Expression and antibody inhibition of P-type calcium channels in human small-cell lung carcinoma cells

P-type channels, a recently described form of voltage-gated calcium channels, are found in many central and peripheral neurons. In the present study, a partial cDNA clone sharing extensive nucleotide identity with a putative P-type voltage-gated calcium channel alpha 1 subunit was isolated from a small-cell lung carcinoma (SCLC) cell line. Anti-peptide antibodies generated to a unique acidic stretch in the IVS5-S6 linker region of the putative SCLC P-type channel reacted specifically with a SCLC fusion protein produced in bacteria and with a cell surface molecule in SCLC cells. Calcium currents in SCLC cells, measured by whole-cell patch clamp, were inhibited by these antibodies and by the P-type channel-specific toxin omega-agatoxin IVA. The inhibitory effects of the antibody and the toxin were not additive, consistent with their proposed action on the same type of channel. These results provide evidence for the expression of P-type calcium channels by SCLC cells. The expression of neuron-related molecules by these cells is of particular interest because small-cell lung carcinoma is frequently associated with paraneoplastic disorders affecting the nervous system

Insights from Water Quality of High Andean Springs for Human Consumption in Perú

The headwaters of the high Andean basin in Peru accumulate water from the mist, rain, snow, and hail, and it is transported superficially and underground to low-lying areas, mostly used for drinkable purposes. The natural water in these areas might be altered due to legal and illegal mining extraction. The aim of the study was to evaluate the water quality for human consumption. Seventeen water samples were examined from Andahuaylas (A), San Jerónimo (S), Talavera (T), and Chiara (CH) districts located between 2813 and 4004 m altitude in the Andes. We used physic ochemical, microbiological, and metal parameters, and the results were compared to permissible levels established by the WHO and ECA-Peru to examine samples collected in the dry and rainy seasons in 2019. Application of principal component analysis (PCA) identified areas and conditioning parameters. Extractive mining activity influences the quality of springs due to the presence of metals, especially antimony (Sb), arsenic (As), cadmium (Cd), and lead (Pb), values of which are higher than values permissible for human consumption, being higher in the dry season (p < 0.05). In addition, the presence of cations and particulate matter affects physico-chemical parameters, for example turbidity. PCA showed that parameters for water characterization are season-independent, and water quality in the springs would be conditioned by the presence of metals, especially in Andahuaylas and Talavera zones, as well as the parameters that are associated with dissolved solids in the water (turbidity and fluorides). A frequent monitoring program of springs and groundwater is recommended, with the purpose to protect water from contamination and guarantee safe water availability in low-lying and urbanized areas

Proposal of a water-quality index for high andean basins: application to the Chumbao river, Andahuaylas, Peru

Thewater fromthe high Andean rivers is peculiar due to its composition and the geomorphology of its sources, and naturally or anthropogenically contamination is not discarded along its course. This water is used for agriculture and human consumption, therefore knowing its quality is important. This research aimed to proposing and formulate a water-quality index for high Andean basins through the Delphimethod, and its application in the Chumbao River located in Andahuaylas-Peru. Forty-three water-quality parameters were evaluated through the Delphi method, and the water-quality index (WQIHA) was formulated with a weighted average of the weights of the selected parameters, it was compared with the WQI Dinius. For this purpose, ten sampling points were considered along the Chumbao River located between 4274 and 2572 m of altitude and theWQIHA was applied. In addition, field and laboratory analyses were carried out in 2018, 2019, and 2021, in dry and rainy seasons. Twenty parameters were grouped in the physicochemical sub-index (SIPC), heavy metals sub-index (SIHM), and organic matter sub-index (SIOM). Each group contributed with weights of 0.30, 0.30, and 0.40, respectively, for theWQIHA formulation. The SIPC and SIOM showed that the areas near the head of the basin presented excellent and good quality, while the urbanized areas were qualified as marginal to poor; SIHM reported good quality in all points and seasons. Regarding the WQIHA, the index shows good quality in the zones above 3184 m of altitude, contrasting with poor quality downstream, decreasing notably in both seasons, suggesting continuous degradation of the water body

COVID-19 and the Global Impact on Colorectal Practice and Surgery

Background: The novel severe acute respiratory syndrome coronavirus 2 virus that emerged in December 2019 causing coronavirus disease 2019 (COVID-19) has led to the sudden national reorganization of health care systems and changes in the delivery of health care globally. The purpose of our study was to use a survey to assess the global effects of COVID-19 on colorectal practice and surgery. Materials and Methods: A panel of International Society of University Colon and Rectal Surgeons (ISUCRS) selected 22 questions, which were included in the questionnaire. The questionnaire was distributed electronically to ISUCRS fellows and other surgeons included in the ISUCRS database and was advertised on social media sites. The questionnaire remained open from April 16 to 28, 2020. Results: A total of 287 surgeons completed the survey. Of the 287 respondents, 90% were colorectal specialists or general surgeons with an interest in colorectal disease. COVID-19 had affected the practice of 96% of the surgeons, and 52% were now using telemedicine. Also, 66% reported that elective colorectal cancer surgery could proceed but with perioperative precautions. Of the 287 respondents, 19.5% reported that the use of personal protective equipment was the most important perioperative precaution. However, personal protective equipment was only provided by 9.1% of hospitals. In addition, 64% of surgeons were offering minimally invasive surgery. However, 44% reported that enough information was not available regarding the safety of the loss of intra-abdominal carbon dioxide gas during the COVID-19 pandemic. Finally, 61% of the surgeons were prepared to defer elective colorectal cancer surgery, with 29% willing to defer for ≤ 8 weeks. Conclusion: The results from our survey have demonstrated that, globally, COVID-19 has affected the ability of colorectal surgeons to offer care to their patients. We have also discussed suggestions for various practical adaptation strategies for use during the recovery period. We have presented the results of a survey used to assess the global impact of coronavirus disease 2019 (COVID-19) on the delivery of colorectal surgery. Despite accessible guidance information, our results have demonstrated that COVID-19 has significantly affected the ability of colorectal surgeons to offer care to patients. We have also discussed practical adaptation strategies for use during the recovery phase

Autoantibodies to Agrin in Myasthenia Gravis Patients

To determine if patients with myasthenia gravis (MG) have antibodies to agrin, a proteoglycan released by motor neurons and is critical for neuromuscular junction (NMJ) formation, we collected serum samples from 93 patients with MG with known status of antibodies to acetylcholine receptor (AChR), muscle specific kinase (MuSK) and lipoprotein-related 4 (LRP4) and samples from control subjects (healthy individuals and individuals with other diseases). Sera were assayed for antibodies to agrin. We found antibodies to agrin in 7 serum samples of MG patients. None of the 25 healthy controls and none of the 55 control neurological patients had agrin antibodies. Two of the four triple negative MG patients (i.e., no detectable AChR, MuSK or LRP4 antibodies, AChR-/MuSK-/LRP4-) had antibodies against agrin. In addition, agrin antibodies were detected in 5 out of 83 AChR+/MuSK-/LRP4- patients but were not found in the 6 patients with MuSK antibodies (AChR-/MuSK+/LRP4-). Sera from MG patients with agrin antibodies were able to recognize recombinant agrin in conditioned media and in transfected HEK293 cells. These sera also inhibited the agrin-induced MuSK phosphorylation and AChR clustering in muscle cells. Together, these observations indicate that agrin is another autoantigen in patients with MG and agrin autoantibodies may be pathogenic through inhibition of agrin/LRP4/MuSK signaling at the NMJ

Homeostatic regulation of the endoneurial microenvironment during development, aging and in response to trauma, disease and toxic insult

The endoneurial microenvironment, delimited by the endothelium of endoneurial vessels and a multi-layered ensheathing perineurium, is a specialized milieu intérieur within which axons, associated Schwann cells and other resident cells of peripheral nerves function. The endothelium and perineurium restricts as well as regulates exchange of material between the endoneurial microenvironment and the surrounding extracellular space and thus is more appropriately described as a blood–nerve interface (BNI) rather than a blood–nerve barrier (BNB). Input to and output from the endoneurial microenvironment occurs via blood–nerve exchange and convective endoneurial fluid flow driven by a proximo-distal hydrostatic pressure gradient. The independent regulation of the endothelial and perineurial components of the BNI during development, aging and in response to trauma is consistent with homeostatic regulation of the endoneurial microenvironment. Pathophysiological alterations of the endoneurium in experimental allergic neuritis (EAN), and diabetic and lead neuropathy are considered to be perturbations of endoneurial homeostasis. The interactions of Schwann cells, axons, macrophages, and mast cells via cell–cell and cell–matrix signaling regulate the permeability of this interface. A greater knowledge of the dynamic nature of tight junctions and the factors that induce and/or modulate these key elements of the BNI will increase our understanding of peripheral nerve disorders as well as stimulate the development of therapeutic strategies to treat these disorders