Search

In this expository essay, we introduce some elements of the study of groups by analysing the braid pattern on a knitted blanket. We determine that the blanket features pure braids with a minimal number of crossings. Moreover, we determine polynomial invariants associated to the links obtained by closing the braid patterns of the blanket. [ABSTRACT FROM AUTHOR]

Previous studies have examined Hong Kong's hybrid regime by investigating the interactions among activists, the local government, and the Chinese national government. This article adopts the lens of contentious politics and a multi-level approach to understand regime evolution within the local-national-regional-global nexus. It presents an original dataset that records movement tactics and state responses in four major protests and delineates three phases of state-society contention between 2003 and 2020. It explains regime evolution by highlighting five intertwining factors: activists' tactical learning; organisational ecology in civil society; state repression strategies; regional politics in Greater China; and international political economy. It finds that the first phase (2003–2012) was characterised by an increasing use of disruptive tactics, an emergent call for de-centred mobilisation, and a limited deployment of state security forces. The second phase (2013–2015) exhibited nascent applications of violent tactics, while the state employed more forceful police repression, re-engineered the electoral field, and sponsored counter-mobilisation. The most recent phase (2016–2020) showed activists' intensified use of violent tactics and a strong intention to seek international support. The state responded to local threats and international pressure with violent crackdowns and stricter institutional arrangements, which has resulted in an electoral authoritarian regime that is less-than-competitive. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) remains a global health concern because it contributes to the initiation of various HPV-associated cancers such as anal, cervical, oropharyngeal, penile, vaginal, and vulvar cancer. In HPV-associated cancers, oncogenesis begins with an HPV infection, which is linked to the activation of the Janus protein tyrosine kinase (JAK)/STAT signaling pathway. Various STAT signaling pathways, such as STAT3 activation, have been well documented for their tumorigenic role, yet the role of STAT1 in tumor formation remains unclear. In the current study, STAT1−/− mice were used to investigate the role of STAT1 in the tumorigenesis of a spontaneous HPV E6/E7-expressing oral tumor model. Subsequently, our candidate HPV DNA vaccine CRT/E7 was administered to determine whether the STAT1−/− host preserves a therapeutic-responsive tumor microenvironment. The results indicated that STAT1−/− induces robust tumorigenesis, yet a controlled tumor response was attained upon CRT/E7 vaccination. Characterizing this treatment effect, immunological analysis found a higher percentage of circulating CD4+ and CD8+ T cells and tumor-specific cytotoxic T cells. In addition, a reduction in exhaustive lymphocyte activity was observed. Further analysis of a whole-cell tumor challenge affirmed these findings, as spontaneous tumor growth was more rapid in STAT1−/− mice. In conclusion, STAT1 deletion accelerates tumorigenesis, but STAT1−/− mice maintains immunocompetency in CRT/E7 treatments. [ABSTRACT FROM AUTHOR]

Moyamoya disease (MMD) is characterized by progressive occlusion of the intracranial internal carotid arteries, leading to ischemic and hemorrhagic events. Significant clinical differences exist between ischemic and hemorrhagic MMD. To understand the molecular profiles in the cerebrospinal fluid (CSF) of MMD patients, we investigated 62 secreted factors in both MMD subtypes (ischemic and hemorrhagic) and examined their relationship with preoperative perfusion status, the extent of postoperative angiographic revascularization, and functional outcomes. Intraoperative CSF was collected from 32 control and 71 MMD patients (37 ischemic and 34 hemorrhagic). Multiplex Luminex assay analysis showed that 41 molecules were significantly elevated in both MMD subtypes when compared to controls, including platelet-derived growth factor-BB (PDGF-BB), plasminogen activator inhibitor 1 (PAI-1), and intercellular adhesion molecule 1 (ICAM1) (p < 0.001). Many of these secreted proteins have not been previously reported in MMD, including interleukins (IL-2, IL-4, IL-5, IL-7, IL-8, IL-9, IL-17, IL-18, IL-22, and IL-23) and C-X-C motif chemokines (CXCL1 and CXCL9). Pathway analysis indicated that both MMD subtypes exhibited similar cellular/molecular functions and pathways, including cellular activation, migration, and inflammatory response. While neuroinflammation and dendritic cell pathways were activated in MMD patients, lipid signaling pathways involving nuclear receptors, peroxisome proliferator-activated receptor (PPAR), and liver X receptors (LXR)/retinoid X receptors (RXR) signaling were inhibited. IL-13 and IL-2 were negatively correlated with preoperative cerebral perfusion status, while 7 factors were positively correlated with the extent of postoperative revascularization. These elevated cytokines, chemokines, and growth factors in CSF may contribute to the pathogenesis of MMD and represent potential future therapeutic targets. [ABSTRACT FROM AUTHOR]

This article considers cultural probes as an experimental qualitative method in promoting collaborative and prefigurative participation in research. While the extant literature tends to frame cultural probes either as the discounted ethnographic tool or the means to gather design inspiration, such a framing also results in an irreconcilable methodological and conceptual dichotomy. Seeking to overcome this binary, this paper draws inspiration from Michel de Certeau's concept of "poaching" to contemplate how cultural probes may elicit and provoke both inspirational and analytical data. Through an empirical study of the everyday waste practices of 10 young university students in Hong Kong, this study discusses the rationale of different cultural probes designs and participants' experience in completing the probes. This paper argues that the cultural probes may offer a speculative and creative qualitative inquiry to cultivate one's "attentiveness", generate "politics of reconfiguration", and make sense of "uncertainty" in knowledge production. [ABSTRACT FROM AUTHOR]

Background: Previous research in FMS-like tyrosine kinase 3 ligands (FLT3L) has primarily focused on their potential to generate dendritic cells (DCs) from bone marrow progenitors, with a limited understanding of how these cells affect CD8 T cell function. In this study, we further investigated the in vivo role of FLT3L for the immunomodulatory capabilities of CD8 T cells. Methods: Albumin-conjugated FLT3L (Alb-FLT3L) was generated and applied for translational medicine purposes; here it was used to treat naïve C57BL/6 and OT1 mice for CD8 T cell response analysis. Syngeneic B16ova and E.G7ova mouse models were employed for adoptive cell transfer to evaluate the effects of Alb-FLT3L preconditioning of CD8 T cells on tumor progression. To uncover the underlying mechanisms of Alb-FLT3L modulation, we conducted bulk RNA-seq analysis of the CD44high CD8 T cells. STAT1-deficient mice were used to elucidate the functional roles of Alb-FLT3L in the modulation of T cells. Finally, antibody blockade of type one interferon signaling and in vitro coculture of plasmacytoid DCs (pDCs) with naive CD8 T cells was performed to determine the role of pDCs in mediating regulation of CD44high CD8 T cells. Results: CD44high CD8 T cells were enhanced in C57BL/6 mice administrated with Alb-FLT3L. These CD8 T cells exhibited virtual memory features and had greater proliferative and effective functions. Notably, the adoptive transfer of CD44high naïve CD8 T cells into C57BL/6 mice with B16ova tumors led to significant tumor regression. RNA-seq analysis of the CD44high naïve CD8 T cells revealed FLT3L to induce CD44high CD8 T cells in a JAK-STAT1 signaling pathway-dependent manner, as supported by results indicating a decreased ability of FLT3L to enhance CD8 T cell proliferation in STAT1-deficient mice as compared to wild-type control mice. Moreover, antibody blockade of type one interferon signaling restricted the generation of FLT3L-induced CD44high CD8 T cells, while CD44 expression was able to be induced in naïve CD8 T cells cocultured with pDCs derived from FLT3L-treated mice. This suggests the crucial role of pDCs in mediating FLT3L regulation of CD44high CD8 T cells. Conclusions: These findings provide critical insight and support the therapeutic potential of Alb-FLT3L as an immune modulator in preconditioning of naïve CD8 T cells for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Introduction: Healthcare professionals frequently experience work-related fatigue, which may jeopardize their health and put patient safety at risk. In this study, we applied a machine learning (ML) approach based on data collected from a smartwatch to construct prediction models of work-related fatigue for emergency clinicians. Methods: We conducted this prospective study at the emergency department (ED) of a tertiary teaching hospital from March 10-June 20, 2021, where we recruited physicians, nurses, and nurse practitioners. All participants wore a commercially available smartwatch capable of measuring various physiological data during the experiment. Participants completed the Multidimensional Fatigue Inventory (MFI) web form before and after each of their work shifts. Wecalculated and labeled the before-and-after-shift score differences between each pair of scores. Using several tree-based algorithms, we constructed the prediction models based on features collected from the smartwatch. Records were split into training/validation and testing sets at a 70:30 ratio, and we evaluated the performances using the area under the curve (AUC) measure of receiver operating characteristic on the test set. Results: In total, 110 participants were included in this study, contributing to a set of 1,542 effective records. Of these records, 85 (5.5%) were labeled as having work-related fatigue when setting the MFI difference between two standard deviations as the threshold. The mean age of the participants was 29.6. Most of the records were collected from nurses (87.7%) and females (77.5%). We selected a union of 31 features to construct the models. For total participants, CatBoost classifier achieved the best performances of AUC (0.838, 95% confidence interval [CI] 0.742-0.918) to identify work-related fatigue. By focusing on a subgroup of nurses <35 years in age, XGBoost classifier obtained excellent performance of AUC (0.928, 95% CI 0.839-0.991) on the test set. Conclusion: By using features derived from a smartwatch, we successfully built ML models capable of classifying the risk of work-related fatigue in the ED. By collecting more data to optimize the models, it should be possible to use smartwatch-based ML models in the future to predict work-related fatigue and adopt preventive measures for emergency clinicians. [ABSTRACT FROM AUTHOR]

The fields of psychiatry and mental health are increasingly recognizing the importance of social determinants of health (SDOH) and their impact on mental health outcomes. In this overview, the authors discuss the recent research, from the past 5 years, on advances made in SDOH work. SDOH frameworks and theories have expanded to include more social conditions, from traumas associated with immigration to psychosocial and community strengths, that impact mental health and well-being. Research has consistently shown the pervasive deleterious impacts of inequitable social conditions (e.g., food insecurity, housing instability) on minoritized populations' physical and mental health. Social systems of oppression (e.g., racism, minoritization) have also been shown to confer higher risk for psychiatric and mental disorders. The COVID-19 pandemic illuminated the inequitable impact of the social determinants of health outcomes. More efforts have been made in recent years to intervene on the social determinants through interventions at the individual, community, and policy levels, which have shown promise in improving mental health outcomes in marginalized populations. However, major gaps remain. Attention should be paid to developing guiding frameworks that incorporate equity and antiracism when designing SDOH interventions and improving methodological approaches for evaluating these interventions. In addition, structural-level and policy-level SDOH efforts are critical for making long-lasting and impactful advances toward mental health equity. [ABSTRACT FROM AUTHOR]

Objectives. To examine whether referral for social determinants of health (SDH) needs decreases psychological distress and posttraumatic stress disorder (PTSD) symptoms and improves level of functioning and quality of care among diverse adults. Methods. Data are from control participants (n = 503 adults) in a randomized controlled trial testing a mental health intervention in North Carolina and Massachusetts. We fitted multilevel mixed-effects models to repeated assessments (baseline, 3, 6, and 12 months) collected between September 2019 and January 2023. Results. After referral to services for trouble paying utility bills, participants reported lower PTSD symptoms. Participants reported better quality of care when receiving referrals to mental health care. After adjusting for income and employment status, we found that participants who were referred more often also had lower PTSD symptoms and better levels of functioning. Conclusions. Referrals for certain SDH needs might decrease PTSD symptoms and improve self-reported quality of care and functioning. However, referrals alone, without ensuring receipt of services, might be insufficient to affect other mental health outcomes. Research is needed on training and providing care managers time for offering interpersonal support, securing services, and understanding agencies' contexts for addressing high SDH needs. (Am J Public Health. 2024;114(S3):S278–S288. https://doi.org/10.2105/AJPH.2023.307442) [ABSTRACT FROM AUTHOR]

Drawing on a five-ethical principles framework, this study examines how the thirteen recruited doctoral students across disciplines in Hong Kong interpret the idea of and experience "exploitative supervision". Findings reveal that doctoral students' lived experiences of exploitation are expressed in five different themes: autonomy exploitation, justice exploitation, fidelity exploitation, beneficent exploitation, and non-maleficence exploitation. The phenomenon was scaffolded through a Foucauldian perspective on power relations. Varied understandings of academic exploitation among doctoral students point to an urgent need to take reference from the employment and labor law to outline the fundamental rights of doctoral students, set up a probation period for the matching of supervisor-supervisee, and establish a higher-level independent inquiry to handle academic exploitation. [ABSTRACT FROM AUTHOR]

The growing complexity of doing a PhD necessarily demands candidates to robustly exercise their agency in navigating the doctoral journey. However, the conceptualisation of how students use their agency across multiple facets of their studies has yet to receive due scholarly attention. Drawing on the subject-centred sociocultural view on agency, this study analysed life story interviews conducted with 16 doctoral students in Hong Kong. Findings show that participants' agency was manifested both in socially and collectively organised enterprises (proactive engagement in a wide array of developmental opportunities, responsiveness to situational research problems, contestation against unsupportive institutional cultures) and as individual-level strategic perspectives and actions (self-management of everyday emotions, imaginative construction of post-graduation prospects). Concurrently, the results shed light on the inextricable and complex linkages between the enactment of agency and the personal, relational, institutional, and broader higher education conditions delimiting students' lived experiences of candidature. Implications for educational practices and future research beneficial to develop doctoral agency are discussed. [ABSTRACT FROM AUTHOR]

The 2019 Anti-Extradition Law Amendment Bill protests in Hong Kong culminated in diverse forms of political participation, but as yet little attention has been paid to the impact on the pro-democracy movement at the micro-level. This paper explores pro-democracy protesters' evolving views of politics and their new modes of political participation during and after the protests. Using interview data, this paper shows that participants in the pro-democracy movement have increasingly recognized the inseparable relationship between everyday life and political life. This paper examines two forms of everyday political participation – political consumption and digital activism – that have been widely deployed by protesters to express political claims, circulate political information, and garner support from local and international audiences. While the politicization of everyday life provided impetus to street demonstrations in 2019, it has continued despite the adoption of a wider scope of repressive measures by the Chinese and Hong Kong governments after the protests. Through the case of Hong Kong, this paper demonstrates how, in an authoritarian context, everyday resistance is applied to struggle for regime change and democratization. [ABSTRACT FROM AUTHOR]

For locally invasive/in-transit cutaneous melanoma, we have advocated combination therapy with intralesional interleukin (IL)-2 and topical imiquimod and tretinoin, which can completely eradicate melanoma in a T cell-dependent fashion.1,2 However, its ability to augment systemic therapies remains uninvestigated. (H) PET/CT after 1 month of treatment with BRAF/MEK inhibitor therapy showing several new mediastinal metastases indicative of progressive disease. Advances in immunotherapy have expanded the armamentarium of treatments for metastatic melanoma. [Extracted from the article]

As our understanding of the genetic underpinnings of SSc increases, questions regarding the environmental trigger(s) that induce and propagate SSc in the genetically predisposed individual emerge. The interplay between the environment, the immune system, and the microbial species that inhabit the patient's skin and gastrointestinal tract is a pathobiological frontier that is largely unexplored in SSc. The purpose of this review is to provide an overview of the methodologies, experimental study results and future roadmap for elucidating the relationship between the SSc host and his/her microbiome. [ABSTRACT FROM AUTHOR]

Is noun dominance in early lexical acquisition a widespread or a language-specific phenomenon? Thirty Singaporean bilingual English–Mandarin learning toddlers and their mothers were observed in a mother-child play interaction. For both English and Mandarin, toddlers' speech and reported vocabulary contained more nouns than verbs across book reading and toy playing. In contrast, their mothers' speech contained more verbs than nouns in both English and Mandarin but differed depending on the context of the interaction. Although toddlers demonstrated a noun bias for both languages, the noun bias was more pronounced in English than in Mandarin. Together, these findings support early noun dominance as a widespread phenomenon in the lexical acquisition debate but also provide evidence that language specificity also plays a minor role in children's early lexical development. [ABSTRACT FROM AUTHOR]

To explore effective growth mindset intervention that is applicable for the higher education setting, study 1 conducted a systematic review to analyze relevant literature published between 2010 and 2021. We identified 13 papers and synthesized the results of these studies to understand how the intervention was designed, conducted, and evaluated, pointing out the lack of attention to visual images as mindset intervention in the existing literature. Accordingly, in study 2, a set of infographic materials was developed and delivered to thirty participants recruited in a university to cultivate a growth mindset. The participants were randomly assigned to an experimental or control group. To measure the effectiveness of the intervention, participants are required to complete a pre-and post-survey. Significant differences were found between the two groups after 6-week intervention, as the experimental group perceived intelligence significantly more malleable. Weekly reflections were analyzed to evaluate the impacts of the designed materials. [ABSTRACT FROM AUTHOR]

Surgical excision is standard-of-care for primary invasive melanoma, but best care can be unclear for patients who are surgically high-risk or for whom resection may be excessively morbid. Alternatives to surgical excision have emerged for treatment of metastatic melanoma but have not yet been explored for primary invasive melanoma. Two elderly patients with primary invasive melanoma with many medical co-morbidities who were not surgical candidates were determined to be appropriate candidates for an intralesional IL-2 based regimen. Herein we report their clinical and histological outcome. An intralesional-based regimen (intralesional IL-2, topical imiquimod cream 5%, and tretinoin cream 0.1% under occlusion to the treatment site) was administered over the course of six to seven weeks, followed by two weeks of topical-only therapy. A complete response was seen after eight to nine weeks of treating invasive melanomas that were ≥1.85 mm and 5.5 mm thick. For patients with primary invasive melanoma on high morbidity sites and patients who are poor surgical candidates, a neoadjuvant intralesional IL-2-based approach may be a reasonable alternative. The two cases presented here suggest that alternative intralesional-based treatment modalities may minimize the size of the excision site and can be associated with complete histological clearance of invasive melanoma. [ABSTRACT FROM AUTHOR]

Past studies revealed that Resident Assistants' (RAs) behavioural patterns are related to experiences and life outcomes of student residents. In this paper, the researchers aimed to investigate the struggles that new RAs encounter in university residential halls in Hong Kong, and to provide practical recommendations based on the findings. Photovoice was adopted to facilitate the participatory approach of the study; and six new RAs were recruited from different residential halls in a university for one semester to co-construct reliable knowledge. Four domains of struggles were identified in the study; difficulties to blend in, levels of involvement, workloads and performance, and role ambiguity. Further research is needed in different contexts to provide more insights to refine policies and approaches for better RAs' residential environment, as it is believed that by improving their residential experiences, it can further enhance students' residential experiences and foster positive residence life outcomes. [ABSTRACT FROM AUTHOR]

A major problem in human cognition is to understand how newly acquired information and long-standing beliefs about the environment combine to make decisions and plan behaviors. Over-dependence on long-standing beliefs may be a significant source of suboptimal decision-making in unusual circumstances. While the contribution of long-standing beliefs about the environment to search in real-world scenes is well-studied, less is known about how new evidence informs search decisions, and it is unclear whether the two sources of information are used together optimally to guide search. The present study expanded on the literature on semantic guidance in visual search by modeling a Bayesian ideal observer's use of long-standing semantic beliefs and recent experience in an active search task. The ability to adjust expectations to the task environment was simulated using the Bayesian ideal observer, and subjects' performance was compared to ideal observers that depended on prior knowledge and recent experience to varying degrees. Target locations were either congruent with scene semantics, incongruent with what would be expected from scene semantics, or random. Half of the subjects were able to learn to search for the target in incongruent locations over repeated experimental sessions when it was optimal to do so. These results suggest that searchers can learn to prioritize recent experience over knowledge of scenes in a near-optimal fashion when it is beneficial to do so, as long as the evidence from recent experience was learnable. [ABSTRACT FROM AUTHOR]

Post-stroke optogenetic stimulation has been shown to enhance neurovascular coupling and functional recovery. Neuronal nitric oxide synthase (nNOS) has been implicated as a key regulator of the neurovascular response in acute stroke; however, its role in subacute recovery remains unclear. We investigated the expression of nNOS in stroke mice undergoing optogenetic stimulation of the contralesional lateral cerebellar nucleus (cLCN). We also examined the effects of nNOS inhibition on functional recovery using a pharmacological inhibitor targeting nNOS. Optogenetically stimulated stroke mice demonstrated significant improvement on the horizontal rotating beam task at post-stroke days 10 and 14. nNOS mRNA and protein expression was significantly and selectively decreased in the contralesional primary motor cortex (cM1) of cLCN-stimulated mice. The nNOS expression in cM1 was negatively correlated with improved recovery. nNOS inhibitor (ARL 17477)-treated stroke mice exhibited a significant functional improvement in speed at post-stroke day 10, when compared to stroke mice receiving vehicle (saline) only. Our results show that optogenetic stimulation of cLCN and systemic nNOS inhibition both produce functional benefits after stroke, and suggest that nNOS may play a maladaptive role in post-stroke recovery. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Advanced Nursing (John Wiley & Sons, Inc.) is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aims and objectives: This study aims to explore nurses' perceptions and experiences regarding pressure injuries caused by medical devices and to understand the perceived challenges and barriers nurses face in preventing medical device‐related pressure injuries. Background: Nurses have a responsibility to prevent pressure injuries and play a major role in their prevention. As there has been a lack of research on medical device‐related pressure injuries, not much is known about nurses' perceptions and experiences. This therefore hinders the establishment of effective and efficient interventions in nurses' education and in the practical environment. Design: A descriptive qualitative design was adopted, and the COREQ checklist was employed to report on the current study. Methods: The study was conducted at an acute care hospital in Singapore. Purposive sampling was used, and a total of 21 enrolled and registered nurses who had recent experiences with medical device‐related pressure injuries were recruited between August and December 2018. Face‐to‐face interviews were conducted using a semi‐structured interview guide. A thematic analysis was performed to analyse the qualitative data. Results: Five themes emerged regarding pressure injuries: (1) preventable yet unavoidable, (2) everyone's responsibility, (3) harmonising theory with practice reality, (4) pre‐existing conditions may limit injury prevention and management; and (5) nurses expressed a need for experiential training. Conclusions: The study's findings could be used to develop improvements in nursing practice and policy at acute care hospitals, as well as to improve awareness of medical device‐related pressure injuries among healthcare professionals. Moreover, the findings can also inform future research studies to develop effective evidence‐based practices and improve patient outcomes. Relevance to the clinical practice: This study reveals the unique challenges and dilemmas that nurses face and will help to inform healthcare institutions and management in developing programmes and improving protocols to reduce the incidence rate of pressure injuries caused by medical device. [ABSTRACT FROM AUTHOR]

Can residential experiences help undergraduates develop holistic competencies? To answer this question, a study was conducted based on the insights of 211 residents in Hong Kong. Deductive and inductive content analyses were respectively used to examine residence life outcomes, particularly in holistic competencies, and to categorise the types of residential experiences deemed to be effective for these outcomes. Results revealed that participation in hall activities led to the development of residence life outcomes, including justice, humanity, wisdom, courage, transcendence, and wellbeing. Furthermore, planning/organising hall activities greatly improved students' sense of justice while interpersonal dynamics facilitated the improvement of humanity only. The analyses indicated that students without specific engagement in hall activities were also able to develop temperance, particularly in self-regulation. Recommendations are suggested based on the analyses. It is hoped that this study might help inform policy-making processes to provide better residential environment that is beneficial to student holistic development. [ABSTRACT FROM AUTHOR]

The cerebellum is best known for its role in controlling motor behaviors. However, recent work supports the view that it also influences non-motor behaviors. The contribution of the cerebellum towards different brain functions is underscored by its involvement in a diverse and increasing number of neurological and neuropsychiatric conditions including ataxia, dystonia, essential tremor, Parkinson's disease (PD), epilepsy, stroke, multiple sclerosis, autism spectrum disorders, dyslexia, attention deficit hyperactivity disorder (ADHD), and schizophrenia. Although there are no cures for these conditions, cerebellar stimulation is quickly gaining attention for symptomatic alleviation, as cerebellar circuitry has arisen as a promising target for invasive and non-invasive neuromodulation. This consensus paper brings together experts from the fields of neurophysiology, neurology, and neurosurgery to discuss recent efforts in using the cerebellum as a therapeutic intervention. We report on the most advanced techniques for manipulating cerebellar circuits in humans and animal models and define key hurdles and questions for moving forward. [ABSTRACT FROM AUTHOR]

Eosinophilic fasciitis is a rare connective tissue disorder characterized by inflammation of the fascia that leads to painful, indurated skin. Because of its variable clinical presentation and overlap with conditions, such as morphea, the diagnosis of eosinophilic fasciitis can be challenging and relies on clinical presentation, histopathologic and laboratory analysis, and response to therapy. Herein, we present an unusual, solitary, isolated plaque with pathologic features and response to therapy most consistent with eosinophilic fasciitis. [ABSTRACT FROM AUTHOR]

Scurvy is a clinical syndrome, resulting from ascorbic acid deficiency. Prevalence of the condition is now extremely low in the Western population and its diagnosis can be challenging without a high index of suspicion. When cases do present, they are often misdiagnosed initially. Therefore, a thorough history, physical exam, and laboratory evaluation are key to showing this now rare but extremely well‐known disease. We report a case of scurvy manifesting as persistent non‐healing lower‐extremity ulcerations, initially mistaken for pyoderma gangrenosum. The patient responded to appropriate replacement therapy, but ulcers were slow to heal. As was the case in our patient, symptom reversal may require additional nutritional replacement. We encourage physicians to consider nutritional deficiencies in their differential diagnoses and highlight the incidence of malnutrition in the proper clinical setting to avoid diagnostic delay. [ABSTRACT FROM AUTHOR]

Objectives: We sought to assess the presence and reporting quality of peer-reviewed literature concerning the accuracy, precision, and reliability of home monitoring technologies for vital signs and glucose determinations in older adult populations.Methods: A narrative literature review was undertaken searching the databases Medline, Embase, and Compendex. Peer-reviewed publications with keywords related to vital signs, monitoring devices and technologies, independent living, and older adults were searched. Publications between the years 2012 and 2018 were included. Two reviewers independently conducted title and abstract screening, and four reviewers independently undertook full-text screening and data extraction with all disagreements resolved through discussion and consensus.Results: Two hundred nine articles were included. Our review showed limited assessment and low-quality reporting of evidence concerning the accuracy, precision, and reliability of home monitoring technologies. Of 209 articles describing a relevant device, only 45 percent (n = 95) provided a citation or some evidence to support their validation claim. Of forty-eight articles that described the use of a comparator device, 65 percent (n = 31) used low-quality statistical methods, 23 percent (n = 11) used moderate-quality statistical methods, and only 12 percent (n = 6) used high-quality statistical methods.Conclusions: Our review found that current validity claims were based on low-quality assessments that do not provide the necessary confidence needed by clinicians for medical decision-making purposes. This narrative review highlights the need for standardized health technology reporting to increase health practitioner confidence in these devices, support the appropriate adoption of such devices within the healthcare system, and improve health outcomes. [ABSTRACT FROM AUTHOR]

Stroke is a leading cause of death and disability in the USA, yet treatment options are very limited. Functional recovery can occur after stroke and is attributed, in part, to rewiring of neural connections in areas adjacent to or remotely connected to the infarct. A better understanding of neural circuit rewiring is thus an important step toward developing future therapeutic strategies for stroke recovery. Because stroke disrupts functional connections in peri-infarct and remotely connected regions, it is important to investigate brain-wide network dynamics during post-stroke recovery. Optogenetics is a revolutionary neuroscience tool that uses bioengineered light-sensitive proteins to selectively activate or inhibit specific cell types and neural circuits within milliseconds, allowing greater specificity and temporal precision for dissecting neural circuit mechanisms in diseases. In this review, we discuss the current view of post-stroke remapping and recovery, including recent studies that use optogenetics to investigate neural circuit remapping after stroke, as well as optogenetic stimulation to enhance stroke recovery. Multimodal approaches employing optogenetics in conjunction with other readouts (e.g., in vivo neuroimaging techniques, behavior assays, and next-generation sequencing) will advance our understanding of neural circuit reorganization during post-stroke recovery, as well as provide important insights into which brain circuits to target when designing brain stimulation strategies for future clinical studies. [ABSTRACT FROM AUTHOR]

Purpose: In this systematic review, we aimed to synthesize data that identify factors contributing to patient satisfaction in dermatology care using qualitative methods. Materials and methods: We performed a comprehensive search of the literature using the PubMed database for articles published between January 1, 2000 and February 9, 2015. The initial search yielded 186 articles, of which 13 were included after applying inclusion and exclusion criteria. Results: The systematic review of 13 articles included a total of 330 patients. Using in-field observations and semistructured interviews, studies found that qualitative methods and analysis increased the provider’s sensitivity to patient needs and enhanced patient care. Analyses using qualitative methods found increased patient satisfaction in their healthcare provider is associated with (1) confidence in the provider’s diagnosis, (2) perception of patient-centered, individualized recommendations and (3) quality of patient education and provider explanation during a visit. Conclusions: Patient satisfaction is measured using either quantitative or qualitative methods. Quantitative methods result in standardized data that often does not capture the nuances of patient experience. In contrast, qualitative methodology is integral to gathering patient perspectives on patient care and satisfaction and should be included in future research models. [ABSTRACT FROM AUTHOR]

Background: Pyoderma gangrenosum (PG) is a debilitating ulcerative skin disease that is one of the most common associated diseases seen in patients with inflammatory bowel disease and rheumatoid arthritis. Although PG is classified as a neutrophilic dermatosis, its pathophysiology is poorly understood. Objective: Use data obtained from patient-reported histories, immunohistochemistry, and gene expression analysis to formulate a hypothesis on PG pathophysiology. Methods: Ten PG patients participated and answered questions about new ulcer formation. Skin biopsies of healed prior ulcers and adjacent normal skin were obtained from four patients for immunohistochemistry. Scars from healthy patients and patients with discoid lupus were used as additional controls. New onset PG papules were analyzed using immunohistochemistry and gene expression analysis via quantitative real-time PCR. Results: All PG patients reported that healed sites of previous ulceration are refractory to re-ulceration. Simultaneous biopsies of healed and uninvolved skin triggered ulceration only in the latter. On immunohistochemistry, healed PG scars showed complete loss of pilosebaceous units, which were present in normal skin, and to a lesser extent in control scars, and discoid scars. Early PG papules showed perivascular and peripilosebaceous T cell infiltrates, rather than neutrophils. These early inflammatory events were dominated by increased gene expression of CXCL9, CXCL10, CXCL11, IL-8, IL-17, IFNG, and IL-36G and transcription factors consistent with Th1 phenotype. Limitations: Small sample size was the main limitation. Conclusion: We put forth the hypothesis that PG is a T cell response resulting in the destruction of pilosebaceous units. [ABSTRACT FROM AUTHOR]

Background: Cathelicidin (LL-37) is an antimicrobial peptide known to be associated with various autoimmune diseases. We attempt to determine if cathelicidin can accurately reflect IBD disease activity. We hypothesize that serum cathelicidin correlates with mucosal disease activity, stricture, and clinical prognosis of IBD patients.Methods: Serum samples were collected from two separate cohorts of patients at the University of California, Los Angeles. Cohort 1 consisted of 50 control, 23 UC, and 28 CD patients. Cohort 2 consisted of 20 control, 57 UC, and 67 CD patients. LL-37 levels were determined by ELISA. Data from both cohorts were combined for calculation of accuracies in indicating mucosal disease activity, relative risks of stricture, and odds ratios of predicting disease development.Results: Serum cathelicidin levels were inversely correlated with Partial Mayo Scores of UC patients and Harvey-Bradshaw Indices of CD patients. Among IBD patients with moderate or severe initial disease activity, the patients with high initial LL-37 levels had significantly better recovery than the patients with low initial LL-37 levels after 6-18 months, suggesting that high LL-37 levels correlate with good prognosis. Co-evaluation of LL-37 and CRP levels was more accurate than CRP alone or LL-37 alone in the correlation with Mayo Endoscopic Score of UC patients. Low LL-37 levels indicated a significantly elevated risk of intestinal stricture in CD patients.Conclusion: Co-evaluation of LL-37 and CRP can indicate mucosal disease activity in UC patients. LL-37 can predict future clinical activity in IBD patients and indicate risk of intestinal stricture in CD patients. [ABSTRACT FROM AUTHOR]

Aspergillus spp. are a leading cause of mortality in chronic granulomatous disease ( CGD), but other fungi have emerged in the era of mould prophylaxis. Of these, Phellinus spp. are an under-recognised cause of invasive fungal infections ( IFIs) in CGD, and data on their presentation and management are scarce. We present a patient with CGD who developed disseminated IFI involving the lungs and brain. Surgical specimens grew a basidiomycete which was disregarded as a contaminant. After three months of progressive disease despite antifungals, he was diagnosed with Phellinus tropicalis by internal transcribed spacer ( ITS) sequencing. He improved with amphotericin B and isavuconazole but required haematopoietic stem cell transplantation ( HSCT). We review the literature on Phellinus infections in CGD and conclude that: (i) these infections emerge on mould-active prophylaxis and are indolent; (ii) they typically cause locally destructive disease but can disseminate; (iii) diagnosis is delayed and requires molecular methods; (iv) amphotericin B is most active in vitro; and (v) treatment is protracted and requires surgery and possibly HSCT. In conclusion, Phellinus spp. are emerging pathogens in CGD. Every effort should be made to establish the diagnosis of non- Aspergillus IFIs in patients with CGD by sending tissue specimens for molecular diagnostics. [ABSTRACT FROM AUTHOR]

A case study of a 64-year-old man who reported of metastatic choroidal melanoma with a 3-month history of progressive skin tightening is presented. It notes that the examinations favored a sclerosing disorder including morphea and eosinophilic fasciitis. The article discusses the use of pembrolizumab in the treatment of generalized morphea which is a programmed cell death inhibitor. It notes that pembrolizumab was stopped, and prednisone was initiated and notes that patient showed improvement.

Prokineticin 2 (PK2) has been indicated as an output signaling molecule for the suprachiasmatic nucleus (SCN) circadian clock. Most of these studies were performed with nocturnal animals, particularly mice and rats. In the current study, the PK2 and its receptor, PKR2, was cloned from a species of diurnal macaque monkey. The macaque monkey PK2 and PKR2 were found to be highly homologous to that of other mammalian species. The mRNA expression of PK2 and PKR2 in the macaque brain was examined byin situhybridization. The expression patterns of PK2 and PKR2 in the macaque brain were found to be quite similar to that of the mouse brain. Particularly, PK2 mRNA was shown to oscillate in the SCN of the macaque brain in the same phase and with similar amplitude with that of nocturnal mouse brain. PKR2 expression was also detected in known primary SCN targets, including the midline thalamic and hypothalamic nuclei. In addition, we detected the expression of PKR2 mRNA in the dorsal raphe nucleus (DR) of both macaque and mouse brains. As a likely SCN to dorsal raphe projection has previously been indicated, the expression of PKR2 in the raphe nuclei of both macaque and mouse brain signifies a possible role of DR as a previously unrecognized primary SCN projection target. [ABSTRACT FROM AUTHOR]

Background: Cathelicidin (LL-37 in humans and mCRAMP in mice) represents a family of endogenous antimicrobial and anti-inflammatory peptides. Cancer-associated fibroblasts can promote the proliferation of colon cancer cells and growth of colon cancer tumors. Methods: We examined the role of cathelicidin in the development of colon cancer, using subcutaneous human HT-29 colon-cancer-cell-derived tumor model in nude mice and azoxymethane- and dextran sulfate-mediated colon cancer model in C57BL/6 mice. We also determined the indirect antitumoral mechanism of cathelicidin via the inhibition of epithelialmesenchymal transition (EMT) of colon cancer cells and fibroblast-supported colon cancer cell proliferation. Results: Intravenous administration of cathelicidin expressing adeno-associated virus significantly reduced the size of tumors, tumor-derived collagen expression, and tumor-derived fibroblast expression in HT-29-derived subcutaneous tumors in nude mice. Enema administration of the mouse cathelicidin peptide significantly reduced the size and number of colonic tumors in azoxymethane- and dextran sulfate-treated mice without inducing apoptosis in tumors and the adjacent normal colonic tissues. Cathelicidin inhibited the collagen expression and vimentinpositive fibroblast expression in colonic tumors. Cathelicidin did not directly affect HT-29 cell viability, but did significantly reduce tumor growth factor-ß1-induced EMT of colon cancer cells. Media conditioned by the human colonic CCD-18Co fibroblasts promoted human colon cancer HT-29 cell proliferation. Cathelicidin pretreatment inhibited colon cancer cell proliferation mediated by media conditioned by human colonic CCD-18Co fibroblasts. Cathelicidin disrupted tubulin distribution in colonic fibroblasts. Disruption of tubulin in fibroblasts reduced fibroblast-supported colon cancer cell proliferation. Conclusion: Cathelicidin effectively inhibits colon cancer development by interfering with EMT and fibroblast-supported colon cancer cell proliferation. [ABSTRACT FROM AUTHOR]