Dehydration stress and Mayaro virus vector competence in Aedes aegypti.

IMPORTANCE: Relative humidity (RH) is an environmental variable that affects mosquito physiology and can impact pathogen transmission. Low RH can induce dehydration in mosquitoes, leading to alterations in physiological and behavioral responses such as blood-feeding and host-seeking behavior. We evaluated the effects of a temporal drop in RH (RH shock) on mortality and Mayaro virus vector competence in Ae. aegypti. While dehydration induced by humidity shock did not impact virus infection, we detected a significant effect of dehydration on mosquito mortality and blood-feeding frequency, which could significantly impact transmission dynamics.

[Late-onset hereditary transthyretin amyloidosis with polyneuropathy. Report of one case]. / Polineuropatía por amiloidosis por transtiretina de inicio tardío. Caso clínico.

Hereditary transthyretin amyloidosis is a multisystemic autosomal dominant genetic disorder characterized by progressive distal sensory-motor polyneuropathy or restrictive cardiomyopathy, secondary to amyloid deposits. Its pathogenesis lies in the TTR gene mutation, and the Val50Met mutation is the most frequent. Patients have significant differences in the onset and severity of clinical presentation according to their country of origin. The diagnosis of this pathology is complex, even more in countries where it is not considered endemic. However, early suspicion and management are essential to improve survival and avoid unnecessary diagnostic and therapeutic strategies. We report a 69-year-old woman who presented a sensory-motor polyneuropathy, predominantly sensory, associated with distal neuropathic pain and bilateral vitritis. The history of her Italian father with polyneuropathy of unspecified etiology stood out. A vitreous biopsy identified amyloid substance deposits (congo red positive). These were also confirmed on a superficial peroneal nerve biopsy. During the etiological study of her polyneuropathy, an increased Kappa/Lambda index of 2.55 mg/L stood out. Therefore, light chain amyloidosis was suspected, and chemotherapy treatment was indicated without favorable response. After 10 years of progressive neurological and ophthalmological involvement, a genetic study confirmed the first case of late-onset hereditary transthyretin amyloidosis Val50Met with polyneuropathy in Chile.

Fronto-Orbital Advance in a Patient With Roberts Syndrome.

Roberts Syndrome is an extremely rare syndrome reporting about 150 cases in the literature, with a very low survival rate. The authors present a case of a female patient with Roberts Syndrome who also had a coronal craniosynostosis. The aim of this case report is to present a case of a patient with Roberts Syndrome with a brachycephaly that required management of fronto-orbital advancement. In conclusion Roberts Syndrome is a rare disease, which can have different skeletal variations. This syndrome can manifest itself with craniosynostosis, with the requirement of a comprehensive management to correct it and avoid compression of the brain with endocranial hypertension.

AL amyloidosis in the Chilean public health system: a pending debt. Multicenter study of the Chilean Monoclonal Gammopathies Cooperative Group.

BACKGROUND: Immunoglobulin light chain (AL) amyloidosis is a rare and underdiagnosed entity. AIM: To characterize patients with AL amyloidosis in Chilean public health centers. MATERIAL AND METHODS: We conducted a retrospective, multicenter study. Public centers of the Chilean Monoclonal Gammopathies Cooperative Group were asked to search for patients with AL amyloidosis in their databases. Epidemiological, clinical and laboratory characteristics were evaluated. RESULTS: Forty-two patients aged 22 to 84 years were found. Twenty four percent had localized AL amyloidosis; 64% had a lambda light chain clone; 47% were associated with multiple myeloma and 9% with non-Hodgkin lymphoma. The most commonly involved organ was the kidney (76%). Serum free light chains were measured in 31% and an echocardiogram was performed in 74% of patients. Seventeen percent of patients received only palliative care, 17% were treated with bortezomib, 21% with thalidomide, and 40% with melphalan. No patient was transplanted. The mean overall survival (OS) of the group was 19 months. The 5-year OS was 28%. CONCLUSIONS: It is important to obtain these realistic, national data to initiate strategies to improve early diagnosis and proper management of this disease.

Determination of volatile compounds in cider apple juices using a covalently bonded ionic liquid coating as the stationary phase in gas chromatography.

A chromatographic method for the separation of volatile compounds in Asturian cider apple juices has been developed. For this separation purpose, a monocationic imidazolium-based ionic liquid bearing a reactive terminal iodine atom was synthesized by a quaternization-anion exchange chemical sequence. Next, the gas chromatography (GC) stationary phase was prepared by covalently linking the imidazolium monolith to the reactive silanol groups of the inner capillary wall at 70 °C. This coated GC column exhibited good thermal stability (290 °C), as well as good efficiency (2000 plates/m) in the separation of volatile compounds from Asturian apple cider juices, and was characterized using the Abraham solvation parameter model. The intra-day and inter-day precision of the chromatographic method was evaluated, obtaining relative standard deviations from 3.7 to 12.9% and from 7.4 to 18.0%, respectively. Furthermore, recoveries from 82.5 to 122% were achieved. Graphical Abstract Covalent bonding of an ionic liquid to inner column wall led to a great improvement of the separation efficiencies of stationary phases in gas chromatography.

Schwann Cell and Axon: An Interlaced Unit-From Action Potential to Phenotype Expression.

Here we propose a model of a peripheral axon with a great deal of autonomy from its cell body-the autonomous axon-but with a substantial dependence on its ensheathing Schwann cell (SC), the axon-SC unit. We review evidence in several fields and show that (i) axons can extend sprouts and grow without the concurrence of the cell body, but regulated by SCs; (ii) axons synthesize their proteins assisted by SCs that supply them with ribosomes and, probably, with mRNAs by way of exosomes; (iii) the molecular organization of the axoplasm, i.e., its phenotype, is regulated by the SC, as illustrated by the axonal microtubular content, which is down-regulated by the SC; and (iv) the axon has a program for self-destruction that is boosted by the SC. The main novelty of this model axon-SC unit is that it breaks with the notion that all proteins of the nerve cell are specified by its own nucleus. The notion of a collaborative specification of the axoplasm by more than one nucleus, which we present here, opens a new dimension in the understanding of the nervous system in health and disease and is also a frame of reference to understand other tissues or cell associations.

Method development and validation study for quantitative determination of nifedipine and related substances by ultra-high-performance liquid chromatography.

A novel stability-indicating reversed phase ultra-high performance liquid chromatography (UPLC) coupled photodiode array gradient method was developed for determination of the nifedipine and related compounds. Furthermore, based on the chromatographic conditions and forced degradation studies performed through the development of the related substances method a UPLC isocratic method was validated for the determination of the assay of this active substance. An Acquity Shield RP18 (50 × 3.0 mm 1.7 µm) column was used for separation of nifedipine and its five potential impurities within 11 min, which is 5-fold less than the official method. A mobile phase consisting of 10 mm ammonium formate (pH 4.5) and methanol, delivered at a flow rate 0.5 mL/min, was employed to achieve a minimum resolution of 2.0 for all consecutive pairs of compounds. The precision value expressed as percentage relative standard deviation for method repeatability and reproducibility was <5.0%. The recoveries for all the related compounds were in the range of 99-105.0%. Linearity was found to be acceptable over the concentration range of 0.25-1.5 µg/mL for nifedipine and its impurities. The limit of quantification for nifedipine was 0.05 µg/mL, which is much less than the European Pharmacopoeia method.

A chemometric approach to characterization of ionic liquids for gas chromatography.

A chemometric study was carried out to characterize three ionic liquid types (ILs) with hexacationic imidazolium, polymeric imidazolium, and phosphonium cationic cores, using a range of contra-anions such as halogens, thiocyanate, boron anions, triflate, and bistriflimide. The solvation parameter model developed by Abraham et al., unsupervised techniques as cluster analysis (CA), and supervised techniques as linear discriminant analysis (LDA), step-LDA, quadratic discriminant analysis (QDA), and multivariate regression techniques as discriminant partial least squares (D-PLS), or multiple linear regression (MLR) were used to characterize the functionalized ILs above. CA established two main groups of phases, those with an acidic H-bond and those with basic ones. Once detected, the two natural groups, a linear and quadratic delimiters with good classification (>96 %) and prediction (>92 %) capacities were computed. The use of step-LDA technique allowed us to establish that a, b, and s solvation parameters were the most discriminant variables. These variables were used for modeling purposes, and a D-PLS and MLR models were constructed using a binary response. The explained variance of categorical variable by the model validated by cross-validation was 65 %, and 94.5 % of ILs were correctly predicted. IL characterization carried out would allow the appropriate selection of phases for gas chromatography (GC).

Temperature affects viral kinetics and vectorial capacity of Aedes aegypti mosquitoes co-infected with Mayaro and Dengue viruses.

BACKGROUND: Increasing global temperatures and unpredictable climatic extremes have contributed to the spread of vector-borne diseases. The mosquito Aedes aegypti is the main vector of multiple arboviruses that negatively impact human health, mostly in low socioeconomic areas of the world. Co-circulation and co-infection of these viruses in humans have been increasingly reported; however, how vectors contribute to this alarming trend remains unclear. METHODS: Here, we examine single and co-infection of Mayaro virus (D strain, Alphavirus) and dengue virus (serotype 2, Flavivirus) in Ae. aegypti adults and cell lines at two constant temperatures, moderate (27 °C) and hot (32 °C), to quantify vector competence and the effect of temperature on infection, dissemination and transmission, including on the degree of interaction between the two viruses. RESULTS: Both viruses were primarily affected by temperature but there was a partial interaction with co-infection. Dengue virus quickly replicates in adult mosquitoes with a tendency for higher titers in co-infected mosquitoes at both temperatures, and mosquito mortality was more severe at higher temperatures in all conditions. For dengue, and to a lesser extent Mayaro, vector competence and vectorial capacity were higher at hotter temperature in co- vs. single infections and was more evident at earlier time points (7 vs. 14 days post infection) for Mayaro. The temperature-dependent phenotype was confirmed in vitro by faster cellular infection and initial replication at higher temperatures for dengue but not for Mayaro virus. CONCLUSIONS: Our study suggests that contrasting kinetics of the two viruses could be related to their intrinsic thermal requirements, where alphaviruses thrive better at lower temperatures compared to flaviviruses. However, more studies are necessary to clarify the role of co-infection at different temperature regimes, including under more natural temperature settings.

Asymmetric synthesis of nonracemic primary amines via spiroborate-catalyzed reduction of pure (E)- and (Z)-O-benzyloximes: applications toward the synthesis of calcimimetic agents.

Highly enantiopure (1-aryl)- and (1-naphthyl)-1-ethylamines were synthesized by the borane-mediated reduction of single-isomeric (E)- and (Z)-O-benzyloxime ethers using the stable spiroborate ester derived from (S)-diphenyl valinol and ethylene glycol as the chiral catalyst. Primary (R)-arylethylamines were prepared by the reduction of pure (Z)-ethanone oxime ethers in up to 99% ee using 15% of catalyst. Two convenient and facile approaches to the synthesis of new and known calcimimetic analogues employing enantiopure (1-naphthalen-1-yl)ethylamine as chiral precursor are described.

Temperature affects viral kinetics and vectorial capacity of Aedes aegypti mosquitoes co-infected with Mayaro and Dengue viruses.

Increasing global temperatures and unpredictable climatic extremes have contributed to the spread of vector-borne diseases. The mosquito Aedes aegypti is the main vector of multiple arboviruses that negatively impact human health, mostly in low socioeconomic areas of the world. Co-circulation and co-infection of these viruses in humans have been increasingly reported; however, how vectors contribute to this alarming trend remains unclear. Here, we examine single and co-infection of Mayaro virus (-D strain, Alphavirus) and dengue virus (serotype 2, Flavivirus) in Ae. aegypti adults and cell lines at two constant temperatures, moderate (27°C) and hot (32°C), to quantify vector competence and the effect of temperature on infection, dissemination and transmission, including on the degree of interaction between the two viruses. Both viruses were primarily affected by temperature but there was a partial interaction with co-infection. Dengue virus quickly replicates in adult mosquitoes, with a tendency for higher titers in co-infected mosquitoes at both temperatures and mosquito mortality was more severe at higher temperatures in all conditions. For dengue, and to a lesser extent Mayaro, vector competence and vectorial capacity were higher at hotter temperature in co- vs single infections and was more evident at earlier timepoints (7 vs 14 days post infection). The temperature-dependent phenotype was confirmed in vitro by faster cellular infection and initial replication at higher temperatures for dengue but not for Mayaro virus. Our study suggests that contrasting kinetics of the two viruses could be related to their intrinsic thermal requirements, where alphaviruses thrive better at lower temperatures compared to flaviviruses, but further studies are necessary to clarify the role of co-infection at different and variable temperature regimes.

Axonal degeneration is mediated by the mitochondrial permeability transition pore.

Axonal degeneration is an active process that has been associated with neurodegenerative conditions triggered by mechanical, metabolic, infectious, toxic, hereditary and inflammatory stimuli. This degenerative process can cause permanent loss of function, so it represents a focus for neuroprotective strategies. Several signaling pathways are implicated in axonal degeneration, but identification of an integrative mechanism for this self-destructive process has remained elusive. Here, we show that rapid axonal degeneration triggered by distinct mechanical and toxic insults is dependent on the activation of the mitochondrial permeability transition pore (mPTP). Both pharmacological and genetic targeting of cyclophilin D, a functional component of the mPTP, protects severed axons and vincristine-treated neurons from axonal degeneration in ex vivo and in vitro mouse and rat model systems. These effects were observed in axons from both the peripheral and central nervous system. Our results suggest that the mPTP is a key effector of axonal degeneration, upon which several independent signaling pathways converge. Since axonal and synapse degeneration are increasingly considered early pathological events in neurodegeneration, our work identifies a potential target for therapeutic intervention in a wide variety of conditions that lead to loss of axons and subsequent functional impairment.

Characterization of hexacationic imidazolium ionic liquids as effective and highly stable gas chromatography stationary phases.

Polycationic ionic liquids (ILs) are an attractive class of ILs with great potential applicability as gas chromatography stationary phases. A family of hexacationic imidazolium ILs derived from the cycloalkanol family was chemically first prepared in a straightforward manner and then applied for analytical separation purposes. Four tuneable engineering vectors, namely cation ring size structure, anion nature, spatial disposition of cycloalkanol substituents and O-substitution, were considered as experimental parameters for the design of the desired ionic liquids. A total number of five new phases based on a common benzene core respectively exhibited column efficiencies around to 2500 plates/m, broad operating temperature ranges and also, even more importantly, good thermal stabilities (bleeding temperature between 260 and 365°C), finding variations in the selectivity and analytes elution orders depending on the IL structures. Their solvation characteristics were evaluated using the Abraham solvation parameter model, establishing clear correlations between their cation structure and retention capability with respect to certain analytes. The study of relationships between the ILs structure and solvation parameters gives us an idea of the IL stationary phase to be used for specific separations.

Relationship between Attention Capacity and Hand-Eye Reaction Time in Adolescents between 15 and 18 Years of Age.

Some experiences demonstrate a direct correlation between attention capacity and reaction capacity. However, the evidence from adolescents enrolled in the Chilean school system is scarce. The purpose of this study was to determine the relationship between attention capacity and hand-eye reaction time (RT) in adolescents between 15 and 18 years of age. Thirty-one adolescents participated voluntarily in this study. The variables were: attention capacity, evaluated through the Evalúa-10 battery (item 1.1), and hand-eye RT, assessed through a simple RT test (SRT) and complex RT (CRT). The relationship between the variables was performed through Pearson's correlation. Comparisons between males and females were performed with the t-test for independent samples (p ˂ 0.05). There was a moderate correlation between attention and CRT (r = -0.43), a very high correlation between attention and SRT in males (r = -0.73), and between attention and CRT in females (r = -0.73). Between males and females, there was no difference in attention (p ˃ 0.05), while males showed better RT in all tests (p ˂ 0.05). Attention positively influences hand-eye RT in both males and females. Likewise, male adolescents present better hand-eye RT than their female peers.

Evaluation of new ionic liquids as high stability selective stationary phases in gas chromatography.

Two ionic liquids (ILs), namely (S,S)-1-butyl-3-(2'-hydroxy-cyclohexyl)-3H-imidazol-1-ium tetrafluoroborate and (S,S)-1-butyl-3-(2'-acetyl-cyclohexyl)-3H-imidazol-1-ium tetrafluoroborate have been employed as stationary phases in capillary gas chromatography. These new phases exhibit a column efficiency of 1,600 and 2,100 plates m(-1) for IL 1 and IL 2, respectively, a wide operating temperature range and good thermal stability (bleeding temperature of 250 °C for IL 1 and 160 °C for IL 2). Inverse gas chromatography (GC) analyses were used to study the solvation properties of these ILs through a linear solvation energy model. The application of these ILs as new GC stationary phases was studied. These stationary phases exhibited unique selectivity for many organic substances, such as alkanes, ketones, esters, and aromatic compounds. The efficient separation of several mixtures containing compounds of different polarities and the good separation of fatty acid methyl esters (FAMEs) and cis/trans isomers indicate that these ILs may be applicable as a new type of GC stationary phases.

Experimental design applied to the analysis of volatile compounds in apple juice by headspace solid-phase microextraction.

A simple and fast method based on solid-phase microextraction (SPME) followed by fast gas chromatography (Fast GC) has been developed for the analysis of volatile compounds in Asturian apple juices employed in the cider production. Three different fiber coatings have been checked (PDMS, PDMS-DVB and CAR-PDMS) and PDMS-DVB has been presented to be the most suitable one. Experimental design has been employed in the optimization of extraction factors and robustness assessment. The use of Fast GC allowed the separation of 14 compounds (esters, aldehydes and alcohols) in approximately 4 min, clearly reducing the analysis time when compared to conventional GC. Good linearity, recoveries and repeatability of the solid-phase microextraction were obtained with r(2) values, recoveries and relative standard deviations ranging from 0.9822 to 0.9998, 83.2 to 109.8% and 0.5 to 11.7%, respectively, using standard solution.

Slow axoplasmic transport under scrutiny.

The origin of axoplasmic proteins is central for the biology of axons. For over fifty years axons have been considered unable to synthesize proteins and that cell bodies supply them with proteins by a slow transport mechanism. To allow for prolonged transport times, proteins were assumed to be stable, i.e., not degraded in axons. These are now textbook notions that configure the slow transport model (STM). The aim of this article is to cast doubts on the validity of STM, as a step toward gaining more understanding about the supply of axoplasmic proteins. First, the stability of axonal proteins claimed by STM has been disproved by experimental evidence. Moreover, the evidence for protein synthesis in axons indicates that the repertoire is extensive and the amount sizeable, which disproves the notion that axons are unable to synthesize proteins and that cell bodies supply most axonal proteins. In turn, axoplasmic protein synthesis gives rise to the metabolic model (MM). We point out a few inconsistencies in STM that MM redresses. Although both models address the supply of proteins to axons, so far they have had no crosstalk. Since proteins underlie every conceivable cellular function, it is necessary to re-evaluate in-depth the origin of axonal proteins. We hope this will shape a novel understanding of the biology of axons, with impact on development and maintenance of axons, nerve repair, axonopathies and plasticity, to mention a few fields.

Temporomandibular joint meniscopexy with Mitek mini anchors.

PURPOSE: The purpose of this study is to show long-term results with the use of Mitek mini anchors (DePuy Mitek, Raynham, MA) in the surgical treatment (meniscopexy or discoplasty) of internal derangements that lead to a dysfunctional temporomandibular joint (TMJ). PATIENTS AND METHODS: We evaluated 50 patients, 32 women and 18 men, ranging in age from 19 to 53 years, with a mean age of 33.5 years. All patients included in the study were diagnosed with anterior disc displacement without reduction. Each patient underwent surgical meniscopexy and placement of Mitek mini anchors with No. 2-0 nylon monofilament sutures. The variables taken into account in this study include range of mouth opening, painful symptoms (evaluated with the visual analog verbal scale), and the presence of any clicks in the TMJ. RESULTS: Preoperative analysis showed painful symptoms in 100% of evaluated patients, the presence of clicks of the TMJ in 76%, and a mean mouth opening range of 23.5 mm. Postoperative analysis showed that 92% of the patients had no painful symptoms, 90% did not have any associated clicks in the TMJ, and the mean mouth opening range on postoperative evaluation was 38.3 mm, with a mean increase of 14.8 mm. CONCLUSIONS: We conclude that surgical placement of Mitek mini anchors represents an alternative that can be considered a tool of great utility for discoplasty procedures, showing evident clinical improvement.