Novel renal replacement therapies, such as a bioartificial kidney (BAK), are needed to improve current hemodialysis treatment of end-stage renal disease (ESRD) patients. As BAK applications may reveal safety concerns, we assessed the alloimmunization and related safety aspects of readily available conditionally immortalized human proximal tubule epithelial cell (ciPTEC) lines to be used in BAK. Two ciPTEC lines, originally derived from urine and kidney tissue, were characterized for the expression and secretion of relevant molecules involved in alloimmunization and inflammatory responses, such as HLA class-I, HLA-DR, CD40, CD80, CD86, as wells as soluble HLA class I and proinflammatory cytokines (IL-6, IL-8 and TNF-α). A lack of direct immunogenic effect of ciPTEC was shown in co-culture experiments with peripheral blood mononuclear cells (PBMC), after appropriate stimulation of ciPTEC. Tight epithelial cell monolayer formation on polyethersulfone flat membranes was confirmed by zonula occludens-1 (ZO-1) expression in the ciPTEC tight junctions, and by restricted inulin-FITC diffusion. Co-culture with (activated) PBMC did not jeopardize the transepithelial barrier function of ciPTEC. In conclusion, the absence of allostimulatory effects and the stability of ciPTEC monolayers show that these unique cells could represent a safe option for BAK engineering application.

CRISPR (clustered regularly interspaced short palindromic repeats) and associated proteins (Cas) act as adaptive immune systems in bacteria and archaea. Some CRISPR-Cas systems have been found to be associated with putative reverse transcriptases (RT), and an RT-Cas1 fusion associated with a type III-B system has been shown to acquire RNA spacers in vivo. Nevertheless, the origin and evolutionary relationships of these RTs and associated CRISPR-Cas systems remain largely unknown. We performed a comprehensive phylogenetic analysis of these RTs and associated Cas1 proteins, and classified their CRISPR-Cas modules. These systems were found predominantly in bacteria, and their presence in archaea may be due to a horizontal gene transfer event. These RTs cluster into 12 major clades essentially restricted to particular phyla, suggesting host-dependent functioning. The RTs and associated Cas1 proteins may have largely coevolved. They are, therefore, subject to the same selection pressures, which may have led to coadaptation within particular protein complexes. Furthermore, our results indicate that the association of an RT with a CRISPR-Cas system has occurred on multiple occasions during evolution.

Blood monocytes are expanded during obesity. However, the differential contribution of monocyte subsets in obesity-related metabolic disorders remains unknown. The aim of the study was to define the role of the Gr1low monocyte subset upon high-fat diet (HFD).

The study aimed to describe the kinetics of various cytokines from day 1 to day 14 of the onset of fever in neutropenic children and to evaluate their performances as discriminators of sepsis in the first 24 hours of fever, the possible influence of filgrastim, and the functioning of the IL-23/IL-17 axis.

Agitation poses a significant challenge in the treatment of schizophrenia. Electroconvulsive therapy (ECT) is a fast, effective and safe treatment for a variety of psychiatric disorders, but no meta-analysis of ECT treatment for agitation in schizophrenia has yet been reported.

Recent advancements in biotechnology have enabled the rapid identification and subsequent expression of pathogenic microbial major antigens that induce protective immune responses. However, subunit vaccines have not been successfully commercialized mainly due to the lack of sufficient levels of neutralizing antibodies (NAs). High levels of NA rely on the efficient recognition and cross-linking of multiple neutralizing epitopes with B-cell receptors (BCRs). Nanoparticles are able to display coupled antigenic arrays at high density and provide multiple binding molecular scenarios with BCRs. The high-resolution antigenic structure makes it possible to accurately display stable neutralizing epitopes. Therefore, the development of a nanovaccine that orientationally displays neutralizing epitopes is a feasible strategy. To address this hypothesis, the capsid (Cap) protein of porcine circovirus type 2 as model antigen was conjugated to gold nanoparticles (AuNPs) through direct reaction of the mercapto group of the unique cysteines with AuNPs, rendering Cap-AuNPs to have neutralizing epitopes on outer surface and an immunodominant epitope buried within the inner surface. In vitro studies showed that AuNPs promoted the phagocytosis of Cap protein and NA levels were significantly improved, meanwhile antibody levels against the immunodominant epitope was significantly reduced. In mouse studies, Cap-AuNP-immunized mice displayed a high production of interleukin (IL)-4, IL-10, and interferon-γ, suggesting that Cap-AuNPs can effectively activate CD4+ and CD8+ T cells and balance Th1 and Th2 cellular responses. This study presents a new vaccine design strategy based on antigen structure, where nanoparticles are coupled to antigens in well-ordered arrays and orientationally display neutralizing epitopes to enhance NA levels.

PD-L1 has been reported to be expressed in diverse human malignancies. However, the prognostic value of PD-L1 in digestive system cancers remains inconclusive. Therefore, we conducted this meta-analysis to evaluate the prognostic impact of PD-L1 expression in digestive system cancers.

Alcohol dehydrogenase (ADH) isoenzymes have been reported as a potential diagnostic marker for pancreatic cancer, but their prognostic value in pancreatic cancer remains unclear. The aim of this investigation was to identify the prognostic value of ADH genes in human patients with pancreatic adenocarcinoma (PAAD).

Influenza is a malady related to the human respiratory system, and its influenza-like illness (ILI) can cause an economic and social burden, especially among children and the elderly. This study was conducted to estimate the cost of illness based on a social perspective of ILI cases. A prospective study was conducted between February and March of 2016 in pharmacies, private clinics at Khanh Hoa, Lam Dong, Tay Ninh, Dong Nai Province, and Ho Chi Minh City, and Hospital of Tropical Diseases. Demographic and clinical information were collected by face-to-face interview. Direct costs (e.g., diagnosis and therapeutics) and indirect costs (e.g., cost of day loss) are included as treatment costs. The average cost of treatment associated with ILI was US$ 88.09 per case for all age groups; direct non-medical cost was higher compared to direct medical cost: 39.5% in pharmacies, 71.1% in clinics, and 64.2% in hospital. The indirect cost was US$27.49 per episode. The average total cost for children below 14 years old was much higher than that for the other age groups. The cost of illness of ILI was, therefore, the reason for the economic burden of influenza patients and their families. This study provides a database for future research and programs, and policies that can be adopted for influenza or ILI in Vietnam.

The aim of this article is to review the safety and efficacy data of dapagliflozin, saxagliptin, and their combination in the management of patients with type 2 diabetes. Evidence for the use of the single-tablet combination formulation is also presented.

Vaso-occlusive pain crises (VOCs) are the "hallmark" of sickle-cell disease (SCD) and can lead to sympathetic nervous system dysfunction. Increased sympathetic nervous system activation during VOCs and/or pain can result in vasoconstriction, which may increase the risk for subsequent VOCs and pain. Hypnosis is a neuromodulatory intervention that may attenuate vascular and pain responsiveness. Due to the lack of laboratory-controlled pain studies in patients with SCD and healthy controls, the specific effects of hypnosis on acute pain-associated vascular responses are unknown. The current study assessed the effects of hypnosis on peripheral blood flow, pain threshold, tolerance, and intensity in adults with and without SCD.

Patients with long-standing diabetes often demonstrate intestinal dysfunction, characterized as constipation or colonic hypersensitivity. Our previous studies have demonstrated the roles of voltage-gated sodium channels NaV1.7 and NaV1.8 in dorsal root ganglion (DRG) in colonic hypersensitivity of rats with diabetes. This study was designed to determine roles of antioxidant α-lipoic acid (ALA) on sodium channel activities and colonic hypersensitivity of rats with diabetes.

Beach plum, Prunus maritima Marshall, 1785 not Wangenh., 1787 (Rosaceae), currently under development as a potential crop, represents an under-acknowledged host plant for several Lepidoptera that have undergone declines in the northeastern USA. The Coastal Heathland Cutworm, Abagrotis nefascia (Smith, 1908), and the Dune Noctuid, Sympistis riparia (Morrison, 1875), are unrelated species of psammophilic noctuines (Lepidoptera: Noctuidae) regularly encountered on a localized basis in coastal southern New England and New York, and whose precise life history requirements are undocumented. We inferred and, based on field observation and rearing, corroborated beach plum as a larval host for these species in Massachusetts; the plant's role in sustaining other moths with limited or contracting regional distributions is discussed. Sympistis riparia, belonging to a widely distributed complex of closely related species, has been associated specifically with both maritime and freshwater dunes. The eastern populations of Abagrotis nefascia represent a conspicuous range disjunction, separated from the nearest western populations by more than 2000 miles, and originally described by Franclemont as race benjamini of Abagrotis crumbi, both later synonymized with Abagrotis nefascia. Following examination of types and other material, an evaluation of putatively diagnostic features from both the original description and our own observations, genitalic characters, and the results of provisional barcode analyses, Abagrotis benjamini Franclemont, stat. rev., is elevated to the rank of a valid species rather than representing eastern populations of Abagrotis nefascia (=crumbi) to which it originally referred.

A new leech species Helobdella blinnisp. n., is described from Montezuma Well, an isolated travertine spring mound located in central Arizona, USA. In its native habitat, Helobdella blinni had been previously identified as Helobdella stagnalis (Linnaeus, 1758), which was later reclassified to Helobdella modesta (Verrill, 1872). Similar to the European Helobdella stagnalis and North American Helobdella modesta, Helobdella blinni has six pairs of testisacs, five pairs of smooth crop caecae, one lobed pair of posteriorly-directed crop caecae, one pair of eyes, a nuchal scute, and diffuse salivary glands. However, the pigmentation of this new species ranges from light to dark brown, unlike Helobdella modesta which tends to be light grey in color. Also, Helobdella modesta produces a clutch of 12--35 pink eggs, whereas Helobdella blinni produces smaller clutches of white eggs (7-14, 0.5 ± 0.15 mm, N = 7) and consequently broods fewer young (1-14, 7 ± 3.3 mm, N = 97). Helobdella blinni are also able to breed year-round due to the constant warm water conditions in Montezuma Well. Their breeding season is not restricted by seasonal temperatures. These species are morphologically similar, however, comparing the COI mtDNA sequences of Helobdella blinni with sequences from nearby populations of Helobdella modesta and other Helobdella species from GenBank indicate that Helobdella blinni is genetically distinct from these other Helobdella populations.

The Palaearctic species of the Cheilosia caerulescens group (Diptera: Syrphidae) are revised in this work. The species group belongs to the genus Cheilosia subgenus Taeniocheilosia Oldenberg. One new species is described from north Caucasus, Cheilosia (Taeniocheilosia) circassica sp. n.Cheilosia primulae Hering is established as a junior synonym of Cheilosia laeviventris Loew. Four lectotype designations are made. The species of the Cheilosia caerulescens group are redescribed and illustrated, and a table of diagnostic characters and an identification key to species are provided. MtDNA COI barcodes were generated for several specimens of C. (T.) caerulescens Meigen and other Cheilosia (Taeniocheilosia) and Cheilosia s. str. taxa. Parsimony and maximum likelihood analyses did not place the morphologically similar C. hercyniae Loew in the C. caerulescens group but among other Cheilosia (Taeniocheilosia) taxa. The following eight taxa are included in the Cheilosia (T.) caerulescens group of species: Cheilosia armeniaca Stackelberg, 1960, C. caerulescens caerulescens (Meigen, 1822), C. caerulescens calculosa Skufjin, 1977, C. circassica sp. n., C. herculana Brădescu, 1982, C. kerteszi Szilády, 1938, C. laeviventris Loew, 1857, and C. venosa Loew, 1857.

A second species of Qingryllus Chen & Zheng is described and illustrated, Q. jiguanshanensissp. n., from Sichuan, China. This new species is similar to Q. striofemorus Chen & Zheng, 1995, but differs from the latter by the posterior margin of pronotum being distinctly widened, the veins of tegmina yellowish-white only on lateral side of dorsal area, and the epiphallus distinctly widened posteriorly. A distribution map of the species of this genus and habitus photographs of the new species are presented.

A new species of flanged bombardier beetles is described from Jiangxi and Sichuan, China, Paussus (Scaphipaussus) zhouchaoi sp. n. (Coleoptera, Carabidae, Paussinae, Paussini). All the type specimens were collected from colonies of the host ant Pheidole sp. (Hymenoptera, Formicidae, Myrmicinae). Important morphological characters of the new species are illustrated by color plates.

The genus Platymessa Mello-Leitão, 1941 is represented by two species in the Andes of Colombia: P. h-inscriptum Mello-Leitão, 1941 and P. ectroxantha Mello-Leitão, 1941. Platymessa victoriae Pinzón-M. & Townsend, sp. n. is described on the basis of somatic morphological characters and the structure of the penis. The placement of this new species in the genus Platymessa is based upon multiple characters including the outline of dorsal scutum, the presence of a blunt spine on coxa IV, having short and strong legs with femora III and IV having five longitudinal rows of small tubercles, the shape of the basitarsomeres of male leg I, the distribution and relative sizes of the marginal setae on the ventral plate of the penis, and the morphology of the chelicerae and cheliceral sockets. In contrast to other members of the genus, P. victoriae has a pair of triangular tubercles on scutal area III, lacks paired paramedian tubercles on scutal area V, and does not have a ladder mask color pattern on the dorsal scutum. The description of this species expands the distribution of the genus to north of the Oriental Cordillera in the Cesar Department of Colombia.

Longidorus piceicola, a new geographical and host record from Romania, was described and illustrated on the basis of two populations originating from a coniferous and a deciduous forest. The main morphological characters of specimens from Romania correspond very well with the type material collected from the soil around Picea abies L. (Slovakia) except for the shorter body and tail. The D2-D3 fragment of 28S rDNA from both populations was amplified and sequenced, and the sequences were identical to L. piceicola sequence from Slovakia. The partial 18S-ITS1-5.8S-ITS2 rDNA regions from one of the populations were sequenced for the first time. The evolutionary relationships between L. piceicola and the closest species L. intermedius based on D2-D3 sequence divergence and single-nucleotide polymorphisms are discussed. Although having very low sequence dissimilarity (0.3-0.9 %) both species have distinct morphology and biology. Longidorus piceicola differs from L. intermedius in having a much longer odontostyle, body, distance anterior end - guide ring, a wider lip region, more ventromedian supplements (11 vs 5-7) in the male, and develops through four rather than three juvenile stages. Furthermore, L. piceicola occurs more frequently in association with conifers, while L. intermedius is found mainly in oak forests.

Yumtaax Boucher (Coleoptera: Passalidae) is an endemic genus from the temperate sierras of Mexico and includes six narrowly distributed species. Yumtaax species have been assigned to several genera of Passalidae throughout history, and a phylogenetic approach is necessary to understand species delimitation and interspecific relationships. This study reconstructed the molecular phylogeny of six Yumtaax morphotypes using parsimony and Bayesian analysis of DNA sequence data from the ribosomal nuclear gene region 28S and the mitochondrial gene regions 12S and cytochrome oxidase I (COI) in addition to morphological characters. Analyses recovered two well-supported Yumtaax clades (the Yumtaax laticornis and Yumtaax imbellis clades) that are possible sister lineages. One synapomorphic morphological character state and the geographic isolation of the group provide corroborative evidence for monophyly. Molecular phylogenetic analyses and traditional morphological examinations also resulted in the discovery of two undescribed Yumtaax species and the discovery of two separate evolutionary lineages (cryptic species) within Yumtaax recticornis. As a result we describe three new species (Yumtaax veracrucensis Beza-Beza, Reyes-Castillo & Jameson, sp. n., Yumtaax cameliae Beza-Beza, Reyes-Castillo & Jameson, sp. n., and Yumtaax jimenezi Beza-Beza, Reyes-Castillo & Jameson, sp. n.), redescribe two species (Yumtaax recticornis [Burmeister 1847] and Yumtaax laticornis [Truqui 1857]), and provide a key to all nine Yumtaax species. This study is one of two studies to use molecular data to evaluate the evolutionary relationships of a genus of Bess Beetles (Passalidae), an ecologically important insect group exhibiting low morphological variability and heretofore lacking molecular phylogenetic study.