Evaluation of Abbott ID NOW COVID-19 POC test performance characteristics and integration in the regional health network workflows to improve health care delivery.

With the recent global surge of SARS-CoV-2 Delta variant, there continues to be high demand for COVID-19 diagnostic testing. Abbott ID NOW is a rapid, CLIA-waived, COVID-19 diagnostic test ideally suited for use in urgent care settings or where access to diagnostic testing is limited. In this study we describe the results of rigorous validation of ID NOW and post-implementation study of POC test utilization patterns within community hospitals and clinics. Performance of ID NOW was validated by comparison of the results from 207 consecutive, paired, specimens tested on the ID NOW and on the m2000/Alinity m platforms. Once validated, ID NOW devices were placed for clinical use at four regional hospitals and clinics. We found that the ID NOW and m2000/Alinity m positive and negative percent agreement were 94.5% (95% CI, 85.1% to 98.1%) and 99.3% (95% CI, 96.4% to 99.9%), respectively. As of August 2021, a total of 2,301 tests were performed by ID NOW at individual regional network sites. The population tested consisted of 55.5% White and 42.9% Black patients, with Black patients presenting predominantly in the hospitals, while White patients were more evenly distributed between hospital and clinic sites. Disease prevalence observed among patients tested by ID NOW (12.3%) was aligned with overall prevalence seen at regional sites (11.3%). In summary, the ID NOW test can provide rapid and accurate results in a variety of near-to-patient and POC settings. If used correctly, it could serve as a valuable diagnostic tool to enable equal access to care and improve healthcare delivery within large health network systems.

Y-chromosomal haplogroup distribution in the Tuzla Canton of Bosnia and Herzegovina: A concordance study using four different in silico assignment algorithms based on Y-STR data.

Y-chromosomal haplogroups are sets of ancestrally related paternal lineages, traditionally assigned by the use of Y-chromosomal single nucleotide polymorphism (Y-SNP) markers. An increasingly popular and a less labor-intensive alternative approach has been Y-chromosomal haplogroup assignment based on already available Y-STR data using a variety of different algorithms. In the present study, such in silico haplogroup assignments were made based on 23-loci Y-STR data for 100 unrelated male individuals from the Tuzla Canton, Bosnia and Herzegovina (B&H) using the following four different algorithms: Whit Athey's Haplogroup Predictor, Jim Cullen's World Haplogroup & Haplogroup-I Subclade Predictor, Vadim Urasin's YPredictor and the NevGen Y-DNA Haplogroup Predictor. Prior in-house assessment of these four different algorithms using a previously published dataset (n=132) from B&H with both Y-STR (12-loci) and Y-SNP data suggested haplogroup misassignment rates between 0.76% and 3.02%. Subsequent analyses with the Tuzla Canton population sample revealed only a few differences in the individual haplogroup assignments when using different algorithms. Nevertheless, the resultant Y-chromosomal haplogroup distribution by each method was very similar, where the most prevalent haplogroups observed were I, R and E with their sublineages I2a, R1a and E1b1b, respectively, which is also in accordance with the previously published Y-SNP data for the B&H population. In conclusion, results presented herein not only constitute a concordance study on the four most popular haplogroup assignment algorithms, but they also give a deeper insight into the inter-population differentiation in B&H on the basis of Y haplogroups for the first time.

Tubulo-interstitial involvement in lupus nephritis with emphasis on pathogenesis.

Glomerular lesions in lupus nephritis have been extensively studied in recent decades, but much less attention has been paid to the tubulo-interstitial compartment. The aim of this study was to contribute to the understanding of the pathogenesis of tubulo-interstitial lesions in lupus nephritis by analysing their incidence, character, and their associations. One hundred and ninety kidney biopsies of 190 patients fulfilling American Rheumatology Association (ARA) criteria of systemic lupus erythematosus (SLE) were examined by traditional light, immunofluorescence and electron microscopy. Interstitial inflammatory infiltration and tubulo-interstitial immune deposits concurred in 72 cases (37.9%). Their frequency was the highest in WHO class IV lupus glomerulonephritis. By multivariate analysis, the intensity of interstitial inflammatory infiltration correlated best with the percentage of renal corpuscules with extracapillary crescents and the extent of interstitial fibrosis. On immunohistochemical assessment, the inflammatory infiltrate was found to be composed of CD45RO positive T lymphocytes (191.3/mm2), CD68 positive macrophages (101.7/mm2) and CD45RA positive B lymphocytes (17.2/mm2). For all cell types the median value was higher in cases with extracapillary crescents, and did not correlate with presence and intensity of tubulo-interstitial immune deposits. Infiltration showed the tendency of periglomerular distribution, especially around glomeruli showing extracapillary proliferation and destruction of the capsular basal membrane. Rare S100 positive cells were only found in the interstitium. Tubulo-interstitial lesions estimated semiquantitatively correlated with the degree of proteinuria. Our findings suggest that tubulo-interstitial deposits do not play a major role in the pathogenesis of tubulo-interstitial lesions. The formation of interstitial cell infiltrates appears to be greatly influenced by the development of extracapillary crescents, perhaps by direct transmission of the severe inflammatory process to the adjacent interstitium. The composition of the infiltrate, including antigen presenting cells may signalize an additional involvement of cell-mediated immune mechanisms acting against so far hypothetical tubular epithelial neoantigens.

[Comparative analysis of pathomorphologic changes in the adrenal glands using ultrasound and computer tomography]. / Usporedna analiza patomorfoloskih promjena nadbubreznih zlijezda ultrazvukom i kompjutoriziranom tomografijom.

A prospective study of the possibilities and achievements of ultrasonography of the adrenal glands is presented. The adrenal glands of 146 patients with abnormalities suspected clinically were examined with ultrasound. Patients were also evaluated with computed tomography where there are firm criteria for the evaluation of adrenal pathology. Positive findings were detected by ultrasound in 46 patients, whereas computed tomography disclosed pathologic changes in 65 patients. In 81 patients, the finding of computed tomography was normal. With ultrasound, false positives were obtained in 3 cases and false negatives in 19 cases (14 hyperplasias, 5 tumors). Ultrasound findings were additionally compared with angiographic and clinical tests as well as with pathohistologic results of surgery and autopsy.

Role of essential glycoproteins gII and gp50 in transneuronal transfer of pseudorabies virus from the hypoglossal nerves of mice.

The propagation of pseudorabies virus (PrV) mutants deficient in essential glycoproteins gp50 and gII was studied after inoculation of transcomplemented gp50- and gII- PrV into the motor hypoglossal (XII) nerves of mice. In this model, viral spread from the infected XII motoneurons involves specific transneuronal transfer to connected cells and local, nonspecific transfer. For comparison, a PrV mutant lacking the nonessential nonstructural glycoprotein gX was included. Although the efficiencies of first-cycle replication were similar for the three viruses, only gX- and gp50- progeny mutants could spread from XII motoneurons via transneuronal and local transfer. The extents of transfer of gX- and gp50- PrV were comparable. The results show that the absence of gp50 does not alter the pattern of transneuronal or local spread of PrV, whereas gII is essential for both processes.

A study of primary neuronal infection by mutants of herpes simplex virus type 1 lacking dispensable and non-dispensable glycoproteins.

Cultures of primary rat dorsal root ganglia neurones were inoculated with various doses of herpes simplex virus mutants deficient in glycoproteins B, D, H, C, G, E, I or J, and the proportion of infected neurones was determined. The behaviour of these mutants on primary neurones was broadly similar to their behaviour on fibroblasts or epithelial cells. Thus, virions lacking the 'nondispensable' glycoproteins B, D or H were incapable of infecting primary neurones, whereas mutants lacking glycoproteins G, E, I or J infected primary neurones with the same efficiency as wild-type virions. Two independently derived mutants lacking gC displayed a marginal phenotype, infecting neurones with a five- to tenfold reduced efficiency relative to wild-type virus and relative to non-neuronal cells in the same cultures. We conclude that the virion glycoprotein requirements for infection of mammalian neurones are similar to those required for infection of fibroblasts and epithelial cells but that glycoprotein C may enhance infection of neurones.

Deletion of glycoprotein gE reduces the propagation of pseudorabies virus in the nervous system of mice after intranasal inoculation.

A pseudorabies virus (PrV) mutant, deficient in the nonessential glycoprotein E (gE) and expressing the LacZ gene (gE- beta gal+ PrV), and its rescued virus were inoculated intranasally in mice. The median lethal dose of gE- beta gal+ PrV was similar to that of the parental Kaplan strain, but mice survived longer and did not develop symptoms of pseudorabies. In the nasal mucosa, gE- beta gal+ PrV replicated less efficiently than rescued virus. gE- beta gal+ PrV could infect first-order trigeminal and sympathetic neurons innervating the nasal mucosa. However, transneuronal transfer to second-order cells groups did not occur in trigeminal pathways and was severely reduced in sympathetic pathways. The mutant was also unable to propagate in the parasympathetic system. In contrast, gE-rescued virus was transferred transneuronally in trigeminal, sympathetic, and parasympathetic pathways, like wild-type PrV. These findings provide further evidence that deletion of gE specifically affects transneuronal transfer of PrV more than penetration and multiplication of the virus in first-order neurons.

The absence of glycoprotein gL, but not gC or gK, severely impairs pseudorabies virus neuroinvasiveness.

Penetration and propagation of herpesviruses in the nervous system require the action of several glycoproteins. To assay for a function of glycoproteins gC, gK, and gL in the neuroinvasiveness of pseudorabies virus (PrV), deletion mutants lacking one of these glycoproteins and corresponding rescuants were inoculated in the nasal cavity of adult mice. We demonstrate that the lack of gL almost prevented the virus from penetrating and propagating in trigeminal, sympathetic, and parasympathetic tracks innervating the nasal cavity, while the lack of gC and gK only slowed the invasion of the nervous system. The conclusion of this and previous studies is that only gB, gD, gH, and gL are indispensable for penetration into neurons, while gB, gH, and gL (and, in some categories of neurons, also gE and gI) are necessary for transneuronal transfer in the mouse model. The deletion of other glycoprotein genes has little effect on PrV neuroinvasiveness although it may affect the dissemination of the virus.

[Serum angiotensin converting enzyme in patients with primary liver carcinoma]. / Serumska aktivnost angiotenzin konvertirajuceg enzima u pacijenata sa primarnim karcinomom jetre.

Recent studies have shown that serum activity of angiotensin-converting enzyme (ACE; EC 3.4.15.1) significantly decreases in patients with carcinoma of different localizations. There is no information in literature about measuring this enzyme in primary liver carcinoma patients. The serum activity of ACE has been examined on 15 primary liver carcinoma patients, 10 patients with cirrhosis, and 26 healthy subjects. Serum activity has been determined by spectrophotometric method using synthetic substrate Hip-His-Leu. The results were given in units which correspond to one nmol of hippuric acid released by enzymatic hydrolyze of Hip-His-Leu substrate in one minute on serum milliliter. The results have shown that serum activity of ACE increased in patients with cirrhosis (37.06 +/- 2.9; X +/- SEM; p < 0.05), and decreased in primary liver carcinoma patients (23.44 +/- 1.87; p < 0.01), what was statistically significant in comparison with the activity of the same enzyme in healthy subjects (29.90 +/- 2.72). These results point out the possibility of clinical application of measuring serum ACE activity as one of primary liver carcinoma marker in differential diagnosis of the disease.

Glycoprotein gH of pseudorabies virus is essential for penetration and propagation in cell culture and in the nervous system of mice.

Glycoprotein H (gH) of pseudorabies virus (PrV) is a structural component of the virion and forms a complex with another glycoprotein, gL. For a detailed analysis of the function of PrV gH, we isolated a gH-deficient mutant on trans-complementing gH-expressing cells after insertion of a beta-galactosidase expression cassette into a partially deleted gH gene. The absence of gH did not affect primary or secondary attachment of PrV but the mutant was not infectious. The defect in infectivity could partially be overcome by experimentally induced membrane fusion using PEG, which suggests that gH was necessary for fusion between virion and cellular membranes. After intranasal inoculation into mice, the LD50 of complemented gH- PrV was more than four orders of magnitude higher than that of wild-type PrV. Infection of the respiratory epithelium was much less efficient with complemented gH- PrV as compared with rescued PrV, reflecting the lack of direct cell-to-cell spread. Complemented gH- PrV was able to penetrate into a few trigeminal and sympathetic first order neurons accessible from the nasal cavity, whereas transneuronal transfer in the second order neurons was not observed. In summary, gH is essential for entry and cell-to-cell spread in cell culture, and for propagation in the nervous system of mice. This substantiates the hypothesis that transneuronal spread in vivo and direct cell-to-cell spread in cell culture are governed by similar mechanisms.

Propagation of pseudorabies virus in the nervous system of the mouse after intranasal inoculation.

The propagation of pseudorabies virus (PrV) in the mouse nervous system was studied after intranasal inoculation of a PrV mutant expressing beta-galactosidase after insertion of the Escherichia coli Lac-Z gene into the gene encoding the nonstructural, nonessential glycoprotein gG. This allowed rapid detection of infected cells by a single step reaction with the substrate X-gal. The gG-beta-gal+ mutant behaved like the wild-type Kaplan strain of origin. The incubation period was very short and the animals did not survive more than 52 hr after inoculation. In the nasal cavity, the virus infected almost exclusively the respiratory epithelium. The virus propagated to the nervous system via three neuronal pathways: (i) the trigeminal route, with primary infection in the trigeminal ganglion followed by anterograde transneuronal transfer to the spinal trigeminal nucleus; (ii) the sympathetic route, with a first cycle of replication in the superior cervical ganglion and retrograde transneuronal transfer to sympathetic preganglionic neurons in the intermediolateral nucleus in the spinal cord; and (iii) the parasympathetic route, with primary infection in the pterygopalatine ganglion, followed by retrograde transneuronal transfer and replication in the superior salivatory nucleus. In contrast, the olfactory system was rarely found infected, probably because of the short survival of the animals.

Adrenal cavernous hemangioma: MRI, CT, and US appearance.

Two cases of rare adrenal cavernous hemangiomas are reported, one imaged with conventional X-ray techniques, US, CT, and MRI, and the other with US and CT. The CT technique clearly demonstrated calcifications and the internal structure of the lesions in both cases and peripheral rim enhancement on the postcontrast scan in one patient. Although MRI demonstrated accurately the complex nature of the lesion, the inability to visualize the calcified areas do not allow to make a specific histologic diagnosis.

[Nitric oxide--a potential modulator of left ventricular diastolic function in hemodialysis patients treated with erythropoietin]. / Dusicni oksid--potencijalni modulator dijastolne funkcije lijeve srcane komore u hemodijaliznih pacijenata tretiranih eritropoetinom.

UNLABELLED: Left ventricular hypertrophy (LVH) is commonly present in hemodialysis patients (HD pts) and is considered as an independent risk factor for high mortality. Many studies have confirmed sound connection between anemia and LVH in this patients. OBJECTIVE: To analyse dystolic function of LVH in uraemic pts during the 6 months human recombinant erythropoectin (rHu-Epo) treatment of anemia, with emphasis on the role of nitric oxide (NO), whose role in regulation of LV diastolic distensibility has been hinted in some recent studies. PATIENTS AND METHODS: The study included 20 HD pts, aged 39.6 +/- 5.3 yrs, with the same condition of HD treatment, signs of anemia and echocardiographically verified LVH. Pulse Doppler echocardiography confirmed LV diastolic function as a ratio of early to late diastolic mitral flow velocity (E/A). Nitrate concentration was determined by colorimetric method using Greiss reagent. Renal anemia was treated with rHuEpo. RESULTS: Six months rHuEpo treatment of anemia in HD pts with LVH caused significant reduction of LV mass index (p = 0.008). However, we observed unfavourable fall in LV diastolic function (E/A = 0.83, p = 0.007). In the same time, it was found that the serum NO level was higher for 11.8% in HD pts with LVH as compared with the pts with normal LV mass. Also, the significant positive correlation was found between the level of NO and LV mass index before (p = 0.004) and after rHuEpo therapy (p = 0.03), as well as a significant positive correlation between NO and E/A in the same conditions (p = 0.002) and p = 0.049). Level of NO negatively correlates with blood hemoglobin level, but without statistical significance. CONCLUSIONS: Correction of anemia with rHuEpo leads to the significant partial regression of LVH. Reduction of diastolic function of LV, observed after diminished LV mass index, could be related to the significant fall of NO level and damaged response of LV to NO. The results of the study strongy suggest that NO can present an important determinant of LV diastolic function in uraemic pts.