Psychological distress over 12 months post-diagnosis in an early inflammatory arthritis cohort.

OBJECTIVES: People with inflammatory arthritis (IA) experience worsened mental wellbeing alongside disease progression. Using the National Early Inflammatory Arthritis Audit (NEIAA), we assessed trends in psychological distress during 12-months following IA diagnosis, mapping these against clinical outcomes to identify associations. METHODS: This is a prospective study of people recruited to NEIAA receiving an IA diagnosis and completing the baseline patient survey. Patient reported outcomes (PROs) at baseline, 3-months and 12-months were collected, including psychological distress (assessed using Patient Health Questionnaire Anxiety and Depression Screener (PHQ4ADS)). Mixed effects linear regression models estimated associations between predictor variables with psychological distress at baseline and over time. RESULTS: Of 6,873 eligible patients, 3,451 (50.2%) showed psychological distress at baseline. Of those completing follow-ups, 30.0% and 24.1% were distressed at 3-months and 12-months, respectively. Higher psychological distress at diagnosis was more commonly reported by younger, female, and non-white patients. Clinical factors, including higher counts of comorbidities, prior depression, and higher disease activity at diagnosis were associated with higher distress. Higher distress at baseline was associated with poorer outcomes over time in quality of life, disability, work performance, disease activity, as well as reduced likelihood of achieving good treatment response by EULAR criteria. CONCLUSION: Half of patients with IA show significant mental health comorbidity at presentation, which associated with worse disease outcomes and quality of life. Screening for anxiety and depression should be a universal standard, and access to effective mood therapies alongside arthritis treatments is essential. Strategies should be culturally valid and consider multi-morbidities.

Information needs of Lynch syndrome and BRCA 1/2 mutation carriers considering risk-reducing gynecological surgery: a qualitative study of the decision-making process.

BACKGROUND: Risk-reducing gynecological surgery (RRGS) is a prophylactic procedure that may be offered to BRCA1, BRCA2, and Lynch syndrome (LS) mutation carriers to reduce the risk of developing gynecological cancer. This study was conducted to better understand patients' information needs and evaluate how patients weigh different sources of information in their decision-making process surrounding RRGS. METHODS: This study used a qualitative approach to understanding women's perspectives towards RRGS. Semi-structured interviews were conducted virtually with 8 women. Women offered RRGS between 35 and 70 years of age who are English-speaking and have an identifiable BRCA or LS mutation were included. Data from interviews was coded with constant comparative analysis to develop themes. RESULTS: Of the eight women, six had selected to undergo either prophylactic hysterectomy or oophorectomy: 5 decided yes to RRGS; 1 decided no; 2 were undecided. Thematic analysis found that the key factors affecting women's decisions around prophylactic surgery were cancer risk, surgical menopause, and psychological readiness. To make an informed decision, women relied most heavily on information provided by healthcare professionals (e.g. doctors, genetic counselors) and family members with prior cancer experience. However, some women reported that they did not feel adequately informed enough to make a decision and identified COVID-19 as a significant barrier affecting access to information. CONCLUSION: This qualitative study revealed the key sources of information influencing attitudes regarding RRGS and how women consulted different sources of information to reach a decision. Results underscore the need for greater attention to women's information needs in the context of psychological readiness, particularly amidst the pandemic. Research involving a larger sample size may help to better inform how support can be provided to individuals with BRCA and LS mutations considering RRGS.

Public health and clinical implications of Dobbs v. Jackson for patients and healthcare providers: A scoping review.

INTRODUCTION: On June 24, 2022, the U.S. Supreme Court's decision in Dobbs v. Jackson reversed the precedent set forth by Roe v. Wade, empowering individual states to regulate abortion care. This aftermath of this ruling has given rise to widespread bans, limiting the accessibility of abortion services for patients and impeding providers' ability to deliver a comprehensive spectrum of reproductive health services. Of particular concern is the disproportionate impact on medically underserved groups, further heightening existing social and structural disparities in reproductive health. METHODS: We conducted a scoping review to broadly evaluate the clinical and public health impact of Dobbs on patients' access to abortion care and related reproductive health services, in addition to the training and clinical practice of healthcare providers. We searched eight bibliographic databases (PubMed, Scopus, Embase, PsycINFO, Google Scholar, Science Direct, JSTOR, and Web of Science) and three preprint servers (medRxiv, bioRxiv, and Europe PMC) using various combinations of keywords related to 'abortion', 'Dobbs', and 'Roe' on March 22, 2023. Four reviewers independently screened the studies based on pre-specified eligibility criteria and one reviewer performed data extraction for pre-identified themes. The search was conducted based on PRISMA Extension for Scoping Reviews (PRSIMA-ScR) guidelines. RESULTS: Eighteen studies, comprising 12 peer-reviewed articles and 6 study abstracts, met the inclusion criteria. The studies demonstrated that Dobbs increased demand for contraception, magnified existing travel- and cost-related barriers to access, further polarized views on abortion and complex family planning on social media (e.g., Twitter), and evoked substantial concerns among medical trainees regarding their scope of practice and potential legal repercussions for providing abortion care. CONCLUSION: In the wake of Dobbs v. Jackson, further public health and clinical interventions are urgently needed to bridge disparities in abortion care and reproductive health, mitigating the deleterious consequences of this emerging public health crisis.

Printing of In Situ Functionalized Mesoporous Silica with Digital Light Processing for Combinatorial Sensing.

Combinatorial sensing is especially important in the context of modern drug development to enable fast screening of large data sets. Mesoporous silica materials offer high surface area and a wide range of functionalization possibilities. By adding structural control, the combination of structural and functional control along all length scales opens a new pathway that permits larger amounts of analytes being tested simultaneously for complex sensing tasks. This study presents a fast and simple way to produce mesoporous silica in various shapes and sizes between 0.27-6 mm by using light-induced sol-gel chemistry and digital light processing (DLP). Shape-selective functionalization of mesoporous silica is successfully carried out either after printing using organosilanes or in situ while printing through the use of functional mesopore template for the in situ functionalization approach. Shape-selective adsorption of dyes is shown as a demonstrator toward shape selective screening of potential analytes.

Primary prevention of venous thromboembolism for cancer patients in randomized controlled trials: a bibliographical analysis of funding and trial characteristics.

Background: The majority of randomized controlled trials (RCTs) investigating venous thromboembolism (VTE) prophylaxis in patients with cancer involve commercial sponsorship. Commercial sponsorship overcomes feasibility limitations inherent in RCTs, such as recruitment and funding, but has attracted scrutiny for its potential for bias. Objectives: In RCTs of VTE prophylaxis in patients with cancer, how do trial characteristics compare between commercially sponsored RCTs and noncommercially sponsored RCTs? Methods: Medline, Embase, and Cochrane Central Register of Controlled Trials were searched for RCTs that investigated at least 1 pharmacologic intervention for VTE prophylaxis in adult patients with cancer. Screening and data extraction were conducted by independent reviewers. Outcomes included trial characteristics, reporting of favorable outcomes, protocol-manuscript discrepancies, and appraisal of spin. Outcomes were compared using the independent t-test, Mann-Whitney U-test, Pearson chi-squared test, and Fisher's exact test. Logistic regression was performed to identify factors associated with possible bias. Results: Of the 54 trials analyzed, 34 (63%) reported commercial sponsorship. Commercial sponsorship was not associated with the reporting of favorable outcomes, presence of spin, retrospective registration, or protocol-manuscript discrepancy. Spin was most prevalent in the abstract conclusions (9 out of 17 [53.3%]) and manuscript conclusions (8 out of 17 [46.7%]).Commercially sponsored trials had a higher rate of intention-to-treat analysis. Noncommercially sponsored trials were more likely to report retrospective registration of trial protocol and the use of composite primary outcomes. Conclusion: There were few significant differences between trial characteristics, suggesting that the evidence from commercially sponsored trials investigating VTE prophylaxis in patients with cancer is unlikely to be subject to bias attributable to commercial sponsorship.

Acute Dystonic Reaction After Propofol Administration: A Pediatric Case Report.

We present a case of a 12-year-old female with a history of infantile spasms who developed a propofol-associated acute dystonic reaction after emergence from general anesthesia for foot surgery. Uniquely, the patient's postoperative symptoms of an acute dystonic reaction were refractory to standard treatment with anticholinergics but were successfully treated with corticosteroids. The absence of any dystonic symptoms following subsequent foot surgery under general anesthesia without propofol supported a propofol-associated etiology. This case may contribute to a better understanding of the underlying mechanisms of propofol-associated acute dystonic reactions and adds a possible new treatment option.

Therapeutic role of curcumin in adult neurogenesis for management of psychiatric and neurological disorders: a scientometric study to an in-depth review.

Aberrant neurogenesis is a major factor in psychiatric and neurological disorders that have significantly attracted the attention of neuroscientists. Curcumin is a primary constituent of curcuminoid that exerts several positive pharmacological effects on aberrant neurogenesis. First, it is important to understand the different processes of neurogenesis, and whether their dysfunction promotes etiology as well as the development of many psychiatric and neurological disorders; then investigate mechanisms by which curcumin affects neurogenesis as an active participant in pathophysiological events. Based on scientometric studies and additional extensive research, we explore the mechanisms by which curcumin regulates adult neurogenesis and in turn affects psychiatric diseases, i.e., depression and neurological disorders among them traumatic brain injury (TBI), stroke, Alzheimer's disease (AD), Gulf War Illness (GWI) and Fragile X syndrome (FXS). This review aims to elucidate the therapeutic effects and mechanisms of curcumin on adult neurogenesis in various psychiatric and neurological disorders. Specifically, we discuss the regulatory role of curcumin in different activities of neural stem cells (NSCs), including proliferation, differentiation, and migration of NSCs. This is geared toward providing novel application prospects of curcumin in treating psychiatric and neurological disorders by regulating adult neurogenesis.

Adaptive responsivity: a Youth-Driven Model for Thriving in Foster Care.

With notable and growing exceptions, there is a dearth of research on mechanisms by which youth in foster care build resilience and achieve positive outcomes. We report on data from an interview study with young adults exiting or recently exited foster care in Maryland (N=15) designed to understand what facilitates their engagement with courts. Our findings indicate that despite challenges of ?being in foster care?, youth found ways to pursue their goals and make their voices heard through developing stable relationships with supportive adults (including judges, caseworkers, or lawyers) and demanding that child welfare professionals ?speak to me not at me.? Youth indicated that their needs, capabilities, and goals changed as they matured and as their circumstances changed. Such changes helped them find their voices but also created tensions within their child welfare system interactions. This led us to develop the theory of adaptive responsivity, according to which child welfare stakeholders should respond appropriately to developmental and circumstantial changes to help child-welfare involved youth face difficult circumstances and thrive. Such responses include providing developmentally and situationally appropriate information and decision-making power to youth in their own cases as well as opportunities to weigh in on systems change.

Physiology of Glymphatic Solute Transport and Waste Clearance from the Brain.

This review focuses on the physiology of glymphatic solute transport and waste clearance, using evidence from experimental animal models as well as from human studies. Specific topics addressed include the biophysical characteristics of fluid and solute transport in the central nervous system, glymphatic-lymphatic coupling, as well as the role of cerebrospinal fluid movement for brain waste clearance. We also discuss the current understanding of mechanisms underlying increased waste clearance during sleep.

Sustained correction of hippocampal neurogenic and cognitive deficits after a brief treatment by Nutlin-3 in a mouse model of fragile X syndrome.

BACKGROUND: Fragile X syndrome (FXS), the most prevalent inherited intellectual disability and one of the most common monogenic forms of autism, is caused by a loss of fragile X messenger ribonucleoprotein 1 (FMR1). We have previously shown that FMR1 represses the levels and activities of ubiquitin ligase MDM2 in young adult FMR1-deficient mice, and treatment by a MDM2 inhibitor Nutlin-3 rescues both hippocampal neurogenic and cognitive deficits in FMR1-deficient mice when analyzed shortly after the administration. However, it is unknown whether Nutlin-3 treatment can have long-lasting therapeutic effects. METHODS: We treated 2-month-old young adult FMR1-deficient mice with Nutlin-3 for 10 days and then assessed the persistent effect of Nutlin-3 on both cognitive functions and adult neurogenesis when mice were 6-month-old mature adults. To investigate the mechanisms underlying the persistent effects of Nutlin-3, we analyzed the proliferation and differentiation of neural stem/progenitor cells isolated from these mice and assessed the transcriptome of the hippocampal tissues of treated mice. RESULTS: We found that transient treatment with Nutlin-3 of 2-month-old young adult FMR1-deficient mice prevents the emergence of neurogenic and cognitive deficits in mature adult FXS mice at 6 months of age. We further found that the long-lasting restoration of neurogenesis and cognitive function might not be mediated by changing intrinsic properties of adult neural stem cells. Transcriptomic analysis of the hippocampal tissue demonstrated that transient Nultin-3 treatment leads to significant expression changes in genes related to the extracellular matrix, secreted factors, and cell membrane proteins in the FMR1-deficient hippocampus. CONCLUSIONS: Our data indicates that transient Nutlin-3 treatment in young adults leads to long-lasting neurogenic and behavioral changes likely through modulating adult neurogenic niche that impact adult neural stem cells. Our results demonstrate that cognitive impairments in FXS may be prevented by an early intervention through Nutlin-3 treatment.

Sustained glymphatic transport and impaired drainage to the nasal cavity observed in multiciliated cell ciliopathies with hydrocephalus.

BACKGROUND: Hydrocephalus (increased ventricular size due to CSF accumulation) is a common finding in human ciliopathies and in mouse models with genetic depletion of the multiciliated cell (MCC) cilia machinery. However, the contribution of MCC to CSF dynamics and, the mechanism by which impaired MCC function leads to hydrocephalus remains poorly understood. The aim of our study was to examine if defects in MCC ciliogenesis and cilia-generated CSF flow impact central nervous system (CNS) fluid homeostasis including glymphatic transport and solute waste drainage. METHODS: We used two distinct mouse models of MCC ciliopathy: MCC-specific CEP164 conditional knockout mice (FOXJ1-Cre;CEP164fl/fl (N = 10), 3-month-old) and p73 knock-out (p73-/- (N = 8), 5-month-old) mice. Age-matched, wild-type littermates for each of the mutants served as controls. Glymphatic transport and solute drainage was quantified using in vivo T1 mapping by magnetic resonance imaging (MRI) after CSF infusion of gadoteric acid. Brain morphometry and aquaporin 4 expression (AQP4) was also assessed. Intracranial pressure (ICP) was measured in separate cohorts. RESULTS: In both of the two models of MCC ciliopathy we found the ventriculomegaly to be associated with normal ICP. We showed that FOXJ1-Cre;CEP164fl/fl mice with hydrocephalus still demonstrated sustained glymphatic transport and normal AQP4 expression along capillaries. In p73-/- mice glymphatic transport was even increased, and this was paralleled by an increase in AQP4 polarization around capillaries. Further, solute drainage via the cribriform plate to the nasal cavity was severely impaired in both ciliopathy models and associated with chronic rhinitis and olfactory bulb hypoplasia. CONCLUSIONS: The combination of sustained glymphatic transport, impaired solute drainage via the cribriform plate to the nasal cavity and hydrocephalus has not previously been reported in models of MCC ciliopathy. Our data enhance our understanding of how different types of ciliopathies contribute to disruption of CNS fluid homeostasis, manifested in pathologies such as hydrocephalus.

Puerarin action on stem cell proliferation, differentiation and apoptosis: Therapeutic implications for geriatric diseases.

BACKGROUND: Aging is associated with a decline in cognitive and physical functions and various geriatric diseases, such as cardiovascular and neurodegenerative diseases. Puerarin (Pue), one of the main active flavonoids of Radix Puerariae (R. pueraria), is reportedly effective in treating geriatric diseases, including cardiovascular disease and hypertension. PURPOSE: This review aims to summarize and discuss the profound physiological impact of Pue on various stem cell populations and provide new insights into the use of Pue for the prevention and treatment of geriatric diseases. METHODS: The literature was retrieved from the core collection of electronic databases, such as Web of Science, Google Scholar, PubMed, and Science Direct, using the following keywords and terms: Puerarin, Stem Cell, Proliferation, Differentiation, Apoptosis, and Geriatric diseases. These keywords were used in multiple overlapping combinations. RESULTS: Pue is effective in the treatment and management of age-related diseases, such as cardiovascular disease, diabetes, hypertension, and cerebrovascular disease. Pue exerts significant physiological effects on various stem cell populations, including their self-renewal/proliferation, differentiation and apoptosis. Most importantly, it could improve the efficiency and accuracy of stem cell therapy for treating various geriatric diseases. Further studies are essential to improve our understanding of the underlying mechanisms and elucidate their significance for future clinical applications. CONCLUSION: The effects of Pue on various stem cell populations and their regulatory mechanisms are discussed in detail to provide new insights into the use of Pue in the prevention and treatment of geriatric diseases.

Simultaneous Nanolocal Polymer and In Situ Readout Unit Placement in Mesoporous Separation Layers.

Bioinspired solid-state nanopores and nanochannels have attracted interest in the last two decades, as they are envisioned to advance future sensing, energy conversion, and separation concepts. Although much effort has been made regarding functionalization of these materials, multifunctionality and accurate positioning of functionalities with nanoscale precision still remain challenging. However, this precision is necessary to meet transport performance and complexity of natural pores in living systems, which are often based on nonequilibrium states and compartmentalization. In this work, a nanolocal functionalization and simultaneous localized sensing strategy inside a filtering mesoporous film using precisely placed plasmonic metal nanoparticles inside mesoporous films with pore accessibility control is demonstrated. A single layer of gold nanoparticles is incorporated into mesoporous thin films with precise spatial control along the nanoscale layer thickness. The local surface plasmon resonance is applied to induce a photopolymerization leading to a nanoscopic polymer shell around the particles and thus nanolocal polymer placement inside the mesoporous material. As near-field modes are sensitive to the dielectric properties of their surrounding, the in situ sensing capability is demonstrated using UV-vis spectroscopy. It is demonstrated that the sensing sensitivity only slightly decreases upon functionalization. The presented nanolocal placement of responsive functional polymers into nanopores offers a simultaneous filtering and nanoscopic readout function. Such a nanoscale local control is envisioned to have a strong impact onto the development of new transport and sensor concepts, especially as the system can be developed into higher complexity using different metal nanoparticles and additional design of mesoporous film filtering properties.

Capsaicin on stem cell proliferation and fate determination - a novel perspective.

Capsaicin (CAP), a member of the vanilloid family, is the main active component of chili peppers, which has been widely explored for its various pharmacological effects and influence on cell physiology, such as axonal growth and apoptosis of tumor cells. In particular, CAP plays a crucial role in determining the proliferation and fate specification of stem cells by modulating a variety of signaling pathways, such as PPARγ, C/EBPα and Notch signaling. Since CAP-mediated processes are complex and multifactorial, we hope to achieve a better understanding of these processes and their implications in clinical applications. This review aims to shed light on the influences and mechanisms of CAP on the actions of various stem cells in adults and discusses the role of CAP in the different process of stem cell behaviors, including proliferation and differentiation. Our purpose is to provide certain prospects for the application of CAP and stem cell therapy in treating diseases.

Ozone Decreased Enteric Methane Production by 20% in an in vitro Rumen Fermentation System.

Ozone (O3) is volatile, highly oxidative, and has theoretical potential to reduce ruminant enteric methanogenesis by interactions between archaea and bacteria, and substrate and oxygen. The effects of O3 on the rumen microbiota, fermentation parameters, and CH4 emissions were studied through in vitro fermentation using a RUSITEC apparatus with O3 dissolved in the salivary buffer. The substrate consisted of maize silage or grain concentrates, and the treatments were (1) control (no O3) and (2) O3 at 0.07 ± 0.022 mg/L in the buffer. A 4-day adaptation period followed by a 6-day experimental period was used for measuring gas production and composition, as well as fermentation characteristics, which included ruminal volatile fatty acids (VFA) and liquid- and solid-associated microbial communities. Ozone treatment decreased total gas production by 15.4%, most notably CH4 production by 20.4%, and CH4 gas concentration by 5.8%, without compromising dry matter digestibility (DMD) of either maize silage or grain concentrates. There were no significant effects of O3 treatment on VFA production or pH. Ozone treatment reduced the relative abundance of methanogens, particularly Methanomicrobium. This study demonstrates the potential use of O3 as a method to reduce ruminant enteric methanogenesis.

Establishing essential cardiopulmonary physiotherapy services in acute care settings in China.

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Recent trends in nanopore polymer functionalization.

Functional nanopores play an essential role in many biotechnological applications such as sensing, or drug delivery. Prominent examples are polymer functionalized ceramic or solid state nanopores. Intensive research efforts led to a discovery of a plethora of polymer functionalized nanopores demonstrating gated molecular transport upon basically all common stimuli. Nevertheless, nature's biological pore transport precision is unreached. This can be, among others, ascribed to limits in design precision especially with respect to functionalization. Recent trends in polymer functionalized nanopores address the role of confinement and polymerization control, strategies toward more sustainable reaction conditions, such as visible light initiation and strategies toward nanoscale local placement of polymer functionalization. The resulting multi-stimuli responsive nanopore performance enables concerted release or transport, side selective separation and selective detection.

Benzimidazole-2-pyrazole HIF Prolyl 4-Hydroxylase Inhibitors as Oral Erythropoietin Secretagogues.

HIF prolyl 4-hydroxylases (PHD) are a family of enzymes that mediate key physiological responses to hypoxia by modulating the levels of hypoxia inducible factor 1-α (HIF1α). Certain benzimidazole-2-pyrazole carboxylates were discovered to be PHD2 inhibitors using ligand- and structure-based methods and found to be potent, orally efficacious stimulators of erythropoietin secretion in vivo.

Benzazoles as allosteric potentiators of metabotropic glutamate receptor 2 (mGluR2): efficacy in an animal model for schizophrenia.

Metabotropic glutamate receptor 2 (mGluR2) has been implicated in a variety of CNS disorders, including schizophrenia. Disclosed herein is the development of a new series of allosteric potentiators of mGluR2. Structure-activity relationship studies in conjunction with pharmacokinetic data led to the discovery of indole 5, which is active in an animal model for schizophrenia.