Direct Measurement of ATP7B Peptides Is Highly Effective in the Diagnosis of Wilson Disease

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Presence of Recombinant Bat Coronavirus GCCDC1 in Cambodian Bats

Bats have been recognized as an exceptional viral reservoir, especially for coronaviruses. At least three bat zoonotic coronaviruses (SARS-CoV, MERS-CoV and SARS-CoV-2) have been shown to cause severe diseases in humans and it is expected more will emerge. One of the major features of CoVs is that they are all highly prone to recombination. An extreme example is the insertion of the P10 gene from reoviruses in the bat CoV GCCDC1, first discovered in Rousettus leschenaultii bats in China. Here, we report the detection of GCCDC1 in four different bat species (Eonycteris spelaea, Cynopterus sphinx, Rhinolophus shameli and Rousettus sp.) in Cambodia. This finding demonstrates a much broader geographic and bat species range for this virus and indicates common cross-species transmission. Interestingly, one of the bat samples showed a co-infection with an Alpha CoV most closely related to RsYN14, a virus recently discovered in the same genus (Rhinolophus) of bat in Yunnan, China, 2020. Taken together, our latest findings highlight the need to conduct active surveillance in bats to assess the risk of emerging CoVs, especially in Southeast Asia.     

The role of STK 11 gene testing in individuals with oral pigmentation

Peutz–Jeghers syndrome (PJS) is a rare, autosomal dominant condition characterised by mucocutaneous pigmented lesions, gastrointestinal polyposis and a significant risk of cancer. Laugier–Hunziker syndrome (LHS) is a benign condition with similar dermatological features, but with no systemic complications. STK 11 gene testing allows clinicians to differentiate between these two disorders. This case report compares the dermatological similarities in four individuals with PJS or LHS and illustrates the potential benefit of genetic testing. There is > 90% likelihood of identifying a mutation in STK 11 if a patient fulfils the diagnostic criteria for PJS. Lifelong risk management is advised for these individuals with confirmed PJS. Diagnostic confirmation is important to provide rational management, in particular, endoscopic cancer surveillance, and psychological support. STK 11 testing can confirm those at risk of PJS, who require lifelong surveillance, and possibly release those with a simple dermatosis, such as LHS, from invasive and thus potentially harmful surveillance.     

New insights into the competition between antioxidant activities and pro-oxidant risks of rosmarinic acid

Direct and indirect antioxidant activities of rosmarinic acid (RA) based on HOO˙/CH₃OO˙ radical scavenging and Fe(iii)/Fe(ii) ion chelation were theoretically studied using density functional theory at the M05-2X/6-311++G(2df,2p) level of theory. First, four antioxidant mechanisms including hydrogen atom transfer (HAT), radical adduct formation (RAF), proton loss (PL) and single electron transfer (SET) were investigated in water and pentyl ethanoate (PEA) phases. Regarding the free radical scavenging mechanism, HAT plays a decisive role with overall rate coefficients of 1.84 × 10³ M⁻¹ s⁻¹ (HOO˙) and 4.49 × 10³ M⁻¹ s⁻¹ (CH₃OO˙) in water. In contrast to PL, RAF and especially SET processes, the HAT reaction in PEA is slightly more favorable than that in water. Second, the [Fe(iii)(H₂O)₆]³⁺ and [Fe(ii)(H₂O)₆]²⁺ ion chelating processes in an aqueous phase are both favorable and spontaneous especially at the O5, site-1, and site-2 positions with large negative Δ_rG⁰ values and great formation constant K_f. Finally, the pro-oxidant risk of RA⁻ was also considered via the Fe(iii)-to-Fe(ii) complex reduction process, which may initiate Fenton-like reactions forming reactive HO˙ radicals. As a result, RA⁻ does not enhance the reduction process when ascorbate anions are present as reducing agents, whereas the pro-oxidant risk becomes remarkable when superoxide anions are found. The results encourage further attempts to verify the speculation using more powerful research implementations of the antioxidant activities of rosmarinic acid in relationship with its possible pro-oxidant risks.

Direct and indirect antioxidant activities of rosmarinic acid (RA) based on HOO˙/CH₃OO˙ radical scavenging and Fe(iii)/Fe(ii) ion chelation were theoretically studied using density functional theory at the M05-2X/6-311++G(2df,2p) level of theory.     

The Influence of Media Coverage and Governmental Policies on Google Queries Related to COVID-19 Cutaneous Symptoms: Infodemiology Study

BackgroundDuring COVID-19, studies have reported the appearance of internet searches for disease symptoms before their validation by the World Health Organization. This suggested that monitoring of these searches with tools including Google Trends may help monitor the pandemic itself. In Europe and North America, dermatologists reported an unexpected outbreak of cutaneous acral lesions (eg, chilblain-like lesions) in April 2020. However, external factors such as public communications may also hinder the use of Google Trends as an infodemiology tool.ObjectiveThe study aimed to assess the impact of media announcements and lockdown enforcement on internet searches related to cutaneous acral lesions during the COVID-19 outbreak in 2020.MethodsTwo searches on Google Trends, including daily relative search volumes for (1) “toe” or “chilblains” and (2) “coronavirus,” were performed from January 1 to May 16, 2020, with the United States, the United Kingdom, France, Italy, Spain, and Germany as the countries of choice. The ratio of interest over time in “chilblains” and “coronavirus” was plotted. To assess the impact of lockdown enforcement and media coverage on these internet searches, we performed an interrupted time-series analysis for each country.ResultsThe ratio of interest over time in “chilblains” to “coronavirus” showed a constant upward trend. In France, Italy, and the United Kingdom, lockdown enforcement was associated with a significant slope change for “chilblain” searches with a variation coefficient of 1.06 (SE 0.42) (P=0.01), 1.04 (SE 0.28) (P<.01), and 1.21 (SE 0.44) (P=0.01), respectively. After media announcements, these ratios significantly increased in France, Spain, Italy, and the United States with variation coefficients of 18.95 (SE 5.77) (P=.001), 31.31 (SE 6.31) (P<.001), 14.57 (SE 6.33) (P=.02), and 11.24 (SE 4.93) (P=.02), respectively, followed by a significant downward trend in France (–1.82 [SE 0.45]), Spain (–1.10 [SE 0.38]), and Italy (–0.93 [SE 0.33]) (P<.001, P=0.004, and P<.001, respectively). The adjusted R² values were 0.311, 0.351, 0.325, and 0.305 for France, Spain, Italy, and the United States, respectively, suggesting an average correlation between time and the search volume; however, this correlation was weak for Germany and the United Kingdom.ConclusionsTo date, the association between chilblain-like lesions and COVID-19 remains controversial; however, our results indicate that Google queries of “chilblain” were highly influenced by media coverage and government policies, indicating that caution should be exercised when using Google Trends as a monitoring tool for emerging diseases.     

Brain MR perfusion‐weighted imaging with alternate ascending/descending directional navigation

In this study, a new arterial spin labeling technique that requires no separate spin preparation pulse was developed. Sequential two‐dimensional slices were acquired in ascending and descending orders by turns using balanced steady state free precession for pair‐wise subtraction. Simulation studies showed this new technique, alternate ascending/descending directional navigation (ALADDIN), has high sensitivity to both slow‐ (1–10 cm/sec) and fast‐moving (>10 cm/sec) blood because of the presence of multiple labeling planes proximal to imaging planes and sensitivity of balanced steady state free precession to initial magnetization differences. ALADDIN provided high‐resolution multislice perfusion‐weighted images in ～3 min. About 80–90% of signals in a slice were ascribed to spins saturated in the four prior slices. Three to five edge slices on each side of imaging group were affected by transient magnetization transfer effects and incomplete T₁ recovery between successive acquisitions. ALADDIN signals were dependent on many imaging parameters, implying room for improvement. Sagittal and coronal ALADDIN images demonstrated perfusion direction in gray matter regions was mostly from center to lateral, anterior, or posterior, whereas that in some white matter regions was reversed. ALADDIN is likely useful for many studies requiring perfusion‐weighted imaging with short scan time, insensitiveness to arterial transit time, directional information, high resolution, and/or wide coverage. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

Progression of Epididymal Maldevelopment Into Hamartoma-like Neoplasia in VHL Disease

Inactivation of the von Hippel-Lindau (VHL) gene and activation of the hypoxia-inducible factor (HIF) in susceptible cells precedes formation of tumorlets and frank tumor in the epididymis of male VHL patients. We performed detailed histologic and molecular pathologic analysis of tumor-free epididymal tissues from VHL patients to obtain further insight into early epididymal tumorigenesis. Four epididymides from two VHL patients were serially sectioned to allow for three-dimensional visualization of morphologic changes. Areas of interest were genetically analyzed by tissue microdissection, immunohistochemistry for HIF and markers for mesonephric differentiation, and in situ hybridization for HIF downstream target vascular endothelial growth factor. Structural analysis of the epididymides revealed marked deviations from the regular anatomic structure resulting from impaired organogenesis. Selected efferent ductules were represented by disorganized mesonephric cells, and the maldeveloped mesonephric material was VHL-deficient by allelic deletion analysis. Furthermore, we observed maldeveloped mesonephric material near cystic structures, which were also VHL-deficient and were apparent derivatives of maldeveloped material. Finally, a subset of VHL-deficient cells was structurally integrated in regular efferent ductules; proliferation of intraductular VHL-deficient cells manifests itself as papillary growth into the ductular lumen. Furthermore, we clarify that that there is a pathogenetic continuum between microscopic tumorlets and formation of tumor. In multiple locations, three-dimensional reconstruction revealed papillary growth to extend deeply into ductular lumina, indicative of progression into early hamartoma-like neoplasia. We conclude epididymal tumorigenesis in VHL disease to occur in two distinct sequential steps: maldevelopment of VHL-deficient mesonephric cells, followed by neoplastic papillary proliferation.     

Structure-activity relationships of some 3-substituted-4-hydroxycoumarins as HIV-1 protease inhibitors

The screening of the HIV-1 protease (PR) inhibitory activity (IC-50) of various substituted 3-phenyl-4-hydroxycoumarins, 3-benzyl-4-hydroxycoumarins, 3-phenoxy-4-hydroxy-coumarins, 3-benzenesulfonyl-4-hydroxycoumarins and 3-(7-coumarinyloxy)-4-hydroxycoumarins was performed. The data indicate the importance of substituents at positions 5 and 7 of the coumarin ring on the inhibitory potency of the HIV-1-PR.