Dynamics and Spatial Genomics of the Nascent Transcriptome by Intron seqFISH.

Visualization of the transcriptome and the nuclear organization in situ has been challenging for single-cell analysis. Here, we demonstrate a multiplexed single-molecule in situ method, intron seqFISH, that allows imaging of 10,421 genes at their nascent transcription active sites in single cells, followed by mRNA and lncRNA seqFISH and immunofluorescence. This nascent transcriptome-profiling method can identify different cell types and states with mouse embryonic stem cells and fibroblasts. The nascent sites of RNA synthesis tend to be localized on the surfaces of chromosome territories, and their organization in individual cells is highly variable. Surprisingly, the global nascent transcription oscillated asynchronously in individual cells with a period of 2 hr in mouse embryonic stem cells, as well as in fibroblasts. Together, spatial genomics of the nascent transcriptome by intron seqFISH reveals nuclear organizational principles and fast dynamics in single cells that are otherwise obscured.

Review of radiofrequency microneedling: history, devices and uses.

Radiofrequency microneedling (RFM) has recently become a popular choice for the treatment of various dermatologic conditions and rejuvenation. Many studies have sought to evaluate the efficacy of RFM. However, its role in the management of these conditions remains unclear. A comprehensive literature search including randomized controlled trials, cohort studies, and case series evaluating the efficacy of RFM in various skin conditions was performed. In this review, we discuss the history and mechanism of RFM, describe various device features, and discuss the use of RFM in various skin conditions and rejuvenation.

Synthesis, Characterization, Thermal Analysis, DFT, and Cytotoxicity of Palladium Complexes with Nitrogen-Donor Ligands.

Three new palladium complexes ([Pd(DABA)Cl2], [Pd(CPDA)Cl2], and [Pd(HZPY)Cl2]) bearing dinitrogen ligands (DABA: 3,4-diaminobenzoic acid; CPDA: 4-chloro-o-phenylenediamine; HZPY: 2-hydraziniopyridine) were synthesized, characterized, and tested against breast cancer (MCF-7), prostate carcinoma cell line (PC3) and liver carcinoma cell line (HEPG2). [Pd(DABA)Cl2] complex exhibited the highest inhibition percentage, lying between 68-71%. The hydrolysis mechanism of each palladium complex, the key step preceding the binding to the biological target, as well as their photophysical properties were explored by means of DFT and TDDFT computations. Results indicate a faster hydrolysis process for the Pd(DABA)Cl2 complex. The computed activation energies for the first and second hydrolysis processes suggest that all the compounds could reach DNA in their monohydrated form.

Psoriasis and Co-morbidity.

Psoriasis is associated with multiple co-morbid medical conditions. The purpose of this study is to evaluate the relationships between psoriasis and cardiovascular disease, psoriatic arthritis, mental health conditions, and immune-mediated diseases, respectively. A literature search was performed during the study period January 1, 2015 to December 18, 2018. Of 2,499 records identified, 28 met our criteria selection and were included in this review. The relationships between psoriasis and these multiple comorbid disease conditions are discussed and are important to consider when developing the treatment plan and overall management of patients with psoriasis. Early recognition and treatment of comorbid disease conditions is important to help improve the quality of life for these patients.

Persisting Ulcerating Lesions After Cyclosporine Therapy for Erosions Found in Flexural Sites.

In February 2012, a patient with a 15-year history of painful, pruritic eruptions presented with a severe exacerbation that had lasted for the previous week. The patient also reported severe headaches, a fever of 38.9°C (102.1°F), a cough, and diarrhea, which had now resolved. Physical examination showed erythematous macerated patches with erosions in the left submammary region, bilateral axillae, and vaginal area (Figure 1), and greasy scale covering the scalp. Despite lessening of the lesions in the submammary region and abdomen with the administration of minocycline 100 mg twice per day and cyclosporine 100 mg three times per day, the patient continued to complain of persistent painful ulcerations in the labia majora and perianal area (Figure 2). The patient was started on acyclovir 400 mg three times per day for 10 days for positive herpes simplex viral culture and ampicillin for Proteus infection of the area.

A Novel Germline Pathogenic Variant of RECQL4 Gene in an Iranian Pedigree with Familial Squamous Cell Carcinoma: A Brief Report.

Squamous cell carcinoma (SCC) is the most common human solid tumor and the leading cause of cancer death. SCC of the breast is a very rare type of cancer that has not been well researched. Early identification of the genetic factors involved can lead to early diagnosis and targeted treatment. The present study was conducted in 2018 at Isfahan University of Medical Sciences (Isfahan, Iran). The proband was a 66-year-old woman with SCC of the breast and a positive family history of cancer. Blood DNA samples were used for whole-exome sequencing to identify germline pathogenic variants. Variant annotation and prioritization were done on variant call format files using bioinformatics software tools. The screened variants were confirmed using the Sanger sequencing method. Co-segregation analysis was performed on the blood DNA samples of the first- and second-degree relatives of the proband to assess the presence of the mutation. A novel germline pathogenic variant was identified in the RECQL4 gene of the family. RECQL4 is a known protein in DNA repair and replication. Considering its effect on other types of SCC, it may play an important role in SCC initiation and progression in the breast.

Review of European registries for psoriasis.

BACKGROUND: Patient registries are databases that contain clinical data for patients with a specific disease or medical condition. OBJECTIVE: The purpose was to identify psoriasis registries in Europe and examine their characteristics and implications. METHODS: We searched Google, the Registry of Patient Registries, and ClinicalTrials.gov to generate a list of European psoriasis registries. We also conducted a literature review for publications related to the psoriasis registries in Europe using PubMed. RESULTS: We identified 13 psoriasis patient registries in Europe. CONCLUSIONS: Patient registries are routinely used in dermatology and psoriasis registries offer pertinent long-term safety information regarding conventional systemic therapies and biologic agents for psoriasis.

Risk for appendicitis, cholecystitis, or diverticulitis in patients with psoriasis.

Numerous comorbidities have been associated with psoriasis; however, no studies have considered the relationship between psoriasis and appendicitis, cholecystitis, or diverticulitis. To determine the incidence rate and hazard risk (HR) ratio of appendicitis, cholecystitis, or diverticulitis in patients with psoriasis, we compared psoriasis patients with healthy controls from the Kaiser Permanente Southern California (KPSC) health network. The Cox proportional hazards regression model was used to examine the risk for appendicitis, cholecystitis, or diverticulitis. Patients with psoriasis had a 1.16 times greater risk for developing diverticulitis compared to controls (P < .01). There was no significant difference in risk for developing appendicitis or cholecystitis. Patients with psoriasis may have an elevated risk for diverticulitis compared to the general population and therefore might require additional monitoring by clinicians.

Rates of latent tuberculosis infection in patients treated with TNF inhibitors for psoriasis: a retrospective chart review.

BACKGROUND: Although tuberculosis screening guidelines for psoriasis patients on TNF inhibitors exist, few studies have reported the prevalence of latent tuberculosis infection (LTBI) and conversion rates in this population. OBJECTIVE: To determine the incidence of LTBI and active tuberculosis in patients with psoriasis receiving TNF inhibitor therapy. METHODS: A total of 138 patients were included in our retrospective study of patients treated from September 2004 to September 2017. Tuberculin skin test was considered positive with an induration of greater than 5 mm. History of Bacillus Calmette-Guérin vaccination, follow-up tests and prophylaxis were recorded. RESULTS: Among 99 biologic-naïve patients, 14 had LTBI before starting biologic therapy and five developed LTBI during TNF inhibitor therapy. One biologic-naïve patient developed LTBI, then active tuberculosis. Among 39 non-biologic-naïve patients, three had LTBI before starting any biologic therapy, and one developed LTBI during treatment. LIMITATIONS: Limitations include small sample size and limited information documented in the medical chart. CONCLUSIONS: LTBI appears to be prevalent among psoriasis patients. Screening for LTBI in patients on biologics may reduce risk of active tuberculosis; however, current methods may not be fully effective. Clinicians may need to use other tools including risk factor assessment to fully evaluate risk.

Drug survival of biologic treatments in psoriasis: a systematic review.

Drug survival measures the length of time until discontinuation of a drug. The length of time a patient remains on a biologic drug is impacted by several factors such as tolerability, side effects, safety profile and effectiveness. To evaluate the long-term drug survival, data of the most commonly prescribed biologic medications used in the treatment of psoriasis, a systematic review was conducted. A literature search using PubMed, the Cochrane Library and the Cumulative Index to Nursing and Allied Health Literature from January 1 2010 to October 28 2016 identified 3734 abstracts. Of which, 36 publications with over 40,000 patients met the inclusion criteria. The median overall drug survival for ustekinumab, adalimumab, infliximab and etanercept was 38.0, 36.5, 26.6 and 24.7 months, respectively. The mean annual drug survival rate of TNF inhibitors was 70%, 57%, 51%, 45% and 41% at years-1, 2, 3, 4 and 5, respectively. The 5-year mean annual drug survival rate of ustekinumab was 87%, 78%, 70%, 71% and 51%, respectively. Based on our findings, ustekinumab appears to have a longer drug survival with lower rates of discontinuation compared to tumor necrosis factor inhibitors.

Review of IL-17 inhibitors for psoriasis.

Background: The development of biologic agents directed against distinct cytokines and receptors has advanced the therapeutic options available for psoriasis patients. Evidence from preclinical studies suggests that IL-17 may contribute to the pathogenesis of psoriasis. Objective: The objective was to review the safety and efficacy profile for each IL-17 inhibitor by evaluating phase III clinical trial data. Methods: We reviewed the results of phase III clinical trials for the IL-17 inhibitors secukinumab, ixekizumab, and brodalumab. Results: At week 12, the proportion of patients reaching Psoriasis Area and Severity Index (PASI 75) was above 60% for the most efficacious dose of each agent with favorable and comparable safety profiles. The most commonly reported adverse events were nasopharyngitis, headache, and upper respiratory tract infection. Conclusions: The clinical improvement among psoriasis patients on IL-17 inhibitors is similar or superior to the improvement seen with commercially produced biologic agents available accompanied by a favorable short-term safety profile. The results of the phase III trials indicate that IL-17 inhibitors are effective therapeutic options for psoriasis patients.

A systematic review of active comparator controlled clinical trials in patients with moderate-to-severe psoriasis.

PURPOSE: Interleukin (IL)-17 and IL-23 inhibitors are the newest biologic agents used in the management of moderate-to-severe psoriasis. Active comparator studies allow for direct comparison of different biologic agents. We sought to systematically investigate the efficacy of newer biologic agents compared to earlier biologics. MATERIALS AND METHODS: We conducted a literature search for randomized control trials that compared the efficacy of a biologic agent with an active comparator. Articles from January 1 2010 to June 26 2017 were searched. Reference lists were also reviewed for studies for inclusion. RESULTS: Twelve studies were included, a majority being phase III trials. All of the studies compared the efficacy of IL-17 and IL-23 inhibitors with adalimumab, etanercept, or ustekinumab with the exception of one study that compared the efficacy of ustekinumab with etanercept. IL-17 and IL-23 inhibitors consistently demonstrate superior efficacy over TNF inhibitors and ustekinumab as assessed by 75%, 90%, and 100% improvement in baseline Psoriasis Area and Severity Index (PASI) scores at week 12. CONCLUSIONS: Overall, IL-17 and IL-23 inhibitors appear to demonstrate superior efficacy and more rapid clinical improvement when compared to older biologic agents. This review may help predict patient outcomes, manage patient expectations, and biologic agent utilization.

Choosing First-Line Biologic Treatment for Moderate-to-Severe Psoriasis: What Does the Evidence Say?

An advanced understanding of the pathogenesis of psoriasis has led to the development of multiple therapeutic options for moderate-to-severe psoriasis. Tumor necrosis factor inhibitors, ustekinumab, interleukin-17 inhibitors, and guselkumab (an interleukin-23 inhibitor recently approved for psoriasis) are commercially available biologic agents for psoriasis. Evidence from clinical trials provides pertinent information regarding the safety and efficacy of biologic agents for psoriasis, which should be integrated into clinical decision making. However, disease presentations, disease severity, and comorbid conditions can complicate the choice of initial treatment, which underscores the importance of providing personalized therapy for patients with psoriasis. Furthermore, each biologic agent offers unique benefits and limitations for the treatment of patients with psoriasis. Here, evidence-based recommendations are presented and discussed regarding first-line biologic therapy options for patients with psoriasis and distinct comorbid conditions or patient-related factors. We discuss the comorbid conditions of psoriatic arthritis, multiple sclerosis, congestive heart failure, inflammatory bowel disease, hepatitis B, and latent tuberculosis. Moreover, we describe treatment recommendations for distinct patient populations with psoriasis, including pediatric patients with psoriasis and patients with psoriasis of childbearing potential and nursing.

Atopic dermatitis 2017: where we were 10-15 years ago in psoriasis.

Novel and innovative treatment options for atopic dermatitis (AD) are underway. The recent advancements in understanding AD are reminiscent of the progress made in psoriasis research over a decade ago.

Do psoriasis patients engage in vigorous physical activity?

Psoriasis is associated with cardiovascular risk factors and myocardial infarction, but regular physical activity is known to decrease the risk of coronary heart disease. We performed a systematic review of PubMed articles indexed for MEDLINE as well as articles in the Embase database and Cochrane Library using the search terms psoriasis and physical activity to determine the likelihood of psoriasis patients to engage in vigorous physical activity. A total of 353 nonduplicate articles were identified, and of 4 relevant studies, one provided sufficient data and was included in our review. Results from our review indicate that individuals with psoriasis are less likely to participate in vigorous physical activity compared to individuals without psoriasis. Further research is necessary to clarify this relationship.

Emerging therapies in psoriasis: a systematic review.

Many new biologics are being studied for use in psoriasis. In this review, we evaluate and summarize findings about emerging biologic therapies for psoriasis. We reviewed published data from phase 2 and 3 clinical trials of 2 IL-17 inhibitors (ixekizumab and brodalumab); 3 IL-23 inhibitors (guselkumab, tildrakizumab, and risankizumab); and 1 tumor necrosis factor (TNF) inhibitor (certolizumab pegol). Janus kinase inhibitors were not included in our review, as they currently are not approved by the US Food and Drug Administration (FDA) and there are no plans to further develop this class for treatment of psoriasis. Overall, the clinical improvement provided by and the safety profiles of these agents are promising; they may be equal to or more efficacious than available therapeutic options for treating the symptoms of psoriasis. Long-term studies are still needed, however, to further establish safety and efficacy profiles for these biologic agents.