Oral administration of a recombinant modified RBD antigen of SARS-CoV-2 as a possible immunostimulant for the care of COVID-19.

BACKGROUND: Developing effective vaccines against SARS-CoV-2 that consider manufacturing limitations, equitable access, and acceptance is necessary for developing platforms to produce antigens that can be efficiently presented for generating neutralizing antibodies and as a model for new vaccines. RESULTS: This work presents the development of an applicable technology through the oral administration of the SARS-CoV-2 RBD antigen fused with a peptide to improve its antigenic presentation. We focused on the development and production of the recombinant receptor binding domain (RBD) produced in E. coli modified with the addition of amino acids extension designed to improve antigen presentation. The production was carried out in shake flask and bioreactor cultures, obtaining around 200 mg/L of the antigen. The peptide-fused RBD and peptide-free RBD proteins were characterized and compared using SDS-PAGE gel, high-performance chromatography, and circular dichroism. The peptide-fused RBD was formulated in an oil-in-water emulsion for oral mice immunization. The peptide-fused RBD, compared to RBD, induced robust IgG production in mice, capable of recognizing the recombinant RBD in Enzyme-linked immunosorbent assays. In addition, the peptide-fused RBD generated neutralizing antibodies in the sera of the dosed mice. The formulation showed no reactive episodes and no changes in temperature or vomiting. CONCLUSIONS: Our study demonstrated the effectiveness of the designed peptide added to the RBD to improve antigen immunostimulation by oral administration.

Giant corneal keloid following Descemet stripping automated endothelial keratoplasty for the treatment of corneal decompensation secondary to trauma.

PURPOSE: This report aims to present a case of corneal keloid caused by chronic corneal insult after trauma and Descemet stripping automated endothelial keratoplasty (DSAEK). CASE PRESENTATION: A 35-year-old male with a history of vision loss in the right eye was referred to our hospital. The patient underwent Ahmed Glaucoma Valve Implantation to alleviate elevated intraocular pressure after ocular trauma to the same eye. One year following the procedure, the eye developed endothelial failure, leading to the performance of Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK) with repositioning of the shunt tube. Upon initial examination, a well-circumscribed elevated white opaque lesion involving the central corneal surface of the RE was observed. Based on the patient's clinical history, slit lamp examination, and UBM findings, the diagnosis of corneal keloid was established. Superficial keratectomy was performed. Histopathological analysis confirmed the diagnosis of corneal keloid. Following the procedure, BCVA improved slightly. However, 3 months later, the patient underwent a penetrating keratoplasty for visual rehabilitation. CONCLUSION: Corneal keloids should be considered following any form of ocular trauma, particularly in cases involving ocular surgery. Diagnosing corneal keloids can sometimes be challenging due to the variety of potential differentials; however, by carefully evaluating the patient's medical history and clinical presentation, we can effectively narrow down the differential diagnosis of corneal conditions.

Attitudes About the Human Papillomavirus Vaccine Among Patients With and Without Cervical Dysplasia.

OBJECTIVES: The aims of the study are to examine the perception of the human papillomavirus (HPV) vaccine among those with and without a history of cervical dysplasia and to examine perceptions of the vaccine for their children. MATERIALS AND METHODS: Patients were recruited to complete a survey about the HPV vaccine for both themselves and their children. Patients in a colposcopy clinic with a history of abnormal cervical cytology and patients in a benign gynecology clinic without a history of abnormal cervical cytology were recruited. Participants' medical records were reviewed. Demographics and survey answers were described, and Fisher exact test was used to compare the groups. RESULTS: One hundred eighty-three patients participated: 73 in colposcopy clinic and 110 in benign clinic. The majority self-identified as Black (74% colposcopy, 71% benign, p = .588) and reported an income less than $39,000 a year (77% colposcopy, 65% benign, p = .089). Fifty-six percent in benign clinic agreed the HPV vaccine is a good way to protect oneself from disease compared with 48% in colposcopy clinic ( p = .022). When examining results based on cytology, fewer patients in the highest-grade cytology group agreed the vaccine was effective (30% high-grade, 48% normal, 57% low-grade, p = .027) or a good way to protect themselves from disease (29% high-grade, 53% normal, 62% low-grade, p = .002). There was otherwise no statistically significant difference between the groups on questions regarding self or child vaccination. CONCLUSIONS: In a majority Black, low-income population, patients without a history of abnormal cervical cytology have more favorable perceptions of the HPV vaccine's effectiveness in preventing disease. Those with the highest-grade cytology had more negative perceptions of the vaccine's effectiveness and protectability.

Effect of Sargassum on the Behavior and Survival of the Earthworm Eisenia Fetida.

The massive influx of Sargassum natans and S. fluitans to the shores of the Mexican Caribbean has raised concerns regarding their potential impact on soil quality and health in coastal and agroecosystems. The effects of Sargassum accumulation remain largely unexplored. This study aimed to assess the impact of Sargassum on soil ecosystems by examining the behavior and survival of the epigean earthworm Eisenia fetida. The earthworm was exposed to varying concentrations of Sargassum (0, 25, 50, 75, and 100%) in two toxicological tests. Results from the avoidance test demonstrated that E. fetida exhibited strong aversion (> 80%) to a diet containing 100% Sargassum. Conversely, the acute test revealed minimal mortality, but growth decreased with increasing Sargassum concentrations. These findings can serve as early warning bioindicators for assessing the environmental risk posed by Sargassum in soil ecosystems.

Don't Miss Me: Midfoot Sprains, A Point-of-Care Review.

Athletes practicing high-contact sports are exposed to an increased risk of midfoot injuries, namely midtarsal sprains. The complexity of reaching an accurate diagnosis is clearly depicted in the reported incidence of midtarsal sprains, ranging from 5% to 33% of ankle inversion injuries. Because the focus of the treating physician and physical therapist is on lateral stabilizing structures, midtarsal sprains are missed at initial evaluation in up to 41% of patients, with delayed treatment as a result.Detecting acute midtarsal sprains requires a high degree of clinical awareness. Radiologists must become familiar with the characteristic imaging findings of normal and pathologic midfoot anatomy to avoid adverse outcomes such as pain and instability. In this article we describe Chopart joint anatomy, mechanisms of midtarsal sprains, clinical importance, and key imaging findings with a focus on magnetic resonance imaging. A team effort is essential to provide optimal care for the injured athlete.

Concomitant Bandage Contact Lens, Oral Nicergoline, and Topical Autologous Serum for Severe Neurotrophic Keratitis.

BACKGROUND: To report the outcomes of using the combination of oral nicergoline, autologous serum, and contact lens to enhance corneal epithelization in neurotrophic keratitis and to discuss the clinical potential of this management. METHODS: This was a prospective consecutive case series study of eight patients treated for neurotrophic keratitis at the "Conde de Valenciana" Institute of Ophthalmology. Oral nicergoline, autologous serum, and bandage contact lens were initiated at the same time, immediately after stage 3 diagnosis keratitis was confirmed clinically, and until corneal epithelialization was achieved or eminent corneal perforation was seen. In patients where diabetes was a cause, glycosylate hemoglobin was measured to asses metabolic control. Corneal esthesiometry and corrected distance visual acuity were assessed before and after treatment. RESULTS: This study included eight eyes of eight patients (5 men [62.5%], average age 57±17.9 years). All patients completed at least 1 month of follow-up after nicergoline and contact lens suspension. Of the eight eyes, no one had positive culture growth and complete epithelial healing was achieved in all cases. Half of patients had diabetes and had a poor metabolic control. Corneal sensitivity improved in all eyes almost 2 centimeters in Cochet-Bonnet esthesiometry ( P= 0.01). In addition, final visual acuity gains were obtained ( P= 0.100). CONCLUSIONS: The combination of oral nicergoline, autologous serum, and bandage contact lens simultaneously could be an alternative in the management of stage 3 neurotrophic keratitis when conventional medical treatment has no improvement of corneal epithelization.

Structural and Physicochemical Properties of Starch from Rejected Chestnut: Hydrothermal and High-Pressure Processing Dependence.

The quality standards for the export of chestnuts generate large quantities of rejected fruits, which require novel processing technologies for their safe industrial utilization. This study aimed to investigate the impact of high-pressure processing (HPP) and hydrothermal treatments (HT) on the physicochemical properties of rejected chestnut starch. Chestnuts were treated by HPP at 400, 500, and 600 MPa for 5 min and HT at 50 °C for 45 min. In general, all HPP treatments did not induce starch gelatinization, and their granules preserved the integrity and Maltese-cross. Moreover, starch granules' size and resistant starch content increased with the intensity of pressure. Native and HT chestnut starches were the most susceptible to digestion. HPP treatments did not affect the C-type crystalline pattern of native starch, but the crystalline region was gradually modified to become amorphous. HPP-600 MPa treated starch showed modified pasting properties and exhibited the highest values of peak viscosity. This study demonstrates for the first time that after HPP-600 MPa treatment, a novel chestnut starch gel structure is obtained. Moreover, HPP treatments could increase the slow-digesting starch, which benefits the development of healthier products. HPP can be considered an interesting technology to obtain added-value starch from rejected chestnut fruits.

Ophthalmic findings in patients with autosomal recessive lamellar ichthyosis due to TGM1 mutations in an isolated population.

PURPOSE: To describe the ocular clinical characteristics of a group of Mexican patients with lamellar ichthyosis (LI) arising from TGM1 pathogenic variants. METHODS: Ophthalmological exploration, pedigree analysis and genetic screening were performed in patients with an established clinical diagnosis of lamellar ichthyosis from families located in a small community in the Southeast of Mexico. RESULTS: Nine patients with LI in five families were identified. There were six affected females. All patients (9/9) demonstrated eye lid abnormalities with eight patients showing lid margin abnormalities. Madarosis was present in only three individuals and corneal scarring was documented in two. All nine individuals carried biallelic TGM1 variants, either homozygously or as compound heterozygous. CONCLUSION: Ocular anomalies are common in individuals with TGM1-related LI. The occurrence of a variety of private or rare mutations hampers the identification of a genotype-phenotype correlation for ocular anomalies in this disorder.

A novel homozygous ZNF469 variant causing brittle cornea syndrome is associated with corneal ectasias in heterozygous carriers.

AIM: To describe a family segregating a novel truncating ZNF469 homozygous mutation causing brittle cornea syndrome type 1 in a male patient and associated with corneal ectasia in his two heterozygous young children. METHODS: A 49-year-old affected male and his 12- and 8-year-old, apparently healthy, siblings underwent phenotypic and genetic assessment. An Oculus Pentacam Scheimpflug topographer system was employed for keratometries and central corneal thickness measurements. Exome sequencing was performed in DNA from the index case with subsequent Sanger sequencing confirmation of the ZNF469 gene causal variant in his relatives. RESULTS: The index case had a history of bilateral keratoglobus, corneal perforations, bilateral hypoacusia, and skeletal anomalies. His two children exhibited topographic anomalies compatible with keratoconus suspects as well as mild skeletal anomalies. Genetic analysis identified a novel homozygous c.2340delC variant in the ZNF469 gene, which predicts a p.(Arg781Glufs*19) truncated protein. Sanger sequencing identified heterozygosity for the c.2340delC variant in DNA from both siblings. CONCLUSION: Our results expand the mutational spectrum associated with brittle cornea syndrome and provide the first demonstration of early corneal anomalies in subjects carrying monoallelic ZNF469 variants.

Results of one decade of optical keratoplasty in pediatric patients.

BACKGROUND: Keratoplasty in the pediatric population has been considered a high-risk procedure. OBJECTIVE: To know the demographic data of patients younger than 18 years treated with optical keratoplasty, indications for surgery and its results. MATERIAL AND METHODS: A retrospective study was carried out at Conde de Valenciana Ophthalmology Institute, in which the medical records of patients younger than 18 years treated with optical keratoplasty from 2009 to 2019 were analyzed. RESULTS: A total of 53 eyes were included. The most common diagnosis and procedure were keratoconus and penetrating keratoplasty, respectively. Mean initial visual acuity was 2.05 ± 0.99 logMAR, and 0.82 ± 1.33 at last visit. Survival time was 130.34 months. Four failures were recorded. As for associated surgeries, corneal wound closure was recorded in seven eyes prior to transplant; during the keratoplasty procedure, anterior vitrectomy in two eyes, and after the transplant, Ahmed valve implantation and re-suture. A total of eight eyes had glaucoma, five of them diagnosed prior to transplantation. Regarding rejection, 15 eyes had an episode during follow-up, and mean time to transplant rejection was 10.8 months. CONCLUSION: Prolonged graft survival can be achieved with better knowledge and management of different associated factors.

ANTECEDENTES: La queratoplastia en población pediátrica ha sido considerada un procedimiento de alto riesgo. OBJETIVO: Conocer datos demográficos de pacientes menores de 18 años tratados con queratoplastia óptica, indicaciones de la cirugía y sus resultados. MATERIAL Y MÉTODOS: Se realizó un estudio retrospectivo en el Instituto de Oftalmología Conde de Valenciana, en el que se revisaron expedientes de pacientes menores de 18 años tratados con queratoplastia óptica de 2009 a 2019. RESULTADOS: Un total de 53 ojos fueron incluidos. El diagnóstico y el procedimiento más comunes fueron el queratocono y la queratoplastia penetrante. El promedio de agudeza visual inicial fue de 2.05 ± 0.99 logMAR y en la última visita, 0.82 ± 1.33. El tiempo de supervivencia del injerto fue de 130.34 meses. Se registraron cuatro fallas. En cuanto a las cirugías asociadas, antes del trasplante se registró cierre de herida corneal en siete ojos y durante la queratoplastia, vitrectomía anterior en dos ojos y después del trasplante, implante de válvula de Ahmed y resutura. Un total de ocho ojos tuvieron glaucoma, cinco con diagnóstico antes del trasplante. Respecto al rechazo, 15 ojos tuvieron un episodio durante el seguimiento y el tiempo promedio de rechazo al trasplante fue de 10.8 meses. CONCLUSIÓN: Se puede lograr una supervivencia prolongada del injerto con el mejor conocimiento y manejo de los diferentes factores asociados.

Visual impairment associated with diabetic retinopathy and macular edema: a hospital-based study.

BACKGROUND: Data on visual impairment (VI) in patients with diabetes are necessary in order to guide economic and human resources for reducing its prevalence. OBJECTIVE: To estimate the prevalence of diabetic retinopathy-related VI in patients with type 2 diabetes in a hospital-based setting. MATERIAL AND METHODS: Cross-sectional study carried out from 2014 to 2019 in an ophthalmology outpatient clinic. Any VI was defined as corrected pin-hole visual acuity in the better eye of ≥ 0.24 logMAR. The presence of diabetic retinopathy (DR), diabetic macular edema (DME) and cataract was evaluated. RESULTS: A total of 840 patients were included; median diabetes duration was 15 years. The prevalence of VI was 30%. DR was found in 62% of patients (30% had sight-threatening DR [STDR]), 17% had referable DME, and 3%, cataracts. The odds ratio for moderate or worse VI was 9.02 for STDR (p < 0.001), 5.89 for referable DME (p = 0.001), and 2.51 for cataract (p = 0.006). CONCLUSION: Thirty percent of participants had some degree of VI. Moderate or worse VI showed a strong association with STDR and referable DME.

ANTECEDENTES: Los datos sobre discapacidad visual (DV) en pacientes con diabetes son necesarios para orientar los recursos económicos y humanos que disminuyan su prevalencia. OBJETIVO: Estimar la prevalencia de DV relacionada con retinopatía diabética en pacientes con diabetes tipo 2 en un entorno hospitalario. MATERIAL Y MÉTODOS: Estudio transversal realizado de 2014 a 2019 en una consulta externa de oftalmología. Cualquier DV se definió como agudeza visual corregida con agujero estenopeico en el ojo con mejor visión (≥ 0.24 logMAR). Se evaluó la presencia de retinopatía diabética, edema macular diabético (EMD) y cataratas. RESULTADOS: Se incluyeron 840 pacientes; la mediana de duración de la diabetes fue de 15 años. La prevalencia de DV fue de 30 %. Se encontró retinopatía diabética en 62 % (30 % tenía retinopatía diabética que amenazaba la visión [RDAV]); 17 %, EMD y 3 %, cataratas. La razón de momios para DV moderada o de mayor gravedad fue de 9.02 para RDAV (p < 0.001), 5.89 para EMD referible (p = 0.001) y 2.51 para catarata (p = 0.006). CONCLUSIÓN: Treinta por ciento de los participantes tenía algún grado de DV. La DV moderada o de mayor gravedad mostró una fuerte asociación con RDAV y EMD referible.

Policies Restricting Overlapping Surgeries Negatively Impact Access to Care, Clinical Efficiency, and Hospital Revenue: A Forecasting Model for Surgical Scheduling.

OBJECTIVE: To model the financial impact of policies governing the scheduling of overlapping surgeries, and to identify optimal solutions that maximize operating efficiency that satisfy the fiduciary duty to patients. BACKGROUND: Hospitals depend on procedural revenue to maintain financial health as the recent pandemic has revealed. Proposed policies governing the scheduling of overlapping surgeries may dramatically impact hospital revenue. To date, the potential financial impact has not been modeled. METHODS: A linear forecasting model based on a logic matrix decision tree enabled an analysis of surgeon productivity annualized over a fiscal year. The model applies procedural and operational variables to policy constraints limiting surgical scheduling. Model outputs included case and financial metrics modeled over 1000-surgeon-year simulations. case metrics included annual case volume, case mix, operating room (OR) utilization, surgeon utilization, idle time, and staff overtime hours. Financial outputs included annual revenue, expenses, and contribution margin. RESULTS: The model was validated against surgical data. case and financial metrics decreased as a function of increasingly restrictive scheduling scenarios, with the greatest contribution margin loses ($1,650,000 per surgeon-year) realized with the introduction of policies mandating that a second patient could not enter the OR until the critical portion of the first surgery was completed. We identify an optimal scheduling scenario that maximizes surgeon efficiency, minimizes OR idle time and revenue loses, and satisfies ethical obligations to patients. CONCLUSIONS: Hospitals may expect significant financial loses with the introduction of policies restricting OR scheduling. We identify an optimal solution that maximizes efficiency while satisfying ethical duty to patients. This forecast is immediately relevant to any hospital system that depends upon procedural revenue.

Development of a text message-based intervention for follow-up colposcopy among predominately underserved Black and Hispanic/Latinx women.

PURPOSE: Underserved Black and Hispanic/Latinx women show low rates of follow-up care after an abnormal Pap test, despite the fact that cervical cancer is one of the few preventable cancers if detected early. However, extant literature falls short on efficacious interventions to increase follow-up for this population. A concurrent mixed methods study was completed to evaluate the acceptability of a text message-based intervention and identify perceived barriers and facilitators to follow-up after an abnormal Pap test among underserved predominantly Black and Hispanic/Latinx women. METHODS: Patients who completed follow-up for an abnormal Pap test were recruited to complete a cross-sectional survey, qualitative interview assessing barriers and facilitators to follow-up, and text message content evaluation (N = 28). Descriptive statistics were performed to describe background variables and to evaluate the acceptability of text messages. A directed content analysis was completed for the qualitative interviews. RESULTS: Participants expressed interest in a text message-based intervention to increase abnormal Pap test follow-up. In the qualitative interviews, low knowledge about cervical risk and negative affect toward colposcopy/test results were identified as barriers to follow-up. Facilitators of follow-up included feeling relieved after the colposcopy and adequate social support. Participants rated the text messages as understandable, personally relevant, and culturally appropriate. CONCLUSION: The findings suggest that underserved Black and Hispanic/Latinx women experience cognitive and emotional barriers that undermine their ability to obtain follow-up care and a text message-based intervention may help women overcome these barriers. Future research should develop and evaluate text message-based interventions to enhance follow-up after an abnormal Pap test.

Discrete field potentials produced by coherent activation of spinal dorsal horn neurons.

In addition to the action potentials generated by the ongoing activation of single dorsal horn neurons in the anesthetized cat, we often recorded small negative field potentials with a fast-rising phase and a slow decay (dIFPs). These potentials could be separated in different classes, each with a specific and rather constant shape and amplitude. They were largest in spinal laminae III-V and gradually faded at deeper locations, without showing the polarity reversal displayed at these depths by the focal potentials produced by stimulation of muscle and cutaneous afferents. We propose that the dIFPs are postsynaptic field potentials generated by strongly coupled sets of dorsal horn neurons displaying a spatial orientation that generates closed field potentials in response to stimulation of high-threshold cutaneous and muscle afferents. These neuronal sets could form part of the spinal inhibitory circuitry that mediates presynaptic inhibition and Ib non-reciprocal postsynaptic inhibition and could be involved in the sensory-motor transformations activated by stimulation of high-threshold cutaneous afferents.

The pre-induction temperature affects recombinant HuGM-CSF aggregation in thermoinducible Escherichia coli.

The overproduction of recombinant proteins in Escherichia coli leads to insoluble aggregates of proteins called inclusion bodies (IBs). IBs are considered dynamic entities that harbor high percentages of the recombinant protein, which can be found in different conformational states. The production conditions influence the properties of IBs and recombinant protein recovery and solubilization. The E. coli growth in thermoinduced systems is generally carried out at 30 °C and then recombinant protein production at 42 °C. Since the heat shock response in E. coli is triggered above 34 °C, the synthesis of heat shock proteins can modify the yields of the recombinant protein and the structural quality of IBs. The objective of this work was to evaluate the effect of different pre-induction temperatures (30 and 34 °C) on the growth of E. coli W3110 producing the human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) and on the IBs structure in a λpL/pR-cI857 thermoinducible system. The recombinant E. coli cultures growing at 34 °C showed a ~ 69% increase in the specific growth rate compared to cultures grown at 30 °C. The amount of rHuGM-CSF in IBs was significantly higher in cultures grown at 34 °C. Main folding chaperones (DnaK and GroEL) were associated with IBs and their co-chaperones (DnaJ and GroES) with the soluble protein fraction. Finally, IBs from cultures that grew at 34 °C had a lower content of amyloid-like structure and were more sensitive to proteolytic degradation than IBs obtained from cultures at 30 °C. Our study presents evidence that increasing the pre-induction temperature in a thermoinduced system allows obtaining higher recombinant protein and reducing amyloid contents of the IBs. KEY POINTS: • Pre-induction temperature determines inclusion bodies architecture • In pre-induction (above 34 °C), the heat shock response increases recombinant protein production • Inclusion bodies at higher pre-induction temperature show a lower amyloid content.

Energetic and structural effects of the Tanford transition on ligand recognition of bovine ß-lactoglobulin.

Bovine ß-lactoglobulin, an abundant protein in whey, is a promising nanocarrier for peroral administration of drug-like hydrophobic molecules, a process that involves transit through the different acidic conditions of the human digestive tract. Among the several pH-induced conformational rearrangements that this lipocalin undergoes, the Tanford transition is particularly relevant. This transition, which occurs with a midpoint around neutral pH, involves a conformational change of the E-F loop that regulates accessibility to the primary binding site. The effect of this transition on the ligand binding properties of this protein has scarcely been explored. In this study, we carried out an energetic and structural characterization of ß-lactoglobulin molecular recognition at pH values above and below the zone in which the Tanford transition occurs. The combined analysis of crystallographic, calorimetric, and molecular dynamics data sheds new light on the interplay between self-association, ligand binding, and the Tanford pre- and post-transition conformational states, revealing novel aspects underlying the molecular recognition mechanism of this enigmatic lipocalin.

Integrative overview of antibodies against SARS-CoV-2 and their possible applications in COVID-19 prophylaxis and treatment.

SARS-CoV-2 is a novel ß-coronavirus that caused the COVID-19 pandemic disease, which spread rapidly, infecting more than 134 million people, and killing almost 2.9 million thus far. Based on the urgent need for therapeutic and prophylactic strategies, the identification and characterization of antibodies has been accelerated, since they have been fundamental in treating other viral diseases. Here, we summarized in an integrative manner the present understanding of the immune response and physiopathology caused by SARS-CoV-2, including the activation of the humoral immune response in SARS-CoV-2 infection and therefore, the synthesis of antibodies. Furthermore, we also discussed about the antibodies that can be generated in COVID-19 convalescent sera and their associated clinical studies, including a detailed characterization of a variety of human antibodies and identification of antibodies from other sources, which have powerful neutralizing capacities. Accordingly, the development of effective treatments to mitigate COVID-19 is expected. Finally, we reviewed the challenges faced in producing potential therapeutic antibodies and nanobodies by cell factories at an industrial level while ensuring their quality, efficacy, and safety.

Association between the TAP1 gene polymorphisms and recurrent respiratory papillomatosis in patients from Western Mexico: A pilot study.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a respiratory tract disease that affects children and adults and is characterized by the recurrent proliferation of multiple papillomas. The etiologic agent is the human papillomavirus, mainly genotypes 6 and 11. Furthermore, polymorphisms in TAP1 appear to influence the selection of antigenic peptides and the transport process to the rough endoplasmic reticulum, for their subsequent presentation to T lymphocytes, an essential process against viral diseases and tumor processes. Previous studies have shown that individuals with those polymorphisms are susceptible to immune, infectious, and tumor-related diseases. The present study aimed to determine the association between the TAP1 rs1057141 (c.1177A>G) and rs1135216 (c.2090A>G) single nucleotide polymorphisms (SNPs) and RRP. METHODS: A case-control study was carried out on a group of 70 individuals (35 controls and 35 patients). RRP diagnosis, HPV genotyping, and viral load were determined through histology and PCR. SNPs rs1057141 and rs1135216 were identified through allelic discrimination, using real-time PCR. The haplotypic analyses were performed using the Arlequin 3.5 program. RESULTS: HPV-6 and HPV-11 were the genotypes found in the samples. In the polymorphism analysis, rs1057141 showed no significant differences (p = 0.049, CI = 0.994-7.331). In contrast, a significant difference was found in rs1135216 (p = 0.039, OR = 2.4) in the allelic analysis, as well as in the dominant (p = 0.027, OR = 3.06), codominant (p = 0.033, OR = 3.06), and additive model (p = 0.043, OR = 2.505) in subjects with the G allele. CONCLUSION: The G allele in rs1135216 was associated with a genetic risk of susceptibility for RRP in a population in Western Mexico.

Primate somatosensory cortical neurons are entrained to both spontaneous and peripherally evoked spindle oscillations.

Recurrent thalamocortical circuits produce a number of rhythms critical to brain function. In slow-wave sleep, spindles (7-16 Hz) are a prominent spontaneous oscillation generated by thalamic circuits and triggered by cortical slow waves. In wakefulness and under anesthesia, brief peripheral sensory stimuli can evoke 10-Hz reverberations due potentially to similar thalamic mechanisms. Functionally, sleep spindles and peripherally evoked spindles may play a role in memory consolidation and perception, respectively. Yet, rarely have the circuits involved in these two rhythms been compared in the same animals and never in primates. Here, we investigated the entrainment of primary somatosensory cortex (S1) neurons to both rhythms in ketamine-sedated macaques. First, we compared spontaneous spindles in sedation and natural sleep to validate the model. Then, we quantified entrainment with spike-field coherence and phase-locking statistics. We found that S1 neurons entrained to spontaneous sleep spindles were also entrained to the evoked spindles, although entrainment strength and phase systematically differed. Our results indicate that the spindle oscillations triggered by top-down spontaneous cortical activity and bottom-up peripheral input share a common cortical substrate.NEW & NOTEWORTHY Brief sensory stimuli evoke 10-Hz oscillations in thalamocortical neuronal activity and in perceptual thresholds. The mechanisms underlying this evoked rhythm are not well understood but are thought to be similar to those generating sleep spindles. We directly compared the entrainment of cortical neurons to both spontaneous spindles and peripherally evoked oscillations in sedated monkeys. We found that the entrainment strengths to each rhythm were positively correlated, although with differing entrainment phases, implying involvement of similar networks.

Clinical, histopathological, and in silico pathogenicity analyses in a pedigree with familial amyloidosis of the Finnish type (Meretoja syndrome) caused by a novel gelsolin mutation.

Purpose: Familial amyloidosis of the Finnish type (FAF) is an inherited amyloidosis arising from mutations in the gelsolin protein (GSN). The disease includes facial paralysis, loose skin, and lattice corneal dystrophy. To date, FAF has been invariably associated with substitution of Asp214 in GSN. We describe the clinical, histopathological, and genetic features of a family with FAF due to a novel GSN mutation. Methods: Five affected adult individuals in a three-generation FAF pedigree were included in the study. Histopathological analysis was performed on an eyelid skin biopsy from one patient. Genetic analysis included next-generation sequencing (NGS) and Sanger sequencing for confirmation of the GSN variant. Several tools for in silico analysis of pathogenicity for the novel variant and to predict the effect of the amino acid replacement on protein stability were used. Results: Three older adult affected patients exhibited corneal lattice dystrophy, cutis laxa, and facultative peripheral neuropathy. Two younger adult individuals presented only with corneal amyloid deposits. NGS identified a heterozygous GSN c.1631T>G transversion, predicting a novel p.Met544Arg mutation. All in silico tools indicated that p.Met544Arg is deleterious for GSN functionality or stability. Conclusions: The results expand the molecular spectrum of GSN-linked systemic amyloidosis. The novel p.Met544Arg pathogenic variant is predicted to affect gelsolin function, presumably by impairing a potential calcium-sensitive, actin-binding region.