Mortality in children under five years old in Brazil: evolution from 2017 to 2020 and the influence of COVID-19 in 2020

Abstract Objective: To analyse the mortality trends in children under five years old in Brazil from 2017 to 2020 and the influence of COVID-19 in 2020. Methods: A retrospective study employing secondary data from the Brazilian Mortality Information System. Deaths according to cause were extracted and disaggregated into early, late, post-neonatal, and 1 to 4-year-old periods. Corrected mortality rates per 1, 000 live births and relative risk ratio for the cause of death were calculated. Results: There were 34, 070 deaths, being 417 (1.2%) from COVID-19 in 2020. COVID-19 mortality was 0.17 per 1000 live births, reaching 0.006 in the early neonatal period, 0.007 in the late neonatal, 0.09 in the postneonatal, and 0.06 in 1 to 4-year-old. Mortality decreased mostly for some diseases that originated in the perinatal period, congenital anomalies, diseases of the respiratory system and external causes, in this order. In 2020, the highest rate was in the early neonatal period, with a fall from 7.2 to 6.5, followed by the postneonatal (3.9 to 3.4) and late neonatal (2.3 to 2.1). Among children aged 1 to 4-year-old, external causes had the highest proportional rate, and diseases of the respiratory system showed the highest decline. Conclusion: The mortality rate declined from 2017 to 2020, and this variation was higher in the early neonatal period. The risk of death from COVID-19 was 14 times higher in the postneonatal period and 10 times higher in children aged 1 to 4 year-old compared to the early neonatal period.

Mortality in children under five years old in Brazil: evolution from 2017 to 2020 and the influence of COVID-19 in 2020.

OBJECTIVE: To analyse the mortality trends in children under five years old in Brazil from 2017 to 2020 and the influence of COVID-19 in 2020. METHODS: A retrospective study employing secondary data from the Brazilian Mortality Information System. Deaths according to cause were extracted and disaggregated into early, late, postneonatal, and 1 to 4-year-old periods. Corrected mortality rates per 1,000 live births and relative risk ratio for the cause of death were calculated. RESULTS: There were 34,070 deaths, being 417 (1.2%) from COVID-19 in 2020. COVID-19 mortality was 0.17 per 1000 live births, reaching 0.006 in the early neonatal period, 0.007 in the late neonatal, 0.09 in the postneonatal, and 0.06 in 1 to 4-year-old. Mortality decreased mostly for some diseases that originated in the perinatal period, congenital anomalies, diseases of the respiratory system and external causes, in this order. In 2020, the highest rate was in the early neonatal period, with a fall from 7.2 to 6.5, followed by the postneonatal (3.9 to 3.4) and late neonatal (2.3 to 2.1). Among children aged 1 to 4-year-old, external causes had the highest proportional rate, and diseases of the respiratory system showed the highest decline. CONCLUSION: The mortality rate declined from 2017 to 2020, and this variation was higher in the early neonatal period. The risk of death from COVID-19 was 14 times higher in the postneonatal period and 10 times higher in children aged 1 to 4 year-old compared to the early neonatal period.

miR-210 and miR-152 as Biomarkers by Liquid Biopsy in Invasive Ductal Carcinoma.

Detecting circulating microRNAs (miRNAs; miRs) by means of liquid biopsy is an important tool for the early diagnosis and prognosis of breast cancer (BC). We aimed to identify and validate miR-210 and miR-152 as non-invasive circulating biomarkers, for the diagnosis and staging of BC patients, confirming their involvement in tumor angiogenesis. METHODS: RT-qPCR was performed and MiRNA expression analysis was obtained from plasma and fragments of BC and benign breast condition (BBC) women patients, plus healthy subjects. Additionally, the immunohistochemistry technique was carried out to analyze the expression of target proteins. RESULTS: Tumor fragments showed increased expression of oncomiR-210 and decreased expression of miR-152 tumoral suppressor. Both miRNAs were increased in plasma samples from BC patients. The receiver operating characteristic (ROC) curve analysis revealed that only the expression of oncomiR-210 in tissue samples and only the expression of the miR-152 suppressor in plasma have the appropriate sensitivity and specificity for use as differential biomarkers between early/intermediate and advanced stages of BC patients. In addition, there was an increase in the expression of hypoxia-inducible factor 1-alpha (HIF-1α), insulin-like growth factor 1 receptor (IGF-1R), and vascular endothelial growth factor (VEGF) in BC patients. On the contrary, a decrease in Von Hippel-Lindau (VHL) protein expression was observed. CONCLUSIONS: This study showed that increased levels of miR-210 and decreased levels of miR152, in addition to the expressions of their target proteins, could indicate, respectively, the oncogenic and tumor suppressive role of these miRNAs in fragments. Both miRNAs are potential diagnostic biomarkers for BC by liquid biopsy. In addition, miR-152 proved to be a promising biomarker for disease staging.

Melatonin Treatment Combined with TGF-ß Silencing Inhibits Epithelial- Mesenchymal Transition in CF41 Canine Mammary Cancer Cell Line.

BACKGROUND: Mammary cancer is the most prevalent type of cancer in female dogs. The main cause of mortality is the occurrence of metastasis. The metastatic process is complex and involves the Epithelial- Mesenchymal Transition (EMT), which can be activated by Transforming Growth Factor beta (TGF-ß) and involves changes in cellular phenotype, as well as, in the expression of proteins such as E-cadherin, N-cadherin, vimentin and claudin-7. Melatonin is a hormone with oncostatic and anti-metastatic properties and appears to participate in the TGF-ß pathway. Thus, the present work aimed to evaluate the expression of EMT markers, E-cadherin, N-cadherin, vimentin and claudin-7, as well as, the cell migration of the canine mammary cancer cell line, CF41, after treatment with melatonin and TGF-ß silencing. METHODS: Canine mammary cancer cell line, CF41, was cultured and characterized in relation to markers ER, PR and HER2. Cell line CF41 with reducing expression level of TGF-ßwas performed according to Leonel et al. (2017). Expression of the protein E-caderin, N-cadherin, vimentin and claudin-7 was evaluated by immunocytochemistry and quantified by optical densitometry. The analysis of cell migration was performed in transwell chambers with 8µM pore size membrane. RESULTS: CF41 cells present a triple negative phenotype, which is an aggressive phenotype. Immunocytochemistry staining showed increased expression of E-caderin and claudin-7 (P˂0.05) and decreased expression of N-cadherin and vimentin (P˂0.05) in CF41 cells after treatment with 1mM melatonin and TGF-ß silencing. Moreover, treatment with melatonin and TGF-ß silencing was able to reduce migration in cell line CF41 (P˂0.05). CONCLUSION: Our data suggests that therapies combining TGF- ß1 silencing and melatonin may be effective in suppressing the process of EMT, corroborating the hypothesis that melatonin acts on the TGF-ß1 pathway and can reduce the metastatic potential of CF41 cells. This is so far the first study that reports melatonin treatment in CF41 cells with TGF-ß1 silencing and its effect on EMT. Thus, further studies are needed to confirm this hypothesis.

Heart rate variability assessment with fingertip photoplethysmography and polar RS800cx as compared with electrocardiography in obese adolescents.

AIM: This study investigated the accuracy and reliability of short-term resting heart rate variability (HRV) assessment by fingertip photoplethysmography (PPG) and using a cardiofrequencimeter (Polar RS800cx) in obese adolescents. Obesity in adolescents may be related to autonomic dysfunction due to insulin resistance and/or increased central fat. This fact may affect the accuracy and reliability of the evaluation of autonomic activity at rest. METHODS: Fourteen adolescents (15±2 years) classified as obese and exhibiting insulin resistance underwent the following procedures: (a) anthropometric measurements, and (b) two 25-min HRV recordings in a supine position conducted simultaneously using ECG, PPG, and Polar RS800cx. RESULTS: The results showed significant correlations between HRV markers obtained using Polar RS800cx and PPG and those obtained from ECG, with coefficients of determination (R) and intraclass correlation coefficients ranging from 0.60 to 0.98 (P-value ranging from 0.03 to 0.05) and 0.70 to 0.99 (P-value ranging from 0.01 to 0.05), respectively. The technical error of measurement and intraclass correlation coefficients for test-retest reliability ranged from 8.9 to 45.8% and 0.38 to 0.68 for ECG, 8.0 to 30.5% and 0.29 to 0.61 for Polar RS800cx, and 7.2 to 54.6% and 0.45 to 0.64 for PPG, respectively. CONCLUSION: HRV indices calculated by Polar RS800cx and PPG appear to be as accurate and reproducible as data from ECG when evaluating the autonomic control of heart rate at rest in obese adolescents.

Relevance of endoscopic ultrasound in the management of esophagus cancer therapy.

INTRODUCTION: The objective of this case series study by retrospective analysis was to determine the relevance of endoscopic ultrasound (EUS) in therapeutic decision esophageal cancer. MATERIAL AND METHODS: Using medical records of the Department of Endoscopy of Santa Casa de São Paulo, we have collected data from 16 patients, in 4 years, diagnosed of esophageal cancer, and presented in the form of clinical cases to a specialist surgeon in esophageal cancer and a clinical oncologist, for therapeutic evaluation before and after the outcome of EUS. RESULTS: Both of them choose non-resective and not curative methods (68.8% by surgeon vs. 87.5% oncologist) before EUS. The best treatment by the surgeon was chemotherapy and palliative radiotherapy associated (25%) and palliative endoscopic prostheses (25%), and by the oncologist, neoadjuvant chemotherapy and radiotherapy associated (56.2%). After EUS, the resective surgical treatment was the both choice in only 6.2% of cases, and the rest of 93.8%, non-resective. The surgeon choice was chemotherapy and palliative radiotherapy associated (44%), and oncologist choice was neoadjuvant chemotherapy and radiotherapy associated (44%). Analysis by the Chi-square method, comparing respective versus non-resective treatment, surgeon versus oncologist, with and without the EUS, obtained values of P = 0.39 and P = 0.46, respectively. The comparison between healing and non-healing treatment had the same P value. Regarding the change in behavior (resective vs. non-resective), there was a change of approach by the surgeon in 25% of cases (P = 0.17) and the oncologist moved conduct in 6.25% of cases. Comparing the changing of behavior among experts, the P value was 0.33. Despite evidence of behavior change after the EUS, the statistical point of view, the P value had no significant relevance. The main factor involved is probably due to a reduced number of sample cases. However, this is a pilot study, and is needed other with a larger number of cases. CONCLUSION: The data obtained allow us to conclude that EUS proved to be an important test for the change in staging and therapeutic management of esophageal cancer.

Determination of cadmium in river water samples by flame AAS after on-line preconcentration in mini-column packed with 2-aminothiazole-modified silica gel.

A rapid and sensitive method was developed to determine trace levels of Cd2+ ions in an aqueous medium by flame atomic absorption spectrometry, using on-line preconcentration in a mini-column packed with 100 mg of 2-aminothiazol modified silica gel (SiAT). The Cd2+ ions were sorbed at pH 5.0. The preconcentrated Cd2+ ions were directly eluted from the column to the spectrometer's nebulizer-burner system using 100 microL of 2 mol L(-1) hydrochloric acid. A retention efficiency of over 95% was achieved. The enrichment factor (calculated as the ratio of slopes of the calibration graphs) obtained with preconcentrations in a mini-column packed with SiAT (A = -1.3 x 10(-3) + 1.8 x 10(-3)[Cd2+]) and without preconcentrations (A = 4 x 10(-5) + 3.5 x 10(-5)[Cd2+]), was 51 and the detection limit calculated was 0.38 microg L(-1). The preconcentration procedure was applied to determine trace levels of Cd in river water samples. The optimum preconcentration conditions are discussed herein.

Use of topical mitomycin C in myoplasty of the medial rectus muscle of rabbits.

To possibly reduce postoperative adhesions that occur after ocular myoplasties, we investigated the topical effects of 0.04% mitomycin C on the repaired areas of the medial rectus muscle using an equine renal capsule preserved in 98% glycerin for reinforcement of the sutures. Twenty-four rabbits, divided into two groups of 12 animals each [untreated (control) and treated group (MMC)], were submitted to surgical rupture of the medial rectus muscle of one eye and repair of the defect 24 h later with sutures and an equine renal capsule. Post-operative prophylactic treatment of the two groups consisted of the administration of eye drops containing neomycin, polymyxin B and dexamethasone at regular 6-h intervals for eight consecutive days and daily rinsing with physiological saline. MMC animals received additional treatment with topical 0.04% mitomycin C every 6 h for 14 consecutive days. Slit lamp biomicroscopy showed greater irritation of the ocular surface in MMC animals during the first days post operatively. Adhesions were observed at 15 and 30 days of assessment in the two groups, but were more extensive in control animals at 60 days. Histopathology revealed inflammatory exudation in both groups, which was greater in MMC animals. Mitomycin C (0.04%) instilled at 6-h intervals for 14 consecutive days reduced the occurrence of fibrosis in the myoplastic areas. However, the equine renal capsule was found to be of little benefit for the reinforcement of myoplasties.

Uveodermatologic syndrome in a Brazilian Fila dog.

A 5-year-old Brazilian Fila dog was presented with a history of vision loss, alopecia, and generalized depigmentation of the skin and hair. Clinical examination confirmed generalized depigmentation and pyodermitis. On ophthalmic examination there was depigmentation at the eyelid mucocutaneous junction, associated with anterior uveitis, and bilateral posterior synechia at 360 degrees. Both the complete blood count and skin scraping were normal. Skin biopsy showed histiocytary lichenoid interface dermatitis with an absence of pigment within the queratinocytes, and a moderate lymphomononuclear infiltrate and predominance of histiocytes in the papilar derma suggestive of uveodermatologic syndrome. Clinical management consisted of oral and topical administration of prednisone, associated with 1% indometacine eye drops. Methylprednisone was also used twice via the subconjunctival route, at an interval of 15 days. To prevent the development of secondary glaucoma due to posterior synechiae, dorzolamide and timolol eye drops were indicated. Both dermatologic and ophthalmic signs showed good improvement, vision was preserved, and some repigmentation of the skin and hair occurred.

Orbital cellulitis associated with Toxocara canis in a dog.

Reports of Toxocara canis ocular larva migrans are uncommon in animals, with only a few cases reported. Most reports involve larval migration into the retina and choroid, with parasitic invasion of the orbit reported only in experimental studies. This is the first clinical case of Toxocara canis infection in the retrobulbar region of a 10-year-old, cross-bred male dog presenting with unilateral orbital cellulitis. Ophthalmic signs included protrusion of the nictitating membrane, chemosis, exophthalmos and hypertropia. The parasite was diagnosed by histologic and parasitologic examination of orbital tissues, which were removed during enucleation.

Naproxen, clenbuterol and insulin administration ameliorates cancer cachexia and reduce tumor growth in Walker 256 tumor-bearing rats.

Cancer cachexia is characterized by anorexia and intense peripheral catabolism. We examine the potential benefits of combination of different anabolic agents such as insulin and clenbuterol associated to prostaglandin synthesis inhibitor (naproxen) on tumor growth, cachexia and renal function in Walker 256 tumor-bearing rats (WK). Groups were separated into WK, and WK with naproxen (WK N) or naproxen plus clenbuterol (WK NCb) or naproxen plus clenbuterol plus insulin (WK NCbI). Treatment begins at the 4th day after tumor inoculation, at the 14th day they were killed, glycemia, lacticidemia, glycogen content from liver, soleus and gastrocnemius muscles, tumor mass, body weight and kidney function were determined. Glycemia and glycogen content were reduced and lacticidemia increased in WK (p<0.05) as compared to control rats. The glycogen content recovered in all treated groups. Tumor weight was significantly reduced by the different treatments. At the 14th weight change (carcass-initial body weight) in the control increased by 38% and in the WK -2%. Naproxen treatment (WK N) induced an increased by 14%. The inclusion of clenbuterol (WK NCb) and insulin (WK NCbI) by 38 and 41%, respectively. Mean glomerular filtration rate (GFR) increased in the WK (p<0.05) as compared to control, but in the WK NCb the GFR was similar to control. Our results suggest that naproxen is able to reduce tumor growth and its association with insulin and clenbuterol induce mass weight gain and recovery energy fuel.

Evaluation of indoor exposition to benzene, toluene, ethylbenzene, xylene, and styrene by passive sampling with a solid-phase microextraction device.

A solid-phase microextraction (SPME) sampling method is developed to evaluate indoor exposure to benzene, toluene, ethylbenzene, xylene, and styrene with gas chromatography and flame ionization detection for quantitative analysis. An SPME holder with a 100-pm polydimethylsiloxane (PDMS) and 65-pm PDMS-divinylbenzene fiber coating is tested in different air relative humidity conditions. The method gives good resolution, shows a linear response, is repeatable, and presents high sensitivity. This method is compared with National Institute of Occupational Safety and Health (NIOSH) active sampling.

Depolarization-evoked GABA release from myenteric plexus is partially coupled to L-, N-, and P/Q-type calcium channels.

1. There are many evidences suggesting that gamma-aminobutyrate (GABA) is an important neurotransmitter and/or neuromodulator in the gut. 2. Using the myenteric plexus-longitudinal muscle preparation from the guinea pig ileum, we investigated the evoked release of [3H] GABA from enteric neurons by electrical pulses or high KCl, which occurs in a calcium-dependent and -independent way. In addition, using selective calcium channel blockers, we report the participation of distinct subtypes of calcium channels in the evoked release, showing a minor participation of L- and Q-type calcium channels, while N- and P-type have a participation of approximately 15%, each. However, regardless of the combination of Ca2+ channel blockers, we did not observe an inhibition greater than 50% of the calcium-dependent component of [3H] GABA release. 3. Thus, while the observed Ca2+-independent release mostly probable occur via reversal of the membrane GABA transporter, in our conditions, a considerable portion of the Ca2+-dependent evoked release of [3H] GABA is not coupled to L-, N-, or P/Q-type calcium channels, suggesting the involvement of intracellular calcium stores or other ways of getting calcium across the membrane.