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Introduction: Optisol-GS is the most widely used corneal preservation medium worldwide, there is little evidence to compare it against Eusol-C as a corneal preservation medium. Objectives: To evaluate the viability of endothelial cells between two different corneal preservation media. Materials and Methods: It is a prospective, longitudinal, and comparative study, which was carried out in the eye bank of Hospital General de México “Dr. Eduardo Liceaga”, from where the corneas of suitable donors were collected, the right cornea was preserved in Optisol-GS and the left in Eusol-C. Two evaluations were carried out on day 1 and 5. Endothelial cell density, coefficient of cell variation and hexagonality were analysed. Results: The decrease in endothelial cells on day 5 after collection of the corneoscleral tissue was 8.149% in the corneas stored in Optisol-GS and 7.614% in Eusol-C p=0.006. Cell variation increased 1.634% in Optisol-GS and 8.942% in Eusol-C p=0.948. Cell hexagonality decreased 6.988% in Optisol-GS and 9.480% in Eusol-C p=0.936. Conclusions: No superiority was found when comparing these two media, which shows that Eusol-C is as effective as Optisol-GS for corneal preservation for at least five days.

Objectives: To describe the clinical results of limbal stem cell graft of cadaveric donor in patients with bilateral limbal stem cell deficiency (LSCD). Materials and methods: Prospective, longitudinal and observational study where patients with bilateral LSCD undergoing surgery using cadaveric donor limbal stem cell graft were evaluated. Visual acuity, symblepharon, conjunctivalization, neovascularization, keratinization and corneal opacity were evaluated before and after surgery, with a follow-up to 6 months. We considered a successful treatment with improvement of 4 of 6 criteria. Limbal stem cells graft was obtained from remaining sclerocorneal caps of cadaveric donors, from corneal transplant surgeries. Results: We included 6 patients with bilateral LSCD and 1 patient with unilateral deficiency. The average age was 34.1 (range 16-59 years). The most common etiology was corneal burn (57.14%) followed by Stevens Johnson Syndrome (42.86%). Using the statistical analysis of chi2, no significant difference was observed in visual acuity (p = 0.504), however a significant difference was observed in symblepharon (p = 0.007), neovascularization (p = 0.009), opacity (p = 0.016), conjunctivalization (p = 0.004) and keratinization (p = 0.001) both from baseline to 6 months follow-up. Conclusions: This is a pilot and exploratory study, which analyzes the results of the limbal stem cells graft from cadaveric donors being a successful and reliable technique to improve the ocular surface conditions in bilateral LSCD but not in visual acuity. It could be useful for future studies where the number of patients is expanded and followed up for at least one year.

Este artículo presenta una investigación que tiene como objetivo proponer una mejora en los servicios que brinda una mediana empresa de Tabasco. Buscamos que la empresa brinde flexibilidad en la atención al cliente optimizando los tiempos para lograr la satisfacción del cliente. Para ello, se aplica la metodología ITIL, que permite adecuar los procesos internos con la ayuda de sus cinco fases: estrategia, diseño, transición, operación y mejora continua del servicio. A través de un sistema de ayuda en línea, la empresa automatizará sus técnicas, procesos y procedimientos, incluido el mantenimiento de la competitividad. Todo esto se aplicará a nuestra empresa de estudio.

Recurrent episodes of weakness in periodic paralysis are caused by intermittent loss of muscle fibre excitability, as a consequence of sustained depolarization of the resting potential. Repolarization is favoured by increasing the fibre permeability to potassium. Based on this principle, we tested the efficacy of retigabine, a potassium channel opener, to suppress the loss of force induced by a low-K+ challenge in hypokalaemic periodic paralysis (HypoPP). Retigabine can prevent the episodic loss of force in HypoPP. Knock-in mutant mouse models of HypoPP (Cacna1s p.R528H and Scn4a p.R669H) were used to determine whether pre-treatment with retigabine prevented the loss of force, or post-treatment hastened recovery of force for a low-K+ challenge in an ex vivo contraction assay. Retigabine completely prevents the loss of force induced by a 2 mM K+ challenge (protection) in our mouse models of HypoPP, with 50% inhibitory concentrations of 0.8 ± 0.13 μM and 2.2 ± 0.42 μM for NaV1.4-R669H and CaV1.1-R528H, respectively. In comparison, the effective concentration for the KATP channel opener pinacidil was 10-fold higher. Application of retigabine also reversed the loss of force (rescue) for HypoPP muscle maintained in 2 mM K+. Our findings show that retigabine, a selective agonist of the KV7 family of potassium channels, is effective for the prevention of low-K+ induced attacks of weakness and to enhance recovery from an ongoing loss of force in mouse models of type 1 (Cacna1s) and type 2 (Scn4a) HypoPP. Substantial protection from the loss of force occurred in the low micromolar range, well within the therapeutic window for retigabine.

The dynamic behavior of the interface between the lithium metal electrode and a solid-state electrolyte plays a critical role in all-solid-state battery performance. The evolution of this interface throughout cycling involves multiscale mechanical and chemical heterogeneity at the micro- and nano-scale. These features are dependent on operating conditions such as current density and stack pressure. Here we report the coupling of operando acoustic transmission measurements with nuclear magnetic resonance spectroscopy and magnetic resonance imaging to correlate changes in interfacial mechanics (such as contact loss and crack formation) with the growth of lithium microstructures during cell cycling. Together, the techniques reveal the chemo-mechanical behavior that governs lithium metal and Li7La3Zr2O12 interfacial dynamics at various stack pressure regimes and with voltage polarization.

Initiation of skeletal muscle contraction is triggered by rapid activation of RYR1 channels in response to sarcolemmal depolarization. RYR1 is intracellular and has no voltage-sensing structures, but it is coupled with the voltage-sensing apparatus of CaV1.1 channels to inherit voltage sensitivity. Using an opto-electrophysiological approach, we resolved the excitation-driven molecular events controlling both CaV1.1 and RYR1 activations, reported as fluorescence changes. We discovered that each of the four human CaV1.1 voltage-sensing domains (VSDs) exhibits unique biophysical properties: VSD-I time-dependent properties were similar to ionic current activation kinetics, suggesting a critical role of this voltage sensor in CaV1.1 activation; VSD-II, VSD-III, and VSD-IV displayed faster activation, compatible with kinetics of sarcoplasmic reticulum Ca2+ release. The prominent role of VSD-I in governing CaV1.1 activation was also confirmed using a naturally occurring, charge-neutralizing mutation in VSD-I (R174W). This mutation abolished CaV1.1 current at physiological membrane potentials by impairing VSD-I activation without affecting the other VSDs. Using a structurally relevant allosteric model of CaV activation, which accounted for both time- and voltage-dependent properties of CaV1.1, to predict VSD-pore coupling energies, we found that VSD-I contributed the most energy (~75 meV or ∼3 kT) toward the stabilization of the open states of the channel, with smaller (VSD-IV) or negligible (VSDs II and III) energetic contribution from the other voltage sensors (

Mutations in the voltage sensor domain (VSD) of CaV1.1, the α1S subunit of the L-type calcium channel in skeletal muscle, are an established cause of hypokalemic periodic paralysis (HypoPP). Of the 10 reported mutations, 9 are missense substitutions of outer arginine residues (R1 or R2) in the S4 transmembrane segments of the homologous domain II, III (DIII), or IV. The prevailing view is that R/X mutations create an anomalous ion conduction pathway in the VSD, and this so-called gating pore current is the basis for paradoxical depolarization of the resting potential and weakness in low potassium for HypoPP fibers. Gating pore currents have been observed for four of the five CaV1.1 HypoPP mutant channels studied to date, the one exception being the charge-conserving R897K in R1 of DIII. We tested whether gating pore currents are detectable for the other three HypoPP CaV1.1 mutations in DIII. For the less conserved R1 mutation, R897S, gating pore currents with exceptionally large amplitude were observed, correlating with the severe clinical phenotype of these patients. At the R2 residue, gating pore currents were detected for R900G but not R900S. These findings show that gating pore currents may occur with missense mutations at R1 or R2 in S4 of DIII and that the magnitude of this anomalous inward current is mutation specific.

INTRODUCTION: Latinx college students are at high risk of suffering from depressive symptoms. A factor posited to influence depressive symptoms among Latinx college students is racial/ethnic discrimination. However, the mechanisms which link racial/ethnic discrimination to depressive symptoms are not well understood. This study examined the mediating role of racism-related vigilance and sleep-related factors (i.e., sleep quality, sleep efficiency) on the relationship between perceived intergroup racial/ethnic discrimination and depressive symptoms. METHODS: Participants were 194 Latinx college students enrolled at a Midwestern university designated as a Hispanic-Serving Institution. Path analysis was conducted to investigate whether racism-related vigilance and sleep-related factors (i.e. sleep quality, sleep efficiency) are potential pathways in the relationship between intergroup racial/ethnic discrimination and depressive symptoms. RESULTS: Path analysis revealed that racism-related vigilance and sleep quality sequentially mediated the effect of perceived intergroup racial/ethnic discrimination on depressive symptoms. Sleep efficiency did not mediate the relationship between racial/ethnic discrimination and depressive symptoms. DISCUSSION: This study is among the first to document that intergroup racial/ethnic discrimination is negatively related to mental health through both cognitive and behavioral mechanisms. This research has important implications for understanding how discrimination may influence mental health outcomes among Latinx college students.

A critical race theory framework was used to examine the role of music listening practices in the academic and social contexts of Latino college students enrolled at a predominantly White institution. An inductive thematic analysis examined themes in participants' open-ended responses. Awareness of their Latino identity in music and the use of digital music players served to construct sonic counterspaces, an affirming auditory realm that is comprised of emotional, psychological, and physical space activated through intentional listening practices. Sonic counterspaces facilitated their academic experience and helped them navigate negative social encounters.

The chloride gradient plays an important role in regulating cell volume, membrane potential, pH, secretion, and the reversal potential of inhibitory glycine and GABAA receptors. Measurement of intracellular chloride activity, [Formula: see text], using liquid membrane ion-selective microelectrodes (ISM), however, has been limited by the physiochemical properties of Cl- ionophores which have caused poor stability, drift, sluggish response times, and interference from other biologically relevant anions. Most importantly, intracellular [Formula: see text] may be up to 4 times more abundant than Cl- (e.g. skeletal muscle) which places severe constraints on the required selectivity of a Cl- - sensing ISM. Previously, a sensitive and highly-selective Cl- sensor was developed in a polymeric membrane electrode using a trinuclear Hg(II) complex containing carborane-based ligands, [9]-mercuracarborand-3, or MC3 for short. Here, we have adapted the use of the MC3 anion carrier in a liquid membrane ion-selective microelectrode and show the MC3-ISM has a linear Nernstian response over a wide range of aCl (0.1 mM to 100 mM), is highly selective for Cl- over other biological anions or inhibitors of Cl- transport, and has a 10% to 90% settling  time of 3  sec. Importantly, over the physiological range of aCl (1 mM to 100 mM) the potentiometric response of the MC3-ISM is insensitive to [Formula: see text] or changes in pH. Finally, we demonstrate the biological application of an MC3-ISM by measuring intracellular aCl, and the response to an external Cl-free challenge, for an isolated skeletal muscle fiber.

Periodic paralysis is an ion channelopathy of skeletal muscle in which recurrent episodes of weakness or paralysis are caused by sustained depolarization of the resting potential and thus reduction of fiber excitability. Episodes are often triggered by environmental stresses, such as changes in extracellular K+, cooling, or exercise. Rest after vigorous exercise is the most common trigger for weakness in periodic paralysis, but the mechanism is unknown. Here, we use knock-in mutant mouse models of hypokalemic periodic paralysis (HypoKPP; NaV1.4-R669H or CaV1.1-R528H) and hyperkalemic periodic paralysis (HyperKPP; NaV1.4-M1592V) to investigate whether the coupling between pH and susceptibility to loss of muscle force is a possible contributor to exercise-induced weakness. In both mouse models, acidosis (pH 6.7 in 25% CO2) is mildly protective, but a return to pH 7.4 (5% CO2) unexpectedly elicits a robust loss of force in HypoKPP but not HyperKPP muscle. Prolonged exposure to low pH (tens of minutes) is required to cause susceptibility to post-acidosis loss of force, and the force decrement can be prevented by maneuvers that impede Cl- entry. Based on these data, we propose a mechanism for post-acidosis loss of force wherein the reduced Cl- conductance in acidosis leads to a slow accumulation of myoplasmic Cl- A rapid recovery of both pH and Cl- conductance, in the context of increased [Cl]in/[Cl]out, favors the anomalously depolarized state of the bistable resting potential in HypoKPP muscle, which reduces fiber excitability. This mechanism is consistent with the delayed onset of exercise-induced weakness that occurs with rest after vigorous activity.

ObjectiveTo identify the genetic and physiologic basis for recessive myasthenic congenital myopathy in 2 families, suggestive of a channelopathy involving the sodium channel gene, SCN4A.MethodsA combination of whole exome sequencing and targeted mutation analysis, followed by voltage-clamp studies of mutant sodium channels expressed in fibroblasts (HEK cells) and Xenopus oocytes.ResultsMissense mutations of the same residue in the skeletal muscle sodium channel, R1460 of NaV1.4, were identified in a family and a single patient of Finnish origin (p.R1460Q) and a proband in the United States (p.R1460W). Congenital hypotonia, breathing difficulties, bulbar weakness, and fatigability had recessive inheritance (homozygous p.R1460W or compound heterozygous p.R1460Q and p.R1059X), whereas carriers were either asymptomatic (p.R1460W) or had myotonia (p.R1460Q). Sodium currents conducted by mutant channels showed unusual mixed defects with both loss-of-function (reduced amplitude, hyperpolarized shift of inactivation) and gain-of-function (slower entry and faster recovery from inactivation) changes.ConclusionsNovel mutations in families with myasthenic congenital myopathy have been identified at p.R1460 of the sodium channel. Recessive inheritance, with experimentally established loss-of-function, is a consistent feature of sodium channel based myasthenia, whereas the mixed gain of function for p.R1460 may also cause susceptibility to myotonia.

Although college enrollment rates among Black and Latinx students have risen, inequities in graduation rates across racial and ethnic groups persist. Guided by the integration of strength-based frameworks, the proposed manuscript will discuss how experiential learning and teaching may serve a dual purpose: helping students enact social change while simultaneously reaching their education goals. The proposed manuscript will integrate the culturally engaging campus environments model with the transformative social-emotional learning (T-SEL) framework. Also, drawing from the existing literature, the proposed manuscript will describe a range of experiential learning activities and how they may involve T-SEL. We then conclude with implications for experiential education and future research. Embedding T-SEL in experiential learning may help increase educational equity in ways that are meaningful in the short- and long-run for college students, especially minoritized young adults.

Abstract To evaluate the influence of mitochondrial DNA haplogroups on the risk of knee OA in terms of their interaction with obesity, in a population from Mexico. Samples were obtained from (n = 353) knee OA patients (KL grade ≥ I) and (n = 364) healthy controls (KL grade = 0) from Mexico city and Torreon (Mexico). Both Caucasian and Amerindian mtDNA haplogroups were assigned by single base extension assay. A set of clinical and demographic variables, including obesity status, were considered to perform appropriate statistical approaches, including chi-square contingency tables, regression models and interaction analyses. To ensure the robustness of the predictive model, a statistical cross-validation strategy of B = 1000 iterations was used. All the analyses were performed using boot, GmAMisc and epiR package from R software v4.0.2 and SPSS software v24. The frequency distribution of the mtDNA haplogroups between OA patients and healthy controls for obese and non-obese groups showed the haplogroup A as significantly over-represented in knee OA patients within the obese group (OR 2.23; 95% CI 1.22–4.05; p-value = 0.008). The subsequent logistic regression analysis, including as covariate the interaction between obesity and mtDNA haplogroup A, supported the significant association of this interaction (OR 2.57; 95% CI 1.24–5.32; p-value = 0.011). The statistical cross-validation strategy confirmed the robustness of the regression model. The data presented here indicate a link between obesity in knee OA patients and mtDNA haplogroup A.

This study explored the use of pili nutshells as aggregates and the economic value compared to standard aggregates. It involved observation, experimentation, analysis, and interpretation of data to determine the most appropriate design mixture of pili nutshells in concrete and the compressive strength of concrete using shells to ascertain its suitability as a replacement to aggregates in the production of the concrete mixture. Findings revealed that standard mixture and concrete with 25% pili nutshells replacement as fine aggregates has high workability. However, concrete with 25% pili nutshells replacement as coarse aggregates had medium workability. Furthermore, standard concrete is more economical compared to concrete with pili nutshells as coarse and fine aggregates. Researchers concluded that pili nutshells are more effective as fine aggregates than as coarse aggregates. Further studies on the properties/components of pili nutshells shall be made to determine the necessary treatment before they can be used as aggregates.

Social support is important to well-being, and people with more supportive social networks tend to be healthier. Sexual minorities are generally at risk of worse health outcomes, and as "double minorities," sexual minorities of color are vulnerable to experiences of both homophobia and racism. Yet, we know little about how they navigate their social relationships or how efficacious these relationships are. This study draws from 25 in-depth interviews of Black and Latino/a sexual minority adults, finding that respondents experience conditional social support from their networks. Familial ties are ill-equipped to provide support related to their sexual identity but more equipped to provide support related to racism. Inversely, ties to the LGBTQ community provide support related to sexual identity but impose challenges related to racial identity. Our analysis makes two novel contributions regarding social belonging among sexual minorities of color: First, strong ties and shared identity are not inherently predictive of the accessibility or quality of social support. Second, social integration and isolation are not mutually exclusive but can be experienced simultaneously. Given that social support and community ties can be health protective, this study provides insight into effective community building that meets the comprehensive needs of sexual minorities of color. [ABSTRACT FROM AUTHOR]

An important aspect of the educational process is the language that is utilized as the medium of instruction. It affects both students' and teachers' ability to learn new information efficiently. The transition from mother tongue to English as a medium of instruction brings a variety of obstacles and difficulties among teachers and learners. According to the literature, teachers perform critical roles in any educational program. This study utilized the Husserlian Phenomenology research design in elucidating the lived experiences of teachers during the transition process. Coliazzi's descriptive phenomenology was used in analyzing the participants' experiences. Before collecting data, the researchers utilized bracketing and a purposeful sampling strategy to reduce researcher bias. There were seven (7) participants in this study when the data saturation was reached. The interview was conducted using a semi-structured questionnaire. Based on the data analysis, four emerging themes were extracted: The Gap, The Bridge, The Aftermath, and The Triumph. These themes are evident signs of how teachers managed and survived the transition hurdles. It is recommended for an educational institution to find ways and support teachers to enhance their language teaching skills. [ABSTRACT FROM AUTHOR]

Mutations of CaV1.1, the pore-forming subunit of the L-type Ca2+ channel in skeletal muscle, are an established cause of hypokalemic periodic paralysis (HypoPP). However, functional assessment of HypoPP mutant channels has been hampered by difficulties in achieving sufficient plasma membrane expression in cells that are not of muscle origin. In this study, we show that coexpression of Stac3 dramatically increases the expression of human CaV1.1 (plus α2-δ1b and β1a subunits) at the plasma membrane of Xenopus laevis oocytes. In voltage-clamp studies with the cut-open oocyte clamp, we observe ionic currents on the order of 1 μA and gating charge displacements of ∼0.5-1 nC. Importantly, this high expression level is sufficient to ascertain whether HypoPP mutant channels are leaky because of missense mutations at arginine residues in S4 segments of the voltage sensor domains. We show that R528H and R528G in S4 of domain II both support gating pore currents, but unlike other R/H HypoPP mutations, R528H does not conduct protons. Stac3-enhanced membrane expression of CaV1.1 in oocytes increases the throughput for functional studies of disease-associated mutations and is a new platform for investigating the voltage-dependent properties of CaV1.1 without the complexity of the transverse tubule network in skeletal muscle.