Drug therapy in juvenile spondyloarthritis.

PURPOSE OF REVIEW: This review summarizes latest developments in treatment of juvenile spondyloarthritis (JSpA), specifically enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA). RECENT FINDINGS: There has been addition of biologic disease modifying antirheumatic drugs (bDMARDs) beyond tumor necrosis factor inhibitors (TNFi) for JSpA such as IL-17 blockers, IL-23 blockers, and janus activating kinase inhibitors with favorable safety profile. Conducting robust clinical trials for this subpopulation of JIA remains a challenge; extrapolation studies are being used to obtain approval from regulatory agencies. SUMMARY: Newer drug therapies have expanded the scope of treatment for patients with JSpA. bDMARDs such as adalimumab, etanercept, infliximab, and secukinumab have demonstrated clinically significant treatment efficacy in ERA and JPsA. Based on extrapolation studies, intravenous golimumab, etanercept, abatacept, and ustekinumab have gained Food and Drug Administration (FDA) approval for JPsA. Long-term follow-up studies continue to demonstrate acceptable safety profiles. There is need for more real-world data on drug efficacy from Registry studies and research on effective de-escalation strategies.

The hole in my heart is closing: Indigenous relative reunification identity verification.

OBJECTIVE: The current study explored the experience of reunification as place identity verification for Indigenous individuals who were fostered/adopted as youth. BACKGROUND: Research on reunification tends to focus on disproportionality in child welfare and the factors associated with reunification. Few studies focus on experiences of reunification among Indigenous individuals including their perceptions and comprehensions about the reunification experience. METHOD: Data from 70 fostered/adopted Indigenous individuals that reunified during adulthood were analyzed from the Experiences of Adopted and Fostered Individuals Project. Inductive thematic analysis was used to examine open-ended survey data about experience of reunification. RESULTS: Three themes inductively emerged including: (1) relative reunification, (2) perceptions about reunification, and (3) comprehensions about reunification. During relative reunification, participants reunified with parent(s), extended caregiver(s), grandparent(s), sibling(s), cousin(s), niece(s)/nephew(s), and tribe. Participant's perceptions about reunification included happiness, relief, anger, mourning, and anxiety/excitement. Participant's comprehensions about reunification related to belonging, sense of place, history/heritage, healing, and resemblance. All five functions of place identity verification were met in reunification according to the Indigenous participant's voices. CONCLUSIONS: This study explored the experience of relative reunification of Indigenous individuals who were separated from their families of origin during childhood by foster care and adoption.

Longing to belong: The ambiguous loss of Indigenous fostered/adopted individuals.

BACKGROUND: Indigenous fostered/adopted individuals report high levels of grief because of their foster care/adoption. Little has been done, however, to explore how grief is experienced and the factors that contribute to said grief for fostered/adopted Indigenous individuals. OBJECTIVE: This study examined the experiences of loss and grief of Indigenous individuals fostered/adopted during childhood. PARTICIPANTS AND SETTING: Participants were 102 Indigenous fostered/adopted individuals who described the experiences of loss and grief related to adoption. METHODS: This study utilized secondary data from the Fostered and Adopted Individuals Project. Inductive thematic analysis was conducted on open-ended survey data. RESULTS: Two themes emerged: (1) ambiguous loss as a result of foster care and adoption and (2) the effects of the ambiguous loss that stem from foster care and adoption. Indigenous fostered/adopted persons experienced ambiguous loss in foster care and adoption. Their loss remained unresolved due to a loss of access to information about their family and tribe of origin. Although family of origin, tribal community, and culture were not physically present due to separation by foster care/adoption, they remained psychologically present. As a result of ambiguous loss, participants experienced disenfranchised grief, wondering and longing to belong, and mental health and substance abuse. CONCLUSION: This study is the first of its kind to explore the loss and grief experiences of fostered/adopted Indigenous individuals using ambiguous loss theory. Ambiguous loss theory offers a framework for contextualizing the loss and grief that begins at separation and is present in adulthood.

Impact of Air Pollution on Atopic Dermatitis: A Comprehensive Review.

Air pollution is associated with multiple health problems worldwide, contributing to increased morbidity and mortality. Atopic dermatitis (AD) is a common allergic disease, and increasing evidence has revealed a role of air pollution in the development of atopic dermatitis. Air pollutants are derived from several sources, including harmful gases such as nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO), as well as particulate matter (PM) of various sizes, and bioaerosols. Possible mechanisms linking air pollution to atopic dermatitis include damage to the skin barrier through oxidative stress, increased water loss, physicochemical injury, and an effect on skin microflora. Furthermore, oxidative stress triggers immune dysregulation, leading to enhanced sensitization to allergens. There have been multiple studies focusing on the association between various types of air pollutants and atopic dermatitis. Since there are many confounders in the current research, such as climate, synergistic effects of mixed pollutants, and diversity of study population, it is not surprising that inconsistencies exist between different studies regarding AD and air pollution. Still, it is generally accepted that air pollution is a risk factor for AD. Future studies should focus on how air pollution leads to AD as well as effective intervention measures.

An Inter-professional Antiracist Curriculum Is Paramount to Addressing Racial Health Inequities.

Legal, medical, and public health professionals have been complicit in creating and maintaining systems that drive health inequities. To ameliorate this, current and future leaders in law, medicine, and public health must learn about racism and its impact along the life course trajectory and how to engage in antiracist practice and health equity work.

The duration of antibiotic treatment is associated with carriage of toxigenic and non-toxigenic strains of Clostridioides difficile in dogs.

Clostridioides difficile is a leading cause of human antibiotic-associated diarrhoeal disease globally. Zoonotic reservoirs of infection are increasingly suspected to play a role in the emergence of this disease in the community and dogs are considered as one potential source. Here we use a canine case-control study at a referral veterinary hospital in Scotland to assess: i) the risk factors associated with carriage of C. difficile by dogs, ii) whether carriage of C. difficile is associated with clinical disease in dogs and iii) the similarity of strains isolated from dogs with local human clinical surveillance. The overall prevalence of C. difficile carriage in dogs was 18.7% (95% CI 14.8-23.2%, n = 61/327) of which 34% (n = 21/61) were toxigenic strains. We found risk factors related to prior antibiotic treatment were significantly associated with C. difficile carriage by dogs. However, the presence of toxigenic strains of C. difficile in a canine faecal sample was not associated with diarrhoeal disease in dogs. Active toxin was infrequently detected in canine faecal samples carrying toxigenic strains (2/11 samples). Both dogs in which active toxin was detected had no clinical evidence of gastrointestinal disease. Among the ten toxigenic ribotypes of C. difficile detected in dogs in this study, six of these (012, 014, 020, 026, 078, 106) were ribotypes commonly associated with human clinical disease in Scotland, while nontoxigenic isolates largely belonged to 010 and 039 ribotypes. Whilst C. difficile does not appear commonly associated with diarrhoeal disease in dogs, antibiotic treatment increases carriage of this bacteria including toxigenic strains commonly found in human clinical disease.

The transition to teletherapy in marriage and family therapy training settings during COVID-19: What do the data tell us?

In the wake of the COVID-19 pandemic, little is known about how university training programs transitioned to teletherapy. This study describes the transition of two university marriage and family therapy (i.e., master's and doctoral) training clinics to teletherapy and presents preliminary analyses of the types of clients and cases that converted to teletherapy. A series of chi-square analyses, a t-test, a logistic regression model, and a multiple linear regression model were employed. Four key findings emerged: (1) most cases converted to teletherapy; (2) Hispanic ethnicity was the only demographic characteristic to significantly predict conversion to teletherapy; (3) individual cases were significantly more likely to convert to teletherapy than relational cases; and (4) the number of prior in-person sessions attended significantly predicted conversion to teletherapy. Teletherapy conversion implications are discussed across four systemic levels: client, student trainee, supervision, and larger systems.

Congenital dyserythropoietic anemia type I: First report from the Congenital Dyserythropoietic Anemia Registry of North America (CDAR).

Congenital dyserythropoietic anemias (CDAs) are characterized by ineffective erythropoiesis and distinctive erythroblast abnormalities; the diagnosis is often missed or delayed due to significant phenotypic heterogeneity. We established the CDA Registry of North America (CDAR) to study the natural history of CDA and create a biorepository to investigate the pathobiology of this heterogeneous disease. Seven of 47 patients enrolled so far in CDAR have CDA-I due to biallelic CDAN1 mutations. They all presented with perinatal anemia and required transfusions during infancy. Anemia spontaneously improved during infancy in three patients; two became transfusion-independent rapidly after starting interferon-α2; and two remain transfusion-dependent at last follow-up at ages 5 and 30 y.o. One of the transfusion-dependent patients underwent splenectomy at 11 y.o due to misdiagnosis and returned to medical attention at 27 y.o with severe hemolytic anemia and pulmonary hypertension. All patients developed iron overload even without transfusions; four were treated with chelation. Genetic testing allowed for more rapid and accurate diagnosis; the median age of confirmed diagnosis in our cohort was 3 y.o compared to 17.3 y.o historically. In conclusion, CDAR provides an organized research network for multidisciplinary clinical and research collaboration to conduct natural history and biologic studies in CDA.

Polypeptoid polymers: Synthesis, characterization, and properties.

Polypeptoids, a class of peptidomimetic polymers, have emerged at the forefront of macromolecular and supramolecular science and engineering as the technological relevance of these polymers continues to be demonstrated. The chemical and structural diversity of polypeptoids have enabled access to and adjustment of a variety of physicochemical and biological properties (eg, solubility, charge characteristics, chain conformation, HLB, thermal processability, degradability, cytotoxicity and immunogenicity). These attributes have made this synthetic polymer platform a potential candidate for various biomedical and biotechnological applications. This review will provide an overview of recent development in synthetic methods to access polypeptoid polymers with well-defined structures and highlight some of the fundamental physicochemical and biological properties of polypeptoids that are pertinent to the future development of functional materials based on polypeptoids.

Surgical Management of Ruptured Isolated Aneurysm of Artery of Adamkiewicz: Interesting Report and Overview of Literature.

BACKGROUND: Spinal subarachnoid hemorrhage due to rupture of an isolated spinal aneurysm is extremely rare. Patients usually present with symptoms and signs resulting from spinal cord compression. No standard guidelines are available for the treatment of this condition. CASE ILLUSTRATION: In this report we present the case of a 78-year-old Caucasian male who presented with sudden-onset back pain and bilateral lower extremity weakness. Spinal angiogram revealed an isolated aneurysm of the artery of Adamkiewicz. The aneurysm was successfully managed by surgical clipping, and the patient recovered well with rehabilitation. At 46 months' follow-up, the patient was able to ambulate and perform activities of daily living independently. CONCLUSION: Our case is the first description of surgical clipping of a ruptured isolated spinal aneurysm of the artery of Adamkiewicz with a long-term successful outcome and shows that it is a safe and feasible option in carefully selected patients.

Surgical Excision of a Symptomatic Thoracic Nerve Root Perineural Cyst Resulting in Complete Resolution of Symptoms: A Case Report.

Tarlov (perineural) cysts of the nerve root are common and usually incidental findings during magnetic resonance imaging (MRI) of the lumbosacral spine. There are a few case reports where symptomatic thoracic perineural cysts have been described in the literature. We report a case of a high thoracic nerve root perineural cyst that failed conservative therapy, requiring surgical intervention. Our patient presented with radicular symptoms involving the left hand. Imaging workup revealed a cystic lesion of the left T1 nerve root at the level of the foramen. Surgical resection resulted in significant improvement in patient symptoms, and pathology revealed a perineural cyst. We conclude that a thoracic perineural (Tarlov) cyst can be symptomatic by causing nerve root compression and can be mistaken as a nerve root sheath tumor on imaging. Surgical treatment can be curative.

Cationic Polypeptoids with Optimized Molecular Characteristics toward Efficient Nonviral Gene Delivery.

The rational design of gene vectors relies on the understanding of their structure-property relationship. Polypeptoids, which are structural isomers of natural polypeptides, hold great potential as gene delivery vectors due to their facile preparation, structural tunability, and most importantly, their desirable proteolytic stability. We herein designed a library of polypeptoids with different cationic side-chain terminal groups, degree of polymerizations (DPs), side-chain lengths, and incorporated aliphatic side chains, to unravel the structure-property relationships so that gene delivery efficiency can be maximized and cytotoxicity can be minimized. In HeLa cells, a polypeptoid bearing a primary amine side-chain terminal group exhibited remarkably higher transfection efficiency than that of its analogues containing secondary, tertiary, or quaternary amine groups. Elongation of the polypeptoid backbone length (from 28 to 251 mer) led to enhanced DNA condensation as well as cellular uptake levels, however it also caused higher cytotoxicity. Upon a proper balance between DNA uptake and cytotoxicity, the polypeptoid with a DP of 46 afforded the highest transfection efficiency. Elongating the aliphatic spacer between the backbone and side amine groups enhanced the hydrophobicity of the side chains, which resulted in notably increased membrane activities and transfection efficiency. Further incorporation of hydrophobic decyl side chains led to an improvement in transfection efficiency of ∼6 fold. The top-performing material identified, P11, mediated successful gene transfection under serum-containing conditions, outperforming the commercial transfection reagent poly(ethylenimine) by nearly 4 orders of magnitude. Reflecting its excellent serum-resistant properties, P11 further enabled effective transfection in vivo following intratumoral injection to melanoma-bearing mice. This study will help the rational design of polypeptoid-based gene delivery materials, and the best-performing material identified may provide a potential supplement to existing gene vectors.

The Association of Marital Status and Offers of Employer-based Health Insurance for Employed Women Aged 27-64: United States, 2014-2015.

KEY FINDINGS: Data from the National Health Interview Survey •Among employed women aged 27-64, unmarried women (72.2%) were more likely than married women (69.3%) to have been offered health insurance by their employer. •Among employed married women aged 27-64, 16.8% were offered health insurance only through their spouse's employer. •Considering all offers of health insurance (through a woman's employer or her spouse's employer), employed married women aged 27-64 (86.1%) were more likely than employed unmarried women (72.2%) to have had an employer offer of health insurance. •Regardless of educational attainment, and for most income and racial groups, employed married women aged 27-64 were more likely than employed unmarried women to have been offered health insurance by their employer or their spouse's employer. In 2015, women were less likely than men to have been insured through their own employer and more likely to have been covered as a dependent (1). This report describes the association of marital status and the presence of employer-based health insurance offers among employed women in the United States. Analyses are limited to women aged 27-64 to exclude offers associated with parental employment for those under age 27. An offer of employer-based health insurance includes offers by the woman's employer or her spouse's employer. The presence of an offer does not indicate offer take up.

YAC128 Huntington's disease transgenic mice show enhanced short-term hippocampal synaptic plasticity early in the course of the disease.

Huntington's disease (HD) is a progressive and fatal neurodegenerative disorder caused by a polyglutamine expansion in the gene encoding the protein huntingtin. The disease progresses over decades, but often patients develop cognitive impairments that precede the onset of the classical motor symptoms. Similar to the disease progression in humans, the yeast artificial chromosome (YAC) 128 HD mouse model also exhibits cognitive dysfunction that precedes the onset of the neuropathological and motor impairments characteristic of HD. Thus, the purpose of this study was to evaluate whether short- and long-term synaptic plasticity in the hippocampus, two related biological models of learning and memory processes, were altered in YAC128 mice in early stages of disease progression. We show that the YAC128 hippocampal dentate gyrus (DG) displays marked reductions in paired-pulse depression both at 3 and 6 months of age. In addition, significantly enhanced post-tetanic and short-term potentiation are apparent in YAC128 mice after high-frequency stimulation at this time. Early and late forms of long-term plasticity were not altered at this stage. Together these findings indicate that there may be elevated neurotransmitter release in response to synaptic stimulation in YAC128 mice during the initial phase of disease progression. These abnormalities in short-term plasticity detected at this stage in YAC128 HD transgenic mice indicate that aberrant information processing at the level of the synapses may contribute, at least in part, to the early onset of cognitive deficits that are characteristic of this devastating neurodegenerative disorder.

Hippocampal neurogenesis levels predict WATERMAZE search strategies in the aging brain.

The hippocampus plays a crucial role in the formation of spatial memories, and it is thought that adult hippocampal neurogenesis may participate in this form of learning. To better elucidate the relationship between neurogenesis and spatial learning, we examined both across the entire life span of mice. We found that cell proliferation, neuronal differentiation, and neurogenesis significantly decrease with age, and that there is an abrupt reduction in these processes early on, between 1.5-3 months of age. After this, the neurogenic capacity continues to decline steadily. The initial abrupt decline in adult neurogenesis was paralleled by a significant reduction in Morris Water Maze performance, however overall learning and memory remained constant thereafter. Further analysis of the search strategies employed revealed that reductions in neurogenesis in the aging brain were strongly correlated with the adoption of spatially imprecise search strategies. Overall, performance measures of learning and memory in the Morris Water Maze were maintained at relatively constant levels in aging animals due to an increase in the use of spatially imprecise search strategies.

Physician attitudes toward dissemination of optical spectroscopy devices for cervical cancer control: an industrial-academic collaborative study.

BACKGROUND: Optical spectroscopy has been studied for biologic plausibility, technical efficacy, clinical effectiveness, patient satisfaction, and cost-effectiveness. OBJECTIVE: We sought to identify health care provider attitudes or practices that might act as barriers or to the dissemination of this new technology. METHODS: Through an academic-industrial partnership, we conducted a series of focus groups to examine physician barriers to optical diagnosis. The study was conducted in 2 stages. First, a pilot group of 10 physicians (8 obstetrician gynecologists and 2 family practitioners) was randomly selected from 8 regions of the United States and each physician was interviewed individually. Physicians were presented with the results of a large trial (N = 980) testing the accuracy of a spectroscopy-based device in the detection of cervical neoplasia. They were also shown a prototype of the device and were given a period of time to ask questions and receive answers regarding the device. They were also asked to provide feedback on a questionnaire that was then revised and presented to 3 larger focus groups (n = 13, 15, and 17 for a total N = 45). The larger focus groups were conducted during national scientific meetings with 20 obstetrician gynecologists and 25 primary care physicians (family practitioners and internists). RESULTS: When asked about the dissemination potential of the new cervical screening technology, all study groups tended to rely on established clinical guidelines from their respective professional societies with regard to the screening and diagnosis of cervical cancer. In addition, study participants consistently agreed that real-time spectroscopy would be viewed positively by their patients. Participants were positive about the new technology's potential as an adjunct to colposcopy and agreed that the improved accuracy would result in reduced health care costs (due to decreased biopsies and decreased visits). Although all participants saw the potential of real-time diagnosis, there were many perceived barriers. These barriers included changes in scheduling and work-flow, liability, documentation, ease of use, length of training, device cost, and reimbursement by third-party payers. CONCLUSIONS: Barriers exist to the dissemination of optical technologies into physician practice. These will need to be addressed before cervical screening and diagnosis programs can take advantage of spectroscopy-based instruments for cancer control.

Neurogenesis in Huntington's disease: can studying adult neurogenesis lead to the development of new therapeutic strategies?

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an unstable expansion of CAG repeats in the HD gene. The symptoms include cognitive dysfunction and severe motor impairments. The neuropathology is characterized by neuronal loss mainly in the striatum and cortex, although other regions including the hippocampus are also affected. In this review we discuss the different mouse models of HD, and how the process of neurogenesis in the dentate gyrus (DG) of the hippocampus and the subventricular zone (SVZ) is affected in each. Deficits in adult hippocampal neurogenesis have been repeatedly shown in different genetic models of HD, raising the possibility that an impairment of the neurogenic process might underlie some of the cognitive deficits associated with this neurodegenerative disorder. On the other hand, an increase in SVZ neurogenesis has been observed in human HD brains while no differences in SVZ cell proliferation have been detected in the mouse models. In this review we will discuss the discrepancies between these findings as well as the several mechanisms that might contribute to a dysregulation of adult neurogenesis in HD. Finally, we will provide an overview of the various therapeutic strategies aimed at stimulating the endogenous neurogenic capacity that have been tested in HD genetic models. Ultimately, the insights obtained from these and future studies will greatly improve our understanding of the cognitive impairment characteristic of HD.

Altered adult hippocampal neurogenesis in the YAC128 transgenic mouse model of Huntington disease.

Perturbations in neurogenesis in the adult brain have been implicated in impaired learning and memory. In the present study, we investigated which stages of the neurogenic process are affected in the transgenic YAC128 mouse model of Huntington disease (HD). Hippocampal neuronal proliferation was altered in the dentate gyrus (DG) of YAC128 mice as compared with wild-type (WT) littermate controls in early symptomatic to end-stage mice. In addition, we detected a significantly lower number of immature neurons in the DG of young, pre-symptomatic YAC128 mice. This decrease in neuronal differentiation persisted through the progression of the disease, and resulted in an overall reduction in the number of new mature neurons in the DG of YAC128 mice. There were no changes in cell proliferation and differentiation in the subventricular zone (SVZ). In this study, we demonstrate decreases in neurogenesis in the DG of YAC128 mice, and these deficits may contribute to the cognitive abnormalities observed in these animals.