Methylmercury neurotoxicity in Amazonian children downstream from gold mining.

In widespread informal gold mining in the Amazon Basin, mercury is used to capture the gold particles as amalgam. Releases of mercury to the environment have resulted in the contamination of freshwater fish with methylmercury. In four comparable Amazonian communities, we examined 351 of 420 eligible children between 7 and 12 years of age. In three Tapajós villages with the highest exposures, more than 80% of 246 children had hair-mercury concentrations above 10 microg/g, a limit above which adverse effects on brain development are likely to occur. Neuropsychological tests of motor function, attention, and visuospatial performance showed decrements associated with the hair-mercury concentrations. Especially on the Santa Ana form board and the Stanford-Binet copying tests, similar associations were also apparent in the 105 children from the village with the lowest exposures, where all but two children had hair-mercury concentrations below 10 microg/g. Although average exposure levels may not have changed during recent years, prenatal exposure levels are unknown, and exact dose relationships cannot be generated from this cross-sectional study. However, the current mercury pollution seems sufficiently severe to cause adverse effects on brain development.     

A capture enzyme-linked immunosorbent assay for species-specific detection of Bothrops venoms

A direct sandwich enzyme-linked immunosorbent assay (ELISA), employing affinity purified antivenom antibodies specifically recognizing the homologous venom, was developed for species-specific detection of bothropic venom. The method is based on a two-step affinity purification of the specific antibodies. A species monovalent antivenom is adsorbed onto a venom adsorbent containing heterologous venoms from the Bothrops, Crotalus and Lachesis genera. The species-specific antibodies obtained, are then adsorbed onto a second venom adsorbent containing only the homologous venom for the removal of non antivenom antibodies. Venom concentrations of 0.1 and 1,000 ng/ml were specifically identified for Bothrops jararacussu and B. alternatus venom respectively.     

COVID-19 Treatment: Drug Safety Prior to Conception and During Pregnancy and Breastfeeding

In December 2019, a new viral respiratory infection known as coronavirus disease 2019 (COVID-19) was first diagnosed in the city of Wuhan, China. COVID-19 quickly spread across the world, leading the World Health Organization to declare it a pandemic on March 11, 2020. The disease is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a similar virus to those involved in other epidemics such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Epidemiological studies have shown that COVID-19 frequently affects young adults of reproductive age and that the elderly and patients with chronic disease have high mortality rates. Little is known about the impact of COVID-19 on pregnancy and breastfeeding. Most COVID-19 cases present with mild flu-like symptoms and only require treatment with symptomatic relief medications, whereas other cases with COVID-19 require treatment in an intensive care unit. There is currently no specific effective treatment for COVID-19. A large number of drugs are being used to fight infection by SARS-CoV-2. Experience with this therapeutic arsenal has been gained over the years in the treatment of other viral, autoimmune, parasitic, and bacterial diseases. Importantly, the search for an effective treatment for COVID-19 cannot expose pregnant women infected with SARS-CoV-2 to the potential teratogenic risks of these drugs. Therefore, it is necessary to determine and understand the safety of anti-COVID-19 therapies prior to conception and during pregnancy and breastfeeding.Key words: COVID-19, SARS-CoV-2, antiviral, pregnancy, breastfeeding     

Factors influencing contralateral lymph node metastasis from oral carcinoma

BACKGROUND: An ipsilateral neck dissection is mandatory during initial treatment stages II-IV oral carcinomas. However, no consensus exists whether or not to perform an elective contralateral neck dissection. METHODS: Five hundred thirteen consecutive cases of squamous cell carcinoma (269 tongue, 135 floor of the mouth, 44 inferior gingiva, 65 retromolar trigone) were reviewed. Tumor stages were: 69 T1, 227 T2, 217 T3-T4, 263 N0, 250 N1-N3. A total of 563 neck dissections were performed in 448 patients. Univariate and multivariate analysis of risk factors were performed using logistic regression. RESULTS: Two hundred twenty-three patients (49.8%) had positive nodes in the specimen (182 ipsilateral, 36 bilateral, 5 contralateral). Contralateral neck recurrences occurred in 38 cases (33 not submitted to a contralateral neck dissection initially). Multivariate logistic regression analysis demonstrated that clinical stage (p = .0001), tumor crossing midline (p = .0011), and floor of the mouth involvement (p = .0236) were the most important predictors of contralateral metastasis. CONCLUSION: The contralateral side of the neck is a common and potentially preventable site of recurrence in tumors of the oral cavity. The multivariate model obtained discriminates patients with low and high risk (more than 20%) of contralateral metastasis. The application of this mathematical model can be useful for the indication of contralateral neck dissections, because not all tumors crossing midline are associated to a high risk (stages I and II tumors not involving the floor of the mouth) and not all tumors not crossing midline are at low risk (stages III and IV tumors involving the floor of the mouth).     

Comparison of the neuropsychological assessment in a girl with bilateral cerebrovascular disease (moyamoya) before and after surgical intervention

Moyamoya is a chronic progressive cerebrovascular disease with characteristic angiographic findings and a clinical picture with episodes of transient ischemic attacks, headache, seizures, hemiparesis, which may resolve after surgical treatment. We describe the case of a girl with the typical findings of the disease, comparing them before and after surgery with the use of neuropsychological tests, neurological examination and laboratory tests.     

Dentate gyrus-selective colchicine lesion and disruption of performance in spatial tasks: difficulties in "place strategy" because of a lack of flexibility in the use of environmental cues?

The effects of intradentate colchicine injections on the performance of tasks requiring spatial working and reference memory are controversial. Multiple-site colchicine injections (7 microg/microl; via a drawn micropipette) throughout the dentate gyrus (DG) of rats (nine sites in each hemisphere, 0.06 microl at each site) selectively destroy about 90% of the DG granule cells, as revealed by quantitative stereological estimates; stereology also revealed minor neuronal losses in the CA4 (33%) and CA1 (23%) subfields, but lack of damage to the CA3 hippocampal subfield. Spatial reference and working memory were assessed in Morris' water maze; in the reference memory task, the rats were required to learn a single, fixed location for the platform over several days of training; in the working memory task, animals were required to learn a new platform location every day, in a matching-to-place procedure. Compared to sham-operated controls, lesioned rats showed significant disruption in acquisition of the reference memory water maze task; however, the data reveal that these rats did acquire relevant information about the task, probably based on guidance and orientation strategies. In a subsequent probe test, with the platform removed, lesioned rats showed disruption in precise indexes of spatial memory (e.g., driving search towards the surroundings of the former platform location), but not in less precise indexes of spatial location. Finally, the lesioned rats showed no improvement in the match-to-place procedure, suggesting that their working memory for places was disrupted. Thus, although capable of acquiring relevant information about the task, possibly through guidance and/or orientation strategies, DG-lesioned rats exhibit a marked difficulty in place strategies. This is particularly evident when these rats are required to deal with one-trial place learning in a familiar environment, such as in the working memory version of the water maze task, which requires flexibility in the use of previously acquired information.     

Tremor frequency patterns in mercury vapor exposure, compared with early Parkinson's disease and essential tremor

A new portable tremometer allows determination of tremor intensities at different tremor frequencies. Based on past studies, two tremor frequency windows of similar size were chosen at 3.0-6.5 Hz and 6.6-10.0 Hz to reflect major tremor intensities in Parkinson's disease and mercury vapor poisoning, respectively. In 81 healthy controls, total tremor intensity was higher for the preferred hand and depended on age. Ten patients treated for Parkinson's disease showed substantially increased tremor intensity, especially within the low-frequency window. This pattern was also apparent in 14 patients with de novo Parkinson's disease whose overall tremor intensity was only mildly elevated. In contrast, ten patients with essential tremor had peak frequencies in both windows, and some patients had increased tremor on one side only. Sixty-three Brazilian gold traders exposed to mercury vapor showed increased tremor predominantly in the high-frequency window. Three of the gold traders had a narrower tremor peak at frequencies of 7-8 Hz. While the urine-mercury concentration was significantly associated with the current number of burning sessions per week, it did not correlate with tremor intensities. However, eight traders had a urinary mercury excretion level above 50 microg and at the same time a greatly increased average tremor intensity within the high-frequency window. These patterns were statistically significant for relative tremor intensities, but were less clear when total intensities were used. These observations suggest that the relative distribution of tremor intensities in specific frequency bands may be a valuable supplement to current diagnostic methods for subjects with mercury vapor exposure.     

Long-term effects of finasteride on prostate tissue composition

OBJECTIVES: To determine the long-term effects of finasteride treatment on prostate tissue composition; to relate these effects to clinical outcomes; and to test the hypothesis that finasteride exerts a selective or preferential action on the transition zone. METHODS: Nineteen men with symptomatic benign prostatic hyperplasia (BPH) who completed a 6-month double-blind trial of finasteride were enrolled in a 24-month open-label extension study of drug responders. Magnetic resonance imaging and prostate biopsy for morphometric analysis were performed together 70 times: at baseline (n = 19), after treatment periods of intermediate duration (6 to 18 months, n = 32), and after long-term drug treatment (24 to 30 months, n = 19). At baseline, prostate volume averaged 51 cc, of which 57% was transition zone. RESULTS: Decreases in symptom score, dihydrotestosterone and prostate-specific antigen levels, and prostate volume occurred at 6 months (P <0.01), stabilized, and were maintained without further long-term decreases. Prostate epithelium contracted progressively from baseline (19.2% tissue composition; 6.0-cc volume; 3.2 stroma/epithelial ratio) to intermediate (12.5%, 3.3 cc, and 5.6, respectively) to long-term treatment (6.4%, 2.0 cc, and 17.4, respectively, P <0.01 for all). Percent epithelial contraction was similar in the peripheral and transition zones (P = NS). The transition zone remained a relatively constant proportion (53% to 58%) of whole-prostate volume from baseline to long-term observation. CONCLUSIONS: Long-term finasteride treatment (24 to 30 months) results in a marked involution of the prostate epithelium, which continues to progress for many months after clinical effects stabilize. The effect on the epithelium is similar in the peripheral and transition zones for both morphometric and volumetric changes. Progressive contraction of the prostate epithelium appears to constitute the underlying mechanism for sustained action of finasteride.