Prevalence of Parainfluenza Viruses in Seoul, 2021 - 2022.

BACKGROUND: Parainfluenza virus (PIV) is a significant etiological agent of acute lower respiratory tract infections (ALRIs) in infants and young children. The present study has been conducted to investigate the prevalence of recently identified respiratory viruses. METHODS: In total, 543 oropharyngeal or nasopharyngeal swab samples collected from hospitalized patients with acute respiratory symptoms (ARS) between January and December 2021 (5,653 females and 4,950 males) were tested for respiratory viruses using RT-PCR. RESULTS: At least one respiratory virus was detected by RT-PCR in 119 out of 175 samples (68%). The most frequently detected virus was human rhinovirus (HRV) (34, 6.5%), followed by human parainfluenza viruses (HPIVs) (19, 3.6%), human bocavirus (HBoV) (8, 1.5%), human adenovirus (HAdV) (7, 1.3%), and human respiratory syncytial virus (HRSV) (4, 0.8%). HPIV-3 accounted for 3.6% (19/175) of all viral pathogens and was the second most frequently detected viral pathogen in our study. HPIV-3 infections peaked in the fall (November) of 2021. Phylogenetic analysis of the coding region of the viral protein HA revealed that all 35 (100%) of 35 HPIV-infected patients were infected with HPIV-3. CONCLUSIONS: HPIV was an important causative pathogen associated with ALRI in children hospitalized in Korea in the late fall of 2021, as the social distancing rules for COVID-19 were relaxed. These findings highlight the im-portance of HPIV as a cause of ALRI.

Efficacy and Safety of Surgical Resection in Elderly Patients with Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Background/Aims: : With increased life expectancy, the management of elderly hepatocellular carcinoma (HCC) patients became a crucial issue, yet it is still challenging due to comorbidities and high surgical risks. While surgical resection is considered as primary treatment for eligible HCC patients, systematic evidence on its outcomes in elderly patients remains scarce. In this review, we aimed to analyze the efficacy and safety outcomes of surgical resection in elderly HCC patients. Methods: : The studies included in this meta-analysis were selected from Ovid-MEDLINE, Ovid-Embase, CENTRAL, KoreaMed, KMbase, and KISS databases following a predefined protocol. Efficacy outcomes included overall survival and disease-free survival, while the safety outcomes included postoperative mortality and complications. Results: : Patients in the elderly group (≥65 years) who underwent surgery exhibited non-inferior overall survival (hazard ratio [HR], 1.26; 95% confidence interval [CI], 0.92 to 1.74) and disease-free survival (HR, 1.03; 95% CI, 0.99 to 1.08) compared to the non-elderly group. Overall postoperative mortality exhibited no statistical difference (odds ratio [OR], 1.07; 95% CI, 0.87 to 1.31), but 30-day, 90-day, and in-hospital mortality were higher in the elderly group. The incidence of overall complications was higher in the elderly group (OR, 1.44; 95% CI, 1.22 to 1.69). Sensitivity analysis for the super elderly group (≥80 years) showed significantly higher in-hospital mortality compared to the non-super elderly group (OR, 2.51; 95% CI, 1.16 to 5.45). Conclusions: : The efficacy outcome of surgical resection in the elderly HCC patients was not worse than that in the non-elderly HCC patients, while in-hospital mortality and complications rates were higher. Therefore, surgical resection should be purposefully considered in the elderly population, with careful candidate selection.

Association of Urine (pH < 5.5) with Community Periodontal Index (CPI) and the Number of Remaining Teeth in Korean Adults: A Cross-Sectional Study Using Data from Korea National Health and Nutrition Examination Survey 2016-2018.

This study aims to determine the association between UpH (<5.5), Community Periodontal Index (CPI), and the number of remaining teeth-cumulative indicators of oral health-using data from the 7th Korea National Health and Nutrition Examination Survey (KNHANES, 2016-2018), which represents the Korean population. Data from 12,689 adults aged 19 years and older who had periodontal examinations were analyzed. Logistic regression analysis was performed after adjusting for demographic, health, and health-related behavioral factors as covariates to determine the association between UpH, CPI, and the number of remaining teeth. This study found that UpH (<5.5) was associated with CPI and the number of remaining teeth. For UpH (<5.5), the odds ratio for CPI (≥4 mm) was 1.19 times (95% CI: 1.06-1.33). The risk of tooth loss was 1.25 times (95% CI: 1.06-1.48) for those with 0-19 remaining teeth and 1.20 times (95% CI: 1.07-1.34) for those with 20-27 teeth. The results revealed an association between UpH, CPI, and the number of remaining teeth. However, further longitudinal research on UpH and oral status is necessary.

Centrosome amplification and aneuploidy driven by the HIV-1-induced Vpr•VprBP•Plk4 complex in CD4+ T cells.

HIV-1 infection elevates the risk of developing various cancers, including T-cell lymphoma. Whether HIV-1-encoded proteins directly contribute to oncogenesis remains unknown. We observe that approximately 1-5% of CD4+ T cells from the blood of people living with HIV-1 exhibit over-duplicated centrioles, suggesting that centrosome amplification underlies the development of HIV-1-associated cancers by driving aneuploidy. Through affinity purification, biochemical, and cellular analyses, we discover that Vpr, an accessory protein of HIV-1, hijacks the centriole duplication machinery and induces centrosome amplification and aneuploidy. Mechanistically, Vpr forms a cooperative ternary complex with an E3 ligase subunit, VprBP, and polo-like kinase 4 (Plk4). Unexpectedly, however, the complex enhances Plk4's functionality by promoting its relocalization to the procentriole assembly and induces centrosome amplification. Loss of either Vpr's C-terminal 17 residues or VprBP acidic region, the two elements required for binding to Plk4 cryptic polo-box, abrogates Vpr's capacity to induce these events. Furthermore, HIV-1 WT, but not its Vpr mutant, induces multiple centrosomes and aneuploidy in human primary CD4+ T cells. We propose that the Vpr•VprBP•Plk4 complex serves as a molecular link that connects HIV-1 infection to oncogenesis and that inhibiting the Vpr C-terminal motif may reduce the occurrence of HIV-1-associated cancers.

Early-onset vasomotor symptoms and development of depressive symptoms among premenopausal women.

BACKGROUND: We investigated the association between vasomotor symptoms (VMSs) and the onset of depressive symptoms among premenopausal women. METHODS: This cross-sectional study included 4376 premenopausal women aged 42-52 years, and the cohort study included 2832 women without clinically relevant depressive symptoms at baseline. VMSs included the symptoms of hot flashes and night sweats. Depressive symptoms were evaluated using the Center for Epidemiological Studies Depression Scale; a score of ≥16 was considered to define clinically relevant depressive symptoms. RESULTS: Premenopausal Women with VMSs at baseline exhibited a higher prevalence of depressive symptoms compared with women without VMSs at baseline (multivariable-adjusted prevalence ratio 1.76, 95 % confidence interval [CI] 1.47-2.11). Among the 2832 women followed up (median, 6.1 years), 406 developed clinically relevant depressive symptoms. Women with versus without VMSs had a significantly higher risk of developing clinically relevant depressive symptoms (multivariable-adjusted hazard ratio, 1.72; 95 % CI 1.39-2.14). VMS severity exhibited a dose-response relationship with depressive symptoms (P for trend <0.05). LIMITATIONS: Self-reported questionnaires were only used to obtain VMSs and depressive symptoms, which could have led to misclassification. We also could not directly measure sex hormone levels. CONCLUSIONS: Even in the premenopausal stage, women who experience hot flashes or night sweats have an increased risk of present and developed clinically relevant depressive symptoms. It is important to conduct mental health screenings and provide appropriate support to middle-aged women who experience early-onset VMSs.

A multiplex real-time RT-qPCR assay for simultaneous detection of porcine epidemic diarrhea virus, porcine deltacoronavirus, and swine acute diarrhea syndrome coronavirus.

Porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV) cause intestinal diseases with similar manifestations in suckling piglets. In this study, we developed a multiplex real-time PCR for differential diagnosis of PEDV, PDCoV, and SADS-CoV. The assay demonstrated high specificity with a detection limit of 5 copies/µl for each virus. The assay specifically detected PEDV, PDCoV, and SADS-CoV and excluded all other swine pathogens circulating in pigs. Furthermore, the assay exhibited satisfactory performance in analyzing clinical samples. The data indicate that the newly developed multiplex real-time PCR method can be applied for differential diagnosis of porcine enteric coronaviruses.

Porcine Epidemic Diarrhea: Insights and Progress on Vaccines.

Porcine epidemic diarrhea (PED) is a swine-wasting disease caused by coronavirus infection. It causes great economic damage to the swine industry worldwide. Despite the continued use of vaccines, PED outbreaks continue, highlighting the need to review the effectiveness of current vaccines and develop additional vaccines based on new platforms. Here, we review existing vaccine technologies for preventing PED and highlight promising technologies that may help control PED virus in the future.

Relation Between Masticatory Performance and Skeletal Properties in Patients With Skeletal Class III Malocclusion.

This study aimed to measure masticatory performance (MP) using ß-carotene gummy jelly to investigate its relationship with skeletal properties in decompensated patients diagnosed with skeletal class III malocclusion. The study included 78 patients (38 men and 40 women) diagnosed with skeletal class III malocclusion without temporomandibular joint disorder and periodontal disease. MP was measured using a new masticatory measuring device and ß-carotene in the gummy jelly. Lateral and posteroanterior cephalograms were obtained, and skeletal properties (Me deviation, ANB, SNB, APDI, Wits, ODI, facial axis, body length, ramus length, SN-GoGn, anterior facial height, posterior facial height, saddle angle, articular angle, and gonial angle) were evaluated. MP differences according to age and sex and the effect of skeletal properties on MP were analyzed using multiple linear regression analysis. The MP of all patients was 3690.55±1428.77 mm², MP of the male group was 4043.05±1498.09 mm², and MP of the female group was 3355.68±1272.19 mm². Among the items investigated, the variable that affected MP was posterior facial height. Posterior facial height showed a positive correlation (P=0.022). There was no significant difference between MP and other skeletal properties (P>0.05). The severity of the hypodivergency in skeletal class III could affect MP. The relationship between facial asymmetry or skeletal relation and MP could not be explained in this study.

Creatine supplementation with exercise reduces α-synuclein oligomerization and necroptosis in Parkinson's disease mouse model.

Parkinson's disease (PD) is an incurable neurological disorder that causes typical motor deficits. In this study, we investigated the effects of creatine supplementation and exercise in the subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. We found that 2% creatine supplementation and/or exercise intervention for 4 weeks elicited neurobehavioral recovery and neuroprotective effects regarding dopaminergic cell loss in MPTP-treated mice; this effect implies functional preservation of dopaminergic cells in the substantia nigra, as reflected by tyrosine hydroxylase expression recovery. Creatine and exercise reduced necroptotic activity in dopaminergic cells by lowering mixed lineage kinase domain-like protein (MLKL) modification to active phenotypes (phosphorylation at Ser345 and oligomerization) and phosphorylated receptor-interacting protein kinase 1 (RIPK1) (Ser166-p) and RIPK3 (Ser232-p) levels. In addition, creatine and exercise reduced the MPTP-induced increase in pathogenic α-synuclein forms, such as Ser129 phosphorylation and oligomerization. Furthermore, creatine and exercise had anti-inflammatory and antioxidative effects in MPTP mice, as evidenced by a decrease in microglia activation, NF-κB-dependent pro-inflammatory molecule expression, and increase in antioxidant enzyme expression. These phenotypic changes were associated with the exercise/creatine-induced AMP-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor 2 (Nrf2) and sirtuin 3 (SIRT3)/forkhead box O3 (FoxO3a) signaling pathways. In all experiments, combining creatine with exercise resulted in considerable improvement over either treatment alone. Consequently, these findings suggest that creatine supplementation with exercise has anti-inflammatory, antioxidative, and anti-α-synucleinopathy effects, thereby reducing necroptotic cell death in a PD mouse model.

Radiofrequency Ablation versus Surgical Resection in Elderly Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Although the disease burden of elderly cancer patients is rapidly increasing, reliable scientific information, value and preference information of domestic patients, and standardized guidelines for determining the treatment of elderly cancer patients are lacking. The aim of this study is to compare the therapeutic effects of radiofrequency ablation (RFA) and surgery in hepatocellular carcinoma (HCC) patients aged 65 years or older. For the meta-analysis, the databases including PubMed (MEDLINE), EMBASE, OVID Medline, and the Cochrane Library were systematically searched. After the abstract-based review by two investigators, selected manuscripts were read in detail. The surgery group showed higher overall survival (OS) (HR 1.44, 95% CI 1.22-1.70) and disease-free survival (DFS) (HR 1.40, 95% CI 1.00-1.97) than the RFA group. This was also shown in small HCC of less than 3 cm (OS, HR 1.42, 95% CI 1.00-2.03; DFS, HR 1.32, 95% CI 0.91-1.91). This might be related to the high local recurrence in the RFA group (OR 4.90, 95% 2.16-11.08). On the other hand, adverse events were significantly lower in the RFA group (OR 0.22, 95% CI 0.14-0.36), which led to a decrease in the duration of hospital stay (mean difference -14.88 days, 95% CI -22.44--7.32). In elderly HCC patients, survival in the surgery group was significantly higher than in the RFA group, but various complications tended to increase; so, appropriate patient selection is required.

Effects of Adsorption and Desorption of Low-Boiling-Point Total Hydrocarbon Gases on Activated Carbon.

In this study, we selected materials that efficiently adsorb total hydrocarbons (THCs) from petrochemical storage facilities and applied four types of activated carbons to adsorb THCs to evaluate their properties. Four gases with low boiling points, namely, ethylene, ethane, propylene, and propane, generated via petrochemical storage facilities, were selected and mixed to a constant concentration with four types of materials and used to investigate the adsorption capacities and desorption properties. The adsorbents comprised two raw materials and two chemically activated materials. The specific surface areas of activated palm (2085 m2/g) and coal (1752 m2/g), which are chemically activated carbons, exhibited a twofold increase compared to those of raw palm (1232 m2/g) and coal (946 m2/g). Thus, we identified the correlations between the physical properties of the activated carbon adsorption materials and their adsorption capacities for four low-boiling-point THCs generated by petrochemical storage facilities.

Comparative Effects of Bivalent, Quadrivalent, and Nonavalent Human Papillomavirus Vaccines in The Prevention of Genotype-Specific Infection: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Human papillomavirus (HPV) infection is a major global disease burden and the main cause of cervical cancer. Certain HPV genotypes, with are the most common etiologic pathogens and cause a significant disease burden, are being targeted for vaccine development. However, few studies have focused on the comparative effectiveness of the bivalent HPV (2v-HPV), quadrivalent HPV (4v-HPV), and nonavalent HPV (9v-HPV) vaccines against HPV strain-specific infection. This study investigated the comparative effects of these vaccines against genotype-specific infection. MATERIALS AND METHODS: We conducted a pairwise and network meta-analysis of published randomized clinical trials of HPV vaccines according to sex and HPV infection status for nine HPV genotypes (HPV 6/11/16/18/31/33/45/52/58). RESULTS: Overall, 10 randomized controlled trials (12 articles) were included in this study. In the network meta-analysis, no statistically significant differences were observed in the prevention of carcinogenic HPV strains (16/18/31/33/45/52/58) between the 2v-HPV and 4v-HPV vaccines in female HPV infection-naïve populations. However, the 9v-HPV vaccine showed a significantly superior effect compared with 2v-HPV and 4v-HPV vaccines in preventing HPV 31/33/45/52/58 infections. Although 2v-HPV and 4v-HPV vaccines provided some cross-protection against HPV 31/33/45/52/58 infections, the effect was significant only on HPV 31 infection. For HPV 16 and 18, neither statistically significant nor small differences were found in the prevention of HPV infection among the 2v-HPV, 4v-HPV, and 9v-HPV vaccines. CONCLUSION: Our study complements previous understanding of how the effect of HPV vaccines differs according to the HPV genotype. This is important because HPV genotype prevalence varies among countries. We advocate for continued efforts in vaccinating against HPV, while public health agencies should consider the difference in the vaccine effect and HPV genotype prevalence when implementing HPV vaccination in public vaccination programs.

Cost-effectiveness of the anti-vascular endothelial growth factor intravitreal injection and panretinal photocoagulation for patients with proliferative diabetic retinopathy in South Korea.

BACKGROUND: We determined the cost-effectiveness of the anti-vascular endothelial growth factor (VEGF) intravitreal injection versus panretinal photocoagulation (PRP) for patients with proliferative diabetic retinopathy (PDR) in South Korea. METHODS: We simulated four treatment strategies using PRP and the anti-VEGF injection by constructing a Markov model for a hypothetical cohort of 50-year-old PDR patients: (1) PRP only; (2) anti-VEGF injection only; (3) PRP first; and (4) anti-VEGF injection first. RESULTS: In this cost-effectiveness analysis, compared with only-PRP, the incremental cost-effectiveness ratio was $95,456 per quality-adjusted life-year (QALY) for PRP first, $34,375 per QALY for anti-VEGF injection first, and $33,405 per QALY for anti-VEGF injection only from a healthcare perspective. From the societal and payer perspective, strategy (2) was more cost-saving and effective than (1). In the probabilistic sensitivity analysis, only-PRP was cost-effective up to the willingness-to-pay (WTP) of about $42,000, while anti-VEGF injection only was cost-effective from a healthcare perspective. From the societal and payer perspectives, regardless of the value of WTP, anti-VEGF injection only was the most cost-effective strategy. CONCLUSION: In our study, the anti-VEGF injection for PDR was cost-effective from the payer and societal perspectives.

Evaluation of Multiplex Rapid Antigen Tests for the Simultaneous Detection of SARS-CoV-2 and Influenza A/B Viruses.

Single-target rapid antigen tests (RATs) are commonly used to detect highly transmissible respiratory viruses (RVs), such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses. The simultaneous detection of RVs presenting overlapping symptoms is vital in making appropriate decisions about treatment, isolation, and resource utilization; however, few studies have evaluated multiplex RATs for SARS-CoV-2 and other RVs. We assessed the diagnostic performance of multiplex RATs targeting both the SARS-CoV-2 and influenza A/B viruses with the GenBody Influenza/COVID-19 Ag Triple, InstaView COVID-19/Flu Ag Combo (InstaView), STANDARDTM Q COVID-19 Ag Test, and STANDARDTM Q Influenza A/B Test kits using 974 nasopharyngeal swab samples. The cycle threshold values obtained from the real-time reverse transcription polymerase chain reaction results showed higher sensitivity (72.7-100%) when the values were below, rather than above, the cut-off values. The InstaView kit exhibited significantly higher positivity rates (80.21% for SARS-CoV-2, 61.75% for influenza A, and 46.15% for influenza B) and cut-off values (25.57 for SARS-CoV-2, 21.19 for influenza A, and 22.35 for influenza B) than the other two kits, and was able to detect SARS-CoV-2 Omicron subvariants. Therefore, the InstaView kit is the best choice for routine screening for both SARS-CoV-2 and influenza A/B in local communities.

Molecular Characterization of Porcine Epidemic Diarrhea Virus from Field Samples in South Korea.

Porcine epidemic diarrhea virus (PEDV) is a highly contagious enteric pathogen of swine. PEDV has been a major problem in the pig industry since its first identification in 1992. The aim of this study was to investigate the diversity, molecular characteristics, and phylogenetic relationships of PEDVs in field samples from Korea. Six PEDVs were identified from the field samples, and the full spike (S) glycoprotein gene sequences were analyzed. A phylogenetic analysis of the S gene sequences from the six isolates revealed that they were clustered into the G2b subgroup with genetic distance. The genetic identity of the nucleotide sequences and deduced amino acid sequences of the S genes of those isolates was 97.9-100% and 97.4-100%, respectively. A BLAST search for new PEDVs revealed an identity greater than 99.5% compared to the highest similarity of two different Korean strains. The CO-26K equivalent (COE) epitope had a 521H→Y/Q amino acid substitution compared to the subgroup G2b reference strain (KNU-1305). The CNU-22S11 had 28 amino acid substitutions compared to the KNU-1305 strain, which included two newly identified amino acid substitutions: 562S→F and 763P→L in the COE and SS6 epitopes, respectively. Furthermore, the addition and loss of N-linked glycosylation were observed in the CNU-22S11. The results suggest that various strains of PEDV are prevalent and undergoing evolution at swine farms in South Korea and can affect receptor specificity, virus pathogenicity, and host immune system evasion. Overall, this study provides an increased understanding of the prevalence and control of PEDV in South Korea.

Astrocytic Nrf2 Mediates the Neuroprotective and Anti-Inflammatory Effects of Nootkatone in an MPTP-Induced Parkinson's Disease Mouse Model.

This study aims to investigate the neuroprotective effects of nootkatone (NKT), a sesquiterpenoid compound isolated from grapefruit, in an MPTP-induced Parkinson's disease (PD) mouse model. NKT restored MPTP-induced motor impairment and dopaminergic neuronal loss and increased the expression of neurotrophic factors like BDNF, GDNF, and PGC-1α. In addition, NKT inhibited microglial and astrocyte activation and the expression of pro-inflammatory markers like iNOS, TNF-α, and IL-1ß and oxidative stress markers like 4-HNE and 8-OHdG. NKT increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)-driven antioxidant enzymes like HO-1 and NQO-1 in astrocytes, but not in neurons or microglia in MPTP-treated mice. To investigate whether Nrf2 mediates the anti-inflammatory, antioxidant, or neuroprotective effects of NKT, mice were pretreated with Nrf2-specific inhibitor brusatol (BT) prior to NKT treatment. BT attenuated the NKT-mediated inhibition of 4-HNE and 8-OHdG and the number of Nrf2+/HO-1+/NQO1+ cells co-localized with GFAP+ astrocytes in the substantia nigra of MPTP-treated mice. In addition, BT reversed the effects of NKT on dopaminergic neuronal cell death, neurotrophic factors, and pro-/anti-inflammatory cytokines in MPTP-treated mice. Collectively, these data suggest that astrocytic Nrf2 and its downstream antioxidant molecules play pivotal roles in mediating the neuroprotective and anti-inflammatory effects of NKT in an MPTP-induced PD mouse model.

Specific inhibition of an anticancer target, polo-like kinase 1, by allosterically dismantling its mechanism of substrate recognition.

Polo-like kinase 1 (Plk1) is considered an attractive target for anticancer therapy. Over the years, studies on the noncatalytic polo-box domain (PBD) of Plk1 have raised the expectation of generating highly specific protein-protein interaction inhibitors. However, the molecular nature of the canonical PBD-dependent interaction, which requires extensive water network-mediated interactions with its phospholigands, has hampered efforts to identify small molecules suitable for Plk1 PBD drug discovery. Here, we report the identification of the first allosteric inhibitor of Plk1 PBD, called Allopole, a prodrug that can disrupt intracellular interactions between PBD and its cognate phospholigands, delocalize Plk1 from centrosomes and kinetochores, and induce mitotic block and cancer cell killing. At the structural level, its unmasked active form, Allopole-A, bound to a deep Trp-Phe-lined pocket occluded by a latch-like loop, whose adjoining region was required for securely retaining a ligand anchored to the phospho-binding cleft. Allopole-A binding completely dislodged the L2 loop, an event that appeared sufficient to trigger the dissociation of a phospholigand and inhibit PBD-dependent Plk1 function during mitosis. Given Allopole's high specificity and antiproliferative potency, this study is expected to open an unexplored avenue for developing Plk1 PBD-specific anticancer therapeutic agents.

Centrosome amplification and aneuploidy driven by the HIV-1-induced Vpr•VprBP•Plk4 complex in CD4+ T cells.

HIV-1 infection elevates the risk of developing various cancers, including T-cell lymphoma. Whether HIV-1-encoded proteins directly contribute to oncogenesis remains unknown. We observed that approximately 1-5% of CD4+ T cells from the blood of people living with HIV-1 exhibit over-duplicated centrioles, suggesting that centrosome amplification underlies the development of HIV-1-associated cancers by driving aneuploidy. Through affinity purification, biochemical, and cell biology analyses, we discovered that Vpr, an accessory protein of HIV-1, hijacks the centriole duplication machinery and induces centrosome amplification and aneuploidy. Mechanistically, Vpr formed a cooperative ternary complex with an E3 ligase subunit, VprBP, and polo-like kinase 4 (Plk4). Unexpectedly, however, the complex enhanced Plk4's functionality by promoting its relocalization to the procentriole assembly and induced centrosome amplification. Loss of either Vpr's C-terminal 17 residues or VprBP acidic region, the two elements required for binding to Plk4 cryptic polo-box, abrogated Vpr's capacity to induce all these events. Furthermore, HIV-1 WT, but not its Vpr mutant, induced multiple centrosomes and aneuploidy in primary CD4+ T cells. We propose that the Vpr•VprBP•Plk4 complex serves as a molecular link that connects HIV-1 infection to oncogenesis and that inhibiting the Vpr C-terminal motif may reduce the occurrence of HIV-1-associated cancers.

Evaluation of Rapid Multiplex Reverse Transcription-Quantitative Polymerase Chain Reaction Assays for SARS-CoV-2 Detection in Individual and Pooled Samples.

Although coronavirus disease 2019 (COVID-19) is no longer a Public Health Emergency of International Concern (PHEIC), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has had a vast impact to date. Hence, continuous management is required, given the uncertainty caused by the potential evolution of SARS-CoV-2. Reverse transcription-quantitative PCR (RT-qPCR) diagnosis has been fundamental in overcoming this issue. In this study, the performances of two rapid RT-qPCR assays (Real-Q Direct SARS-CoV-2 Detection Kit and Allplex™ SARS-CoV-2 fast PCR Assay) with short PCR times were comparatively evaluated using a STANDARD M nCoV Real-Time Detection Kit (STANDARD M, conventional RT-qPCR assay). All kits showed a limit of detection values (102-103 copies/reaction). The evaluation showed that the two rapid assay tests had ≥97.89% sensitivity and ≥99.51% specificity (κ = 0.98) for individual samples and ≥97.32% sensitivity and ≥97.67% specificity for pooled samples compared to STANDARD M. These results indicate that the two rapid RT-qPCR kits, which showed significant time reduction in performance, are as effective as a conventional RT-qPCR assay. They are likely to increase not only the number of tests that can be performed but also the efficiency of sustainable management of COVID-19 in the long term.