Post-Autologous Hematopoietic Cell Transplant Care in the "Home Sweet Home" Setting: A Treatment Paradigm Shift.

BACKGROUND: Multiple myeloma (MM) is the second most common hematologic malignancy, with 34,470 estimated new cases in 2022. High-dose therapy followed by autologous hematopoietic cell transplantation (auto-HCT) remains a standard treatment for MM even in the era of novel therapies. This is usually performed in hospital-based settings, either in the inpatient or outpatient units. Advanced Care at Home (ACH) represents a virtual hybrid hospital-at-home program that combines a virtual provider-staffed command center with a vendor-mediated supply chain capable of delivering high-acuity care in the comfort of the patients' own homes. In our program, we used the existing ACH platform to deliver post-HCT care for recipients of auto-HCT. PATIENTS AND METHODS: Four patients (female = 2, 50%) with MM, with a median age of 60 (range, 40-74) years, were admitted to the inpatient Blood and Marrow Transplant (BMT) unit. The conditioning regimen consisted of melphalan 200 mg/m2, administered on day -2. All patients received stem cell infusion (day 0) in the inpatient setting, with a median dose of 3.64 (range, 2.92-8.22) × 106/kg CD34 cells. RESULTS: Patients were discharged to their homes after completing the infusion on day 0 or day +1 at the latest. Post-infusion care was provided by the ACH team in coordination with the BMT team. The median time intervals to absolute neutrophil count and platelet engraftment were 12 (range, 11-13) and 11 (range, 9-16) days, respectively. All patients were successfully discharged from the ACH program at a median of day +14 (range, day +14 to day +15). CONCLUSIONS: Our results highlight the feasibility of delivering post-HCT care for auto-HCT recipients in the home setting and confirm the generalizability of this approach.

Quantity and fate of synthetic microfiber emissions from apparel washing in California and strategies for their reduction.

Synthetic microfibers have been identified as the most prevalent type of microplastic in samples from aquatic, atmospheric, and terrestrial environments across the globe. Apparel washing has shown to be a major source of microfiber pollution. We used California as a case study to estimate the magnitude and fate of microfiber emissions, and to evaluate potential mitigation approaches. First, we quantified synthetic microfiber emissions and fate from apparel washing in California by developing a material flow model which connects California-specific data on synthetic fiber consumption, apparel washing, microfiber generation, and wastewater and biosolid management practices. Next, we used the model to assess the effectiveness of different interventions to reduce microfiber emissions to natural environments. We estimate that in 2019 as much as 2.2 kilotons (kt) of synthetic microfibers were generated by apparel washing in California, a 26% increase since 2008. The majority entered terrestrial environments (1.6 kt), followed by landfills (0.4 kt), waterbodies (0.1 kt), and incineration (0.1 kt). California's wastewater treatment network was estimated to divert 95% of microfibers from waterbodies, mainly to terrestrial environments and primarily via land application of biosolids. Our analysis also reveals that application of biosolids on agricultural lands facilitates a directional flow of microfibers from higher-income urban counties to lower-income rural communities. Without interventions, annual synthetic microfiber emissions to California's natural environments are expected to increase by 17% to 2.1 kt by 2026. Further increasing the microfiber retention efficiency at the wastewater treatment plant would increase emissions to terrestrial environments, which suggests that microfibers should be removed before entering the wastewater system. In our model, full adoption of in-line filters in washing machines decreased annual synthetic microfiber emissions to natural environments by 79% to 0.5 kt and offered the largest reduction of all modeled scenarios.

Alloparental care in the sea: Brood parasitism and adoption within and between two species of coral reef Altrichthys damselfish?

The evolution of parental care opens the door for the evolution of brood parasitic strategies that allow individuals to gain the benefits of parental care without paying the costs. Here we provide the first documentation for alloparental care in coral reef fish and we discuss why these patterns may reflect conspecific and interspecific brood parasitism. Species-specific barcodes revealed the existence of low levels (3.5% of all offspring) of mixed interspecific broods, mostly juvenile Amblyglyphidodon batunai and Pomacentrus smithi damselfish in Altrichthys broods. A separate analysis of conspecific parentage based on microsatellite markers revealed that mixed parentage broods are common in both species, and the genetic patterns are consistent with two different modes of conspecific brood parasitism, although further studies are required to determine the specific mechanisms responsible for these mixed parentage broods. While many broods had offspring from multiple parasites, in many cases a given brood contained only a single foreign offspring, perhaps a consequence of the movement of lone juveniles between nests. In other cases, broods contained large numbers of putative parasitic offspring from the same parents and we propose that these are more likely to be cases where parasitic adults laid a large number of eggs in the host nest than the result of movements of large numbers of offspring from a single brood after hatching. The evidence that these genetic patterns reflect adaptive brood parasitism, as well as possible costs and benefits of parasitism to hosts and parasites, are discussed.

Assessment of External Guide Sequences' (EGS) Efficiency as Inducers of RNase P-Mediated Cleavage of mRNA Target Molecules.

RNase P is a ribozyme consisting of a catalytic RNA molecule and, depending on the organism, one or more cofactor proteins. It was initially identified as the enzyme that mediates cleavage of precursor tRNAs at the 5'-end termini to generate the mature tRNAs. An important characteristic of RNase P is that its specificity depends on the structure rather than the sequence of the RNA substrate. Any RNA species that interacts with an antisense molecule (called external guide sequence, EGS) and forms the appropriate structure can be cleaved by RNase P. This property is the basis for EGS technology, an antisense methodology for inhibiting gene expression by eliciting RNase P-mediated cleavage of a target mRNA molecule. EGS technology is being developed to design therapies against a large variety of diseases. An essential milestone in developing EGSs as therapies is the assessment of the efficiency of antisense molecules to induce cleavage of the target mRNA and evaluate their effect in vivo. Here, we describe simple protocols to test the ability of EGSs to induce cleavage of a target mRNA in vitro and to induce a phenotypic change in growing cells.

Assessment of configurations and chemistries of bridged nucleic acids-containing oligomers as external guide sequences: a methodology for inhibition of expression of antibiotic resistance genes.

EGSs (external guide sequences) are short antisense oligoribonucleotides that elicit RNase P-mediated cleavage of a target mRNA, which results in inhibition of gene expression. EGS technology is used to inhibit expression of a wide variety of genes, a strategy that may lead to development of novel treatments of numerous diseases, including multidrug-resistant bacterial and viral infections. Successful development of EGS technology depends on finding nucleotide analogs that resist degradation by nucleases present in biological fluids and the environment but still elicit RNase P-mediated degradation when forming a duplex with a target mRNA. Previous results suggested that locked nucleic acids (LNA)/DNA chimeric oligomers have these properties. LNA are now considered the first generation of compounds collectively known as bridged nucleic acids (BNA), modified ribonucleotides that contain a bridge at the 2',4'-position of the ribose. LNA and the second generation BNA, known as BNANC, differ in the chemical nature of the bridge. Chimeric oligomers containing LNA or BNANC and deoxynucleotide monomers in different configurations are nuclease resistant and could be excellent EGS compounds. However, not all configurations may be equally active as EGSs. RNase P cleavage assays comparing LNA/DNA and BNANC/DNA chimeric oligonucleotides that share identical nucleotide sequence but with different configurations were carried out using as target the amikacin resistance aac(6')-Ib mRNA. LNA/DNA gapmers with 5 and 3/4 LNA residues at the 5'- and 3'-ends, respectively, were the most efficient EGSs while all BNANC/DNA gapmers showed very poor activity. When the most efficient LNA/DNA gapmer was covalently bound to a cell penetrating peptide (CPP), the hybrid compound conserved the EGS activity as determined by RNase P cleavage assays and reduced the levels of resistance to amikacin when added to Acinetobacter baumannii cells in culture, an indication of cellular uptake and biological activity.

Inhibition of aminoglycoside 6'-N-acetyltransferase type Ib-mediated amikacin resistance in Klebsiella pneumoniae by zinc and copper pyrithione.

The in vitro activity of the aminoglycoside 6'-N-acetyltransferase type Ib [AAC(6')-Ib] was inhibited by CuCl2 with a 50% inhibitory concentration (IC50) of 2.8 µM. The growth of an amikacin-resistant Klebsiella pneumoniae strain isolated from a neonate with meningitis was inhibited when amikacin was supplemented by the addition of Zn(2+) or Cu(2+) in complex with the ionophore pyrithione. Coordination complexes between cations and ionophores could be developed for their use, in combination with aminoglycosides, to treat resistant infections.

Asymmetric connectivity of spawning aggregations of a commercially important marine fish using a multidisciplinary approach.

Understanding patterns of larval dispersal is key in determining whether no-take marine reserves are self-sustaining, what will be protected inside reserves and where the benefits of reserves will be observed. We followed a multidisciplinary approach that merged detailed descriptions of fishing zones and spawning time at 17 sites distributed in the Midriff Island region of the Gulf of California with a biophysical oceanographic model that simulated larval transport at Pelagic Larval Duration (PLD) 14, 21 and 28 days for the most common and targeted predatory reef fish, (leopard grouper Mycteroperca rosacea). We tested the hypothesis that source-sink larval metapopulation dynamics describing the direction and frequency of larval dispersal according to an oceanographic model can help to explain empirical genetic data. We described modeled metapopulation dynamics using graph theory and employed empirical sequence data from a subset of 11 sites at two mitochondrial genes to verify the model predictions based on patterns of genetic diversity within sites and genetic structure between sites. We employed a population graph describing a network of genetic relationships among sites and contrasted it against modeled networks. While our results failed to explain genetic diversity within sites, they confirmed that ocean models summarized via graph and adjacency distances over modeled networks can explain seemingly chaotic patterns of genetic structure between sites. Empirical and modeled networks showed significant similarities in the clustering coefficients of each site and adjacency matrices between sites. Most of the connectivity patterns observed towards downstream sites (Sonora coast) were strictly asymmetric, while those between upstream sites (Baja and the Midriffs) were symmetric. The best-supported gene flow model and analyses of modularity of the modeled networks confirmed a pulse of larvae from the Baja Peninsula, across the Midriff Island region and towards the Sonoran coastline that acts like a larval sink, in agreement with the cyclonic gyre (anti-clockwise) present at the peak of spawning (May-June). Our approach provided a mechanistic explanation of the location of fishing zones: most of the largest areas where fishing takes place seem to be sustained simultaneously by high levels of local retention, contribution of larvae from upstream sites and oceanographic patterns that concentrate larval density from all over the region. The general asymmetry in marine connectivity observed highlights that benefits from reserves are biased towards particular directions, that no-take areas need to be located upstream of targeted fishing zones, and that some fishing localities might not directly benefit from avoiding fishing within reserves located adjacent to their communities. We discuss the implications of marine connectivity for the current network of marine protected areas and no-take zones, and identify ways of improving it.

Population structure and phylogeography in Nassau grouper (Epinephelus striatus), a mass-aggregating marine fish.

To address patterns of genetic connectivity in a mass-aggregating marine fish, we analyzed genetic variation in mitochondrial DNA (mtDNA), microsatellites, and single nucleotide polymorphisms (SNPs) for Nassau grouper (Epinephelus striatus). We expected Nassau grouper to exhibit genetic differentiation among its subpopulations due to its reproductive behavior and retentive oceanographic conditions experienced across the Caribbean basin. All samples were genotyped for two mitochondrial markers and 9 microsatellite loci, and a subset of samples were genotyped for 4,234 SNPs. We found evidence of genetic differentiation in a Caribbean-wide study of this mass-aggregating marine fish using mtDNA (FST = 0.206, p<0.001), microsatellites (FST = 0.002, p = 0.004) and SNPs (FST = 0.002, p = 0.014), and identified three potential barriers to larval dispersal. Genetically isolated regions identified in our work mirror those seen for other invertebrate and fish species in the Caribbean basin. Oceanographic regimes in the Caribbean may largely explain patterns of genetic differentiation among Nassau grouper subpopulations. Regional patterns observed warrant standardization of fisheries management and conservation initiatives among countries within genetically isolated regions.

Permanent genetic resources added to molecular ecology resources database 1 April 2012 - 31 May 2012.

This article documents the addition of 123 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Brenthis ino, Cichla orinocensis, Cichla temensis, Epinephelus striatus, Gobio gobio, Liocarcinus depurator, Macrolophus pygmaeus, Monilinia vaccinii-corymbosi, Pelochelys cantorii, Philotrypesis josephi, Romanogobio vladykovi, Takydromus luyeanus and Takydromus viridipunctatus. These loci were cross-tested on the following species: Cichla intermedia, Cichla ocellaris, Cichla pinima, Epinephelus acanthistius, Gobio carpathicus, Gobio obtusirostris, Gobio sp. 1, Gobio volgensis, Macrolophus costalis, Macrolophus melanotoma, Macrolophus pygmaeus, Romanogobio albipinnatus, Romanogobio banaticus, Romanogobio belingi, Romanogobio kesslerii, Romanogobio parvus, Romanogobio pentatrichus, Romanogobio uranoscopus, Takydromus formosanus, Takydromus hsuehshanesis and Takydromus stejnegeri.