Explore the vast range of titles available.

High arsenic concentrations in groundwater have been documented in La Laguna Region (LLR) in arid northern Mexico, where arsenic poisoning is both chronic and endemic. A heated debate has continued for decades on its origin. LLR consisted of a series of ancient connected lakes that developed at the end of a topographic depression under closed basin conditions. This study addresses the isotopic, chemical composition of the groundwater and geochemical modeling in the southeasternmost part of the LLR to determine the origin of arsenic. Groundwater samples were obtained from a carbonate and granular aquifers and from a clayey aquitard at terminal Viesca Lake. Results show that groundwater originated as meteoric water that reached the lakes mainly via abundant springs in the carbonate aquifer and perennial flooding of the Nazas–Aguanaval Rivers. Paleo-lake water underwent progressive evaporation as demonstrated by the enrichment of δ 18 O, δ 2 H and characteristic geochemical patterns in the granular aquifer and aquitard that resulted in highly saline (>90,000 mS/cm), arsenic-rich (up to 5000 μg/L) paleo-groundwater (>30,000 years BP). However, adsorption or co-precipitation on iron oxides, clay-mineral surfaces and organic carbon limited arsenic concentration in the groundwater. Arsenic-rich groundwater and other solutes are advancing progressively from the lacustrine margins toward the main granular aquifer, due to reversal of hydraulic gradients caused by intensive groundwater exploitation and the reduction in freshwater runoff provoked by dam construction on the main rivers. Desorption of arsenic will incorporate additional concentrations of arsenic into the groundwater and continue to have significant negative effects on human health and the environment.

The cornea is the most densely innervated and sensitive tissue in the body. The cornea is exclusively innervated by C- and A-delta fibers, including mechano-nociceptors that are triggered by noxious mechanical stimulation, polymodal nociceptors that are excited by mechanical, chemical, and thermal stimuli, and cold thermoreceptors that are activated by cooling. Noxious stimulations activate corneal nociceptors whose cell bodies are located in the trigeminal ganglion (TG) and project central axons to the trigeminal brainstem sensory complex. Ocular pain, in particular, that driven by corneal nerves, is considered to be a core symptom of inflammatory and traumatic disorders of the ocular surface. Ocular surface injury affecting corneal nerves and leading to inflammatory responses can occur under multiple pathological conditions, such as chemical burn, persistent dry eye, and corneal neuropathic pain as well as after some ophthalmological surgical interventions such as photorefractive surgery. This review depicts the morphological and functional changes of corneal nerve terminals following corneal damage and dry eye disease (DED), both ocular surface conditions leading to sensory abnormalities. In addition, the recent fundamental and clinical findings of the importance of peripheral and central neuroimmune interactions in the development of corneal hypersensitivity are discussed. Next, the cellular and molecular changes of corneal neurons in the TG and central structures that are driven by corneal nerve abnormalities are presented. A better understanding of the corneal nerve abnormalities as well as neuroimmune interactions may contribute to the identification of a novel therapeutic targets for alleviating corneal pain.

Objective To report the high incidence of lung cancer (LC) and malignant mesothelioma (MM) linked to environmental exposure to erionite fibres in a rural village of central Mexico. Methods This is a retrospective survey of clinical and mortality records from the years 2000–2012, accompanied by an environmental survey for nine Group-1 lung and pleura carcinogenic agents listed by the International Agency for Research on Cancer (IARC). Results Out of a total of 45 deaths between 2000 and 2012, 14 deaths correspond to different neoplasms of the lung, and at least four deaths to MM. The ages at diagnosis of MM were between 30 and 54 years. Annual age-standardised mortality rates per thousand due to LC and MM in the village (age >20 years) are 7.09 and 2.48 for males, and 4.75 and 1.05 for females, respectively. Erionite fibres were found in exposed rocks and soils, which can easily become airborne and be carried into streets and recreational areas near schools and homes. Other carcinogenic elements and minerals are found only in trace amounts, except for quartz dust and asbestos (chrysotile) cement sheeting, which are also present in the neighbouring villages. Conclusions These results indicate that environmental exposure to erionite is the main cause of the high rates of MM mortality in the Village of Tierra Blanca, supporting previous similar reports for people exposed to erionite fibres in villages in Turkey.

Aquitard consolidation in the Chalco Plain is the most recent of a series of major land subsidence problems near Mexico City caused by leaky‐aquifer pumping and involving a complex distribution of basalt flows within a lacustrine sequence. This study first conducted a ground magnetic survey combined with lithologic logs to map the extension of basalts. Then it assessed the evolution of ground surface elevations and updated hydraulic heads in the aquifer and aquitard in order to verify the accuracy of previous simulations and develop new predictions on land subsidence employing a one‐dimensional, nonlinear, groundwater flow‐consolidation model. Results show the presence of shallow basalts that extend from Sierra Santa Catarina into the Chalco Plain, causing a differential consolidation that controls both the distribution of large‐scale fractures in the aquitard and the shape of a new lake. Cumulative land subsidence in the center of the Chalco Plain reached 13 m in 2006, thus closely matching previous numerical estimations. Since 1985, the ground surface decline has continued at a rate of ∼0.40 m/yr, while the potentiometric surface decline in the aquifer proceeds at an average rate of approximately 1.5 m/yr, indicating that the flow system has not yet reached steady‐state conditions. Numerical predictions show that under current pumping rates, where the aquitard is 300 m, total land subsidence will reach approximately 19 m by the year 2020; while where the aquitard is 140 m thick, total land subsidence will reach approximately 12 m, and increase the risk of flooding and aquitard fracturing for nearby urban centers.

Introduction Stage III non‐small‐cell lung cancer (NSCLC) management is challenging given the heterogeneous nature of the disease. The LATAM subset of the real‐world, global KINDLE study reported the treatment patterns and clinical outcomes for LATAM from the pre‐immuno‐oncology era. Methods The study was conducted in seven countries (Argentina, Chile, Colombia, Dominican Republic, Mexico, Peru and Uruguay) in stage III NSCLC (American Joint Committee on Cancer, 7th edition) diagnosed between January 2013 and December 2017. Retrospective data from patients' medical records (index date to the end of follow‐up) were collected. Summary statistics, Kaplan–Meier survival estimates and a two‐sided 95% confidence interval (CI) were provided. Cox proportional hazard model was used for univariate and multi‐variate analyses. Results A total of 231 patients was enrolled, the median age was 65.0 years (range 21.0–89.0), 60.6% were males, 76.6% had smoking history, 64.0% had adenocarcinoma and 28.7% underwent curative resection. Multiple treatment regimens (>25) were used; chemotherapy alone was the most common (24.8%). The overall median progression‐free survival (mPFS) and median overall survival (mOS) were 14.8 months (95% CI, 12.1–18.6) and 48.6 months (95% CI, 34.7 to not calculable). Significantly better mPFS and mOS were observed for stage IIIA with curative surgery and resectable tumours and stage IIIB with an Eastern Cooperative Oncology Group score of 0/1, female gender, resectable tumours, adenocarcinoma and curative surgery (p < 0.05). Conclusion Results show diversity in treatment practices and the corresponding clinical outcomes in stage III NSCLC. There is a need to streamline treatment selection and sequencing to decrease relapse rates after initial therapy. Frequent Treatment Modalities for Stage III NSCLC ‐ Initial Therapy. The frequency of the various initial treatment modalities used, are shown by stage (IIIA vs IIIB) and overall. cCRT, concurrent chemoradiotherapy; NSCLC, non‐small‑cell lung cancer; sCRT, sequential chemoradiotherapy. Note: The cut‑off used for selection of treatment modalities is 5% in either of the groups.

An approach is presented to investigate the regional evolution of groundwater in the basin of the Amacuzac River in Central Mexico. The approach is based on groundwater flow cross-sectional modeling in combination with major ion chemistry and geochemical modeling, complemented with principal component and cluster analyses. The hydrogeologic units composing the basin, which combine aquifers and aquitards both in granular, fractured and karstic rocks, were represented in sections parallel to the regional groundwater flow. Steady-state cross-section numerical simulations aided in the conceptualization of the groundwater flow system through the basin and permitted estimation of bulk hydraulic conductivity values, recharge rates and residence times. Forty-five water locations (springs, groundwater wells and rivers) were sampled throughout the basin for chemical analysis of major ions. The modeled gravity-driven groundwater flow system satisfactorily reproduced field observations, whereas the main geochemical processes of groundwater in the basin are associated to the order and reactions in which the igneous and sedimentary rocks are encountered along the groundwater flow. Recharge water in the volcanic and volcano-sedimentary aquifers increases the concentration of HCO 3 – , Mg 2+ and Ca 2+ from dissolution of plagioclase and olivine. Deeper groundwater flow encounters carbonate rocks, under closed CO 2 conditions, and dissolves calcite and dolomite. When groundwater encounters gypsum lenses in the shallow Balsas Group or the deeper Huitzuco anhydrite, gypsum dissolution produces proportional increased concentration of Ca 2+ and SO 4 2– ; two samples reflected the influence of hydrothermal fluids and probably halite dissolution. These geochemical trends are consistent with the principal component and cluster analyses.

Background Dry eye disease (DED) is a multifactorial disease of the ocular surface accompanied by neurosensory abnormalities. Here, we evaluated the effectiveness of transient receptor potential vanilloid-1 (TRPV1) blockade to alleviate ocular pain, neuroinflammation, and anxiety-like behavior associated with severe DED. Methods Chronic DED was induced by unilateral excision of the Harderian and extraorbital lacrimal glands of adult male mice. Investigations were conducted at 21 days after surgery. The mRNA levels of TRPV1, transient receptor potential ankyrin-1 (TRPA1), and acid-sensing ion channels 1 and 3 (ASIC1 and ASIC3) in the trigeminal ganglion (TG) were evaluated by RNAscope in situ hybridization. Multi-unit extracellular recording of ciliary nerve fiber activity was used to monitor spontaneous and stimulated (cold, heat, and acid) corneal nerve responsiveness in ex vivo eye preparations. DED mice received topical instillations of the TRPV1 antagonist (capsazepine) twice a day for 2 weeks from d7 to d21 after surgery. The expression of genes involved in neuropathic and inflammatory pain was evaluated in the TG using a global genomic approach. Chemical and mechanical corneal nociception and spontaneous ocular pain were monitored. Finally, anxiety-like behaviors were assessed by elevated plus maze and black and white box tests. Results First, in situ hybridization showed DED to trigger upregulation of TRPV1, TRPA1, ASIC1, and ASIC3 mRNA in the ophthalmic branch of the TG. DED also induced overexpression of genes involved in neuropathic and inflammatory pain in the TG. Repeated instillations of capsazepine reduced corneal polymodal responsiveness to heat, cold, and acidic stimulation in ex vivo eye preparations. Consistent with these findings, chronic capsazepine instillation inhibited the upregulation of genes involved in neuropathic and inflammatory pain in the TG of DED animals and reduced the sensation of ocular pain, as well as anxiety-like behaviors associated with severe DED. Conclusion These data provide novel insights on the effectiveness of TRPV1 antagonist instillation in alleviating abnormal corneal neurosensory symptoms induced by severe DED, opening an avenue for the repositioning of this molecule as a potential analgesic treatment for patients suffering from chronic DED.

Euglenoids (Euglenida) are unicellular flagellates possessing exceptionally wide geographical and ecological distribution. Euglenoids combine a biotechnological potential with a unique position in the eukaryotic tree of life. In large part these microbes owe this success to diverse genetics including secondary endosymbiosis and likely additional sources of genes. Multiple euglenoid species have translational applications and show great promise in production of biofuels, nutraceuticals, bioremediation, cancer treatments and more exotically as robotics design simulators. An absence of reference genomes currently limits these applications, including development of efficient tools for identification of critical factors in regulation, growth or optimization of metabolic pathways. The Euglena International Network (EIN) seeks to provide a forum to overcome these challenges. EIN has agreed specific goals, mobilized scientists, established a clear roadmap (Grand Challenges), connected academic and industry stakeholders and is currently formulating policy and partnership principles to propel these efforts in a coordinated and efficient manner.

Reprogramming of macrophages into the inflammatory state (also known as M1) is currently considered as an effective way of eliminating cancer cells, but systemic deployment of this strategy is likely to induce dangerous autoimmune reactions. Consequently, converting immunosuppressive M2-type macrophages into M1 systemically is not a safe and effective therapeutic approach against cancer. Through cleavable covalent linking of curcumin to the chemotherapeutic agent Paclitaxel (Taxol), we have created a novel prodrug (STO-1) that, upon intravenous delivery, selectively reprograms tumor-associated microglia and macrophages (TAMs) and eliminates glioblastoma (GBM) without triggering autoimmunity. Demonstrating its therapeutic efficacy, prolonged treatment of six orthotopic GBM-bearing mice with STO-1 resulted in 67% long-term survival, with three surviving mice exhibiting complete tumor clearance and one displaying minimal residual disease, as confirmed by high-resolution ex vivo T2-weighted MRI 85 days after tumor inoculation. In contrast, the vehicle-treated mice displayed extensive intracranial tumors with edema and hemorrhage. Mechanistically, scRNA-seq analysis indicated induction of multiple M1-associated transcripts (ccrl2, cxcl9, ccr2, ccl5) consistent with robust TAMs reprogramming. In striking contrast to the M2⟶M1 reprogramming of TAMs, M1-type macrophages were suppressed in the spleens of STO-1-treated cancer-free mice. Therefore, STO-1 induces selective anti-tumor immunity and GBM elimination without triggering systemic autoimmune reactions.

Leishmania major cutaneous leishmaniasis is an infectious zoonotic disease. It is produced by a digenetic parasite, which resides in the phagolysosomal compartment of different mammalian macrophage populations. There is an urgent need to develop new therapies (drugs) against this neglected disease that hits developing countries. The main goal of this work is to establish an easier and cheaper tool of choice for real-time monitoring of the establishment and progression of this pathology either in BALB/c mice or in vitro assays. To validate this new technique we vaccinated mice with an attenuated Δhsp70-II strain of Leishmania to assess protection against this disease. We engineered a transgenic L. major strain expressing the mCherry red-fluorescent protein for real-time monitoring of the parasitic load. This is achieved via measurement of fluorescence emission, allowing a weekly record of the footpads over eight weeks after the inoculation of BALB/c mice. In vitro results show a linear correlation between the number of parasites and fluorescence emission over a range of four logs. The minimum number of parasites (amastigote isolated from lesion) detected by their fluorescent phenotype was 10,000. The effect of antileishmanial drugs against mCherry+L. major infecting peritoneal macrophages were evaluated by direct assay of fluorescence emission, with IC(50) values of 0.12, 0.56 and 9.20 µM for amphotericin B, miltefosine and paromomycin, respectively. An experimental vaccination trial based on the protection conferred by an attenuated Δhsp70-II mutant of Leishmania was used to validate the suitability of this technique in vivo. A Leishmania major strain expressing mCherry red-fluorescent protein enables the monitoring of parasitic load via measurement of fluorescence emission. This approach allows a simpler, faster, non-invasive and cost-effective technique to assess the clinical progression of the infection after drug or vaccine therapy.