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1.
Sci Rep ; 13(1): 23003, 2023 12 27.
Artículo en Inglés | MEDLINE | ID: mdl-38155227

RESUMEN

The COVID-19 pandemic has severely affected global health, leading to the suspension of numerous routine healthcare services and posing challenges in efforts to control other diseases, such as HIV/AIDS. This study aimed to assess the impact of the COVID-19 pandemic on HIV/AIDS diagnoses and mortality rates in Brazil during 2020 and 2021. The percentage change was calculated to determine whether there was an increase or decrease in HIV/AIDS diagnoses and mortality, considering the average numbers from the last 5 years. Additionally, a Joinpoint regression model and an interrupted time series analysis were applied to assess time trends before and after the onset of the pandemic. Lastly, choropleth maps were prepared. We observed a reduction of 22.4% (2020) and 9.8% (2021) in the diagnosis of HIV/AIDS in Brazil. Conversely, there was a significant increase in the percentage change of late diagnosis of AIDS deaths in 2020 (6.9%) and 2021 (13.9%), with some states showing an increase of over 87%. Decreasing time trends in the diagnosis of HIV/AIDS were identified before the pandemic in Brazil, especially in the Southeast and South regions, and then time trends stabilized after including the pandemic years. Along with the dissemination of COVID-19, there was a reduction in the diagnosis of HIV/AIDS and an increase in late diagnosis AIDS deaths, signaling a serious impact of the pandemic on HIV/AIDS control strategies in Brazil. Therefore, we highlight the need for continuous efforts to control both diseases, that is, maintaining regular health services even in crisis situations.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , COVID-19 , Infecciones por VIH , Humanos , Síndrome de Inmunodeficiencia Adquirida/diagnóstico , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Pandemias , Diagnóstico Tardío , Brasil/epidemiología , COVID-19/diagnóstico , COVID-19/epidemiología , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Prueba de COVID-19
2.
Clin Endosc ; 56(6): 761-768, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37491991

RESUMEN

BACKGROUND/AIMS: Self-expandable metallic stents (SEMSs) are widely adopted for the palliation of dysphagia in patients with malignant esophageal strictures. An important adverse event is the development of SEMS-induced esophagorespiratory fistulas (SEMS-ERFs). This study aimed to assess the risk factors related to the development of SEMS-ERF after SEMS placement in patients with esophageal cancer. METHODS: This retrospective study was performed at the Instituto do Cancer do Estado de São Paulo. All patients with malignant esophageal strictures who underwent esophageal SEMS placement between 2009 and 2019 were included in the study. RESULTS: Of the 335 patients, 37 (11.0%) developed SEMS-ERF, with a median time of 129 days after SEMS placement. Stent flare of 28 mm (hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.15-5.51; p=0.02) and post-stent chemotherapy (HR, 2.0; 95% CI, 1.01-4.00; p=0.05) were associated with an increased risk of developing SEMS-ERF, while lower-third tumors were a protective factor (HR, 0.5; 95% CI, 0.26-0.85; p=0.01). No difference was observed in overall survival. CONCLUSION: The incidence of SEMS-ERFs was 11%, with a median time of 129 days after SEMS placement. Post-stent chemotherapy and a 28 mm stent flare were associated with a higher risk of SEMS-ERF.

3.
Inorg Chem ; 62(17): 6808-6816, 2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-37125414

RESUMEN

TbIII and EuIII systems have been investigated as ratiometric luminescent temperature probes in luminescent coordination polymers due to TbIII → EuIII energy transfer (ET). To help understand how ion-ion separation, chain conformation as well as excitation channel impact their thermometric properties, herein, [Eu(tfaa)3(µ-L)Tb(tfaa)3]n one-dimensional (1D) coordination polymers (tfaa- = trifluoroacetylacetonate, and L = [(diphenylphosphoryl)R](diphenyl)phosphine oxide, R = ethyl - dppeo - or butyl - dppbo) were synthesized. The short µ-dppeo bridge ligand leads to a more linear 1D polymeric chain, while the longer µ-dppbo bridge leads to tighter packed chains. As the temperature rises from 80 K, upon direct TbIII excitation at 488 nm, the TbIII emission intensity decreases, while the EuIII emission intensity increases after 160 and 200 K when L = dppeo or dppbo, respectively. The temperature-dependent emission intensities, due to TbIII → EuIII ET, enable the development of ratiometric luminescent temperature probes featuring maximum relative thermal sensitivity up to 3.8% K-1 (250 K, L = dppbo, excitation at 488 nm). On the other hand, the same system displays maximum thermal sensitivity up to 3.5% K-1 (323 K) upon ligand excitation at 300 nm. Thus, by changing the excitation channel and bridge ligand that leads to modification of the polymer conformations, the maximum relative thermal sensitivity can be tuned.

4.
J Opt Soc Am A Opt Image Sci Vis ; 40(4): C46-C52, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37132953

RESUMEN

The performance of a visible light communication (VLC) system based on power-domain nonorthogonal multiple access (PD-NOMA) is experimentally evaluated in this paper. The simplicity of the adopted nonorthogonal scheme is provided by the fixed power allocation method at the transmitter and the single one-tap equalization executed before the successive interference cancellation at the receiver. The experimental results proved the successful transmission of the PD-NOMA scheme with three users in VLC links of up to 2.5 m, after a proper choice of the optical modulation index. All users achieved error vector magnitude (EVM) performances below forward error correction limits in all evaluated transmission distances. At 2.5 m, the user with the best performance reaches an E V M=2.3%.

5.
Microbiol Spectr ; 11(3): e0444022, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37022264

RESUMEN

Hyperlipidemia is a key risk factor for cardiovascular disease, and it is associated with lipid metabolic disorders and gut microbiota dysbiosis. Here, we aimed to investigate the beneficial effects of 3-month intake of a mixed probiotic formulation in hyperlipidemic patients (n = 27 and 29 in placebo and probiotic groups, respectively). The blood lipid indexes, lipid metabolome, and fecal microbiome before and after the intervention were monitored. Our results showed that probiotic intervention could significantly decrease the serum levels of total cholesterol, triglyceride, and low-density lipoprotein cholesterol (P < 0.05), while increasing the levels of high-density lipoprotein cholesterol (P < 0.05) in patients with hyperlipidemia. Probiotic recipients showing improved blood lipid profile also exhibited significant differences in their lifestyle habits after the 3-month intervention, with an increase in daily intake of vegetable and dairy products, as well as weekly exercise time (P < 0.05). Moreover, two blood lipid metabolites (namely, acetyl-carnitine and free carnitine) significantly increased after probiotic supplementation cholesterol (P < 0.05). In addition, probiotic-driven mitigation of hyperlipidemic symptoms were accompanied by increases in beneficial bacteria like Bifidobacterium animalis subsp. lactis and Lactiplantibacillus plantarum in patients' fecal microbiota. These results supported that mixed probiotic application could regulate host gut microbiota balance, lipid metabolism, and lifestyle habits, through which hyperlipidemic symptoms could be alleviated. The findings of this study urge further research and development of probiotics into nutraceuticals for managing hyperlipidemia. IMPORTANCE The human gut microbiota have a potential effect on the lipid metabolism and are closely related to the disease hyperlipidemia. Our trial has demonstrated that 3-month intake of a mixed probiotic formulation alleviates hyperlipidemic symptoms, possibly by modulation of gut microbes and host lipid metabolism. The findings of the present study provide new insights into the treatment of hyperlipidemia, mechanisms of novel therapeutic strategies, and application of probiotics-based therapy.


Asunto(s)
Bifidobacterium animalis , Microbioma Gastrointestinal , Hiperlipidemias , Probióticos , Humanos , Carnitina/farmacología , Colesterol , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/metabolismo , Estilo de Vida , Metabolismo de los Lípidos , Lípidos
6.
Clinical Endoscopy ; : 761-768, 2023.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1000064

RESUMEN

Background/Aims@#Self-expandable metallic stents (SEMSs) are widely adopted for the palliation of dysphagia in patients with malignant esophageal strictures. An important adverse event is the development of SEMS-induced esophagorespiratory fistulas (SEMS-ERFs). This study aimed to assess the risk factors related to the development of SEMS-ERF after SEMS placement in patients with esophageal cancer. @*Methods@#This retrospective study was performed at the Instituto do Cancer do Estado de São Paulo. All patients with malignant esophageal strictures who underwent esophageal SEMS placement between 2009 and 2019 were included in the study. @*Results@#Of the 335 patients, 37 (11.0%) developed SEMS-ERF, with a median time of 129 days after SEMS placement. Stent flare of 28 mm (hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.15–5.51; p=0.02) and post-stent chemotherapy (HR, 2.0; 95% CI, 1.01–4.00; p=0.05) were associated with an increased risk of developing SEMS-ERF, while lower-third tumors were a protective factor (HR, 0.5; 95% CI, 0.26–0.85; p=0.01). No difference was observed in overall survival. @*Conclusions@#The incidence of SEMS-ERFs was 11%, with a median time of 129 days after SEMS placement. Post-stent chemotherapy and a 28 mm stent flare were associated with a higher risk of SEMS-ERF.

7.
Oecologia ; 200(1-2): 199-207, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36127474

RESUMEN

Frost effects on savanna plant communities have been considered as analogous to those from fire, both changing community structure and filtering species composition. However, while frost impacts have been well-studied for the woody component of savannas, it is still poorly explored for the ground-layer community. Here, we investigated effects of frost in the Cerrado along a gradient of tree cover, focusing on ground-layer plant species, near the southern limit of the Cerrado in Brazil. We aimed to elucidate if the pattern already described for the tree layer also extends to the ground layer in terms of mimicking the effects of fire on vegetation structure and composition. We assessed how damage severity differs across species and across the tree-cover gradient, and we examined the recovery process after frost in terms of richness and community structure along the canopy cover gradient. Frost caused immediate and widespread dieback of the perennial ground-layer, with greatest impact on community structure where tree cover was lowest. However, frost did not reduce the number of species, indicating community resilience to this natural disturbance. Although frost mimicked the effects of fire in some ways, in other ways it differed substantially from fire. Unlike fire, frost increases litter cover and decreases the proportion of bare soil, likely hindering crucial processes for recovery of plant populations, such as seed dispersal, seed germination and plant resprouting. This finding calls attention to the risk of misguided conclusions when the ground layer is neglected in ecological studies of tropical savannas and grasslands.


Asunto(s)
Incendios , Árboles , Brasil , Ecosistema , Plantas , Suelo , Árboles/fisiología
9.
J Cell Mol Med ; 26(10): 2793-2807, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35460166

RESUMEN

Tryptophyllins constitute a heterogeneous group of peptides that are one of the first classes of peptides identified from amphibian's skin secretions. Here, we report the structural characterization and antioxidant properties of a novel tryptophyllin-like peptide, named PpT-2, isolated from the Iberian green frog Pelophylax perezi. The skin secretion of P. perezi was obtained by electrical stimulation and fractionated using RP-HPLC. De novo peptide sequencing was conducted using MALDI MS/MS. The primary structure of PpT-2 (FPWLLS-NH2 ) was confirmed by Edman degradation and subsequently investigated using in silico tools. PpT-2 shared physicochemical properties with other well-known antioxidants. To test PpT-2 for antioxidant activity in vitro, the peptide was synthesized by solid phase and assessed in the chemical-based ABTS and DPPH scavenging assays. Then, a flow cytometry experiment was conducted to assess PpT-2 antioxidant activity in oxidatively challenged murine microglial cells. As predicted by the in silico analyses, PpT-2 scavenged free radicals in vitro and suppressed the generation of reactive species in PMA-stimulated BV-2 microglia cells. We further explored possible bioactivities of PpT-2 against prostate cancer cells and bacteria, against which the peptide exerted a moderate antiproliferative effect and negligible antimicrobial activity. The biocompatibility of PpT-2 was evaluated in cytotoxicity assays and in vivo toxicity with Galleria mellonella. No toxicity was detected in cells treated with up to 512 µg/ml and in G. mellonella treated with up to 40 mg/kg PpT-2. This novel peptide, PpT-2, stands as a promising peptide with potential therapeutic and biotechnological applications, mainly for the treatment/prevention of neurodegenerative disorders.


Asunto(s)
Antioxidantes , Fármacos Neuroprotectores , Animales , Antioxidantes/metabolismo , Anuros/metabolismo , Masculino , Ratones , Microglía/metabolismo , Péptidos/química , Ranidae/metabolismo , Relación Estructura-Actividad , Espectrometría de Masas en Tándem
10.
Environ Sci Pollut Res Int ; 29(34): 51651-51664, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35249192

RESUMEN

Photocatalytic activation of persulfate (PS) is recently emerged as an energy-efficient and environmentally sustainable approach for pollutants degradation, which enables to leverage the strengths of low-cost solar energy and heterogeneous catalysis. Herein, we investigated the photocatalytic decomposition of reactive red 120 (RR120) dye using PS-activated Fe2O3 nanoparticles and elucidated the effect of their facets, α-Fe2O3 (001), ß-Fe2O3 (100), and γ-Fe2O3 (111). ß-Fe2O3 not only boosted the charge carrier separation but also provided more active sites for PS activation resulting in 6- and 3.5-fold higher photocatalytic activities compared to α-Fe2O3 and γ-Fe2O3, respectively. Response surface methodology and artificial neural network coupled with genetic algorithm models were utilized to optimize and foresee Fe2O3/PS system under visible light. Almost 100% color removal and 82% organic removal were observed under the optimum conditions at 20 mg/L RR120, 22 mg/L ß-Fe2O3, 18 mg/L PS, and pH: 3. Scavenger test indicated that both sulfate and hydroxyl radicals are responsible for the observed RR120 removal. Although cell viability test indicated that cytotoxicity of wastewater is not significantly reduced after treatment. All the results proposed that ß-Fe2O3/PS at relatively low doses has a great potential to decompose and mineralize recalcitrant dyes in wastewater under invisible light.


Asunto(s)
Nanopartículas , Procesos Fotoquímicos , Triazinas/química , Aguas Residuales , Contaminantes Químicos del Agua/química , Purificación del Agua/métodos , Catálisis , Colorantes , Compuestos Férricos , Luz , Sulfatos/química , Triazinas/análisis , Contaminantes Químicos del Agua/análisis
11.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20219949

RESUMEN

In the face of new diseases, medicine needs to reinvent itself in order to contain and control epidemics, such as the one we have recently faced, COVID-19, a disease with a wide spectrum of clinical severity. A new moment has been established, since the application of well known, effective and safe medications for other diseases, has shown high success rates in the treatment of COVID-19. Thereunto, studies with early intervention are needed, which can change the unfavorable outcome of patients. In this article, we report the successful experience using an oral strategy during the collapse of Belem do Para Health System, Brazil. Two hundred and ten patients were diagnosed with respiratory failure due to COVID-19, with no option of hospital treatment due to lack of beds and resources. These patients were then started on therapeutic regimen consisting of prednisolone, enoxaparin and macrolides associated and followed in outpatient facilities. Two hundred and eight patients had excellent therapeutic response and there were only two fatalities. These results push research boundaries, valuing outpatient treatment with early use of prednisolone in the initial pulmonary phase, preventing severe COVID-19 pneumonitis. Adoption of the proposed treatment intends to reduce the need for hospitalization, as well as lethality, with social robust benefits and incalculable economic savings since involves the use of accessible, safe and not expensive medications.

12.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21251758

RESUMEN

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSImportanceC_ST_ABSA predictive model to automatically identify the earliest determinants of both hospital discharge and mortality in hospitalized COVID-19 patients could be of great assistance to caregivers if the predictive information is generated and made available in the immediate hours following admission. ObjectiveTo identify the most important predictors of hospital discharge and mortality from measurements at admission for hospitalized COVID-19 patients. DesignObservational cohort study. SettingElectronic records from hospitalized patients. ParticipantsPatients admitted between March 3rd and August 24th with COVID-19 in Johns Hopkins Health System hospitals. Exposures216 phenotypic variables collected within 48 hours of admission. Main OutcomesWe used age-stratified (<60 and >=60 years) random survival forests with competing risks to identify the most important predictors of death and discharge. Fine-Gray competing risk regression (FGR) models were then constructed based on the most important RSF-derived covariates. ResultsOf 2212 patients, 1913 were discharged (age 57{+/-}19, time-to-discharge 9{+/-}11 days) while 279 died (age 75{+/-}14, time to death 14{+/-}15 days). Patients >= 60 years were nearly 10 times as likely to die within 60 days of admission as those <60. As the pandemic evolved, the rate of hospital discharge increased in both older and younger patients. Incident death and hospital discharge were accurately predicted by measures of respiratory distress, inflammation, infection, renal function, red cell turn over and cardiac stress. FGR models for each of hospital discharge and mortality as outcomes based on these variables performed well in the older (AUC 0.80-0.85 at 60-days) and younger populations (AUC >0.90 at 60-days). Conclusions and RelevanceWe identified markers collected within 2 days of admission that predict hospital discharge and mortality in COVID-19 patients and provide prediction models that may be used to guide patient care. Our proposed model suggests that hospital discharge and mortality can be forecasted with high accuracy based on 8-10 variables at this stage of the COVID-19 pandemic. Our findings also point to several specific pathways that could be the focus of future investigations directed at reducing mortality and expediting hospital discharge among COVID-19 patients. Probability of hospital discharge increased over the course of the pandemic. KO_SCPLOWEYC_SCPLOW PO_SCPLOWOINTSC_SCPLOWO_ST_ABSQuestionC_ST_ABSCan we predict the likelihood of hospital discharge as well as mortality from data obtained in the first 48 hours from admission in hospitalized COVID-19 patients? FindingsModels based on extensive phenotyping mined directly from electronic medical records followed by variable selection, accounted for the competing events of hospital death versus discharge, predicted both death and discharge with area under the receiver operating characteristic curves of >0.80. MeaningHospital discharge and mortality can be forecasted with high accuracy based on just 8-10 variables, and the probability of hospital discharge increased over the course of the pandemic.

13.
Preprint en Inglés | bioRxiv | ID: ppbiorxiv-426114

RESUMEN

The SARS-CoV-2 pandemic has caused a significant number of fatalities and worldwide disruption. To identify drugs to repurpose to treat SARS-CoV-2 infections, we established a screen to measure dimerization of ACE2, the primary receptor for the virus. This screen identified fenofibric acid, the active metabolite of fenofibrate. Fenofibric acid also destabilized the receptor binding domain (RBD) of the viral spike protein and inhibited RBD binding to ACE2 in ELISA and whole cell binding assays. Fenofibrate and fenofibric acid were tested by two independent laboratories measuring infection of cultured Vero cells using two different SARS-CoV-2 isolates. In both settings at drug concentrations which are clinically achievable, fenofibrate and fenofibric acid reduced viral infection by up to 70%. Together with its extensive history of clinical use and its relatively good safety profile, these studies identify fenofibrate as a potential therapeutic agent requiring urgent clinical evaluation to treat SARS-CoV-2 infection. TeaserThe approved drug fenofibrate inhibits infection by SARS-COV-2

14.
Breast ; 54: 46-51, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32911309

RESUMEN

INTRODUCTION: Radiation therapy (RT) is frequently used for post-operative treatment in breast cancer (BC) patients who received preoperative systemic therapy (PST) and surgery. Nevertheless, the optimal timing to start RT is unclear. MATERIAL AND METHODS: Data from BC patients who underwent chemotherapy as PST, breast surgery and RT at 3 Institutions in Brazil and Canada from 2008 to 2014 were evaluated. Patients were classified into three groups regarding to the time to initiation of RT after surgery: <8 weeks, 8-16 weeks and >16 weeks. RESULTS: A total of 1029 women were included, most of them (59.1%; N = 608) had clinical stage III. One hundred and forty-one patients initiated RT within 8 weeks, 663 between 8 and 16 weeks and 225 beyond 16 weeks from surgery. With a median follow-up of 32 months, no differences in disease-free survival (DFS), overall survival and locoregional recurrence-free survival (LRRFS) were observed of time to indicated RT (<8 weeks versus 8-16 weeks versus >16 weeks). However, in luminal subtype patients (46.5%; N = 478), initiation of RT up to 8 weeks after surgery was associated with better LRRFS (<8 weeks versus >16 weeks: HR 0.22; 95%CI 0.05-0.86; p = 0.03), with a tendency to a better DFS (<8 weeks versus >16 weeks: HR 0.50; 95%CI 0.25-1.00). CONCLUSION: RT initiated up to 8 weeks after surgery was related to better LRRFS in luminal BC patients who underwent PST. Our results suggest that early start of RT is important for these patients.


Asunto(s)
Neoplasias de la Mama/terapia , Mastectomía , Radioterapia Adyuvante/métodos , Factores de Tiempo , Adulto , Brasil , Neoplasias de la Mama/patología , Canadá , Quimioterapia Adyuvante/métodos , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/etiología , Recurrencia Local de Neoplasia/prevención & control , Estadificación de Neoplasias , Periodo Posoperatorio , Estudios Retrospectivos , Resultado del Tratamiento
15.
Clin Colorectal Cancer ; 19(4): e264-e271, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32741580

RESUMEN

BACKGROUND: Screening protocols for colorectal cancer are broadly recommended and effective in reducing mortality. However, populations from different age groups can harbor distinct pathologic and molecular profiles that can also be influenced by screening and polyp resection, especially in older ages. PATIENTS AND METHODS: We retrospectively analyzed tumors from stage IV colorectal cancer patients from a central pathology laboratory in Brazil that is a reference for mutational profiling countrywide. Patients were classified into age groups as follows: prescreening age (PrSA; < 45 years old), screening age (SA; 45-75 years old), and postscreening age (PoSA; > 75 years old). Every tumor was centrally reviewed by the pathologist. Groups were compared regarding clinicopathologic features, and the presence of RAS (renin-angiotensin system) and BRAF (v-Raf murine sarcoma viral oncogene homolog B) mutations. RESULTS: We included 1635 patients (215 PrSA, 1213 SA, 207 PoSA). There was no difference among groups regarding sidedness (P = .65) and KRAS (Kirsten rat sarcoma viral oncogene) mutations (P = .57). Stage IV disease at diagnosis (P = .04), the presence of a signet-ring cell component (P < .001), and poorly differentiated tumors (P = .02) were most common in young patients, while BRAF and NRAS (neuroblastoma RAS viral (v-ras) oncogene homolog) mutations were significantly more common among PoSA patients (P = .002 and .03, respectively). When divided by age decade, KRAS mutations seem to have a stable frequency among all ages, while the BRAF mutation rate increased with increasing age. CONCLUSION: BRAF mutations are more frequent among PoSA patients, and this seems to be a continuous trend. PrSA and PoSA patients seem to present a distinct profile from SA, including differences in molecular and pathologic aspects. These findings could impact the frequency of screening tests among different age groups.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Colorrectales/genética , Detección Precoz del Cáncer/normas , Adulto , Factores de Edad , Anciano , Colonoscopía/estadística & datos numéricos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Análisis Mutacional de ADN/estadística & datos numéricos , Detección Precoz del Cáncer/estadística & datos numéricos , Femenino , GTP Fosfohidrolasas/genética , Humanos , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Mutación , Estadificación de Neoplasias , Guías de Práctica Clínica como Asunto , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Estudios Retrospectivos
16.
J Food Sci Technol ; 57(9): 3474-3481, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32728294

RESUMEN

This study evaluated the effect of phytase treatment on the bioavailability of iron (Fe), calcium (Ca), zinc (Zn), and myo-inositol phosphate fractions in sorghum flour; and characterized its macronutrients and minerals. The proximate composition and mineral content indicated that, sorghum flour has a nutritional potential superior to wheat and maize. The results obtained in the solubility and dialysis assays indicated that, naturally occurring minerals (without phytase treatment) in sorghum flour, presented considerable bioaccessibility; reaching 32, 47 and 67% of dialyzable Fe, Zn, and Ca respectively. The use of phytase had a positive influence on the reduction of myo-inositol phosphates, mainly the IP6 fraction, present in sorghum flour samples, and an increase in the soluble percentage (Fe 52% for one sample, for Zn higher than 266%) and dialyzed minerals (Fe 7.8-150%; Zn 19.7 for one sample; and Ca 5-205%) for most samples. Therefore, the essential minerals naturally occurring in sorghum have an absorption potential; and the use of phytase reduced the IP6 fraction and improved the availability of the minerals evaluated.

17.
Preprint en Inglés | bioRxiv | ID: ppbiorxiv-169334

RESUMEN

Heparan sulfate (HS) is a cell surface polysaccharide recently identified as a co-receptor with the ACE2 protein for recognition of the S1 spike protein on SARS-CoV-2 virus, providing a tractable new target for therapeutic intervention. Clinically-used heparins demonstrate inhibitory activity, but world supplies are limited, necessitating alternative solutions. Synthetic HS mimetic pixatimod is a drug candidate for cancer with immunomodulatory and heparanase-inhibiting properties. Here we show that pixatimod binds to and destabilizes the SARS-CoV-2 spike protein receptor binding domain (S1-RBD), and directly inhibits its binding to human ACE2, consistent with molecular modelling identification of multiple molecular contacts and overlapping pixatimod and ACE2 binding sites. Assays with multiple clinical isolates of live SARS-CoV-2 virus show that pixatimod potently inhibits infection of monkey Vero E6 and human bronchial epithelial cells at concentrations within its safe therapeutic dose range. Furthermore, in a K18-hACE2 mouse model pixatimod demonstrates that pixatimod markedly attenuates SARS-CoV-2 viral titer and COVID-19-like symptoms. This demonstration of potent anti-SARS-CoV-2 activity establishes proof-of-concept for targeting the HS-Spike protein-ACE2 axis with synthetic HS mimetics. Together with other known activities of pixatimod our data provides a strong rationale for its clinical investigation as a potential multimodal therapeutic to address the COVID-19 pandemic.

18.
Rev. salud pública ; 21(5): e208, sep.-oct. 2019. tab, graf
Artículo en Portugués | LILACS | ID: biblio-1150160

RESUMEN

RESUMO Objetivo Analisar o perfil e a sobrevida de adultos jovens com carcinoma de células escamosas oral, atendidos entre 2010 a 2016 na Unidade de Alta Complexidade em Oncologia de Feira de Santana, Brasil. Métodos Coorte retrospectiva, realizada através das informações dos prontuários de todos os pacientes jovens atendidos no referido centro. Foi realizada análise descritiva das variáveis, teste exato de Fisher, curva de Kaplan-Meier e teste log rank. Resultados Um total de 35 pacientes foram registrados. A maioria era do sexo masculino, fumantes e etilistas. Os tumores estavam localizados predominantemente em língua, diagnosticados tardiamente e classificados como bem diferenciado, tendo como tratamento de escolha cirurgia associada a radioterapia e quimioterapia. O tempo mediano de sobrevida foi de 31 meses e 22,8% dos pacientes foram a óbito. As variáveis que apresentaram significância estatística em relação ao tempo de sobrevida foram a localização do tumor e o tipo de tratamento. Conclusão O perfil e o baixo tempo de sobrevida refletem a necessidade de uma maior atenção à doença nesta população.(AU)


ABSTRACT Objective To analyze the profile and survival in young adults with oral squamous cell carcinoma, attended at the High Complexity in Oncology of Feira de Santana, Brazil, between 2010 and 2016. Methods Retrospective cohort, performed through the information of the medical records of all young patients attended in the referred center. Descriptive analysis of the variables, Fisher's exact test, Kaplan-Meier curve and log-rank test were performed. Results A total of 35 patients were registered. The majority were male, smokers and former alcoholics. Tumors were predominantly localized in the tongue, diagnosed at late stages, classified as well differentiated and treated mainly with surgery associated to radiotherapy and chemotherapy. The median survival time was 31 months and 22.8% of the patients died. The variables that presented statistical significance in relation to the survival time were the tumor site and the type of treatment. Conclusion The profile and low survival time reflect the need for greater attention to the disease in this population.(AU)


RESUMEN Objetivo Analizar el perfil y la supervivencia de adultos jóvenes con carcinoma de células escamosas atendidos en el Centro de Alta Complejidad en Oncología de Feira de Santana (Brasil), durante el periodo 2010-2016. Métodos cohorte retrospectivo realizado mediante la información de registros médicos de todos los pacientes jóvenes atendidos en el centro médico mencionado. Asimismo, se hizo un análisis descriptivo de las variables, test exacto de Fisher, curva de Kaplan-Meier y una prueba de rango logarítmico. Resultados Se registró un total de 35 pacientes: la mayoría, hombres fumadores y exalcohólicos. Gran parte de los tumores fueron hallados en la lengua y diagnosticados en la última fase; asimismo, se clasificaron, se diferenciaron y se trataron con cirugía apoyada en radioterapia y quimioterapia. El tiempo promedio de supervivencia fue de 31 meses. El 22,8% de los pacientes fallecieron. Las variables que demostraron una gran significancia estadística en relación con el tiempo de supervivencia fueron la ubicación del tumor y el tipo de tratamiento. Conclusión El perfil y el escaso tiempo de supervivencia demuestran que es necesaria una mejor atención de la enfermedad que padece esta población.(AU)


Asunto(s)
Humanos , Adulto , Perfil de Salud , Carcinoma de Células Escamosas/diagnóstico , Pronóstico , Brasil/epidemiología , Carcinoma de Células Escamosas/epidemiología , Análisis de Supervivencia , Estudios Retrospectivos , Estudios Longitudinales
19.
Artículo en Inglés | MEDLINE | ID: mdl-31336318

RESUMEN

The main aim of this study was to define the optimal adsorption and elution conditions for the purification of human immunoglobulin G (IgG) by mixed-mode chromatography using the multimodal resin Capto MMC. To this end, Central Composite Experimental Design (ED) was performed for both the adsorption and desorption stages. In the first case, the conditions were systematically studied in batch mode while in the latter case, these were performed in column. For both studies, the experimental design was conducted using high-purity human IgG samples. Buffer pH and concentration as well as the salt concentration were the parameters under study in the ED. Adsorption kinetics and equilibrium experiments were performed under the best conditions defined in the ED (phosphate buffer 60 mmol/L, pH 6.75, no salt). The equilibrium experimental data were fit to the Langmuir equation, with maximum uptake qmax equal to 549.2 mg/g. The qmax value found for IgG in Capto MMC was quite high as compared to other chromatographic techniques that employ single modes of interaction. Regarding elution, the best conditions were obtained with acetate buffer (56.40 mmol/L), pH 5.2 and 0.2 mol/L NaCl. An ultimate recovery of 46.96% for high-purity IgG was achieved. Thus, the effectiveness of Capto MMC for IgG adsorption and recovery could be confirmed. Moreover, electrophoretic runs in the human serum indicated that although co-elution of HSA and IgG proteins occurs, substantial HSA removal and a high IgG recovery were achieved in the elution step.


Asunto(s)
Cromatografía/métodos , Inmunoglobulina G/aislamiento & purificación , Adsorción , Cromatografía/instrumentación , Humanos , Inmunoglobulina G/química , Cinética , Proyectos de Investigación
20.
J Glob Oncol ; 5: 1-8, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30779600

RESUMEN

PURPOSE: Reported treatment outcomes for patients with advanced germ cell tumors (aGCT) are based mainly on series from developed nations. Data from low- and middle-income countries are underrepresented. MATERIAL AND METHODS: From 2000 to 2015, a retrospective analysis identified 300 patients with aGCT treated at our institution. Kaplan-Meier methods were used for analysis of progression-free survival (PFS) and overall survival (OS) according to the International Germ Cell Consensus Classification Group (IGCCCG). RESULTS: Patients' median age was 28 years. According to the IGCCCG, 57% had good-, 18.3% intermediate-, and 24.7% poor-risk disease. Median α-fetoprotein levels were 2.9, 243, and 3,998 ng/mL, and those of human chorionic gonadotropin were 0.4, 113, and 301.5 mUI/mL in IGCCCG good-, intermediate-, and poor-risk groups, respectively. At a median 46 months of follow-up, 93 PFS events and 45 deaths had occurred and estimated 5-year PFS and OS were 69% and 85%, respectively, including 83% and 95.3% in good-risk, 70.9% and 83.6% in intermediate-risk, and 35.1% and 62.2% in poor-risk patients, respectively. In multivariable analysis, Eastern Cooperative Oncology Group performance status ≥ 2 was a significant independent prognostic factor with a hazard ratio of 2.58 (95% CI, 1.55 to 4.29; P < .001) and 6.20 (95% CI, 2.97 to 12.92; P < .001) for PFS and OS, respectively. CONCLUSION: Brazilian patients with aGCT in this cohort had similar outcomes as patients in the IGCCCG database. In comparison with contemporary series, patients with intermediate- and poor-risk aGCT had slightly inferior PFS and OS, possibly due to a high percentage of patients with poor performance status and less use of high-dose chemotherapy.


Asunto(s)
Gonadotropina Coriónica/metabolismo , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/mortalidad , Neoplasias Testiculares/tratamiento farmacológico , alfa-Fetoproteínas/metabolismo , Adolescente , Adulto , Brasil , Supervivencia sin Enfermedad , Quimioterapia , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neoplasias de Células Germinales y Embrionarias/metabolismo , Pronóstico , Estudios Retrospectivos , Centros de Atención Terciaria , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/mortalidad , Resultado del Tratamiento , Adulto Joven
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