Bio-Technical Resources (United States)

Maxillary sinusitis is a common inflammatory condition often diagnosed through imaging modalities such as "cone-beam computedtomography (CBCT)". A prospective clinical research was conducted involving 200 patients with suspected maxillary sinusitis. The AImodel achieved a sensitivity of 89.1%, specificity of 91.7%, positive predictive value of 92.5% and negative predictive value of 87.8%and overall accuracy of 90.4%. The area under the ROC curve was 0.948, indicating excellent diagnostic discrimination. AI demonstrateshigh reliability in diagnosing maxillary sinusitis on CBCT scans and may serve as an effective adjunct in clinical imaging interpretation,enhancing diagnostic efficiency and consistency.

In January 2023, ICHQ9 was updated to include expanded guidance on risk-based decision-making, emphasizing its application in informing science-driven and strategic decisions. The revised guidance highlights that while quality risk management can aid decision-making, it does not eliminate the industry's obligation to comply with regulatory requirements. This article introduces a framework for evaluating the risks and benefits of pre-use/post-sterilization integrity testing (PUPSIT) using risk management principles. It provides a structured approach to assess the acceptability of alternative methods to the EU Annex 1 PUPSIT requirement, which acknowledges that PUPSIT may not always be feasible due to constraints such as the filtration of small solution volumes. In such cases, Annex 1 permits alternative approaches if a comprehensive risk assessment is conducted and effective controls are implemented to mitigate the risk of non-integral filtration systems. The proposed framework considers three critical domainspatient safety, process integrity, and regulatory complianceto ensure decisions are well-informed and balanced. By applying this science- and risk-based approach, organizations can navigate PUPSIT requirements effectively, ensuring compliance while addressing operational limitations.

In January 2023, ICH Q9 was updated to include expanded guidance on risk-based decision-making, emphasizing its application in informing science-driven and strategic decisions. The revised guidance highlights that while quality risk management can aid decision-making, it does not eliminate the industry's obligation to comply with regulatory requirements. This article introduces a framework for evaluating the risks and benefits of pre-use/post-sterilization integrity testing (PUPSIT) using risk management principles. It provides a structured approach to assess the acceptability of alternative methods to the EU Annex 1 PUPSIT requirement, which acknowledges that PUPSIT may not always be feasible due to constraints such as the filtration of small solution volumes. In such cases, Annex 1 permits alternative approaches if a comprehensive risk assessment is conducted and effective controls are implemented to mitigate the risk of non-integral filtration systems. The proposed framework considers three critical domains-patient safety, process integrity, and regulatory compliance-to ensure decisions are well-informed and balanced. By applying this science- and risk-based approach, organizations can navigate PUPSIT requirements effectively, ensuring compliance while addressing operational limitations.

Using live microbes as therapeutic candidates is a strategy that has gained traction across multiple therapeutic areas. In the skin, commensal microorganisms play a crucial role in maintaining skin barrier function, homeostasis, and cutaneous immunity. Alterations of the homeostatic skin microbiome are associated with a number of skin diseases. Here, we present the design of an engineered commensal organism, Staphylococcus epidermidis, for use as a live biotherapeutic product (LBP) candidate for skin diseases. The development of novel bacterial strains whose growth can be controlled without the use of antibiotics or genetic elements conferring antibiotic resistance enables modulation of therapeutic exposure and improves safety. We therefore constructed an auxotrophic strain of S. epidermidis that requires exogenously supplied d-alanine. The S. epidermidis NRRL B-4268 Δalr1 Δalr2 Δdat strain (SEΔΔΔ) contains deletions of three biosynthetic genes: two alanine racemase genes, alr1 and alr2 (SE1674 and SE1079), and the d-alanine aminotransferase gene, dat (SE1423). These three deletions restricted growth in d-alanine-deficient medium, pooled human blood, and skin. In the presence of d-alanine, SEΔΔΔ colonized and increased expression of human β-defensin 2 in cultured human skin models in vitro. SEΔΔΔ showed a low propensity to revert to d-alanine prototrophy and did not form biofilms on plastic in vitro. These studies support the potential safety and utility of SEΔΔΔ as a live biotherapeutic strain whose growth can be controlled by d-alanine.IMPORTANCE The skin microbiome is rich in opportunities for novel therapeutics for skin diseases, and synthetic biology offers the advantage of providing novel functionality or therapeutic benefit to live biotherapeutic products. The development of novel bacterial strains whose growth can be controlled without the use of antibiotics or genetic elements conferring antibiotic resistance enables modulation of therapeutic exposure and improves safety. This study presents the design and in vitro evidence of a skin commensal whose growth can be controlled through d-alanine. The basis of this strain will support future clinical studies of this strain in humans.

The scarcity of financial resources on the national scene and the high costs of maintaining research laboratories have prompted the search for new sources of funding and partnerships for research and development institutions. Therefore, a way in which research laboratories operate as internal and external service providers has been discussed in Bio-Manguinhos. LAMAM as a laboratory specialized in the field of macromolecules matches the concept of outsourcing of service as many biotechnology companies abroad. For this purpose, it is necessary to apply a laboratory management model for quick decision-making and for the choice of technological platforms to be made available to potential partners. Objective: Apply a laboratory management model based on indicators to evaluate bottlenecks and select potential technological plataforms executed on LAMAM to provide internal demands and external services. Methodology: We selected the SMART method (Specific, Measurable, Achievable, Relevant, Time-Based) for laboratory management, which is a model based on the choice of key performance indicators, subdivided in different categories: Performance (number of demanded procedures, developed activities, introduction of processes control); Human Resources (academic formation and produtivity), External Sources (grants founding obtained, external partnerships) and Regulatory Compliance. As for database were used the records of the last five to ten years of LAMAM. Results: Regarding to the performance indicators the most requested platform is the chromatographic followed by physico-chemical characterizations, corresponding to 55.4% and 23.0% of the executed demands over the last 5 years. The number of collaborations in projects of Bio-Manguinhos portfolio is around 11, however the level of requisition for activities performed increased considerably with the introduction of internal process controls since 2015. Over the last ten years LAMAM has continuously invested in the training of its professionals, which reflected directly the increase, since 2009, of published manuscripts (2.3/ year), pos-graduated students (1.8/year), external collaborations (11 collaborations/year, since 2017), contemplated projects (6 since 2014) and effective participations in three collaborative FIOCRUZ networks (Nano, Cancer and Chagas). LAMAM has all its employees properly trained in Good Laboratories Practices and Biosafety and since 2015, the laboratory began to produce operating instructions and standard operating procedures. The forecast for 2019 is an implementation of a sistematic study for valuation and cost of activities. Conclusion: Over the last 10 years, LAMAM has effectively acted in the training of human resources. The increase of internal and external demands has evidenced the applicability of LAMAM as a facility in the area of macromolecules. According to the inventory, technological platforms to be iniatially offered for external services could be chromatographic and physicochemical characterization, which are the lab's expertises. The use of these selected indicators may guide the next management decisions to be taken in order for LAMAM to provide external services.

The reductive amination chemistry is a synthetic approach normally used in the development of conjugate vaccines. In this approach, a high carrier protein reactivity is desirable. This improvement occurs by converting the side carboxylate groups of aspartic and glutamic residues into their respective hydrazides. The measurement of this conversion is an analytical challenge due to sample complexity and low concentrations of analytes. The determination of relative activation rate will allow us to monitorize the reproducibility of the method bringing innovation to process quality control Objective: The aim of this study is to quantify levels of aspartic and glutamic amino acids in proteins hydrolysates. Such quantification will be performed in those chemically modified proteins by isotopic labeling with aTRAQ reagent and (LC-SRM/MS) analysis. These procedures intend to determine the degree of activation of protein.

The first standard developed by the newly formed ASTM C7 Committee on Lime in 1912 was ASTM C5 Standard Specification for Quicklime for Structural Purposes. It was first approved in 1913 and is one of the oldest active standards for ASTM. It reflects a time when construction on a large scale had begun in North America and the characterization of construction materials was essential to ensuring performance and value in use. These expectations remain relevant and have expanded to other uses for lime and limestone as reflected in the current scope of the committee: To stimulate research and development; facilitate communication among producers, users, and other interested parties; and formulate specifications, practices, methods of test, and terminology relating to lime (quicklime, hydrated lime hydraulic lime and associated calcareous materials) and limestone used for industrial, environmental, chemical, construction, and agricultural applications.

Mevalonate kinase can be conveniently assayed by coupling to two other reactions and monitoring the consumption of NADH optically at 340 nm. No mevalonate kinase was detected in crude extracts of Saccharomyces cerevisiae strains, however, because of background interference measured in the absence of mevalonate. A strain of S. cerevisiae over-expressing mevalonate kinase was used to establish conditions for reduction of background interference. This method has been successfully applied to S. cerevisiae strains containing a wild type level of mevalonate kinase.

A silicone tubing sensor controlled a constant methanol concentration in a fermenter up to 72 hours without the need for on-line gas chromatography or complex feeding schemes based on dissolved oxygen spikes. Methanol concentration was controlled up to 1.0% (v/v) with control around a given set point of ± 0.24%. The length of tubing, airflow through the tubing, pump speed and medium formulation had no effect on the control of methanol concentration.