Nasolabial flap - alternative uses for a classic but versatile technique.

The nasolabial flap is one of the most ancient techniques used in orofacial surgery. The authors report two cases of patients with skin cancer treated surgically with variations of the classic nasolabial flap by transposition (bilateral and folded) that highlight the broad applicability of this technique.

Are dose-response relationships of resistance training reliable to improve functional performance in frail and pre-frail older adults? A systematic review with meta-analysis and meta-regression of randomized controlled trials.

This systematic review with meta-analyses investigates the impact of resistance training (RT), using meta-regressions, on functional performance in frail and pre-frail adults aged ≥ 65 years to determine the key variables of RT. Ten randomized controlled trials involving 1303 participants were analyzed. Five studies assessed habitual walking speed (HWS), three studies evaluated performance in the timed-up-and-go test (TUG), three studies evaluated performance in the Short Physical Performance Battery (SPPB), and three studies assessed performance in the sit-to-stand test (STS). RT alone improved STS time and SPPB scores in frail and pre-frail older adults. RT improved STS performance (Effect Size (ES):- 0.536; 95% CI - 0.874 to - 0.199; p = .002) and led to a 2.261-point increase in SPPB performance (ES:1.682; 95% CI 0.579-2.786; p = .003). At least two weekly training sessions are required to increase SPPB scores, and three sessions seem to optimize the improvements. Higher training volume per exercise and volume per session reduce the gains in SPPB performance. We did not observe any association between different doses of RT and STS time improvements. RT alone positively influenced TUG performance only in community-dwelling older frail and pre-frail adults but not in institutionalized older individuals. RT alone did not improve the HWS compared to the non-active control group.

Retrospective cohort study to evaluate the continuous use of anticholesterolemics and diuretics in patients with COVID-19.

Purpose: The purpose of this study is to evaluate the interference of the continuous use of drug classes in the expression of biomarkers during the first week of hospitalization and in the prognosis of patients with COVID-19. Methods: The patients diagnosed with COVID-19 and confirmed with SARS-CoV-2 by RT-qPCR assay underwent the collection of fasting whole blood samples for further analysis. Other data also extracted for this study included age, sex, clinical symptoms, related comorbidities, smoking status, and classes of continuous use. Routine serum biochemical parameters, including alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, C-reactive protein, N-terminal fragment of B-type natriuretic peptide, and cardiac troponin, were measured. Results: In this cross-sectional study, a total of 176 patients with COVID-19 hospitalizations were included. Among them, 155 patients were discharged (88.5%), and 21 patients died (12%). Among the drug classes evaluated, we verified that the continuous use of diuretic 4.800 (1.853-11.67) (p = 0.0007) and antihypercholesterolemic 3.188 (1.215-7.997) (p = 0.0171) drug classes presented a significant relative risk of death as an outcome when compared to the group of patients who were discharged. We evaluated biomarkers in patients who used continuous antihypercholesterolemic and diuretic drug classes in the first week of hospitalization. We observed significant positive correlations between the levels of CRP with cardiac troponin (r = 0.714), IL-6 (r = 0.600), and IL-10 (r = 0.900) in patients who used continuous anticholesterolemic and diuretic drug classes and were deceased. In these patients, we also evaluated the possible correlations between the biomarkers AST, NT-ProBNP, cardiac troponin, IL-6, IL-8, and IL-10. We observed a significantly negative correlations in AST levels with NT-ProBNP (r = -0.500), cardiac troponin (r = -1.00), IL-6 (r = -1.00), and IL-10 (r = -1.00) and a positive correlation with IL-8 (r = 0.500). We also observed significant negative correlation in the levels of NT-ProBNP with IL-10 (r = -0.800) and a positive correlation with cardiac troponin (r = 0.800). IL-6 levels exhibited positive correlations with cardiac troponin (r = 0.800) and IL-10 (r = 0.700). Conclusion: In this study, we observed that hospitalized COVID-19 patients who continued using anticholesterolemic and diuretic medications showed a higher number of correlations between biomarkers, indicating a poorer clinical prognosis. These correlations suggest an imbalanced immune response to injuries caused by SARS-CoV-2.

Letter: Primary cutaneous marginal zone B cell lymphoma of the face: a challenging diagnosis.

The primary cutaneous marginal zone B cell lymphoma is a small B cell lymphoma, including cells of the marginal zone, lymphoplasmacytic cells, and plasma cells. Clinically it manifests as erythematous or erythematous-violaceous papules, plaques, or nodules, single or multiple, most often located to the extremities. Its course is usually indolent, with a survival at 5 years of approximately 97 percent. The tumor exhibits a tendency towards local recurrence, but spread to locations outside the skin is extremely rare. We present a case report of a man, 80 years of age, with a primary cutaneous marginal B cell lymphoma of the chin, an atypical location.

Letter: Transient peripheral facial nerve paralysis after local anesthetic procedure.

Complications may arise after laser therapy of the face. The most common ones are bleeding and infections; facial nerve paresis or paralysis is rarely reported. We describe a case of a transient peripheral facial nerve paralysis after laser therapy of an epidermal verrucous nevus localized at the left preauricular area.

Impaired expression of serine/arginine protein kinase 2 (SRPK2) affects melanoma progression.

Melanoma is one of the most aggressive tumors, and its lethality is associated with the ability of malignant cells to migrate and invade surrounding tissues to colonize distant organs and to generate widespread metastasis. The serine/arginine protein kinases 1 and 2 (SRPK1 and SRPK2) are classically related to the control of pre-mRNA splicing through SR protein phosphorylation and have been found overexpressed in many types of cancer, including melanoma. Previously, we have demonstrated that the pharmacological inhibition of SRPKs impairs pulmonary colonization of metastatic melanoma in mice. As the used compounds could target at least both SRPK1 and SRPK2, here we sought to obtain additional clues regarding the involvement of these paralogs in melanoma progression. We analyzed single-cell RNA sequencing data of melanoma patient cohorts and found that SRPK2 expression in melanoma cells is associated with poor prognosis. Consistently, CRISPR-Cas9 genome targeting of SRPK2, but not SRPK1, impaired actin polymerization dynamics as well as the proliferative and invasive capacity of B16F10 cells in vitro. In further in vivo experiments, genetic targeting of SRPK2, but not SRPK1, reduced tumor progression in both subcutaneous and caudal vein melanoma induction models. Taken together, these findings suggest different functional roles for SRPK1/2 in metastatic melanoma and highlight the relevance of pursuing selective pharmacological inhibitors of SRPK2.

The SRPK inhibitor N-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl) isonicotinamide (SRPIN340) increases the immune response against metastatic melanoma in mice.

Cancers have a strong relationship with immune cells in their microenvironment, which significantly influences tumor proliferation and progression. Thus, pharmacological strategies that stimulate the immune system to combat tumor cells are promising for better therapeutic efficacy. Deregulated expression of the splicing regulatory serine arginine protein kinases (mostly SRPK1 and SRPK2) has been found in different cancer types, leading to the expression of isoforms related to tumor growth and metastasis. The microenvironment of melanoma exhibits a strong presence of immune cells, which significantly influences tumor progression, and around 50% of cutaneous melanoma patients benefit from targeted immunotherapy. Here, we analyzed human malignant melanoma single-cell gene expression data and observed that SRPK1/2 overexpression correlates with immune system pathway alterations. In further analysis, we observed an increased presence of immune cells in biopsies from mice bearing metastatic melanoma treated with SRPIN340, a well-known SRPK1/2 pharmacological inhibitor. Local treatments increased the expression of proinflammatory cytokines at the tumor lesions and the activity of the spleen, accompanied by reduced pulmonary metastasis foci, edema formation, and alveolar congestion. In in vitro assays, SRPIN340 also potentiated immunological susceptibility, by increasing the expression of the antigen presenting MHCI and MHCII molecules and by increasing the ability of B16F10 cells to attract splenic cells in transwell assays. Taken together, these results reveal that the antimetastatic effect of SRPIN340 can also involve an increased immune response, which suggests additional functional clues for SRPKs in tumor biology.

Giant cutaneous horn on the lower lip.

Cutaneous horn is a conical hyperkeratotic projection of the skin composed of compact keratin. A wide range of pathologic conditions may be found at its base, including a significant proportion of malignant tumors. A notable, giant cutaneous horn uncovering a keratoacanthoma/well-differentiated squamous cell carcinoma is presented, highlighting the importance of histopathological examination to rule out malignancy because clinical features cannot assure a correct diagnosis.

Letter: Penile Kaposi sarcoma: A case of complete resolution with highly active antiretroviral therapy alone.

Kaposi sarcoma remains an important cause of morbidity in HIV-infected patients. Regardless of the recent pharmacological progress, treatment of this malignancy is still disappointing. We report the case of a patient with Kaposi sarcoma in an unusual localization, the penis, which completely resolved with highly active antiretroviral therapy alone.

[Non-Necrotizing Acute Dermo-Hypodermal Infections: Erysipela and Infectious Cellulitis]. / Dermo-Hipodermites Bacterianas Agudas Não Necrotizantes: Erisipela e Celulite Infeciosa.

Non-necrotizing acute dermo-hypodermal infections are infectious processes that include erysipela and infectious cellulitis, and are mainly caused by group A ß-haemolytic streptococcus. The lower limbs are affected in more than 80% of cases and the risk factors are disruption of cutaneous barrier, lymphoedema and obesity. Diagnosis is clinical and in a typical setting we observe an acute inflammatory plaque with fever, lymphangitis, adenopathy and leucocytosis. Bacteriology is usually not helpful because of low sensitivity or delayed positivity. In case of atypical presentations, erysipela must be distinguished from necrotizing fasciitis and acute vein thrombosis. Flucloxacillin and cefradine remain the first line of treatment. Recurrence is the main complication, so correct treatment of the risk factors is crucial.

As dermo-hipodermites bacterianas agudas não necrotizantes são processos infeciosos que incluem a erisipela e a celulite infeciosa, e são geralmente causadas por estreptococos ß­hemolíticos do grupo A. Em mais de 80% dos casos situam-se nos membros inferiores e são fatores predisponentes a existência de solução de continuidade na pele, o linfedema crónico e a obesidade. O seu diagnóstico é essencialmente clínico e o quadro típico baseia-se na presença de placa inflamatória associada a febre, linfangite, adenopatia e leucocitose. Os exames bacteriológicos têm baixa sensibilidade ou positividade tardia. Nos casos atípicos é importante o diagnóstico diferencial com a fasceíte necrotizante e a trombose venosa profunda. A flucloxacilina ou a cefradina são os fármacos de primeira linha. A recidiva constitui a complicação mais frequente, sendo fundamental o correto tratamento dos fatores de risco.

Obesity is associated with postural balance on unstable surfaces but not with fear of falling in older adults.

BACKGROUND: There are inconsistent findings regarding the relationship between body mass index (BMI), fear of falling and body balance, especially on unstable surfaces. OBJECTIVES: To investigate whether obesity is associated with worse postural balance and fear of falling in older adults. METHODS: A cross-sectional study was conducted with 201 older adults, classified as normal weight, overweight, or obese according to BMI. Postural balance was evaluated on stable and unstable surfaces on the Biodex Balance System platform under three visual conditions: with and without visual feedback and with eyes closed. Fear of falling was identified by a dichotomous question and the Falls Efficacy Scale. These data were compared between groups and included in adjusted multiple linear regression analysis. RESULTS: The study showed no significant differences (p > 0.05) in body oscillations on a stable surface between the three groups. On an unstable surface, the obese older adults exhibited body oscillations from 0.61° [95% CI 0.07, 1.30] to 1.63° [95% CI 0.84, 2.41] greater than those with normal weight in the three visual conditions. The obese older adults also displayed larger mediolateral oscillations with visual feedback (mean difference: 0.50° [95% CI 0.01, 0.98]) as well as greater global oscillations without visual feedback (mean difference of 0.82° [95% CI 0.18, 1.81]) and with progressive instability (mean difference: 0.80° [95% CI 0.05, 1.66]) than the overweight older adults. BMI explained from 6 to 12% of body swings investigated on unstable surface. Obesity was not associated with fear of falling. CONCLUSION: Obesity was associated with reduced postural stability on unstable surfaces but not with fear of falling in older adults.

Combined SRPK and AKT pharmacological inhibition is synergistic in T-cell acute lymphoblastic leukemia cells.

The serine/arginine protein kinases respond to the EGFR-PI3K-AKT signaling module in the context of pre-mRNA alternative splicing regulation. These enzymes (notably SRPK1 and SRPK2) have been found dysregulated in a variety of cancers, which suggests them as promising drug targets in oncology. SRPK2 has been related to leukemia cells proliferation and found preferentially overexpressed in T-cell acute lymphoblastic leukemia (T-ALL). Previously, synergistic combination between vincristine and SRPK inhibitors has been observed in leukemia cells in vitro. Herein we sought to evaluate the in vitro combinatory effects of inhibiting SRPK and multiple other kinase targets from the EGFR pathway in T-ALL, a hematological malignancy with a still poor prognosis. We found that the combined SRPK and AKT pharmacological inhibition is synergistic in Jurkat, CCRF-CEM, and TALL-1 (all T-ALL) but not in HL60, an acute myelogenous leukemia cell lineage. Combined treatments also impaired SR proteins phosphorylation in accordance with an improved suppression of SRPK activity. Furthermore, the synergism of treatments seemed associated with apoptosis triggering, as revealed by flow cytometry analyses. Taken together, these results suggest the therapeutic potential of the combined SRPK and AKT pharmacological inhibition against T-ALL.

Acute treatment with Mangifera indica L. leaf extract attenuates liver inflammation in rats fed a cafeteria diet.

This study investigates the acute anti-inflammatory activity of Mangifera indica L. leaf extract and mangiferin in the liver of rats fed a cafeteria diet. This study was a randomized longitudinal experimental study. The animals were divided into three groups - Control: cafeteria diet (CD); Extract: CD + leaf extract (250 mg kg-1); and Mangiferin: CD + mangiferin (40 mg kg-1). Body weight and food intake were measured every week. On day eight, mRNA and protein expression of inflammatory markers were evaluated in the liver. Also, liver weight, SOD activity and malondialdehyde concentration were measured. Treatment for only eight days with mango leaf extract and mangiferin increased SOD activity. Mangiferin intake increased the mRNA expression of PPAR-α and HSP72. The leaf extract treatment enhanced PPAR-α mRNA expression. Mangiferin and leaf extract consumption caused a lower concentration of NFκB (p65) in nuclear extracts, and greater IL-10 mRNA and protein levels. This study highlights the potential of acute treatment with mango leaf extract and mangiferin to prevent liver inflammation caused by fat-rich diets. These results indicate a new use for a product that has low cost, is found in great amounts, and is not routinely used.

Leukemia cutis resembling a flare-up of psoriasis.

Leukemia cutis represents a skin infiltration by leukemic cells. Clinically it can mimic a wide variety of dermatoses. We describe the case of a 64-year-old man with psoriasis who presented with a 4-day history of erythematous, slightly scaly, asymptomatic plaques distributed on the trunk and upper-extremities, and associated asthenia, myalgias, and anorexia. A skin biopsy revealed a leukemic infiltrate. Studies of peripheral blood and bone marrow provided a diagnosis of acute monocytic leukemia. This case report shows the importance of the clinical suspicion for the diagnosis of leukemia.

Neuroprotective effect of Sapucaia nuts (Lecythis pisonis)on rats fed with high-fat diet.

BACKGROUND: Lecythis pisonis Cambess is commonly known as "castanha de sapucaia" in Brazil. Chemical composition studies revealed that this nut is an excellent source of anti-oxidant minerals and of essential lipids. OBJECTIVE: The aim of the present study is to assess the anti-oxidant and anti-inflammatory effect of Lecythis pisonis Cambess on the brain tissue of Wistar rats. MATERIAL AND METHODS: The animals were divided in four experimental groups (n = 6), total of forty-eight rats. Treatments included the standard diet (AIN-93G) and high-fat food, supplemented with Sapucaianut from 14 to 28 days. The gene expression markers TNF-α, NFkB, ZnSOD and HSP-72 were defined through reverse transcriptase polymerase chain reaction (rtPCR). The anti-oxidant effect was assessed through the thiobarbituric acid-reactive substances (TBARS) and the measurement of the activity performed by superoxide dismutase enzymes. RESULTS: Accordingly, the gene expression of the inflammatory markers NFkB (p65) and TNF-αwas lower in rats fed on diets supplemented with "sapucaia", and they presented significant difference in the Tukey test (p < 0.05). The heat-shock HSP-72 protein and the ZnSOD enzyme raised the gene expression and showed significant statistical difference (p < 0.05) in both groups fed on Sapucaia nut-based diet. CONCLUSION: Thus, the nutritional properties of the Sapucaia nuts perform important neuroprotective activities because they modulated the anti-oxidant activity and the brain tissue inflammatory process in the assessed animals.

Congenital multiple clustered dermatofibroma and multiple eruptive dermatofibromas--unusual presentations of a common entity.

Dermatofibroma is one of the most common entities seen in dermatology clinical practice. Several clinical subtypes have nevertheless been described, all of them of uncommon occurrence. The authors present two rare clinical variants of dermatofibromas: congenital multiple clustered dermatofibroma (the presented case is the 4th congenital case to be reported so far) and multiple eruptive dermatofibromas developing in the setting of a Sjögren's syndrome. Since the uncommon subtypes may not be clinically evident, dermatologists should familiarize themselves with their main features and we advise a high level of clinical suspicion in order to reach the correct diagnosis.