Comparative Genomics and Characterization of SARS-CoV-2 P.1 (Gamma) Variant of Concern From Amazonas, Brazil.

BACKGROUND: P.1 lineage (Gamma) was first described in the State of Amazonas, northern Brazil, in the end of 2020, and has emerged as a very important variant of concern (VOC) of SARS-CoV-2 worldwide. P.1 has been linked to increased infectivity, higher mortality, and immune evasion, leading to reinfections and potentially reduced efficacy of vaccines and neutralizing antibodies. METHODS: The samples of 276 patients from the State of Amazonas were sent to a central referral laboratory for sequencing by gold standard techniques, through Illumina MiSeq platform. Both global and regional phylogenetic analyses of the successfully sequenced genomes were conducted through maximum likelihood method. Multiple alignments were obtained including previously obtained unique human SARS-CoV-2 sequences. The evolutionary histories of spike and non-structural proteins from ORF1a of northern genomes were described and their molecular evolution was analyzed for detection of positive (FUBAR, FEL, and MEME) and negative (FEL and SLAC) selective pressures. To further evaluate the possible pathways of evolution leading to the emergence of P.1, we performed specific analysis for copy-choice recombination events. A global phylogenomic analysis with subsampled P.1 and B.1.1.28 genomes was applied to evaluate the relationship among samples. RESULTS: Forty-four samples from the State of Amazonas were successfully sequenced and confirmed as P.1 (Gamma) lineage. In addition to previously described P.1 characteristic mutations, we find evidence of continuous diversification of SARS-CoV-2, as rare and previously unseen P.1 mutations were detected in spike and non-structural protein from ORF1a. No evidence of recombination was found. Several sites were demonstrated to be under positive and negative selection, with various mutations identified mostly in P.1 lineage. According to the Pango assignment, phylogenomic analyses indicate all samples as belonging to the P.1 lineage. CONCLUSION: P.1 has shown continuous evolution after its emergence. The lack of clear evidence for recombination and the positive selection demonstrated for several sites suggest that this lineage emergence resulted mainly from strong evolutionary forces and progressive accumulation of a favorable signature set of mutations.

Epidermal necrolysis: SCORTEN performance in AIDS and non-AIDS patients.

BACKGROUND: Stevens-Johnson syndrome and toxic epidermal necrolysis are life-threatening blistering drug reactions with high incidence of ocular sequela. The term 'Epidermal Necrolysis' has been recently used to better describe the full spectrum of the disease that includes Stevens-Johnson syndrome and toxic epidermal necrolysis at opposite ends, which differ by the extent of body surface area with epidermal detachment. SCORTEN is a mortality prognosis score for 'Epidermal Necrolysis' cases that still needed validation in acquired immunodeficiency syndrome. OBJECTIVE: To evaluate the SCORTEN performance in acquired immunodeficiency syndrome, and the differences in outcomes between acquired immunodeficiency syndrome and non- acquired immunodeficiency syndrome cohorts. METHODS: Retrospective cohort study of AIDS and non-AIDS 'Epidermal Necrolysis' cases admitted to a Brazilian reference center from 1990-2014. RESULTS: Five deaths (16.7%) occurred as a consequence of EN in 30 AIDS patients, and seven (17.9%) in 39 non-AIDS patients, relative risk (RR) .92 (p=1.0). SCORTEN showed great performance, with an Area Under the Receiver Operating Curve (AUC) (ROC) of 0.90 with a 95% confidence interval ranging from .81 to .99. The performance of SCORTEN was better among non- AIDS patients than AIDS patients: AUC non- acquired immunodeficiency syndrome =0.99 (CI 05% 0.96-1.00), AUC acquired immunodeficiency syndrome = 0.74 (CI 95% 0.53-0.95), p=.02. STUDY LIMITATIONS: Heterogeneity of cases, wide variation of systemic corticosteroid doses when used. CONCLUSION: SCORTEN is valid for the Brazilian population, including among those patients with acquired immunodeficiency syndrome, and, as such, its use is recommended for aiding treatment choice in this subgroup of patients.

Epidermal necrolysis: SCORTEN performance in AIDS and non-AIDS patients

Abstract: Background: Stevens-Johnson syndrome and toxic epidermal necrolysis are life-threatening blistering drug reactions with high incidence of ocular sequela. The term 'Epidermal Necrolysis' has been recently used to better describe the full spectrum of the disease that includes Stevens-Johnson syndrome and toxic epidermal necrolysis at opposite ends, which differ by the extent of body surface area with epidermal detachment. SCORTEN is a mortality prognosis score for 'Epidermal Necrolysis' cases that still needed validation in acquired immunodeficiency syndrome. Objective: To evaluate the SCORTEN performance in acquired immunodeficiency syndrome, and the differences in outcomes between acquired immunodeficiency syndrome and non- acquired immunodeficiency syndrome cohorts. Methods: Retrospective cohort study of AIDS and non-AIDS 'Epidermal Necrolysis' cases admitted to a Brazilian reference center from 1990-2014. Results: Five deaths (16.7%) occurred as a consequence of EN in 30 AIDS patients, and seven (17.9%) in 39 non-AIDS patients, relative risk (RR) .92 (p=1.0). SCORTEN showed great performance, with an Area Under the Receiver Operating Curve (AUC) (ROC) of 0.90 with a 95% confidence interval ranging from .81 to .99. The performance of SCORTEN was better among non- AIDS patients than AIDS patients: AUC non- acquired immunodeficiency syndrome =0.99 (CI 05% 0.96-1.00), AUC acquired immunodeficiency syndrome = 0.74 (CI 95% 0.53-0.95), p=.02. Study Limitations: Heterogeneity of cases, wide variation of systemic corticosteroid doses when used. Conclusion: SCORTEN is valid for the Brazilian population, including among those patients with acquired immunodeficiency syndrome, and, as such, its use is recommended for aiding treatment choice in this subgroup of patients.

Pesquisa de opinião sobre eficácia, custos e cicatrização de procedimentos de resurfacing para rugas estáticas faciais / Expert survey on the efficacy, costs and healing of resurfacing procedures for facial static wrinkles

Foi realizada uma pesquisa de opinião entre especialistas em "resurfacing" cutâneo com a finalidade de compararem-se custos e benefícios entre as técnicas de laser de CO2 totalmente ablativo, lasers fracionados ablativos, lasers fracionados não ablativos, radiofrequência fracionada ablativa, microagulhamento, dermabrasão, peelings médios e peelings de fenol- -óleo de cróton. A opção mais eficaz para tratamento de rugas estáticas faciais foi peeling de fenol-óleo de cróton, ranqueado em primeiro lugar por 71,4% dos experts, seguido de laser de CO2 totalmente ablativo, por 28,6%. Sobre "downtime", os procedimentos elencados com recuperação mais rápida foram microagulhamento e laser fracionado não ablativo, com 42,9% cada um, seguidos por radiofrequência fracionada ablativa, com 14,3%. O período para recuperação completa dos efeitos colaterais e adversos foi percebido como mais curto no microagulhamento por 50% dos experts. Sobre os custos operacionais, o procedimento menos custoso foram peelings médios, de acordo com a opinião de 71,4% dos especialistas. Tais resultados apontam para melhor custo/benefício de procedimentos como peelings químicos e microagulhamento, de acordo com a opinião dos 14 especialistas brasileiros que responderam ao questionário.

A survey on the opinion of specialists regarding skin resurfacing was performed, with the objective of comparing costs and benefits between the techniques: totally ablative CO2 laser, fractional ablative lasers, fractional non-ablative lasers, ablative fractional radiofrequency, microneedling, dermabrasion, medium peels, phenol-croton oil peels. The most effective option for the treatment of static wrinkles was the phenol-croton oil peel, in first place by 71.4% of the experts, followed by totally ablative CO2 laser, by 28.6%. Regarding downtime, procedures ranked as fastest recovery were microneedling and fractional non-ablative lasers, with 42.9% each, followed by ablative fractional radiofrequency, with 14.3%. Complete recovery period for side and adverse effects was perceived as shorter with microneedling by 50% of the experts. Regarding operating costs. The less costly procedure was medium peels, according to the opinion of 71.4% of the experts. Such results point towards a better cost/benefit of procedures such as chemical peels and micro-needling, according to the opinion of 14 Brazilian specialists who answered the questionnaire.

Th17 Response of Borderline-Lepromatous Leprosy Inhibits Rash Manifestation of Dapsone Hypersensitivity Syndrome: Case Report.

BACKGROUND: Dapsone hypersensitivity syndrome (DHS) is a rare, but potentially life-threatening reaction to dapsone. OBJECTIVE: Evaluation of immunological factors involved in the sparing of borderline-lepromatous (BL) leprosy patches by the severe exanthema related to DHS. METHODS: The authors describe a 19-year-old man with borderline-lepromatous leprosy with a recent diffuse rash, sparing only the hypochromic patches of leprosy, generalized lymphadenopathy, hepatomegaly, and jaundice 25 days after the start of multibacillary multidrug therapy. RESULTS: Laboratory testing was remarkable for leukocytosis with eosinophilia, atypical lymphocytosis, and elevated liver and canalicular enzymes. Immunohistopathology of the rash showed stronger expression of Th1 cytokines (IL1ß, TNFα, IFNγ, and iNOS), and limited expression of IL17, TGFb, IL4, and IL10. Whereas the hypochromic leprosy patches showed high expression of inflammatory cytokines IL1ß, TNFα, IFNγ, iNOS, and TGFß (Th1), and presented strong expression of IL17 and TGFß with no IL4 and IL10 expression, by the inflammatory infiltrate, characterizing a participation of Th17 response. CONCLUSION: Th17 response, coupled with the presence of subepidermal collagen band, seems to be directly related to the absence of DHS rash in these hypochromic leprosy patches.

Alopecia em barba causada por desoxicolato para tratamento de gordura submentoniana / Beard alopecia caused by deoxycholic acid for the treatment of submental fat

Segundo relato de caso da literatura de alopecia em região de barba observada após terceira sessão de injeções de desoxicolato a 1% para redução de gordura submentoniana.

Second case report in the literature regarding beard alopecia observed after the third session of injections of 1% deoxycholic acid for reduction of submental fat.

Bob marley's disease: cerebral metastasis of acral melanoma / A doença de Bob Marley: metástases cerebrais de melanoma acral

Bob Marley's had a great importance to Jamaica, Caribbean popular music, and Pan-Africanism. Under the name of the Wailers, several Marley's success reggae albums were recorded between 1969 and 1975. After this, at the solo career, he was placed as the most important reggae singer. The disease that ruined Bob Marley was an acral melanoma (right hallux) that had a late diagnosis and treatment, followed by metastases to the abdomen, the lungs and the brain. Seizures have been the warning sign that the melanoma had spread, three years after the initial injury. We presented here the history of the disease of this famous singer and reported another patient with a case quite similar to him, calling his illness as "Bob Marley's disease".

Bob Marley representou um marco para a Jamaica, para a música popular do Caribe, e para o Pan-Africanismo. Com o nome de Wailers, vários álbuns de reggae foram gravados com sucesso entre 1969 e 1975. Em sua carreira solo, ele foi considerado o mais importante cantor de reggae. A doença que dizimou Bob Marley foi um melanoma acral (hálux direito) que teve um diagnóstico e tratamento tardios, seguido de metástases para o abdome, pulmões e encéfalo. Crises convulsivas foram o sinal de alerta, três anos após a lesão inicial, de que o melanoma estava disseminado. Nós apresentamos aqui a história da doença deste famoso cantor e relatamos um outro paciente com um caso similar ao qual denominamos "doença de Bob Marley".

Factors associated with seropositivity for APGL-Iamong household contacts of leprosy patients.

INTRODUCTION: Leprosy is mainly transmitted among family members who share genetic and ambient factors. The clinical form of leprosy in the index case and kinship could be risk factors for leprosy transmission. High antibody levels in household contacts (HC) in the absence of neural or skin lesions may characterize latent infection. This study aimed to evaluate the association between seropositivity for anti-phenolic glycolipid-I immunoglobulin M antibodies (APGL-I) in HC and the clinical classification of the index case and to analyze the association between APGL-I positivity with other factors such as age, kinship, and gender. METHODS: We performed a survey among 320 HC of 120 leprosy patients who were evaluated and followed-up in a leprosy outpatient clinic of a university hospital. All HC underwent complete skin examination, peripheral nerve palpation, skin sensory tests, and serologic tests for the detection and quantification of APGL-I. RESULTS: The overall seropositivity rate was 20%, and was greatly affected by kinship. APGL-I seropositivity was higher in siblings (41%), followed by parents (28%), spouses (26%), other (19%), and offspring (14%). Independent risk factors for seropositivity were being siblings (OR 3.3) and being a HC of an index case with indeterminate leprosy (OR 5.3). APGL-I seropositivity was associated with index cases with a bacillary index of 4 (88%; p<.001). Seropositivity among HC was not significantly associated with their gender and age. There was no statistical difference in the seropositivity rates of HC of index patients with paucibacillary and multibacillary leprosy. CONCLUSIONS: Strict evaluation and follow-up of HC with positive results for APGL-I is recommended. Special attention should be paid during the screening of siblings of the index cases, HC of patients with a high bacillary index, and HC of patients with indeterminate leprosy.

Factors associated with seropositivity for APGL-Iamong household contacts of leprosy patients

Abstract: INTRODUCTION: Leprosy is mainly transmitted among family members who share genetic and ambient factors. The clinical form of leprosy in the index case and kinship could be risk factors for leprosy transmission. High antibody levels in household contacts (HC) in the absence of neural or skin lesions may characterize latent infection. This study aimed to evaluate the association between seropositivity for anti-phenolic glycolipid-I immunoglobulin M antibodies (APGL-I) in HC and the clinical classification of the index case and to analyze the association between APGL-I positivity with other factors such as age, kinship, and gender. METHODS: We performed a survey among 320 HC of 120 leprosy patients who were evaluated and followed-up in a leprosy outpatient clinic of a university hospital. All HC underwent complete skin examination, peripheral nerve palpation, skin sensory tests, and serologic tests for the detection and quantification of APGL-I. RESULTS: The overall seropositivity rate was 20%, and was greatly affected by kinship. APGL-I seropositivity was higher in siblings (41%), followed by parents (28%), spouses (26%), other (19%), and offspring (14%). Independent risk factors for seropositivity were being siblings (OR 3.3) and being a HC of an index case with indeterminate leprosy (OR 5.3). APGL-I seropositivity was associated with index cases with a bacillary index of 4 (88%; p<.001). Seropositivity among HC was not significantly associated with their gender and age. There was no statistical difference in the seropositivity rates of HC of index patients with paucibacillary and multibacillary leprosy. CONCLUSIONS: Strict evaluation and follow-up of HC with positive results for APGL-I is recommended. Special attention should be paid during the screening of siblings of the index cases, HC of patients with a high bacillary index, and HC of patients with indeterminate leprosy.

Gamasoidosis illustrated--from the nest to dermoscopy.

Gamasoidosis (acariasis, avian-mite dermatitis or bird-mite dermatitis) is a challenging diagnosis that is becoming more common because of the frequent use of window air conditioners in tropical countries. These devices may serve as shelters for nests of urban birds such as pigeons. Dermatologists should become familiar with this infestation to establish the correct diagnosis and treatment.