Genomic modifications for enhanced antibiotic production in rifamycin derivative-producing S699 strains: focusing on and genes.

Rifamycin and its derivatives are natural products that belong to the class of antibiotic-active polyketides and have significant therapeutic relevance within the therapy scheme of tuberculosis, a worldwide infectious disease caused by . Improving the oral bioavailability of rifamycin B was achieved through semisynthetic modifications, leading to clinically effective derivatives such as rifampicin. Genetic manipulation of the rifamycin polyketide synthase gene cluster responsible for the production of rifamycin B in the strain S699 represents a promising tool to generate new rifamycins.

Feasibility and Acceptability of Collecting Passive Smartphone Data for Potential Use in Digital Phenotyping Among Family Caregivers and Patients With Advanced Cancer.

Purpose: Modeling passively collected smartphone sensor data (called digital phenotyping) has the potential to detect distress among family caregivers and patients with advanced cancer and could lead to novel clinical models of cancer care. The purpose of this study was to assess the feasibility and acceptability of collecting passive smartphone data from family caregivers and their care recipients with advanced cancer over 24 weeks.

Methods: This was an observational feasibility study.

Facilitators and Barriers to Values Discussions Following LVAD Implantation: Perspectives from Diverse Patients and Family Caregivers.

Background: Delivering care that is responsive to who or what is most important to patients and family caregivers is a key aspect of quality care, yet it remains unclear how clinicians can best support individuals in expressing their personal values. We aimed to describe patient- and family caregiver-identified facilitators and barriers to engaging in values discussions with clinicians following implantation of a left ventricular assist device (LVAD).

Methods And Results: Using a qualitative descriptive approach, patients with an LVAD and their caregivers participated in 1-on-1 semistructured interviews and self-reported sociodemographics (January 2023-July 2023).

Olikomycin A-A Novel Calcium-Dependent Lipopeptide with Antibiotic Activity Against Multidrug-Resistant Bacteria.

Research into new antibiotics is becoming increasingly important as antibiotic resistance increases worldwide. The genus Streptomyces in particular is able to produce a wide range of antimicrobial products due to the large number of biosynthetic gene clusters (BGCs) in its genome. However, not all BGCs are expressed under laboratory conditions.

RS24090, a TetR family transcriptional repressor, negatively affects the rimocidin biosynthesis in Streptomyces rimosus M527.

The TetR family of regulators (TFRs), commonly reported as repressors, plays a role in regulating secondary metabolite production in Streptomyces. In this study, we sought to elucidate the relationship between TFRs and rimocidin production of Streptomyces rimosus M527. Through transcriptomic analysis, we identified the protein RS24090, which exhibited significant differential expression.

Analysis of the cryptic biosynthetic gene cluster encoding the RiPP curacozole reveals a phenylalanine-specific peptide hydroxylase.

Curacozole is representative of a cyanobactin-like sub-family of ribosomally synthesized and post-translationally modified peptides (RiPPs). The molecule is distinguished by its small macrocyclic structure, a poly-azole sequence that includes a phenyloxazole moiety, and a d--Ile residue. The enzymatic steps required for its formation are not well understood.

Identifying priority challenges of older adults with COPD: A multiphase intervention refinement study.

Background: Identifying priority challenges of older adults with chronic obstructive pulmonary disease (COPD) is critical to designing interventions aimed at improving their well-being and independence.

Objective: To prioritize challenges of older adults with COPD and those who care for them to guide refinement of a telephonic nurse coach intervention for patients with COPD and their family caregivers (EPIC: Empowering People to Independence in COPD).

Design: Multiphase study guided by Baltes Theory of Successful Aging and the 5Ms Framework: Phase 1: Nominal group technique (NGT), a structured process of prioritizing responses to a question through group consensus.

"Things That You Thought Mattered, None of That Matters": A Qualitative Exploration of Family Caregiver Values following Left Ventricular Assist Device Implantation.

Background: Intentional exploration, or elicitation, of patient and family values-who/what matters most-is critical to the delivery of person-centered care, yet the values elicitation experiences of family caregivers have been understudied. Understanding caregiver experiences discussing, reflecting upon, and acting on their values is critical to optimizing health decisions after left ventricular assist device (LVAD) implantation.

Objective: The aim of this study was to explore the values elicitation experiences of family caregivers of individuals with an LVAD in the postimplantation period.

"When I do have some time, rather than spend it polishing silver, I want to spend it with my grandkids": a qualitative exploration of patient values following left ventricular assist device implantation.

Background: Values are broadly understood to have implications for how individuals make decisions and cope with serious illness stressors, yet it remains uncertain how patients and their family and friend caregivers discuss, reflect upon, and act on their values in the post-left ventricular assist device (LVAD) implantation context. This study aimed to explore the values elicitation experiences of patients with an LVAD in the post-implantation period.

Methods: Qualitative descriptive study of LVAD recipients.

Project EPIC (Empowering People to Independence in COPD): Study protocol for a hybrid effectiveness-implementation pilot randomized controlled trial of telephonic, geriatrics-palliative care nurse-coaching in older adults with COPD and their family caregivers.

Background: EPIC (Empowering People to Independence in COPD) is a geriatric-palliative care telephonic, nurse coach intervention informed by Baltes' Theory of Successful Aging and adapted from the ENABLE (Educate, Nurture, Advise, Before Life Ends) intervention. EPIC, focused on improving independence, mobility, well-being, and COPD symptoms, has undergone formative and summative evaluation for adults with COPD.

Methods: The primary study aim is to assess the refined EPIC intervention's feasibility and acceptability via a pilot hybrid effectiveness-implementation randomized control trial in community-dwelling older adults with moderate to severe COPD and their family caregivers.

Transposon-based identification of genes involved in the rimocidin biosynthesis in Streptomyces rimosus M527.

The transposon mutagenesis strategy has been employed to generate random insertion mutants and analyze the correlation between genes and secondary metabolites in the genus Streptomyces. In this study, our primary objective was to identify an unknown gene involved in rimocidin biosynthesis and elucidate its role in rimocidin production in Streptomyces rimosus M527. To achieve this, we established a random mutant library of S.

P450-mediated dehydrotyrosine formation during WS9326 biosynthesis proceeds dehydrogenation of a specific acylated dipeptide substrate.

WS9326A is a peptide antibiotic containing a highly unusual -methyl--2-3-dehydrotyrosine (NMet-Dht) residue that is incorporated during peptide assembly on a non-ribosomal peptide synthetase (NRPS). The cytochrome P450 encoded by (P450) has been shown to be essential for the formation of the alkene moiety in NMet-Dht, but the timing and mechanism of the P450-mediated ,-dehydrogenation of Dht remained unclear. Here, we show that the substrate of P450 is the NRPS-associated peptidyl carrier protein (PCP)-bound dipeptide intermediate ()-2-pent-1'-enyl-cinnamoyl-Thr--Me-Tyr.

Family caregiver roles and challenges in assisting patients with cancer treatment decision-making: Analysis of data from a national survey.

Background: We aimed to describe the roles and challenges of family caregivers involved in patients' cancer treatment decision-making.

Methods: Family caregiver-reported data were analyzed from a national survey conducted in the United States by CancerCare® (2/2021-7/2021). Four select-all-that-apply caregiver roles were explored: (1) observer (patient as primary decision-maker); (2) primary decision-maker; (3) shared decision-maker with patient and (4) decision delegated to healthcare team.

Decision support training for advanced cancer family caregivers: Study protocol for the CASCADE factorial trial.

Background: Patients with advanced cancer face numerous decisions when diagnosed and often receive decision support from family caregivers. The CASCADE (CAre Supporters Coached to be Adept DEcision partners) factorial trial intervention aims to train caregivers in skills to provide effective decision support to patients and identify most effective intervention components.

Methods: This is a 2-site, single-blind, 2 factorial trial to test components of the CASCADE decision support training intervention for family caregivers of patients with newly-diagnosed advanced cancer delivered by specially-trained, telehealth, palliative care lay coaches over 24 weeks.

How Values Are Discussed, Reflected Upon, and Acted On by Patients and Family Caregivers in the Context of Heart Failure: A Scoping Review.

Purpose: Values are critical to how individuals make decisions and cope, yet the values of heart failure (HF) patients and their family caregivers (FCGs) remain understudied. We sought to report the state of the science on how values are discussed, reflected upon, and acted on by patients with HF, their FCGs, or both related to health-related decision making and coping.

Method: A scoping review was conducted of empirical studies using the following keywords: "heart failure," "values," "decision-making," and "coping.

Identification of RimR2 as a positive pathway-specific regulator of rimocidin biosynthesis in Streptomyces rimosus M527.

Background: Streoptomyces rimosus M527 is a producer of the polyene macrolide rimocidin which shows activity against various plant pathogenic fungi. Notably, the regulatory mechanisms underlying rimocidin biosynthesis are yet to be elucidated.

Results: In this study, using domain structure and amino acid alignment and phylogenetic tree construction, rimR2, which located in the rimocidin biosynthetic gene cluster, was first found and identified as a larger ATP-binding regulators of the LuxR family (LAL) subfamily regulator.

Double-reporter-guided targeted activation of the oxytetracycline silent gene cluster in Streptomyces rimosus M527.

In Streptomyces rimosus M527, the oxytetracycline (OTC) biosynthetic gene cluster is not expressed under laboratory conditions. In this study a reported-guided mutant selection (RGMS) procedure was used to activate the cluster. The double-reporter plasmid pAGT was constructed in which gusA encoding a β-glucuronidase and tsr encoding a thiostrepton resistance methyltransferase were placed under the control of the native promoter of oxyA gene (P ).

Improvement of rimocidin production in Streptomyces rimosus M527 by reporter-guided mutation selection.

In this study, we employed a reporter-guided mutation selection (RGMS) strategy to improve the rimocidin production of Streptomyces rimosus M527, which is based on a single-reporter plasmid pAN and atmospheric and room temperature plasma (ARTP). In plasmid pAN, PrimA, a native promoter of the loading module of rimocidin biosynthesis (RimA) was chosen as a target, and the kanamycin resistance gene (neo) under the control of PrimA was chosen as the reporter gene. The integrative plasmid pAN was introduced into the chromosome of S.

Project EPIC (Early Palliative Care In COPD): A Formative and Summative Evaluation of the EPIC Telehealth Intervention.

Context: Early, concurrent palliative care interventions in chronic obstructive pulmonary disease (COPD) are limited. Project EPIC (Early Palliative Care In COPD) is a multiphase mixed methods study working to fill this gap.

Objectives: To conduct a formative and summative evaluation of EPIC, a telephonic nurse coach-led early palliative care intervention for COPD adapted from the ENABLE© intervention in cancer.

Intratumoral delivered novel circular mRNA encoding cytokines for immune modulation and cancer therapy.

The success of the two mRNA vaccines developed by Moderna and BioNTech during the COVID-19 pandemic increased research interest into the application of mRNA technologies. Compared with the canonical linear mRNA used in these vaccines, circular mRNA has been found to mediate more potent and durable protein expression and demands a simpler manufacturing procedure. However, the application of circular mRNA is still at the initiation stage, and proof of concept for its use as a future medicine or vaccine is required.

Bias reported by family caregivers in support received when assisting patients with cancer-related decision-making.

Background: Family caregivers play an increasing role in cancer treatment decision-making. We examined bias reported by family caregivers in the support they and their patient received from their healthcare team when making these decisions, including associations with distress.

Methods: Analysis of 2021 national survey data of family caregivers of patients with cancer (N = 2703).

Revealing Genome-Based Biosynthetic Potential of sp. BR123 Isolated from Sunflower Rhizosphere with Broad Spectrum Antimicrobial Activity.

Actinomycetes, most notably the genus , have great importance due to their role in the discovery of new natural products, especially for finding antimicrobial secondary metabolites that are useful in the medicinal science and biotechnology industries. In the current study, a genome-based evaluation of sp. isolate BR123 was analyzed to determine its biosynthetic potential, based on its in vitro antimicrobial activity against a broad range of microbial pathogens, including gram-positive and gram-negative bacteria and fungi.

and Studies Reveal AA-18 as a Potential Candidate for Bioremediation of Mercury-Contaminated Wastewater.

Mercury (Hg) pollution is a worldwide problem and increasing day by day due to natural and anthropogenic sources. In this study, mercury-resistant (Hg) bacterial isolates were isolated from industrial wastewater of Ittehad Chemicals Ltd., Kala Shah Kaku, Lahore, Pakistan.