Search

Introduction: Migraine is a polygenic multifactorial disorder with a neuronal initiation of a cascade of neurochemical processes leading to incapacitating headaches. Headaches are generally unilateral, throbbing, 4–72 h in duration, and associated with nausea, vomiting, photophobia, and sonophobia. Chronic migraine (CM) is the presence of a headache at least 15 days per month for ≥3 months and has a high global impact on health and economy, and therapeutic guidelines are lacking. Methods: Using the Grading of Recommendations, Assessment, Development, and Evaluations system, we conducted a search in MEDLINE and Cochrane to investigate the current evidence and generate recommendations of clinical practice on the identification of risk factors and treatment of CM in adults. Results: We recommend avoiding overmedication of non-steroidal anti-inflammatory drugs (NSAIDs); ergotamine; caffeine; opioids; barbiturates; and initiating individualized prophylactic treatment with topiramate eptinezumab, galcanezumab, erenumab, fremanezumab, or botulinum toxin. We highlight the necessity of managing comorbidities initially. In the acute management, we recommend NSAIDs, triptans, lasmiditan, and gepants alone or with metoclopramide if nausea or vomiting. Non-pharmacological measures include neurostimulation. Conclusions: We have identified the risk factors and treatments available for the management of CM based on a grading system, which facilitates selection for individualized management.

Neurocysticercosis (NCC) is a common disease produced by helminths (larval form of Taenia Solium) in the Central Nervous System (CNS). It is one of the common causes of epilepsy in the world. Without aggressive treatment, it continues to be associated with high mortality, with intracranial hypertension, and a lack of seizure control. This chapter reviews several cases of patients with secondary epilepsy who meet the diagnostic criteria for NCC and compares 2001 and 2016 diagnostic criteria: one of the cases with a definitive diagnosis, and the rest with a probable diagnosis. This problem is common for residents of regions where cysticercosis is an endemic zone, like in Mexico. Most patients presented clinical courses and image studies highly suggestive of NCC and positive ELISA testing for cysticerci in CSF. We emphasize the importance of ruling out the differential diagnosis, especially in endemic areas, questioning the use of ELISA in the CSF testing for cysticerci antibodies seems to be not enough, and advise caution when interpreting cystic lesions as having a discernible scolex because potential mimics are not infrequent.

The protein alpha-synuclein (α-Syn) has been linked to neuroinflammatory conditions. We investigated whether the presence of α-Syn in peripheral tissues is a surrogate of brain inflammatory status in a small group of relapsing-remitting multiple sclerosis (RRMS) patients in a pilot cross-sectional study. Skin biopsies and peripheral blood were sampled from 34 healthy controls and 23 MS patients for measurement of α-Syn levels. Within the RRMS group 15 patients were in remission, and 8 patients were in the relapsing phase. The protein α-Syn was evaluated by means of immunohistochemistry and flow cytometry in skin and nucleated blood cells, respectively. In the skin, α-Syn levels were lower in relapsing MS than in the other groups, both in positive area (p = .021) and staining intensity (p = .004). In blood, the percentage of α-Syn-positive lymphocytes and monocytes were not statistically different between study groups. Moreover, the use of systemic steroids did not affect α-Syn positivity in MS-relapse patients. Finally, epidermic Langerhans cells did not stain positively for α-Syn. Overall, the levels of α-Syn positivity were lower in inflammatory relapse of RRMS patients when measured in peripheral tissues. We discuss the role of α-Syn levels in inflammation according to the obtained results.

Our objective is to review the initial presentation, evolution, progression, final stage, and images in the follow up of an adult patient who presented an uncommon peroxisomal disease (1/20,000 males) that occurred by ABCD1 gene mutation in the Xq28 chromosome; to bring forward the imaging features (which nowadays is the most useful and accessible diagnostic tool) and clinical presentation of adrenoleukodystrophy in adulthood; to propose a differential diagnosis in aid of a prompt recognition of the disease hereafter from a neurologist approach. In relation of a clinical case we reviewed the literature to correlate the principal findings and evolution of the disease. This thrilling but at the same time unfortunate disease is not only a diagnostic problem is also a therapeutic quest besides all the related familial, labor, and social related problems. The very-long chain fatty acids (VLCFA) accumulation leads to a not completely understood mechanisms that precipitate the specific malfunction of the nervous system and adrenal gland. The initial corticospinal bilateral involvement provokes a spastic paraparesis but with the affection of others pathways multiple manifestations appears, with dementia and finally loss of the most of cortical functions secondary to the white matter affection. Since the hematopoietic stem cell transplantation can be treated with variable results, other treatments, as the Lorenzo's oil, have not been consistent with a substantial improvement of the affected individual. The genetic advice and support to the patient and the family are essentials as well as the screening in individuals at risk before the onset of the disease., Highlights • Being more common in the pediatric population adrenoleukodystrophy is not well understood if it presents in adulthood. • The imaging features are almost unequivocal and should be helpful to differentiate from clinically similar diseases. • The disease onset with predominant affection of upper motor neuron is a diagnosis challenging. • The screening is a promising approach before the onset of the disease for counseling and therapeutic consideration. • Stem cell transplant, Lorenzo’s oil, and diet modifications are still insufficient to stop the progression of the disease. • The pathogenesis should be understood to search new and sufficient therapeutic approaches.

Dose individualization is essential in epilepsy treatment, especially in antiepileptic drugs that present high interindividual variability such as lamotrigine. We aimed an observational study to develop a population pharmacokinetic model for quantitative evaluation of the factors that influence lamotrigine pharmacokinetics in Mexican adults with epilepsy. Patients on stable treatment with lamotrigine therapy were included, plasma concentrations were analyzed by a high-performance liquid chromatography method and UGT2B7–161C > T polymorphism was determined. The data were analyzed by NONMEM® 7.3, model validation was performed using bootstrap approach and visual predictive check. Finally, stochastic simulations were carried out to propose dosage regimens. A total of 73 lamotrigine plasma concentrations from 2 h after last dose and up to 0.5 h prior to next administration were fitted to a one-compartment open model. The final population pharmacokinetic model for lamotrigine indicates that concomitant treatment with valproic acid and carbamazepine should be considered to individualize epilepsy treatment with this drug. Based on this model, we proposed dosage regimens to achieve trough lamotrigine concentrations within reference interval (2.5–15 mg/L). These results provide clinical useful data to give more rational anticonvulsant therapy in our population.

Background: Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disorder characterized by deterioration of the substantia nigra, resulting in a deficiency of dopamine. PD is considered a movement disorder associated with numerous non-motor symptoms related to Autonomic Nervous System failures which can precede the motor ones. Therefore, their awareness could be helpful in the diagnosis of PD at an early stage. Methods: Heart Rate Variability (HRV) is assessed by time and frequency domain indices, and by nonlinear indices based on symbolic dynamics and multiscale symbolic entropy. The features obtained were used to classify between PD patients and control volunteers using a support vector machine. Volunteers performed cardiovascular autonomic reflex tests: active standing, post- hyperventilation and controlled breathing. Results: Temporal and frequency indices showed significantly lower values in PD patients compared to control volunteers. Symbolic dynamics and multiscale symbolic entropy results suggest a decrease in the complexity of the HRV signal in PD patients, in contrast with a more variable pattern of words for control volunteers. During controlled breathing differences between groups were found with most of the indices computed. Additionally, classification process achieves good separability during cardiorespiratory maneuvers (>95% of accuracy) and features based on symbolic dynamics showed high discrimination between groups. Conclusions: The results found in this work suggest that the proposed methodological approach can classify PD patients in an early disease stage from healthy controls and give additional information about the cardiorespiratory system, which could be useful for diagnosis and follow up of PD patients.

Objective The purpose of this study was to evaluate the relation between cognitive performance and white matter (WM) integrity in patients with temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS). Methods We included 26 patients with TLE (10 right, 16 left onset) as well as 24 healthy controls matched for age, gender, and years of education. In addition to quantitative hippocampal volume and transverse relaxation (T2) evaluation, whole-brain WM was analyzed using fractional anisotropy (FA) maps, derived from the diffusion tensor model. Average FA values were obtained from 38 regions of interest (ROI) of the main WM fascicles using an atlas-based approach. All subjects underwent extensive coFignitive assessments, Wechsler Adult Intelligence Scale (WAIS-IV) and Wechsler Memory Scale (WMS-IV). Fractional anisotropy was correlated with neuropsychological scores, and group effects were evaluated. Finally, patients were clustered based on their cognitive performance to evaluate if clinical and structural variables relate to specific cognitive profiles. Results Patients had differential alterations in the integrity of the WM dependent on seizure laterality and presence of hippocampal sclerosis. Patients with TLE showed, on average, lower scores in most of the cognitive assessments. Correlations between cognition and WM followed specific trajectories per group with TLE, particularly in Left-TLE, in which we found a marked association between cognitive abilities and WM abnormalities. Cluster analysis of cognitive performance revealed three cognitive profiles, which were associated with the degree and spread of WM abnormalities. Significance White matter diffusion characteristics differ between patients, particularly in relation to seizure laterality and hippocampal damage. Moreover, WM abnormalities are associated with cognitive performance. The extent of WM alterations leads to disrupted cerebral intercommunication and therefore negatively affects cognition.

COVID-19 has shown different neurological manifestations even sometimes there are the initial or the main presentation.The following case report is about a middle-aged woman who, over 3 days, developed fever, clinical neurological alterations (stupor, muteness, fixed gaze and catatonia), cerebrospinal fluid (16 lymphocytes) and an electroencephalogram (EEG) (4–6 Hz generalised activity) with characteristics of encephalitis. A serum IgG, IgM, nasopharyngeal swab PCR for SARS-CoV-2. The patient responded positively to support measures, symptomatic and corticosteroid treatment. At discharge, the patient was independent and improved considerably.We report the presence of catatonia as a possible and atypical manifestation of encephalitis in association with COVID-19.

Objective This study characterizes the expression of tau (p‐tau) and α‐synuclein (α‐syn) by immunohistochemistry in the skin of three different populations: healthy control (HC), Parkinson disease (PD), and progressive supranuclear paralysis (PSP) subjects, with the purpose of finding a biomarker that could differentiate between subjects with PD and PSP. Material and Methods We evaluated the presence of p‐tau and α‐syn in a pilot study in the skin of three distinct groups of patients: 17 healthy subjects, 17 patients with PD, and 10 patients with PSP. Four millimeters punch biopsies were obtained from the occipital area and analyzed by immunohistochemistry using antibodies against α‐syn and phosphorylated species of tau. PHF (paired helical filaments) antibody identifies p‐tau in both normal and pathological conditions and AT8 recognizes p‐tau characteristic of pathological conditions. Differences between the three groups were assessed by quantification of immunopositive areas in the epidermis. Results The immunopositivity pattern of p‐tau and α‐syn was significantly different among the three groups. Healthy subjects showed minimal staining using AT8 and α‐syn. The PD group showed significantly higher α‐syn and AT8 immunopositivity, while the PSP group only expressed higher AT8 immunopositivity than HCs. Conclusion These data suggest that the skin reflects brain pathology. Therefore, immunohistochemical analysis of p‐tau and α‐syn in the skin can be useful for further characterization of PD and PSP.

Objective The presence in the brain of α-synuclein containing Lewy neurites, or bodies, is the histological hallmark of Parkinson's disease (PD). The discovery of α-synuclein aggregates in nerve endings of the heart, digestive tract, and skin has lent support to the concept of PD as a systemic disease. Our goals were, first, to demonstrate the presence of α-synuclein inclusions in the skin and, second, to detect quantitative differences between patients with PD and atypical parkinsonism (AP). Methods Skin biopsies were taken from 67 patients and 20 controls. The biopsies underwent immunohistochemistry (IHC) and immunofluorescence (IF) testing for α-synuclein, whereupon its presence was quantified as the percentage of positive cells. Patients were divided into those with PD and those with AP. AP patients included AP with neurodegenerative disease (proteinopathies) and secondary AP. Results Sixty-seven patients (34 with PD) and 20 controls were recruited. In the PD group, α-synuclein was detected in 58% of the cells in the spinous cell layer (SCL), 62% in the pilosebaceous unit (PSU), and 58% in the eccrine glands (EG). The AP-proteinopathies group showed 7%, 7%, and 0% expression of α-synuclein, respectively. No expression was found in the skin of the control group. Conclusions The expression of α-synuclein in the skin was relatively high in the PD group, scarce in AP, and null for the individuals in the control group. While these findings require further confirmation, this minimally invasive technique may aid in the improvement of the accuracy of PD diagnoses.

Background The misfolding and prion-like propagation of the protein alpha-synuclein (α-syn) is the leading molecular signature in Parkinson's disease (PD). There is a significant co-incidence of PD and melanoma which may suggest a shared pathophysiology. This study compared the presence of α-syn in neural crest-derived tissues, such as nevi, melanoma, skin tags and skin biopsies from PD cases and controls. Methods Biopsies from PD participants were obtained from patients of a tertiary referral center for dermatology and neurology in Mexico and a dermatopathology private center in Florida, USA, between January 2015 and March 2016. Biopsies from 7 patients with melanoma, 15 with nevi, 9 with skin tags, 8 with PD, and 9 skin biopsies from healthy volunteers were analyzed for immunohistochemical determination of α-syn and tyrosinase. All analyses were performed by pathologists blinded with respect to the clinical diagnosis. Results In healthy controls, α-syn immunopositivity was restricted to scattered cells in the basal layer of the epidermis and accounted for 1± 0.8% of the analyzed area. In PD patients, there was increased staining for α-syn PD (3.3 ± 2.3%), with a higher percentage of positive cells in nevi (7.7 ± 5.5%) and melanoma (13.6 ± 3.5%). There was no increased staining in skin tags compared to healthy controls. Conclusions Patients with PD and melanoma have increased staining for α-syn in their skin. We propose that neurons and melanocytes, both derived from neuroectodermal cells, may share protein synthesis and regulation pathways that become dysfunctional in PD and melanoma. This article is protected by copyright. All rights reserved.

Amyotrophic lateral sclerosis is a degenerative disorder of motor neurons that typically develops in the 6th decade and is uniformly fatal, usually within 5 years. To identify genetic variants associated with susceptibility and phenotypes in sporadic ALS, we performed a genome-wide SNP analysis in sporadic ALS cases and controls. A total of 288,357 SNPs were screened in a set of 1,821 sporadic ALS cases and 2,258 controls from the U.S. and Europe. Survival analysis was performed using 1,014 deceased sporadic cases. Top results for susceptibility were further screened in an independent sample set of 538 ALS cases and 556 controls. SNP rs1541160 within the KIFAP3 gene (encoding a kinesin-associated protein) yielded a genome-wide significant result ( P = 1.84 × 10 −8 ) that withstood Bonferroni correction for association with survival. Homozygosity for the favorable allele (CC) conferred a 14.0 months survival advantage. Sequence, genotypic and functional analyses revealed that there is linkage disequilibrium between rs1541160 and SNP rs522444 within the KIFAP3 promoter and that the favorable alleles of rs1541160 and rs522444 correlate with reduced KIFAP3 expression. No SNPs were associated with risk of sporadic ALS, site of onset, or age of onset. We have identified a variant within the KIFAP3 gene that is associated with decreased KIFAP3 expression and increased survival in sporadic ALS. These findings support the view that genetic factors modify phenotypes in this disease and that cellular motor proteins are determinants of motor neuron viability.

Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative disorder of upper and lower motor neurons. Genetic variants in the paraoxonase gene cluster have been associated with susceptibility to sporadic ALS. Because these studies have yielded conflicting results, we have further investigated this association in a larger data set. Twenty SNPs spanning the paraoxonase gene cluster were genotyped on a panel of 597 case and 692 control samples and tested for association with risk of sporadic ALS and with ALS sub-phenotypes. Our study revealed two SNPs, rs987539 and rs2074351, within the paraoxonase gene cluster that are associated with susceptibility to sporadic ALS (uncorrected p=6.47E-04 and 7.87E-04, respectively). None of the 20 SNPs displayed significant associations with age of onset, site of onset or disease survival. Using a sliding window approach, we have also identified a 5-SNP haplotype that is significantly associated with risk of sporadic ALS (p=2.75E-05). We conclude that a common haplotype within the PON1 promoter region is associated with susceptibility to sporadic ALS.

Summary Purpose To assess the multiple-dose pharmacokinetics of levetiracetam and its major metabolite ucb L057 in children with partial-onset seizures and determine whether it is affected by adjunctive carbamazepine or valproate. To correlate levetiracetam concentrations in plasma and saliva and to assess its safety and clinical response. Methods Design was an open-label, multicenter study. Twenty-one children (4–12 years old) with epilepsy taking carbamazepine (13) or valproate (8) received adjunctive levetiracetam. Levetiracetam was initiated at 20mg/(kgday) and titrated at 2-week intervals to 40 and then 60mg/(kgday). Twelve-hour pharmacokinetics were determined at the end of each 2-week period. Efficacy was estimated from the partial seizure frequency per week and Global Evaluation Scale. Results Levetiracetam was rapidly absorbed following oral dosing, with median t max of 0.5h. Dose proportional increases were observed for C max and AUC (0–12) over the dose range; t 1/2 was 4.9h. Pharmacokinetics of levetiracetam and ucb L057 were not markedly different with concomitant carbamazepine or valproate; clearance was only 7–13% faster and AUC was decreased by only 15–24% in those on carbamazepine compared to valproate. Levetiracetam did not affect trough carbamazepine or valproate. Concentration in saliva and plasma were strongly correlated. Seizure frequency declined by 50% or more in 43% of subjects in the intent-to-treat population ( n =21) and in 56% of those with seizures at baseline ( n =16). Marked or moderate improvement occurred in 80% and 75% of patients based on Global Evaluation Scale ratings by investigators and parents/guardians, respectively. Levetiracetam was well tolerated. Conclusion Levetiracetam exhibits simple pharmacokinetics in children, with rapid absorption and dose-proportional kinetics. Small but not clinically relevant differences were observed between subjects receiving carbamazepine and valproate, suggesting significant dose adjustment is usually not necessary. This substantiates prior assessments that levetiracetam clearance is higher in children than adults, necessitating a higher dose in children on a mg/kg basis, and suggests it is useful add-on therapy for children with partial-onset seizures regardless of baseline therapy.

This cross-sectional study examined the effects of chronic exposure to lead (Pb), arsenic (AS) and undernutrition on the neuropsychological development of children. Two populations chronically exposed to either high (41 children) or low (39 children) levels of As and Pb were analyzed using the Wechsler Intelligence Scale for Children, Revised Version, for México (WISC-RM). Geometric means of urinary arsenic (AsU) and lead in blood (PbB) were 62.9+/-0.03 (microgAs/g creatinine) and 8.9+/-0.03 (microg/dl) for the exposed group and 40.2+/-0.03 (microgAs/g creatinine) and 9.7+/-0.02 (microg/dl) for the reference group. The height for age index (HAI) was used as an indicator of chronic malnutrition and sociodemographic information was obtained with a questionnaire. Lead and arsenic were measured by atomic absorption spectrophotometry. Data on full, verbal, and performance intelligence quotients (IQ) scores, long-term memory, linguistic abstraction, attention span, and visuospatial organization were obtained through the WISC-RM. After controlling for significant potential confounders verbal IQ (P0.01) decreased with increasing concentrations of AsU. The HAI correlated positively with full-scale and performance IQ (P0.01). Higher levels of AsU were significantly related to poorer performance on WISC-RM factors examining long-term memory and linguistic abstraction, while lower scores in WISC-RM factors measuring attention were obtained at increasing values of PbB. Our results suggest that exposure to As and chronic malnutrition could have an influence on verbal abilities and long-term memory, while Pb exposure could affect the attention process even at low levels.

Three clustered, homologous paraoxonase genes (PON1, PON2 and PON3) have roles in preventing lipid oxidation and detoxifying organophosphates. Recent reports describe a genetic association between the PON genes and sporadic amyotrophic lateral sclerosis (ALS). We now report that in genomic DNA from individuals with familial and sporadic ALS we have identified at least seven PON gene mutations that are predicted to alter PON function.

Background and study aims Spontaneous intracerebral hemorrhage (ICH) represents the most fatal kind of stroke, and there is still no treatment available that improves the outcome. Statins are cholesterol reducers, and during the last few years many additional effects have been demonstrated that might be neuroprotective. We designed a pilot clinical study in order to evaluate whether the administration of statins is associated with a better outcome. Patients and methods From August to December 2006 we carried out a prospective/retrospective non-randomized clinical study. The prospective group was treated with rosuvastatin (20 mg) and the retrospective control group was taken from our clinical records with a relation of 1:3. We included patients of both sexes, aged > or =15 years with proven ICH in CT-scan. Exclusion criteria were a history of neoplasm, head injury four weeks before admission, non-hypertensive reasons, brainstem hemorrhage, steroid administration, cranial surgery, initial hydrocephalus, and NIHSS > or =30. Results We analyzed 18 patients treated with rosuvastatin and 57 controls with similar basic characteristics. The mortality rate during hospitalization was 1 (5.6%) patient in the statin group and 9 (15.8%) in the control group; the hazard ratio adjusted by the initial Glasgow Coma Scale (GCS), intubation, admission in intensive care unit, disruption into the subarachnoid space was 0.20 (95% CI 0.02-1.67). The odds ratio for NIHSS > or =15 at release was 0.04 (95% CI 0.003-0.93). Conclusions The use of statins during the acute phase of ICH could be associated with a better outcome. Further clinical trials are necessary to confirm a possible therapeutic effect and evaluate the toxicity of statins.

ContextAtherothrombosis is the leading cause of cardiovascular morbidity and mortality around the globe. To date, no single international database has characterized the atherosclerosis risk factor profile or treatment intensity of individuals with atherothrombosis.ObjectiveTo determine whether atherosclerosis risk factor prevalence and treatment would demonstrate comparable patterns in many countries around the world.Design, Setting, and ParticipantsThe Reduction of Atherothrombosis for Continued Health (REACH) Registry collected data on atherosclerosis risk factors and treatment. A total of 67 888 patients aged 45 years or older from 5473 physician practices in 44 countries had either established arterial disease (coronary artery disease [CAD], n = 40 258; cerebrovascular disease, n = 18 843; peripheral arterial disease, n = 8273) or 3 or more risk factors for atherothrombosis (n = 12 389) between 2003 and 2004.Main Outcome MeasuresBaseline prevalence of atherosclerosis risk factors, medication use, and degree of risk factor control.ResultsAtherothrombotic patients throughout the world had similar risk factor profiles: a high proportion with hypertension (81.8%), hypercholesterolemia (72.4%), and diabetes (44.3%). The prevalence of overweight (39.8%), obesity (26.6%), and morbid obesity (3.6%) were similar in most geographic locales, but was highest in North America (overweight: 37.1%, obese: 36.5%, and morbidly obese: 5.8%; P

Objective: The objective was to demonstrate that the detection of α-synuclein in skin biopsies may be a useful biomarker for diagnosis of Parkinson9s disease. Background Parkinson9s disease is a progressive neurodegenerative disease characterized by: Tremor, Rigidity, Akinesia/bradykinesia and Postural changes. Atypical Parkinsonism (AP) may be initially misdiagnosed as Parkinson9s disease; the lack of an early biomarker makes the differential diagnosis difficult. Design/Methods: Sixty skin biopsies from 30 patients with Parkinsonism Syndrome; 30 were taken from the retro auricular region in cervical area, and 30 in the lower back. These were evaluated immunohistochemically with α-synuclein antibody. Its expression was compared with 20 skin biopsies of normal control subjects. Midbrain sections from a patient with Parkinson9s disease were used as positive control to determine the cut-off dilution. Results: We investigate the frequency of intranuclear inclusions in spinous cells layer (SCL) and in pilosebaceous unit (PSU)and eccrine gland (EG); the analysis of patients with PD demonstrated strong, intranuclear positivity with small nodular accumulation of 1-2 µm in diameter. The number of cells with intranuclear inclusions in PD was contrasted against AP and normal control for the SCL, PSU and EG. Differences in the expression among the three structures were significant among PD, AP and control (Kruskall-Wallis, p= Conclusions: The detection of α-synuclein in skin biopsy is an effective, inexpensive method for distinguishing Atypical Parkinsonism from Parkinson9s disease in the early stage of the disease. It could be a safe and less invasive diagnostic marker of Parkinson9s disease. Supported by: COPOCYT (Consejo Potosino de Ciencia y Tecnologia) through grant FS1611. Disclosure: Dr. Rodriguez-Leyva has received personal compensation for activities with Novartis and Boehringer Ingelheim as a speaker. Dr. Renteria-Palomo has nothing to disclose. Dr. Calderon-Garciduenas has nothing to disclose. Dr. Fuentes-Ahumada has nothing to disclose. Dr. Hernandez has nothing to disclose. Dr. Mendoza-Esquivel has nothing to disclose. Dr. Castanedo-Cazares has nothing to disclose.