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The Amazonian indigenous peoples depend on natural resources to live, but human activities’ growing impacts threaten their health and livelihoods. Our objectives were to present the principal results of an integrated and multidisciplinary analysis of the health parameters and assess the mercury (Hg) exposure levels in indigenous populations in the Brazilian Amazon. We carried out a cross-sectional study based on a census of three Munduruku indigenous villages (Sawré Muybu, Poxo Muybu, and Sawré Aboy), located in the Sawré Muybu Indigenous Land, between 29 October and 9 November 2019. The investigation included: (i) sociodemographic characterization of the participants; (ii) health assessment; (iii) genetic polymorphism analysis; (iv) hair mercury determination; and (v) fish mercury determination. We used the logistic regression model with conditional Prevalence Ratio (PR), with the respective 95% confidence intervals (CI95%) to explore factors associated with mercury exposure levels ≥6.0 µg/g. A total of 200 participants were interviewed. Mercury levels (197 hair samples) ranged from 1.4 to 23.9 μg/g, with significant differences between the villages (Kruskal–Wallis test: 19.9; p-value < 0.001). On average, the general prevalence of Hg exposure ≥ 6.0 µg/g was 57.9%. For participants ≥12 years old, the Hg exposure ≥6.0 µg/g showed associated with no regular income (PR: 1.3; CI95%: 1.0–1.8), high blood pressure (PR: 1.6; CI95%: 1.3–2.1) and was more prominent in Sawré Aboy village (PR: 1.8; CI95%: 1.3–2.3). For women of childbearing age, the Hg exposure ≥6.0 µg/g was associated with high blood pressure (PR: 1.9; CI95%: 1.2–2.3), with pregnancy (PR: 1.5; CI95%: 1.0–2.1) and was more prominent among residents in Poxo Muybu (PR: 1.9; CI95%: 1.0–3.4) and Sawré Aboy (PR: 2.5; CI95%: 1.4–4.4) villages. Our findings suggest that chronic mercury exposure causes harmful effects to the studied indigenous communities, especially considering vulnerable groups of the population, such as women of childbearing age. Lastly, we propose to stop the illegal mining in these areas and develop a risk management plan that aims to ensure the health, livelihoods, and human rights of the indigenous people from Amazon Basin.

BackgroundCentral post-stroke pain (CPSP) is a neuropathic pain syndrome associated with somatosensory abnormalities due to central nervous system lesion following a cerebrovascular insult. Post-stroke pain (PSP) refers to a broader range of clinical conditions leading to pain after stroke, but not restricted to CPSP, including other types of pain such as myofascial pain syndrome (MPS), painful shoulder, lumbar and dorsal pain, complex regional pain syndrome, and spasticity-related pain. Despite its recognition as part of the general PSP diagnostic possibilities, the prevalence of MPS has never been characterized in patients with CPSP patients. We performed a cross-sectional standardized clinical and radiological evaluation of patients with definite CPSP in order to assess the presence of other non-neuropathic pain syndromes, and in particular, the role of myofascial pain syndrome in these patients.MethodsCPSP patients underwent a standardized sensory and motor neurological evaluation, and were classified according to stroke mechanism, neurological deficits, presence and profile of MPS. The Visual Analogic Scale (VAS), McGill Pain Questionnaire (MPQ), and Beck Depression Scale (BDS) were filled out by all participants.ResultsForty CPSP patients were included. Thirty-six (90.0%) had one single ischemic stroke. Pain presented during the first three months after stroke in 75.0%. Median pain intensity was 10 (5 to 10). There was no difference in pain intensity among the different lesion site groups. Neuropathic pain was continuous-ongoing in 34 (85.0%) patients and intermittent in the remainder. Burning was the most common descriptor (70%). Main aggravating factors were contact to cold (62.5%). Thermo-sensory abnormalities were universal. MPS was diagnosed in 27 (67.5%) patients and was more common in the supratentorial extra-thalamic group (P <0.001). No significant differences were observed among the different stroke location groups and pain questionnaires and scales scores. Importantly, CPSP patients with and without MPS did not differ in pain intensity (VAS), MPQ or BDS scores.ConclusionsThe presence of MPS is not an exception after stroke and may present in association with CPSP as a common comorbid condition. Further studies are necessary to clarify the role of MPS in CPSP.

Thrombosis of tunneled central venous catheters (CVC) in hemodialysis (HD) patients is common and it can lead to the elimination of vascular sites. This study aimed to evaluate the incidence of thrombotic obstruction of tunneled CVC in HD patients and the efficacy of occlusion treatment with alteplase use, and identify factors associated with thrombotic occlusion. It was a prospective cohort study performed in two centers which evaluated the diagnosis and treatment of thrombotic occlusion of CVC in HD patients for 24 consecutive months. The catheter occlusion was defined as the difficulty infusing or withdrawing fluid from their paths. Alteplase dose was infused to fill the lumen of the occluded catheter and remained for 50 min. As there was no obstruction of the catheter, the procedure was repeated. Three hundred and thirty-nine CVC in 247 patients were evaluated and followed, totalling 67,244 CVC-days. One hundred fifty-seven patients had only one CVC, 88 patients had two CVC during the study, and two patients had three CVC. The median age was 58 (47-66) years, patients were predominantly men (54%), with diabetic nephropathy as the main cause of chronic kidney disease (44%), the internal jugular vein as the main site of implantation (82%), and duration of dialysis before CVC implantation of 119 (41.5 to 585.5) days. Eight hundred and fifteen occlusion episodes were diagnosed (12 episodes/1000 CVC-days), with primary success with alteplase in 596 episodes (77%) and secondary in 81 cases (10%). In 99 episodes (13%), success was not achieved after the second dose of alteplase. Two hundred and thirty CVC were removed during the study and the removal causes were arteriovenous fistula use in 88 patients (38.3%), infectious and mechanical complications in 89 (38.7%) and 21 (9.1%), respectively, and others (transplantation, transfer, or death) in 32 patients (13.9%). Adverse effects were also not observed. In the multivariate analysis, we identified the greatest number of days with CVC (OR = 1.02, CI = 1.01-1.04, P = 0.004), the presence of diabetes (OR = 1.560, CI = 1.351-1.894, P = 0.015), and exit site infection (ESI) (OR = 1.567 CI = 1347-1926, P = 0.023) as factors associated with obstruction. Thrombotic occlusion showed frequent mechanical complication in CVC of HD patients. We observed 12 episodes of obstruction per 1000 CVC-days, with a high success rate after alteplase use (87%). In the multivariate analysis, the time with CVC, the presence of diabetes, and ESI were identified as variables associated with thrombotic obstruction.

Central post-stroke pain affects up to 12% of stroke survivors and is notoriously refractory to treatment. However, stroke patients often suffer from other types of pain of non- neuropathic nature (musculoskeletal, inflammatory, complex regional) and no head-to-head comparison of their respective clinical and somatosensory profiles has been performed so far. We compared 39 patients with definite central neuropathic post-stroke pain with two matched- control groups: 32 patients with exclusively non-neuropathic pain developed after stroke and 31 stroke patients not complaining of pain. Patients underwent deep phenotyping via a comprehensive assessment including clinical exam, questionnaires and quantitative sensory testing to dissect central post-stroke pain from chronic pain in general and stroke. While central post-stroke pain was mostly located in the face and limbs, non-neuropathic pain was predominantly axial and located in neck, shoulders and knees (p&lt;0.05). Neuropathic Pain Symptom Inventory clusters burning (82.1%, n=32, p&lt;0.001), tingling (66.7%, n= 26, p&lt;0.001) and evoked by cold (64.1%, n=25, p&lt;0.001) occurred more frequently in central post-stroke pain. Hyperpathia, thermal and mechanical allodynia also occurred more commonly in this group (p&lt;0.001), which also presented higher levels of deafferentation (p&lt;0.012) with more asymmetric cold and warm detection thresholds compared to controls. In particular, cold hypoesthesia (considered when the threshold of the affected side was less than 41% of the contralateral threshold) odds ratio was 12 (95%CI: 3.8-41.6) for neuropathic pain. Additionally, cold detection threshold/ warm detection threshold ratio correlated with the presence of neuropathic pain (ρ=-0.4, p&lt; 0.001). Correlations were found between specific neuropathic pain symptom clusters and quantitative sensory testing: paroxysmal pain with cold (ρ=-0.4; p=0.008) and heat pain thresholds (ρ=0.5; p=0.003), burning pain with mechanical detection (ρ= -0.4; p=0.015) and mechanical pain thresholds (ρ=-0.4, p&lt;0.013), evoked pain with mechanical pain threshold (ρ= -0.3; p=0.047). Logistic regression showed that the combination of cold hypoesthesia on quantitative sensory testing, the Neuropathic Pain Symptom Inventory, and the allodynia intensity on bedside examination explained 77% of the occurrence of neuropathic pain. These findings provide insights into the clinical-psychophysics relationships in central post-stroke pain and may assist more precise distinction of neuropathic from non-neuropathic post-stroke pain in clinical practice and in future trials.

Background: Central neuropathic pain (CNP) is often refractory to available therapeutic strategies and there are few evidence-based treatment options. Many patients with neuropathic pain are not diagnosed or treated properly. Thus, consensus-based recommendations, adapted to the available drugs in the country, are necessary to guide clinical decisions. Objective: To develop recommendations for the treatment of CNP in Brazil. Methods: Systematic review, meta-analysis, and specialists opinions considering efficacy, adverse events profile, cost, and drug availability in public health. Results: Forty-four studies on CNP treatment were found, 20 were included in the qualitative analysis, and 15 in the quantitative analysis. Medications were classified as first-, second-, and third-line treatment based on systematic review, meta-analysis, and expert opinion. As first-line treatment, gabapentin, duloxetine, and tricyclic antidepressants were included. As second-line, venlafaxine, pregabalin for CND secondary to spinal cord injury, lamotrigine for CNP after stroke, and, in association with first-line drugs, weak opioids, in particular tramadol. For refractory patients, strong opioids (methadone and oxycodone), cannabidiol/delta-9-tetrahydrocannabinol, were classified as third-line of treatment, in combination with first or second-line drugs and, for central nervous system (CNS) in multiple sclerosis, dronabinol. Conclusions: Studies that address the treatment of CNS are scarce and heterogeneous, and a significant part of the recommendations is based on experts opinions. The CNP approach must be individualized, taking into account the availability of medication, the profile of adverse effects, including addiction risk, and patients' comorbidities.

Genetic polymorphisms involved in mercury toxicokinetics and toxicodynamics may be associated with severe mercury toxicity. This study aimed to investigate the impact of an ALAD polymorphism on chronic mercury exposure and the health situation of indigenous children from the Brazilian Amazon. One-hundred-and-three indigenous children (under 15 years old) were included and genotyped (rs1800435) using a TaqMan validated assay. The mean age was 6.6 ± 4.5 years old, 60% were female, 49% presented with anemia, and the mean hair mercury concentration was 7.0 ± 4.5 (1.4–23.9) µg/g, with 49% exceeding the reference limit (≥6.0 µg/g). Only two children were heterozygous ALAD, while the others were all wild type. Minor allele frequency (ALAD G) and heterozygous genotype (ALAD CG) were 1% and 2%, respectively. The two children (12 and 14 years old) with the ALAD polymorphism had mercury levels above the average as well as had neurological symptoms related to chronic mercury exposure, such as visual field alterations, memory deficit, distal neuropathy, and toe amyotrophy. Both children also reported frequent consumption of fish in the diet, at least three times a week. In conclusion, our data confirm that an ALAD polymorphism can contribute to mercury half-life time, harmful effects, and neuropsychological disorders in indigenous children with chronic mercury exposure to gold mining activity.

There has been increasing evidence about mercury (Hg) contamination in traditional populations from the Amazon Basin due to illegal gold mining. The most concerning health impact is neurotoxicity caused by Hg in its organic form: methylmercury (MeHg). However, the severity and extent of the neurotoxic effects resulting from chronic environmental exposure to MeHg are still unclear. We conducted a clinical-epidemiological study to evaluate the neurological impacts of chronic MeHg exposure in Munduruku indigenous people, focusing on somatosensory, motor, and cognitive abnormalities. All participants were subjected to a systemized neurological exam protocol, including Brief Cognitive Screening Battery (BCSB), verbal fluency test, and Stick Design Test. After the examination, hair samples were collected to determine MeHg levels. Data collection took place between 29 October and 9 November 2019, in three villages (Sawré Muybu, Poxo Muybu, and Sawré Aboy) from Sawré Muybu Indigenous Land, Southwest of Pará state. One hundred and ten individuals >12 years old were included, 58 of which were men (52.7%), with an average age of 27.6 years (range from 12 to 72). Participants’ median MeHg level was 7.4 µg/g (average: 8.7; S.D: 4.5; range: 2.0–22.8). In Sawré Aboy village, the median MeHg level was higher (12.5 µg/g) than in the others, showing a significant statistical exposure gradient (Kruskal–Wallis test with p-value < 0.001). Cerebellar ataxia was observed in two participants with MeHg levels of 11.68 and 15.68 µg/g. Individuals with MeHg exposure level ≥10 µg/g presented around two-fold higher chances of cognitive deficits (RP: 2.2; CI 95%: 1.13–4.26) in BCSB, and in the verbal fluency test (RP: 2.0; CI 95%: 1.18–3.35). Furthermore, adolescents of 12 to 19 years presented three-fold higher chances of verbal development deficits, according to the fluency test (RP: 3.2; CI 95%: 1.06–9.42), than individuals of 20 to 24 years. The worsened motor and cognitive functions are suggestive of neurotoxicity due to chronic MeHg exposure. In conclusion, we believe monitoring and follow-up measures are necessary for chronic mercury exposed vulnerable people, and a basic care protocol should be established for contaminated people in the Brazilian Unified Health System.