Experimental Study of White Light Interferometry in Mach-Zehnder Interferometers Based on Standard Single Mode Fiber.

In this work, we experimentally analyzed and demonstrated the performance of an in-line Mach-Zehnder interferometer in the visible region, with an LED light source. The different waist diameter taper and asymmetric core-offset interferometers proposed used a single-mode fiber (SMF). The visibility achieved was V = 0.14 with an FSR of 23 nm for the taper MZI structure and visibilities of V = 0.3, V = 0.27, and V = 0.34 with FSRs of 23 nm, 17 nm, and 8 nm and separation lengths L of 2.5 cm, 4.0 cm, and 5.0 cm between the core-offset structure, respectively. The experimental investigation of the response to the temperature sensor yielded values from 50 °C to 300 °C; the sensitivity obtained was 3.53 a.u./°C, with R2 of 0.99769 and 1% every 1 °C in the transmission. For a range of 50 °C to 150 °C, 20.3 pm/°C with a R2 of 0.96604 was obtained.

Promising predictive molecular biomarkers for cervical cancer (Review).

Cervical cancer (CC) constitutes a serious public health problem. Vaccination and screening programs have notably reduced the incidence of CC worldwide by >80%; however, the mortality rate in low­income countries remains high. The staging of CC is a determining factor in therapeutic strategies: The clinical management of early stages of CC includes surgery and/or radiotherapy, whereas radiotherapy and/or concurrent chemotherapy are the recommended therapeutic strategies for locally advanced CC. The histopathological characteristics of tumors can effectively serve as prognostic markers of radiotherapy response; however, the efficacy rate of radiotherapy may significantly differ among cancer patients. Failure of radiotherapy is commonly associated with a higher risk of recurrence, persistence and metastasis; therefore, radioresistance remains the most important and unresolved clinical problem. This condition highlights the importance of precision medicine in searching for possible predictive biomarkers to timely identify patients at risk of treatment response failure and provide tailored therapeutic strategies according to genetic and epigenetic characteristics. The present review aimed to summarize the evidence that supports the role of several proteins, methylation markers and non­coding RNAs as potential predictive biomarkers for CC.

Chronic consumption of imbalance diets high in sucrose or fat induces abdominal obesity with different pattern of metabolic disturbances and lost in Langerhans cells population.

AIM: Obesity is a worldwide health issue, associated with development of type 2 Diabetes Mellitus. The aim of this study is to analyze the effect of consumption of two hypercaloric diets on metabolic disturbance and beta cells damage. MAIN METHODS: Male Wistar rats were subjected to twelve months consumption of three diets: a Control balanced diet (CTD, carbohydrates 58 %, proteins 29 %, lipids 13 %) and two hypercaloric diets, high in sucrose (HSD, carbohydrates 68 %, proteins 22 %, lipids 10 %) or high in fat (HFD, carbohydrates 31 %, proteins 14 %, lipids 55 %). Serum levels of glucose, triglycerides and free fatty acids were measured after zoometric parameters determination. Antioxidant enzymes activity and oxidative stress-marker were measured in pancreas tissue among histological analysis of Langerhans islets. KEY FINDINGS: Although diets were hypercaloric, the amount of food consumed by rats decreased, resulting in an equal caloric consumption. The HSD induced hypertriglyceridemia and hyperglycemia with higher levels in free fatty acids (FFA, lipotoxicity); whereas HFD did not increased neither the triglycerides nor FFA, nevertheless the loss of islets' cell was larger. Both diets induced obesity with hyperglycemia and significant reduction in Langerhans islets size. SIGNIFICANCE: Our results demonstrate that consumption of HSD induces more significant metabolic disturbances that HFD, although both generated pancreas damage; as well hypercaloric diet consumption is not indispensable to becoming obese; the chronic consumption of unbalanced diets (rich in carbohydrates or lipids) may lead to abdominal obesity with metabolic and functional disturbances, although the total amount of calories are similar.

Gene expression of cardiovascular risk markers in mononuclear cells of pregnant woman in relation to plasma leptin and homocysteine levels: A cross sectional study.

OBJECTIVE: To investigate the relationship between anthropometric, biochemical, and hematologic parameters and serum leptin and homocysteine (Hcy) levels. Also, to determine the effect of leptin and Hcy on expression of genes associated with cardiovascular disease susceptibility (APOA1, LRP1, COX-1, and COX-2) in mononuclear cells of healthy pregnant women. METHODS: Between August 2018 and January 2020, a cross-sectional study was conducted on 161 healthy pregnant women in Tabasco, southeastern Mexico. The study population was classified by trimester, according to gestational pregnancy. Anthropometric, biochemical (leptin and homocysteine), and hematologic data were obtained under fasting conditions. APOA1, LRP1, COX-1, and COX-2 expression in mononuclear cells was evaluated using RT-qPCR. RESULTS: Red cell indices (hemoglobin, hematocrit, and erythrocytes) were negatively and positively correlated with leptin and Hcy levels, respectively, in the first- and second-trimester groups. Increased leptin levels and low red cell indices were significantly associated with BMI <25.0 in the second-trimester group; however, no significant differences were observed in Hcy levels. Increased leptin and Hcy levels were significantly associated with high lipid indicators in the first- and third-trimester groups, respectively. High APOA1 and COX-2 expression was significantly associated with reduced leptin and increased Hcy levels in the second- and third-trimester groups. CONCLUSION: Increased leptin and Hcy levels during pregnancy, mainly associated with modifications in erythrocytes and lipid indices, may lead to early modification of genes related to lipid metabolism (APOA1) and proinflammatory response (COX-2) and, thereby, increase cardiovascular disease risk.

Leukocytoclastic Vasculitis in an Adolescent with New-Onset Crohn's Disease.

Extraintestinal manifestations frequently affect patients with inflammatory bowel disease. They can involve virtually any organ, with the musculoskeletal and integumentary systems being the most common. Leukocytoclastic vasculitis is a rare extraintestinal manifestation of inflammatory bowel disease, especially at disease onset. It has been reported to occur in association with Crohn's disease and trimethoprim/sulfamethoxazole (TMP-SMX) exposure independently. We report a case of a 14-year-old female who developed leukocytoclastic vasculitis after exposure to TMP-SMX and was ultimately diagnosed with Crohn's disease. The patient presented with purpura, oral ulcers, abdominal pain, and intermittent bloody stools. Colonoscopy showed colonic inflammation, and biopsies revealed severe chronic active colitis with crypt abscesses. A skin biopsy confirmed the diagnosis of leukocytoclastic vasculitis. Management consisted of high-dose steroids and infliximab, with resolutions of her symptoms. This case emphasizes that extraintestinal manifestations are multifactorial in nature, with the example of an existing genetic predisposition through Crohn's disease and a triggering factor such as TMP-SMX.

HEK293 producing the extracellular domain HER1: Full datasets of continuous fermentation process and metabolites analysis.

The data for provide evidences of the multi steady state of the human cell line HEK 293 was obtained from 2 L bioreactor continuous culture. A HEK 293 cell line transfected to produce soluble HER1 receptor was used. The bioreactor was operated at three different dilution rates in sequential manner. Daily samples of culture broth were collected, a total of 85 samples were processed. Viable cell concentration and culture viability was addressing by trypan blue exclusion method using a hemocytometer. Heterologous HER1 supernatant concentration was quantified by a specific ELISA and the metabolites by mass spectrometry coupled to a liquid chromatography. The primary data were collected in excel files, where it was calculated the kinetic and other variables by using mass balance and mathematical principles. It was compared the steady states behavior each other's to find out the existence of steady states' multiplicity, taking into account the stationary phase with respect to the cell density (which means its coefficient of variation is less than 20 %). From the metabolic measurements by using Liquid Chromatography coupled to mass spectrometry (LC-MS), it was also built the data matrix with the specific rates of the 76 metabolites obtained. The data were processed and analyzed, using multivariate data asssnalysis (MVDA) to reduce the complexity and to find the main patterns present in the data. We describe also the full data of the metabolites not only for steady states but also in the time evolution, which could help others in terms of modeling and deep understanding of HEK293 metabolism, especially under different culture conditions.

Nanocomposites of Silicon Oxides and Carbon: Its Study as Luminescent Nanomaterials.

In this work, hybrid structures formed by nanostructured layers, which contain materials, such as porous silicon (PSi), carbon nanotubes (CNTs), graphene oxide (GO), and silicon-rich oxide (SRO), were studied. The PSi layers were obtained by electrochemical etching over which CNTs and GO were deposited by spin coating. In addition, SRO layers, in which silicon nanocrystals are embedded, were obtained by hot filament chemical vapor deposition (HFCVD) technique. Photoluminescence (PL) spectra were obtained from the hybrid structures with which a comparative analysis was completed among different PL ones. The SRO layers were used to confine the CNTs and GO. The main purpose of making these hybrid structures is to modulate their PL response and obtain different emission energy regions in the PL response. It was found that the PL spectra of the CNTs/SRO and GO/SRO structures exhibit a shift towards high energies compared to those obtained from the PSi layers; likewise, the PSi/CNTs/SRO and PSi/GO/SRO structures show a similar behavior. To identify the different emission mechanisms originated by PSi, GO, CNTs, and SRO, the PL spectra were deconvolved. It was found that the Psi/CNTs/SRO and Psi/GO/SRO structures exhibit a PL shift in respect to the PSi layers, for this reason, the modulation of the PL emission of the structures makes these hybrid structures promising candidates to be applied in the field of photonic and electroluminescent devices.

Differential disruption on glucose and insulin metabolism in two rat models of diet-induced obesity, based on carbohydrates or lipids.

Obesity is a relevant health public issue and is the main factor for glucose metabolism dysregulation and diabetes progression; however, the differential role of a high-fat diet or high sugar diet consumption on glucose metabolism and insulin processing is not well understood and has been scarcely described. Our research aimed to analyze the effects of chronic consumption of both high sucrose and high-fat diets on glucose and insulin metabolism regulation. Wistar rats were fed with high-sugar or high-fat diets for 12 months; after that, fasting glucose and insulin levels were measured along with a glucose tolerance test (GTT). Proteins related to insulin synthesis and secretion were quantified in pancreas homogenates, whereas islets were isolated to analyze ROS generation and size measurement. Our results show that both diets induce metabolic syndrome, linked with central obesity, hyperglycemia, and insulin resistance. We observed alterations in the expression of proteins related with insulin synthesis and secretion, along with diminution of Langerhans islets size. Interestingly, the severity and number of alterations were more evident in the high-sugar diet than in the high-fat diet group. In conclusion, obesity and glucose metabolism dysregulation induced by carbohydrate consumption, led to worst outcomes than high-fat diet.

Current Advances of Plant-Based Vaccines for Neurodegenerative Diseases.

Neurodegenerative diseases (NDDs) are characterized by the progressive degeneration and/or loss of neurons belonging to the central nervous system, and represent one of the major global health issues. Therefore, a number of immunotherapeutic approaches targeting the non-functional or toxic proteins that induce neurodegeneration in NDDs have been designed in the last decades. In this context, due to unprecedented advances in genetic engineering techniques and molecular farming technology, pioneering plant-based immunogenic antigen expression systems have been developed aiming to offer reliable alternatives to deal with important NDDs, including Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Diverse reports have evidenced that plant-made vaccines trigger significant immune responses in model animals, supported by the production of antibodies against the aberrant proteins expressed in the aforementioned NDDs. Moreover, these immunogenic tools have various advantages that make them a viable alternative for preventing and treating NDDs, such as high scalability, no risk of contamination with human pathogens, cold chain free production, and lower production costs. Hence, this article presents an overview of the current progress on plant-manufactured vaccines for NDDs and discusses its future prospects.

Modulating epigenetic modifications for cancer therapy (Review).

Cancer is a global public health concern. Alterations in epigenetic processes are among the earliest genomic aberrations occurring during cancer development and are closely related to progression. Unlike genetic mutations, aberrations in epigenetic processes are reversible, which opens the possibility for novel pharmacological treatments. Non­coding RNAs (ncRNAs) represent an essential epigenetic mechanism, and emerging evidence links ncRNAs to carcinogenesis. Epigenetic drugs (epidrugs) are a group of promising target therapies for cancer treatment acting as coadjuvants to reverse drug resistance in cancer. The present review describes central epigenetic aberrations during malignant transformation and explains how epidrugs target DNA methylation, histone modifications and ncRNAs. Furthermore, clinical trials focused on evaluating the effect of these epidrugs alone or in combination with other anticancer therapies and other ncRNA­based therapies are discussed. The use of epidrugs promises to be an effective tool for reversing drug resistance in some patients with cancer.

High sugar but not high fat diet consumption induces hepatic metabolic disruption and up-regulation of mitochondrial fission-associated protein Drp1 in a model of moderate obesity.

Identification of new modifications and the association with diet patterns are essential for the prevention of non-alcoholic fatty liver disease (NAFLD). To address this problem, we feed rats with high caloric diets based on high sucrose (HSD) and high fat (HFD) and analysed metabolic and mitochondrial alterations. Both diets induce moderated obesity and fat accumulation in the liver after 8, 10 and 12 months of diet. The HSD induces both hyperleptinemia and hyperinsulinemia, as well as up-regulation of transcription factors SRBEP1 and PPARγ along slight increase nitrosylation of proteins and increased mitochondrial fission. In contrast, HFD induced hyperleptinemia without changes in neither insulin levels nor oxidative stress, SREBP1, PPARγ, or mitochondrial dynamics. In conclusion, chronic consumption of high sucrose content diets induces more pathological and metabolic alteration in liver in comparison with consumption of high-fat content diets, although both induces obesity and liver steatosis in these animal models.

MIS-Like Structures with Silicon-Rich Oxide Films Obtained by HFCVD: Their Response as Photodetectors.

MIS-type structures composed of silicon-rich oxide (SRO), thin films deposited by hot filament chemical vapor deposition (HFCVD), show interesting I-V and I-t properties under white light illumination and a response as photodetectors. From electrical measurements, it was found that at a reverse bias of -4 V, the illumination current increased by up to three orders of magnitude relative to the dark current, which was about 82 nA, while the photogenerated current reached a value of 25 µA. The reported MIS structure with SRO as the dielectric layer exhibited a hopping conduction mechanism, and an ohmic conduction mechanism was found with low voltage. I-t measurements confirmed the increased photogenerated current. Furthermore, the MIS structure, characterized by current-wavelength (I-λ) measurements, exhibited a maximum responsivity value at 254 mA/W, specific detectivity (D*) at 2.21 × 1011 cm Hz1/2 W-1, and a noise equivalent power (NEP) of 49 pW at a wavelength of 535 nm. The structure exhibited good switching behavior, with rise and fall times between 120 and 150 ms, respectively. These rise and decay times explain the generation and recombination of charge carriers and the trapping and release of traps, respectively. These results make MIS-type structures useful as photodetectors in the 420 to 590 nm range.

Chronic exposure to ozone induces cardiac antioxidant response and overexpression of either mitochondrial fision protein DRP1 and hipertrophyc-related proteins.

Pollution is considered a risk factor for cardiovascular disease; however, the mechanisms to explain this relationship are not well understood; ozone is one of the most abundant and studied air contaminants. Our study aimed to evaluate the effect of chronic exposition of rats to controlled low doses of ozone on oxidative stress, apoptosis, mitochondrial dynamics, and cardiac hypertrophy. Male Wistar rats were daily exposed to low ozone doses during 7, 15, 30, and 60 days, 4 h/day. Hearts were dissected, and homogenates were prepared. Oxidative stress was evaluated by TBARS and protein nitrosylation in addition to Superoxide dismutase 1 (SOD1) and Catalase levels; the apoptosis related-proteins caspase 3, caspase 9, Bax, Bcl-2, and the mitochondrial dynamic-associated proteins Fis1, Drp1, OPA1, and Mfn1 were quantified by western blot among the cardiac hypertrophy indicator alpha-actin (cardiac actin). There were no changes in the oxidative stress markers, however SOD1 expression increases. Caspase 3 expression decreased, whereas caspase 9 increased without changes in Bax or Bcl-2. Mitochondrial fission may be favored according to the increased expression of Drp1 but not changes in fusion-related proteins OPA1 and Mfn1. Finally, the molecular marker for cardiac hypertrophy was overexpressed after 30 and 60 days of ozone exposition. The chronic exposition to ozone induces a deleterious effect on cardiac mitochondria. Antioxidant defenses also show changes in relation to exposure time, as well as an apparent pro-hypertrophic effect associated with altered mitochondrial dynamics.

Green remediation potential of immobilized oxidoreductases to treat halo-organic pollutants persist in wastewater and soil matrices - A way forward.

The alarming presence of hazardous halo-organic pollutants in wastewater and soils generated by industrial growth, pharmaceutical and agricultural activities is a major environmental concern that has drawn the attention of scientists. Unfortunately, the application of conventional technologies within hazardous materials remediation processes has radically failed due to their high cost and ineffectiveness. Consequently, the design of innovative and sustainable techniques to remove halo-organic contaminants from wastewater and soils is crucial. Altogether, these aspects have led to the search for safe and efficient alternatives for the treatment of contaminated matrices. In fact, over the last decades, the efficacy of immobilized oxidoreductases has been explored to achieve the removal of halo-organic pollutants from diverse tainted media. Several reports have indicated that these enzymatic constructs possess unique properties, such as high removal rates, improved stability, and excellent reusability, making them promising candidates for green remediation processes. Hence, in this current review, we present an insight of green remediation approaches based on the use of immobilized constructs of phenoloxidases (e.g., laccase and tyrosinase) and peroxidases (e.g., horseradish peroxidase, chloroperoxidase, and manganese peroxidase) for sustainable decontamination of wastewater and soil matrices from halo-organic pollutants, including 2,4-dichlorophenol, 4-chlorophenol, diclofenac, 2-chlorophenol, 2,4,6-trichlorophenol, among others.

Anthropometric, biochemical, and haematological indicators associated with hyperhomocysteinemia and their relation to global DNA methylation in a young adult population.

Increased homocysteine (Hcy) levels have been associated with a higher risk of cardiovascular and neurodegenerative diseases. Passive DNA demethylation has been suggested as one of the mechanisms implicated in the development of these conditions, and most studies have investigated this relationship in older adult populations. Therefore, this study aimed to evaluate the relationship between corporal composition and biochemical and haematological indicators with plasma homocysteine levels and genome-wide methylation (Alu, LINE-1, and SAT2) in a population of healthy young adults (median age, 18 years). We showed that the prevalence of hyperhomocysteinemia was significantly higher in men (18.5%) than in women (6.6%) (P = 0.034). Increased Hcy level was substantially associated with higher levels of body mass index and visceral fat in females, whereas in males, it was significantly associated with reduced red cell distribution width and high-density lipoprotein (HDL) cholesterol (HDL-C) levels and increased low-density lipoprotein/HDL ratio. Hypomethylation of Alu was significantly associated with reduced levels of HDL-C (<40.0 mg dL-1), whereas hypomethylation of LINE-1 and SAT2 was significantly associated with higher levels of skeletal muscle (<39.3%) in males. These results highlight the participation of hormonal factors in regulating Hcy metabolism, primarily in the female population, whereas changes in DNA methylation observed in males might be associated with the consumption of a protein diet with high levels of methionine, independent of increased Hcy levels.

Surgical correction of juvenile idiopathic scoliosis. our patients' perception of their quality of life / Correção cirúrgica da escoliose idiopática juvenil - percepção de nossos pacientes sobre sua qualidade de vida / Corrección quirúrgica de escoliosis idiopática juvenil - percepción de nuestros pacientes sobre su calidad de vida

ABSTRACT Objective: To report the results of our patients who underwent scoliosis correction surgery in relation to their quality of life. Introduction: Juvenile idiopathic scoliosis affects between 1 and 3% of the population during puberty. Treatment will be conservative in most cases. The goal of surgical treatment is to improve coronal and sagittal alignment. The SRS 22 questionnaire is a useful tool for assessing quality of life in these patients. Methods: A retrospective study of 22 patients submitted to corrective surgery for juvenile idiopathic scoliosis between October 2017 and January 2020 was conducted. All of them had curves greater than 45 degrees managed through instrumentation and arthrodesis. Post-surgical quality of life was assessed using the SRS 22 questionnaire. Results: The average age of our patients at the time of the intervention was 15.5 years with a predominance of female patients. The application of the SRS 22 questionnaire generated the following mean scores: pain 4.6, function 4.3, self-image 4.41, mental health 4.89, and satisfaction 5.0. Conclusions: The development of surgical techniques has allowed good results to be achieved in the treatment of scoliosis. The evaluation of our patients using the SRS 22 questionnaire reflects a good quality of life in the 5 parameters evaluated. The main limitations of this study were the small sample size and its retrospective nature. Level of Evidence III; Retrospective, longitudinal, descriptive, observational study.

RESUMO Objetivo: Relatar os resultados de nossos pacientes operados para correção de escoliose com relação à sua qualidade de vida. Introdução: A escoliose idiopática juvenil afeta entre 1% e 3% da população durante a puberdade. O tratamento será conservador na maioria dos casos. O tratamento cirúrgico terá como objetivo melhorar o alinhamento coronal e sagital. O questionário SRS 22 é uma ferramenta útil para avaliar a qualidade de vida desses pacientes. Métodos: Foi realizado um estudo retrospectivo de 22 pacientes operados entre outubro de 2017 e janeiro de 2020 devido à escoliose idiopática juvenil. Todos tinham curvas superiores a 45 graus tratadas com instrumentação e artrodese. A qualidade de vida pós-operatória foi avaliada por meio do questionário SRS-22. Resultados: A média de idade dos nossos pacientes no momento da intervenção foi 15,5 anos, com predominância do sexo feminino. A aplicação do questionário SRS-22 gerou os seguintes escores médios: dor 4,6; função 4,3; autoimagem 4,41; saúde mental 4,89 e satisfação 5,0. Conclusões: O desenvolvimento das técnicas cirúrgicas permitiu obter bons resultados no tratamento da escoliose. A avaliação de nossos pacientes por intermédio do questionário SRS 22 reflete boa qualidade de vida nos cinco parâmetros avaliados. As principais limitações deste estudo foram o pequeno tamanho da amostra e seu caráter retrospectivo. Nível de Evidência III; Estudo retrospectivo, longitudinal, descritivo, observacional.

RESUMEN Objetivo: Reportar los resultados de nuestros pacientes operados para corrección de escoliosis en relación a su calidad de vida. Introducción: La escoliosis idiopática juvenil afecta entre el 1% y 3% de la población durante la pubertad. El tratamiento será, en la mayoría, de los casos conservador. El tratamiento quirúrgico tendrá como objetivo mejorar la alineación coronal y sagital. El cuestionario SRS 22 es una herramienta útil para la valoración de la calidad de vida en estos pacientes. Métodos: Se realizó un estudio retrospectivo de 22 pacientes intervenidos entre octubre de 2017 y enero de 2020 debido a la escoliosis idiopática juvenil. Todos tenían curvas mayores de 45 grados manejadas mediante instrumentación y artrodesis. Se realizó la evaluación de la calidad de vida posquirúrgica mediante el cuestionario SRS-22. Resultados: La edad promedio de nuestros pacientes en el momento de la intervención fue de 15,5 años con predominio de pacientes del sexo femenino. La aplicación del cuestionario SRS-22 generó las siguientes puntuaciones medias: dolor 4,6; función 4,3; autoimagen 4,41; salud mental 4,89 y satisfacción 5,0. Conclusiones: El desarrollo de las técnicas quirúrgicas ha permitido obtener buenos resultados en el tratamiento de la escoliosis. La evaluación de nuestros pacientes mediante el cuestionario SRS 22 refleja una buena calidad de vida en los 5 parámetros evaluados. Las limitaciones principales de este estudio han sido el pequeño tamaño de la muestra y su carácter retrospectivo. Nivel de Evidencia III; Estudio retrospectivo, longitudinal, descriptivo, observacional.

Case Report: The Association of Wilson Disease in a Patient With Ataxia and GLUT-1 Deficiency.

Background: Wilson disease (WD) and glucose transporter type 1 (GLUT1) deficiency syndrome are two syndromes with different modes of inheritance but share certain similarities on neurological presentation. To date we have not found previous reports of an association between these two disorders. Case Presentation: Here we describe a 9-year-old male with global developmental delay that presented with intermittent and sudden onset weakness that first occurred at age 3. He was diagnosed with a mutation in the SLC2A1 (Solute Carrier Family 2 Member 1) gene, which results in GLUT1 deficiency. A ketogenic diet could not be started because of unexplained elevated liver enzymes. Due to his liver enzymes' persistent elevation, further investigations demonstrated mildly decreased ceruloplasmin levels, high basal 24-h urinary copper excretion, and an elevated hepatic parenchymal copper concentration on liver biopsy, consistent with WD. Genetic testing revealed two separate mutations in the ATP7B (ATPase Copper Transporting Beta) gene, consistent with WD. The patient was treated with a low copper diet, zinc acetate, and trientine hydrochloride. When liver enzymes normalized, he was subsequently started on a ketogenic diet with improvement in neurological symptoms. His neurological symptoms were most likely secondary to GLUT1 deficiency syndrome, as WD's neurological symptoms are primarily observed in the second decade of life. Conclusion: Recent studies have demonstrated the importance of genetic testing upon unexplained persistent elevation of liver enzymes. This case highlights the importance of carefully evaluating a patient with an unexplained liver disorder, even in the presence of primary neurological disease, as it can have significant therapeutic implications.

Cholbam® and Zellweger spectrum disorders: treatment implementation and management.

BACKGROUND: Zellweger spectrum disorders (ZSDs) are a rare, heterogenous group of autosomal recessively inherited disorders characterized by reduced peroxisomes numbers, impaired peroxisomal formation, and/or defective peroxisomal functioning. In the absence of functional peroxisomes, bile acid synthesis is disrupted, and multisystem disease ensues with abnormalities in the brain, liver, kidneys, muscle, eyes, ears, and nervous system. MAIN BODY: Liver disease may play an important role in morbidity and mortality, with hepatic fibrosis that can develop as early as the postnatal period and often progressing to cirrhosis within the first year of life. Because hepatic dysfunction can have numerous secondary effects on other organ systems, thereby impacting the overall disease severity, the treatment of liver disease in patients with ZSD is an important focus of disease management. Cholbam® (cholic acid), approved by the U.S. Food and Drug Administration in March 2015, is currently the only therapy approved as adjunctive treatment for patients with ZSDs and single enzyme bile acid synthesis disorders. This review will focus on the use of CA therapy in the treatment of liver disease associated with ZSDs, including recommendations for initiating and maintaining CA therapy and the limitations of available clinical data supporting its use in this patient population. CONCLUSIONS: Cholbam is a safe and well-tolerated treatment for patients with ZSDs that has been shown to improve liver chemistries and reduce toxic bile acid intermediates in the majority of patients with ZSD. Due to the systemic impacts of hepatic damage, Cholbam should be initiated in patients without signs of advanced liver disease.

Albendazole Release from Silica-Chitosan Nanospheres. In Vitro Study on Cervix Cancer Cell Lines.

In this work, a pH-responsive drug-carrier based on chitosan-silica nanospheres was developed as a carrier for Albendazole (ABZ), a poorly water-soluble anthelmintic drug. Spherical silica nanoparticles were obtained by Stöber method and further etched to obtain mesoporous particles with sizes ranging from 350 to 400 nm. The specific BET area of nanoparticles increased from 15 m2/g to 150 m2/g for etched silica, which also exhibited a uniform pore size distribution. X-ray powder diffraction showed the presence of amorphous phase of silica and a low-intensity peak attributed to ABZ for the drug-loaded nanoparticles. A uniform layer of chitosan was obtained ranging from 10 to 15 nm in thickness due to the small concentration of chitosan used (0.45 mg of chitosan/mg of SiO2). The in vitro evaluation of hybrid nanoparticles was performed using four cervical cancer cell lines CaSki, HeLa, SiHa and C33A, showing a significant reduction in cell proliferation (>85%) after 72 h. Therefore, we confirmed the encapsulation and bioavailability of the drug, which was released in a controlled way, and the presence of chitosan delayed the release, which could be of interest for the development of prolonged release drug delivery systems.