Water resources affected by potentially toxic elements in an area under current and historical mining in northwestern Mexico.

Rio Sonora watershed and its aquifer-located in northwest Mexico-have been influenced by mining operations for 140 years, possibly causing emissions of potentially toxic elements (PTE) and affecting health of exposed populations. On the basis of available data from governmental surveys (2014-2017) and recent sampling (2018), this study constructed reliable PTE total concentration database that allowed us to report temporal/spatial variations in surface and groundwater and their associated health risks to the population living in the central part of the Rio Sonora basin. The data clearly showed that a mining spill that took place in 2014 has had an adverse impact on total PTE concentrations in surface water. They also indicated the presence of different PTE point source locations that have continued to cause contamination of surface water at levels of health concern. Data also suggested slight impacts of the spill event on groundwater possibly related to soil neutralizing potential. Two metal groups were detected for surface waters (Pb-Cd-As-Ni-Cr and of Zn-Al-Cr) and groundwaters (Cr-As-Cu-Cd and Zn-Al), which suggest that they have different sources or are being released by different processes. The potential health impacts of PTE concentrations were associated with specific age groups, dates, and areas. The results indicate that in this complex semi-arid rural system, current and historical mining activities, as well as contrasting hydrological conditions, have impacted surface and groundwater quality with important ecological and human health risks.

Mobility and accessibility of Zn, Pb, and As in abandoned mine tailings of northwestern Mexico.

Generation, storage, and management of waste coming from industrial processes are a growing worldwide problem. One of the main contributors is the mining industry, in particular tailings generated by historical mining, which are barely maintained, especially in developing countries. Assessing the impact of a mining site to surrounding soils and ecosystems can be complex, especially when determining mobility and accessibility of the contaminants is required to perform ecological and human health risk assessment. As an effort to obtain information regarding mobility and accessibility of some potentially toxic elements (Zn, Pb, and As) from an historical mining site of northwestern Mexico, the abandoned mine tailings of San Felipe de Jesús in central Sonora and adjacent agricultural soils were investigated. Mobility and accessibility were assessed by means of sequential extraction procedures and using simulated physiological media. Additionally, an assessment of accidental oral intake was calculated considering the bioaccessible fractions. Results show that higher concentrations of contaminants were found in sulfide-rich tailings (Zn = 92,540; Pb = 21,288; As = 19,740 mg kg-1) compared with oxide-rich tailings (Zn = 43,240; Pb = 14,763; As = 13,401 mg kg-1). Concentrations in agricultural soils were on average Zn = 4755, Pb = 2840, and As = 103 mg kg-1. Zinc was mainly recovered from labile fractions in oxide-rich tailings (~ 60%) and in a lower amount from sulfide-rich tailings (~ 30%). Pb and As were mainly associated with residual fractions (80-95%) in both types of tailings. The percentage of mobile fractions (sum of water-soluble, exchangeable, and bound to carbonate fractions) in agricultural soils was as follows: Zn ~ 60%, Pb ~ 15%, and As ~ 70%. Regarding the phytoaccessible fraction, the studied elements in mine tailings and agricultural soil samples exceeded the threshold limits, except for As in agricultural soils. According to data obtained, toxic effects were also calculated. As for daily oral intake for non-carcinogenic effects in adults and children, only Pb and As exceeded reference dose values, especially in children exposed to sulfide-rich tailings and agricultural soils. Regarding carcinogenic effects of Pb and As, most of the samples were above acceptable risk values.

LipoDDx: a mobile application for identification of rare lipodystrophy syndromes.

BACKGROUND: Lipodystrophy syndromes are a group of disorders characterized by a loss of adipose tissue once other situations of nutritional deprivation or exacerbated catabolism have been ruled out. With the exception of the HIV-associated lipodystrophy, they have a very low prevalence, which together with their large phenotypic heterogeneity makes their identification difficult, even for endocrinologists and pediatricians. This leads to significant delays in diagnosis or even to misdiagnosis. Our group has developed an algorithm that identifies the more than 40 rare lipodystrophy subtypes described to date. This algorithm has been implemented in a free mobile application, LipoDDx®. Our aim was to establish the effectiveness of LipoDDx®. Forty clinical records of patients with a diagnosis of certainty of most lipodystrophy subtypes were analyzed, including subjects without lipodystrophy. The medical records, blinded for diagnosis, were evaluated by 13 physicians, 1 biochemist and 1 dentist. Each evaluator first gave his/her results based on his/her own criteria. Then, a second diagnosis was given using LipoDDx®. The results were analysed based on a score table according to the complexity of each case and the prevalence of the disease. RESULTS: LipoDDx® provides a user-friendly environment, based on usually dichotomous questions or choice of clinical signs from drop-down menus. The final result provided by this app for a particular case can be a low/high probability of suffering a particular lipodystrophy subtype. Without using LipoDDx® the success rate was 17 ± 20%, while with LipoDDx® the success rate was 79 ± 20% (p < 0.01). CONCLUSIONS: LipoDDx® is a free app that enables the identification of subtypes of rare lipodystrophies, which in this small cohort has around 80% effectiveness, which will be of help to doctors who are not experts in this field. However, it will be necessary to analyze more cases in order to obtain a more accurate efficiency value.

N2O emission factors from a wastewater irrigated land in a semiarid environment in Mexico.

Irrigation with wastewater is an increasing practice around the world triggered by the large needs of water for agriculture. Many times this source of water is added by flooding to the fields, creating short temporal oxygen-depleted environments, where nitrous oxide (N2O) emissions are promoted. Agriculture is responsible for up to 60% of the global annual emissions of this gas, and its emission factors (EF) must be reported. During 21 months, we installed closed chambers to measure the N2O emissions from a wastewater irrigated plot in the Mezquital Valley. Here, alfalfa, rye grass, and maize were grown in succession, receiving mainly organic N contained in the untreated wastewater and the residues of the previous crop; only maize received extra mineral fertilization of 100 kg of N ha-1. We obtained a time series where the gaps were filled by linear interpolation. EF and N2O direct emissions were estimated by the Tier 1 approach of the IPCC. We found that the alfalfa and rye grass, which only receive organic nitrogen, produced minor N2O emissions, that reflected in lower EF (0.004 and 0.001, respectively), compared with the default value of the IPCC (0.01). In contrast, maize, which receives organic and inorganic N, lost 1% of this N input as N2O, the same as the default value (0.01). It seems that the form of N, the crop age and type influence greatly the N dynamics in this wastewater irrigated land-use system. Therefore, the Tier I approach of the IPCC seems to underestimate the N efficiency of this agroecosystem and overestimates the N2O direct emissions from alfalfa and rye grass.

Does Seipin Play a Role in Oxidative Stress Protection and Peroxisome Biogenesis? New Insights from Human Brain Autopsies.

Seipin is a widely expressed protein but with highest levels found in the brain and testes. Seipin function is not yet completely understood, therefore the aim of this study was to evaluate the expression of BSCL2 transcripts in the central nervous system (CNS) of humans and investigate the effect of their overexpression on a neuron model and their relationship with oxidative stress protection, as well as shed light on the pathogenic mechanisms of Celia's Encephalopathy. We analyzed the expression of BSCL2 transcripts using real-time RT-PCR in samples across the brain regions of subjects who underwent necropsy and from a case with Celia's Encephalopathy. The transcript encoding the long seipin isoform (BSCL2-203, 462 aa) is expressed primarily in the brain and its expression is inversely correlated with age in the temporal lobe, amygdala, and hypothalamus. Strong positive correlations were found between BSCL2 expression and some genes encoding protective enzymes against oxidative stress including SOD1 and SOD2, as well as peroxisome proliferator-activated receptor gamma (PPARG) in the amygdala. These results were experimentally corroborated by overexpressing BSCL2 transcripts in SH-SY5Y cells with lentiviral transduction and assessing their effects on neuron differentiated cells. Confocal microscopy studies showed that both seipin and PEX16 are closely expressed in the hypothalami of healthy human brains, and PEX16 was absent in the same region of the PELD case. We hypothesize that seipin has specific CNS functions and may play a role in peroxisome biogenesis.

Association of metreleptin treatment and dietary intervention with neurological outcomes in Celia's encephalopathy.

Celia's encephalopathy (progressive encephalopathy with/without lipodystrophy, PELD) is a recessive neurodegenerative disease that is fatal in childhood. It is caused by a c.985C>T variant in the BSCL2/seipin gene that results in an aberrant seipin protein. We evaluated neurological development before and during treatment with human recombinant leptin (metreleptin) plus a dietary intervention rich in polyunsaturated fatty acids (PUFA) in the only living patient. A 7 years and 10 months old girl affected by PELD was treated at age 3 years with metreleptin, adding at age 6 omega-3 fatty acid supplementation. Her mental age was evaluated using the Battelle Developmental Inventory Screening Test (BDI), and brain PET/MRI was performed before treatment and at age 5, 6.5, and 7.5 years. At age 7.5 years, the girl remains alive and leads a normal life for her mental age of 30 months, which increased by 4 months over the last 18 months according to BDI. PET images showed improved glucose uptake in the thalami, cerebellum, and brainstem. This patient showed a clear slowdown in neurological regression during leptin replacement plus a high PUFA diet. The aberrant BSCL2 transcript was overexpressed in SH-SY5Y cells and was treated with docosahexaenoic acid (200 µM) plus leptin (0.001 mg/ml) for 24 h. The relative expression of aberrant BSCL2 transcript was measured by qPCR. In vitro studies showed significant reduction (32%) in aberrant transcript expression. This therapeutic approach should be further studied in this devastating disease.

Bone mineral density in familial partial lipodystrophy.

OBJECTIVE: Type 1 and type 2 familial partial lipodystrophies (FPLD) are characterized by the loss or increase in subcutaneous fat in certain body regions, as well as metabolic disorders. Higher muscle volume and mass have also been described. However, so far, possible bone involvement has not been studied. The aim of this study was to evaluate bone mineral density (BMD) in patients with type 1 and type 2 FPLD. METHODS: A total of 143 women were selected and distributed into three groups (17 women with FPLD2, 82 women with FPLD1 and 44 nonlipodystrophic obese female controls). A thorough history and physical examination were carried out on all subjects, as well as the measurement of anthropometric features. BMD along with fat and fat-free mass (FFM) were determined by DXA (dual-energy X-ray absorptiometry). Statistical analyses, primarily using the χ2 , ANOVA and ANCOVA tests, were performed, using age, height, fat and FFM as covariables. RESULTS: After eliminating the possible influences of age, height, fat and FFM, we observed that there were no significant differences in total BMD between patients with FPLD and the control group, showing total BMD values of 1.092 ± 0.037 g/cm2 in the FPLD2 group, 1.158 ± 0.013 g/cm2 in the FPLD1 group and 1.173 ± 0.018 g/cm2 in the control group (P = .194). Similarly, no significant differences were found in segmental BMD. CONCLUSIONS: Unlike in other types of laminopathy in which bone is affected, in the case of FPLD, there are no differences in BMD compared to nonlipodystrophic subjects.

Skipped BSCL2 Transcript in Celia's Encephalopathy (PELD): New Insights on Fatty Acids Involvement, Senescence and Adipogenesis.

OBJECTIVE: PELD (Progressive Encephalopathy with or without Lipodystrophy or Celia's Encephalopathy) is a fatal and rare neurodegenerative syndrome associated with the BSCL2 mutation c.985C>T, that results in an aberrant transcript without the exon 7 (Celia seipin). The aim of this study was to evaluate both the process of cellular senescence and the effect of unsaturated fatty acids on preadipocytes from a homozygous c.985C>T patient. Also, the role of aberrant seipin isoform on adipogenesis was studied in adipose-derived human mesenchymal stem cells. MATERIAL AND METHODS: Cellular senescence was evaluated using ß-galactosidase staining of preadipocytes obtained from a homozygous c.985C>T patient. Moreover, these cells were cultured during 24 hours with Intralipid, a soybean oil-based commercial lipid emulsion. The expression of the different BSCL2 transcripts was measured by qPCR. Adipose-derived human mesenchymal stem cells were differentiated to a fat lineage using StemPRO adipogenesis kit, and the expression of BSCL2 transcripts and several adipogenesis-related genes was measured by qPCR. RESULTS: the treatment of preadipocytes with unsaturated fatty acids significantly reduced the expression of the BSCL2 transcript without exon 7 by 34 to 63%. On the other hand, at least in preadipocytes, this mutation does not disturb cellular senescence rate. Finally, during adipocyte differentiation of adipose-derived human mesenchymal stem cells, the expression of adipogenic genes (PPARG, LPIN1, and LPL) increased significantly over 14 days, and noteworthy is that the BSCL2 transcript without exon 7 was differentially expressed by 332 to 723% when compared to day 0, suggesting an underlying role in adipogenesis. CONCLUSIONS: our results suggest that Celia seipin is probably playing an underestimated role in adipocyte maturation, but not in senescence, and its expression can be modified by exogenous factors as fatty acids.

Type 1 familial partial lipodystrophy: understanding the Köbberling syndrome.

Familial partial lipodystrophy are Mendelian disorders involving abnormal body fat distribution and insulin resistance. The current classification includes the Köbberling syndrome (type 1 familial partial lipodystrophy), characterized by fat loss in the lower limbs and abnormal fat accumulation in other areas. Type 1 familial partial lipodystrophy appears to be heritable, but little is known about it, including putative contributing mutations. We aimed to characterize this syndrome better by evaluating a group of women with phenotypic features of type 1 familial partial lipodystrophy. This is a case-controlled study in which 98 women with type 1 familial partial lipodystrophy that lacked classical mutations known to cause familial partial lipodystrophy were compared with 60 women without lipodystrophy and 25 patients with type 2 familial partial lipodystrophy (Dunnigan disease). Clinical course, body composition by dual-energy X-ray absorptiometry, HbA1c, lipid profile, insulin, leptin and family history were evaluated in all of the participants. Analyses of receiver-operating characteristic curve were performed for type 1 familial partial lipodystrophy diagnosis, comparing different truncal/limbs ratios. Among patients with type 1 familial partial lipodystrophy, 68 % developed recognizable lipodystrophy before adolescence, and most displayed an autosomal-dominant pattern (86 %). Women with type 1 familial partial lipodystrophy had less lower-limb adipose tissue than women without lipodystrophy, but significantly more than patients with Dunnigan disease. Moreover, metabolic disturbances occurred more frequently in the type 1 familial partial lipodystrophy group (81 %) than in the non-lipodystrophic group (30 %, p<0.05). The severity of metabolic disturbances was inversely proportional to the percentage of fat in the lower extremities and directly proportional to the amount of visceral adipose tissue. Metabolic profiles were worse in type 1 familial partial lipodystrophy than in Dunnigan disease. According to the receiver-operating characteristic curve analysis, the best ratio was subscapular/calf skinfolds (KöB index), with a cut-off value of 3.477 (sensitivity: 89 %; specificity: 84 %). Type 1 familial partial lipodystrophy was an early-onset, autosomal-dominant lipodystrophy, characterized by fat loss in the lower limbs and abnormal fat accumulation in the abdominal visceral region, associated to insulin resistance and metabolic disorders. A KöB index >3.477 is highly suggestive of this syndrome.

Recombinant human leptin treatment in genetic lipodystrophic syndromes: the long-term Spanish experience.

Lipodystrophies are a group of diseases mainly characterized by a loss of adipose tissue and frequently associated with insulin resistance, hypertriglyceridemia, and hepatic steatosis. In uncommon lipodystrophies, these complications frequently are difficult to control with conventional therapeutic approaches. This retrospective study addressed the effectiveness of recombinant methionyl leptin (metreleptin) for improving glucose metabolism, lipid profile, and hepatic steatosis in patients with genetic lipodystrophic syndromes. We studied nine patients (five females and four males) with genetic lipodystrophies [seven with Berardinelli-Seip syndrome, one with atypical progeroid syndrome, and one with type 2 familial partial lipodystrophy (FPLD)]. Six patients were children under age 9 years, and all patients had baseline triglycerides levels >2.26 mmol/L and hepatic steatosis; six had poorly controlled diabetes mellitus. Metreleptin was self-administered subcutaneously daily at a final dose that ranged between 0.05 and 0.24 mg/(kg day) [median: 0.08 mg/(kg day)] according to the body weight. The duration of treatment ranged from 9 months to 5 years, 9 months (median: 3 years). Plasma glucose, hemoglobin A1c (Hb A1c), lipid profile, plasma insulin and leptin, and hepatic enzymes were evaluated at baseline and at least every 6 months. Except for the patient with FPLD, metreleptin replacement significantly improved metabolic control (Hb A1c: from 10.4 to 7.1 %, p < 0.05). Plasma triglycerides were reduced 76 % on average, and hepatic enzymes decreased more than 65 %. This study extends knowledge about metreleptin replacement in genetic lipodystrophies, bearing out its effectiveness for long periods of time.

A new seipin-associated neurodegenerative syndrome.

BACKGROUND: Seipin/BSCL2 mutations can cause type 2 congenital generalised lipodystrophy (BSCL) or dominant motor neurone diseases. Type 2 BSCL is frequently associated with some degree of intellectual impairment, but not to fatal neurodegeneration. In order to unveil the aetiology and pathogenetic mechanisms of a new neurodegenerative syndrome associated with a novel BSCL2 mutation, six children, four of them showing the BSCL features, were studied. METHODS: Mutational and splicing analyses of BSCL2 were performed. The brain of two of these children was examined postmortem. Relative expression of BSCL2 transcripts was analysed by real-time reverse transcription-polymerase chain reaction (RT-PCR) in different tissues of the index case and controls. Overexpressed mutated seipin in HeLa cells was analysed by immunofluorescence and western blotting. RESULTS: Two patients carried a novel homozygous c.985C>T mutation, which appeared in the other four patients in compound heterozygosity. Splicing analysis showed that the c.985C>T mutation causes an aberrant splicing site leading to skipping of exon 7. Expression of exon 7-skipping transcripts was very high with respect to that of the non-skipped transcripts in all the analysed tissues of the index case. Neuropathological studies showed severe neurone loss, astrogliosis and intranuclear ubiquitin(+) aggregates in neurones from multiple cortical regions and in the caudate nucleus. CONCLUSIONS: Our results suggest that exon 7 skipping in the BSCL2 gene due to the c.985C>T mutation is responsible for a novel early onset, fatal neurodegenerative syndrome involving cerebral cortex and basal ganglia.