the quadrant. Additionally, MT therapy alleviated hippocampus neurodegeneration and neuronal loss while lowering levels of pathogenic factors (LPS) and inflammatory indicators (IL-1ß, IL-6, TNF-α, iNOS, and COX2). Furthermore, MT treatment reversed the high expression of Aß42 and Iba1 as well as the low expression of ZO-1 and occludin, and inhibited the SD-induced TLR4/MyD88/NF-κB signaling pathway. In summary, MT ameliorated spatial recognition and learning memory dysfunction in SD rats by reducing neuroinflammation and increasing neuroprotection while inhibiting the TLR4/MyD88/NF-κB signaling pathway. Our study supports the use of MT as an alternate treatment for SD with cognitive impairment.

Neighborhood disadvantage, race, and clinical outcomes in neuromyelitis optica spectrum disorder.

BACKGROUND: Little is known about the relationship between neighborhood disadvantage and neuromyelitis optica spectrum disorder (NMOSD) outcomes. OBJECTIVE: The objective is to determine the impact of neighborhood disadvantage on time from symptom onset to diagnosis and annualized relapse rate (ARR). METHODS: Neighborhood disadvantage were captured with the Area Deprivation Index (ADI), a validated measure of neighborhood-level disadvantage. Negative binomial regression models assessed the impact of ADI on diagnostic delay (⩾3 months between symptom onset and diagnosis) and ARR. RESULTS: A total of 158 NMOSD patients were identified, a majority of whom were White (56.3%) and female (89.9%) with a mean age of 46 years at diagnosis. The ADI did not significantly affect odds of diagnostic delay (odds ratio (OR) = 0.99, p = 0.26). In univariable models, the ADI was not significantly associated with ARR (OR = 1.004, p = 0.29), but non-White race (OR = 1.541, p = 0.02) and time on immunosuppressive therapies (ISTs; OR = 0.994, p = 0.03) were. White patients used IST for an average of 81% of the follow-up period, compared to an average of 65% for non-White patients (p < 0.01). CONCLUSION: No significant relationship between neighborhood-level disadvantage and diagnostic delay or ARR in NMOSD patients was observed. Non-White patients had a higher ARR, which may be related to less IST use.