US regulatory compliance for medical combination products: an overview.

This article provides a high-level overview of US regulatory review and approval processes for the growing field of medical combination products (CPs; those merging drugs with devices and/or biological products). US law defines drugs, medical devices, and CPs in specific ways, and the components of a CP are still subject to their respective regulations while combined. The Food and Drug Administration's Office of Combination Products (OCP) oversees the review and classification of CPs, which is based on their primary mode of action.

Navigating regulatory and policy challenges for AI enabled combination devices.

In recent years, the Artificial Intelligence (AI) has enabled conventional Combination Devices (CDs) to innovate in healthcare merging with technology sectors. However, the challenges like reliance on predicate devices in US Food and Drug Administration (FDA's 510(k) pathway, especially for perpetually updating AI are stressed. Though the European Union (EU's new Medical Device Regulations address software and AI, fitting adaptive algorithms into conformity assessments remains difficult.

Medical Device Sterilization and Reprocessing in the Era of Multidrug-Resistant (MDR) Bacteria: Issues and Regulatory Concepts.

The emergence of multidrug-resistant (MDR) bacteria threatens humans in various health sectors, including medical devices. Since formal classifications for medical device sterilization and disinfection were established in the 1970's, microbial adaptation under adverse environmental conditions has evolved rapidly. MDR microbial biofilms that adhere to medical devices and recurrently infect patients pose a significant threat in hospitals.

Selective inhibition of Helicobacter pylori methionine aminopeptidase by azaindole hydroxamic acid derivatives: Design, synthesis, in vitro biochemical and structural studies.

Methionine aminopeptidases (MetAPs) are an important class of enzymes that work co-translationally for the removal of initiator methionine. Chemical inhibition or gene knockdown is lethal to the microbes suggesting that they can be used as antibiotic targets. However, sequence and structural similarity between the microbial and host MetAPs has been a challenge in the identification of selective inhibitors.

Extracellular Synthesis and Characterization of Silver Nanoparticles from Alkaliphilic sp.

Bio-nanotechnology offers eco-friendly processes for the synthesis of stable nanoparticles (NPs). We hypothesized that microorganisms isolated from the root nodules of leguminous plants would biosynthesize silver (Ag) bio-nanoparticles. Clover root nodules enriched with nutrient broth (NB) produced four distinct colonies on NA plates.

Spirocyclic sulfonamides with carbonic anhydrase inhibitory and anti-neuropathic pain activity.

A novel series of 4-oxo-spirochromane bearing primary sulfonamide group were synthetized as Carbonic Anhydrase inhibitors (CAIs) and tested for their management of neuropathic pain. Indeed, CAs have been recently validated as novel therapeutic targets in neuropathic pain. All compounds, here reported, showed strong activity against hCA II and hCA VII with K values in the low or sub-nanomolar range.

Microbial occurrence and antibiotic resistance in ready-to-go food items.

Foodborne pathogens, such as and , are commonly prevalent in contaminated food products seen through annual food recalls. Excessive use of antibiotics through the past few decades has led to a multitude of antibiotic resistant bacteria, including foodborne pathogens. We investigated microbial occurrence and their antibiotics resistances in ready-to-go food items, i.

Draft genome sequence of , the pearl millet downy mildew pathogen.

pathogen is the most important biotic production constraints of pearl millet in India, Africa and other parts of the world. We report a whole genome assembly and analysis of pathotype 1, one of the most virulent pathotypes of from India. The draft genome assembly contained 299,901,251 bp with 65,404 genes.

Extremophiles as sources of inorganic bio-nanoparticles.

Industrial use of nanotechnology in daily life has produced an emphasis on the safe and efficient production of nanoparticles (NPs). Traditional chemical oxidation and reduction methods are seen as inefficient, environmentally unsound, and often dangerous to those exposed and involved in NP manufacturing. However, utilizing microorganisms for biosynthesis of NPs allows efficient green production of a range of inorganic NPs, while maintaining specific size, shape, stability, and dispersity.

Human microbiome versus food-borne pathogens: friend or foe.

As food safety advances, there is a great need to maintain, distribute, and provide high-quality food to a much broader consumer base. There is also an ever-growing "arms race" between pathogens and humans as food manufacturers. The human microbiome is a collective organ of microbes that have found community niches while associating with their host and other microorganisms.

Commensals and Foodborne Pathogens can Arbitrate Epithelial-carcinogenesis.

Major shifts in intestinal commensal bacteria often result in changes in CD4 T lymphocyte populations, leading to an influx of Th17 cells, chronic inflammation, and eventually cancer. Consequently, the inappropriate propagation of certain commensal species in the gut has been associated with mucosal inflammatory diseases and cancer development. Recent experiments investigating the relationships between food-borne pathogens, enteric bacteria, and cancer have exposed the ability of certain bacterial species to significantly reduce tumor size and tumor progression in mice.

Synthetic immunosurveillance systems: nanodevices to monitor physiological events.

The field of nanotechnology has recently seen vast advancements in its applications for therapeutic strategy. This technological revolution has led way to nanomedicine, which spurred the development of clever drug delivery designs and ingenious nanovehicles for the monitoring of cellular events in vivo. The clinical implementations of this technology are innumerable and have demonstrated utility as diagnostic tools and fortifying machineries for the mammalian immune system.

Antibiotrophs: The complexity of antibiotic-subsisting and antibiotic-resistant microorganisms.

Widespread overuse of antibiotics has led to the emergence of numerous antibiotic-resistant bacteria; among these are antibiotic-subsisting strains capable of surviving in environments with antibiotics as the sole carbon source. This unparalleled expansion of antibiotic resistance reveals the potent and diversified resistance abilities of certain bacterial strains. Moreover, these strains often possess hypermutator phenotypes and virulence transmissibility competent for genomic and proteomic propagation and pathogenicity.

Bioremediation: a genuine technology to remediate radionuclides from the environment.

Radionuclides in the environment are a major human and environmental health concern. Like the Chernobyl disaster of 1986, the Fukushima Daiichi nuclear disaster in 2011 is once again causing damage to the environment: a large quantity of radioactive waste is being generated and dumped into the environment, and if the general population is exposed to it, may cause serious life-threatening disorders. Bioremediation has been viewed as the ecologically responsible alternative to environmentally destructive physical remediation.

Emergence of Antibiotic-Producing Microorganisms in Residential Versus Recreational Microenvironments.

Aims: To identify novel antibiotic-producing microbial strains with unprecedented pertinence. We hypothesize that site-specific soil samples will contain a variety of antibiotic-producing species (APS) with diverse specificity of molecular elements.

Place And Duration Of Study: Laboratory of Microbiology, Division of Biological and Health Sciences, University of Pittsburgh, Bradford, PA-16701, USA, between August 2010 and May 2011.

Ultraviolet-radiation-resistant isolates revealed cellulose-degrading species of Cellulosimicrobium cellulans (UVP1) and Bacillus pumilus (UVP4).

Among extremophiles, microorganisms resistant to ultraviolet radiation (UVR) have been known to produce a variety of metabolites (i.e., extremolytes).

Ultra-structural mapping of sugarcane bagasse after oxalic acid fiber expansion (OAFEX) and ethanol production by Candida shehatae and Saccharomyces cerevisiae.

Background: Diminishing supplies of fossil fuels and oil spills are rousing to explore the alternative sources of energy that can be produced from non-food/feed-based substrates. Due to its abundance, sugarcane bagasse (SB) could be a model substrate for the second-generation biofuel cellulosic ethanol. However, the efficient bioconversion of SB remains a challenge for the commercial production of cellulosic ethanol.

Ir(I)-catalyzed enantioselective decarboxylative allylic etherification: a general method for the asymmetric synthesis of aryl allyl ethers.

Ir(I)-catalyzed enantioselective decarboxylative allylic etherification of aryl allyl carbonates provides aryl allyl ethers. Key to the generality and high stereoselection of the reaction is the use of the intramolecular decarboxylative allylation process and [Ir(dbcot)Cl](2) as an Ir(I) source. Ir(I)-catalyzed diastereoselective decarboxylative allylic etherification, combined with asymmetric aldehyde crotylation and cross metathesis, can furnish monoprotected 2-methyl-1,3-diols (starting from simple aldehydes) with high diastereoselectivities.

Radiation-resistant extremophiles and their potential in biotechnology and therapeutics.

Extremophiles are organisms able to thrive in extreme environmental conditions. Microorganisms with the ability to survive high doses of radiation are known as radioresistant or radiation-resistant extremophiles. Excessive or intense exposure to radiation (i.

The Warburg effect: insights from the past decade.

Several decades ago, Otto Warburg discovered that cancer cells produce energy predominantly by glycolysis; a phenomenon now termed "Warburg effect". Warburg linked mitochondrial respiratory defects in cancer cells to aerobic glycolysis; this theory of his gradually lost its importance with the lack of conclusive evidence confirming the presence of mitochondrial defects in cancer cells. Scientists began to believe that this altered mechanism of energy production in cancer cells was more of an effect than the cause.

Emergence of antibiotic-resistant extremophiles (AREs).

Excessive use of antibiotics in recent years has produced bacteria that are resistant to a wide array of antibiotics. Several genetic and non-genetic elements allow microorganisms to adapt and thrive under harsh environmental conditions such as lethal doses of antibiotics. We attempt to classify these microorganisms as antibiotic-resistant extremophiles (AREs).

Two-dimensional gel electrophoresis: discovering neuropathic pain-associated synaptic biomarkers in spinal cord dorsal horn.

Nerve injury-induced neuropathic pain is a major public health problem worldwide. Current treatment for neuropathic pain has had limited success because the mechanisms that underlie the induction and maintenance of neuropathic pain are incompletely understood. However, recent advances in proteomics may allow us to uncover complicated biological mechanisms that occur under neuropathic pain conditions.

Bioconversion of Saccharum spontaneum (wild sugarcane) hemicellulosic hydrolysate into ethanol by mono and co-cultures of Pichia stipitis NCIM3498 and thermotolerant Saccharomyces cerevisiae-VS₃.

The lignocellulosic biomass is a low-cost renewable resource for eco-benign liquid fuel 'ethanol'. To resolve the hydrolysis of mixed sugars in lignocellulosic substrate Saccharum spontaneum, the microbial co-cultures of Pichia stipitis NCIM 3498 and thermotolerant Saccharomyces cerevisiae-VS(3) were analyzed for efficient bioconversion of mixed sugars into ethanol. Among the hydrolysis conditions, the acid hydrolysis released maximum sugars along with furans, phenolics and acetic acid.

Weedy lignocellulosic feedstock and microbial metabolic engineering: advancing the generation of 'Biofuel'.

Lignocellulosic materials are the most abundant renewable organic resources (~200 billion tons annually) on earth that are readily available for conversion to ethanol and other value-added products, but they have not yet been tapped for the commercial production of fuel ethanol. The lignocellulosic substrates include woody substrates such as hardwood (birch and aspen, etc.) and softwood (spruce and pine, etc.

Molecular methods in the diagnosis and management of chronic hepatitis B.

Chronic hepatitis B (CHB) infection remains a major global problem but the recent advances in molecular methods have revolutionized the diagnosis and management of CHB. Hepatitis B virus (HBV) DNA quantitation is the most useful molecular marker for the diagnosis and management of CHB. There is increasing evidence that the clinical outcome and efficacy of antiviral therapy for CHB could vary with the infecting HBV genotype, core promoter and precore mutations.