Rejected

Psoriasis is an immune-mediated chronic and painful disease characterized by red raised patches of inflamed skin that may have desquamation, silvery-white scales, itching and cracks. The susceptibility of developing psoriasis depends on multiple factors, with a complex interplay between genetic and environmental factors. Studies have suggested an association between autosomal dominant CARD14 (caspase recruitment domain-containing protein 14) gain-of-function mutations with the pathophysiology of psoriasis. In this study, non-synonymous single-nucleotide polymorphisms (nsSNPs) of CARD14 gene were assessed to determine their association with psoriasis in Pakistani population. A total of 123 subjects (63 patients with psoriasis and 60 normal controls) were included in this study. DNA was extracted from blood, and PCR analysis was performed followed by Sanger sequencing for 18 CARD14 specific nsSNPs (14 previously reported and the 4 most pathogenic nsSNPs identified using bioinformatics analysis). Among the 18 tested SNPs, only 2 nsSNP, rs2066965 (R547S) and rs34367357 (V585I), were found to be associated with psoriasis. Furthermore, rs2066965 heterozygous genotype was found to be more prevalent in patients with joint pain. Additionally, the 3D structure of CARD14 protein was predicted using alpha-fold2. NMSim web server was used to perform coarse grind simulations of wild-type CARD14 and two mutated structures. R547S increases protein flexibility, whereas V353I is shown to promote CARD14-induced NF-kappa B activation. This study confirms the association between two CARD14 nsSNPs, rs2066965 and rs34367357 with psoriasis in a Pakistani population, and could be helpful in identifying the role of CARD14 gene variants as potential genetic markers in patients with psoriasis.

Prescribed opioids are commonly used in the older community-dwelling population for the treatment of chronic pain. Although the harmful effects of opioid abuse and overdose are well understood, little is known about the long-term cardiovascular (CV) effects of prescribed opioids. The aim of this study was to investigate the CV effects associated with prescribed opioid use.

Human parvovirus B19 causes life-threatening anemia due to transient red cell aplasia (TRCA) in individuals with sickle cell disease (SCD). Children with SCD experiencing profound anemia during TRCA often require red blood cell transfusions and hospitalization. The prevalence of vitamin deficiencies in SCD is high and deficiencies are associated with respiratory and pain symptoms, but the effects of vitamins on acute infection with parvovirus B19 remain unclear. We performed a clinical study in which 20 SCD patients hospitalized with parvovirus B19 infections (Day 0) were monitored over a 120-day time course to query relationships between vitamins A and D and clinical outcomes. There were significant negative correlations between Day 0 vitamin levels and disease consequences (e.g., red blood cell transfusion requirements, inflammatory cytokines). There were significant positive correlations (i) between Day 0 vitamins and peak virus-specific antibodies in nasal wash, and (ii) between Day 0 virus-specific serum plus nasal wash antibodies and absolute reticulocyte counts. There was a significant negative correlation between Day 0 virus-specific serum antibodies and virus loads. To explain the results, we propose circular and complex mechanisms. Low baseline vitamin levels may weaken virus-specific immune responses to permit virus amplification and reticulocyte loss; consequent damage may further reduce vitamin levels and virus-specific immunity. While the complex benefits of vitamins are not fully understood, we propose that maintenance of replete vitamin A and D levels in children with SCD will serve as prophylaxis against parvovirus B19-induced TRCA complications.

The ever-growing amount of health information available on the web is increasing the demand for tools providing personalized and actionable health information. Such tools include symptom checkers that provide users with a potential diagnosis after responding to a set of probes about their symptoms. Although the potential for their utility is great, little is known about such tools' actual use and effects.

Posttraumatic stress disorder (PTSD) and chronic pain are highly prevalent and co-morbid among veterans. Moral injury (MI), which results from traumatic experiences that conflict with deeply held moral beliefs, is also associated with pain. However, relationships between different types of exposures to potentially morally injurious events (PMIEs) and pain have not yet been investigated. In the current study, we investigated these relationships between exposure to PMIEs (betrayal, witnessing, and perpetration) and different types of pain (joint pain, muscle pain, and overall pain intensity), while controlling for other relevant variables (including PTSD symptoms, combat exposure, adverse childhood experiences, age, gender, and race/ethnicity). We also examined gender differences in these associations. Participants were 11,871 veterans drawn from a nationwide, population-based survey who self-reported exposure to PMIEs, PTSD symptoms, frequency of adverse childhood experiences, combat exposure, sociodemographic information, past six-month joint pain, past six-month muscle pain, and past week overall pain intensity. Population weighted regression models demonstrated that PMIEs were not significantly associated with joint or muscle pain, but that betrayal was associated with past week overall pain intensity, even when controlling for all other variables. Models investigating men and women separately found that for women, betrayal was associated with joint pain and pain intensity, but for men, betrayal was not associated with any pain outcome. These findings suggest that it may be especially important to assess betrayal when treating patients with a history of trauma and chronic pain.

Dupilumab is the first biologic licensed to treat patients with moderate-to-severe atopic dermatitis (AD) who require systemic therapy. PROLEAD was designed to document the real-world effectiveness and safety of dupilumab in patients with moderate-to-severe AD. The present study aims to describe the baseline characteristics of patients treated with dupilumab in Germany.

Itch (or pruritus) is an unpleasant sensation, inducing the desire to scratch. It is also a major and distressing symptom of many skin and systemic diseases. The involvement of histamine, which is a major itch mediator, has been extensively examined. Recent studies suggest that histamine-independent pathways may play roles in chronic itch. Therefore, antihistamines are not always effective in the treatment of patients with chronic itch. The development of biologics and κ-opioid receptor (KOR) agonists has contributed to advances in the treatment of itch; however, since biologics are expensive for patients to purchase, some patients may limit or discontinue their use of these agents. Furthermore, KOR agonists need to be prescribed with caution due to risks of side effects in the central nervous system. Janus kinase (JAK) inhibitors are sometimes associated with side effects, such as infection. In this review, we summarize antidepressants, antineuralgics, cyclosporine A, antibiotics, crotamiton, phosphodiesterase 4 inhibitor, botulinum toxin type A, herbal medicines, phototherapy, and acupuncture therapy as itch treatment options other than antihistamines, biologics, opioids, and JAK inhibitors; we also explain their underlying mechanisms of action.

To study the effectiveness of periarticular infiltration (PI), including the proximal donor site vs. placebo in anterior cruciate ligament (ACL) reconstruction.

Neuropathic pain is a common complication in neuromyelitis optica spectrum disorder (NMOSD), which seriously affects the quality of life of NMOSD patients, with no satisfactory treatment. And risk factors of neuropathic pain are still uncertain.

Drug hypersensitivity syndrome (DHS) induced by sulfasalazine is a serious systemic delayed adverse drug reaction, which is associated with significant morbidity and mortality.