Benefits and Risks of Testosterone Treatment in Men with Age-Related Decline in Testosterone.

The substantial increase in life expectancy of men has focused growing attention on quality-of-life issues associated with reproductive aging. Serum total and free testosterone levels in men, after reaching a peak in the second and third decade of life, decline gradually with advancing age. The trajectory of age-related decline is affected by comorbid conditions, adiposity, medications, and genetic factors. Testosterone treatment of older men with low testosterone levels improves overall sexual activity, sexual desire, and erectile function; improves areal and volumetric bone density, as well as estimated bone strength in the spine and the hip; corrects unexplained anemia of aging; increases skeletal muscle mass, strength and power, self-reported mobility, and some measures of physical function; and modestly improves depressive symptoms. The long-term effects of testosterone on major cardiovascular events and prostate cancer risk remain unclear. The Endocrine Society recommends against testosterone therapy of all older men with low testosterone levels but suggests consideration of treatment on an individualized basis in men who have consistently low testosterone levels and symptoms or conditions suggestive of testosterone deficiency.

Radiographic dental age estimation applying and comparing Demirjian's seven (1973) and four (1976) teeth methods.

To apply Demirjian's seven (1973, D7) and four (1976, D4) teeth methods in a sample of Brazilian children and compare their performances for age estimation. Panoramic radiographs of 1200 children (600 females and 600 males) were collected from Southeast Brazil. The children were equally distributed (n = 60 females and 60 males) between age intervals of 1 year between 6 and 15.9 (mean age = 10.9; standard deviation [SD]: 2.9) years. D7 and D4 dental age estimation methods were applied by two observers and were compared based on their error rates (error = estimated age-chronological age). Both methods overestimated the chronological age (p < 0.0001). D7 led to overestimations of 0.71 (p < 0.0001) in females and 0.83 (p < 0.0001) in males, while the overestimations with D4 were 0.14 (p = 0.0067) and 0.73 (p < 0.0001) for females and males, respectively. The mean age estimated by D7 was 11.7 (SD: 3.1) years, while for D4, it was 11.3 (SD: 3.3) years. Intra- and interobserver agreement was ≥ 0.98. D4 optimized the performance of radiographic dental age estimation compared to D7. Improvements were reflected in the total sample and separately for female and male children from Southeast Brazil.

Prognostic role of hydronephrosis in the treatment of patients with locally advanced cervical cancer: a retrospective cohort.

BACKGROUND: Obstructive uropathy is present in almost 50% of patients with advanced cervical cancer and is associated with worse outcomes. OBJECTIVE: To estimate the prognostic role of hydronephrosis and the impact of ureteral obstruction resolution in patients with locally advanced cervical cancer undergoing treatment. METHODS: A retrospective cohort study was conducted of patients with International Federation of Gynecology and Obstetrics 2018 stage IIIB to IVA treated in a tertiary oncologic referral center in Brazil between January 2009 and June 2018. Three different groups were evaluated: (I) without hydronephrosis, (II) with hydronephrosis and urinary diversion, and (III) with hydronephrosis but no urinary diversion. Kaplan-Meier curves and log-rank tests estimated overall survival and progression-free survival based on the presence of hydronephrosis and urinary diversion. Clinicopathological variables were evaluated using univariate and multivariate Cox proportional hazard regression model for overall survival and progression-free survival. RESULTS: A total of 151 patients were evaluated: group I - 62 (41.1%); II - 44 (29.1%), and III - 45 (29.8%). Stage, histological type or grade, tumor size, parametrial or lymph node involvement were not statistically different between groups. Group I had more favorable overall survival than groups II (p<0.003) and III (p<0.02); however, no difference was noted between groups II and III. Progression-free survival was similar between groups (log-rank test p=0.95). Univariate analysis revealed hydronephrosis (p=0.002) and concurrent chemoradiotherapy (p<0.001) as a prognostic factor for worse overall survival; while tumor size (p=0.023), pelvic lymphadenopathy (p=0.015), and histological type (p=0.03) were associated with worse progression-free survival. On multivariate analysis, hydronephrosis remained as an independently associated factor with worse overall survival (HR=2.06; 95% CI 1.12 to 3.79, p=0.02). CONCLUSION: Patients with locally advanced cervical cancer with hydronephrosis had lower overall survival even after controlling for potential confounding factors, but no difference in progression-free survival. Urinary diversion showed no impact on overall survival or progression-free survival.

Protein and volatile contents in the mandibular gland of the sugarcane borer Diatraea saccharalis (Lepidoptera: Crambidae).

The sugarcane borer Diatraea saccharalis (Lepidoptera: Crambidae) is an important sugarcane pest and mechanical injuries caused through the mandibles can allow pathogen infections. The mandibles of D. saccharalis, as well as other insects, are associated with mandibular glands with a possible function in food intake and mouthparts lubrication; however, the chemical composition of the secretion is poorly known and its elucidation is important for the comprehensive understanding of plant-insect interactions. This study characterized some proteins and volatiles in the mandibular glands of D. saccharalis larvae. MALDI-TOF/TOF mass spectrometry allowed the identification of 24 predicted proteins within 10 functional classes, including the transport and metabolism of carbohydrates, lipids, amino acids, and nucleotides; Posttranslational protein modifications; energy conversion; intracellular trafficking; transcription; translation; and cytoskeleton function. Metabolites identified from GC/MS analysis revealed the presence of hydrocarbons classified as alcohols, ether, alkanes, and esters with differences in their relative abundance. Linolenic acid, the most abundant metabolite found in this gland, when conjugated with amino acids, can be an elicitor in the plant-herbivore interaction. The results suggest the occurrence of digestive and defensive biochemical components, which may contribute to understanding of the multifunctional roles of the mandibular gland secretion of D. saccharalis larvae during feeding activity.

An updated gene regulatory network reconstruction of multidrug-resistant Pseudomonas aeruginosa CCBH4851.

BACKGROUND: Healthcare-associated infections due to multidrug-resistant (MDR) bacteria such as Pseudomonas aeruginosa are significant public health issues worldwide. A system biology approach can help understand bacterial behaviour and provide novel ways to identify potential therapeutic targets and develop new drugs. Gene regulatory networks (GRN) are examples of in silico representation of interaction between regulatory genes and their targets. OBJECTIVES: In this work, we update the MDR P. aeruginosa CCBH4851 GRN reconstruction and analyse and discuss its structural properties. METHODS: We based this study on the gene orthology inference methodology using the reciprocal best hit method. The P. aeruginosa CCBH4851 genome and GRN, published in 2019, and the P. aeruginosa PAO1 GRN, published in 2020, were used for this update reconstruction process. FINDINGS: Our result is a GRN with a greater number of regulatory genes, target genes, and interactions compared to the previous networks, and its structural properties are consistent with the complexity of biological networks and the biological features of P. aeruginosa. MAIN CONCLUSIONS: Here, we present the largest and most complete version of P. aeruginosa GRN published to this date, to the best of our knowledge.

Decreased Native T1 Values and Impaired Myocardial Contractility in Anabolic Steroid Users.

Anabolic androgenic steroid (AAS) abuse leads to myocardial toxicity. Human studies are conflicting about the myocardial fibrosis in AAS users. We evaluated cardiac tissue characterization, left ventricle (LV) function, and cardiac structure by cardiovascular magnetic resonance (CMR). Twenty strength-trained AAS users (AASU) aged 29±5 yr, 20 strength-trained AAS nonusers (AASNU), and 7 sedentary controls (SC) were enrolled. Native T1 mapping, late-gadolinium enhancement (LGE), extracellular volume (ECV), and myocardial strain were evaluated. AASU showed lower Native T1 values than AASNU (888±162 vs. 1020±179 ms p=0.047). Focal myocardial fibrosis was found in 2 AASU. AASU showed lower LV radial strain (30±8 vs. 38±6%, p<0.01), LV circumferential strain (-17±3 vs. -20±2%, p<0.01), and LV global longitudinal strain (-17±3 vs. -20±3%, p<0.01) than AASNU by CMR. By echocardiography, AASU demonstrated lower 4-chamber longitudinal strain than AASNU (-15±g3 vs. -18±2%, p=0.03). ECV was similar among AASU, AASNU, and SC (28±10 vs. 28±7 vs. 30±7%, p=0.93). AASU had higher LV mass index than AASNU and SC (85±14 vs. 64±8 vs. 58±5 g/m2, respectively, p<0.01). AAS abuse may be linked to decreased myocardial native T1 values, impaired myocardial contractility, and focal fibrosis. These alterations may be associated with maladaptive cardiac hypertrophy in young AAS users.

Optical Biosensor for the Detection of Infectious Diseases Using the Copolymer F8T2 with Application to COVID-19.

The coronavirus pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has accelerated the development of biosensors based on new materials and techniques. Here, we present our effort to develop a fast and affordable optical biosensor using photoluminescence spectroscopy for anti-SARS-CoV-2 antibody detection. The biosensor was fabricated with a thin layer of the semiconductor polymer Poly[(9,9-di-n-octylfluorenyl-2,7-diyl)-alt-2,2'-bithiophene-5,5'-diyl)] (F8T2) as a signal transducer material. We mounted the biosensors by depositing a layer of F8T2 and an engineered version of RBD from the SARS-CoV-2 spike protein with a tag to promote hydrophobic interaction between the protein and the polymeric surface. We validated the biosensor sensitivity with decreasing anti-RBD polyclonal IgG concentrations and challenged the biosensor specificity with human serum samples from both COVID-19 negative and positive individuals. The antibody binding to the immobilized antigen shifted the F8T2 photoluminescence spectrum even at the low concentration of 0.0125 µg/mL. A volume as small as one drop of serum (100 µL) was sufficient to distinguish a positive from a negative sample without requiring multiple washing steps and secondary antibody reactions.

Sacubitril/valsartan versus enalapril on exercise capacity in patients with heart failure with reduced ejection fraction: A randomized, double-blind, active-controlled study.

Sacubitril/valsartan reduces mortality in patients with heart failure with reduced ejection fraction (HFrEF) when compared with enalapril. However, it is unknown the effect of both treatments on exercise capacity. We compared sacubitril/valsartan versus enalapril in patients with HFrEF based on peak oxygen consumption (VO2) and 6-minute walk test (6-MWT). METHODS: We included 52 participants with HFrEF with a left ventricular ejection fraction <40% to receive either sacubitril/valsartan (target dose of 400 mg daily) or enalapril (target dose of 40 mg daily). Peak VO2 was measured by using cardiopulmonary exercise testing. Six-minute walk test was also performed. RESULTS: At 12 weeks, the sacubitril/valsartan (mean dose 382.6 ± 57.6 mg daily) group had increased peak VO2 of 13.1% (19.35 ± 0.99 to 21.89 ± 1.04 mL/kg/min) and enalapril (mean dose 34.4 ± 9.2 mg daily) 5.6% (18.58 ± 1.19 to 19.62 ± 1.25 mL/kg/min). However, no difference was found between groups (P = .332 interaction). At 24 weeks, peak VO2 increased 13.5% (19.35 ± 0.99 to 21.96 ± 0.98 mL/kg/min) and 12.0% (18.58 ± 1.19 to 20.82 ± 1.18 mL/kg/min) in sacubitril/valsartan (mean dose 400 ± 0 mg daily) and enalapril (mean dose 32.7 ± 11.0 mg daily), respectively. However, no differences were found between groups (P= .332 interaction). At 12 weeks, 6-MWT increased in both groups (sacubitril/valsartan: 459 ± 18 to 488 ± 17 meters [6.3%] and enalapril: 443 ± 22 to 477 ± 21 meters [7.7%]). At 24 weeks, sacubitril/valsartan increased 18.3% from baseline (543 ± 26 meters) and enalapril decreased slightly to 6.8% (473 ± 31 meters), but no differences existed between groups (P= .257 interaction). CONCLUSIONS: Compared to enalapril, sacubitril/valsartan did not substantially improve peak VO2 or 6-MWT after 12 or 24 weeks in participants with HFrEF. (NEPRIExTol-HF Trial, ClinicalTrials.gov number, NCT03190304).

Immunologic biomarkers, morbidity and mortality among HIV patients hospitalised in a Tertiary Care Hospital in the Brazilian Amazon.

BACKGROUND: The irregular use of antiretroviral therapy (ART) and late diagnosis still account for a large part of HIV-associated mortality in people living with HIV (PLHIV). Herein, we describe HIV-associated morbidity among hospitalised HIV/AIDS patients with advanced immunosuppression and assess the comorbidities, laboratory parameters, and immunological markers associated with mortality. METHODS: The cross-sectional study was conducted at the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD) in Manaus, Brazil. In all, 83 participants aged between 12 and 70 years were enrolled by convenience within 72 h of their hospitalisation. Clinical and laboratory data were obtained from electronic medical records. We prospectively measured the cytokines Th1/Th2/Th17 and inflammatory cytokines IL-8, IL-1ß, and IL-12 using cytometric bead array, and the soluble CD14 using in-house enzyme-linked immunosorbent assay. RESULTS: The HIV/AIDS inpatients presented a scenario of respiratory syndromes as the most prevalent comorbidity. Almost all patients had CD4 T counts below 350 cells/mL and the mortality rate was 20.5%. Pulmonary tuberculosis, neurotoxoplasmosis and oropharyngeal-esophageal candidiasis were the most prevalent opportunistic infections. TB and weight loss were more prevalent in HIV/AIDS inpatients who died. The Mann Whitney analysis showed that those who died had higher platelet distribution width (PDW) on admission, which is suggestive for platelet activation. The Poisson multivariate analysis showed the prevalence of TB, digestive syndrome and increases in IL-8 and lactate dehydrogenase (LDH) associated to death. CONCLUSIONS: The advanced immunosuppression characterized by the opportunistic infections presented in these HIV/AIDS inpatients was the major factor of mortality. The role of platelet activation in worse outcomes of hospitalisation and the IL-8 associated with the context of advanced immunosuppression may be promising markers in the prediction of mortality in HIV/AIDS patients.

Novel Hg (II) selective fluorescent green sensor based on carbon dots synthesized from starch and functionalized with methimazole.

We describe a green new method for the synthesis of water-soluble photoluminescent carbon dots (CDs) that were functionalized with methimazole (MTZ) and applied to determine Hg2+ based on the fluorescence extinction. Starch obtained from rice was used as a natural source for the production of CDs by hydrothermal treatment. Also, it was proposed a factorial design to optimize the parameters for CD synthesis and the results showed that the luminescence intensity is a function of temperature and not of the heating time in the hydrothermal process. The synthesized CDs were characterized using fluorescence techniques, Fourier transform infrared spectroscopy (FTIR), and UV-Vis spectroscopy. Through transmission electron microscopy (TEM) and dynamic light scattering (DLS), it was found the formation of CDs on a nanometer scale with an average size of 11 nm. The functionalization with MTZ, eliminated all interferences from other metals, indicating a selective response to Hg2+ ions. The method was applied to Hg2+ determination in waters. Under optimal conditions, was obtained a limit of detection of 1.8 × 10-7 mol L-1 with a linear range from 3.3 × 10-7 to 50.0 × 10-6 mol L-1. Therefore, the proposed method can be considered a simple, selective, and precise alternative that minimizes the number of reagents used for Hg2+ determination in natural waters, and can be applied on a large scale in environmental analyzes.

Investigation of 8-methoxy-3-(4-nitrobenzoyl)-6-propyl-2H-chromen-2-one as a promising coumarin compound for the development of a new and orally effective antileishmanial agent.

Changes in host immunity and parasite resistance to drugs are among the factors that contribute to decreased efficacy of antiparasitic drugs such as the antimonial compounds pentamidine, amphotericin (AMP B) and miltefosine. Bioactive natural products could be alternatives for the development of new drugs to treat neglected human diseases such as leishmaniasis. Natural coumarins and synthetic analogues have shown leishmanicidal activity, mainly in vitro. This study investigated the in vitro and in vivo leishmanicidal activity of synthetic coumarin compounds (C1-C5) in parasites Leishmania (L.) amazonensis and L. (L.) infantum chagasi. The cytotoxicity of these compounds in mammalian cells and their influence on production of reactive oxygen species was also investigated. In vitro assays showed that 8-methoxy-3-(4-nitrobenzoyl)-6-propyl-2H-chromen-2-one (C4) was as active as AMP B mainly in the amastigote form (p < 0.05); C4 presented a selectivity index (65.43) four times higher than C2 (15.4) in L. amazonensis and six times higher (33.94) than C1 (5.46) in L. infantum chagasi. Additionally, coumarin C4 reduced the H2O2 concentration 32.5% more than the control group in L. amazonensis promastigotes during the lag phase of proliferation. No interference of C4 was observed on the mitochondrial membrane potential of the parasites. In vivo, coumarin C4 in corn oil (oral route) led to a reduction in the number of amastigotes from L. infantum chagasi to 1.31 × 106 and 4.09 × 104 in the spleen and liver, respectively (p < 0.05). Thus, C4 represents a candidate for further studies aiming at new treatments of leishmaniasis.

COVID-19: instruments for the allocation of mechanical ventilators-a narrative review.

After the World Health Organization declared COVID-19 to be a pandemic, the elaboration of comprehensive and preventive public policies became important in order to stop the spread of the disease. However, insufficient or ineffective measures may have placed health professionals and services in the position of having to allocate mechanical ventilators. This study aimed to identify instruments, analyze their structures, and present the main criteria used in the screening protocols, in order to help the development of guidelines and policies for the allocation of mechanical ventilators in the COVID-19 pandemic. The instruments have a low level of scientific evidence, and, in general, are structured by various clinical, non-clinical, and tiebreaker criteria that contain ethical aspects. Few instruments included public participation in their construction or validation. We believe that the elaboration of these guidelines cannot be restricted to specialists as this question involves ethical considerations which make the participation of the population necessary. Finally, we propose seventeen elements that can support the construction of screening protocols in the COVID-19 pandemic.

University Hospital Financial Status Does Not Influence Subjective Perception of General Surgery Residents on Training Adequacy.

BACKGROUND: Surgical residency training is a complex and costly task. Hospital economic health is dependent on different variables, but it is especially linked to the country macroeconomics that may be extremely fluctuating, especially in underdeveloped countries. This study analyzed the correlation between a single-center university hospital financial status and subjective perception of general surgery residents on program support and adequacy. METHODS: We surveyed former residents that started general surgery residency program in a tertiary university hospital between 1999 and 2017. Individuals answered a questionnaire about the perception of the influence of the hospital´s financial status on training. Hospital´s financial status was estimated yearly by the current liquidity ratio (CLR) that measures whether or not a company has enough resources to meet its short-term obligations. RESULTS: Two hundred and fifty-seven (96%) were still in surgical practice; 242 (93%) were satisfied with their residency training; 210 (78%) believed training was affected by financial status; 183 (68%) believed they were prepared for independent practice; 180 (67%) practiced in an academic environment; 146 (54%) felt the need to complete specialty training beyond residency; and 56 (21%) believed hospital financial status was adequate. The rate of positive or negative answers did not correlate with the current liquidity ratio, except for the need to complete specialty training that was indirectly related to CLR. CONCLUSIONS: University hospital financial status did not influence subjective perception of general surgery residents on training, program support and adequacy.

Cardiophrenic lymph node resection in cytoreduction for primary advanced or recurrent epithelial ovarian carcinoma: a cohort study.

OBJECTIVES: To evaluate the clinical outcomes of epithelial ovarian carcinoma patients who underwent cardiophrenic lymph node resection. METHODS: We retrospectively reviewed the records of all surgically treated patients with advanced epithelial ovarian carcinoma (stages IIIC-IV) who underwent cardiophrenic lymph node resection between 2002 and 2018. Only those in whom cardiophrenic lymph node involvement was the only detectable extra-abdominal disease were included. Patients with suspected cardiophrenic lymph node metastasis on staging images underwent a transdiaphragmatic incision to access the para-cardiac space after complete abdominal cytoreduction achievement. Data on disease-free survival, overall survival, and surgical procedures performed concurrently with cardiophrenic lymph node resection were collected. RESULTS: Of the total 456 patients, 29 underwent cardiophrenic lymph node resection; of these, 24 patients met the inclusion criteria. Twenty-two, one, and one patients had high grade serous epithelial ovarian carcinoma, low grade epithelial ovarian carcinoma, and ovarian carcinosarcoma, respectively. Ten patients had recurrent disease (recurrence group). Fourteen patients underwent cytoreduction during primary treatment (primary debulking group); four underwent cytoreduction after neoadjuvant chemotherapy. Cardiophrenic lymph node resection was performed on the right side in 19 patients, left side in three, and bilaterally in two. The average procedural duration was 28 minutes, with minimal blood loss and no severe complications. Twenty-one patients had cardiophrenic lymph node positivity. The median disease-free intervals were 17 and 12 months in the recurrent and primary debulking surgery groups, respectively. The mediastinum was the first recurrence site in 10 patients. Five patients developed brain metastases. Five patients had an overall survival beyond 50 months. CONCLUSIONS: Although rare, the cardiophrenic lymph nodes may be a site of metastasis of ovarian cancer. Although their presence might indicate future recurrence, some patients may achieve long-term survival. Resection should be considered in cases of suspicious involvement to confirm extra-abdominal disease and achieve complete cytoreduction.

Retrograde and oscillatory shear rate in young anabolic androgenic steroid users.

Disturbed shear rate (SR), characterized by increased retrograde and oscillatory SR in the brachial artery, is associated with inflammation, atherosclerosis, endothelial dysfunction, and sympathetic hyperactivity. Young subjects do not have disturbed SR; however, elderly subjects do, which seems to be associated with sympathetic hyperactivity. Anabolic androgenic steroids (AAS) abuse in young is associated with increased muscle sympathetic nerve activity (MSNA). We hypothesized that AAS users might have disturbed SR. We tested the association between retrograde and oscillatory SR with MSNA. In addition, we measured the high-sensitivity C-reactive protein (hs-CRP). We evaluated 10 male AAS users, age 27 ± 4 years, and 10 age-matched AAS nonusers, age 29 ± 5 years. At rest, retrograde and oscillatory SR were evaluated by Doppler ultrasound, MSNA was measured with microneurography, and hs-CRP was measured in blood sample. Flow-mediated dilation (FMD) was also assessed. AAS users had higher retrograde SR (24.42 ± 17.25 vs 9.15 ± 6.62 s- 1 , P = 0.01), oscillatory SR (0.22 ± 0.13 vs 0.09 ± 0.07 au P = 0.01), and MSNA (42 ± 9 vs 32 ± 4 bursts/100 heart beats, P = 0.018) than nonusers. MSNA (bursts/100 heart beats) was correlated with retrograde SR (r = 0.50, P = 0.050) and oscillatory SR (r = 0.51, P = 0.042). AAS users had higher hs-CRP [1.17 (0.44-3.63) vs 0.29 (0.17-0.70) mg/L, P = 0.015] and decreased FMD (6.42 ± 2.07 vs 8.28% ± 1.53%, P = 0.035) than nonusers. In conclusion, AAS abuse is associated with retrograde and oscillatory SR which were associated with augmented sympathetic outflow. In addition, AAS seems to lead to inflammation characterized by increased hs-CRP. These alterations may have the potential of increasing the early risk of atherosclerotic disease in young AAS users.

Gene regulatory network inference and analysis of multidrug-resistant Pseudomonas aeruginosa.

BACKGROUND: Healthcare-associated infections caused by bacteria such as Pseudomonas aeruginosa are a major public health problem worldwide. Gene regulatory networks (GRN) computationally represent interactions among regulatory genes and their targets. They are an important approach to help understand bacterial behaviour and to provide novel ways of overcoming scientific challenges, including the identification of potential therapeutic targets and the development of new drugs. OBJECTIVES: The goal of this study was to reconstruct the multidrug-resistant (MDR) P. aeruginosa GRN and to analyse its topological properties. METHODS: The methodology used in this study was based on gene orthology inference using the reciprocal best hit method. We used the genome of P. aeruginosa CCBH4851 as the basis of the reconstruction process. This MDR strain is representative of the sequence type 277, which was involved in an endemic outbreak in Brazil. FINDINGS: We obtained a network with a larger number of regulatory genes, target genes and interactions as compared to the previously reported network. Topological analysis results are in accordance with the complex network representation of biological processes. MAIN CONCLUSIONS: The properties of the network were consistent with the biological features of P. aeruginosa. To the best of our knowledge, the P. aeruginosa GRN presented here is the most complete version available to date.

PAI-1, CAIX, and VEGFA expressions as prognosis markers in oral squamous cell carcinoma.

BACKGROUND: In oral squamous cell carcinoma (OSCC), the HIF-1 complex promotes the expression of genes involved in specific mechanisms of cell survival under hypoxic conditions, such as plasminogen activator inhibitor-1 (PAI-1), carbonic anhydrase 9 (CAIX), and vascular endothelial growth factor A (VEGFA). The study aimed to investigate the presence and prognostic value of PAI-1, CAIX, and VEGFA in OSCC. MATERIALS AND METHODS: Immunohistochemistry was used to analyze the expressions of these proteins in 52 tumoral tissue samples of patients with OSCC, surgically treated and followed by a minimum of 24 months after surgery. The correlations between protein expressions and clinicopathological parameters and prognosis were analyzed. RESULTS: Positive PAI-1 membrane expression was significantly associated with local disease relapse (P = .027). Multivariate analysis revealed that the positive PAI-1 membrane expression is an independent marker for local disease relapse, with approximately 14-fold increased risk when compared to negative expression (OR = 14.49; CI = 1.40-150.01, P = .025). Strong PAI-1 cytoplasmic expression was significantly associated with the less differentiation grade (P = .027). Strong CAIX membrane expression was significantly associated with local disease-free survival (P = .038). Positive CAIX cytoplasmic expression was significantly associated with lymph node affected (P = .025) and with disease-specific survival (P = .022). Multivariate analysis revealed that the positive CAIX cytoplasmic expression is an independent risk factor for disease-related death, increasing their risk approximately 3-fold when compared to negative expression (HR = 2.84; CI = 1.02-7.87, P = .045). Positive VEGFA cytoplasmic expression was significantly associated with less differentiation grade (P = .035). CONCLUSION: Our results suggest a potential role for these expressions profiles as tumor prognostic markers in OSCC patients.

Terpenoid constituents of cinnamon and clove essential oils cause toxic effects and behavior repellency response on granary weevil, Sitophilus granarius.

This study evaluated toxic effects, repellency and respiration rate caused by terpenoid constituents of cinnamon and clove essential oils and against Sitophilus granarius L. (Coleoptera: Curculionidae). The lethal concentrations (LC50 and LC90), repellent effect, and behavior repellency response on adults of S. granarius after exposure to six concentrations of each essential oil and terpenoids were evaluated. The chemical composition of the cinnamon oil was also determined and primary compounds were eugenol (10.5%), trans-3-caren-2-ol (10.2%), benzyl benzoate (9.99%), caryophyllene (9.34%), eugenyl acetate (7.71%), α-phellandrene (7.41%), and α-pinene (7.14%). In clove essential oil, the primary compounds were eugenol (27.1%), caryophyllene (24.5%), caryophyllene oxide (18.3%), 2-propenoic acid (12.2%), α-humulene (10.8%), γ-cadinene (5.01%), and humulene oxide (4.84%). Cinnamon and clove essential oil was toxic to S. granarius. In toxic terpenoids compounds, eugenol has stronger contact toxicity in S. granarius than caryophyllene oxide, followed by α-pinene, α-humulene, and α-phellandrene. Insects reduced their respiratory rates after being exposed to essential oil terpenoids and avoided or reduced their mobility on terpenoid-treated surfaces. Cinnamon and clove essential oil, and their terpenoid constituents were toxic and repellent to adult S. granarius and, therefore, have the potential to prevent or retard the development of insecticide resistance.

Design and Synthesis of New Benzophenone Derivatives with In Vivo Anti-Inflammatory Activity through Dual Inhibition of Edema and Neutrophil Recruitment.

A series of novel benzophenone derivatives containing a thiazole heterocyclic nucleus were designed by molecular hybridization. Molecular docking studies have demonstrated the inhibitory potential of the designed compounds against cyclooxygenase (COX) isoenzymes. These compounds were synthesized, characterized, and evaluated for their anti-inflammatory properties by the croton oil-induced ear edema assay to examine their effect on both prostaglandin (PG) production and neutrophils recruitment. The thiazole derivatives displayed a potent effect in terms of reducing ear edema. The analysis suggested that the presence of 4-phenyl-2-hydrazinothiazole and the absence of C4'-OCH3 on the benzophenone derivative structure are strongly related to the inhibition of PG production. In addition, the derivatives 2e, 3a and 3c concomitantly inhibit PG production and neutrophil recruitment, which may be a mechanism of action better than of common NSAIDs due to their inability to inhibit the neutrophil recruitment. Thus, these compounds can be considered as potential lead compounds toward the development of new anti-inflammatory drugs with an innovating mechanism of action.

Family perspectives on organ and tissue donation for transplantation: A principlist analysis.

BACKGROUND:: The family interview context is permeated by numerous ethical issues which may generate conflicts and impact on organ donation process. OBJECTIVE:: This study aims to analyze the family interview process with a focus on principlist bioethics. METHOD:: This exploratory, descriptive study uses a qualitative approach. The speeches were collected using the following prompt: "Talk about the family interview for the donation of organs and tissues for transplantation, from the preparation for the interview to the decision of the family to donate or not." For the treatment of qualitative data, we chose the method of content analysis and categorical thematic analysis. PARTICIPANTS:: The study involved 18 nurses who worked in three municipal organ procurement organizations in São Paulo, Brazil, and who conducted family interviews for organ donation. ETHICAL CONSIDERATIONS:: The data were collected after approval of the study by the Research Ethics Committee of the School of Nursing of the University of São Paulo. RESULTS:: The results were classified into four categories and three subcategories. The categories are the principles adopted by principlist bioethics. DISCUSSION:: The principles of autonomy, beneficence, non-maleficence, and justice permeate the family interview and reveal their importance in the organs and tissues donation process for transplantation. CONCLUSION:: The analysis of family interviews for the donation of organs and tissues for transplantation with a focus on principlist bioethics indicates that the process involves many ethical considerations. The elucidation of these aspects contributes to the discussion, training, and improvement of professionals, whether nurses or not, who work in organ procurement organizations and can improve the curriculum of existing training programs for transplant coordinators who pursue ethics in donation and transplantation as their foundation.