Neuropeptide S Attenuates the Alarm Pheromone-Evoked Defensive and Risk Assessment Behaviors Through Activation of Cognate Receptor-Expressing Neurons in the Posterior Medial Amygdala

Neuropeptide S (NPS) acts by activating its cognate receptor (NPSR). High level expression of NPSR in the posterior medial amygdala suggests that NPS-NPSR system should be involved in regulation of social behaviors induced by social pheromones. The present study was undertaken to investigate the effects of central administration of NPS or with NPSR antagonist on the alarm pheromone (AP)-evoked defensive and risk assessment behaviors in mice. Furthermore, H129-H8, a novel high-brightness anterograde multiple trans-synaptic virus, c-Fos and NPSR immunostaining were employed to reveal the involved neurocircuits and targets of NPS action. The mice exposed to AP displayed an enhancement in defensive and risk assessment behaviors. NPS (0.1–1 nmol) intracerebroventricular (i.c.v.) injection significantly attenuated the AP-evoked defensive and risk assessment behaviors. NPSR antagonist [D-Val5]NPS at the dose of 40 nmol completely blocked the effect of 0.5 nmol of NPS which showed the best effective among dose range. The H129-H8-labeled neurons were observed in the bilateral posterodorsal medial amygdala (MePD) and posteroventral medial amygdala (MePV) 72 h after the virus injection into the unilateral olfactory bulb (OB), suggesting that the MePD and MePV receive olfactory information inputs from the OB. The percentage of H129-H8-labeled neurons that also express NPSR were 90.27 ± 3.56% and 91.67 ± 2.46% in the MePD and MePV, respectively. NPS (0.5 nmol, i.c.v.) remarkably increased the number of Fos immunoreactive (-ir) neurons in the MePD and MePV, and the majority of NPS-induced Fos-ir neurons also expressed NPSR. The behavior characteristic of NPS or with [D-Val5]NPS can be better replicated in MePD/MePV local injection within lower dose. The present findings demonstrated that NPS, via selective activation of the neurons bearing NPSR in the posterior medial amygdala, attenuates the AP-evoked defensive and risk assessment behaviors in mice.

Spontaneous Mutation in the Movement Protein of Citrus Leprosis Virus C2, in a Heterologous Virus Infection Context, Increases Cell-to-Cell Transport and Generates Fitness Advantage

Previous results using a movement defective alfalfa mosaic virus (AMV) vector revealed that citrus leprosis virus C (CiLV-C) movement protein (MP) generates a more efficient local movement, but not more systemic transport, than citrus leprosis virus C2 (CiLV-C2) MP, MPs belonging to two important viruses for the citrus industry. Here, competition experiment assays in transgenic tobacco plants (P12) between transcripts of AMV constructs expressing the cilevirus MPs, followed by several biological passages, showed the prevalence of the AMV construct carrying the CiLV-C2 MP. The analysis of AMV RNA 3 progeny recovered from P12 plant at the second viral passage revealed the presence of a mix of progeny encompassing the CiLV-C2 MP wild type (MPWT) and two variants carrying serines instead phenylalanines at positions 72 (MPS72F) or 259 (MPS259F), respectively. We evaluated the effects of each modified residue in virus replication, and cell-to-cell and long-distance movements. Results indicated that phenylalanine at position 259 favors viral cell-to-cell transport with an improvement in viral fitness, but has no effect on viral replication, whereas mutation at position 72 (MPS72F) has a penalty in the viral fitness. Our findings indicate that the prevalence of a viral population may be correlated with its greater efficiency in cell-to-cell and systemic movements.

Efficacy of Glecaprevir/Pibrentasvir for Real-World HCV Infected Patients in the Northern Part of Tokyo, Japan

Hepatis virus C (HCV) infection causes liver cirrhosis and hepatocellular carcinoma (HCC) worldwide. The objective of our study was to examine the effects of the HCV nonstructural protein (NS) 3/4A inhibitor glecaprevir/NS5A inhibitor pibrentasvir on real-world HCV patients in the northern part of Tokyo, Japan. Although 106 patients were consecutively included, a total of 102 HCV-infected patients with chronic hepatitis or compensated cirrhosis, who received 8- or 12-week combination treatment with glecaprevir/pibrentasvir and were followed up to week 12 after the end of treatment were analyzed retrospectively. Only three patients discontinued treatment due to adverse events; however, they achieved a sustained virologic response at 12 weeks (SVR12). Finally, SVR rates were 99.0% (101/102). Only one patient without liver cirrhosis was a treatment relapser who received hepatic resection for HCC approximately two years after commencement of the 8-week combination treatment with glecaprevir/pibrentasvir. After the exclusion of patients with HCV genotype 1b and P32 deletion in the HCV NS5A region, a 12-week combination of glecaprevir/pibrentasvir led to SVR12 in all nine direct-acting antiviral-experienced patients. Glecaprevir/pibrentasvir had a high efficacy and an acceptable safety profile for real-world HCV patients in a single hospital in Japan.

COVID-19, Pre-Eclampsia, and Complement System

COVID-19 is characterized by virus-induced injury leading to multi-organ failure, together with inflammatory reaction, endothelial cell (EC) injury, and prothrombotic coagulopathy with thrombotic events. Complement system (C) via its cross-talk with the contact and coagulation systems contributes significantly to the severity and pathological consequences due to SARS-CoV-2 infection. These immunopathological mechanisms overlap in COVID-19 and pre-eclampsia (PE). Thus, mothers contracting SARS-CoV-2 infection during pregnancy are more vulnerable to developing PE. SARS-CoV-2 infection of ECs, via its receptor ACE2 and co-receptor TMPRSS2, can provoke endothelial dysfunction and disruption of vascular integrity, causing hyperinflammation and hypercoagulability. This is aggravated by bradykinin increase due to inhibition of ACE2 activity by the virus. C is important for the progression of normal pregnancy, and its dysregulation can impact in the form of PE-like syndrome as a consequence of SARS-CoV-2 infection. Thus, there is also an overlap between treatment regimens of COVID-19 and PE. C inhibitors, especially those targeting C3 or MASP-2, are exciting options for treating COVID-19 and consequent PE. In this review, we examine the role of C, contact and coagulation systems as well as endothelial hyperactivation with respect to SARS-CoV-2 infection during pregnancy and likely development of PE.

First report of garlic viruses A, B and C on garlic (Allium sativum L.) in Tunisia

Mite-borne viruses belonging to the genus Allexivirus (family Alphaflexiviridae) commonly occur on garlic in many parts of the world. There are usually asymptomatic and cause small damage to the plants, but often occur in mixed infection with potyviruses and carlaviruses, with synergistic effects reducing crop quality and leading to higher losses (Taglienti et al. 2017). Their occurrence on Tunisian garlic crops was studied here in the same garlic germplasm collection mentioned in a previous first report (Ayed et al. 2019). Leaf samples from a total of 66 garlic accessions were tested by DAS-ELISA using specific antibodies (DSMZ, Germany) against garlic virus A (GarV-A), garlic virus B (GarV-B) and garlic virus C (GarV-C). These serological tests showed individual virus incidence of respectively 56.4%, 67.7% and 10%. Our findings corroborate with the results of Chodorska et al (2012). In order to confirm the presence of these viruses, RT-PCR assays were performed using total RNAs extracted using two silica-capture extraction procedures according to Foissac et al (2005) and specific primers targeting the coat protein genes of the various viruses. These primers, designed for the present study are (GarV-A-F: 5' YCTYTTCTCHYTDGCHTGGACYTG 3' and GarV-A-R: 5' RCCYTTCCTAGACCARTTRGCRGG 3' for GarV-A; GarV-B-F: 5' TGGGCYTGYTACCACAAYGGATC 3' and GarV-B-R 5' TCTGCGCGVGTGGADACCATRTT 3' for GarV-B; GarV-C-F: 5' ARGAYCTYTTYTCMCTYGCRTGGGC 3' and GarV-C-R: 5' GGAGGYTCRTGAATYTGTTGTTG 3' for GarV-C). The viruses were detected by a two-step RT-PCR as described by Marais et al (2015). PCRs consisted of one cycle at 95 °C for 5 min; followed by 40 cycles of denaturation at 95 °C for 45 s, annealing at 45 °C for 45 s, and elongation at 72 °C for 45s; and a final extension step at 72 °C for 10 min. Products of the expected size (214 bp for GarV-A, 363 bp for GarV-B and 439 bp for GarV-C) were amplified from 58 (88%), 47 (71%) and 56 (85%) accessions, respectively. Forty three samples (65%) were co-infected by the three viruses. Higher numbers of positives revealed by RT-PCR especially in the case of GarV-C may reflect the higher sensitivity and efficiency of this technique compared to ELISA. Direct sequencing of selected amplicons of the expected size obtained for GarV-A, -B, and -C Tunisian isolates was performed and the sequences submitted to GenBank, validating the specificity of the three RT-PCR assays. The two sequenced GarV-A isolates (MK599147 and MN995836) shared 98% nucleotide (nt) sequence identity with each other, and 93-94% identity with the closest isolate in GenBank, the “G118” isolate from China (MN059320). The three sequenced GarV-B isolates (MN995829 to MN995831) shared 88-98% nt identity with each other. For “GarV-B 18.1” (MN995830) and “GarV-B 36.2” (MN995831) the closest isolate was “1109.1” (JX682828) from Spain (92-93% nt identity). For “GarVB 17.2” (MN995829), the closest isolate was “B-Sp-3” (LC97167) from Spain (90% nt identity). The sequenced GarV-C isolate (MN995834) showed the highest sequence nt identity (93%) with the “GarV-9” isolate (HQ724848) from Spain. To our knowledge this is the first report of the presence of GarV-A, -B and -C in Tunisia. The presence of these allexiviruses may pose a threat to the preservation of the Tunisian garlic germplasm and, more broadly, to garlic production in Tunisia. For this reason, the scrupulous identification of viruses occurring in garlic plants will help to use the appropriate strategy to decrease viral incidence in garlic growing area.

Applicability of the medication level variability index (MLVI) in adult hepatic transplantation and association with graft rejection rates

Introduction: Calculation of the Tacrolimus variation index by using the MLVI (Medication Level Variability Index) is set in pediatric liver transplant patients, and it is useful in controlling treatment adherence by associating MLVI values > 2.5 to acute graft liver rejection. Purpose: To verify the association between MLVI values and rejection in adult liver transplant patients. Methods: A retrospective cohort study including liver transplant patients over 18 years of age from December 2012 to December 2017 using orally tacrolimus. For MLVI calculation, tacrolimus serum level outpatient samples were used after 1 year of transplantation. Results: A total of 125 patients were transplanted, of which 86 met criteria for inclusion in the study. The most frequent reason for transplantation was C virus infection (55.8%, n = 48). Rejection was identified in 18.6% of patients (n = 16). The mean MLVI among rejection and nonrejection patients was 2.5 and 2.1 respectively (RR = 0.95, CI: 0.4-2.1, p = 0.57). The frequency of non-immunological complications was 56.2% (n = 9) in patients with rejection versus 62.8% (n = 44) in patients without rejection, most of them with recurrence of virus C (56,8%, n = 25). Conclusion: Although the mean value of MLVI was higher in patients with rejection, our data showed no statistical difference between both groups, which differs from previous studies in pediatric patients. A higher number of nonimmune complications were observed in patients without rejection. The findings suggest that new MLVI cutoffs should be explored in the adult population.

ẢNH HƯỞNG TÌNH TRẠNG VIÊM GAN VIRUS ĐẾN KẾT QUẢ ĐIỀU TRỊ SORAFENIB TRÊN BỆNH NHÂN UNG THƯ BIỂU MÔ TẾ BÀO GAN

Sorafenib được chỉ định trong điều trị ung thư biểu mô tế bào gan giai đoạn tiến triển. Nhiều nghiên cứu được thực hiện để xác định yếu tố tiên lượng ảnh hưởng kết quả điều trị, song chưa có sự đồng thuận, trong đó nhiễm viêm gan virus là 1 yếu tố còn gây tranh cãi. Nghiên cứu này được thực hiện để đánh giá ảnh hưởng của tình trạng viêm gan virus đến kết quả điều trị sorafenib. Đây là nghiên cứu mô tả hồi cứu, tiến cứu trên 110 bệnh nhân ung thư biểu mô tế bào gan điều trị tại bệnh viện K và bệnh viện đại học y Hà nội từ 1-2010 đến 31-11-2018. Kết quả cho thấy tỷ lệ viêm gan virus B (VGB) 75,5%, viêm gan virus C (VGC) 3,6%, đồng nhiễm viêm gan virus B và C 0,9%, không viêm gan virus 20%.Tỷ lệ kiểm soát bệnh ở nhóm VGB, VGC, đồng nhiễm VGB+VGC tương ứng là 55,4%, 50,0%, 100%, 72,7%. Thời gian sống bệnh không tiến triển (PFS) trung vị ở nhóm VGB, VGC, đồng nhiễm VGB+VGC, không viêm gan tương ứng là 4,4 tháng, 2,1 tháng, 5,1 tháng, 6,7 tháng (p>0,05). Thời gian sống toàn bộ (OS) trung vị ở nhóm VGB, VGC, đồng nhiễm VGB+VGC, không viêm gan tương ứng là 5,9 tháng, 2,5 tháng, 17,1 tháng, 13,1 tháng (p>0,05). Trong phân tích đa biến, VGB là yếu tố tiên lượng độc lập đến kết quả điều trị OS, VGB làm tăng gấp 2,5 lần nguy cơ tử vong so với không nhiễm virus VGB (HR= 2,542, 95% CI: 1,327-4,870).

Molecular Identification of Sweet potato virus C on Sweetpotato in Bali, Indonesia

A survey was conducted in several sweet potato cultivations in Bali Province. Survey found that many plants exhibited potyvirus symptom, such as chlorosis blotches. This study was to determine disease incidence, detection and identification of the virus causing these symptoms on sweet potato plants in Bali. Samples were collected by purposive sampling of 10 plants from each location in Bali (Denpasar, Gianyar, Badung, Buleleng, Tabanan, Klungkung, Karangasem, Jembrana, Bangli). Disease insidence was observed based on viral symptoms in the field. Identification of nucleic acids was done using Potyvirus universal primer and DNA sequencing. Disease incidence in Bangli, Buleleng, and Denpasar Regencies was > 50%. RT-PCR and CiFor/CiRev Potyvirus universal primers successfully amplified ± 700 bp of CI genes from all samples from Bangli, while samples from 8 other districts were not amplified using the same primers. The SPVC isolate of sweet potato showed nucleotide and amino acid homology similarities with the sweet potato isolate from East Timor (MF572066), 96.8% and 97.4%, respectively and these were referred to the "Asian" strain. This indicates that SPVC has spread in East Java and Bali.