Psoriasis immunometabolism: progress on metabolic biomarkers and targeted therapy.

Psoriasis is a common inflammatory disease that affects mainly the skin. However, the moderate to severe forms have been associated with several comorbidities, such as psoriatic arthritis, Crohn's disease, metabolic syndrome and cardiovascular disease. Keratinocytes and T helper cells are the dominant cell types involved in psoriasis development via a complex crosstalk between epithelial cells, peripheral immune cells and immune cells residing in the skin. Immunometabolism has emerged as a potent mechanism elucidating the aetiopathogenesis of psoriasis, offering novel specific targets to diagnose and treat psoriasis early. The present article discusses the metabolic reprogramming of activated T cells, tissue-resident memory T cells and keratinocytes in psoriatic skin, presenting associated metabolic biomarkers and therapeutic targets. In psoriatic phenotype, keratinocytes and activated T cells are glycolysis dependent and are characterized by disruptions in the TCA cycle, the amino acid metabolism and the fatty acid metabolism. Upregulation of the mammalian target of rapamycin (mTOR) results in hyperproliferation and cytokine secretion by immune cells and keratinocytes. Metabolic reprogramming through the inhibition of affected metabolic pathways and the dietary restoration of metabolic imbalances may thus present a potent therapeutic opportunity to achieve long-term management of psoriasis and improved quality of life with minimum adverse effects.

Using Virtual Objects With Hand-Tracking: The Effects of Visual Congruence and Mid-Air Haptics on Sense of Agency.

Virtual reality expands the possibilities of human action. With hand-tracking technology, we can directly interact with these environments without the need for a mediating controller. Much previous research has looked at the user-avatar relationship. Here we explore the avatar-object relationship by manipulating the visual congruence and haptic feedback of the virtual object of interaction. We examine the effect of these variables on the sense of agency (SoA), which refers to the feeling of control over our actions and their effects. This psychological variable is highly relevant to user experience and is attracting increased interest in the field. Our results showed that implicit SoA was not significantly affected by visual congruence and haptics. However, both of these manipulations significantly affected explicit SoA, which was strengthened by the presence of mid-air haptics and was weakened by the presence of visual incongruence. We propose an explanation of these findings that draws on the cue integration theory of SoA. We also discuss the implications of these findings for HCI research and design.

Cutaneous body image in patients with hidradenitis suppurativa: a hospital-based cross-sectional study.

Hidradenitis suppurativa (HS) has been linked with body image (BI) impairment and reduced quality of life (QoL). We sought to evaluate the associations between Cutaneous Body Image Scale (CBIS) and disease severity in HS patients.Between July 2020 and January 2022, a cross-sectional study was carried out including consecutive HS patients above the age of 16 who attended a Tertiary Referral Hospital in Greece. Disease Severity was graded with the Hurley stage, HS-Physician's Global Assessment (HS-PGA) scale, and the Modified Sartorius scale (MSS). Patients completed at their first visit ten survey instruments including Patients' Severity of disease, pain and pruritus scale, CBIS, Multidimensional Body-Self Relations Questionnaire (MBSRQ) including 5 subscales: Appearance Evaluation (AE), Appearance Orientation (AO), Body Areas Satisfaction Scale (BASS), Overweight Preoccupation (OWP), and Self Classified Weight (SCW) , Dermatology Quality of Life Index (DLQI), Skindex-16, EQ5D 5L, EQ- visual analogue scale (VAS), PHQ9, and GAD7. In total, 70 HS patients above 16 years old participated, mean [SD] age, 34.44 [11.64] years; 49/70 (70%) males and 21/70 (30%) females. Mean ± SD CBI, DLQI, Skindex-16 total, EQ-5D-5L, EQ VAS, PHQ9 and GAD7 were 5.59 ± 1.58, 11.70 ± 8.88, 52.90 ± 27.75, 0.75 ± 0.21, 62.48 ± 21.12, 7.64 ± 5.56, 7.87 ± 5.23 respectively. Moderate to severe CBI dissatisfaction was reported by 36/70 (51.42%) patients. CBI was correlated with appearance evaluation (AE) (p < 0.01, r = 0.544), body areas satisfaction (BASS) (p < 0.01, r = 0.481), and overweight preoccupation subscale (OWPS) (p < 0.01, r = - 0.267), and Skindex-16 (p < 0.01, r = - 0.288). HS patients with affected genital areas scored higher in disease patient's severity score (p = 0.015), and male patients scored higher in Skindex-16 than females(p < 0.01). Our study found that the mean of CBI in HS patients was 5.59 ± SD 1.58. Predictors for CBI dissatisfaction were low scores of MBSRQ Appearance Evaluation (AE) and Body Areas Satisfaction Subscale (BASS).

Pruritogenic Mediators and New Antipruritic Drugs in Atopic Dermatitis.

Atopic dermatitis (AD) is a common highly pruritic chronic inflammatory skin disorder affecting 5-20% of children worldwide, while the prevalence in adults varies from 7 to 10%. Patients with AD experience intense pruritus that could lead to sleep disturbance and impaired quality of life. Here, we analyze the pathophysiology of itchiness in AD. We extensively review the histamine-dependent and histamine-independent pruritogens. Several receptors, substance P, secreted molecules, chemokines, and cytokines are involved as mediators in chronic itch. We also, summarize the new emerging antipruritic drugs in atopic dermatitis.

Microbiomics in Collusion with the Nervous System in Carcinogenesis: Diagnosis, Pathogenesis and Treatment.

The influence of the naturally occurring population of microbes on various human diseases has been a topic of much recent interest. Not surprisingly, continuously growing attention is devoted to the existence of a gut brain axis, where the microbiota present in the gut can affect the nervous system through the release of metabolites, stimulation of the immune system, changing the permeability of the blood-brain barrier or activating the vagus nerves. Many of the methods that stimulate the nervous system can also lead to the development of cancer by manipulating pathways associated with the hallmarks of cancer. Moreover, neurogenesis or the creation of new nervous tissue, is associated with the development and progression of cancer in a similar manner as the blood and lymphatic systems. Finally, microbes can secrete neurotransmitters, which can stimulate cancer growth and development. In this review we discuss the latest evidence that support the importance of microbiota and peripheral nerves in cancer development and dissemination.

Many Voices in a Choir: Tumor-Induced Neurogenesis and Neuronal Driven Alternative Splicing Sound Like Suspects in Tumor Growth and Dissemination.

During development, as tissues expand and grow, they require circulatory, lymphatic, and nervous system expansion for proper function and support. Similarly, as tumors arise and develop, they also require the expansion of these systems to support them. While the contribution of blood and lymphatic systems to the development and progression of cancer is well known and is targeted with anticancer drugs, the contribution of the nervous system is less well studied and understood. Recent studies have shown that the interaction between neurons and a tumor are bilateral and promote metastasis on one hand, and the formation of new nerve structures (neoneurogenesis) on the other. Substances such as neurotransmitters and neurotrophins being the main actors in such interplay, it seems reasonable to expect that alternative splicing and the different populations of protein isoforms can affect tumor-derived neurogenesis. Here, we report the different, documented ways in which neurons contribute to the development and progression of cancer and investigate what is currently known regarding cancer-neuronal interaction in several specific cancer types. Furthermore, we discuss the incidence of alternative splicing that have been identified as playing a role in tumor-induced neoneurogenesis, cancer development and progression. Several examples of changes in alternative splicing that give rise to different isoforms in nerve tissue that support cancer progression, growth and development have also been investigated. Finally, we discuss the potential of our knowledge in alternative splicing to improve tumor diagnosis and treatment.

Pruritic annular and vesicular eruption on trunk and extremities.

We report a case of linear IgA bullous dermatosis, a rare autoimmune blistering disorder that usually presents with the abrupt onset of tense bullae. We also emphasize the importance of direct immunofluorescence for the definitive diagnosis.

Hydroxychloroquine-induced erythema multiforme.

Hydroxychloroquine is a commonly used medication and rarely may result in development of erythema multiforme. This potential cutaneous side effect should be highlighted in information given to patients prior to hydroxychloroquine commencement.

Generalized Lichen Planus-like Eruption Related to Trimebutine.

Trimebutine is a spasmolytic agent with antimuscarinic effects that is used for the treatment of irritable bowel syndrome (IBS) and lower gastrointestinal tract motility disorders. Lichenoid drug eruptions (LDE) to trimebutine maleate have not been previously reported. Here we present the case of a 50-year-old male patient who developed an extensive lichenoid eruption on his upper and lower extremities and trunk 4 weeks after starting treatment with trimebutine maleate 300 mg once daily for IBS. Two months after discontinuation of the drug and administration of topical treatment with emollients and corticosteroids, the LDE cleared completely with no recurrence. The diagnosis of LDE due to trimebutine was made, based upon the clinical features resembling lichen planus, the histological findings of interface dermatitis, the evidence of a temporal relationship between drug intake and the development of skin lesions, and resolution upon discontinuation of the drug. To the best of the authors' knowledge, LDE following trimebutine maleate intake has not been previously reported. Management of trimebutine-induced LDE includes withdrawal of the causative agent and treatment with potent topical corticosteroids. LEARNING POINTS: Cutaneous adverse events due to trimebutine maleate, an antispasmodic agent frequently used for the treatment of irritable bowel syndrome (IBS), have rarely been reported.Lichenoid drug eruption (LDE), also called drug-induced lichen planus, is an uncommon cutaneous adverse effect of several drugs.Here we report the first case of trimebutine maleate-induced LDE.

Lymphomatoid Papulosis Type A: A Case Report of the "Wait-and-See Strategy" in a 27-Year-Old Male Patient with Extensive Disease.

This is the case of a 27-year-old male patient with a newly diagnosed extensive lymphomatoid papulosis type A involving cosmetically sensitive areas (e.g. face), who refused to be treated with a low dose of methotrexate, as recommended by the published literature. The natural course of the disease was proved to be strikingly satisfying though, with a complete regression of all skin lesions at the 4-week follow-up, including an ulcerated nodule 3 x 3 cm in dimension, which was expected to heal at least in months. We report this case to reconsider weighting the risks and the short-term benefits of methotrexate treatment, even in the case of an extensive disease.

Beware of anal fissures: pemphigus vulgaris of the anal canal.

A case of anal pemphigus vulgaris in a 49-year-old female suffering from pemphigus vulgaris of the oral cavity is reported. The oral manifestations were in remission until she presented with episodes of anal pain and bleeding on defecation, initially mimicking anal fissures. Inspection revealed prominent painful erosions in the anal canal with external hemorrhoids and strands of sloughing skin and maceration in the anal verge. Histology and direct immunofluorescence test were consistent with pemphigus vulgaris. The disease was refractory to treatment and complete remission was only achieved with the combination of rituximab and corticosteroids. Anal involvement seems to be an uncommon or underreported manifestation of pemphigus vulgaris. Gastroenterologists should be aware of this entity, especially in areas with a high incidence of the disease, for appropriate diagnosis and management.