Untargeted Metabolomic Study of Lung Cancer Patients after Surgery with Curative Intent.

Lung cancer (LC) is a leading cause of mortality, claiming more than 1.8 million deaths per year worldwide. Surgery is one of the most effective treatments when the disease is in its early stages. The study of metabolic alterations after surgical intervention with curative intent could be used to assess the response to treatment or the detection of cancer recurrence. In this study, we have evaluated the metabolomic profile of serum samples (n = 110) from preoperative (PRE) and postoperative (POST) LC patients collected at two different time points (1 month, A; 3-6 months, B) with respect to healthy people. An untargeted metabolomic platform based on reversed phase (RP) and hydrophilic interaction chromatography (HILIC), using ultra-high performance liquid chromatography (UHPLC) and mass spectrometry (MS), was applied (MassIVE ID MSV000092213). Twenty-two altered metabolites were annotated by comparing all the different studied groups. DG(14,0/22:1), stearamide, proline, and E,e-carotene-3,3'-dione were found altered in PRE, and their levels returned to those of a baseline control group 3-6 months after surgery. Furthermore, 3-galactosyllactose levels remained altered after intervention in some patients. This study provides unique insights into the metabolic profiles of LC patients after surgery at two different time points by combining complementary analytical methods.

Albendazole - Ivermectin combination decreases inflammation in experimental neurocysticercosis.

Neurocysticercosis (NCC) is a public health issue in endemic regions and is considered the main preventable cause of neurologic disease. It is caused by the presence of Taenia solium cysticercus in the central nervous system. The current treatment is performed with anthelminthic drugs - albendazole (ABZ) or praziquantel - associated with anti-inflammatory and corticosteroids in order to prevent the negative effects of the inflammatory reaction to the parasite's death. Ivermectin (IVM) is an anthelminthic drug that has been shown to present an anti-inflammatory effect. The aim of this study was to was to evaluate the histopathologic aspects of experimental NCC after in vivo treatment with a combination of ABZ-IVM. Balb/c mice were intracranially inoculated with T. crassiceps cysticerci and after 30 days of infection were treated with a single dose of NaCl 0.9% (control group), ABZ monotherapy (40 mg/kg), IVM monotherapy (0.2 mg/kg) or a combination of ABZ-IVM. 24h after the treatment the animals were euthanized and the brain was removed for histopathologic analysis. The IVM monotherapy and ABZ-IVM combination showed more degenerated cysticerci, less inflammatory infiltration, meningitis and hyperemia than the other groups. Therefore, it is possible to recommend the combination of albendazole and ivermectin as alternative chemotherapy for NCC due to its antiparasitic and anti-inflammatory effects, with potential to decrease the negative effects of the inflammatory burst when the parasite is killed within the CNS.

Metallomic Signatures of Lung Cancer and Chronic Obstructive Pulmonary Disease.

Lung cancer (LC) is the leading cause of cancer deaths, and chronic obstructive pulmonary disease (COPD) can increase LC risk. Metallomics may provide insights into both of these tobacco-related diseases and their shared etiology. We conducted an observational study of 191 human serum samples, including those of healthy controls, LC patients, COPD patients, and patients with both COPD and LC. We found 18 elements (V, Al, As, Mn, Co, Cu, Zn, Cd, Se, W, Mo, Sb, Pb, Tl, Cr, Mg, Ni, and U) in these samples. In addition, we evaluated the elemental profiles of COPD cases of varying severity. The ratios and associations between the elements were also studied as possible signatures of the diseases. COPD severity and LC have a significant impact on the elemental composition of human serum. The severity of COPD was found to reduce the serum concentrations of As, Cd, and Tl and increased the serum concentrations of Mn and Sb compared with healthy control samples, while LC was found to increase Al, As, Mn, and Pb concentrations. This study provides new insights into the effects of LC and COPD on the human serum elemental profile that will pave the way for the potential use of elements as biomarkers for diagnosis and prognosis. It also sheds light on the potential link between the two diseases, i.e., the evolution of COPD to LC.

Quality appraisal of existing guidelines for the management of headache disorders by the AGREE II's method.

OBJECTIVE: To evaluate the quality of existing clinical practice guidelines for headache management and their main recommendations. BACKGROUND: Evidence-based clinical practice guidelines have been developed to support the clinical decision-making. However, to achieve this goal, the quality of these guidelines must be ensured. METHODS: A systematic search for clinical practice guidelines for headache management was conducted in the PubMed database, in websites of known guideline developers and in websites of known headache associations. The quality appraisal was performed through the Appraisal of Guidelines for Research and Evaluation II method. RESULTS: Twelve guidelines were evaluated. The domains of rigor of development, applicability, and editorial independence, which most influence the overall quality of guidelines, had the lowest average scores and the highest standard deviation rates (61% ± 23; 37% ± 20; 53% ± 31). The main recommendations regarding medication use for acute treatment of episodic tension-type headache and migraine in adult patients consisted of paracetamol, acetylsalicylic acid, and other nonsteroidal anti-inflammatory drugs in all guidelines. CONCLUSIONS: The statistical results indicate that the appraised guidelines have room for both individual and collective improvement. In addition, there is a well-established medication recommendation pattern among all guidelines evaluated.

Prevalence and factors associated with depression in people living with HIV/AIDS in a Brazilian metropolitan region.

The frequent association between mental disorders and HIV infection may be related to several risk factors. The present study aims to determine the prevalence of depression and its associated factors in people living with HIV/AIDS (PLWHA) who attended four outpatient clinics in Fortaleza, Brazil, between September 2014 and April 2015. In addition to the Mini International Neuropsychiatric Interview questionnaire, which was used to identify the prevalence of depressive disorder, the researchers applied a sociodemographic questionnaire, and the Hamilton Depression Scale to classify the severity of depression. In all, 257 participants were included in the analyses. The overall lifetime prevalence of depression was identified to be 29.2% (19.5% in men and 44.9% in women). The prevalence of a current depressive episode was 18.7%. Mild, moderate, and severe depression was identified in 2.1%, 12.5%, and 85.4%, respectively. The factors related to depression were: gender, marital status, income, educational level, current employment status, and family history of depression. This study highlights the importance of lifetime depression as a disorder of high prevalence in PLWHA, and associated with risk factors that are difficult or impossible to be modified. Early diagnosis and treatment of depression may improve quality of life in PLWHA.

Synthesis of Densely Substituted Sulfonylfurans and Dihydrofurans via Cascade Reactions of α-Functionalized Nitroalkenes with ß-Ketosulfones.

The reaction of ß-ketosulfones with different α-functionalized nitroalkenes affords diversely substituted sulfonylfurans and dihydrofurans. Furthermore, ß-ketosulfones react with α-bromonitroalkenes and α-hydrazinonitroalkenes via a cascade Michael addition-cyclization protocol to afford nitrodihydrofurans and hydrazinodihydrofurans, respectively, bearing a key sulfonyl group, in excellent yields with a broad substrate scope. Application of these products has been demonstrated by the synthesis of pyrroles and pyrazoles in good yields. The reaction of ß-ketosulfones with nitroallylic acetates yields tetrasubstituted sulfonyl furans through a cascade SN2'-intramolecular Michael reaction, followed by aromatization. The gram-scale synthesis of a representative example of sulfonylfurans was carried out to demonstrate the synthetic efficiency of the methodology.

[Priorities of clinical drug trials in Brazil and neglected diseases of poverty]. / Prioridades da pesquisa clínica com medicamentos no Brasil e as doenças da pobreza.

OBJECTIVE: To identify clinical drug trials performed in Brazil between 2012 and 2015, with emphasis on those focusing on neglected diseases of poverty. METHOD: Two clinical trial registries, ReBEC (Brazilian registry) and ClinicalTrials.gov were surveyed. The following aspects were investigated: distribution of clinical trials in relation to the burden of disease in Brazil, distribution of trials regarding their focus on diseases of poverty vs. diseases not linked to poverty, phase of trials, performing institution, and type of funding (private, public, or mixed). RESULTS: The search revealed 866 eligible trials, 88 registered in ReBEC and 778 in ClinicalTrials.gov. Of these, 73 (8.5%) were phase I trials, 610 (70.5%) were phase II and III trials, and 183 (21%) were phase IV trials. There were 38 trials (4%) focusing on neglected diseases of poverty. Regarding the burden of disease, 734 (84.8%) trials focused on noncommunicable diseases, which in fact represent the largest burden of disease in Brazil. Most trials were carried out by pharmaceutical companies (55.3%), with predominance of private funding (57.1%); however, if only the diseases of poverty are considered, 63.1% were financed by public resources. CONCLUSIONS: The clinical drug trials carried out in Brazil in the study period are in agreement with the proportional burden of disease for the country. However, the neglected diseases of poverty were not prioritized. More effective action is necessary to redirect clinical research on drug development to meet national needs.

[Indicators for drug selection in health systems: an integrative review]. / Indicadores da seleção de medicamentos em sistemas de saúde: uma revisão integrativa.

OBJECTIVE: To produce a panel of the main drug selection indicators by performing an integrative literature review. METHODS: After the elaboration of a review protocol, searches were conducted in LILACS, MEDLINE, Embase, and SciELO databases. The following search terms were used: "indicators"; "criteria"; "drug selection"; "pharmacy and therapeutics committee"; and "medication form"; with the applicable variations in English and Spanish. Sixteen original articles published between January 1996 and March 2012 were retrieved and reviewed to compose a panel of indicators. RESULTS: Forty-five quantitative and qualitative indicators were identified. These indicators were grouped according to conceptual similarities in three categories: 1) assessment of pharmacy and therapeutics committee structure; 2) evaluation of the general processes of drug selection; and 3) evaluation of the results of drug selection. CONCLUSIONS: The indicators identified reveal relative uniformity in the established patterns for drug selection. The group of indicators established in this study should serve as reference for the development and consolidation of drug selection in public health services.

Clinical guidelines for herpes labialis: recommendations and quality evaluation according to AGREE II.

Cold sores require Healthcare professionals to employ specific approaches for prevention and management, with the need for effective therapeutic guidelines and ongoing improvement in patient care. AIM: To evalúate the methodological quality of Clinical Guidelines (CG), clinical guides and manuals for care of the population affected by herpes labialis, to verify their compliance with evidence-based health standards. MATERIALS AND METHOD: A search was conducted for CG on labial herpes in the MedicalLiteratureAnalysis andRetrieval System Online (Medline) database, Google Scholar, Brazilian Virtual Health Library (BVS), and sites of institutions/professional categories, using the descriptors "herpes labialis" or "oral herpes". Document quality was assessed using the Appraisal of Guidelines for Research & Evaluation Instrument (AGREE II). The Kappa test was used to avoid randomness or poor agreement between results. RESULTS: Analysis of the 12 selected publications on the management of labial herpes revealed flaws in quality, as the publications did not follow a quality standard. The main quality flaws identified were in "rigor in development" and "applicability. ". CONCLUSIONS: Priorities need to be redefined in the development of CG for clinical practice related to fever blisters to reduce the variability of the quality standard, and generate reliable, applicable recommendations.

A Herpes labial requer dos profissionais abordagens específicas para prevenido e manejo, com a ne-cessidade de diretrizes terapéuticas eficazes e continuo aprimoramento do cuidado ao paciente. OBJETIVO: avaliar a qualidade metodológica de documentos que abordaram Diretrizes Clínicas (DC), guias clínicos e manuais para o cuidado da populando afetada pelo herpes labial, verificando sua conformidade com padroes de saúde baseados em evidencias. MATERIAIS E MÉTODO: As DC sobre herpes labial foram pesquisadas na base de dados Medical Literature Analysis and Retrieval System Online (Medline), Google Académico, Biblioteca Virtual em Saúde (BVS) e em sites de instituigoes/categorias profissionais, utilizando os descritores "herpes labial" ou "herpes oral". Utilizamos aferramenta The Appraisal of Guidelines for Research & Evaluation Instrument (AGREE II) para a avaliagdo da qualidade. O teste Kappa também foi utilizado para evitar aleatoriedade ou baixa concordáncia entre os resultados. RESULTADOS: Na análise das 12 publicagoes selecionadas sobre o manejo do herpes labial, foram identificadas falhas na qualidade dos documentos, que ndo seguiram um padrdo de qualidade. As principais falhas de qualidade identificadas foram em "rigor no desenvolvimento" e "aplicabilida-de". CONCLUSÃO: é necessário um reenfoque para definir prioridades no desenvolvimento de DC para a prática clínica do herpes labial, a fim de reduzir a variabilidade do padrdo de qualidade e gerar recomendagoes que possam ser confiáveis e aplicáveis.

1H and 13C NMR analysis of 2-acetamido-3-mercapto-3-methyl-N-aryl-butanamides and 2-acetamido-3-methyl-3-nitrososulfanyl-N-aryl-butanamide derivatives.

The complete assignment of the (1)H and (13)C NMR spectra of various 2-acetamido-3-mercapto-3-methyl-N-aryl-butanamides and 2-acetamide-3-methyl-3-nitrososulfanyl-N-aryl-butanamides with p-methoxy, o-chloro and m-chloro substituents is reported.

Availability of emergency contraception in large Brazilian municipalities: a guaranteed right?

Introduction: Emergency Contraception (EC) is available in Brazil since 1996, when it was adopted as one if the family planning strategies and, in 1998, for use in services assisting victims of sexual violence. In the country, its use is regulated by guidelines. Its access through SUS (Unified Health System), however, does not seem to occur in a standardized manner. Methods: The aim of the study was to analyze the availability and barriers to accessing emergency contraception (levonorgestrel) in Brazilian municipalities with more than 500 thousand inhabitants. The survey was carried out by a form sent to the Municipal Health Departments (SMS) managers and a search on the list of standardized medicines by the hospitals in the same municipalities. Results: The Basic Health Units were identified as the standard access places to EC. However, one of the obstacles mentioned is the need for a prescription for dispensing in almost 80% of the analyzed cities. Access in emergency situations at night and on weekends is also uncertain, since although 67% of the places stated that they dispense at the hospital level, the item was only standardized in 21% of the hospital lists. Discussion: The difficult access this drug in the public system essentially tends to harm the poorest women, who are the ones who suffer most from the consequences of an unwanted pregnancy.

Comparative analysis of the use and control of thalidomide in Brazil and different countries: is it possible to say there is safety?

INTRODUCTION: One of the biggest drug disasters in history has not prevented thalidomide from being used to treat various clinical conditions. Currently, Brazil has a worrying scenario: high consumption of the drug and, cases of pregnant women using thalidomide, even after adopting restrictive legislation. AREAS COVERED: This review of the literature and legislation sought to comparatively analyze the monitoring of thalidomide use in Brazil and other countries that use this drug. Finally, we discuss the differences between the countries. EXPERT OPINION: This analysis allows us to think beyond the safe use of thalidomide, but the safety provided by any type of monitoring system. It seems that out-patients that use unsafe drugs are exposed to some degree of risk. To improve safety, more extensive improvements are needed than monitoring systems related to the use of thalidomide. Its safe use depends on a drastic reduction in the incidence of leprosy and Erythema Nodosum Leprosum in the world; investment in research and development of safe and effective therapeutic alternatives to thalidomide; improvement of health systems and their health surveillance systems, particularly in primary health care; awareness of health professionals and patients for greater responsibility in the use of medicines, especially thalidomide.

Medicine manipulation: An alternative to mitigate therapeutic gaps in the Brazilian Unified Health System?

Despite the various initiatives carried out in Brazil and in the world, the challenge of offering essential medicines in adequate presentations remains, especially to the public affected by diseases considered neglected and the pediatric population, for whom the therapeutic options remain limited. The main objective of this study was to evaluate the production of manipulated medicines as a strategy to mitigate therapeutic and access gaps to essential medicines within the Brazilian public health system, called the Unified Health System (SUS). The evaluation, carried out between 2020 and 2021, identified, among the medicines considered essential to the Brazilian health context, those unavailable, for which strategies were evaluated to mitigate the identified unavailability, which is conventionally called therapeutic gaps. For 57% (n = 235) of pharmaceutical presentations identified as therapeutic gaps in SUS, manipulation was identified as the best strategy to promote access. Of these presentations, 30% (n = 70) were identified as priorities in the context of patient care and were mainly related to the demands of the pediatric public and those affected by poverty-related diseases. Concerning poverty-related diseases, the absence of evidence on the development of a standard formula for drugs with indication for such diseases was demonstrated. The need for an annual investment of approximately US$74.75 per capita was estimated to offer treatments in adequate presentations to SUS users, which should reflect in the improvement of the quality of life of about 26 thousand people. It was observed that this investment amount corresponds to only 3% of the budget for the purchase of medicines financed exclusively by the Ministry of Health thorugh the Strategic Component of Pharmaceutical Assistance (CESAF) approved for 2021.

Treatment of Extensive Soft Tissue Injury with Polypropylene Prosthesis: A Case Study.

Injuries with exposure of soft tissue are frequent in orthopaedics. Innovative therapies using prosthesis as an auxiliary material to treat this type of injury are under development, aiming to overcome applicability and execution limitations of myocutaneous flap techniques. Figueiredo's technique uses a polypropylene prosthesis extracted from sterile saline to treat trauma at the fingertip. It is an alternative technique with a high success rate, reproducible, low cost and easy to apply. This article reports a case of foot injury with exposure of soft tissue treated with a treatment similar to Figueiredo's technique. The patient was admitted with a large and contaminated skin wound, muscle damage, tendon exposure, cuboid fracture and bone loss. Initially, debridement was performed. After 72 hours, a polypropylene prosthesis extracted from a sterile saline bottle was implanted and subsequently replaced after 60 days. After 76 days, the prosthesis was removed. There was no infection. 8 months later, there was total healing by second intention. The patient's motor and sensory functions were preserved. This case study shows that Figueiredo's technique can also be employed in more extensive injuries, representing an alternative to using myocutaneous flaps. The polypropylene prosthesis is extremely affordable, which enables resolution of cases in a greater number of services. This technique still offers the best aesthetic result and does not compromise other body regions.

Isolation of Robinsoniella peoriensis from four human specimens.

Robinsoniella peoriensis is a recently described anaerobic, spore-forming, Gram-positive bacillus originally recovered from swine manure. We report four human cases in which R. peoriensis was isolated from clinical samples.

Mesoscale and wind-driven intra-annual variability in the East Auckland Current.

Intra-annual variability in the East Auckland Current (EAuC) was studied using a year-long timeseries of in situ and remotely-sensed velocity, temperature and salinity observations. Satellite-derived velocities correlated well ([Formula: see text]) with in situ observations and well-represent the long-term ([Formula: see text] days) variability of the upper ocean circulation. Four mesoscale eddies were observed during the year (for 260 days) which generated distinct flows between the continental slope and rise. The EAuC dominated the circulation in the continental shelf break, slope and rise for 110 days and generated the most energetic events associated with wind forcing. Current variability on the continental slope was coherent with along-slope wind stress (wind stress curl) at periods between 4 and 12 days (16 and 32 days). We suggest that along-slope winds generated offshore Ekman transport, uplift on the shelf-break, and a downwind geostrophic jet on the slope. In contrast, positive wind stress curl caused convergence of water, downwelling, and increased the current speed in the region. Bottom Ekman transport, generated by the EAuC, was suggested to have caused the largest temperature anomaly ([Formula: see text]) at the continental shelf-break.

Lexical and grammatical development in a child with cochlear implant and attention deficit: A case study.

This is the first study to explore lexical and grammatical development in a deaf child diagnosed with Attention Deficit Hyperactivity Disorder, Inattentive sub-type (ADHD/I). The child, whose family language was Spanish, was fitted with a cochlear implant (CI) when she was 18 months old. ADHD/I, for which she was prescribed medication, was diagnosed 3;6 years later. Speech samples were videotaped over the first 4 years of CI use and during a follow-up session 1 year later. Samples were transcribed according to CHAT conventions and several measures of expressive language were obtained. Receptive language was evaluated with standardized tests. Results show that while some aspects of her development seemed relatively positive (e.g., acquisition of verbal morphemes at the same auditory age as typical children), other characteristics were atypical for a CI user: (1) preference for paralexical expressions in early lexicon; (2) lexical errors in colours and other abstract words; and (3) low MLU and varied grammatical errors including disorganized discourse. Medication had a positive effect on all these characteristics, providing evidence of a link with ADHD/I. This study concludes that ADHD/I had a direct impact on the lexical and grammatical development in this child, as well as an indirect influence over her communicative style. More studies are needed to explore language characteristics of children with CI and ADHD.

The organization, weaknesses, and challenges of the control of thalidomide in Brazil: A review.

The drug thalidomide has resurged in the world market under restrictive conditions for marketing and use. In Brazil, there are still cases of pregnant women using thalidomide even after the implementation of laws that regulate the control of use (Law No. 10.651/2003 and Collegiate Board Resolution No. 11/2011). The objective of this study was to discuss the control of thalidomide use in Brazil, based on a scoping review of the scientific literature, documents, and data from the Ministry of Health. A total of 51 studies and documents related to the following subthemes were selected: (1) organization of access and use of thalidomide in the health system; (2) epidemiological and population characteristics of people affected by leprosy; and (3) occurrence of pregnancy and cases of embryopathy with the use of thalidomide. The results showed that Brazil has no unified information database about thalidomide patients. Furthermore, there is inconsistency in the accreditation of public health centers that dispense this medicine, in a country that has a high consumption of thalidomide in the Unified Health System. A large part of this amount of dispensed medicine is intended for the treatment of erythema nodosum leprosum, mainly in the North, Northeast, and Central-West regions of the country, which are endemic for leprosy. This disease is the only one among the clinical indications of the medicine approved in Brazil that does not have a Clinical Protocol and Therapeutic Guidelines. The control of thalidomide use in Brazil presents historical regulatory failures. These are currently linked to the organization and structure of primary healthcare in the country, as well as to the lack of leadership of the Ministry of Health and National Health Surveillance Agency when it comes to managing the process of control of this use.

PARKINSONISM AS AN ATYPICAL MANIFESTATION OF PRIMARY HYPERPARATHYROIDISM.

OBJECTIVE: Primary hyperparathyroidism (PHPT) occurs as a result of hyperfunctional parathyroid glands resulting in an elevation of serum calcium levels. The association between hypoparathyroidism and parkinsonism have been frequently reported in the literature, while evidence of hyperparathyroidism associated with parkinsonism is rare. METHODS: The present study reports a case of a patient that had PHPT and developed symptoms of parkinsonism. RESULTS: A 75-year-old female patient with a history of diabetes mellitus, dyslipidemia, and systemic arterial hypertension presented to the emergency room due to unexplained drowsiness. Her serum calcium at the time was 14.2 mg/dL. A cervical ultrasound was performed, and the presence of a 2.5 × 1.9-cm nodule in the left lower parathyroid region was identified. Three days later, scintigraphy with the use of sestamibi showed an increased capture of the marker in the same region, suggesting parathyroid hyperfunction. During hospitalization, the patient developed symptoms of parkinsonism. A left inferior parathyroidectomy was performed, with normalization of serum calcium levels and a remission of drowsiness, in addition to a significant improvement in parkinsonian symptoms. The patient remained free of parkinsonism over 3 years of follow up. CONCLUSION: Parathyroidectomy can provide a significant remission of parkinsonism in a patient with PHPT. Even though it is rare, the relation between parkinsonism and PHPT exists.

The different clinical guideline standards in Brazil: High cost treatment diseases versus poverty-related diseases.

Each year, evidence-based clinical guidelines gain more space in the health professionals' practice and in services organization. Due to the scarcity of scientific publications focused on diseases of poverty, the development of well-founded clinical guidelines becomes more and more important. In view of that, this paper aims to evaluate the quality of Brazilian guidelines for those diseases. The AGREE II method was used to evaluate 16 guidelines for poverty-related diseases (PRD) and 16 guidelines for global diseases whose treatment require high-cost technologies (HCD), with the ultimate aim of comparing the results. It was found that, in general, the guideline development quality standard is higher for the HCD guidelines than for the PRD guidelines, with emphasis on the "rigour of development" (48% and 7%) and "editorial independence" (43% and 1%) domains, respectively, which had the greatest discrepancies. The HCD guidelines showed results close to or above international averages, whereas the PRD guidelines showed lower results in the 6 domains evaluated. It can be concluded that clinical protocol development priorities need some redirecting in order to qualify the guidelines that define the healthcare organization and the care of vulnerable populations.