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irst report of detection of BRSV and BPI-3 from pneumonic cases by RT-PCR and d-FAT from cattle and buffaloes of India, indicating the need for more epidemiological studies. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important porcine viruses worldwide. Recently, severe PRRS outbreaks had occurred in two farms located in eastern and southern Thailand where stringent vaccination had been routinely practiced. Genetic analysis of GP5 identified two highly virulent PRRSVs designated as NA/TH/S001/2015 and NA/TH/E001/2016 from the southern and eastern farms, respectively. Both incidences were the first outbreaks of severe PRRSV since the implementation of the modified live virus (MLV) vaccine, indicating the concurrent emergence of immune-escape viruses. The genetics of the two PRRSV variants, the previous studied sequences from Thailand, and the reference strains were characterized with a focus on the GP5 and NSP2 genes. The results indicated that NA/TH/S001/2015 and NA/TH/E001/2016 shared less than 87% nucleotide similarity to the MLV and PRRSV type 2, lineages 1 and 8.7 (NA), respectively. A comparative analysis of the retrospective GP5 sequences categorized the PRRSVs into five groups based on the clinical outcomes, and both of the novel PRRSV strains were in the same group. Epitope A, T cell epitope, and N-linked glycosylation patterns within GP5 of both PRRSV variants were highly variable and significantly differed from those of MLV. As observed in highly virulent type 2 strains, NA/TH/S001/2015 contained a single amino acid deletion at position 33 in the hypervariable region 1 (HV-1) of GP5. Amino acid analysis of the hypervariable region of NSP2 revealed that NA/TH/E001/2016 had a unique deletion pattern that included two discontinuous deletions a 127-amino acid deletion from residues 301 to 427 and a single amino acid deletion at position 470. These results indicate the emergence of two novel PRRSV strains and highlight the common genetic characteristics of the immune-escaping PRRSV variants. BACKGROUND The anatomy of soft tissues around dental implants is extremely important to prevent inflammatory periimplant diseases and ensure healthy, stable and long-term survival of a dental implant. Various methods and materials for increasing the physiological thickness of tissues have been described including connective tissue graft (CTG) and xenogenic collagen matrix (XCM). While assessing various materials it is necessary to establish objective measurement method to determine the minimum amount of tissue thickness to maintain a stable level of bone around the implant. The aim of the study was to determine the effect of soft tissues in the implant area on the marginal bone level in the implant area and to define of the critical gingival thickness to minimize marginal bone level (MBL) loss. METHODS 75 bone level implants (Conelog® Camlog, Switzerland) were inserted in the aesthetic area. Thickening of soft tissues was performed using CTG and XCM. 12 months after the loading with final restoration, the thickness of soft tissues in the implant area was examined with ultrasound USG device (Pirop®, Echoson, Poland), and each implant was subjected to RVG examination, where MBL loss was determined. RESULTS A tendency to occur less MBL loss was found when thicker gingiva was present. The higher soft tissue thickness was, the lower MBL loss has occurred. A critical value for tissue thickness was determined as TKT ≤ 2.88. CONCLUSIONS In case of thin biotype soft tissue augmentation is required when value of tissue thickness in ultrasound measure is less than 2.88 mm. The avian Wulst is the pallial (analogous to mammalian cortex) termination point of the thalamofugal pathway, one of two main visual pathways in birds, and is considered to be equivalent to primate striate cortex. We recorded neuronal activity from the Wulst in pigeons during two versions of a delayed matching-to-sample procedure. Two birds were trained on a common outcomes (CO) procedure, in which correct responses following both the skateboarder and the flower stimuli were associated with reward. Two other birds were trained on a differential outcomes (DO) procedure in which correct responses following only the skateboarder stimulus were associated with reward, while correct responses following the flower stimulus were not rewarded. In line with previous studies, under CO conditions, and for both excitatory and inhibitory neurons, delay activity in the Wulst was significantly different from baseline activity following both sample stimuli, which may indicate that Wulst delay activity is a neural correlate of working memory for the sample stimulus. On the other hand, under DO conditions, Wulst delay activity appeared to be a neural correlate of the upcoming reward. We argue that Wulst neurons display flexibility in their encoding in that they can encode both sample and reward information, but may default to one type of coding over the other based on the demands of the task. The current study provides the first evidence that delay activity in the Wulst represents both a neural correlate for sample information as well as reward information. BACKGROUND Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the role of hydroxychloroquine on respiratory viral loads. PATIENTS AND METHODS French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point. Selleckchem URMC-099 RESULTS Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported of untreated patients in the literature. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination. CONCLUSION Despite its small sample size our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin. V.Editorial on Frequency-Specific Changes of Resting Brain Activity in Parkinson's Disease A Machine Learning Approach. Endocannabinoids are a class of lipid neuromodulators found throughout the animal kingdom. Among the endocannabinoids, 2-arachydonoyl glycerol (2-AG) is the most prevalent endocannabinoid and monoacylglycerol lipase (MAGL) is a serine hydrolase primarily responsible for metabolizing 2-AG in mammals. In the medicinal leech, Hirudo verbana, 2-AG has been found to be an important and multi-functional modulator of synaptic transmission and behavior. However, very little is known about the molecular components of its synthesis and degradation. In this study we have identified cDNA in Hirudo that encodes a putative MAGL (HirMAGL). The encoded protein exhibits considerable sequence and structural conservation with mammalian forms of MAGL, especially in the catalytic triad that mediates 2-AG metabolism. Additionally, HirMAGL transcripts are detected in the Hirudo central nervous system. When expressed in HEK 293 cells HirMAGL segregates to the plasma membrane as expected. It also exhibits serine hydrolase activity that is blocked when a critical active site residue is mutated. HirMAGL also demonstrates the capacity to metabolize 2-AG and this capacity is also prevented when the active site is mutated. Finally, HirMAGL activity is inhibited by JZL184 and MJN110, specific inhibitors of mammalian MAGL. To our knowledge these findings represent the first characterization of an invertebrate form of MAGL and show that HirMAGL exhibits many of the same properties as mammalian MAGL's that are responsible for 2-AG metabolism. OBJECTIVES This double-blind randomized clinical trial evaluated the influence of pre-treatment with proanthocyanidins (PA) from grape seed extract on the clinical behavior of a simplified etch-and-rinse adhesive placed in non-carious cervical lesions (NCCLs) over 6- and 24-months. MATERIALS AND METHODS A total of 135 restorations were randomly inserted in 45 subjects. The NCCLs were etched with 37 % phosphoric acid for 15 s and distributed into 3 groups Control (PA0) - adhesive ExciTE F applied as per the manufacturer's recommendations; PA2 and PA5 groups - 2 wt% and 5 wt% PA solution, respectively, were applied for 60 s and washed for 30 s prior to application of the adhesive. The resin composite was placed incrementally and light-cured. The restorations were evaluated at baseline, 6 months (6 m) and 24 months (24 m) using both the FDI and USPHS criteria. Statistical analyses were carried out using Friedman repeated-measures analysis of variance by rank and the Wilcoxon test (α = 0.05). RESULTS The retention rates were 98 % (PA0), 98 % (PA2) and 83 % (PA5) after 6 m and 93 % (PA0), 89 % (PA2) and 70 % (PA5) after 24 m. Only PA5 resulted in a significant lower retention rate at 6 m and at 24 m compared with that of baseline (p = 0.03). All groups resulted in a significantly worse marginal adaptation and marginal staining for the FDI criteria when the baseline vs. the 24 m recall data were compared. These differences were considered clinically acceptable under the FDI criteria. CONCLUSIONS The application of PA as a primer did not result in clinical advantages after 24 m of clinical service, regardless of the concentration used. CLINICAL RELEVANCE It has been reported that PA, a collagen crosslinking agent, increases the durability of the dentin-resin interface. However, no effects were found clinically after 24 months. DNA-nanorobot-guided thrombin-inducing tumor infarction (DNA NanorobotTh-ITI) is emerging as a powerful therapeutic strategy for treatment of solid cancers. The technology represents a major advance in the application of DNA nanotechnology for anticancer therapy. More importantly, the technology is being translated from preclinical studies to the clinic owing to its promising anticancer effects with fewer toxicities demonstrated in preclinical settings. However, despite these beneficial effects of the technology, it is important to point out that some important potential clinical concerns remain to be addressed. Here, we raise these clinical concerns along with these beneficial effects of the technology. Hopefully, these newly raised potential clinical concerns could drive forward research in this field to expedite its clinical translation. Computational epitope-based vaccine design is the cornerstone of vaccine development. Owing to the selection of proper compositions [antigens (Ags), epitopes, peptide linkers, and intramolecular adjuvants], epitope-based vaccines are considered a cost- and time-effective approach resulting in the development of vaccines with maximal therapeutic efficacy and minimal adverse reactions. In this review, we provide insights into in silico epitope-based vaccine design and highlight vaccinology procedures used for the development of the next-generation vaccines with high effectiveness.