Tofacitinib in the management of active psoriatic arthritis: patient selection and perspectives.

Tofacitinib is an oral Janus kinase inhibitor approved for the treatment of psoriatic arthritis (PsA). It provides an alternative option for patients who have had an inadequate response and tolerance to other disease modifying antirheumatic drugs (DMARDs). It has demonstrated comparable efficacy to biologics, is effective in the management of treatment resistant disease, and is reported to improve enthesitis, dactylitis, and radiographic progression. Tofacitinib is also associated with an increased risk of serious infections, malignancy, and laboratory abnormalities. There is currently a large armamentarium of therapies for psoriatic arthritis, and choosing among treatments can be challenging. Due to this wide selection, a thorough assessment of psoriatic disease phenotype, patient preference, disease presentation, and comorbidities is critical. This review addresses key considerations in patient selection for the treatment of PsA with tofacitinib

Acrodermatitis continua of Hallopeau: clinical perspectives.

Acrodermatitis continua of Hallopeau (ACH) is a rare, sterile pustular eruption of one or more digits. The condition presents with tender pustules and underlying erythema on the tip of a digit, more frequently arising on a finger than a toe. As far as classification, ACH is considered a localized form of pustular psoriasis. The eruption typically occurs after local trauma or infection, but such a history is not always present and various other etiologies have been described including infectious, neural, inflammatory, and genetic causes. The natural progression of ACH is chronic and progressive, often resulting in irreversible complications such as onychodystrophy that can result in anonychia, as well as osteitis that can result in osteolysis of the distal phalanges. Because of the rarity of ACH, there have been no randomized controlled studies to evaluate therapies, resulting in an absence of standardized treatment guidelines. In clinical practice, a wide variety of treatments have been attempted, with outcomes ranging from recalcitrance to complete resolution. In recent years, the introduction of biologics has provided a new class of therapy that has revolutionized the treatment of ACH. Specifically, rapid and sustained responses have been reported with the use of anti-tumor necrosis factor agents like infliximab, adalimumab, and etanercept; IL-17 inhibitors like secukinumab; IL-12/23 inhibitors like ustekinumab; and IL-1 inhibitors like anakinra. Nevertheless, there remains a considerable need for more research into treatment for the benefit of individual patients with ACH as well as for the clinical knowledge gained by such efforts. The purpose of this review is to provide a comprehensive overview of the key features of ACH as well as a discussion of clinical management strategies for this unique and debilitating condition

Implementation of an Ultraviolet Phototherapy Service at a National Referral Hospital in Western Kenya: Reflections on Challenges and Lessons Learned.

IntroductionIn order to manage skin conditions at a national referral hospital level in Kenya, specialized dermatology services, such as dermatologic surgery, dermatopathology, phototherapy, and sub-specialty care, should be offered, as is typically available in referral hospitals around the world. A Kenyan patient with prurigo nodularis, whose severe itch remitted after phototherapy treatment at the University of California, San Francisco (UCSF), inspired the development of a phototherapy service at Academic Model Providing Access to Healthcare (AMPATH), a partnership in Western Kenya between Moi Teaching and Referral Hospital, Moi University College of Health Sciences, and a consortium of North American academic medical centers.MethodsInitial project funds were raised through a crowdfunding campaign and fundraising events. A new narrowband ultraviolet B phototherapy unit and replacement bulbs were donated and air shipped to Eldoret, Kenya. A team of dermatologists and phototherapy nurses from UCSF conducted a 2-day training session. US-based dermatologists affiliated with AMPATH provide ongoing support through regular communication and on-site visits.ResultsEarly in implementation, challenges faced included training clinical staff with limited experience in phototherapy and improving communication between nurses and clinicians. More recent challenges include frequent rotation of specialty clinic nurses in the dermatology clinic, adaptation of phototherapy guidelines to balance patient volume with service delivery capacity, and training assessment of disease activity in darkly pigmented skin.ConclusionStrategies that have been helpful in addressing implementation challenges include: increasing on-site and remote training opportunities for clinicians and nurses, developing a tiered payment schema, educating patients to combat misconceptions about phototherapy, dynamic phototherapy referral guidelines to accommodate service delivery capacity, and prioritizing the engagement of a multidisciplinary team

Factors Influencing Sleep Difficulty and Sleep Quantity in the Citizen Pscientist Psoriatic Cohort.

IntroductionSleep is essential for overall health and well-being, yet more than one-third of adults report inadequate sleep. The prevalence is higher among people with psoriasis, with up to 85.4% of the psoriatic population reporting sleep disruption. Poor sleep among psoriasis patients is particularly concerning because psoriasis is independently associated with many of the same comorbidities as sleep dysfunction, including cardiovascular disease, obesity, and depression. Given the high prevalence and serious consequences of disordered sleep in psoriasis, it is vital to understand the nature of sleep disturbance in this population. This study was designed to help meet this need by using survey data from Citizen Pscientist, an online patient portal developed by the National Psoriasis Foundation.MethodsOur analysis included 3118 participants who identified as having a diagnosis by a physician of psoriasis alone or psoriasis with psoriatic arthritis. Demographic information, psoriasis severity and duration, sleep apnea status, smoking and alcohol consumption, itch timing, and sleep characteristics were included. Two separate multivariate logistic regression models in STATA were used to determine whether the presence of psoriatic arthritis, age, gender, body mass index, comorbid sleep apnea, psoriasis severity, timing of worst itch, smoking status, or high-risk alcohol consumption were associated with sleep difficulty or low sleep quantity, defined by the American Academy of Sleep Medicine as less than 7 h of sleep per night on average.ResultsResults from the multivariate logistic regressions found that sleep difficulty was associated with psoriatic arthritis (OR 2.15, 95% CI [1.79-2.58]), female gender (2.03 [1.67-2.46]), obese body mass index (BMI ≥ 30) (1.25 [1.00-1.56]), sleep apnea (1.41 [1.07-1.86]), psoriasis severity of moderate (1.59 [1.30-1.94]) or severe (2.40 [1.87-3.08]), and smoking (1.60 [1.26-2.02]). Low sleep quantity was associated with obese BMI (1.62 [1.29-2.03]), sleep apnea (1.30 [1.01-1.68]), psoriasis severity of moderate (1.41 [1.16-1.72]) or severe (1.40 [1.11-1.76]), and smoking (1.62 [1.31-2.00]). Sleep difficulty and low sleep quantity were not associated with age, alcohol consumption, or timing of worst itch.ConclusionThese results are potentially meaningful in several aspects. We identify an important distinction between sleep difficulty and sleep quantity in psoriatic disease, whereby having psoriatic arthritis and being female are each associated with sleep difficulty despite no association with low sleep quantity. Furthermore, there is conflicting evidence from prior studies as to whether psoriasis severity is associated with sleep difficulty, but this well-powered, large study revealed a strong, graded relationship between psoriasis severity and both sleep difficulty and low sleep quantity. Overall, our results show that both sleep difficulty and low sleep quantity were associated with multiple factors in this analysis of a large psoriatic cohort. These findings suggest that dermatologists may gather clinically useful information by screening psoriatic patients for trouble sleeping and low sleep quantity to identify potential comorbidities and to more effectively guide disease management

Decision-Making and Depressive Symptomatology

Difficulty making decisions is a core symptom of depressive illness, but the nature of these difficulties has not been well characterized. The two studies presented herein use the same hypothetical scenarios that call for a decision. In Study 1, participants were asked to make and explain their decisions in a free-response format, as well as to describe their prior experiences with similar situations. The results suggest that those with more depressive symptoms make decisions that are less likely to further their interests. We also identified several interesting associations between features of decision-making and the presence of depressive symptoms. In Study 2, participants were guided through their decisions with simple decision tools to investigate whether the association between depressive symptoms and poor decisions is better accounted for by failure to use of good decision-making strategies, or by other factors, such as differences in priorities or goals. With this minimal intervention the quality of decisions no longer declined significantly as a function of depressive symptom severity. Moreover, few associations between depressive symptom severity and decision-related goals and priorities were evident, suggesting that the previously-exposed difficulties of depressed individuals with decision-making were largely the result of their failure to use effective decision-making techniques

Current Challenges in Detecting Food Allergens by Shotgun and Targeted Proteomic Approaches: A Case Study on Traces of Peanut Allergens in Baked Cookies

There is a need for selective and sensitive methods to detect the presence of food allergens at trace levels in highly processed food products. In this work, a combination of non-targeted and targeted proteomics approaches are used to illustrate the difficulties encountered in the detection of the major peanut allergens Ara h 1, Ara h 2 and Ara h 3 from a representative processed food matrix. Shotgun proteomics was employed for selection of the proteotypic peptides for targeted approaches via selective reaction monitoring. Peanut presence through detection of the proteotypic Ara h 3/4 peptides AHVQVVDSNGNR (m/z 432.5, 3+) and SPDIYNPQAGSLK (m/z 695.4, 2+) was confirmed and the developed method was able to detect peanut presence at trace levels (≥10 μg peanut g−1 matrix) in baked cookies

Expressions 2004-2006

https://openspace.dmacc.edu/expressions/1022/thumbnail.jp

Micro-proteomics with iterative data analysis:proteome analysis in <i>C.elegans</i> at the single worm level

Proteomics studies typically analyze proteins at a population level, using extracts prepared from tens of thousands to millions of cells. The resulting measurements correspond to average values across the cell population and can mask considerable variation in protein expression and function between individual cells or organisms. Here, we report the development of micro-proteomics for the analysis of Caenorhabditis elegans, a eukaryote composed of 959 somatic cells and approximate to 1500 germ cells, measuring the worm proteome at a single organism level to a depth of approximate to 3000 proteins. This includes detection of proteins across a wide dynamic range of expression levels (&gt;6 orders of magnitude), including many chromatin-associated factors involved in chromosome structure and gene regulation. We apply the micro-proteomics workflow to measure the global proteome response to heat-shock in individual nematodes. This shows variation between individual animals in the magnitude of proteome response following heat-shock, including variable induction of heat-shock proteins. The micro-proteomics pipeline thus facilitates the investigation of stochastic variation in protein expression between individuals within an isogenic population of C. elegans. All data described in this study are available online via the Encyclopedia of Proteome Dynamics (), an open access, searchable database resource

A behavioral comparison of male and female adults with high functioning autism spectrum conditions

Autism spectrum conditions (ASC) affect more males than females in the general population. However, within ASC it is unclear if there are phenotypic sex differences. Testing for similarities and differences between the sexes is important not only for clinical assessment but also has implications for theories of typical sex differences and of autism. Using cognitive and behavioral measures, we investigated similarities and differences between the sexes in age- and IQ-matched adults with ASC (high-functioning autism or Asperger syndrome). Of the 83 (45 males and 38 females) participants, 62 (33 males and 29 females) met Autism Diagnostic Interview-Revised (ADI-R) cut-off criteria for autism in childhood and were included in all subsequent analyses. The severity of childhood core autism symptoms did not differ between the sexes. Males and females also did not differ in self-reported empathy, systemizing, anxiety, depression, and obsessive-compulsive traits/symptoms or mentalizing performance. However, adult females with ASC showed more lifetime sensory symptoms (p = 0.036), fewer current socio-communication difficulties (p = 0.001), and more self-reported autistic traits (p = 0.012) than males. In addition, females with ASC who also had developmental language delay had lower current performance IQ than those without developmental language delay (p<0.001), a pattern not seen in males. The absence of typical sex differences in empathizing-systemizing profiles within the autism spectrum confirms a prediction from the extreme male brain theory. Behavioral sex differences within ASC may also reflect different developmental mechanisms between males and females with ASC. We discuss the importance of the superficially better socio-communication ability in adult females with ASC in terms of why females with ASC may more often go under-recognized, and receive their diagnosis later, than males

Causal Network Accounts Of Ill-being: Depression & Digital Well-being

Depression is a common and devastating instance of ill-being which deserves an account. Moreover, the ill-being of depression is impacted by digital technology: some uses of digital technology increase such ill-being while other uses of digital technology increase well-being. So a good account of ill-being would explicate the antecedents of depressive symptoms and their relief, digitally and otherwise. This paper borrows a causal network account of well-being and applies it to ill-being, particularly depression. Causal networks are found to provide a principled, coherent, intuitively plausible, and empirically adequate account of cases of depression in every-day and digital contexts. Causal network accounts of ill-being also offer philosophical, scientific, and practical utility. Insofar as other accounts of ill-being cannot offer these advantages, we should prefer causal network accounts of ill-being