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Port-wine stain (PWS) birthmarks are one class of benign congenital vascular malformation. Laser therapy is the most successful treatment modality of PWS. Unfortunately, this approach has limited efficacy, with only 10% of patients experiencing complete blanching of the PWS. To address this problem, several research groups have developed technologies and methods designed to study treatment outcome and improve treatment efficacy. This article reviews seven optical imaging techniques currently in use or under development to assess treatment efficacy, focusing on: reflectance spectrophotometers/tristimulus colorimeters; laser Doppler flowmetry and laser Doppler imaging; cross-polarized diffuse reflectance colour imaging system; reflectance confocal microscopy; optical coherence tomography; spatial frequency domain imaging; and laser speckle imaging.

Statement of the problem: Presently, various imaging methods are available for the disclosure of proximal caries. Some recent studies have attempted to determine the diagnostic accuracy of available modalities, but they have shown variable results. Aim: This study was carried out to recognize and examine the correctness of cone-beam computed tomography (CBCT), regular radiographs and the nondirect digital system in the disclosure of interproximal caries. Materials and Method: In this observational tryout study, forty-two extracted non-cavitated, unrestored person molar and premolar teeth were placed in the blocks with proximal surfaces in touch. Then they were appraised by CBCT, formal radiographs and the nondirect digital system for the disclosure of interproximal caries. Four oral and maxillofacial radiologists used a 4-point scale to assess the pictures for the existence or absence of proximal caries. Caries depth was specified by histological examination. The gathered data were assessed by SPSS software using Weighted Kappa and Friedman test. Results: Statistics demonstrated that the accuracy of the indirect digital system was somewhat better than conventional systems. The accuracy of the indirect digital system was better than cone beam system, and this difference was statistically significant. Conclusion: The digital system was better than CBCT in the disclosure of proximal caries. The formal radiography fell in between the two other systems without a statistically significant deviation in detecting caries. Thus, CBCT is not advised to detect proximalcaries because of the higher radiation dose. [ABSTRACT FROM AUTHOR]

Background There is a pressing need for research that will lead to the development of new therapeutic approaches for treating inflammatory bowel disease (IBD). The aim of this study was to investigate the effects of tropisetron, a 5-Hydroxytryptamine (5-HT)-3 receptor antagonist with anti-inflammatory properties in a model of experimental colitis in rat. Materials and methods Acetic acid model of colitis in rats was used. Colitis was induced by intracolonal instillation of 4% (v/v) acetic acid. One hour after induction of colitis, intraperitoneal (IP) or intrarectal (IR) tropisetron (2 mg kg−1, either route) or dexamethasone (1 mg kg−1, either route) was administered. The severity of colitis was assessed 24 h later using macroscopic and microscopic changes of damaged colon, measurement of inflammatory cytokines interleukin-1β, interleukin-6 and tumour necrosis factor-α levels and oxidative stress markers myeloperoxidase (MPO) and malondialdehyde (MDA) in colonic tissues. Results Tropisetron decreased colonic macroscopic and microscopic damage scores. This was associated with significant reduction in both neutrophil infiltration indicated by decreased colonic MPO activity and lipid peroxidation measured by MDA content, as well as a decreased colonic inflammatory cytokines. IR tropisetron decreased colonic damage that was associated with decreased neutrophil infiltration, lipid peroxidation and colonic inflammatory cytokines. Beneficial effects of tropisetron were lower than those of dexamethasone. No significant differences were observed between IP and IR administration with the exception of MDA level more diminished by IP tropisetron and dexamethasone. Conclusions Tropisetron exert beneficial effects in experimental rat colitis and therefore might be useful in the treatment of IBD. [ABSTRACT FROM AUTHOR]

Abstract Background Emerging data implicate nicotinamide phosphoribosyl transferase (NAMPT) in the pathogenesis of cancer and inflammation. NAMPT inhibitors have proven beneficial in inflammatory animal models of arthritis and endotoxic shock as well as in autoimmune encephalitis. Given the role of inflammatory responses in spinal cord injury (SCI), the effect of NAMPT inhibitors was examined in this setting. Methods We investigated the effects of the NAMPT inhibitor FK866 in an experimental compression model of SCI. Results Twenty-four hr following induction of SCI, a significant functional deficit accompanied widespread edema, demyelination, neuron loss and a substantial increase in TNF-α, IL-1β, PAR, NAMPT, Bax, MPO activity, NF-κB activation, astrogliosis and microglial activation was observed. Meanwhile, the expression of neurotrophins BDNF, GDNF, NT3 and anti-apoptotic Bcl-2 decreased significantly. Treatment with FK866 (10 mg/kg), the best known and characterized NAMPT inhibitor, at 1 h and 6 h after SCI rescued motor function, preserved perilesional gray and white matter, restored anti-apoptotic and neurotrophic factors, prevented the activation of neutrophils, microglia and astrocytes and inhibited the elevation of NAMPT, PAR, TNF-α, IL-1β, Bax expression and NF-κB activity. We show for the first time that FK866, a specific inhibitor of NAMPT, administered after SCI, is capable of reducing the secondary inflammatory injury and partly reduce permanent damage. We also show that NAMPT protein levels are increased upon SCI in the perilesional area which can be corrected by administration of FK866. Conclusions Our findings suggest that the inflammatory component associated to SCI is the primary target of these inhibitors.

Abstract The aim of this study was to develop a practical model of sciatic ischemia reperfusion (I/R) injury producing serious neurologic deficits and being technically feasible compared with the current time consuming or ineffective models. Thirty rats were divided into 6 groups (n = 5). Animal were anesthetized by using ketamine (50 mg/kg) and xylazine (4 mg/kg). Experimental groups included a sham-operated group and five I/R groups with different reperfusion time intervals (0 h, 3 h, 1 d, 4 d, 7 d). In I/R groups, the right common iliac artery and the right femoral artery were clamped for 3 hrs. Sham-operated animals underwent only laparotomy without induction of ischemia. Just before euthanasia, behavioral scores (based on gait, grasp, paw position, and pinch sensitivity) were obtained and then sciatic nerves were removed for light-microscopy studies (for ischemic fiber degeneration (IFD) and edema). Behavioral score deteriorated among the ischemic groups compared with the control group (p < 0.01), with maximal behavioral deficit occurring at 4 days of reperfusion. Axonal swelling and IFD were found to happen only after 4 and 7 days, respectively. Our observations led to an easy-to-use but strong enough method for inducing and studying I/R injury in peripheral nerves.

A novel radiotracer, [ 11 C]SL25.1188, targets monoamine oxidase-B (MAO-B) enzyme, found primarily in astrocytes, which metabolizes monoamines (including dopamine), particularly in subcortical regions. Altered astrocyte function in schizophrenia is supported by convergent evidence from post-mortem, genetic, transcriptomic, peripheral and preclinical findings. We aimed to test whether levels of MAO-B, an index of astrocyte function are low in the living brains of early psychosis and their high-risk states. Thirty-eight participants including antipsychotic-free/minimally exposed clinical participants with first-episode psychosis (FEP), clinical high-risk (CHR) individuals and healthy volunteers (HVs) underwent a 90-min positron emission tomography (PET) scan with [ 11 C]SL25.1188, to measure MAO-B V T , an index of MAO-B concentration. Participants were excluded if tested positive on urine drug screen (except for cannabis). This study of 14 FEP (mean[SD] age, 25.7[5.7] years; 6 F), 7 CHR (mean[SD] age, 20.9[3.7] years; 4 F) and 17 HV (mean[SD] age, 31.2[13.9] years; 9 F) demonstrated significant group differences in regional MAO-B V T (F (2,37.42)  = 4.56, p = 0.02, Cohen's f = 0.49), controlling for tobacco (F (1,37.42)  = 5.37, p = 0.03) and cannabis use (F (1,37.42)  = 5.11, p = 0.03) with significantly lower MAO-B V T in CHR compared to HV (Cohen's d = 0.99). We report a significant cannabis effect on MAO-B V T (F (1,39.19)  = 12.57, p = 0.001, Cohen's f = 0.57), with a significant group-by-cannabis interaction (F (2,37.30)  = 3.82, p = 0.03, Cohen's f = 0.45), indicating lower MAO-B V T in cannabis-using clinical groups. Lower MAO-B V T levels were more robust in striatal than cortical regions, in both clinical groups (F (12,46.84)  = 2.08, p = 0.04, Cohen's f = 0.73) and in cannabis users (F (6,46.84)  = 6.42, p < 0.001, Cohen's f = 0.91). Lower MAO-B concentration supports astrocyte dysfunction in cannabis-using CHR and FEP clinical populations. Lower MAO-B is consistent with replicated striatal dopamine elevation in psychosis, as well as astrocyte dysfunction in schizophrenia., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The olfactory bulb (OB), a major structure of the limbic system, has been understudied in human investigations of psychopathologies such as depression. To explore more directly the molecular features of the OB in depression, a global comparative proteome analysis was carried out with human post-mortem OB samples from 11 males having suffered from depression and 12 healthy controls. We identified 188 differentially abundant proteins (with adjusted p < 0.05) between depressed cases and controls. Gene ontology and gene enrichment analyses suggested that these proteins are involved in biological processes including the complement and coagulation cascades. Cell type enrichment analysis displayed a significant reduction in several canonical astrocytic proteins in OBs from depressed patients. Furthermore, using RNA-fluorescence in-situ hybridization, we observed a decrease in the percentage of ALDH1L1 + cells expressing canonical astrocytic markers including ALDOC, NFIA, GJA1 (connexin 43) and SLC1A3 (EAAT1). These results are consistent with previous reports of downregulated astrocytic marker expression in other brain regions in depressed patients. We also conducted a comparative phosphoproteomic analysis of OB samples and found a dysregulation of proteins involved in neuronal and astrocytic functions. To determine whether OB astrocytic abnormalities is specific to humans, we also performed proteomics on the OB of socially defeated male mice, a commonly used model of depression. Cell-type specific analysis revealed that in socially defeated animals, the most striking OB protein alterations were associated with oligodendrocyte-lineage cells rather than with astrocytes, highlighting an important species difference. Overall, this study further highlights cerebral astrocytic abnormalities as a consistent feature of depression in humans., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [CHB is the CSO of MRM Proteomics Inc., and the VP of Proteomics at Molecular You. RPZ is CEO of MRM Proteomics. The remaining authors declare no conflict of interest]., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Several reports, including our previous studies, indicate that hyperglycemia and diabetes mellitus exert differential effects on vascular function in males and females. This study examines sex differences in the vascular effects of type 2 diabetes (T2D) in an established monogenic model of obesity-induced T2D, Zucker Diabetic Fatty (ZDF) rats. Acetylcholine (ACh) responses were assessed in phenylephrine pre-contracted rings before and after apocynin, a NADPH oxidase (NOX) inhibitor. The mRNA expressions of aortic endothelial NOS (eNOS), and key NOX isoforms were also measured. We demonstrated the following: (1) diabetes had contrasting effects on aortic vasorelaxation in ZDF rats, impairing relaxation to ACh in females while enhancing it in male ZDF rats; (2) inhibition of NOX, a major source of superoxide in vasculature, restored aortic vasorelaxation in female ZDF rats; and (3) eNOS and NOX4 mRNA expressions were elevated in female (but not male) ZDF rat aortas compared to their respective leans. This study highlights sexual dimorphism in ACh-mediated vasorelaxation in the aorta of ZDF rats, suggesting that superoxide may play a role in the impaired vasorelaxation observed in female ZDF rats.

Background: Adult hippocampal neurogenesis has been extensively characterized in rodent models, but its existence in humans remains controversial. We sought to assess the phenomenon in postmortem human hippocampal samples by combining spatial transcriptomics and multiplexed fluorescent in situ hybridization., Methods: We computationally examined the spatial expression of various canonical neurogenesis markers in postmortem dentate gyrus (DG) sections from young and middle-aged sudden-death males. We conducted in situ assessment of markers expressed in neural stem cells, proliferative cells, and immature granule neurons in postmortem DG sections from infant, adolescent, and middle-aged males., Results: We examined frozen DG tissue from infant ( n = 1, age 2 yr), adolescent ( n = 1, age 16 yr), young adult ( n = 2, mean age 23.5 yr), and middle-aged ( n = 2, mean age 42.5 yr) males, and frozen-fixed DG tissue from middle-aged males ( n = 6, mean age 43.5 yr). We detected very few cells expressing neural stem cell and proliferative markers in the human DG from childhood to middle age. However, at all ages, we observed a substantial number of DG cells expressing the immature neuronal marker DCX . Most DCX + cells displayed an inhibitory phenotype, while the remainder were non-committed or excitatory in nature., Limitations: The study was limited by small sample sizes and included samples only from males., Conclusion: Our findings indicate very low levels of hippocampal neurogenesis throughout life and the existence of a local reserve of plasticity in the adult human hippocampus. Overall, our study provides important insight into the distribution and phenotype of cells expressing neurogenesis markers in the adult human hippocampus., Competing Interests: Competing interests:: None declared., (© 2024 CMA Impact Inc. or its licensors.)

Background: Disparities in ovarian cancer survival for African American women are multifactorial. We evaluated racial and ethnic differences in time to ovarian cancer surgery in members of an integrated health care system., Patients and Methods: In this retrospective cohort study, we identified women diagnosed with invasive epithelial-type ovarian cancer between January 1, 2008, through December 31, 2014, at an integrated health care system in the United States. We extracted data on cancer-related variables and sociodemographic variables from the health care system's cancer registry and electronic health records. We included patients who received ovarian cancer surgery without neoadjuvant chemotherapy. We defined time to surgery as the number of days between diagnostic imaging study and surgery. We used Cox proportional hazards regression to evaluate crude and adjusted association of race and ethnicity with time to surgery., Results: Of 872 patients included, 55.1% were non-Hispanic White (hereafter, White), 24.9% were Hispanic, 14.6% were Asian/Pacific Islander (PI)/Native American, and 5.5% were African American. Median age at diagnosis was 59.0 years. African American patients were diagnosed at an older age and were more likely to come from deprived neighborhoods than other racial and ethnic groups. Median time to surgery was longer for African American patients compared with White, Hispanic, and Asian/PI/Native American patients (median days: 27.5 vs 21.0, 24.5, and 26.0, respectively; P<.0001). In adjusted models, the likelihood of having received surgery at any given time post diagnostic imaging was 31% lower for African American patients compared with White patients (HR, 0.69; 95% CI, 0.51-0.93). This likelihood was also lower for Hispanic and Asian/PI/Native American patients, but not statistically significant., Conclusions: Our findings showed that patients with ovarian cancer from racial and ethnic minorities had a lower likelihood of having received surgery at any given time post diagnostic imaging compared with White patients, demonstrating that racial and ethnic differences exist in time to ovarian cancer surgery in patients with relatively equal access to care.

The extracellular matrix plays a key role in synapse formation and in the modulation of synaptic function in the central nervous system. Recent investigations have revealed that microglia, the resident immune cells of the brain, are involved in extracellular matrix remodeling under both physiological and pathological conditions. Moreover, the dysregulation of both innate immune responses and the extracellular matrix has been documented in stress-related psychopathologies as well as in relation to early-life stress. However, the dynamics of microglial regulation of the ECM and how it can be impacted by early-life adversity have been understudied. This brief review provides an overview of the recent literature on this topic, drawing from both animal model and human post mortem studies. Direct and indirect mechanisms through which microglia may regulate the extracellular matrix-including perineuronal nets-are presented and discussed in light of the interactions with other cell types.

Amniotic fluid embolism (AFE) is a potentially fatal maternal condition demanding awareness from obstetricians and anesthesiologists regarding its different manifestations. The typical presentation involves maternal respiratory distress, cardiovascular collapse, neurological changes, and coagulopathy followed by fetal distress. This unusual case study emphasizes that fetal compromise may precede maternal decompensation as the initial sign of AFE. Fetal distress is a known symptom of AFE and is typically seen due to cardiorespiratory issues that lead to reduced uteroplacental perfusion, resulting in fetal hypoxia. In the case presented, fetal bradycardia occurred before any visible maternal symptoms, suggesting that fetal distress could be induced by factors independent of the mother's cardiopulmonary status. A 34-year-old healthy G4P2012 at 41 weeks and 2 days gestation who was initially laboring on the floor was emergently taken to the operating room for a cesarean delivery due to fetal bradycardia. Around the time the fetus was delivered, the patient displayed seizure activity, followed by a complete loss of consciousness and cardiac arrest. The patient was intubated and underwent cardiopulmonary resuscitation and defibrillation, subsequently converting to a wide complex tachycardia. In the operating room, there was evidence of heavy vaginal bleeding, uterine atony, and a fulminant form of disseminated intravascular coagulopathy (DIC), which required aggressive management over the next four hours. After achieving hemodynamic stability, the patient was transferred to the surgical intensive care unit (SICU), extubated on day 3, and discharged home on day 8., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Wang et al.)

Perineuronal nets (PNNs) are a condensed subtype of extracellular matrix that form a net-like coverings around certain neurons in the brain. PNNs are primarily composed of chondroitin sulfate (CS) proteoglycans from the lectican family that consist of CS-glycosaminoglycan side chains attached to a core protein. CS disaccharides can exist in various isoforms with different sulfation patterns. Literature suggests that CS disaccharide sulfation patterns can influence the function of PNNs as well as their labeling. This study was conducted to characterize such interregional CS disaccharide sulfation pattern differences in adult human (n = 81) and mouse (n = 19) brains. Liquid chromatography tandem mass spectrometry was used to quantify five different CS disaccharide sulfation patterns, which were then compared to immunolabeling of PNNs using Wisteria Floribunda Lectin (WFL) to identify CS-glycosaminoglycans and anti-aggrecan to identify CS proteoglycans. In healthy brains, significant regional and species-specific differences in CS disaccharide sulfation and single versus double-labeling pattern were identified. A secondary analysis to investigate how early-life stress impacts these PNN features discovered that although early-life stress increases WFL+ PNN density, the CS-glycosaminoglycan sulfation code and single versus double PNN-labeling distributions remained unaffected in both species. These results underscore PNN complexity in traditional research, emphasizing the need to consider their heterogeneity in future experiments., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Parkinson's disease is a neurological disorder caused by the loss of dopaminergic neurons in the midbrain. Various mechanisms are involved in the incidence of the disease including oxidative stress. Several herbs and natural products may interfere with the oxidative-stress pathway due to their antioxidant effects., Objective: Herein, we aimed to investigate the neuroprotective role of F. vaillantii extract on Parkinson's in vitro and in vivo model owing to the presence of the bioactive agents with antioxidant properties., Methods: In vitro experments showed that 6-hydroxydopamine could induce toxicity in PC12 cells. The impact of F. vaillantii extract on cell viability was measured by using MTT assay. Nuclear morphological changes were qualitatively evaluated employing Hoechst staining. The antioxidant activity of the extract was determined by ROS and lipid peroxidation assays. Tyrosine hydroxylase protein expression was measured by western blotting in PC12 cells. For in vivo study, movement parameters were evaluated., Results: The results indicated that 75 µΜ of 6-OHDA induced 50% toxicity in PC12 cells for 24 h. Following post-treatment with F. vaillantii extract (0.1 mg/ml) for 72 h, we observed that the extract effectively prevented cell toxicity induced by 6-OHDA and reduced the apoptotic cell population. Furthermore, the extract attenuated the ROS level, lipid peroxidation and increased protein expression of TH after 72 h of treatment. In addition, oral administration of 300 mg/kg of F. vaillantii extract for 14 days improved locomotor activity, catalepsy, bradykinesia, motor coordination and reduced the apomorphine-caused rotation in 6-OHDA- induced Parkinson's disease-like symptoms in male rats., Conclusion: The present study suggests a protective role for the extract of F. vaillantii against oxidative stress-induced cell damage in the PC12 cells exposed to neurotoxin 6-OHDA which was verified in in vivo model by reducing the motor defects induced by 6-OHDA. This extract could be a promising therapeutic agent for the prevention of PD progression., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Cortical parvalbumin interneurons (PV+) are major regulators of excitatory/inhibitory information processing, and their maturation is associated with the opening of developmental critical periods (CP). Recent studies reveal that cortical PV+ axons are myelinated, and that myelination along with perineuronal net (PNN) maturation around PV+ cells is associated with the closures of CP. Although PV+ interneurons are susceptible to early-life stress, their relationship between their myelination and PNN coverage remains unexplored. This study compared the fine features of PV+ interneurons in well-characterized human post-mortem ventromedial prefrontal cortex samples (n = 31) from depressed suicides with or without a history of child abuse (CA) and matched controls. In healthy controls, 81% of all sampled PV+ interneurons displayed a myelinated axon, while a subset (66%) of these cells also displayed a PNN, proposing a relationship between both attributes. Intriguingly, a 3-fold increase in the proportion of unmyelinated PV+ interneurons with a PNN was observed in CA victims, along with greater PV-immunofluorescence intensity in myelinated PV+ cells with a PNN. This study, which is the first to provide normative data on myelination and PNNs around PV+ interneurons in human neocortex, sheds further light on the cellular and molecular consequences of early-life adversity on cortical PV+ interneurons., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

We recently described a novel ribosome-based regulatory mechanism/checkpoint that controls innate immune gene translation and microglial activation in non-sterile inflammation orchestrated by RNA binding protein SRSF3. Here we describe a role of SRSF3 in the regulation of microglia/macrophage activation phenotypes after experimental stroke. Using a model-system for analysis of the dynamic translational state of microglial ribosomes we show that 24 h after stroke highly upregulated immune mRNAs are not translated resulting in a marked dissociation of mRNA and protein networks in activated microglia/macrophages. Next, microglial activation after stroke was characterized by a robust increase in pSRSF3/SRSF3 expression levels. Targeted knockdown of SRSF3 using intranasal delivery of siRNA 24 h after stroke caused a marked knockdown of endogenous protein. Further analyses revealed that treatment with SRSF3-siRNA alleviated translational arrest of selected genes and induced a transient but significant increase in innate immune signaling and IBA1+ immunoreactivity peaking 5 days after initial injury. Importantly, delayed SRSF3-mediated increase in immune signaling markedly reduced the size of ischemic lesion measured 7 days after stroke. Together, our findings suggest that targeting SRSF3 and immune mRNA translation may open new avenues for molecular/therapeutic reprogramming of innate immune response after ischemic injury., Competing Interests: Declaration of interests J.K. and H.B. hold a patent application entitled “Use of SRSF3 agents for the treatment and/or prevention of neurological conditions, cancer, bacterial infections or viral infections.”, (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Inflammatory bowel disease (IBD), a common term for Crohn's disease and ulcerative colitis, is a chronic, relapse-remitting condition of the gastrointestinal tract that is increasing worldwide. Psychiatric comorbidities, including depression and anxiety, are more prevalent in IBD patients than in healthy individuals. Evidence suggests that varying levels of neuroinflammation might underlie these states in IBD patients. Within this context, microglia are the crucial non-neural cells in the brain responsible for innate immune responses following inflammatory insults. Alterations in microglia's functions, such as secretory profile, phagocytic activity, and synaptic pruning, might play significant roles in mediating psychiatric manifestations of IBD. In this review, we discuss the role played by microglia in IBD-associated comorbidities.

Background: Over the past decade, the United States (US) has seen a spike in migration across the US-Mexico border with an increase in hospital admissions of migrants and asylum-seekers under the custody of immigration law enforcement (ILE). This study aimed to determine how the presence of ILE officials affects patient care and provider experience in a teaching hospital setting., Methods: This cross-sectional online survey solicited quantitative and qualitative feedback from medical students, residents, and attending physicians (n = 1364) at a teaching hospital system with two campuses in Arizona. The survey included participant demographics and addressed participants' experience caring for patients in ILE custody, including the perception of respect, violations of patients' privacy and autonomy, and the comfort level with understanding hospital policies and patient rights. Thematic analyses were also performed based on respondent comments., Results: 332 individuals (24%) responded to the survey. Quantitative analyses revealed that 14% of participants described disrespectful behaviors of ILE officials, mainly toward detained patients. Qualitative thematic analyses of respondent comments revealed details on such disrespectful encounters including ILE officers violating the Health Insurance Portability and Accountability Act (HIPAA) and using intimidation tactics with patients. Nearly half of the respondents did not have knowledge of policies about ILE detainees' medical care, detainees' privacy rights, or ILE's authority in patient care., Conclusions: This study points out the complexities, challenges, and ethical considerations of caring for patients in ILE custody in the hospital setting and the need to educate healthcare professionals on both patient and provider rights. It describes the lived experiences and difficulties that providers on the border face in trying to achieve equity in the care they provide to detained migrant patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The neurovascular unit, comprised of vascular cell types that collectively regulate cerebral blood flow to meet the needs of coupled neurons, is paramount for the proper function of the central nervous system. The neurovascular unit gatekeeps blood-brain barrier properties, which experiences impairment in several central nervous system diseases associated with neuroinflammation and contributes to pathogenesis. To better understand function and dysfunction at the neurovascular unit and how it may confer inflammatory processes within the brain, isolation and characterization of the neurovascular unit is needed. Here, we describe a singular, standardized protocol to enrich and isolate microvessels from archived snap-frozen human and frozen mouse cerebral cortex using mechanical homogenization and centrifugation-separation that preserves the structural integrity and multicellular composition of microvessel fragments. For the first time, microvessels are isolated from postmortem ventromedial prefrontal cortex tissue and are comprehensively investigated as a structural unit using both RNA sequencing and Liquid Chromatography with tandem mass spectrometry (LC-MS/MS). Both the transcriptome and proteome are obtained and compared, demonstrating that the isolated brain microvessel is a robust model for the NVU and can be used to generate highly informative datasets in both physiological and disease contexts., Competing Interests: None., (© 2023 The Authors.)

Major depressive disorder (MDD) is a common, heterogenous, and potentially serious psychiatric illness. Diverse brain cell types have been implicated in MDD etiology. Significant sexual differences exist in MDD clinical presentation and outcome, and recent evidence suggests different molecular bases for male and female MDD. We evaluated over 160,000 nuclei from 71 female and male donors, leveraging new and pre-existing single-nucleus RNA-sequencing data from the dorsolateral prefrontal cortex. Cell type specific transcriptome-wide threshold-free MDD-associated gene expression patterns were similar between the sexes, but significant differentially expressed genes (DEGs) diverged. Among 7 broad cell types and 41 clusters evaluated, microglia and parvalbumin interneurons contributed the most DEGs in females, while deep layer excitatory neurons, astrocytes, and oligodendrocyte precursors were the major contributors in males. Further, the Mic1 cluster with 38% of female DEGs and the ExN10&#95;L46 cluster with 53% of male DEGs, stood out in the meta-analysis of both sexes., (© 2023. The Author(s).)

The beneficial cardiovascular effects of exercise are well documented, however the mechanisms by which exercise improves vascular function in diabetes are not fully understood. This study investigates whether there are (1) improvements in blood pressure and endothelium-dependent vasorelaxation (EDV) and (2) alterations in the relative contribution of endothelium-derived relaxing factors (EDRF) in modulating mesenteric arterial reactivity in male UC Davis type-2 diabetes mellitus (UCD-T2DM) rats, following an 8-week moderate-intensity exercise (MIE) intervention. EDV to acetylcholine (ACh) was measured before and after exposure to pharmacological inhibitors. Contractile responses to phenylephrine and myogenic tone were determined. The arterial expressions of endothelial nitric oxide (NO) synthase (eNOS), cyclooxygenase (COX), and calcium-activated potassium channel (K Ca ) channels were also measured. T2DM significantly impaired EDV, increased contractile responses and myogenic tone. The impairment of EDV was accompanied by elevated NO and COX importance, whereas the contribution of prostanoid- and NO-independent (endothelium-derived hyperpolarization, EDH) relaxation was not apparent compared to controls. MIE 1) enhanced EDV, while it reduced contractile responses, myogenic tone and systolic blood pressure (SBP), and 2) caused a shift away from a reliance on COX toward a greater reliance on EDH in diabetic arteries. We provide the first evidence of the beneficial effects of MIE via the altered importance of EDRF in mesenteric arterial relaxation in male UCD-T2DM rats.

Early-life stress (ELS) leads to increased vulnerability to psychiatric disorders including depression later in life. Neuroinflammatory processes have been implicated in ELS-induced negative health outcomes, but how ELS impacts microglia, the main tissue-resident macrophages of the central nervous system, is unknown. Here, we determined the effects of ELS-induced by limited bedding and nesting material during the first week of life (postnatal days [P]2-9) on microglial (i) morphology; (ii) hippocampal gene expression; and (iii) synaptosome phagocytic capacity in male pups (P9) and adult (P200) mice. The hippocampus of ELS-exposed adult mice displayed altered proportions of morphological subtypes of microglia, as well as microglial transcriptomic changes related to the tumor necrosis factor response and protein ubiquitination. ELS exposure leads to distinct gene expression profiles during microglial development from P9 to P200 and in response to an LPS challenge at P200. Functionally, synaptosomes from ELS-exposed mice were phagocytosed less by age-matched microglia. At P200, but not P9, ELS microglia showed reduced synaptosome phagocytic capacity when compared to control microglia. Lastly, we confirmed the ELS-induced increased expression of the phagocytosis-related gene GAS6 that we observed in mice, in the dentate gyrus of individuals with a history of child abuse using in situ hybridization. These findings reveal persistent effects of ELS on microglial function and suggest that altered microglial phagocytic capacity is a key contributor to ELS-induced phenotypes., (© 2022. The Author(s).)

Study Objective: Anesthesiologists are at high risk for needlestick injury. Such injuries pose a serious health threat from exposure to bloodborne pathogens. This retrospective analysis aimed to examine needlestick injury rate among anesthesia providers between 2010 and 2020 at the University of California Los Angeles, Department of Anesthesiology and Perioperative Medicine to determine specialty-specific factors associated with these injuries., Design: Retrospective analysis., Setting: Academic Anesthesiology Department., Patients and Interventions: None., Measurements: All reported incidents of needlestick injuries to employees are sent to the Injury and Illness Prevention Committee. We included all anesthesia residents, fellows, nurse anesthetists, solo anesthesiologists, and supervising anesthesiologists., Main Results: The overall rate of reported needlestick injuries was 5.3%. The rates for anesthesia residents were 2.1%, 13.5%, 7.9%, and 6.7% for post graduate year 1-4 (PGY 1-4) residents. The rates were 14.3%, 4.7%, 2.1%, and 6.9% for fellows, nurse anesthetists, supervising anesthesiologists, and solo anesthesiologists, respectively. We found that PGY2 residents had a higher injury rate than PGY1 residents (p-value<0.001). When grouping PGY2, PGY3, and PGY4 residents together, they had a collective rate of 9.4%. Furthermore, residents had a higher needlestick injury rate than supervising anesthesiologists (p-value <0.001)., Conclusions: PGY2 residents and fellows had the highest rate of needlestick injury. Our study highlights the trend of increasing sharps injuries after PGY1 while supervising anesthesiologists had the lowest rate. Proposed mechanisms for the increased sharps injuries include residents' transition from medicine-based internship to the operating room environment with increased exposure to potentially injurious equipment, overnight call, and increased work-related and cognitive stress. Improving understanding of institution-specific prevention programs, raising awareness during their initial high-intensity training period with one-to-one supervision when habits are formed, and reducing exposure to sharps using a needleless system are some steps toward reducing the incidence of sharps injuries in a field where the risk remains high., (Published by Elsevier Inc.)

To understand how various brain cell types communicate with each other to orchestrate functional processes, it is crucial to comprehend the signals used to relay such information. Therefore, an important challenge to studying complex brain diseases is to interrogate relevant interactions between cell types. The microglia-oligodendroglia interaction is an important example that has fundamental roles in physiological state and brain pathologies. Here, we review the latest findings on microglia-oligodendroglia interplay in physiological and pathological conditions. Furthermore, we provide an in silico ligand-receptor interaction analysis to explore potential druggable targets in multiple sclerosis (MS) and major depressive disorder (MDD)., Competing Interests: Declaration of interests The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Ltd. All rights reserved.)