Narrow-band imaging optical chromocolonoscopy： Advantages and limitations

Narrow-band imaging （NBI） is an innovative optical technology that modifies the center wavelength and bandwidth of an endoscope＇s light into narrow-band illumination of 415 ：1： 30 nm. NBI markedly improves capillary pattern contrast and is an in vivo method for visualizing microvessel morphological changes in superficial neoplastic lesions. The scientific basis for NBI is that short wavelength light falls within the hemoglobin absorption band, thereby facilitating clearer visualization of vascular structures. Several studies have reported advantages and limitations of NBI colonoscopy in the colorectum. One difficulty in evaluating results, however, has been nonstandardization of NBI systems （Sequential and nonsequential）. Utilization of NBI technology has been increasing worldwide, but accurate pit pattern analysis and sufficient skill in magnifying colonoscopy are basic fundamentals required for proficiency in NBI diagnosis of colorectal lesions. Modern optical technology without proper image interpretation wastes resources, confuses untrained endoscopists and delays interinstitutional validation studies. Training in the principles of ＂optical image-enhanced endoscopy＂ is needed to close the gap between technological advancements and their clinical usefulness. Currently available evidence indicates that NBI constitutes an effective and reliable alternative to chromocolonoscopy for in vivo visualization of vascular structures, but further study assessing reproducibility and effectiveness in the colorectum is ongoing at various medical centers.     

Comparison of Two Commercial Tick-Borne Encephalitis Virus IgG Enzyme-Linked Immunosorbent Assays

Despite the availability of protective vaccines, tick-borne encephalitis virus (TBEV) infections have been increasingly reported to the European Centre for Disease Prevention and Control in the past 2 decades. Since the diagnosis of TBEV exposure relies on serological testing, we compared two commercial enzyme-linked immunosorbent assays (ELISAs), i.e., Immunozym FSME IgG assay (ELISA-1) and Euroimmun FSME Vienna IgG assay (ELISA-2). Both assays use whole TBEV antigens, but they differ in viral strains (Neudoerfl for ELISA-1 and K23 for ELISA-2) and cutoff values. In testing of samples from 398 healthy blood donors, ELISA-1 showed higher reactivity levels than ELISA-2 (P < 0.001), suggesting different assay properties. This finding was supported by Bland-Altman analysis of the optical density at 450 nm (OD₄₅₀) (mean bias, +0.32 [95% limits of agreement, −0.31 to +0.95]) and persisted after transformation into Vienna units. Concordant results were observed for 276 sera (69%) (44 positive and 232 negative results). Discordant results were observed for 122 sera (31%); 15 were fully discordant, all being ELISA-1 positive and ELISA-2 negative, and 107 were partially discordant (101 being ELISA-1 indeterminate and ELISA-2 negative and 6 having positive or indeterminate reactivity in both ELISAs). Neutralization testing at a 1:10 dilution yielded positive results for 33 of 44 concordant positive sera, 1 of 15 fully discordant sera, and 1 of 33 partially discordant sera. Indirect immunofluorescence testing revealed high antibody titers of ≥100 for yellow fever virus in 18 cases and for dengue virus in one case, suggesting that cross-reactivity contributed to the ELISA-1 results. We conclude that (i) cross-reactivity among flaviviruses remains a limitation of TBEV serological testing, (ii) ELISA-2 revealed reasonable sensitivity and specificity for anti-TBEV IgG population screening of human sera, and (iii) neutralization testing is most specific and should be reserved for selective questions.     

Lineage fate of ductular reactions in liver injury and carcinogenesis

Ductular reactions (DRs) are observed in virtually all forms of human liver disease; however, the histogenesis and function of DRs in liver injury are not entirely understood. It is widely believed that DRs contain bipotential liver progenitor cells (LPCs) that serve as an emergency cell pool to regenerate both cholangiocytes and hepatocytes and may eventually give rise to hepatocellular carcinoma (HCC). Here, we used a murine model that allows highly efficient and specific lineage labeling of the biliary compartment to analyze the histogenesis of DRs and their potential contribution to liver regeneration and carcinogenesis. In multiple experimental and genetic liver injury models, biliary cells were the predominant precursors of DRs but lacked substantial capacity to produce new hepatocytes, even when liver injuries were prolonged up to 12 months. Genetic modulation of NOTCH and/or WNT/β-catenin signaling within lineage-tagged DRs impaired DR expansion but failed to redirect DRs from biliary differentiation toward the hepatocyte lineage. Further, lineage-labeled DRs did not produce tumors in genetic and chemical HCC mouse models. In summary, we found no evidence in our system to support mouse biliary-derived DRs as an LPC pool to replenish hepatocytes in a quantitatively relevant way in injury or evidence that DRs give rise to HCCs.     

Disentangling the lifespans of hepatitis C virus‐infected cells and intracellular vRNA replication‐complexes during direct‐acting anti‐viral therapy

The decay rate of hepatitis C virus (HCV)‐infected cells during therapy has been used to determine the duration of treatment needed to attain a sustained virologic response, but with direct‐acting anti‐virals (DAA), this rate has been difficult to estimate. Here, we show that it is possible to estimate it, by simultaneously analysing the viral load and alanine aminotransferase (ALT) kinetics during combination DAA therapy. We modelled the HCV RNA and ALT serum kinetics in 26 patients with chronic HCV genotype 1b infection, under four different sofosbuvir‐based combination treatments. In all patients, ALT decayed exponentially to a set point in the normal range by 1‐3 weeks after initiation of therapy. The model indicates that the ALT decay rate during the first few weeks after initiation of therapy reflects the death rate of infected cells, with an estimated median half‐life of 2.5 days in this patient population. This information allows independent estimation of the rate of loss of intracellular replication complexes during therapy. Our model also predicts that the final ALT set point is not related to the release of ALT by dying HCV‐infected cells. Using ALT data, one can separately obtain information about the rate of ‘cure’ of HCV‐infected cells versus their rate of death, something not possible when analysing only HCV RNA data. This information can be used to compare the effects of different DAA combinations and to rationally evaluate their anti‐viral effects.     

Matrix Metalloproteinase Inhibition Lowers Mortality and Brain Injury in Experimental Pneumococcal Meningitis

Pneumococcal meningitis (PM) results in high mortality rates and long-lasting neurological deficits. Hippocampal apoptosis and cortical necrosis are histopathological correlates of neurofunctional sequelae in rodent models and are frequently observed in autopsy studies of patients who die of PM. In experimental PM, inhibition of matrix metalloproteinases (MMPs) and/or tumor necrosis factor (TNF)-converting enzyme (TACE) has been shown to reduce brain injury and the associated impairment of neurocognitive function. However, none of the compounds evaluated in these studies entered clinical development. Here, we evaluated two second-generation MMP and TACE inhibitors with higher selectivity and improved oral availability. Ro 32-3555 (Trocade, cipemastat) preferentially inhibits collagenases (MMP-1, -8, and -13) and gelatinase B (MMP-9), while Ro 32-7315 is an efficient inhibitor of TACE. PM was induced in infant rats by the intracisternal injection of live Streptococcus pneumoniae. Ro 32-3555 and Ro 32-7315 were injected intraperitoneally, starting at 3 h postinfection. Antibiotic (ceftriaxone) therapy was initiated at 18 h postinfection, and clinical parameters (weight, clinical score, mortality rate) were recorded. Myeloperoxidase activities, concentrations of cytokines and chemokines, concentrations of MMP-2 and MMP-9, and collagen concentrations were measured in the cerebrospinal fluid. Animals were sacrificed at 42 h postinfection, and their brains were assessed by histomorphometry for hippocampal apoptosis and cortical necrosis. Both compounds, while exhibiting disparate MMP and TACE inhibitory profiles, decreased hippocampal apoptosis and cortical injury. Ro 32-3555 reduced mortality rates and cerebrospinal fluid TNF, interleukin-1β (IL-1β) and collagen levels, while Ro 32-7315 reduced weight loss and cerebrospinal fluid TNF and IL-6 levels.     

The foot in systemic disease: management of the patient with rheumatoid arthritis or diabetes mellitus

The foot is commonly affected in systemic diseases such as rheumatoid arthritis and diabetes mellitus. Treating patients who suffer with foot pathology secondary to systemic diseases requires a multidisciplinary approach, following the principles outlined within this review. There is little high level evidence in this field, such as prospective controlled clinical trials, hence much of what we know and practise is based upon the expert opinion of key individuals in specialist centres, to whom we owe a great debt.     

Simplifying the digital workflow of facial prostheses manufacturing using a three-dimensional (3D) database: setup,development, and aspects of virtual data validation for reproduction

PurposeTo set up the digital database (DDB) of various anatomical parts, skin details and retention elements in order to simplify the digital workflow of facial prostheses manufacturing; and to quantify the reproduction of skin wrinkles on the prostheses prototypes with stereolithography (SLA) and direct light processing (DLP) methods.MethodsTwo structured light scanners were used to obtain the nasal and auricle forms of 50 probands. Furthermore, the ala nasi and scapha areas were captured with the digital single lens reflex camera and saved in jpeg format. The four magnetic retention elements were remodeled in computer aided design (CAD) software. The 14 test blocks with embossed wrinkles of 0.05–0.8 mm were printed with SLA and DLP methods and afterwards analyzed by means of profilometry and confocal microscopy.ResultsThe introduced DDB allows for production of customized facial prosthesis and makes it possible to consider the integration of concrete retention elements on the CAD stage, which makes the prosthesis modelling more predictable and efficient. The obtained skin structures can be applied onto the prosthesis surface for customization. The reproduction of wrinkles from 0.1 to 0.8 mm in depth may be associated with the loss of 4.5%–11% of its profile with SLA or DLP respectively. Besides, the reproduction of 0.05 mm wrinkles may be met with up to 40% profile increasement.ConclusionsThe utilization of DDB may simplify the digital workflow of facial prostheses manufacturing. The transfer of digitally applied skin wrinkles till the prostheses’ prototypes may be associated with deviations from 11 to 40%.