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El crecimiento de plantas, mayor rendimiento y calidad de frutos, son efectos positivos debido a la absorción de silicio (Si) y cloro (Cl), que contribuye a mitigar el estrés por factores bióticos o abióticos y recuperar el crecimiento de las plantas. El objetivo de la presente investigación fue conocer el efecto que producen las dosis de Si o Cl en variables morfométricas, calidad de producción y rendimiento del cultivo de pepino. Se aplicó un diseño de bloques completos al azar, cuatro repeticiones y diez tratamientos en plántulas: seis dosis de 20, 30 y 50 mg L-1 de Si o Cl, tres dosis con la relación volumen:volumen (v:v) de 20:20, 30:30 y 50:50 mg L-1 Si:Cl, más el testigo. En plantas trasplantadas en suelo, ya con cinco hojas verdaderas, los tratamientos fueron nueve: seis dosis de 20, 30 y 50 mg L-1 de Si o Cl, dos con la relación v:v de 20:20 y 30:30 mg L-1 Si:Cl, y el testigo. En plántulas de pepino ˈpickleˈ, la dosis alta de Cl fue más eficaz para incrementar el verdor de hojas y longitud del tallo; el tamaño de hojas fue superior en plántulas con la dosis alta de Si; mientras que las bajas dosis de Cl o Si ocasionaron mayor peso seco de raíces. En el cultivar ˈModanˈ el verdor no varió, la longitud del tallo fue superior con la dosis intermedia de Si, mientras que el tamaño de hojas se expresó mejor en plantas con la menor dosis de Si. Así que quizás la mayor cantidad de raíces, el contenido de clorofila y el área foliar influyeron para que el rendimiento más alto se expresara donde se fertilizó con Si o Cl, así como para que mejoraran la firmeza, SST y °Brix de los frutos.

Existe evidencia acerca del mejoramiento de la resistencia de las plantas ante factores bióticos y abióticos, el metabolismo fotosintético y la productividad de cultivos por la fertilización con silicio. El objetivo de la investigación fue conocer la influencia del silicio en el crecimiento, rendimiento y calidad postcosecha de tomate saladette indeterminado cultivado en suelo. Se utilizó un diseño de bloques completos al azar con cuatro tratamientos (0/testigo, 20, 30 y 50 mg L-1 de silicio) y tres repeticiones. Las tres dosis de silicio en estudio fueron eficaces para aumentar diámetro de tallo, número de hojas, área foliar, índice de verdor y acidez titulable. La firmeza y contenido de sólidos solubles del fruto no fueron afectados. Mientras que, con la dosis de 50 mg L-1 se indujo el mayor rendimiento de tomate. En general, la producción de tomate mejoró significativamente con la adición de silicio al esquema de fertilización.

El aumento de la capacidad fotosintética, disminución de la tasa transpiración, mayor crecimiento de las plantas, incremento de los rendimientos y la calidad de muchos cultivos, son efectos que ocasionan el silicio (Si) y el cloro (Cl), dichos efectos benéficos que ocasionan ambos elementos depende de las especies y de los genotipos dentro de la misma especie. Por lo anterior, el objetivo de la investigación fue determinar el efecto del silicio y cloro, de manera individual o en combinación, así como las dosis más eficaces en el crecimiento, rendimiento y calidad postcosecha de pepino y tomate. Se sembraron los cultivares ‘Paraíso F1’ y ‘tomate F3’, se regaron cada 24 h y fueron fertilizados con 200 kg ha‑1 de N y 2 L ha-1 de Micro-Min foliar (20-30-10) a los 36 y 56 días después de la siembra. En ambos experimentos se estableció un diseño experimental de bloques completos al azar, manejados en riego por goteo. Los tratamientos consistieron en 20, 30 y 50 mg L-1 de Si o Cl y las combinaciones de 20:20 y 30:30 mg L-1 de Si:Cl, más el testigo. La dosis más alta de Si y las tres de Cl o dos de Si:Cl fueron más eficaces para inducir crecimiento en pepino, pero en rendimiento las más adecuadas fueron las dos más altas de Si y las tres de Cl. Mientras que en tomate la menor dosis de Cl indujo leve incremento del verdor foliar, los dos nutrientes disminuyeron la altura, y la dosis más alta de Si:Cl fue más eficaz para incrementar ligeramente el área foliar, pero el rendimiento no se incrementó. Con respecto a los sólidos solubles totales, la dosis más alta de Cl y la menor combinación de Si:Cl ocasionaron mejor respuesta en pepino; no obstante, en tomate sólo la menor dosis de Cl ocasionó la respuesta más alta.

Magnesium is an essential chemical element in human life. In the brain, it is physiologically responsible for a large number of processes involved in intracellular homeostasis, blood-brain barrier integrity, protein synthesis, neuronal proliferation, aging, and apoptosis. Considering that neurocritical care is a relatively new discipline in certain regions of the world and is an independent protective factor of neurological diseases in critical care, it is essential to disseminate basic concepts and utilities of tools that can positively impact the neurological disease burden. Magnesium and its use in neurocritical care are poorly understood. Therefore, this study aimed to review basic concepts regarding the physiology of magnesium in neurological dynamics, its role in the pathophysiology of neurological disorders, and the outcome of its use in the management of neurocritical illnesses.

Purpose: We aim to evaluate the impact of surgical wound complications in the first 30 postoperative days after incisional hernia repair on the long-term quality of life of patients. In addition, the impact of the surgical technique and preoperative comorbidities on the quality of life of patients will also be evaluated., Method: Prospective cohort study, which evaluates 115 patients who underwent incisional hernioplasty between 2019 and 2020, using the onlay and retromuscular techniques. These patients were initially assessed with regard to surgical wound outcomes in the first 30 postoperative days (surgical site infection (SSI) or surgical site occurrence (SSO)), and then, assessed after three years, through a specific quality of life questionnaire, the Hernia Related Quality of Life Survey (HerQLes)., Results: After some patients were lost to follow-up during the study period, due to death, difficulty in contact, refusal to respond to the questionnaire, eighty patients were evaluated. Of these, 11 patients (13.8%) had SSI in the first 30 postoperative days and 37 (46.3%) had some type of SSO. The impact of both SSI and SSO on quality of life indices was not identified. When analyzing others variables, we observed that the Body Mass Index (BMI) had a significant impact on the patients' quality of life. Likewise, hernia size and mesh size were identified as variables related to a worse quality of life outcome. No difference was observed regarding the surgical techniques used., Conclusion: In the present study, no relationship was identified between surgical wound outcomes (SSO and SSI) and worse quality of life results using the HerQLes score. We observed that both BMI and the size of meshes and hernias showed an inversely proportional relationship with quality of life indices. However, more studies evaluating preoperative quality of life indices and comparing them with postoperative indices should be carried out to evaluate these correlations., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose of this study is to explore the extraction of potentially valuable cosmetic ingredients from rice crop residues, aiming to mitigate their environmental impact., Methods: We employed AOAC methods to analyze the fat, protein, ash, fiber, soluble, and insoluble carbohydrate content in these residues. To identify sugars rich in galactose and acidic sugars, a total soluble carbohydrate extraction was performed. Cellulose, as part of the insoluble carbohydrates, was isolated through alkaline and acid hydrolysis, while sodium silicate was derived from the ash. Characterization of insoluble cellulose and silicate involved techniques like FTIR, DSC, PXRD, microphotography, porosity assessments, and water absorption studies. For proteins, alkaline solubilization and precipitation at the isoelectric point were utilized, with quantification via BCA and amino acid profiling through gas chromatography. Evaluation of radical scavenging capacity using DPPH led to the calculation of apparent molecular weight via SDS-PAGE., Results: The results revealed low levels of gum, mucilage, and pectin in both residues, contrasting with a high concentration of insoluble polysaccharides. Among these, Iβ cellulose displayed potential attributes for cosmetic applications due to its oil and water adsorption characteristics. However, silicates obtained from the ashes did not exhibit direct use potential. In terms of protein extraction, we observed antioxidant properties, with enhanced performance through enzymatic hydrolysis, achieving a hydrolysis degree of 30.41% and a DPPH radical absorption rate exceeding 70%., Conclusion: Rice residues, particularly husk and straw, shown valuable substances suitable for potential cosmetic applications, encompassing cellulose, hydrolyzed proteins, and ash as a silicate precursor., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

ABSTRACT Objetives: Omega-3 (n3) fatty acids have been studied as an option to alleviate the harmful effects of obesity. However, its role in obesity-related behavioral changes is still controversial. This study aimed to evaluate the effects of n3 on behavior and neuroinflammation in obese animals. Methods: Male Wistar rats were divided into four groups: control diet (CT), CT+n3, cafeteria diet (CAF), and CAF+n3. Diet was administered for 13 weeks, and n3 was supplemented during the last 5 weeks. Metabolic and biochemical parameters were evaluated, as well as anxiety-like behaviors. Immunoblots were conducted in the animals' cerebral cortex and hippocampus to assess changes in neuroinflammatory markers. Results: CAF-fed animals showed higher weight gain, visceral adiposity, fasting glucose, total cholesterol, triglycerides, and insulin levels, and n3 improved the lipid profile and restored insulin sensitivity. CAF-fed rats showed anxiety-like behaviors in the open field and light-dark box tasks but not in the contextual aversive conditioning. Omega-3 did not exert any effect on these behaviors. Regarding neuroinflammation, diet and supplementation acted in a region-specific manner. In the hippocampus, CAF reduced claudin-5 expression with no effect of n3, indicating a brain-blood barrier disruption following CAF. Furthermore, in the hippocampus, the glial fibrillary acidic protein (GFAP) and toll-like receptor 4 (TLR-4) were reduced in treated obese animals. However, n3 could not reverse the TLR-4 expression increase in the cerebral cortex. Discussion: Although n3 may protect against some neuroinflammatory manifestations in the hippocampus, it does not seem sufficient to reverse the increase in anxiolytic manifestations caused by CAF.

The feline leukemia virus (FeLV) belongs to the Retroviridae family and Gammaretrovirus genus, and causes a variety of neoplastic and non-neoplastic diseases in domestic cats (Felis catus), such as thymic and multicentric lymphomas, myelodysplastic syndromes, acute myeloid leukemia, aplastic anemia, and immunodeficiency. The aim of the present study was to carry out the molecular characterization of FeLV-positive samples and determine the circulating viral subtype in the city of São Luís, Maranhão, Brazil, as well as identify its phylogenetic relationship and genetic diversity. The FIV Ac/FeLV Ag Test Kit (Alere™) and the commercial immunoenzymatic assay kit (Alere™) were used to detect the positive samples, which were subsequently confirmed by ELISA (ELISA - SNAP® Combo FeLV/FIV). To confirm the presence of proviral DNA, a polymerase chain reaction (PCR) was performed to amplify the target fragments of 450, 235, and 166 bp of the FeLV gag gene. For the detection of FeLV subtypes, nested PCR was performed for FeLV-A, B, and C, with amplification of 2350-, 1072-, 866-, and 1755-bp fragments for the FeLV env gene. The results obtained by nested PCR showed that the four positive samples amplified the A and B subtypes. The C subtype was not amplified. There was an AB combination but no ABC combination. Phylogenetic analysis revealed similarities (78% bootstrap) between the subtype circulating in Brazil and FeLV-AB and with the subtypes of Eastern Asia (Japan) and Southeast Asia (Malaysia), demonstrating that this subtype possesses high genetic variability and a differentiated genotype., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Spider venoms are composed, among other substances, of peptide toxins whose selectivity for certain physiological targets has made them powerful tools for applications such as bioinsecticides, analgesics, antiarrhythmics, antibacterials, antifungals and antimalarials, among others. Bioinsecticides are an environmentally friendly alternative to conventional agrochemicals. In this paper, the primary structure of an insecticidal peptide was obtained from the venom gland transcriptome of the ctenid spider Phoneutria depilata (Transcript ID PhdNtxNav24). The peptide contains 53 amino acids, including 10 Cys residues that form 5 disulfide bonds. Using the amino acid sequence of such peptide, a synthetic gene was constructed de novo by overlapping PCRs and cloned into an expression vector. A recombinant peptide, named delta-ctenitoxin (rCtx-4), was obtained. It was expressed, folded, purified and validated using mass spectrometry (7994.61 Da). The insecticidal activity of rCtx-4 was demonstrated through intrathoracic injection in crickets (LD 50 1.2 μg/g insect) and it was not toxic to mice. rCtx-4 is a potential bioinsecticide that could have a broad spectrum of applications in agriculture.

Mirror-image pain arises from pathologic alterations in the nociceptive processing network that controls functional lateralization of the primary afferent input. Although a number of clinical syndromes related to dysfunction of the lumbar afferent system are associated with the mirror-image pain, its morphophysiological substrate and mechanism of induction remain poorly understood. Therefore, we used ex vivo spinal cord preparation of young rats of both sexes to study organization and processing of the contralateral afferent input to the neurons in the major spinal nociceptive projection area Lamina I. We show that decussating primary afferent branches reach contralateral Lamina I, where 27% of neurons, including projection neurons, receive monosynaptic and/or polysynaptic excitatory drive from the contralateral Aδ-fibers and C-fibers. All these neurons also received ipsilateral input, implying their involvement in the bilateral information processing. Our data further show that the contralateral Aδ-fiber and C-fiber input is under diverse forms of inhibitory control. Attenuation of the afferent-driven presynaptic inhibition and/or disinhibition of the dorsal horn network increased the contralateral excitatory drive to Lamina I neurons and its ability to evoke action potentials. Furthermore, the contralateral Aβδ-fibers presynaptically control ipsilateral C-fiber input to Lamina I neurons. Thus, these results show that some lumbar Lamina I neurons are wired to the contralateral afferent system whose input, under normal conditions, is subject to inhibitory control. A pathologic disinhibition of the decussating pathways can open a gate controlling contralateral information flow to the nociceptive projection neurons and, thus, contribute to induction of hypersensitivity and mirror-image pain. SIGNIFICANCE STATEMENT We show that contralateral Aδ-afferents and C-afferents supply lumbar Lamina I neurons. The contralateral input is under diverse forms of inhibitory control and itself controls the ipsilateral input. Disinhibition of decussating pathways increases nociceptive drive to Lamina I neurons and may cause induction of contralateral hypersensitivity and mirror-image pain., (Copyright © 2023 the authors.)

The methylotrophic yeast Pichia pastoris has been one of the most widely used organisms in recent years as an expression system for a wide variety of recombinant proteins with therapeutic potential. Its popularity as an alternative system to Escherichia coli is mainly due to the easy genetic manipulation and the ability to produce high levels of heterologous proteins, either intracellularly or extracellularly. Being a eukaryotic organism, P. pastoris carries out post-translational modifications that allow it to produce soluble and correctly folded recombinant proteins. This work, evaluated the expression capacity in P. pastoris of two single-chain variable fragments (scFvs) of human origin, 10FG2 and LR. These scFvs were previously obtained by directed evolution against scorpion venom toxins and are able to neutralize different toxins and venoms of Mexican species. The yield obtained in P. pastoris was higher than that obtained in bacterial periplasm (E. coli), and most importantly, biochemical and functional properties were not modified. These results confirm that P. pastoris yeast can be a good expression system for the production of antibody fragments of a new recombinant antivenom., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Baltazar Becerril Lujan has patent COMPOSITION OF HUMAN RECOMBINANT ANTIBODY FRAGMENTS THAT COMPLETELY NEUTRALIZE THE VENOM OF THE SCORPION CENTRUROIDES SCULPTURATUS pending to 17/937,666., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Scorpion neurotoxins such as those that modify the mammalian voltage-gated sodium ion channels (Nav) are the main responsible for scorpion envenomation. Their neutralization is crucial in the production of antivenoms against scorpion stings., Methods: In the present study, two in silico designed genes - one that codes for a native neurotoxin from the venom of the Anatolian scorpion Androctonus crassicauda, named Acra 4 - and another non-native toxin - named consensus scorpion toxin (SccTx) obtained from the alignment of the primary structures of the most toxic neurotoxins from the Middle Eastern and North African scorpions - were recombinantly expressed in E. coli Origami., Results: Following bacterial expression, the two expressed neurotoxins, hereafter named HisrAcra4 and HisrSccTx, were obtained from inclusion bodies. Both recombinant neurotoxins were obtained in multiple Cys-Cys isoforms. After refolding, the active protein fractions were identified with molecular masses of 8,947.6 and 9,989.1 Da for HisrAcra4 and HisrSccTx, respectively, which agreed with their expected theoretical masses. HisrAcra4 and HisrSccTx were used as antigens to immunize two groups of rabbits, to produce either anti-HisrAcra4 or anti-HisrSccTx serum antibodies, which in turn could recognize and neutralize neurotoxins from venoms of scorpion species from the Middle East and North Africa. The antibodies obtained from rabbits neutralized the 3LD 50 of Androctonus australis, Leiurus quinquestriatus hebraeus and Buthus occitanus venoms, but they did not neutralize A. crassicauda and A. mauritanicus venoms. In addition, the anti-HisrAcra4 antibodies did not neutralize any of the five scorpion venoms tested. However, an antibody blend of anti-HisrAcra4 and anti-HisrSccTx was able to neutralize A. crassicauda and A. mauritanicus venoms., Conclusions: Two recombinant Nav neurotoxins, from different peptide families, were used as antigens to generate IgGs for neutralizing scorpion venoms of species from the Middle East and North Africa., Competing Interests: Competing interests: The authors declare that they have no competing interests

Our knowledge about the detailed wiring of neuronal circuits in the spinal dorsal horn (DH), where initial sensory processing takes place, is still very sparse. While a substantial amount of data is available on the somatodendritic morphology of DH neurons, the laminar and segmental distribution patterns and consequential function of individual axons are much less characterized. In the present study, we fully reconstructed the axonal and dendritic processes of 10 projection neurons (PNs) and 15 interneurons (INs) in lamina I of the rat, to reveal quantitative differences in their distribution. We also performed whole-cell patch-clamp recordings to test the predicted function of certain axon collaterals. In line with our earlier qualitative description, we found that lamina I INs in the lateral aspect of the superficial DH send axon collaterals toward the medial part and occupy mostly laminae I-III, providing anatomical basis for a lateromedial flow of information within the DH. Local axon collaterals of PNs were more extensively distributed including dorsal commissural axon collaterals that might refer to those reported earlier linking the lateral aspect of the left and right DHs. PN collaterals dominated the dorsolateral funiculus and laminae IV-VI, suggesting propriospinal and ventral connections. Indeed, patch-clamp recordings confirmed the existence of a dorsoventral excitatory drive upon activation of neurokinin-1 receptors that, although being expressed in various lamina I neurons, are specifically enriched in PNs. In summary, lamina I PNs and INs have almost identical dendritic input fields, while their segmental axon collateral distribution patterns are distinct. INs, whose somata reside in lamina I, establish local connections, may show asymmetry, and contribute to bridging the medial and lateral halves of the DH. PNs, on the other hand, preferably relay their integrated dendritic input to deeper laminae of the spinal gray matter where it might be linked to other ascending pathways or the premotor network, resulting in a putative direct contribution to the nociceptive withdrawal reflex., (© 2022 The Authors. The Journal of Comparative Neurology published by Wiley Periodicals LLC.)

Given consumer trends propelling a movement toward using plant protein in the food industry and searching for alternative protein ingredients by the industry, this study aimed to assess the influence of factors such as protein concentration, medium pH, and the presence of a divalent ion (Ca 2+ ) upon the rheological properties such as viscosity change and gel formation of dispersion proteins extracted from quinoa, black beans, and lentils. A solution of each protein was prepared by varying its concentration (2.5%, 5.0%, and 10%), the pH (5.0, 7.0, and 9.0), and the incorporation of calcium chloride (0.0% and 1.0%). Each obtained solution was subjected to rheological tests to determine the parameters: consistency index (K), flow behavior (n), the storage (G') and loss (G'') modules, and the phase shift angle (δ). The results demonstrate that the incorporation of Ca 2+ , the shift in protein levels, and the decrease in pH modified the rheological behaviors of proteins, which were also influenced by the structural characteristics of each protein studied. However, thermal treatment and protein concentrations caused the most significant impact on proteins' rheological behavior, forming gels independently of other conditions. It was possible to study and interpret the studied proteins' rheological variations according to the environment's conditions.

Objective: We aim to determine the disposal site for biohazardous materials resulting from diabetes surveillance and therapy., Design: Cross-sectional study., Setting: Five Portuguese primary care facilities., Participants: We randomly sampled diabetic patients representative of five primary care facilities. Inclusion criteria consisted in patients≥18 years old with an active diagnosis of diabetes mellitus (DM). Patients unable to provide written informed consent were excluded., Outcome Measure: Sociodemographic variables, diabetes duration, type of treatment, medical sharps disposal practices and whether adequate disposal information were provided., Results: A total of 1436 diabetics were included. Overall, 53.8% of diabetics conducted regular capillary glicemia measurements, although 45.3% of them had no medical indication. Statistically significant predictors of adequate disposal were not having an active professional status (p=0.011) and having a DM duration between 5 and 10 years (p=0.014). Only being professionally inactive remained an independent predictor after multivariate logistic regression. Less than a fifth of patients on injectable therapy report having been advised by healthcare staff regarding sharps disposal. Over a fifth of the latter report having received wrong advice. The majority of diabetics dispose of biohazardous materials in unsorted household waste (68.1% of needles/devices with needles and 71.6% of lancets). Other incorrect disposal sites identified were recycling bins, toilet and home accumulation. Only 19.1% of the needles/devices with needles and 13.1% of the lancets were disposed of at healthcare facilities., Conclusions: Most diabetics have unsafe disposal practices for their biohazardous materials, mostly in unsorted household waste. We identified that being unemployed independently predicts adequate disposal of medical sharps and found evidence of low patient literacy on the topic, as well as poor patient education. Therefore, educating and raising awareness among healthcare professionals is crucial to address this public health issue., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The excessive production of pro-inflammatory mediators, characteristic of obesity, leads to neuroinflammation. Zinc (Zn) and the branched-chain amino acids (BCAA) are supplements known for their immunomodulatory properties. Our goal was to evaluate if Zn or BCAA supplementation can affect long-term recognition memory and neuroinflammatory parameters of obese rats after a high-fat diet (HFD). Three-month-old Wistar rats were divided into six groups: Standard diet (SD) + vehicle; SD + Zn; SD + BCAA; High-fat diet (HFD) + vehicle; HFD + Zn; and HFD + BCAA. Diets were administrated for 19 weeks, Zn (1,2 mg/kg/day) or BCAA (750 mg/kg/day) supplementation was conducted in the last 4 weeks. Long-term recognition memory was evaluated by the novel object recognition test. IL-1β immunoreactivity in the cortex and hippocampus, and IL-6 levels in the cortex tissue were assessed. Astrogliosis were evaluated through GFAP + cell count and morphological analysis (Sholl Method). Zn supplementation improved object recognition memory in HFD-fed rats, which was not observed following BCAA supplementation. The levels of IL-6 in the cerebral cortex were higher after HFD, which was not diminished after neither supplementation. Obesity also led to increased IL-1β immunoreactivity in the cerebral cortex and hippocampus, which was reduced by Zn. BCAA supplementation also diminished IL-1β immunoreactivity, but only in the hippocampus. We also showed that astrocyte reactivity caused by HFD is area-dependent, being the cerebral cortex more susceptible to the diet. Even though BCAA and Zn can affect IL-1β immunoreactivity and astrocyte morphology, only Zn improved memory. Future studies are needed to clarify the pathways by which Zn improves cognition in obesity., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The axon initial segment is a specialized compartment of the proximal axon of CNS neurons where action potentials are initiated. However, it remains unknown whether this domain is assembled in sensory dorsal root ganglion neurons, in which spikes are initiated in the peripheral terminals. Here we investigate whether sensory neurons have an axon initial segment and if it contributes to spontaneous activity in neuropathic pain. Our results demonstrate that myelinated dorsal root ganglion neurons assemble an axon initial segment in the proximal region of their stem axon, enriched in the voltage-gated sodium channels Nav1.1 and Nav1.7. Using correlative immunofluorescence and calcium imaging, we demonstrate that the Nav1.7 channels at the axon initial segment are associated with spontaneous activity. Computer simulations further indicate that the axon initial segment plays a key role in the initiation of spontaneous discharges by lowering their voltage threshold. Finally, using a Cre-based mouse model for time-controlled axon initial segment disassembly, we demonstrate that this compartment is a major source of spontaneous discharges causing mechanical allodynia in neuropathic pain. Thus, an axon initial segment domain is present in sensory neurons and facilitates their spontaneous activity. This study provides a new insight in the cellular mechanisms that cause pathological pain and identifies a new potential target for chronic pain management., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Crotoxin complex CA/CB and crotamine are the main toxins associated with Crotalus envenomation besides the enzymatic activities of phospholipases (PLA 2 ) and proteases. The neutralization at least of the crotoxin complex by neutralizing the subunit B could be a key in the production process of antivenoms against crotalids. Therefore, in this work, a Crotoxin B was recombinantly expressed to evaluate its capacity as an immunogen and its ability to produce neutralizing antibodies against crotalid venoms. A Crotoxin B transcript from Crotalus tzabcan was cloned into a pCR ® 2.1-TOPO vector (Invitrogen, Waltham, MA, USA) and subsequently expressed heterologously in bacteria. HisrCrotoxin B was extracted from inclusion bodies and refolded in vitro. The secondary structure of HisrCrotoxin B was comparable to the secondary structure of the native Crotoxin B, and it has PLA 2 activity as the native Crotoxin B. HisrCrotoxin B was used to immunize rabbits, and the obtained antibodies partially inhibited the activity of PLA 2 from C. tzabcan . The anti-HisrCrotoxin B antibodies neutralized the native Crotoxin B and the whole venoms from C. tzabcan, C. s. salvini , and C. mictlantecuhtli. Additionally, anti-HisrCrotoxin B antibodies recognized native Crotoxin B from different Crotalus species, and they could discriminate venom in species with high or low levels of or absence of Crotoxin B.

The antimicrobial and immunomodulatory capacities of the peptide Css54 and the chemokine MCP-1 were tested. The first, a peptide isolated from the venom of the scorpion Centruroides suffusus suffusus was synthesized chemically. In contrast, the second is a monocyte chemoattractant expressed as a recombinant protein in our lab. It was observed in vitro that Css54 inhibited the growth of Salmonella enterica serovar Typhimurium (6.2 µg/mL). At high concentrations, it was toxic to macrophages (25 µg/mL), activated macrophage phagocytosis (1.5 µg/mL), and bound Salmonella LPS (3 µg/mL). On the other hand, the recombinant MCP-1 neither inhibited the growth of Salmonella Typhimurium nor was it toxic to macrophages (up to 25 µg/mL), nor activated macrophage phagocytosis or bound Salmonella LPS (up to 3 µg/mL). Although it was observed in vivo in mice Balb/C that both Css54 and MCP-1 did not resolve the intraperitoneal infection by S. Typhimurium, Css54 decreased the expression of IL-6 and increased IL-10, IL-12p70, and TNF-α levels; meanwhile, MCP-1 decreased the expression of IFN-γ and increased IL-12p70 and TNF-α. It was also observed that the combination of both molecules Css54 and MCP-1 increased the expression of IL-10 and TNF-α.

Cervical and trigeminal afferents innervate neighboring cranial territories, and their convergence on upper cervical dorsal horn neurons provides a potential substrate for pain referral in primary headache syndromes. Lamina I neurons are central to this mechanism, as they relay convergent nociceptive input to supraspinal pain centers. Unfortunately, little is known about the interactions between trigeminal and cervical afferents supplying Lamina I neurons. Here, we used rats of both sexes to show that cervical and trigeminal afferents interact via presynaptic inhibition, where monosynaptic inputs to Lamina I neurons undergo unidirectional as well as reciprocal presynaptic control. This means that afferent-driven presynaptic inhibition shapes the way trigeminal and cervical Aδ-fiber and C-fiber input reaches Lamina I projection neurons (PNs) and local-circuit neurons (LCNs). We propose that this inhibition provides a feedforward control of excitatory drive to Lamina I neurons that regulates their convergent and cervical-specific or trigeminal-specific processing modes. As a consequence, disruption of the trigeminal and cervical afferent-driven presynaptic inhibition may contribute to development of primary headache syndromes. SIGNIFICANCE STATEMENT Cervical and trigeminal afferents innervate neighboring cranial territories, and their convergence on upper cervical dorsal horn neurons provides a potential substrate for pain referral in primary headache syndromes. Lamina I neurons are central to this mechanism as they relay convergent nociceptive input to supraspinal pain centers. Here, we show that cervical and trigeminal afferents interact via presynaptic inhibition, where inputs to Lamina I neurons undergo unidirectional as well as reciprocal control. The afferent-driven presynaptic inhibition shapes the trigeminocervical Aδ-fiber and C-fiber input to Lamina I neurons. This inhibition provides control of excitatory drive to Lamina I neurons that regulates their convergent and cervical-specific or trigeminal-specific processing modes. Disruption of this control may contribute to development of primary headache syndromes., (Copyright © 2022 the authors.)

The transcriptome of the venom glands of the Phoneutria depilata spider was analyzed using RNA-seq with an Illumina protocol, which yielded 86,424 assembled transcripts. A total of 682 transcripts were identified as potentially coding for venom components. Most of the transcripts found were neurotoxins (156) that commonly act on sodium and calcium channels. Nevertheless, transcripts coding for some enzymes (239), growth factors (48), clotting factors (6), and a diuretic hormone (1) were found, which have not been described in this spider genus. Furthermore, an enzymatic characterization of the venom of P. depilata was performed, and the proteomic analysis showed a correlation between active protein bands and protein sequences found in the transcriptome. The transcriptomic analysis of P. depilata venom glands show a deeper description of its protein components, allowing the identification of novel molecules that could lead to the treatment of human diseases, or could be models for developing bioinsecticides.

Regeneration of adult mammalian central nervous system (CNS) axons is abortive, resulting in inability to recover function after CNS lesion, including spinal cord injury (SCI). Here, we show that the spiny mouse (Acomys) is an exception to other mammals, being capable of spontaneous and fast restoration of function after severe SCI, re-establishing hind limb coordination. Remarkably, Acomys assembles a scarless pro-regenerative tissue at the injury site, providing a unique structural continuity of the initial spinal cord geometry. The Acomys SCI site shows robust axon regeneration of multiple tracts, synapse formation, and electrophysiological signal propagation. Transcriptomic analysis of the spinal cord following transcriptome reconstruction revealed that Acomys rewires glycosylation biosynthetic pathways, culminating in a specific pro-regenerative proteoglycan signature at SCI site. Our work uncovers that a glycosylation switch is critical for axon regeneration after SCI and identifies β3gnt7, a crucial enzyme of keratan sulfate biosynthesis, as an enhancer of axon growth., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Abstract: Afferents from the C2 spinal nerve (SN) and trigeminal nerve (TN) innervate neighboring cranial territories, and their convergence on the upper cervical dorsal horn neurons represents neural substrate of pain referral in primary headache disorders. Unfortunately, little is known about trigeminocervical input to the major spinal nociceptive projection area lamina I. Here, we used ex vivo brainstem-cervical cord preparation for the visually guided whole-cell recording from the upper cervical lamina I neurons. We show that 50% of them receive convergent monosynaptic input from both nerves, whereas 35% and 11% of neurons receive specific supply from the C2 SN and TN, respectively. Altogether, 10 distinct patterns of synaptic input from the C2 SN and TN to lamina I neurons could be identified. Although stimulation of both nerves evoked excitatory/inhibitory responses, more numerous pure inhibitory inputs arose from the TN. We show that cervical and trigeminal nociceptors converge on to lamina I projection and inhibitory neurons. Thus, trigeminocervical input in lamina I is processed in both nerve-specific and convergent circuitries. Afferent convergence on to inhibitory interneurons serves as a feedforward mechanism balancing excitatory drive to projection neurons. Disruption of this balance may cause pain in primary headache syndromes., (Copyright © 2021 International Association for the Study of Pain.)

Introduction: Cardiovascular disease is one of the main causes of morbidity and mortality worldwide. Control of its risk factors, particularly diabetes and dyslipidemia, through reduction of LDL cholesterol, is crucial to reduce cardiovascular risk. This work aims to assess and improve the medical approach to dyslipidemia in diabetic patients., Methods: This is a quality improvement study aimed at family doctors. It included patients with diabetics and dyslipidemia enrolled in the primary health care units of Além D'Ouro, S. Miguel and Oceanos. A quality standard was defined for each of the criteria assessed, and the results were compared using the chi-square test with p-value<0.05. Data analysis was performed using Microsoft Excel 2010® and IBM SPSS®., Results: Comparing the first and second assessments, 14.6% vs. 22.2% (p=0.016) of the patients, respectively, achieved the LDL cholesterol target level of <70 mg/dl. Of those who did not meet the target level, 11.0% vs. 13.6% (p=0.395) had their pharmacological therapy changed and 4.6% vs. 3.3% (p=0.448) had their lipid profile reassessed within three months., Conclusions: Control of dyslipidemia in patients with diabetes continues to be a major factor in the health of these patients, but it is carried out in an unsatisfactory way in the three health units studied. It is essential to increase the literacy of family doctors and to encourage the search for the best possible lipid control, in order to reduce cardiovascular risk, as well as to raise awareness among patients to increase adherence to therapy., (Copyright © 2021 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

This study aimed to evaluate the correlation of seminal plasma IGF-I and total proteins from peripubertal bulls with semen characteristics and onset of puberty. Sixteen dairy Gyr bulls were separated into early (n = 8) and regular (n = 8) groups, according to the onset of puberty. Semen was monthly collected by electroejaculation from 14 to 26 months of age, and the onset of puberty was retrospectively determined (17.0 ± 1.6 and 19.2 ± 1.5 months, to early and regular group, respectively). Five time points were evaluated (day -60, day -30, day 0, day 30 and day 60 days of puberty), being day 0 considered as beginning of puberty. Scrotal circumference and body weight were also assessed. Semen characteristics were evaluated, the seminal plasma was separated by centrifugation and total protein and IGF-I concentrations were determined. There was no difference between groups to concentration of the seminal plasma total proteins, but we found an interaction between group and age. Seminal plasma IGF-I concentrations were not different between early and regular groups; thus, the data were combined for analysis. Combined IGF-I concentrations were positively correlated with sperm motility and concentration, age, body weight and scrotal circumference. Negative correlation was found between IGF-I concentration and total sperm defects. Increased IGF-I was observed in day -30 and day 0 of puberty in early and regular groups, respectively. Seminal plasma total proteins are involved in peripubertal modifications and IGF-I from Zebus dairy bulls can influence the seminal characteristics and the growth factor increase occurs concomitantly with body growth but cannot be used to define puberty bulls earlier., (© 2021 Wiley-VCH GmbH.)

The axon initial segment (AIS) is a specialized region in neurons that encompasses two essential functions, the generation of action potentials and the regulation of the axodendritic polarity. The mechanism controlling the position of the axon initial segment to allow plasticity and regulation of neuron excitability is unclear. Here we demonstrate that plasmalogens, the most abundant ether-phospholipid, are essential for the homeostatic positioning of the AIS. Plasmalogen deficiency is a hallmark of Rhizomelic Chondrodysplasia Punctata (RCDP) and Zellweger spectrum disorders, but Alzheimer's and Parkinson's disease, are also characterized by plasmalogen defects. Neurons lacking plasmalogens displaced the AIS to more distal positions and were characterized by reduced excitability. Treatment with a short-chain alkyl glycerol was able to rescue AIS positioning. Plasmalogen deficiency impaired AKT activation, and we show that inhibition of AKT phosphorylation at Ser473 and Thr308 is sufficient to induce a distal relocation of the AIS. Pathway analysis revealed that downstream of AKT, overtly active ULK1 mediates AIS repositioning. Rescuing the impaired AKT signaling pathway was able to normalize AIS position independently of the biochemical defect. These results unveil a previously unknown mechanism that couples the phospholipid composition of the neuronal membrane to the positional assembly of the AIS., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Abstract: Facial injuries caused by motorcycle accidents represent a challenge for reconstructions. Currently, the most indicated treatment for facial fractures is anatomical reduction and internal fixation, however, this procedure is not exempt from complications, such as infection and exposure of osteosynthesis material, thus requiring a new surgical procedure and repair. In this study, the authors describe a case of a 60-year-old woman who was the victim of a motorcycle accident and developed exposure of osteosynthesis material on the nasal dorsum after treatment of facial fractures. The patient underwent surgical treatment with objective of removing the osteosynthesis material and associated infected tissue, as well as reconstruction using a paramedian frontal flap, which resulted in a harmonic relationship and skin color similar to the recipient area. This case shows the importance of anatomical knowledge and reconstructive techniques for hard and soft tissues., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by Mutaz B. Habal, MD.)

Background: There is no epidemiological registry in Mexico. The information about the epidemiology in our country is obtained by these types of studies, such as multicentric studies. A lot of improvements in the survival in non-Hodgkin lymphoma patients had occurred in the last 20 years. The access to treatment in these types of pathology could change the prognostic factors in Mexican Mestizos patients. The primary objective of the study was to learn what the most frequent histological varieties of non-Hodgkin lymphoma in Mexico are. The secondary objectives included clinical characteristics, treatments used, treatment response, disease-free survival and overall survival., Methods: A retrospective, descriptive study of consecutive cases was carried out in 14 hospitals across 14 Mexican states with patients diagnosed with non-Hodgkin lymphoma using the World Health Organization (WHO) 2008 criteria. Inclusion criteria included: ≥ 18 years of age, male or female, any clinical stage at diagnosis, who had received any chemotherapy regimen, with a known outcome. Descriptive statistics was performed for all variables, and survival was assessed using Kaplan-Meier curves., Results: Totally, 609 patients were enrolled, of which 545 were B-cell lymphomas and 64 were T-cell lymphomas. Median ages were 61 and 50, respectively. B-cell lymphomas were more common in males with 52.1%, and 65.5% of T-cell lymphomas occurred in females. For B-cell lymphomas, the two most frequent histological subtypes were diffuse large B-cell lymphoma in 63.9%, followed by follicular lymphoma at 18%. Meanwhile, 50% of T-cell lymphomas were of the T/natural killer (NK) subtype, and 87.1% of the patients received a CHOP-like regimen. Radiotherapy was given to 31% of B-cell Lymphomas and 46.9% of T-cell lymphomas. Overall survival at 9 years was 84.6% for B-cell lymphomas, and 73.4% for T-cell lymphomas., Conclusions: Diffuse large B-cell lymphoma constitutes the most frequent subtype for B-cell lymphomas in Mexico. The most frequent T-cell lymphoma is the NK/T histological subtype., Competing Interests: The authors have no potential conflict of interest to disclose., (Copyright 2021, Hernandez-Ruiz et al.)

Spider venoms include various peptide toxins that modify the ion currents, mainly of excitable insect cells. Consequently, scientific research on spider venoms has revealed a broad range of peptide toxins with different pharmacological properties, even for mammal species. In this work, thirty animal venoms were screened against hK v 1.5, a potential target for atrial fibrillation therapy. The whole venom of the spider Oculicosa supermirabilis , which is also insecticidal to house crickets, caused voltage-gated potassium ion channel modulation in hK v 1.5. Therefore, a peptide from the spider O. supermirabilis venom, named Osu1, was identified through HPLC reverse-phase fractionation. Osu1 displayed similar biological properties as the whole venom; so, the primary sequence of Osu1 was elucidated by both of N-terminal degradation and endoproteolytic cleavage. Based on its primary structure, a gene that codifies for Osu1 was constructed de novo from protein to DNA by reverse translation. A recombinant Osu1 was expressed using a pQE30 vector inside the E. coli SHuffle expression system. recombinant Osu1 had voltage-gated potassium ion channel modulation of human hK v 1.5, and it was also as insecticidal as the native toxin. Due to its novel primary structure, and hypothesized disulfide pairing motif, Osu1 may represent a new family of spider toxins., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer EU declared a past co-authorship with one of the authors GP to the handling editor., (Copyright © 2021 Diana Alvarado, Cardoso-Arenas, Corrales-García, Clement, Arenas, Montero-Dominguez, Olamendi-Portugal, Zamudio, Agota, Borrego, Panyi, Papp and Corzo.)

Presynaptic inhibition of primary afferent terminals is a powerful mechanism for controlling sensory information flow into the spinal cord. Lamina I is the major spinal nociceptive projecting area and monosynaptic input from C-fibers to this region represents a direct pathway for transmitting pain signals to supraspinal centers. Here we used an isolated spinal cord preparation to show that this pathway is under control of the afferent-driven GABAergic presynaptic inhibition. Presynaptic inhibition of C-fiber input to lamina I projection and local-circuit neurons is mediated by recruitment of Aβ-, Aδ- and C-afferents. C-fiber-driven inhibition of C-fibers functions as a feedforward mechanism, by which the homotypic afferents control sensory information flow into the spinal cord and regulate degree of the primary nociceptive afferent activation needed to excite the second order neurons. The presynaptic inhibition of C-fiber input to lamina I neurons may be mediated by both synaptic and non-synaptic mechanisms, and its occurrence and extent are quite heterogeneous. This heterogeneity is likely to be reflective of involvement of lamina I neurons in diverse circuitries processing specific modalities of sensory information in the superficial dorsal horn. Thus, our results implicate both low- and high-threshold afferents in the modulation of C-fiber input into the spinal cord., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

This study aimed to assess the thermal stability of the bioactive compounds from annatto seed extract, encapsulated by ionic gelation using quinoa proteins, lentil proteins, soy proteins, and sodium caseinate as carrying materials. The 10.0% aqueous dispersions of the different proteins (carriers) were prepared and mixed with the annatto seed extract. The dispersions were then extruded into a calcium chloride solution to induce the extract encapsulation. The capsules were characterized by encapsulation efficiency, particle size, infrared transmission spectroscopy, confocal microscopy, and scanning electron microscopy (SEM). The antioxidant and antimicrobial activities, the polyphenol compounds, and bixin content from the free and encapsulated extract were assessed once stored for 12 d at different temperatures (4 °C, 25 °C, and 65 °C). The results demonstrated the ability of the proteins to encapsulate the annatto extract with encapsulation efficiencies ranging from 58% to 80%, where the protein structure and amino acid content were the relevant factors to obtain high encapsulation efficiencies. The free extracts stored at 65 °C for 12 d experienced a degradation of bixin and polyphenol compounds, respectively. Conversely, the encapsulated extract had degradations from ~34.00% to ~4.05% for polyphenol compounds and ~20.0% for bixin, respectively. These proteins have a potential encapsulation capacity of annatto extract by ionic gelation.

At present, expressing antimicrobial peptides in bacterial models is considered a routine lab bench work. However, low expression yields of these types of proteins are usually obtained. In this work, the antimicrobial peptide human β-defensin 2 (HBD2) was obtained in low expression yields in Escherichia coli BL21(DE3). To improve the expression yields of HBD2, some variables such as cell density, temperature, and length of induction, as well as the inducer concentration, were investigated using a 2 4 -factorial design of experiments (DoE). This approach allowed us to identify the identification of critical variables (main effects and interactions among factors) affecting bacterial HBD2 expression. After the evaluation of 19 different combination, the best condition to express HBD2 had a pre-induction temperature of 37 °C, a cell density of 1.0 U (600 nm), an induction temperature of 20 °C and a 0.1 mM of gene expression inducer (IPTG) over four hours. Under such conditions, the expression yield of the HBD2 peptide was one order of magnitude higher than the peptide expression performed initially., (Copyright © 2019 Elsevier Inc. All rights reserved.)

δ-Atracotoxins, also known as δ-hexatoxins, are spider neurotoxic peptides, lethal to both vertebrates and insects. Their mechanism of action involves the binding to of the S3/S4 loop of the domain IV of the voltage-gated sodium channels (Na v ). Because of the chemical difficulties of synthesizing folded synthetic δ-atracotoxins correctly, here we explore an expression system that is designed to produce biologically active recombinant δ-atracotoxins, and a number of variants, in order to establish certain amino acids implicated in the pharmacophore of this lethal neurotoxin. In order to elucidate and verify which amino acid residues play a key role that is toxic to vertebrates and insects, amino acid substitutes were produced by aligning the primary structures of several lethal δ-atracotoxins with those of δ-atracotoxins-Hv1b; a member of the δ-atracotoxin family that has low impact on vertebrates and is not toxic to insects. Our findings corroborate that the substitutions of the amino acid residue Y22 from δ-atracotoxin-Mg1a (Magi4) to K22 in δ-atracotoxin-Hv1b reduces its mammalian activity. Moreover, the substitutions of the amino acid residues Y22 and N26 from δ-atracotoxin-Mg1a (Magi4) to K22 and N26 in δ-atracotoxin-Hv1b reduces its insecticidal activity. Also, the basic residues K4 and R5 are important for keeping such insecticidal activity. Structural models suggest that such residues are clustered onto two bioactive surfaces, which share similar areas, previously reported as bioactive surfaces for scorpion α-toxins. Furthermore, these bioactive surfaces were also found to be similar to those found in related spider and anemone toxins, which affect the same Na v receptor, indicating that these motifs are important not only for scorpion but may be also for animal toxins that affect the S3/S4 loop of the domain IV of the Na v .

The genus Tobravirus comprises three species: Tobacco rattle virus, Pea early-browning virus and Pepper ringspot virus. The genomes of tobraviruses consist of two positive-sense single-stranded RNA segments (RNA1 and RNA2). Infectious clones of TRV are extensively used as virus-induced gene-silencing (VIGS) vectors for studies of virus-host interactions and functions of plant genes. Complete infectious clones of pepper ringspot virus (PepRSV), the only tobravirus present in Brazil, however, have not yet been reported. Infectious clones will help to identify unique features of PepRSV RNA2 and provide another option for development of VIGS vectors. We constructed infectious clones based on two PepRSV isolates, CAM (RNA1 and RNA2) and LAV (RNA2). The cDNA constructs for both homologous (RNA1 and RNA2 of the CAM isolate) and heterologous (RNA1/CAM and RNA2/LAV) combinations were infectious in Nicotiana benthamiana plants. VIGS vector constructs with green fluorescent protein or phytoene desaturase genes inserted in RNA2 silenced the target genes. The systemic translocation of the PepRSV RNA1 construct alone (nonmultiple infection) was also confirmed in an N. benthamiana plant. These results are similar to those reported for tobacco rattle virus.

Bothropic venoms contain enzymes such as metalloproteases, serine-proteases, and phospholipases, which acting by themselves, or in synergism, are the cause of the envenomation symptoms and death. Here, two mRNA transcripts, one that codes for a metalloprotease and another for a serine-protease, were isolated from a Bothrops ammodytoides venom gland. The metalloprotease and serine-protease transcripts were cloned on a pCR ® 2.1-TOPO vector and consequently expressed in a recombinant way in E. coli (strains Origami and M15, respectively), using pQE30 vectors. The recombinant proteins were named rBamSP&#95;1 and rBamMP&#95;1, and they were formed by an N-terminal fusion protein of 16 amino acid residues, followed by the sequence of the mature proteins. After bacterial expression, each recombinant enzyme was recovered from inclusion bodies and treated with chaotropic agents. The experimental molecular masses for rBamSP&#95;1 and rBamMP&#95;1 agreed with their expected theoretical ones, and their secondary structure spectra obtained by circular dichroism were comparable to that of similar proteins. Additionally, equivalent mixtures of rBamSP&#95;1, rBamMP&#95;1 together with a previous reported recombinant phospholipase, rBamPLA2&#95;1, were used to immunize rabbits to produce serum antibodies, which in turn recognized serine-proteases, metalloproteases and PLA2s from B. ammodytoides and other regional viper venoms. Finally, rabbit antibodies neutralized the 3LD50 of B. ammodytoides venom., Competing Interests: The authors declare no conflict of interest.

Nociceptive trigeminal afferents innervating craniofacial area, eg, facial skin and cranial meninges, project to a broad region in the medullary and upper cervical dorsal horn designated as the trigeminocervical complex. Lamina I neurons in the trigeminocervical complex integrate and relay peripheral inputs, thus playing a key role in both cranial nociception and primary headache syndromes. Because of the technically challenging nature of recording, the long-range trigeminal afferent inputs to the medullary and cervical lamina I neurons were not intensively studied so far. Therefore, we have developed an ex vivo brainstem-cervical cord preparation with attached trigeminal nerve for the visually guided whole-cell recordings from the medullary and cervical lamina I neurons. Two-thirds of recorded neurons generated intrinsic rhythmic discharges. The stimulation of the trigeminal nerve produced a complex effect; it interrupted the rhythmic discharge for hundreds of milliseconds but, if the neuron was silenced by a hyperpolarizing current injection, could elicit a discharge. The monosynaptic inputs from the trigeminal Aδ, high-threshold Aδ, low-threshold C, and C afferents were recorded in the medullary neurons, as well as in the cervical neurons located in the segments C1 to C2 and, to a lesser degree, in C3 to C4. This pattern of supply was consistent with our labelling experiments showing extensive cervical projections of trigeminal afferents. Excitatory inputs were mediated, although not exclusively, through AMPA/kainate and NMDA receptors, whereas inhibitory inputs through both GABA and glycine receptors. In conclusion, the trigeminocervical lamina I neurons receive a complex pattern of long-range monosynaptic and polysynaptic inputs from a variety of the trigeminal nociceptive afferents.

Introduction: Several studies have reported that the single nucleotide polymorphism rs693 of Apo lipoprotein B gene is associated with high levels of plasma lipids and high body mass index, which are risk factors for cardiovascular diseases. The distribution of this single nucleotide polymorphism and its association with the phenotype depend on the genetic background of each population., Objective: To evaluate the distribution of single nucleotide polymorphism rs693 and its association with lipid profile and body mass index in a sample of Colombian Caribbeans., Methods: 108 non-related adult subjects of both gender were included in this study. Body mass index and lipid profile that included total cholesterol, triglycerides, Low Density Lipoprotein and High Density Lipoprotein were determined. The single nucleotide polymorphism rs693 was determined by Polymerase Chain Reaction/Restriction Fragment Length Polymorphism from genomic DNA followed by digestion with the restriction enzyme XbaI . The chi-square test was used to analyze the genotype distribution of rs693 and the genotype-phenotype association was evaluated through different inheritance model., Results: The genotype frequencies for single nucleotide polymorphism rs693 were CC (45.0%), TT (16.5%) and CT (38.5%). The allele frequencies were C (64.0%) and T (36.0%). The single nucleotide polymorphism was in Hardy-Weinberg equilibrium in the studied sample. No association of the single nucleotide polymorphism rs693 with lipid profile nor the body mass index was found ( p >0.05)., Conclusion: There is no significant association between single nucleotide polymorphism rs693 and body mass index nor lipid profile, in a sample of Colombian Caribbeans., Competing Interests: Conflict of interests: The authors declare that there is not a conflict of interest., (Copyright © 2019 Universidad del Valle.)

The objective of this study was to analyze the prevalence of vulnerability and associated factors among older people using family health strategies in Várzea Grande, Brazil. A cross-sectional study was performed with 377 community-dwelling older people. The dependent variable, vulnerability, was assessed using the Vulnerable Elders Survey. The independent variables included sociodemographic characteristics and the health status of the study population assessed using the following validated instruments: the Mini-Mental State Examination; Katz ADL scale and Lawton and Brody IADL scale; Geriatric Depression Scale; and Mini Nutritional Assessment Short-Form. Bivariate analysis was conducted using the Mantel-Haenszel chi-squared test with prevalence ratios and multivariate analysis was performed using Poisson regression. The data showed that 49% of the study population were vulnerable. The variables that showed the strongest association with vulnerability were dependence in IADLs (PR = 4.43), presence of depressive symptoms (PR = 1.34), and being aged 80 and over (PR = 1.34). The prevalence of vulnerability found by the present study was high when compared to other studies with community-dwelling older people. The VES-13 was shown to be easy to use in primary healthcare settings and particularly practical for screening vulnerability among older people.

An adsorbent-heater-thermometer nanomaterial, (ZIF-8,Eu x Tb y )@AuNP, based on ZIF-8 (adsorbent), containing Eu 3+ and/or Tb 3+ ions (thermometer) and gold nanoparticles (AuNPs, heater) was designed, synthetized, characterized, and applied to controlled drug release. These composite materials were characterized as core-shell nanocrystals with the AuNPs being the core, around which the crystalline ZIF-8 has grown (shell) and onto which the lanthanide ions have been incorporated or chemosorbed. This shell of ZIF-8 acts as adsorbent of the drugs, the AuNPs act as heaters, while the luminescence intensities of the ligand and the lanthanide ions are used for temperature monitoring. This thermo-responsive material can be activated by visible irradiation to release small molecules in a controlled manner as established for the model pharmaceutical compounds 5-fluorouracil and caffeine. Computer simulations and transition state theory calculations shown that the diffusion of small molecules between neighboring pores in ZIF-8 is severely restricted and involves high-energy barriers. These findings imply that these molecules are uploaded onto and released from the ZIF-8 surface instead of being inside the cavities. This is the first report of ZIF-8 nanocrystals (adsorbents) containing simultaneously lanthanide ions as sensitive nanothermometers and AuNPs as heaters for controlled drug release in a physiological temperature range. These results provide a proof-of-concept that can be applied to other classes of materials, and offer a novel perspective on the design of self-assembly multifunctional thermo-responsive adsorbing materials that are easily prepared and promptly controllable., (Copyright © 2019. Published by Elsevier B.V.)

Nociceptive discharges caused by the unilateral tissue damage are processed in the spinal cord by both ipsi- and contralateral neuronal circuits. The mechanisms of the neurotransmitter control of this bilateral excitation spread is poorly understood. Spinally administered opiates are known to suppress nociceptive transmission and nociceptive withdrawal reflexes. Here we investigated whether three major types of opioid receptors are involved in the bilateral control of the spinal nociceptive sensorimotor processing. Effects of the µ-, δ- and κ-opioid receptor agonists on the ipsi- and contralateral nociceptive reflexes were studied by recording slow ventral root potentials in an isolated spinal cord preparation of the new-born rat. Absolute levels of expression of the opioid genes were analyzed by the droplet digital PCR. Ipsi- and contralateral slow ventral root potentials were most strongly suppressed by the µ-opioid receptor agonist DAMGO, by 63% and 85%, followed by the κ-opioid receptor agonist U-50488H, by 44% and 73%, and δ-opioid receptor agonist leucine-enkephalin, by 27% and 49%, respectively. All these agonists suppressed stronger contra- than ipsilateral responses. Naloxone prevented effects of the agonists indicating that they act through opioid receptors, which, as we show, are expressed in the neonatal spinal cord at the levels similar to those in adults. Thus, opioid receptor agonists suppress the segmental nociceptive reflexes. Stronger contralateral effects suggest that the endogenous opioid system regulates sensorimotor processing in the spinal commissural pathways. These effects of opioids may be relevant for treatment of symmetric clinical pain symptoms caused by unilateral tissue injury., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We show that filamentous fungi can emit green or red light after the accumulation of particulate lanthanide metal-organic frameworks over the cell wall. These new biohybrids present photoluminescence properties that are unaffected by the components of the cell wall. In addition, the fungal cells internalise lanthanide metal-organic framework particles, storing them into organelles, thereby making these materials promising for applications in living imaging studies.

The increasing demand for renewable energy has been promoting a rapid development of photovoltaic technologies. Given this, photoinduced thermal emission is being explored with the aim of improving solar cell performance by converting low-energy IR photons into visible light. Here, we report the light-induced blackbody emission from LnO2 (Ln = Pr and Tb) as a potential emitter for thermophotovoltaic applications. Lanthanide dioxides display broad IR absorption and a direct optical band gap of 1.49 (PrO2) and 1.51 eV (TbO2). These materials achieve a maximum temperature of ∼1500 K under a power density excitation of 160 W cm-2 and display a stable bright light emission. Thermal emission can be tuned from laser power density modulation.

Plants are becoming an interesting alternative system for the heterologous production of pharmaceutical proteins, providing a more scalable, cost-effective, and biologically safer option than the current expression systems. The development of plant virus expression vectors has allowed rapid and high-level transient expression of recombinant genes, and, in turn, provided an attractive plant-based production platform. Here we report the development of vectors based on the tobamovirus Pepper mild mottle virus (PMMoV) to be used in transient expression of foreign genes. In this PMMoV vector, a middle part of the viral coat protein gene was replaced by the green fluorescent protein (GFP) gene, and this recombinant genome was assembled in a binary vector suitable for plant agroinoculation. The accumulation of GFP was evaluated by observation of green fluorescent signals under UV light and by western blotting. Furthermore, by using this vector, the multiepitope gene for chikungunya virus was successfully expressed and confirmed by western blotting. This PMMoV-based vector represents an alternative system for a high-level production of heterologous protein in plants.

Objective: To investigate the presence of central auditory processing disorder symptoms in children with congenital hypothyroidism., Methods: An exploratory, descriptive, cross-sectional study of 112 patients with congenital hypothyroidism aged ≥5 years old. An interview was held with the parents/caregivers at the time of the medical consultation. Patients with other medical conditions were excluded. As a research instrument, the structured protocol of anamnesis was used to evaluate the auditory processing routinely used by audiologists. For statistical analysis, the chi-square test was used., Results: Sex distribution was similar in both boys and girls (girls: 53.3%). The most prevalent phenotypic form of congenital hypothyroidism was no dysgenesis (88.4%), and 65.3% of the children had an episode of irregular serum thyroid-stimulating hormone (TSH) levels. Among the manifestations of the most frequent central auditory processing disorder symptoms, problems were reported with regard to cognitive functions, as they related to hearing, such as figure-background ability (83.0%), auditory attention (75.9%) and auditory memory (33.0%). Complaints related to school performance were reported in 62.3% of the cases., Conclusions: The data obtained show a high frequency of lag symptoms in cognitive functions related to central auditory processing, particularly with regard to auditory attention, figure-background ability and auditory memory in patients with congenital hypothyroidism.

Introduction: In Mexico, seroprevalence of Entamoeba histolytica is 8.4%. The intestinal amebiasis in patients with acute leukemia of novo, after the start of chemotherapy (CT) in the Hematology Service of the CMN 20 de Noviembre is 12%, even if patients show a negative baseline coprological test., Objective: To find out if the administration of tinidazole, in patients with acute leukemia and negative coprological test, at the beginning of the CT, decreases the incidence of amoebic colitis during the induction to remission., Method: Prospective and not comparative study. Patients with de novo diagnosis of acute leukemia who initiate induction and initial coprological CT. Tinidazole was indicated, 2 g/day for 5 days in the first week of CT started. They were monitored until the induction was concluded and hematopoietic recovery started., Results: 38 patients, 15 women and 23 men with a mean age of 44 years (16-72), with acute lymphoblastic leukemia 19, myeloblastic 16 and promyelocytic 3. Cases without and with intestinal amebiasis were 35 and 3, respectively. Patients with amebiasis only received tinidazole for 3 days and it was given 2 days after the CT started., Conclusion: Tinidazole, in patients with acute de novo leukemia who initiate induction CT, is effective in the prevention of intestinal amebiasis, during the induction stage, if administered at 2 g/day, for five days, starting on day 1 of the CT., (Copyright: © 2019 SecretarÍa de Salud.)

Introduction: In Mexico, seroprevalence of Entamoeba histolytica is 8.4%. The intestinal amebiasis in patients with acute leukemia of novo, after the start of chemotherapy (CT) in the Hematology Service of the CMN 20 de Noviembre is 12%, even if patients show a negative baseline coprological test., Objective: To find out if the administration of tinidazole, in patients with acute leukemia and negative coprological test, at the beginning of the CT, decreases the incidence of amoebic colitis during the induction to remission., Method: Prospective and not comparative study. Patients with de novo diagnosis of acute leukemia who initiate induction and initial coprological CT. Tinidazole was indicated, 2 g/day for 5 days in the first week of CT started. They were monitored until the induction was concluded and hematopoietic recovery started., Results: 38 patients, 15 women and 23 men with a mean age of 44 years (16-72), with acute lymphoblastic leukemia 19, myeloblastic 16 and promyelocytic 3. Cases without and with intestinal amebiasis were 35 and 3, respectively. Patients with amebiasis only received tinidazole for 3 days and it was given 2 days after the CT started., Conclusion: Tinidazole, in patients with acute de novo leukemia who initiate induction CT, is effective in the prevention of intestinal amebiasis, during the induction stage, if administered at 2 g/day, for five days, starting on day 1 of the CT., (Copyright: © 2019 Permanyer.)

The dorsal horn of the spinal cord (laminae I-VI) processes diverse modalities of nociceptive and nonnociceptive sensory information. Antenna-type neurons with cell bodies located in lamina III and large dendritic trees extending from the superficial lamina I to deep lamina IV are best shaped for the integration of a wide variety of inputs arising from primary afferent fibers and intrinsic spinal circuitries. Although the somatodendritic morphology, the hallmark of antenna neurons, has been well studied, little is still known about the axon structure and basic physiological properties of these cells. Here, we did whole-cell recordings in a rat (P9-P12) spinal cord preparation with attached dorsal roots to examine the axon course, intrinsic firing properties, and primary afferent inputs of antenna cells. Nine antenna cells were identified from a large sample of biocytin-filled lamina III neurons (n = 46). Axon of antenna cells showed intensive branching in laminae III-IV and, in half of the cases, issued dorsally directed collaterals reaching lamina I. Antenna cells exhibited tonic and rhythmic firing patterns; single spikes were followed by hyperpolarization or depolarization. The neurons received monosynaptic inputs from the low-threshold Aβ afferents, Aδ afferents, as well as from the high-threshold Aδ, and C afferents. When selectively activated, C-fiber-driven monosynaptic and polysynaptic excitatory postsynaptic potentials were sufficiently strong to evoke firing in the neurons. Thus, lamina III antenna neurons integrate low-threshold and nociceptive high-threshold primary afferent inputs and can function as wide dynamic range neurons able to directly connect deep dorsal horn with the major nociceptive projection area lamina I.

Serotonin is implicated in the regulation of seizures, but whether or not it can potentiate the effects of epileptogenic factors is not fully established. Using the kainic acid model of epilepsy in rats, we tested the effects of serotonin depletion on (1) susceptibility to acute seizures, (2) development of spontaneous recurrent seizures and (3) behavioral and neuroanatomical sequelae of kainic acid treatment. Serotonin was depleted by pretreating rats with p-chlorophenylalanine. In different groups, kainic acid was injected at 3 different doses: 6.5mg/kg, 9.0mg/kg or 12.5mg/kg. A single dose of 6.5mg/kg of kainic acid reliably induced status epilepticus in p-chlorophenylalanine-pretreated rats, but not in saline-pretreated rats. The neuroexcitatory effects of kainic acid in the p-chlorophenylalanine-pretreated rats, but not in saline-pretreated rats, were associated with the presence of tonic-clonic convulsions and high lethality. Compared to controls, a greater portion of serotonin-depleted rats showed spontaneous recurrent seizures after kainic acid injections. Loss of hippocampal neurons and spatial memory deficits associated with kainic acid treatment were exacerbated by prior depletion of serotonin. The present findings are of particular importance because they suggest that low serotonin activity may represent one of the major risk factors for epilepsy and, thus, offer potentially relevant targets for prevention of epileptogenesis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The supramolecular nano-aggregate CUR-CB[7] (CUR = curcumin and CB[7] = cucurbit[7]uril) was efficiently prepared by mixing CUR and CB[7] at a molar ratio of 1 : 1 in ethanol at room temperature. The supramolecular aggregate formation was evidenced by mainly FTIR, 1 H NMR, DOSY and spectroscopy experiments. The supramolecular arrangement promotes the increase in the solubility and stability of CUR without affecting the biological properties of the A549 cells. The luminescence properties of CUR and CUR-CB[7] show anti-Kasha's rule fluorescence, and their remarkable NIR emission enables this material to be used as a luminescent probe and marker for in vivo tracking and structural integrity monitoring of the supramolecular complex.