A case of self-improving collodion ichthyosis associated with a rare variant of the ALOX12B gene.

Collodion baby is usually a manifestation of autosomal recessive congenital ichthyosis, a heterogeneous group of congenital hyperkeratotic genodermatoses with highly variable severity and genetic background. Herein, we report a case of self-improving collodion ichthyosis, a rare subtype of autosomal recessive congenital ichthyosis, characterized by an almost-complete spontaneous resolution of symptoms.

Time-to-treatment initiation for cutaneous melanoma reflects disparities in healthcare access in Brazil: a retrospective study.

OBJECTIVES: This study aimed at identifying the sociodemographic and first treatment characteristics affecting time-to-treatment initiation (TTI) of patients with cutaneous melanoma assisted by the Brazilian Unified Health System (SUS). STUDY DESIGN: Retrospective observational study using cutaneous melanoma cases recorded in the Brazilian Hospital-Based Cancer Registries (HBCR). METHODS: A total of 12,783 cutaneous melanoma cases were included in the analysis. Based on the legislation, TTI in Brazil is 60 days; therefore, the cohort was dichotomized into TTI within 60 days and over. The association among variables was evaluated through the Chi-squared test. Kaplan-Meier method and log-rank hypothesis test were used to determine the probability of initiating treatment within 60 days. Cox proportional hazards regression model was used for multivariate analysis. RESULTS: Median TTI was 28 days (95% CI, 25-29). First treatment in SUS provided more than 60 days after diagnosis (34.8%) was associated with females; low level of formal education; living or getting treatment in northern Brazil; being diagnosed in SUS and treated at different healthcare facilities, in addition to starting treatment with radiotherapy or systemic therapy. There were no significant differences in access to health care before and after the enactment of the 60-day law. CONCLUSION: Increased TTI for cutaneous melanoma is associated with sociodemographic and first treatment characteristics in Brazil; approximately one-third of cases did not have access to first treatment within the period established by law. Receiving the diagnosis and treatment at different healthcare facilities (transitions in care) is the main independent factor associated with TTI longer than 60 days.

Street-level implementers of population-based oral health policies: the case of water fluoridation supply in Brazil's small towns.

BACKGROUND: Knowledge of conditions influencing the performance of street-level operators when implementing population-based policies could increase the understanding of local implementation dynamics. OBJECTIVE: We analyzed how street-level operators claim to act to implement fluoridation policy in the water treatment units of small Brazilian municipalities and identified conditions shaping behavior against adherence to policy. METHODS: A case study using narratives obtained through in-depth interviews with key informants in two pairs of municipalities with contrasting levels of implementation. Analysis identified themes in the data and in the street-level bureaucracy literature. RESULTS: Institutional characteristics such as administrative fragility of local entities, low priority given locally to policy, poor physical structure of the water treatment plants, isolated working relations, low effectiveness of monitoring devices, and local actors' uncertainties about the policy favored the expansion of the discretionary power of street-level operators configuring important barriers for water fluoridation. CONCLUSION: These data highlight the complexity of policy implementation and inform policymakers about the importance of inter-federal and inter-sectoral coordination when implementing population-based health policies in small towns.

Stroke in systemic lupus erythematosus: epidemiology, mechanism, and long-term outcome.

OBJECTIVE: To determine stroke prevalence, mechanisms, and long-term outcome in a cohort of Hispanic patients with systemic lupus erythematosus (SLE). METHODS: We analyzed demographical data, the timing between SLE diagnosis and stroke onset, stroke type, recurrence, and outcomes from an institutional database of 4451 patients with SLE followed from 1993 to 2018. RESULTS: We observed 139 strokes (3.1%), for an incidence rate of 1.25 per 1000 person-years: 81 (58.3%) acute ischemic stroke (AIS), 19 (13.7%) subarachnoid hemorrhage (SAH), 17 (12.2%) cerebral venous thrombosis, 13 (9.4%) intracerebral hemorrhage (ICH), and 9 (6.5%) transient ischemic attack. Median time from SLE diagnosis to acute stroke was 60 months (interquartile range 12-132 months). AIS had a bimodal presentation with 26% occurring within the first year and 30% >10 years after SLE diagnosis. In contrast, 75% of ICH cases occurred >3 years (and 34% >10 years) after SLE diagnosis. The most important cause of AIS was secondary antiphospholipid syndrome (48%). Hypertension was associated with 69% of ICH cases, while aneurysmal rupture was observed in 78% of SAH cases. Excellent recovery at hospital discharge was observed in 65%. Stroke recurrence was observed in 7%. The long-term all-cause fatality rate was 8%. CONCLUSIONS: The prevalence of stroke in this cohort was 3.1%. Ischemic strokes had a bimodal presentation, occurring either early after SLE diagnosis or after a several-year delay. Half of the hemorrhagic strokes occurred >10 years after the diagnosis of SLE. Clinical outcome was usually good with a relatively low recurrence rate.

Degradation of the diuretic hydrochlorothiazide by UV/Solar radiation assisted oxidation processes.

The objective of this study was to analyse the effectiveness of advanced oxidation processes (AOPs) with Solar and UV radiation (UV/H2O2, UV/K2S2O8) for the degradation of hydrochlorothiazide (HCTZ), a widely used diuretic drug, in aqueous solution focusing on the influence of four experimental parameters: initial concentration of HCTZ, solution pH, nature of the water matrix, and initial concentration of radicals. The obtained results showed that using both kinds of direct photolysis (UV and Solar), the percentage of degraded HCTZ was low, but there was a decrease in the degradation rate favored by the increase of the initial concentration of this pollutant. In addition, the degradation rates were higher at acid pHs. With regard to the nature of water, the degradation rate varied in the order: ultrapure > superficial > tap water. This is due to the presence of organic and inorganic matter (bicarbonates, nitrates, and chlorides) in surface and tap water, that react with the radicals generated, which reduces the availability of radical species, generating competitive kinetics. The presence of radical-promoter species increased the degradation rate of the pollutant, reaching a degradation of 100% of HCTZ after 20 min of treatment. The results obtained point out that the degradation rate was higher in the presence of HO radicals. This behavior was attributed to the higher oxidation power of HO versus radicals. The determination of the degradation by-products led to structures very similar to the parent compound. For example, the corresponding hydroxylated dechlorinated derivative of HCTZ was found in all the systems used. The cytotoxicity test showed that these byproducts have a lower toxicity than the original product. Finally, the economic viability study confirmed that the UV/K2S2O8 system has the lowest cost.

Position statement: topical calcineurin inhibitors in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease in both adults and children. Whilst topical calcineurin inhibitors (TCIs), tacrolimus ointment and pimecrolimus cream, have proven efficacy for the treatment of AD, it is important to involve experts to obtain their opinion on its optimal treatment. OBJECTIVE: Using a modified Delphi approach, this project aimed to generate consensus amongst experts on the use of TCIs in the treatment of AD, with a focus on the differentiation between tacrolimus and pimecrolimus. METHODS: Six expert dermatologists from different European countries participated in this project based on their experience with AD and its treatment, which was evaluated by literature analysis and expert opinion. Consensus amongst the experts was generated using a modified Delphi approach, consisting of three distinct phases, during which a web meeting (June 2017), two online rounds of blinded Delphi voting (July-September 2017) and a face-to-face meeting (November 2017) were conducted. The consensus statements concerned two main topics: (i) Background of AD; and (ii) TCIs in AD. Hot topics in the treatment of AD not supported by meta-analysis, clinical trials or large observational studies were also discussed based on clinical experience. RESULTS: In total, 25 consensus statements were defined and validated: eight statements on the general background of AD and 17 statements on the use of TCIs in AD, including their mechanism of action and therapeutic indications in AD, efficacy in adult and paediatric AD patients, pharmacokinetics, incidence of adverse events and safety concerns. Hot topics on the use of TCIs for the treatment of AD included cream vs. ointment, dosages, TCIs contact allergy, burning sensation management, superinfection and vaccination concerns. CONCLUSION: Topical calcineurin inhibitors are a suitable therapy for AD, and selection of the specific TCI should be based on factors which differentiate tacrolimus from pimecrolimus.

Follicular fluid PlGF/sFlt-1 ratio and soluble receptor for advanced glycation end-products correlate with ovarian sensitivity index in women undergoing A.R.T.

PURPOSE: Considering potential roles of soluble receptor for advanced glycation end products (sRAGE) and placental growth factor (PlGF) in ovarian function and embryo implantation, in the present study we have evaluated the association of these factors and also PlGF/sFlt-1 ratio with the ovarian response and implantation rate by dividing patients according to the OSI. METHODS: In a cross-sectional study, 90 infertile women who were undergoing ICSI cycle using long protocol were recruited. The patients were divided according to ovarian sensitivity index (OSI). ICSI cycle outcomes were evaluated for each patient and PlGF, sFlt-1 and sRAGE levels of follicular fluid were assayed using commercial ELISA kits. RESULTS: Follicular fluid (FF) sRAGE levels and PlGF/sFlt-1 ratio were statistically greater in high-responder women than other responders (p < 0.05). Positive correlations were obtained between sRAGE level with the number of oocytes, follicles and OSI level. sRAGE levels with cutoff value of 4.83 (ng/ml) for evaluating the pregnancy outcome showed 81.8 % sensitivity and 60.7 % specificity. Furthermore, there were positive associations between PlGF/sFlt-1 ratio with the number of oocytes, embryos and OSI level. CONCLUSION: In conclusion, the results of current study supported that good ovarian response is independent of pregnancy outcome. Our results showed that FF levels of sRAGE and PlGF/sFlt-1 ratio could be used as markers for determining the high-responder women. Also, FF sRAGE levels could be a good predictor for ART outcome.

Towards an e-Health Cloud Solution for Remote Regions at Bahia-Brazil.

This paper presents CloudMedic, an e-Health Cloud solution that manages health care services in remote regions of Bahia-Brazil. For that, six main modules: Clinic, Hospital, Supply, Administrative, Billing and Health Business Intelligence, were developed to control the health flow among health actors at health institutions. They provided database model and procedures for health business rules, a standard gateway for data maintenance between web views and database layer, and a multi-front-end framework based on web views and web commands configurations. These resources were used by 2042 health actors in 261 health posts covering health demands from 118 municipalities at Bahia state. They also managed approximately 2.4 million health service 'orders and approximately 13.5 million health exams for more than 1.3 million registered patients. As a result, a collection of health functionalities available in a cloud infrastructure was successfully developed, deployed and validated in more than 28% of Bahia municipalities. A viable e-Health Cloud solution that, despite municipality limitations in remote regions, decentralized and improved the access to health care services at Bahia state.

Single-molecule magnet behavior and magnetocaloric effect in ferromagnetically coupled Ln(III)-Ni(II)-Ni(II)-Ln(III) (Ln(III) = Dy(III) and Gd(III)) linear complexes.

New types of linear tetranuclear Ln(III)-Ni(II)-Ni(II)-Ln(III) (Ln(III) = Dy (1), Gd (2)) complexes have been prepared using the multidentate ligand N,N'-bis(3-methoxysalicylidene)-1,3-diaminobenzene, which has two sets of NO and OO' coordination pockets that are able to selectively accommodate Ni(II) and Ln(III) ions, respectively. The X-ray structure analysis reveals that the Ni(II) ions are bridged by phenylenediimine groups forming a 12-membered metallacycle in the central body of the complex, whereas the Ln(III) ions are located at both sides of the metallacycle and linked to the Ni(II) ions by diphenoxo bridging groups. Phenylenediimine and diphenoxo bridging groups transmit ferromagnetic exchange interactions between the two Ni(II) ions and between the Ni(II) and the Ln(III) ions, respectively. Complex 1 shows slow relaxation of the magnetization at zero field and a thermal energy barrier Ueff = 7.4 K with HDC = 1000 Oe, whereas complex 2 exhibits an S = 9 ground state and significant magnetocaloric effect (-ΔSm = 18.5 J kg(-1) K(-1) at T = 3 K and ΔB = 5 T).

Rational design of a new fluorescent 'ON/OFF' xanthene dye for phosphate detection in live cells.

A new fluorescein derivative with ON/OFF features, 9-[1-(4-tert-butyl-2-methoxyphenyl)]-6-hydroxy-3H-xanthen-3-one (Granada Green, GG), was designed and synthesised. The new dye has spectral characteristics similar to those of other xanthenic derivatives but shows a higher pK(a) value for the equilibrium between its neutral and anionic forms. In addition, GG undergoes the same phosphate-mediated excited state proton transfer (ESPT) reaction as other xanthenic derivatives, giving rise to fluorescence decay traces that are dependent on both the phosphate concentration and pH of the medium. The phosphate-mediated ESPT reaction was employed to detect changes in the phosphate concentrations in live, permeabilised MC3T3-E1 preosteoblasts at pH 7.35. Its high pK(a) value indicates that this new dye is more sensitive as an intracellular phosphate sensor than other previously tested dyes, as experimentally demonstrated by its ability to detect a wider range of phosphate concentrations in biomimetic media and by the increased ratio of the phosphate concentration/decay time.

Prospective comparison of acute severe toxicities between smokers and non-smokers during radiotherapy for head and neck cancers.

BACKGROUND AND PURPOSE: The association between smoking and acute radiation toxicities of head and neck cancer (HNC) is currently unproven. The aim of the study was to compare the occurrence of acute severe toxicity between active and non-active smokers treated for HNC by radiotherapy. MATERIALS AND METHODS: A prospective monocentric cohort study included patients treated by (chemo)radiotherapy for HNC from January 2021 to January 2023. Smoking status was recorded. Patients underwent a medical exam weekly during the radiotherapy to report acute toxicities according to the Common Terminology Criteria for Adverse Effects system version 5.0. Primary endpoint was the occurrence of at least one grade ≥ 3 acute toxicity among mucositis, dysphagia and dermatitis. RESULTS: Among the 102 patients included, 27.4 % were active smokers, 58.8 % were former smokers and 13.7 % had never smoked. Regarding toxicity, 23.5 % (n = 24) patients experienced severe mucositis, 37.2 % (n = 38) severe dysphagia, 13.7 % (n = 14) severe dermatitis and 54.9 % (n = 56) experienced at least one of them. Occurrence of severe acute toxicity was not statistically associated with smoking during radiotherapy (64.3 % among active smokers versus 51.3 % among non-active smokers; p = 0.24). On multivariate analysis, concurrent chemotherapy (87.5 % vs 65.2 %; OR = 5.04 [1.64-15.52]; p = 0.004) and 2.12 Gy versus 2 Gy fractionation schedule (64.3 % vs 41.3 %; OR = 2.53 [1.09-5.90]; p = 0.03) were significantly associated with severe acute toxicity. CONCLUSION: This study did not find an association between smoking during radiotherapy for HNC and occurrence of severe acute toxicities.

Distribution of triglyceride-rich lipoproteins and their remnants and their contribution to cardiovascular risk in the Mexican population.

BACKGROUND AND AIMS: In recent years, scientific interest in triglyceride-rich lipoproteins (TRL) and remnant cholesterol has increased, focusing on the evidence that these lipoproteins are a causal factor for developing atherosclerotic cardiovascular disease (ASCVD). Furthermore, a high remnant concentration (>38 mg/dL) has been associated with several non-cardiovascular risks. We aimed in this study to describe the percentile distribution of remnant cholesterol. Additionally, we evaluated the association between remnant cholesterol plasma concentration and epidemiologically relevant cardio-metabolic outcomes such as hypertension, type 2 diabetes (T2D), and ASCVD. METHODS: We analyzed data from 9,591 adults from the National Survey of Health and Nutrition (ENSANUT) 2018 with fasting blood samples and complete medical history questionnaires. We built multivariate models to evaluate the association between chronic diseases and blood remnant concentration. To compare our 2018-sub-sample against a population reference, we used the NHANES (2005-2014) publicly available datasets by ethnicity. RESULTS: Remnants were independently associated with cardiovascular risk, diabetes, hypertension, obesity, and metabolic syndrome. For all outcomes, the blood remnant concentration was a stronger predictor than LDL. At all deciles, the blood remnant concentration was higher in ENSANUT-2018. CONCLUSIONS: A remnant blood concentration above 38 mg/dL was highly prevalent among Mexicans. Remnants were significantly associated with a higher risk of diabetes, hypertension, obesity, and cardiovascular risk. This association occurred independently of other lipid markers.

Brachytherapy versus radical hysterectomy after external beam chemoradiation with gemcitabine plus cisplatin: a randomized, phase III study in IB2-IIB cervical cancer patients.

BACKGROUND: The aim of the present study was to demonstrate that radical hysterectomy (RH) leads to improved survival outcomes in FIGO stage IB2-IIB cervical cancer when compared with standard brachytherapy (BCT) after identical external beam chemoradiation (EBRT-CT). PATIENTS AND METHODS: EBRT-CT treatment consisted of six courses of cisplatin at 40 mg/m² and gemcitabine at 125 mg/m² per week concurrent with 50.4 Gy of radiation. In the BCT arm, EBRT-CT was followed by BCT to reach a point A dose of 85 Gy, whereas in the experimental arm, a type III RH with bilateral pelvic lymph node dissection and para-aortic lymph node sampling (RH) was carried out within 4-6 weeks after EBRT-CT. RESULTS: Between May 2004 and June 2009, 211 patients were enrolled (BCT, 100 and RH, 111). At a median follow-up time of 36 months (3-80), progression-free survival (PFS) and overall survival (OS) rates were similar in both the arms. PFS rates were 74.8% and 71.7% in the BCT and RH arms [HR 0.6516 (95% confidence interval (CI) 0.3504-1.2116)], P = 0.186. OS rates were 76.3% in the BCT versus 74.5% in the surgical arm [HR 0.6981 (95% CI 0.3106-1.3439)], P = 0.236. No differences were observed in the pattern of local and systemic failures. CONCLUSIONS: This study failed to demonstrate that RH after EBRT-CT is superior to standard BCT.

Electrochemical methods for speciation of trace elements in marine waters. Dynamic aspects.

The contribution of electrochemical methods to the knowledge of dynamic speciation of toxic trace elements in marine waters is critically reviewed. Due to the importance of dynamic considerations in the interpretation of the electrochemical signal, the principles and recent developments of kinetic features in the interconversion of metal complex species will be presented. As dynamic electrochemical methods, only stripping techniques (anodic stripping voltammetry and stripping chronopotentiometry) will be used because they are the most important for the determination of trace elements. Competitive ligand exchange-adsorptive cathodic stripping voltammetry, which should be considered an equilibrium technique rather than a dynamic method, will be also discussed because the complexing parameters may be affected by some kinetic limitations if equilibrium before analysis is not attained and/or the flux of the adsorbed complex is influenced by the lability of the natural complexes in the water sample. For a correct data interpretation and system characterization the comparison of results obtained from different techniques seems essential in the articulation of a serious discussion of their meaning.

Dupilumab for atopic dermatitis: a real-world Portuguese multicenter retrospective study.

INTRODUCTION: Atopic dermatitis (AD) is a difficult-to-treat inflammatory skin disease with a high impact on patients' quality of life. Dupilumab, an IL-4 and IL-13 inhibitor, was the first monoclonal antibody approved for the treatment of moderate-to-severe AD and is currently approved in patients aged 6 or older. METHODS: This is a nationwide, multicenter, retrospective, 48-week study designed by the Portuguese Group of AD to assess real-world efficacy and safety of dupilumab for the treatment of AD. RESULTS: A total of 169 patients were enrolled, with a mean disease duration of 22.75 (±11.98) years. The percentage of patients achieving an improvement of at least 75% in Eczema Area and Severity Index (EASI) compared to baseline (EASI75 response) at weeks 12 and 48 was 67.6% and 74.1%, respectively. In the same timepoints, 25.0% and 44.1% achieved an EASI90 response. Patient-reported outcome measures also improved throughout the study period. Regarding safety, 32.0% of the patients developed adverse events, with conjunctivitis (26.6%), persistent facial erythema (4.7%), and arthritis/arthralgia (3.6%) as the more frequently reported. CONCLUSION: Data from real-world populations are crucial to guide clinicians in their daily decisions. This study provides data demonstrating that dupilumab is an effective and safe therapeutic option for AD.

Development of disseminated superficial porokeratosis in a patient with complicated acute pancreatitis.

Porokeratosis is a group of hereditary or acquired diseases with abnormal epidermal keratinization. A 71-year-old man was admitted to the Surgery Department after an attack of acute pancreatitis complicated with pancreatic necrosis, which required surgical resection. Three weeks after the admission, the patient was observed by our Dermatology department with sudden onset of a generalized eruption of asymptomatic flat papules with a hyperkeratotic rim, sparing the face, palms, soles, and mucous membranes. A skin biopsy was performed at the border of a leg lesion, which disclosed the presence of cornoid lamella, confirming the clinical diagnosis of disseminated superficial porokeratosis (DSP). The skin eruption spontaneously subsided about one month after pancreatic resection. The late onset of DSP in our patient may represent a type of immunosuppression-induced porokeratosis. Possibly, the pathologic clone of keratinocytes for porokeratosis was present, but remained latent until there was a decrease in the immunological status. It is possible that this relative and transient state of immunosuppression was the result of the concurrent necrotizing pancreatitis. This case represents an unusually good outcome of DSP. To the authors best knowledge, this is the first case of DSP related to severe acute pancreatitis.