Inappropriateness in laboratory medicine: An elephant in the room?

Appropriateness of diagnostic testing can be conventionally described as prescription of the right test, using the right method, at the right time, to the right patient, with the right costs and for producing the right outcome. There is ongoing debate about the real burden of inappropriateness in laboratory diagnostics. The media coverage of this issue has also recently led to either over- or under-emphasizing the clinical, organizational and economic consequences. This is quite problematic, inasmuch as some reliable data are available in the current scientific literature, showing that inappropriateness of laboratory testing can be as high as 70%. This is especially evident for, though not limited to, cancer biomarkers testing, in which the practice of avoidable tests ordering is dramatically magnified. The reasons beyond inappropriateness are many and multifaceted, entailing wrong habits, resistance to changes, poor culture, insufficient education and healthcare inefficiencies. There are many unfavorable consequences attributable to avoidable testing, including unjustified incremental costs, derangement of laboratory efficiency and potential patient safety issues. The tentative solutions to this important problem necessitate that policymakers, local hospital administrators, laboratory professionals, clinicians, patients' associations and diagnostic companies join the efforts and embark in the same landmark effort for disseminating a better culture of appropriateness

Current laboratory diagnostics of coronavirus disease 2019 (COVID-19)

Laboratory medicine provides an almost irreplaceable contribution to the diagnostic reasoning and managed care of most human pathologies. The novel coronavirus disease 2019 (COVID-19) is not an exception to this paradigm. Although the relatively recent emergence does not allow to draw definitive conclusions on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostics, some standpoints can be conveyed. First and foremost, it seems now clear that we will be living together with this virus for quite a long time, so that our vigilance and responsiveness against the emergence of new local outbreaks shall be maintained at the highest possible levels. The etiological diagnosis of COVID-19 is, and will remain for the foreseeable future, deeply based on direct identification of viral RNA by means of molecular biology techniques in biological materials, especially upper and lower respiratory tract specimens. Whether other materials, such as blood, urine, stools, saliva and throat washing, will become valid alternatives has not been unequivocally defined so far. As concerns serological testing, promising information can be garnered from preliminary investigations, showing that the vast majority of COVID-19 patients seem to develop a sustained immune response against the virus, characterized especially by emergence of anti-SARS-CoV-2 IgG and IgA, 1 to 2 weeks after the onset of fever and/or respiratory symptoms. Whether these antibodies will have persistent neutralizing activity against the virus is still to be elucidated on individual and general basis. The availability of rapid tests for detecting either viral antigens or anti-SARS-CoV-2 antibodies are a potentially viable opportunity for purposes of epidemiologic surveillance, though more information is needed on accuracy and reliability of these portable immunoassays

Water-energy-ecosystem nexus in small run-of-river hydropower : Optimal design and policy

Acknowledgment This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Support from the Helmholtz Centre for Environmental Research - UFZ is gratefully acknowledged.Peer reviewedPublisher PD

Pathogenicity of viral nervous necrosis virus for Guppy fish, Poecilia reticulata

The pathogenicity of a Nervous Necrosis Virus isolate obtained from naturally infected Golden grey mullet (Liza auratus) suffering serious mortalities in Iranian coastline water of the Caspian Sea was investigated for first time. An experimental infection has been performed using three groups, two experimental groups and one control group of Guppy (Poecilia reticulata) with mean weight 0.47±0.09 g, at temperature 25ºC. The infectious dosage (50 ml) with TCID50/ml= 10^4.25 for 2 hours in group 1 and 4 hours in group 2 developed the disease with immersion method. Clear clinical signs associated with significant mortality were observed since 15 dpi. Cumulative mortalities rose to 100% at 30 dpi. While in the control group no mortality was recorded. Virus was re-isolated on SSN-1 cell line that showing typical CPE developed after inoculation with tissues filtrate from dead fish. Histopathological examination of exposed fish, showed clear vacuolization in the granular layer of the retina and cerebellum. TEM micrographs revealed intracytoplasmic vacuoles in the retina of infected Guppy. IHC revealed the presence of viral antigens in the brain and retina. These results confirmed the pathogenicity of the NNV isolate obtained from Golden grey mullet suffering high mortality with regard to suggest that the same agent isolated from golden grey mullet is very likely the cause of the mortality observed in the same species

Whole genome sequencing identifies candidate genes and mutations that can explain diluted and other colour varieties of domestic canaries (Serinus canaria)

The domestic canary (Serinus canaria) is one of the most common pet birds and has been extensively selected and bred over the last few centuries to constitute many different varieties. Plumage pigmentation is one of the main phenotypic traits that distinguish canary breeds and lines. Feather colours in these birds, similarly to other avian species, are mainly depended on the presence of two major types of pigments: carotenoids and melanins. In this study, we exploited whole genome sequencing (WGS) datasets produced from five canary lines or populations (Black Frosted Yellow, Opal, Onyx, Opal × Onyx and Mogno, some of which carrying different putative dilute alleles), complemented with other WGS datasets retrieved from previous studies, to identify candidate genes that might explain pigmentation variability across canary breeds and varieties. Sequencing data were obtained using a DNA pool-seq approach and genomic data were compared using window-based FST analyses. We identified signatures of selection in genomic regions harbouring genes involved in carotenoid-derived pigmentation variants (CYP2J19, EDC, BCO2 and SCARB1), confirming the results reported by previous works, and identified several other signatures of selection in the correspondence of melanogenesis-related genes (AGRP, ASIP, DCT, EDNRB, KITLG, MITF, MLPH, SLC45A2, TYRP1 and ZEB2). Two putative causative mutations were identified in the MLPH gene that may explain the Opal and Onyx dilute mutant alleles. Other signatures of selection were also identified that might explain additional phenotypic differences between the investigated canary populations

Targeted metabolomic profiles of piglet plasma reveal physiological changes over the suckling period

The suckling phase is a critical period for the piglets due to their incomplete immune system development and their rapid growth rates. In this study, we analysed the metabolomic profiles of piglets over this period. Eighteen piglets (nine males and nine females) from three different litters were included in the study. Body weight was recorded at birth (T0), 12 (T1) and 21 (T2) days after birth. Plasma samples were collected at two critical time points of the suckling phase (T1 and T2) and about 180 metabolites of five different biochemical classes (glycerophospholipids, amino acids, biogenic amines, hexoses and acylcarnitines) were analyzed using a target metabolomics approach based on Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Metabolites whose levels could discriminate the plasma profiles at T1 and T2 were identified using the sparse version of Multilevel Partial Least Squares Discriminant Analysis (sMLPLS-DA), coupled with a stability test based on a Leave One Out (LOO) procedure. The level of twenty-three metabolites differed significantly (P < 0.1; both for stability and the effect size) between the two time points. Higher levels of six acylcarnitine (C14:1, C14:1-OH, C16-OH, C4, C5 and C5-OH), serine, threonine and tyrosine, and one phosphatidylcholine (PC ae C42:3) were observed at T1, whereas one biogenic amine (creatinine), eight phosphatidylcholines including PC aa C30:2, PC ae C30:0, PC ae C32:1, PC ae C38:4, PC ae C40:4, PC ae C42:4, PC ae C42:5 and PC ae C44:6, and four sphingomyelins, including SM (OH) C22:1, SM C16:0, SM C16:1 and SM C18:0, were more abundant at T2. The Metabolite Set Enrichment Analysis and the Pathway Analysis modules suggested a perturbation of the \u201cglycine and serine metabolism\u201d and the \u201csphingolipid metabolism\u201d. Differences of these metabolites between these two time points might be related to the rapid growth and immunological maturation phases of the piglets in this period. Our results provided new information that could describe the biological changes of the piglets over the suckling period. The identified metabolites may be useful markers of the developmental processes occurring in the piglets over this critical pre-weaned phase