Showing papers by "Wayne State University published in 2023"

A multi‐organ analysis of the role of <scp>mTOR</scp> in fetal alcohol spectrum disorders

Abstract: Alcohol exposure during gestation can lead to fetal alcohol spectrum disorders (FASD), an array of cognitive and physical developmental impairments. Over the past two and a half decades, Mammalian Target of Rapamycin (mTOR) has emerged at the nexus of many fields of study, and has recently been implicated in FASD etiology. mTOR plays an integral role in modulating anabolic and catabolic activities, including protein synthesis and autophagy. These processes are vital for proper development and can have long lasting effects following alcohol exposure, such as impaired hippocampal and synapse formation, reduced brain size, as well as cognitive, behavioral, and memory impairments. We highlight recent advances in the field of FASD, primarily with regard to animal model discoveries and discuss the interaction between alcohol and mTOR in the context of various tissues, including brain, placenta, bone, and muscle, with respect to developmental alcohol exposure paradigms. The current review focuses on novel FASD research within the context of the mTOR signaling and sheds light on mechanistic etiologies at various biological levels including molecular, cellular, and functional, across multiple stages of development and illuminates the dichotomy between the different mTOR complexes and their unique signaling roles.

Sexual Harassment

Abstract: Abstract Sexual harassment is widely recognized as a serious problem in the workplace, and a nuanced understanding of it is a necessary precondition to effective management. Much of the social science literature contends that sexual harassment is “not about sex but about power.” An evolutionary perspective, though acknowledging the link between sex and power, suggests that the causal implication of social scientists is often backward and that much behavior that is labeled sexual harassment reflects the different sexual strategies of males and females. It is less that men use sex to obtain power over women than it is that they use power to obtain sex, as they have throughout our evolutionary history. The fact that harassers tend to prefer young, attractive targets—that is, those who possess traits that are desirable in a consensual partner—reinforces the view that they are acting on sexual motivations. An understanding of the different sexual psychologies of males and females also sheds light on the question whether a reasonable-person standard or a reasonable-woman standard should be used to assess whether an environment is a hostile one. Men and women often perceive situations differently because of their evolved psychologies, so that an androgynous reasonable-person standard makes little sense. An evolutionary perspective, with its more realistic explanation of sexual harassment than its purely sociological competitors, is more likely to lead to effective mechanisms to combat it.

Assessing Rural-Urban Differences in Screening for Mental Health Needs Among Individuals in County Jails

Abstract: Rural jails are increasingly contributing to the overall jail population and little is known about how they differ from non-rural jails. This study compares demographic, behavioral health and criminal/legal histories of 3,797 individuals who booked into three rural jails and seven non-rural jails. In addition, the study assessed how jails identify mental illness, which was compared to an objective screening instrument (Kessler-6). Individuals in rural jails were more likely to be white, female, have a history of mental health services, misuse substances, and to recidivate. After controlling for these differences, they had 1.5 times greater odds of having a mental illness but lower odds of being identified by the jails. Individuals in rural jails have more behavioral health needs and other criminogenic risk factor and their needs are less likely to be identified by jail staff, which may result in poor connection to diversion or treatment opportunities.

Vascular cell-adhesion molecule 1 (VCAM-1) regulates JunB-mediated IL-8/CXCL1 expression and pathological neovascularization

Abstract: Vascular adhesion molecules play an important role in various immunological disorders, particularly in cancers. However, little is known regarding the role of these adhesion molecules in proliferative retinopathies. We observed that IL-33 regulates VCAM-1 expression in human retinal endothelial cells and that genetic deletion of IL-33 reduces hypoxia-induced VCAM-1 expression and retinal neovascularization in C57BL/6 mice. We found that VCAM-1 via JunB regulates IL-8 promoter activity and expression in human retinal endothelial cells. In addition, our study outlines the regulatory role of VCAM-1-JunB-IL-8 signaling on retinal endothelial cell sprouting and angiogenesis. Our RNA sequencing results show an induced expression of CXCL1 (a murine functional homolog of IL-8) in the hypoxic retina, and intravitreal injection of VCAM-1 siRNA not only decreases hypoxia-induced VCAM-1-JunB-CXCL1 signaling but also reduces OIR-induced sprouting and retinal neovascularization. These findings suggest that VCAM-1-JunB-IL-8 signaling plays a crucial role in retinal neovascularization, and its antagonism might provide an advanced treatment option for proliferative retinopathies.

Globally convergent coderivative-based generalized Newton methods in nonsmooth optimization

Abstract: This paper proposes and justifies two globally convergent Newton-type methods to solve unconstrained and constrained problems of nonsmooth optimization by using tools of variational analysis and generalized differentiation. Both methods are coderivative-based and employ generalized Hessians (coderivatives of subgradient mappings) associated with objective functions, which are either of class $${{\mathcal {C}}}^{1,1}$$ , or are represented in the form of convex composite optimization, where one of the terms may be extended-real-valued. The proposed globally convergent algorithms are of two types. The first one extends the damped Newton method and requires positive-definiteness of the generalized Hessians for its well-posedness and efficient performance, while the other algorithm is of the regularized Newton-type being well-defined when the generalized Hessians are merely positive-semidefinite. The obtained convergence rates for both methods are at least linear, but become superlinear under the semismooth $$^*$$ property of subgradient mappings. Problems of convex composite optimization are investigated with and without the strong convexity assumption on smooth parts of objective functions by implementing the machinery of forward–backward envelopes. Numerical experiments are conducted for Lasso problems and for box constrained quadratic programs with providing performance comparisons of the new algorithms and some other first-order and second-order methods that are highly recognized in nonsmooth optimization.

Recent surgical advances and continued controversies in medically refractory Meniere's disease

Abstract: Meniere's disease is caused by hydropic changes in the endolymphatic system, and manifests as a collection of vertigo, hearing loss, tinnitus, and aural fullness. Although high-quality clinical practice guidelines exist for the diagnosis and initial management of Meniere's disease, there is no strong consensus for treatment of medically refractory Meniere's disease. This review summarizes treatment options and highlights controversies surrounding surgical treatment of Meniere's disease.Intratympanic steroid and intratympanic gentamicin injections continue to be widely used as in-office therapies in medically refractory Meniere's disease. Despite historical controversy surrounding the use of endolymphatic sac (ELS) surgery, the use of ELS decompression has been widely adopted by the international neurotologic community due to high vertigo control rate, coupled with low risk of audiovestibular loss. Wider decompression of the sac and surgical manipulation of the endolymphatic duct may impact outcome and are the subject of discussion. An emerging surgical technique called Triple Semicircular Canal Occlusion (TSCO) holds promise as a partially ablative procedure with high vertigo control rate in Meniere's disease. Cochlear implants may be placed in active Meniere's disease patients, or during an ablative surgery such as labyrinthectomy.For the medically refractory Meniere's disease patient, treatment options include intratympanic steroid injection, endolymphatic sac decompression, medical or surgical labyrinthectomy, and vestibular nerve section. TSCO holds promise as an emerging partially ablative procedure. Cochlear implants maintain an important role in the rehabilitation of hearing loss associated with Meniere's disease.

An Atypical Presentation of Kawasaki Disease and Potential Markers for Diagnosis

Abstract: Cervical lymphadenopathy is seldom the initial symptom of Kawasaki disease (KD), making diagnosis difficult in early node-first Kawasaki disease (NFKD). Early treatment is important to prevent cardiovascular sequelae. This report discusses a case of a 4-year-old African American female with NFKD and retropharyngeal phlegmon who was initially treated with antibiotics for cervical lymphadenitis. She later developed classic symptoms of KD, including mucositis, conjunctivitis, palmar erythema, and truncal rash. KD was then suspected and treated appropriately, with the patient experiencing rapid clinical improvement. Early misdiagnosis of NFKD is not uncommon, but certain indices, such as patient age, elevated absolute neutrophil count, or elevated liver enzymes, may be helpful in increasing clinical suspicion. NFKD and retropharyngeal phlegmon remain a rare presentation of an already known condition. The case presented here emphasizes the need for KD to be a differential diagnosis in cases of cervical lymphadenitis and retropharyngeal abscess refractory to antibiotic treatment.

Risk Factors Associated with Simultaneous Use of Alcohol and Prescription Opioids Among Young Adults in Michigan

Abstract: Purpose: Alcohol can have serious side effects alone and can enhance the side effects of prescription opioids in unpredictable and dangerous ways. This study aims to identify risk factors for simultaneous use of alcohol and prescription opioids among young adults. Methods: Demographic characteristics, substance use, mental well-being, other substance-related factors, and simultaneous use of alcohol and prescription opioids were utilized to run multiple logistic regression analysis ( N = 1751; aged 18–25). Results: Mental well-being ( OR = 0.971, p = .003) and education level ( OR = 0.383, p < .001) were associated with a lower likelihood of simultaneous use. Knowing someone who had a fatal overdose ( OR = 2.443, p < .001), binge drinking ( OR = 1.065, p = .012), and older age ( OR = 1.250, p < .001) were associated with a greater likelihood of simultaneous use. Conclusion: The risk and protective factors identified in the current study point to specific areas for intervention to reduce simultaneous use. Further efforts are needed to minimize the increasing polysubstance-involved overdose mortality among young adults.

A Qualitative Examination of the Detroit Community Food Response to COVID-19

Abstract: The COVID-19 pandemic increased the need for food assistance due to surging unemployment, the closure of in-person schooling, and other factors. This posed a historic challenge to organizations that address food insecurity: meeting the surging need for food while minimizing COVID-19 transmission. This study aimed to identify how food insecurity program operations changed during the pandemic and to examine the facilitators/successes and barriers/challenges to operations. Semi-structured interviews were conducted with staff at 13 organizations involved in addressing food insecurity in Detroit during the pandemic. Interviews were coded by two coders, summarized, and then used to create matrices and concept map displays for each organization. We found that nearly all programs changed to a contactless food distribution format, and most programs experienced an increase in demand for food. Common successes/facilitators included keeping clients and staff safe from COVID-19 and waivers that eased program rules. Common challenges/barriers included the increased need for labor and food. Lack of funding was a barrier for some organizations, and others that experienced an increase in funding reported that it facilitated their work. This research identified the needs of programs addressing food insecurity during the COVID-19 pandemic, which can inform future disaster planning.

Representation, participation, and influence: Comparing Native American advocacy with organized interests at the federal level

Abstract: American Indians occupy a unique space in U.S. politics because they act as governments, businesses, and citizen groups. Yet studies of organized interests and intergovernmental lobbies rarely mention them. This study draws on original research on reported lobbying, reported lobbying expenditures, and advocacy efforts by tribal governments and organizations at the congressional hearing level. It compsares lobbying, lobbying expenditures, and congressional testimony by American Indians to that of organized interests and state and local governments to determine how well represented and successful Natives are in the legislative process. It finds that tribal governments and Native organizations lobby extensively on Indian affairs but constitute only a small portion of all lobbying, spend considerably less on lobbying than businesses and trade associations, and experience the most success in the legislative process when they unify in opposition to federal legislation.

Dividing Authority Three Ways: Federal–Tribal–State Relations after <i>Oklahoma v. Castro-Huerta</i>

Abstract: Abstract The U.S. Supreme Court’s decision in Oklahoma v. Castro-Huerta has the potential to rework the long-standing division of authority among federal, state, and tribal governments. In issuing its decision in this June 2022 case, the majority departed from its previous decisions and congressional policy by enabling state governments to exercise criminal authority over non-Indians in Indian Country. This article examines the implications of Castro-Huerta for federal, tribal, and state governments on the ground in Indian Country as well as for scholarship and teaching on federal–tribal–state relations.

Diagnostic algorithm for sleep-related breathing disorders

Abstract: The diagnostic approach to sleep-related breathing disorders (SRBD), including obstructive sleep apnea hypopnea syndrome (OSAHS) begins with a comprehensive sleep evaluation that includes a complete sleep history and a physical examination focused on the upper airway. If the evaluation suggests a SRBD as the cause of the patient's symptoms, diagnostic testing should be performed. Patients at high risk for OSAHS can be studied by either portable monitoring (if available) or in-laboratory polysomnography. Patients with a lower risk for OSAHS, or have risk factors for a different SRBD (such as central sleep apnea) or have a negative portable monitoring study should be studied in a sleep laboratory. Sleep-related breathing disorders (SRBDs) are increasingly associated with a large variety of outcomes, particularly excessive daytime sleepiness, cognitive dysfunction, and cardiovascular morbidity and mortality. With growing evidence that treatment of SRBDs can ameliorate these negative outcomes, the early recognition and diagnosis of SRBDs are essential. Thus, the timely diagnosis of SRBDs requires the physician to take a careful history, perform a careful physical examination, and refer the patient for appropriate testing. This article provides an overview of the diagnostic algorithm for SRBDs.