Re-examining the evidence that ivermectin induces a melanoma-like state in Xenopus embryos.

Modeling metastasis in animal systems has been an important focus for developing cancer therapeutics. Xenopus laevis is a well-established model, known for its use in identifying genetic mechanisms underlying diseases and disorders in humans. Prior literature has suggested that the drug, ivermectin, can be used in Xenopus to induce melanocytes to convert into a metastatic melanoma-like state, and thus could be ideal for testing possible melanoma therapies in vivo. However, there are notable inconsistencies between ivermectin studies in Xenopus and the application of ivermectin in mammalian systems, that are relevant to cancer and melanoma research. In this review, we examine the ivermectin-induced phenotypes in Xenopus, and we explore the current uses of ivermectin in human research. We conclude that while ivermectin may be a useful drug for many biomedical purposes, it is not ideal to induce a metastatic melanocyte phenotype in Xenopus for testing the effects of potential melanoma therapeutics.

Molecular Basis for Global Incidence of Pemphigoid Diseases and Differences in Phenotypes.

Pemphigoid (Pg) diseases are a group of potentially fatal autoimmune mucocutaneous diseases. They have different clinical phenotypes, involving only the skin or multiple mucous membranes. They occur globally and frequently affect the elderly. The common marker among all variants is the presence of autoantibodies targeting the dermal-epidermal or mucosal-submucosal junctions, or basement membrane zone (BMZ). Four target antigens in the BMZ were studied. These included BPAG1, BPAG2 and subunits of α6 and ß4 human integrins. Our objective was to find a molecular basis for the global incidence of Pg diseases and a mechanism that will explain the vast differences in clinical phenotypes and outcomes. All the variants of Pg that were analyzed had a statistically significant association with HLA-DQß1*03:01 in ten countries on four continents. This explains the reason for global incidence. Prediction models discovered multiple peptides in each of the four antigens that serve as T cell epitopes. These T cell epitopes were shown to bind to HLA-DQß1*03:01. In addition, structure modelling demonstrated the peptide-HLA complex bound to the T cell receptor. These autoreactive T cells would stimulate B cells to produce specific anti-BMZ autoantibodies. Anti-BMZ autoantibodies with different specificities will produce different phenotypes, which will account for involvement of different tissues and organs in different molecules. The contribution this study makes is that it provides a molecular basis of why a similar disease occurs in different racial groups. Furthermore, it provides the basis for the production of autoantibodies with different specificities, which resultantly produces different phenotypes.

Comparing the Efficacy of Intra-dermal Platelet Rich Plasma (PRP) Versus 50% Trichloracetic Acid (TCA) using Cross Technique for Atrophic Acne Scars.

ABSTRACT       Objective: To compare the efficacy of intra-dermal platelet rich plasma (PRP) versus 50% trichloracetic acid (TCA) using chemical reconstruction of skin scars (CROSS) technique in the treatment of atrophic acne scars. STUDY DESIGN: Non-randomised controlled trial. PLACE AND DURATION OF STUDY: Sheikh Zayed Hospital, Rahim Yar Khan, from October 2019 to April 2020. METHODOLOGY: In this study, cases of either gender and age 20 to 40 years with atrophic acne scars were included. The severity of the scar was graded on the basis of global acne scarring grading system. The cases in group A were managed by monthly injections of 1 ml intra-dermal PRP every month; while those in Group B were given treatment with 50% TCA, which was applied by CROSS technique every month. Both treatments were offered for three months. They were assessed at every four weeks for initial three months. Then these cases were followed another three months and final outcome was seen at 6th month. RESULTS: In this study, there were 92 cases, 46 in each group. The mean age in group A and B was 27.72 ± 8.05 vs. 26.50 ± 8.20 years (p= 0.474). The mean global scar score at baseline was 36.07 ± 5.37 vs. 38.70 ± 4.80 (p= 0.015). The mean scar score at 4 weeks was 28.87 ± 5.27 vs. 29.00 ± 3.07 (p= 0.885), at 8 weeks 23.22 ± 4.10 vs. 23.11±2.49 (p=0.878), at 12 weeks 14.15 ± 3.05 vs. 17.57 ± 4.51 (p<0.001), and at 24 weeks it was 7.09 ± 1.46 vs. 10.09 ± 3.58 (p = <0.001). CONCLUSION: PRP is significantly better than 50% TCA in reducing post-acne atrophic scars. Key Words: Acne, Atrophic scar, Platelet rich plasma, 50% TCA.

Comparing the Efficacy of Patelet-rich Plasma (PRP) versus Tranexamic Acid (4mg/mL) as Intradermal Treatments of Melasma.

OBJECTIVE: To compare the efficacy of intradermal platelet-rich-plasma vs. intradermal tranexamic acid in treatment of melasma. STUDY DESIGN: Non-randomised controlled trial. PLACE AND DURATION OF STUDY: Sheikh Zayed Hospital, Rahim Yar Khan from 1st October 2019 to 30th April 2020. METHODOLOGY: Cases of melasma from either gender with age 20-40 years, were included. Diagnosis of melasma was made clinically on the basis of hyperpigmentation at sun-exposed areas and by Wood's lamp.  Severity was labelled on the basis of melasma area and severity index (MASI) score. Cases in group A were managed with 1 ml of intradermal platelet-rich plasma (PRP) and those in group B were offered intradermal tranexamic acid in a dose of 4 mg. The treatment was offered every 4th week and for a total period of 12 weeks; and final outcome was seen at 24th week. At every visit, the cases were noted for their mean MASI score. RESULTS: In this study, there were a total of 64 cases, 32 in each group. There were 19 (59.38%) males in group A and 16 (50%) in group B (p=0.61). Mean age in group A and B was 24.63 ± 9.87 vs. 23.94 ± 8.93 years (p= 0.76). Mean MASI score at baseline was 29.84 ± 5.14 vs. 29.56 ± 4.39, p=0.21. MASI was significantly better in group A at 4 weeks where score was 29.44 ± 5.35 vs. 28.69 ± 4.10, p=0.01. Mean MASI was 12.81 ± 1.78 vs. 18.38 ± 3.50, p=00001 at 12 weeks and 8.72 ± 3.40 vs. 14.97±4.33, p=0.02 at 24 weeks in group A and B, respectively. CONCLUSION: Intradermal PRP is significantly better than intradermal tranexamic acid in management of melasma. Key Words: Melasma, Tranexamic acid, PRP, MASI.

Trichotillomania: a psychopathological perspective and the psychiatric comorbidity of hair pulling.

Trichotillomania, or hair-pulling disorder, is classified as an obsessive-compulsive spectrum disorder and is seen predominantly in females. This is a non-systematic review article focusing on the psychopathological features of hair pulling. It is speculated that hair pulling may function to provide short-term relief from stress and other unwanted emotional states, thus serving as a method of emotion regulation. The prevalence of trichotillomania ranges from 1 to 3%. The most targeted site is the scalp, and other common areas include pubic hair and facial regions such as the eyebrows, eyelashes, and beard. Individuals suffering from this disorder tend to avoid social environments due to embarrassment regarding their appearance and fears of being judged by peers. Trichotillomania is associated with significant functional impairment and increased risks of comorbid psychiatric disorders such as other body-focused repetitive behaviors, depression, anxiety, and addictive disorders. This article reviews the epidemiology, clinical features, diagnostic criteria, and psychopathology of trichotillomania with an emphasis on psychopathology and psychiatric comorbidity.

Induced Pluripotent Stem Cell-Derived Neural Stem Cell Transplantations Reduced Behavioral Deficits and Ameliorated Neuropathological Changes in YAC128 Mouse Model of Huntington's Disease.

Huntington's disease (HD) is a genetic neurodegenerative disorder characterized by neuronal loss and motor dysfunction. Although there is no effective treatment, stem cell transplantation offers a promising therapeutic strategy, but the safety and efficacy of this approach needs to be optimized. The purpose of this study was to test the potential of intra-striatal transplantation of induced pluripotent stem cell-derived neural stem cells (iPS-NSCs) for treating HD. For this purpose, we developed mouse adenovirus-generated iPSCs, differentiated them into neural stem cells in vitro, labeled them with Hoechst, and transplanted them bilaterally into striata of 10-month old wild type (WT) and HD YAC128 mice. We assessed the efficiency of these transplanted iPS-NSCs to reduce motor deficits in YAC128 mice by testing them on an accelerating rotarod task at 1 day prior to transplantation, and then weekly for 10 weeks. Our results showed an amelioration of locomotor deficits in YAC128 mice that received iPS-NSC transplantations. Following testing, the mice were sacrificed, and their brains were analyzed using immunohistochemistry and Western blot (WB). The results from our histological examinations revealed no signs of tumors and evidence that many iPS-NSCs survived and differentiated into region-specific neurons (medium spiny neurons) in both WT and HD mice, as confirmed by co-labeling of Hoechst-labeled transplanted cells with NeuN and DARPP-32. Also, counts of Hoechst-labeled cells revealed that a higher proportion were co-labeled with DARPP-32 and NeuN in HD-, compared to WT- mice, suggesting a dissimilar differentiation pattern in HD mice. Whereas significant decreases were found in counts of NeuN- and DARPP-32-labeled cells, and for neuronal density measures in striata of HD vehicle controls, such decrements were not observed in the iPS-NSCs-transplanted-HD mice. WB analysis showed increase of BDNF and TrkB levels in striata of transplanted HD mice compared to HD vehicle controls. Collectively, our data suggest that iPS-NSCs may provide an effective option for neuronal replacement therapy in HD.