[Juvenile Pompe disease: Undescribed genotype. First report in Quintana Roo]. / Enfermedad de Pompe juvenil: genotipo no descrito. Primer reporte en Quintana Roo.

Background: Pompe disease (PD) is a rare autosomal recessive genetic disorder (1 in 14,000) which affects the synthesis of acid alpha-glucosidase (AGA), leading to intralysosomal glycogen accumulation in muscle tissue. The clinical presentation is heterogeneous, with variable degrees of involvement and progression, classifiable based on the age of onset into infantile (classic or non-classic) and late-onset forms (juvenile or adult). The diagnostic test of choice is the enzymatic analysis of AGA, and the only pharmacological treatment is enzyme replacement therapy (ERT). This document aims to report a clinical case of late-onset PD. Clinical case: 14-year-old male who started at the age of 5 with postural alterations, gait changes, and decreased physical performance compared to his peers. A diagnostic evaluation was initiated in 2022 due to worsening neuromuscular symptoms, accompanied by dyspnea, tachycardia, and chest pain. A suspicion of a lysosomal storage myopathy was established, and through enzymatic determination of AGA the diagnosis of PD was confirmed. The study of the GAA gene revealed the association of 2 previously unreported genomic variants. ERT was initiated, resulting in clinical improvement. Conclusions: The age of symptom onset, severity of clinical presentation, and prognosis of the disease depend on the specific mutations involved. In this case, the identified genetic alterations are associated with different phenotypes. However, based on the clinical presentation, it is categorized as juvenile PD with an indeterminate prognosis.

Introducción: la enfermedad de Pompe (EP) es un padecimiento genético autosómico recesivo poco frecuente (1:14,000) que afecta la síntesis de alfa-glucosidasa ácida (AGA) y condiciona un depósito de glucógeno intralisosomal en tejido muscular. La presentación clínica es heterogénea, con grados variables de afectación y progresión, clasificable según la edad de aparición en infantil (clásica y no clásica) y de inicio tardío (juvenil o de adultez). La prueba diagnóstica de elección es el análisis enzimático de AGA y el único tratamiento farmacológico es la terapia de reemplazo enzimático (TRE). Este documento tiene como objetivo reportar un caso clínico de EP de inicio tardío. Caso clínico: paciente de sexo masculino de 14 años que comenzó a los 5 años con alteraciones de la postura, marcha y desempeño físico. Se inició protocolo de estudio ante agravamiento de los síntomas neuromusculares, a los que se agregaron disnea, taquicardia y dolor torácico. Se sospechó de una miopatía metabólica de depósito lisosomal y mediante determinación enzimática de AGA se confirmó el diagnóstico de EP. El estudio molecular del gen GAA reportó una asociación de 2 variantes genómicas no descritas previamente. Se empleó la TRE con mejoría clínica. Conclusiones: la edad de inicio del cuadro clínico, severidad y pronóstico dependen de las mutaciones presentadas. En este caso, las alteraciones genéticas encontradas están relacionadas con diferentes fenotipos; no obstante, por clínica es categorizado como una EP juvenil con pronóstico indeterminado.

Role of Quinoa (Chenopodium quinoa Willd) and Chickpea (Cicer arietinum L.) Ratio in Physicochemical Stability and Microbiological Quality of Fermented Plant-Based Beverages during Storage.

Three different fermented plant-based beverages were prepared and stored for a long period (50 days) to assess the effect of the quinoa-to-chickpea ratio on physicochemical stability and microbiological quality. Physicochemical stability was evaluated based on pH, acidity, Brix degrees, water-holding capacity (WHC), viscosity, and viscoelasticity. At the end of the long-term storage period, the pH, acidity, and WHC remained stable. During the entire storage period, the beverages maintained good bacterial, fungal, and lactic acid bacteria (LAB) counts. Quinoa and chickpea flour ratios of 50% showed a higher viscosity (18 Pa.s) and WHC (65%) during short-term storage (0-30 d), indicating that the presence of chickpea flour had a positive effect on these parameters, possibly because chickpea starch contains higher amounts of amylose and long-branch chain amylopectin, which impacts the retrogradation pattern under acidic and refrigerated conditions. However, at the end of storage (50 days), the same blend had a higher acidity, lower viscosity (0.78 Pa.s), and lower LAB counts (~1 × 108 CFU/mL), indicating that the increase in chickpea flour had an adverse long-term effect on these parameters. These results suggest that although different ratios of plant sources can improve the physical aspects, they need to be incorporated in a balanced manner to avoid negative effects on both short- and long-term storage, owing to the incorporation of different types of starches and proteins affecting the stability of the system.

Comparison of Aedes aegypti arbovirus transmission thresholds in two communities with differing water supply infrastructure.

BACKGROUND: To assess whether the 'economic boom' in the tropical seaport city of Barranquilla improved tapped water supplies to socio-economically poor neighbourhoods resulting in: (1) their reduced use for domestic water-storage in large (> 1,000-litre) custom-made cement tanks which are their principal Aedes aegypti breeding sites and (2) their pupae/person index (PPI) values to below their established 0.5-1.5 PPI arbovirus transmission-threshold value, compared to matched neighbourhoods in the: (a) pre-economic boom (2004) period in Barranquilla and (b) economically-neglected seaport city of Buenaventura. METHODS: The simple, accurate and robust water surface sweep-net/calibration factor or total count methods were used to determine the total Ae. aegypti pupae numbers in greater or less than 20-litre water-holding container types located 'inside' or 'outside' these neighbourhood premises. The women residents also participated in questionnaire-based responses about their domestic water supplies, water-storage and maintenance and mosquito life stages and disease transmission knowledge, to subsequently plan appropriate resident education programmes. Microsoft Excel 8.0 with OpenEpi was used to determine the samples sizes and the statistical values. RESULTS: Tapped water supplies to the three poor Barranquilla neighbourhoods were dramatically increased from 2004 to 2023 resulting in their residents significantly reducing their: (a) large cement water-storage tanks from 1 per 6.9 (2004) to 1 per 31.2 (2020) premises (z = 10.5: p = 0) and (b) PPI values to 0.16, 0.19 and 0.53 (mean: 0.29: 95% CI ± 0.4) in each study neighbourhood. In contrast, tapped water supplies remained inadequate in the Buenaventura neighborhoods, thereby resulting in their continued use of many large (> 1,000-litre) water-storage containers (Barranquilla: 1 per 31.2 and Buenaventura: 1 per 1.5 premises: z = - 9.26: p = 0), with unacceptably high 0.81, 0.88 and 0.99 PPI values in each study neighbourhood (mean 0.89: 95% CI ± 0.12). CONCLUSIONS: Improved tapped water supplies resulted in reduced numbers of large custom-made stoneware water-containers, as are employed by poor residents throughout the world, as well as their Ae. aegypti PPI transmission threshold values which, together with appropriate residents' education programmes, are also urgently to reduce to prevent/reduce Ae. aegypti transmitted human diseases globally.

Clinicogenetic characterization of cerebrotendinous xanthomatosis in Brazil.

There are few cerebrotendineous xanthomatosis (CTX) case series and observational studies including a significant number of Latin American patients. We describe a multicenter Brazilian cohort of patients with CTX highlighting their clinical phenotype, recurrent variants and assessing possible genotype-phenotype correlations. We analyzed data from all patients with clinical and molecular or biochemical diagnosis of CTX regularly followed at six genetics reference centers in Brazil between March 2020 and August 2023. We evaluated 38 CTX patients from 26 families, originating from 4 different geographical regions in Brazil. Genetic analysis identified 13 variants in the CYP27A1 gene within our population, including 3 variants that had not been previously described. The most frequent initial symptom of CTX in Brazil was cataract (27%), followed by xanthomas (24%), chronic diarrhea (13.5%), and developmental delay (13.5%). We observed that the median age at loss of ambulation correlates with the age of onset of neurological symptoms, with an average interval of 10 years (interquartile range 6.9 to 11 years). This study represents the largest CTX case series ever reported in South America. We describe phenotypic characteristics and report three new pathogenic or likely pathogenic variants.

Morphological analysis and lipid composition of the stable fly Stomoxys calcitrans salivary glands reinforce important features of feeding behaviour.

Stomoxys calcitrans L. (Diptera: Muscidae), the stable fly, is a hematophagous insect of great veterinary importance, because it is a mechanical vector of diverse pathogens in livestock. The saliva of blood-feeding insects presents important pharmacologically active molecules that impair blood clotting, promote vasodilation and modulate the host immune system response, crucial processes for successful feeding. These properties also enable pathogens' transmission. In the present work, we describe an efficient protocol to dissect S. calcitrans salivary glands, their morphological characteristics and lipid profile. The mean length of the tubular gland is 3.23 mm with a bulbous posterior end and a narrow anterior end. Histological analysis revealed a monolayer of large polygonal epithelial cells with voluminous nuclei and high lipid content in their cytoplasm. Ultrastructural analysis showed that the epithelium is rich in mitochondria, free ribosomes, Golgi complex cisternae, presenting a great extension of rough endoplasmic reticulum that contains an electron-dense material. Lipid analysis by thin-layer chromatography showed that neutral fatty acids and phosphatidylcholine are predominant in the fly salivary glands. Lysophosphatidylcholine, an important signalling biomolecule involved in different metabolic processes, including host's immunomodulation and pathogens proliferation and differentiation, is also present.

Stomoxys calcitrans L. (Diptera: Muscidae), a mosca­dos­estábulos, é um inseto hematófago de grande importância veterinária, uma vez que é vetor mecânico de diversos patógenos que infectam animais da pecuária. A saliva de insetos que se alimentam de sangue apresenta importantes moléculas farmacologicamente ativas que impedem coagulação sanguínea, promovem vasodilatação e modulam o sistema imune do hospedeiro, processos cruciais para uma alimentação bem sucedida. Tais propriedades também permitem a transmissão de patógenos. No presente trabalho, nós descrevemos um protocolo eficiente para dissecar as glândulas salivares de S. calcitrans, suas características morfológicas e perfil lipídico. O comprimento médio da glândula tubular é 3.23 mm com uma porção posterior bulbosa e porção anterior estreita. Análises histológicas revelaram uma monocamada de células epiteliais largas e poligonais com núcleos volumosos e alto conteúdo lipídico em seus citoplasmas. Análises ultraestruturais mostraram um epitélio rico em mitocôndria, ribossomos livres, cisternas do complexo de Golgi, apresentando uma grande extensão de retículo endoplasmático que contém um material eletrodenso. A análise lipídica mostrou que ácidos graxos neutros e fosfatidilcolina predominam nas glândulas salivares da mosca. Lisofosfatidilcolina, uma importante biomolécula sinalizadora envolvida em diferentes processos metabólicos, incluindo imunomodulação do hospedeiro e proliferação e diferenciação de patógenos, também se encontra presente.

Physiological and Technological Properties of Probiotic Lacticaseibacillus rhamnosus GG Encapsulated with Alginate-Chitosan Mixture and Its Incorporation in Whole Milk.

This study developed and evaluated chitosan-sodium alginate capsules containing the probiotic Lacticaseibacillus rhamnosus GG using extrusion and emulsification techniques. The encapsulated L. rhamnosus GG cells were also evaluated for technological and probiotic-related physiological functionalities, as well as when incorporated in UHT and powdered milk. Extrusion (86.01 ± 1.26%) and emulsification (74.43 ± 1.41%) encapsulation techniques showed high encapsulation efficiency and high survival rates of L. rhamnosus GG during 28 days of refrigeration and room temperature storage, especially emulsification capsules (> 81%). The encapsulated L. rhamnosus GG cells showed high survival rates during exposure to simulated gastrointestinal conditions (72.65 ± 1.09-114.15 ± 0.44%). L. rhamnosus GG encapsulated by extrusion and emulsification performed satisfactorily in probiotic-related physiological (pH and bile salts tolerance) and technological properties (positive proteolytic activity, diacetyl and exopolysaccharides production, high NaCl tolerance (> 91%), besides having high heat tolerance (> 76%)). L. rhamnosus GG in extrusion and emulsification capsules had high survival rates (> 89%) and did not significantly affect physicochemical parameters in Ultra-High Temperature (UHT) and powdered milk during storage. The results demonstrate that L. rhamnosus GG can be successfully encapsulated with alginate-chitosan as a protective material through extrusion and emulsification techniques. UHT and powdered milk could serve as appropriate delivery systems to increase the intake of this encapsulated probiotic by consumers.

Oxygenated versus non-oxygenated flush out during deceased donor liver procurement: The first proof-of-concept study in humans.

BACKGROUND: Liver transplantation is used for treating end-stage liver disease, fulminant hepatitis, and oncological malignancies and organ shortage is a major limiting factor worldwide. The use of grafts based on extended donor criteria have become internationally accepted. Oxygenated machine perfusion technologies are the most recent advances in organ transplantation; however, it is only applied after a period of cold ischemia. Due to its high cost, we aimed to use a novel device, OxyFlush®, based on oxygenation of the preservation solution, applied during liver procurement targeting the maintenance of ATP during static cold storage (SCS). METHODS: Twenty patients were randomly assigned to the OxyFlush or control group based on a 1:1 ratio. In the OxyFlush group, the perfusion solution was oxygenated with OxyFlush® device while the control group received a non-oxygenated solution. Liver and the common bile duct (CBD) biopsies were obtained at three different time points. The first was at the beginning of the procedure, the second during organ preparation, and the third after total liver reperfusion. Biopsies were analyzed, and adenosine triphosphate (ATP) levels and histological scores of the liver parenchyma and CBD were assessed. Postoperative laboratory tests were performed. RESULTS: OxyFlush® was able to maintain ATP levels during SCS and improved the damage caused by the lack of oxygen in the CBD. However, OxyFlush® did not affect laboratory test results and histological findings of the parenchyma. CONCLUSION: We present a novel low-cost device that is feasible and could represent a valuable tool in organ preservation during SCS.

Exploring the Equilibrium State Diagram of Maltodextrins across Diverse Dextrose Equivalents.

This study investigates the equilibrium state diagram of maltodextrins with varying dextrose equivalents (DE 10 and 30) for quercetin microencapsulation. Using XRD, SEM, and optical microscopy, three transition regions were identified: amorphous (aw 0.07-0.437), semicrystalline (aw 0.437-0.739), and crystalline (aw > 0.739). In the amorphous region, microparticles exhibit a spherical morphology and a fluffy, pale-yellow appearance, with Tg values ranging from 44 to -7 °C. The semicrystalline region shows low-intensity diffraction peaks, merged spherical particles, and agglomerated, intense yellow appearance, with Tg values below 2 °C. The crystalline region is characterized by fully collapsed microstructures and a continuous, solid material with intense yellow color. Optimal storage conditions are within the amorphous region at 25 °C, aw 0.437, and a water content of 1.98 g H2O per g of dry powder. Strict moisture control is required at higher storage temperatures (up to 50 °C) to prevent microstructural changes. This research enhances understanding of maltodextrin behavior across diverse dextrose equivalents, aiding the development of stable microencapsulated products.

Effect of post-storage filters vs. pre-storage filters for leukoreduction of blood components on clinical outcomes: a systematic review and meta-analysis.

BACKGROUND: Leukoreduction has been used to limit the risk of adverse events. The most commonly used methodology is filtration (pre- or post-storage). However, whether pre-storage filtration is better than post-storage filtration needs to be clearly defined, particularly for countries that still use post-storage filtration. This study aimed to synthesize the best available evidence on the effectiveness of pre-storage filters compared with post-storage filters for transfusion reactions, for the occurrence of infections, for the length of hospital stay, and for the death of patients undergoing leukoreduced transfusion. METHODS: We searched the MEDLINE (PubMed), CINAHL (EBSCO), PsycINFO (APA), Scopus (Elsevier), The Cochrane Library (J. Wiley), Web of Science Core Collection (Clarivate Analytics), Embase (Elsevier), and LILACS (VHL) databases and gray literature for eligible studies in August 2020 and updated the search in October 2023. The Joanna Briggs Institute critical assessment tools were applied to analyze the quality appraisal of the studies. GRADE was used to determine the certainty of the evidence. RESULTS: The meta-analysis showed that pre-storage filtration was a protective factor for the occurrence of febrile non-hemolytic transfusion reaction in red blood cells (RR 0.49, 95% CI 0.41-0.59) and platelet concentrate transfusions (RR 0.16, 95% CI 0.12-0.22). The same did not occur for post-surgical infection after platelet concentrate transfusions (RR 0.82, 95% CI 0.65-1.04). Only one study analyzed the length of hospital stay and showed no significant difference between patients who received leukoreduced transfusions according to the type of filter used. According to the GRADE criteria, the certainty of the evidence for febrile non-hemolytic transfusion reactions was low for red blood cells and very low for platelet concentrate due to the high risk of bias. Infection was a low risk due to imprecision. CONCLUSIONS: The results of this review showed that the certainty of recommending the best type of filter (pre- or post-storage) for the benefit of the outcomes analyzed is still fragile; therefore, more robust evidence is needed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020192202.

Enzyme replacement therapy and immunotherapy lead to significant functional improvement in two children with Pompe disease: a case report.

BACKGROUND: Pompe disease, a rare autosomal recessive disorder caused by acid alpha-glucosidase deficiency, results in progressive glycogen accumulation and multisystem dysfunction. Enzyme replacement therapy with recombinant human acid alpha-glucosidase is the standard of care; however, some patients develop anti-recombinant human acid alpha-glucosidase antibodies, leading to reduced efficacy. This case report presents two infants with early-onset Pompe disease who developed IgG antibodies to enzyme replacement therapy and were subsequently treated with methotrexate, highlighting the importance of monitoring antibody development and exploring alternative therapeutic approaches. CASE PRESENTATION: Patient 1, a 10-month-old female from Bogota, Colombia, presented with generalized hypotonia, macroglossia, hyporeflexia, and mild left ventricular hypertrophy. Diagnostic tests confirmed early-onset Pompe disease, and enzyme replacement therapy was started at 12 months. Due to a lack of improvement and high anti-recombinant human acid alpha-glucosidase IgG antibody titers (1:1800), methotrexate was started at 18 months. After 8 months of combined therapy, antibody titers were negative and significant improvement in motor function was observed using the Gross Motor Function Measure 88. Patient 2, a 7-year-old female from Bogota, Colombia, was diagnosed with early-onset Pompe disease at 12 months and initiated enzyme replacement therapy. At 5 years of age, she experienced frequent falls and grip strength alterations. Functional tests revealed motor development delay, generalized hypotonia, and positive anti-recombinant human acid alpha-glucosidase IgG antibody titers (6400). Methotrexate was initiated, leading to a reduction in falls and antibody titers (3200) after 6 months, with no adverse events or complications. Motor function improvement was assessed using the Motor Function Measurement 32. CONCLUSIONS: The presented cases highlight the importance of monitoring patients for anti-recombinant human acid alpha-glucosidase antibody development during enzyme replacement therapy and the potential benefit of methotrexate as an immunomodulatory agent in early-onset Pompe disease. Early diagnosis and timely initiation of enzyme replacement therapy, combined with prophylactic immune tolerance induction, may improve clinical outcomes and reduce the development of anti-recombinant human acid alpha-glucosidase antibodies. The cases also highlight the importance of objective motor function assessment tools, such as Gross Motor Function Measure 88 and Motor Function Measurement 32, in assessing treatment response. Further research is needed to optimize treatment regimens, monitor long-term effects, and address the current limitations of enzyme replacement therapy in Pompe disease.

Potential use of other starch sources in the treatment of glycogen storage disease type Ia - an in vitro study.

BACKGROUND: Glycogen storage disease type Ia (GSD-Ia) is one of the most common hepatic GSD. Its treatment mainly consists of a diet including a high intake of slow-digestion carbohydrates such as raw cornstarch and the restriction of simple sugars. This enables the maintenance of euglycemia and prevents secondary metabolic disorders. Starch is a glucose polymer formed by amylose and amylopectin, which can be obtained from distinct sources. Although uncooked cornstarch has been successfully used in the treatment of GSD-Ia, it can lead to hyperglycemia and weight gain. in vitro andin vivo tests indicated that sweet manioc starch can be potentially used in the treatment of GSD-Ia. RESULTS: The moisture analysis revealed a variation from 10.3 to 12.8% in the sweet manioc starch samples, whereas the moisture content of uncooked cornstarch ranged from 7.3 to 11.1%. Quantifiable sugar was detected in 3/5 samples of sweet manioc starch and 1/3 samples of uncooked cornstarch. Notably, this uncooked cornstarch brand is widely employed in GSD-Ia treatment in Brazil. Products B and E had higher values of amylopectin and undetectable levels of sugars. A clinical trial is warranted to compare samples F and G and determine the impact of sugar trace in the same dietary source of starch. CONCLUSIONS: Collectively, the results demonstrated possible therapeutic alternatives for GSD-Ia in addition to traditional uncooked cornstarch.

Effect of the addition of black garlic on the quality parameters of jerked beef meat with pork.

The objective of this work was to evaluate the effects of the replacement of nitrite by natural antioxidants from black garlic (BG) on the quality parameters of jerked beef meat with pork for 60 days. Four formulations were prepared: control, 0.02% of sodium nitrite in brine curing, w/v (CON); 1.5% BG in brine curing, w/v (ASU); 1.5% BG in dry curing, w/w (ASS); and 1.5% of BG in the brine curing, w/v and 1.5% of BG in dry curing, w/w (ASUS). Nutritional composition, pH, water activity, shear force, fatty acid profile, color, and oxidative stability of the formulations were analyzed. The addition of BG did not affect the nutritional composition, pH, water activity, shear force, and fatty acid profile. On the other hand, it resulted in lower weight loss after centrifugation and lower values of L* and a*. TBARS values from the 30th day of storage were lower in the ASUS formulation, while carbonyl compounds at all times were lower than in the CON formulation. Results suggest that BG was an efficient alternative to nitrite in controlling protein oxidation during storage. Thus, the use of pork for the manufacture of jerked beef can be an alternative, and black garlic can be applied as a natural additive to the replacement of nitrite. In addition, black garlic was efficient in improving the oxidative stability of the jerked beef meat with pork.

Lisosomal storage disease caused by ingestion of Astragalus spp in llamas: an emergent concern.

Lysosomal storage diseases are inherited or acquired disorders characterized by dysfunctional lysosomes that lead to intracytoplasmic accumulation of undegraded substrates, causing impaired cellular function and death. Many acquired lysosomal storage diseases are produced by toxic plants, which have indolizidine alkaloids, including swainsonine, that inhibits lysosomal α-mannosidase and Golgi α-mannosidase II. Swainsonine-induced nervous disease associated with various plants has been reported, including species of the genus Astragalus, Sida, Oxitropis, Swainsona, and Ipomoea. Two species of Astragalus (i.e. Astragalus garbancillo and Astragalus punae) have been found to cause neurologic disease in llamas. In addition, A. garbancillo was also associated with malformations in the offspring, and possibly abortions and neonatal mortality in llamas. The diagnosis of Astragalus spp. intoxication is established based on clinical signs, microscopic and ultrastructural findings, lectin histochemistry, abundance of these plants in the grazing area and determination of swainsonine in plant specimens.

The Response of Naturally Based Coatings and Citrus Fungicides to the Development of Four Postharvest Fungi.

The tomato (Licopersicon esculentum Mill.) is considered to be one of the products with the highest demand due to its nutritional value; however, it is susceptible to infection by fungi during its pre- and postharvest stages. In this research, three commercial products (1% Citrocover, 1% Citro 80, and 0.002% Microdyn) and two coatings based on 1.0% chitosan/0.1% lime or 0.1% orange essential oils were evaluated in vitro and on Saladette tomatoes that were previously inoculated with four postharvest fungi. The application of the commercial citrus-based product Citrocover was highly effective in reducing the in vitro development of Aspergillus flavus, Fusarium oxysporum, and Colletotrichum gloeosporioides, but not Rhizopus stolonifer. The sanitizer Microdyn promoted infections with most fungi. Citrus-based products were effective in reducing infections with A. flavus in the tomatoes during storage. Overall, mycotoxin production was very low for all treatments. The use of commercial citrus-based products and coatings did not alter the weight loss, firmness, or total soluble solid contents of the treated tomatoes. The changes observed were, rather, associated with the normal ripening process of Saladette tomatoes. The commercial citrus-based products satisfactorily controlled the in vitro growth of the fungi Aspergillus flavus, Fusarium oxysporum, and Colletotrichum gloeosporioides.

Disease characteristics, effectiveness, and safety of vestronidase alfa for the treatment of patients with mucopolysaccharidosis VII in a novel, longitudinal, multicenter disease monitoring program.

BACKGROUND: Mucopolysaccharidosis VII (MPS VII) is an ultra-rare, autosomal recessive, debilitating, progressive lysosomal storage disease caused by reduced activity of ß-glucuronidase (GUS) enzyme. Vestronidase alfa (recombinant human GUS) intravenous enzyme replacement therapy is an approved treatment for patients with MPS VII. METHODS: This disease monitoring program (DMP) is an ongoing, multicenter observational study collecting standardized real-world data from patients with MPS VII (N ≈ 50 planned) treated with vestronidase alfa or any other management approach. Data are monitored and recorded in compliance with Good Clinical Practice guidelines and planned interim analyses of captured data are performed annually. Here we summarize the safety and efficacy outcomes as of 17 November 2022. RESULTS: As of the data cutoff date, 35 patients were enrolled: 28 in the Treated Group and seven in the Untreated Group. Mean (SD) age at MPS VII diagnosis was 4.5 (4.0) years (range, 0.0 to 12.4 years), and mean (SD) age at DMP enrollment was 13.9 (11.1) years (range, 1.5 to 50.2 years). Ten patients (29%) had a history of nonimmune hydrops fetalis. In the 23 patients who initiated treatment prior to DMP enrollment, substantial changes in mean excretion from initial baseline to DMP enrollment were observed for the three urinary glycosaminoglycans (uGAGs): dermatan sulfate (DS), -84%; chondroitin sulfate (CS), -55%; heparan sulfate (HS), -42%. Also in this group, mean reduction from initial baseline to months 6, 12, and 24 were maintained for uGAG DS (-84%, -87%, -89%, respectively), CS (-70%, -71%, -76%, respectively), and HS (+ 3%, -32%, and - 41%, respectively). All adverse events (AEs) were consistent with the known vestronidase alfa safety profile. No patients discontinued vestronidase alfa. One patient died. CONCLUSIONS: To date, the DMP has collected invaluable MPS VII disease characteristic data. The benefit-risk profile of vestronidase alfa remains unchanged and favorable for its use in the treatment of pediatric and adult patients with MPS VII. Reductions in DS and CS uGAG demonstrate effectiveness of vestronidase alfa to Month 24. Enrollment is ongoing.

Ultrasound-Assisted Nanoemulsion Loaded with Optimized Antibacterial Essential Oil Blend: A New Approach against Escherichia coli, Staphylococcus aureus, and Salmonella Enteritidis in Trout (Oncorhynchus mykiss) Fillets.

This study aimed to obtain and characterize an oil-in-water nanoemulsion (NE) loaded with an in vitro optimized bactericidal essential oil blend of 50% oregano, 40% thyme, and 10% lemongrass and to evaluate its potential at three different concentrations (0.5%, 1%, and 2%) in the inactivation of Escherichia coli, Staphylococcus aureus, and Salmonella enterica serotype Enteritidis inoculated in rainbow trout fillets stored at 4 °C for 9 days. Regarding the NE, the nanometric size (<100 nm) with low polydispersion (0.17 ± 0.02) was successfully obtained through ultrasound at 2.09 W/cm2. Considering the three concentrations used, S. Enteritidis was the most susceptible. On the other hand, comparing the concentrations used, the NE at 2% showed better activity, reducing S. Enteritidis, E. coli, and S. aureus by 0.33, 0.20, and 0.73 log CFU/g, respectively, in the trout fillets. Thus, this data indicates that this is a promising eco-friendly alternative to produce safe fish for consumption and reduce public health risks.

Endoscope channel drying, storage, and conditions after reprocessing: How safe are they in clinical practice?

INTRODUCTION AND AIMS: Adequate drying and proper storage of flexible endoscopes are essential for maintaining quality in their reprocessing. The aim of the present study was to evaluate the drying stages, storage, and channel conditions of endoscopes through borescope inspection. MATERIAL AND METHODS: The personnel responsible for endoscope reprocessing were interviewed. Storage conditions at 10 endoscopy facilities were inspected and an internal examination of the channels and ports of the stored equipment was carried out, utilizing a borescope. A total of 74 stored endoscope channels were evaluated. RESULTS: Only 10% of the facilities inspected utilized transport cases for storage and only 10% had rooms exclusively used for storage. Sixty percent of the facilities did not perform any shelf-life control. All the channels evaluated were scratched and fluids were present on 69% of them. CONCLUSIONS: Endoscope reprocessing can be improved through the implementation of drying and storage control and validation tools, as well as the use of borescopes and periodic clinical audits.

Alterations in Proteostasis Mechanisms in Niemann-Pick Type C Disease.

Niemann-Pick Type C (NPC) represents an autosomal recessive disorder with an incidence rate of 1 in 150,000 live births, classified within lysosomal storage diseases (LSDs). The abnormal accumulation of unesterified cholesterol characterizes the pathophysiology of NPC. This phenomenon is not unique to NPC, as analogous accumulations have also been observed in Alzheimer's disease, Parkinson's disease, and other neurodegenerative disorders. Interestingly, disturbances in the folding of the mutant protein NPC1 I1061T are accompanied by the aggregation of proteins such as hyperphosphorylated tau, α-synuclein, TDP-43, and ß-amyloid peptide. These accumulations suggest potential disruptions in proteostasis, a regulatory process encompassing four principal mechanisms: synthesis, folding, maintenance of folding, and protein degradation. The dysregulation of these processes leads to excessive accumulation of abnormal proteins that impair cell function and trigger cytotoxicity. This comprehensive review delineates reported alterations across proteostasis mechanisms in NPC, encompassing changes in processes from synthesis to degradation. Additionally, it discusses therapeutic interventions targeting pharmacological facets of proteostasis in NPC. Noteworthy among these interventions is valproic acid, a histone deacetylase inhibitor (HDACi) that modulates acetylation during NPC1 synthesis. In addition, various therapeutic options addressing protein folding modulation, such as abiraterone acetate, DHBP, calnexin, and arimoclomol, are examined. Additionally, treatments impeding NPC1 degradation, exemplified by bortezomib and MG132, are explored as potential strategies. This review consolidates current knowledge on proteostasis dysregulation in NPC and underscores the therapeutic landscape targeting diverse facets of this intricate process.

Coding, Decoding and Retrieving a Message Using DNA: An Experience from a Brazilian Center Research on DNA Data Storage.

DNA data storage based on synthetic oligonucleotides is a major attraction due to the possibility of storage over long periods. Nowadays, the quantity of data generated has been growing exponentially, and the storage capacity needs to keep pace with the growth caused by new technologies and globalization. Since DNA can hold a large amount of information with a high density and remains stable for hundreds of years, this technology offers a solution for current long-term data centers by reducing energy consumption and physical storage space. Currently, research institutes, technology companies, and universities are making significant efforts to meet the growing need for data storage. DNA data storage is a promising field, especially with the advancement of sequencing techniques and equipment, which now make it possible to read genomes (i.e., to retrieve the information) and process this data easily. To overcome the challenges associated with developing new technologies for DNA data storage, a message encoding and decoding exercise was conducted at a Brazilian research center. The exercise performed consisted of synthesizing oligonucleotides by the phosphoramidite route. An encoded message, using a coding scheme that adheres to DNA sequence constraints, was synthesized. After synthesis, the oligonucleotide was sequenced and decoded, and the information was fully recovered.