Peritoneal Dialysis Catheter Implantation: Avoiding Problems and Optimizing Outcomes

The success of peritoneal dialysis (PD) as renal replacement therapy is dependent upon the patient having a functional long‐term peritoneal access. There are a number of identified best practices that must be adhered to during PD catheter placement to achieve a durable and infection‐resistant access. The clinical setting, available resources, and the employed catheter insertion method may not always permit complete adherence to these practices; however, an attempt should be made to comply with them as closely as possible. Although omission of any one of the practices can lead to catheter loss, departures from some are committed more frequently, manifesting as commonly occurring clinical problems, such as drain pain, catheter tip migration, omental entrapment, pericatheter leaks and hernias, and poor exit‐site location. Understanding the technical pitfalls in PD catheter placement that lead to these problems, enable the provider to modify practice habits to avoid them and optimize outcomes.     

Growth characteristics of the chimeric Japanese encephalitis virus vaccine candidate, ChimeriVax-JE (YF/JE SA14--14--2), in Culex tritaeniorhynchus, Aedes albopictus, and Aedes aegypti mosquitoes

The Japanese encephalitis (JE) virus vaccine candidate, ChimeriVax-JE, which consists of a yellow fever (YF) 17D virus backbone containing the prM and E genes from the JE vaccine strain JE SA14--14--2, exhibits restricted replication in non-human primates, producing only a low-level viremia following peripheral inoculation. Although this reduces the likelihood that hematophagous insects could become infected by feeding on a vaccinated host, it is prudent to investigate the replication kinetics of the vaccine virus in mosquito species that are known to vector the viruses from which the chimera is derived. In this study ChimeriVax-JE virus was compared to its parent viruses, as well as to wild-type JE virus, for its ability to replicate in Culex tritaeniorhynchus, Aedes albopictus, and Aedes aegypti mosquitoes. Individual mosquitoes were exposed to the viruses by oral ingestion of a virus-laden blood meal or by intrathoracic (IT) virus inoculation. ChimeriVax-JE virus did not replicate following ingestion by any of the three mosquito species. Additionally, replication was not detected after IT inoculation of ChimeriVax-JE in the primary JE virus vector, Cx. tritaeniorhynchus. ChimeriVax-JE exhibited moderate growth following IT inoculation into Ae. aegypti and Ae. albopictus, reaching titers of 3.6-5.0 log(10) PFU/mosquito. There was no change in the virus genotype associated with replication in mosquitoes. Similar results were observed in mosquitoes of all three species that were IT inoculated or had orally ingested the YF 17D vaccine virus. In contrast, all mosquitoes either IT inoculated with or orally fed wild-type and vaccine JE viruses became infected, reaching maximum titers of 5.4-7.3 log(10) PFU/mosquito. These results indicate that ChimeriVax-JE virus is restricted in its ability to infect and replicate in these mosquito vectors. The low viremia caused by ChimeriVax-JE in primates and poor infectivity for mosquitoes are safeguards against secondary spread of the vaccine virus.     

From the Cover: A global carbon and nitrogen isotope perspective on modern and ancient human diet

Stable carbon and nitrogen isotope analyses are widely used to infer diet and mobility in ancient and modern human populations, potentially providing a means to situate humans in global food webs. We collated 13,666 globally distributed analyses of ancient and modern human collagen and keratin samples. We converted all data to a common “Modern Diet Equivalent” reference frame to enable direct comparison among modern human diets, human diets prior to the advent of industrial agriculture, and the natural environment. This approach reveals a broad diet prior to industrialized agriculture and continued in modern subsistence populations, consistent with the human ability to consume opportunistically as extreme omnivores within complex natural food webs and across multiple trophic levels in every terrestrial and many marine ecosystems on the planet. In stark contrast, isotope dietary breadth across modern nonsubsistence populations has compressed by two-thirds as a result of the rise of industrialized agriculture and animal husbandry practices and the globalization of food distribution networks.

Homo sapiens are the most widely distributed terrestrial mammal on the planet. Over the course of the Holocene, modern human range has extended to all continents, to the farthest islands of every ocean, and above the polar circles. The ability to rapidly adapt to newly encountered environments via technological and cultural innovation, that manifested ultimately in changes to our own genome, enabled this breath-taking range of expansion (1). Our capacity for successful innovation is tightly coupled to our ability to consume as “extreme opportunistic omnivores,” that is, across multiple trophic levels, from the base of a food web to filling the niche of apex predator (2–4). The development of agriculture, animal husbandry, urbanized societies, and commercial trade progressively allowed us to engage in niche construction of increasing complexity and extent (5, 6). As we permanently extended our range to above the Antarctic Circle in the 20th century, we progressively extended our capacity for advanced ecosystem engineering, thereby achieving a high degree of control over the production and distribution of our food supply across the globe (6, 7).The archaeological record documents our expansion into new habitats, our technological and social innovations, changing cultural practices, and the food that sustained us (8). While the physical remains of our diets, such as bones and charred plant remains, provide direct evidence of diet, not all foodstuffs are well-preserved. Moreover, such direct evidence does not indicate the proportion of different components that were consumed. A challenge in recreating past dietary components lies in accounting for taphonomic processes that may impact different dietary items at different rates, leading to underrepresentation of some important taxa (2). In contrast, the stable carbon and nitrogen isotope composition of human tissue (mostly collagen and keratin) has been investigated over the last several decades as a proxy for the proportions of different potential dietary components enabling an accounting for taphonomy (9). Carbon isotope composition (δ¹³C value) provides an indication of relative contributions of aquatic and/or terrestrial sources of carbon in the diet. Nitrogen isotope composition (δ¹⁵N value) is used to draw inferences regarding both the protein source and trophic level of an individual in the months or years before their death (10).To date, studies involving patterns in the stable isotope composition of ancient human remains (mostly bone collagen that can be well-preserved) have tended to focus on regional-scale variations during the Holocene, with the intent of determining wholesale changes in subsistence strategies (e.g., agriculture and pastoralism) and changing technological innovation, as well as social practices and structures (11–13). Although interpretation can sometimes be straightforward when observed differences are large, smaller differences are complicated by the complexities associated with disentangling the ecosystem processes driving C and N isotope fractionation within the food webs supporting human diet (13, 14).A parallel body of research has been conducted on the stable isotope composition of the tissues of contemporary humans (15–18). This research has mostly focused on noninvasive nail and hair keratin to examine the physiological processes in the human body, to deduce the recent movements of individuals (19), or to identify locations for repatriation of human remains (20). Substantial effort has been directed toward developing a spatial understanding of the controls on the stable isotope composition of modern human tissues, mostly as a consequence of the potential forensic application of this type of research (18, 21).Archaeological and modern stable isotope results on human tissues are not readily comparable for multiple reasons (Materials and Methods), hence there has been no attempt to interrogate the full record of dietary breadth and change for a globally distributed, omnivorous species, from the prehistoric to recent times. To address this gap, we collated isotope compositions of collagen as well as hair and nail keratin from three worldwide populations: modern urban (dates AD 1910 to 2020; Materials and Methods), modern subsistence (dates AD 1910 to 2020), and material dating to before the manufacture of industrial fertilizer (before AD 1910; pre-Haber–Bosch; hereafter, PHB). We calibrated all isotope compositions to their modern diet equivalent in order to directly compare modern and PHB distributions on a common scale. We show that the industrialized food system is vastly compressed in niche space and vastly less resilient compared with modern subsistence and PHB diets that are underpinned by complex food webs.We systematically collated (n = 6,879) globally distributed analyses of PHB archaeological bone collagen (pre-1910), with the majority of the data derived from samples of mid-Holocene or later age. We further collated analyses from studies of modern (post-1910) hair and nail keratin from populations of subsistence foragers, fishers, agriculturalists and pastoralists (n = 1,167), and urban populations (n = 5,610). In order to compare populations, we adjusted all measured values onto a common frame of reference; this being the equivalent δ¹³C and δ¹⁵N values of hair keratin in 2010 or modern keratin equivalent. We then used the accepted fractionations between human hair keratin and diet to calculate the modern diet equivalent (δ¹³C_MDE value) and (δ¹⁵N_MDE) values for all samples in 2010 (Materials and Methods).This approach has the advantage of allowing direct comparison of all results against the framework of our much more detailed contemporary understanding of stable isotope systematics in the modern biosphere. Exploiting this link between PHB and modern samples requires the assumption that the environmental conditions that drive the food webs that humans rely upon, wherever they are, have remained stable and that the past can be mapped onto the present. While there have been changes in climate and environment during the Holocene, these have been relatively muted, with most larger-scale landscape change resulting from human intervention beginning at varying times across the world in the Holocene and accelerating rapidly with the rise of industrial agriculture in the 20th Century (22).     

Detection of Entebbe Bat Virus after 54 Years

Entebbe bat virus (ENTV; Flaviviridae: Flavivirus), closely related to yellow fever virus, was first isolated from a little free-tailed bat (Chaerephon pumilus) in Uganda in 1957, but was not detected after that initial isolation. In 2011, we isolated ENTV from a little free-tailed bat captured from the attic of a house near where it had originally been found. Infectious virus was recovered from the spleen and lung, and the viral RNA was sequenced and compared with that of the original isolate. Across the polypeptide sequence, there were 76 amino acid substitutions, resulting in 97.8% identity at the amino acid level between the 1957 and 2011 isolates. Further study of this virus would provide valuable insights into the ecological and genetic factors governing the evolution and transmission of bat- and mosquito-borne flaviviruses.Bat virus investigations in Uganda were initially inspired in the mid-1950s by the isolations of rabies virus and a novel flavivirus, later to become known as Rio Bravo virus (Flaviviridae: Flavivirus), from the salivary glands of insectivorous bats in the United States.^1–3 Subsequently, investigators at the Uganda Virus Research Institute (UVRI) collected bats from the attic of UVRI, dissected salivary glands, and isolated viruses by intracerebral inoculation of triturated salivary gland extracts into neonatal mice.^4,5 This first effort resulted in the isolation of Entebbe bat salivary gland virus, strain IL-30 (Flaviviridae: Flavivirus) from a little free-tailed bat (Chaerephon pumilus) (Cretzchmar).^4,5 The taxon was then recognized by one of its synonyms: Tadarida (Chaerephon) limbata (Peters). Lumsden and others^4,5 determined that this isolate was a novel flavivirus through a series of neutralization tests using immune sera against 20 arboviruses as well as against Rio Bravo virus. By 1964, bat virus research had expanded at UVRI, and sampling of 1,022 additional bats yielded 14 strains of viruses including Dakar bat virus (Flaviviridae: Flavivirus) also from little free-tailed bats, and Bukalasa bat virus (Flaviviridae: Flavivirus) from Angolan free-tailed bats (Mops condylurus) (A. Smith).⁶ Isolation of Mount Elgon bat virus (Rhabdoviridae: Ledantevirus) followed shortly thereafter from an eloquent horseshoe bat (Rhinolophus hildebrandtii eloquens) (K. Anderson) captured in Kenya, with the virus being isolated and characterized at UVRI.^7,8 Additional bat virus discoveries in Uganda later included Kasokero virus (Bunyaviridae, unassigned) from an Egyptian fruit bat (Rousettus aegyptiacus) (E. Geoffroy).⁹ Entebbe bat virus (ENTV, renamed), Bukalasa bat virus, and Dakar bat virus were all isolated from insectivorous bats captured in the attic of UVRI.¹⁰ Serological surveys suggested that the infection prevalence of ENTV in wild populations of little free-tailed bats was high, but ENTV was never isolated again after the original discovery.^10,11To follow up on these early studies, arbovirus surveillance of bats was conducted in Uganda from 2011 to 2013. Bats were captured from attics in several locations around Entebbe and Kampala as part of a larger, country-wide sampling effort to be reported elsewhere. All bat captures were conducted under the approval of CDC/DVBD IACUC protocol 010-015. Bats were captured in attics using mist nets, taking appropriate biosafety precautions. On capture, bats were placed individually in cloth holding bags. Bats were anesthetized with halothane, exsanguinated by cardiac puncture, and euthanized by halothane overdose and cervical dislocation. Blood from bats was collected directly into serum separator tubes, centrifuged in the field, and placed immediately in a nitrogen dry vapor shipper. Liver, spleen, heart, lung, and kidney were all collected directly into cryovials and stored immediately on dry ice. In total, 95 little free-tailed bats and 34 Angolan free-tailed bats were captured in 2011, 15 little free-tailed bats in 2012, and 70 little free-tailed bats in 2013.Virus isolation was attempted first from spleens, and on a positive result, virus isolation was also performed from the remaining tissues harvested from the infected bat. A single virus was isolated from 1 of 180 (0.5%) little free-tailed bats. The infected bat was an adult male, captured in Banga, Nakiwogo (0°04.884′ N, 32°27.030′ E) on June 23, 2011, near UVRI. Infectious virus was isolated from the spleen and lung; no infectious virus was recovered from the heart, liver, or kidney. No other tissues, oral or fecal swabs were collected from the insectivorous bats captured in 2011. The isolate was initially identified as ENTV by sequencing of the flavivirus NS5 amplicon using primers FU2/CFD3,¹² followed by next-generation sequencing (NGS). Virus isolations, nucleic acid preparations, and NGS were performed as described previously.¹³ Novel primers were designed from contigs generated from the NGS data using Primer 3 software (Whitehead Institute for Biomedical Research, Cambridge, MA)¹⁴ (Supplemental Table 1), and the sequence for the entire genome was confirmed by direct sequencing. End terminal sequences were obtained using 5′/3′ RACE (FirstChoice^® RLM-RACE, Life Technologies, Carlsbad, CA) according to the manufacturer''s instructions. Virus-specific RACE primers are provided in Supplemental Table 1. The 5′ outer reaction used primer 514R in combination with the 5′ RACE outer primer. The 5′ RACE inner reactions used primer 388R together with the 5′ RACE inner primer; amplification was also achieved with primers 15F + 388R. The 3′ outer reaction used either primer 9882F or 10328F in combination with the 3′ RACE outer primer. The 3′ inner RACE was not successful. A maximum likelihood phylogenetic tree was generated in MEGA version 6.0¹⁵ (Center for Evolutionary Medicine and Informatics, Biodesign Institute, Tempe, AZ) using 10,493 nucleotides spanning the open reading frame sequence of select flavivirus genomes available in GenBank (Figure 1 ). The analysis was performed using a complete deletion substitution model and 1,000 bootstrap replicates.Open in a separate windowFigure 1.Maximum likelihood tree based on open reading frame sequence (complete gap deletion). Scale bar indicates nucleotide substitutions per site. Bootstrap values > 50% are shown (1,000 replicates). CFAV = cell fusing agent virus (NC001564); DENV1 = dengue type 1 ({"type":"entrez-nucleotide","attrs":{"text":"M87512","term_id":"323660","term_text":"M87512"}}M87512); DENV2 = dengue type 2 ({"type":"entrez-nucleotide","attrs":{"text":"M20558","term_id":"323449","term_text":"M20558"}}M20558); DENV3 = dengue type 3 ({"type":"entrez-nucleotide","attrs":{"text":"M93130","term_id":"323468","term_text":"M93130"}}M93130); DENV4 = dengue type 4 ({"type":"entrez-nucleotide","attrs":{"text":"AF326573","term_id":"12659201","term_text":"AF326573"}}AF326573); EHV = Edge Hill virus ({"type":"entrez-nucleotide","attrs":{"text":"DQ859060","term_id":"146411782","term_text":"DQ859060"}}DQ859060); ENTV = Entebbe bat virus ({"type":"entrez-nucleotide","attrs":{"text":"DQ837641","term_id":"112818954","term_text":"DQ837641"}}DQ837641); RBV = Rio Bravo virus ({"type":"entrez-nucleotide","attrs":{"text":"JQ582840","term_id":"383215103","term_text":"JQ582840"}}JQ582840); SEPV = Sepik virus (NC008719); SLEV = St. Louis encephalitis virus (NC007580); SOKV = Sokoluk virus ({"type":"entrez-nucleotide","attrs":{"text":"NC_026624","term_id":"765702601","term_text":"NC_026624"}}NC_026624); TBEV = tick-borne encephalitis virus (NC001672); WNV = West Nile virus ({"type":"entrez-nucleotide","attrs":{"text":"DQ211652","term_id":"77166600","term_text":"DQ211652"}}DQ211652); WSLV = Wesselsbron virus ({"type":"entrez-nucleotide","attrs":{"text":"DQ859058","term_id":"146411778","term_text":"DQ859058"}}DQ859058); YFV = yellow fever virus ({"type":"entrez-nucleotide","attrs":{"text":"K02749","term_id":"336192","term_text":"K02749"}}K02749); YOKV = Yokose virus (NC005039); ZIKV = Zika virus ({"type":"entrez-nucleotide","attrs":{"text":"AF013415","term_id":"2731554","term_text":"AF013415"}}AF013415).In total, 10,663 nucleotides of the ENTV genome were obtained (GenBank Accession number {"type":"entrez-nucleotide","attrs":{"text":"KP233893","term_id":"873167403","term_text":"KP233893"}}KP233893), of which the polypeptide is encoded between nucleotides 120 and 10,355. Kuno and Chang¹⁶ published the only other existing ENTV genome ({"type":"entrez-nucleotide","attrs":{"text":"DQ837641","term_id":"112818954","term_text":"DQ837641"}}DQ837641) sequenced from the original IL-30 strain. Compared with that original sequence, we report an additional 153 nucleotides in the 3′ noncoding region, but also experienced difficulty in obtaining the complete 3′ terminal sequence.¹⁶ Across the polypeptide sequence, there were 76 amino acid substitutions, resulting in 97.8% identity at the amino acid level between the 1957 and 2011 isolates. Before sequencing, the 1957 isolate had been passaged in suckling mouse brain, but the earlier passage history is unclear; the 2011 isolate was passaged twice in Vero cells. This 2.2% amino acid divergence is within the range that has been observed for other flaviviruses with isolations ranging between 1 and 49 years apart,^17–19 indicating relatively little change in the ENTV genome in 54 years since the first isolation.Every gene had at least one amino acid change except for PrM and M (20 It has also been shown to associate with host cellular vimentin during dengue virus replication to stabilize the replication complex.²¹ The functional significance of this high percentage of amino acid divergence has yet to be determined, but Hahn and others²² surmised that a large number of amino acid substitutions could be accommodated among the small, hydrophobic polypeptides NS2A, NS2B, NS4A, and NS4B so long as the hydrophobicity profile remained unchanged. In this case, changes to the NS4A hydrophobicity profile between these two isolates were inconsequential. Two of the 76 amino acid changes occurred at the junctions of NS2A/NS2B, and at NS4A/2K. The lengths of all of the genes were identical to those previously reported.¹⁶

Table 1

Length of each gene region in the Entebbe bat virus genome and the number (%) of amino acid (aa) substitutions in the 2011 isolate ({"type":"entrez-nucleotide","attrs":{"text":"KP233893","term_id":"873167403","term_text":"KP233893"}}KP233893) relative to the 1957 isolate ({"type":"entrez-nucleotide","attrs":{"text":"DQ837641","term_id":"112818954","term_text":"DQ837641"}}DQ837641)

Ultrafast photodriven intramolecular electron transfer from an iridium-based water-oxidation catalyst to perylene diimide derivatives

Photodriving the activity of water-oxidation catalysts is a critical step toward generating fuel from sunlight. The design of a system with optimal energetics and kinetics requires a mechanistic understanding of the single-electron transfer events in catalyst activation. To this end, we report here the synthesis and photophysical characterization of two covalently bound chromophore-catalyst electron transfer dyads, in which the dyes are derivatives of the strong photooxidant perylene-3,4:9,10-bis(dicarboximide) (PDI) and the molecular catalyst is the Cp^∗Ir(ppy)Cl metal complex, where ppy = 2-phenylpyridine. Photoexcitation of the PDI in each dyad results in reduction of the chromophore to PDI^•- in less than 10 ps, a process that outcompetes any generation of ^3∗PDI by spin-orbit-induced intersystem crossing. Biexponential charge recombination largely to the PDI-Ir(III) ground state is suggestive of multiple populations of the PDI^•--Ir(IV) ion-pair, whose relative abundance varies with solvent polarity. Electrochemical studies of the dyads show strong irreversible oxidation current similar to that seen for model catalysts, indicating that the catalytic integrity of the metal complex is maintained upon attachment to the high molecular weight photosensitizer.