BackgroundNeoadjuvant immunochemotherapy is increasingly used for resectable locally advanced gastric cancer (LAGC) and gastroesophageal junction (EGJ) adenocarcinoma, yet the optimal chemotherapy backbone for PD-1 blockade remains unclear. We compared neoadjuvant PD-1 inhibitor plus S-1+oxaliplatin (SOX) versus PD-1 inhibitor plus 5-FU+oxaliplatin+Docetaxel+Leucovorin (FLOT) in a real-world cohort.MethodsThis single-center retrospective study included patients with resectable, HER2-negative LAGC/EGJ adenocarcinoma (cT3–4b, any N+, M0; ECOG 0–1) treated between July 2020 and July 2025. Patients received neoadjuvant PD-1 inhibitor plus SOX or PD-1 inhibitor plus FLOT (3–5 cycles) followed by D2 gastrectomy. The primary endpoint was pathological complete response (pCR). Secondary endpoints included major pathological response (MPR), radiologic response (RECIST v1.1), perioperative outcomes, treatment-related adverse events (CTCAE v5.0), recurrence-free survival (RFS), and overall survival (OS). Survival was analyzed using Kaplan–Meier methods and Cox proportional hazards models.ResultsOverall, 247 patients were enrolled (PD-1+SOX, n=141; PD-1+FLOT, n=106) with comparable baseline characteristics. Radiologic outcomes were similar between groups (ORR: 70.92% vs 66.98%, p=0.507; DCR: 87.23% vs 85.85%, p=0.752). Pathological responses did not differ significantly (pCR: 20.57% vs 16.98%, p=0.477; MPR: 37.59% vs 31.13%, p=0.292). Any-grade treatment-related adverse events occurred in 67.38% and 75.47% of patients, and grade ≥3 events in 19.15% and 26.42%, respectively; no treatment-related deaths occurred. R0 resection rates were high (100% vs 99.06%). Operative time and estimated blood loss were higher in the PD-1+FLOT group (p=0.010 and p=0.040), while postoperative complication rates were comparable. With median follow-up of 21 months (12–52) and 20 months (10–46), there were no significant differences in OS (HR 1.155, 95% CI 0.624–2.138) or RFS (HR 0.805, 95% CI 0.461–1.405). In multivariable analyses, non-MPR was an independent risk factor for both OS and RFS.ConclusionsNeoadjuvant PD-1 inhibitor plus SOX and plus FLOT yielded comparable response rates, survival outcomes, and safety profiles in patients with resectable LAGC/EGJ adenocarcinoma. PD-1+SOX was associated with less operative burden, and MPR remained independently associated with OS and RFS, supporting its value for risk stratification and treatment optimization.
Pati Aji Achdiat,1 Raka Ghufran Wibowo,1 Ranisa Larasati,1 Rasmia Rowawi,1 Hermin Aminah Usman,2 Retno Hesty Maharani1 1Department of Dermatology and Venereology, Faculty of Medicine, Universitas Padjadjaran – Dr. Hasan Sadikin Hospital, Bandung, West Java, Indonesia; 2Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran – Dr. Hasan Sadikin Hospital, Bandung, West Java, IndonesiaCorrespondence: Pati Aji Achdiat, Department of Dermatology and Venereology, Faculty of Medicine, Universitas Padjadjaran – Dr. Hasan Sadikin Hospital, Jl. Pasteur 38, Bandung, West Java, 40161, Indonesia, Email pati.aji.achdiat@unpad.ac.idAbstract: Sexual abuse is any non-consensual sexual act or behavior using force, with significant concern in “men who have sex with men” (MSM), and younger individuals. The incidence of sexually transmitted infections (STI) is also prevalent in the cases of sexual abuse in this population, showing the need for comprehensive medical and psychological intervention. This study presents a case of a 15-year-old Indonesian MSM adolescent who experienced three forced sexual intercourse with a mid-thirties male friend 6 months before the consultation. Psychological evaluation showed signs of moderate depression, then the patient reported erythematous macules and collarettes on the palms and soles. These symptoms appeared 1 month before consultation, without associated pain or pruritus. Additionally, moist, skin-colored verrucous papules and plaques were observed in the perianal area, along with a history of unintentional weight loss. The Kinsey score was calculated as three, showing bisexuality. Testing confirmed positive results for both HIV and syphilis, leading to the secondary diagnosis. The patient tested negative for additional STI and was treated with benzathine benzylpenicillin G 2.4 million international unit (IU) and antiretroviral therapy. After one month, the skin lesions improved and the patient was referred to the psychiatric department for psychological treatment. Syphilis and HIV are the predominant infections, showing the critical necessity of administering appropriate medical treatment, such as antiretroviral therapy and comprehensive STI management, with psychological assessment and management to enhance the psychological well-being of sexually abused individuals.Keywords: bisexual, human immunodeficiency virus, Indonesian, men sex with men, secondary syphilis, sexual abuse
Merle Henderson, Alexandra Blenkinsop, Oliver Ratmann
et al.
Abstract Introduction Low bone mineral density (BMD) has been described in children and young people with perinatally acquired HIV (PHIV), which may be related to both traditional (e.g. low body mass index and malnutrition) and HIV‐related risk factors (e.g. longstanding exposure to HIV and antiretroviral therapy [ART], with immune suppression, chronic immune activation and inflammation). Here, we evaluate BMD in a U.K. cohort of young people with PHIV by age and ART. Methods This longitudinal, observational study was conducted at a U.K. tertiary PHIV service between November 2018 and March 2022. Bone health was assessed in 130 individuals aged 15–19 (n = 50), 20−24 (n = 50) and 25 years and older (n = 30) by dual‐energy X‐ray absorptiometry, bone mineralization and turnover markers. Low BMD was defined as lumbar spine (LS) and/or femur‐BMD z‐score below −2, relative to age, sex and ethnicity‐matched U.K. population‐based normative controls. Two‐year follow‐up evaluation was performed in those aged 15−19 (n = 42) and 20−24 years (n = 43) at enrolment, which included a group who switched from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) ART at baseline. Bayesian logistic regression models examined predictors of low BMD and the effect of ART‐backbone on BMD accrual. Results At baseline, 57% were female and 82% of black ethnicity, with 31 (24%) on TDF‐ART. Sixteen (12%) had low baseline BMD. Over a median follow‐up duration of 26 (interquartile range [IQR] 25–29) months, BMD accrual was lower‐than‐expected in those aged 15−19 years (mean change LS‐BMD z‐score −0.15 (standard deviation [SD] 0.44)), when compared to normative controls. No associations were seen with HIV parameters or the ART regimen. Participants who switched to TAF‐ART had similar BMD accrual 26 (IQR 24–32) months post switch, when compared to those on non‐TAF/TDF‐ART (mean change LS‐BMD z‐score TAF −0.01 [SD 0.41] vs. non‐TAF/TDF −0.03 [SD 0.54]). Conclusions While rates of low BMD were reassuringly low in this cohort, lower‐than‐expected BMD accrual was observed in younger individuals, relative to normative controls. Overall, BMD accrual on TAF‐ART was non‐inferior to non‐TAF/TDF‐ART.
IntroductionSilicosis is a progressive fibrotic lung disease without effective treatment options, and its pathogenesis remains incompletely understood, particularly the role of endothelial cells (ECs).MethodsHere, we utilized single-cell RNA sequencing to characterize endothelial responses in lungs from silica-exposed mice.ResultsWe identified two functionally distinct endothelial subpopulations: 1. An inflammatory EC subtype, exhibiting significantly increased abundance and characterized by high expression of neutrophil-recruiting factors such as Spp1 (osteopontin), CCL (C-C motif chemokine ligand), and ESAM (endothelial cell–selective adhesion molecule), suggesting active involvement in neutrophil influx and persistent inflammation. 2. A reparative EC subtype, marked by upregulation of angiogenesis and vascular repair pathways, which exhibited decreased abundance and functional suppression within the silicotic lung microenvironment.DiscussionThese results indicate a pathological shift toward inflammation-amplifying endothelial cells and impaired reparative capacity during silicosis progression. Our findings provide new mechanistic insights into endothelial cell dysfunction in silicosis and highlight potential targets for therapeutic intervention.
IntroductionVarious immune cell types play critical roles in sepsis with numerous distinct subsets exhibiting unique phenotypes even within the same cell population. Single-cell RNA sequencing (scRNA-seq) enables comprehensive transcriptome profiling and unbiased cell classification. In this study, we have unveiled the transcriptomic landscape of immune cells in sepsis through scRNA-seq analysis.MethodsWe induced sepsis in mice by cecal ligation and puncture. 20 h after the surgery, the spleen and peritoneal lavage were collected. Single-cell suspensions were processed using a 10× Genomics pipeline and sequenced on an Illumina platform. Count matrices were generated using the Cell Ranger pipeline, which maps reads to the mouse reference transcriptome, GRCm38/mm10. Subsequent scRNA-seq analysis was performed using the R package Seurat.ResultsAfter quality control, we subjected the entire data set to unsupervised classification. Four major clusters were identified as neutrophils, macrophages, B cells, and T cells according to their putative markers. Based on the differentially expressed genes, we identified activated pathways in sepsis for each cell type. In neutrophils, pathways related to inflammatory signaling, such as NF-κB and responses to pathogen-associated molecular patterns (PAMPs), cytokines, and hypoxia were activated. In macrophages, activated pathways were the ones related to cell aging, inflammatory signaling, and responses to PAMPs. In B cells, pathways related to endoplasmic reticulum stress were activated. In T cells, activated pathways were the ones related to inflammatory signaling, responses to PAMPs, and acute lung injury. Next, we further classified each cell type into subsets. Neutrophils consisted of four clusters. Some subsets were activated in inflammatory signaling or cell metabolism, whereas others possessed immunoregulatory or aging properties. Macrophages consisted of four clusters, namely, the ones with enhanced aging, lymphocyte activation, extracellular matrix organization, or cytokine activity. B cells consisted of four clusters, including the ones possessing the phenotype of cell maturation or aging. T cells consisted of six clusters, whose phenotypes include molecular translocation or cell activation.ConclusionsTranscriptomic analysis by scRNA-seq has unveiled a comprehensive spectrum of immune cell responses and distinct subsets in the context of sepsis. These findings are poised to enhance our understanding of sepsis pathophysiology, offering avenues for targeting novel molecules, cells, and pathways to combat infectious diseases.
Emily A Hemann, Megan L Knoll, Courtney R Wilkins
et al.
Abstract Retinoic acid–inducible gene I (RIG-I) is essential for activating host cell innate immunity to regulate the immune response against many RNA viruses. We previously identified that a small molecule compound, KIN1148, led to the activation of IFN regulatory factor 3 (IRF3) and served to enhance protection against influenza A virus (IAV) A/California/04/2009 infection. We have now determined direct binding of KIN1148 to RIG-I to drive expression of IFN regulatory factor 3 and NF-κB target genes, including specific immunomodulatory cytokines and chemokines. Intriguingly, KIN1148 does not lead to ATPase activity or compete with ATP for binding but activates RIG-I to induce antiviral gene expression programs distinct from type I IFN treatment. When administered in combination with a vaccine against IAV, KIN1148 induces both neutralizing Ab and IAV-specific T cell responses compared with vaccination alone, which induces comparatively poor responses. This robust KIN1148-adjuvanted immune response protects mice from lethal A/California/04/2009 and H5N1 IAV challenge. Importantly, KIN1148 also augments human CD8+ T cell activation. Thus, we have identified a small molecule RIG-I agonist that serves as an effective adjuvant in inducing noncanonical RIG-I activation for induction of innate immune programs that enhance adaptive immune protection of antiviral vaccination.
Endocytic recycling regulates the cell surface receptor composition of the plasma membrane. The surface expression levels of the T cell receptor (TCR), in concert with signal transducing co-receptors, regulate T cell responses, such as proliferation, differentiation, and cytokine production. Altered TCR expression contributes to pro-inflammatory skewing, which is a hallmark of autoimmune diseases, such as systemic lupus erythematosus (SLE), defined by a reduced function of regulatory T cells (Tregs) and the expansion of CD4+ helper T (Th) cells. The ensuing secretion of inflammatory cytokines, such as interferon-γ and interleukin (IL)-4, IL-17, IL-21, and IL-23, trigger autoantibody production and tissue infiltration by cells of the adaptive and innate immune system that induce organ damage. Endocytic recycling influences immunological synapse formation by CD4+ T lymphocytes, signal transduction from crosslinked surface receptors through recruitment of adaptor molecules, intracellular traffic of organelles, and the generation of metabolites to support growth, cytokine production, and epigenetic control of DNA replication and gene expression in the cell nucleus. This review will delineate checkpoints of endosome traffic that can be targeted for therapeutic interventions in autoimmune and other disease conditions.
BackgroundPostoperative systemic inflammatory dysregulation (PSID) is characterised by strongly interlinked immune and metabolic abnormalities. However, the hub genes responsible for the interconnections between these two systemic alterations remain to be identified.MethodsWe analysed differentially expressed genes (DEGs) of individual peripheral blood nucleated cells in patients with PSID (n = 21, CRP > 250 mg/L) and control patients (n = 25, CRP < 75 mg/L) following major abdominal surgery, along with their biological functions. Correlation analyses were conducted to explore the interconnections of immune-related DEGs (irDEGs) and metabolism-related DEGs (mrDEGs). Two methods were used to screen hub genes for irDEGs and mrDEGs: we screened for hub genes among DEGs via 12 algorithms using CytoHubba in Cytoscape, and also screened for hub immune-related and metabolic-related genes using weighted gene co-expression network analysis. The hub genes selected were involved in the interaction between changes in immunity and metabolism in PSID. Finally, we validated our results in mice with PSID to confirm the findings.ResultsWe identified 512 upregulated and 254 downregulated DEGs in patients with PSID compared with controls. Gene enrichment analysis revealed that DEGs were significantly associated with immune- and metabolism-related biological processes and pathways. Correlation analyses revealed a close association between irDEGs and mrDEGs. Fourteen unique hub genes were identified via 12 screening algorithms using CytoHubba in Cytoscape and via weighted gene co-expression network analysis. Among these, CD28, CD40LG, MAPK14, and S100A12 were identified as hub genes among both immune- and metabolism-related genes; these genes play a critical role in the interaction between alterations in immunity and metabolism in PSID. The experimental results also showed that the expression of these genes was significantly altered in PSID mice.ConclusionThis study identified hub genes associated with immune and metabolic alterations in patients with PSID and hub genes that link these alterations. These findings provide novel insights into the mechanisms underlying immune and metabolic interactions and new targets for clinical treatment can be proposed on this basis.
Infecting a wide range of hosts, members of Reovirales (formerly Reoviridae) consist of a genome with different numbers of segmented double stranded RNAs (dsRNA) encapsulated by a proteinaceous shell and carry out genome replication and transcription inside the virion. Several cryo-electron microscopy (cryo-EM) structures of reoviruses with 9, 10 or 11 segmented dsRNA genomes have revealed insights into genome arrangement and transcription. However, the structure and genome arrangement of 12-segmented Reovirales members remain poorly understood. Using cryo-EM, we determined the structure of mud crab reovirus (MCRV), a 12-segmented dsRNA virus that is a putative member of Reovirales in the non-turreted Sedoreoviridae family, to near-atomic resolutions with icosahedral symmetry (3.1 Å) and without imposing icosahedral symmetry (3.4 Å). These structures revealed the organization of the major capsid proteins in two layers: an outer T = 13 layer consisting of VP12 trimers and unique VP11 clamps, and an inner T = 1 layer consisting of VP3 dimers. Additionally, ten RNA dependent RNA polymerases (RdRp) were well resolved just below the VP3 layer but were offset from the 5-fold axes and arranged with D5 symmetry, which has not previously been seen in other members of Reovirales. The N-termini of VP3 were shown to adopt four unique conformations; two of which anchor the RdRps, while the other two conformations are likely involved in genome organization and capsid stability. Taken together, these structures provide a new level of understanding for capsid stabilization and genome organization of segmented dsRNA viruses.
IntroductionSARS-CoV-2 nucleocapsid (N) protein plays a key role in multiple stages of the viral life cycle such as viral replication and assembly. This protein is more conserved than the Spike protein of the virus and can induce both humoral and cell-mediated immune responses, thereby becoming a target for clinical diagnosis and vaccine development. However, the immunogenic characteristics of this protein during natural infection are still not completely understood.MethodsPatient-derived monoclonal antibodies (mAbs) against SARS-CoV-2 N protein were generated from memory B cells in the PBMCs using the antigen-specific B cell approach. For epitope mapping of the isolated hmAbs, a panel of series-truncated N proteins were used , which covered the N-terminal domain (NTD, aa 46-174 ) and C-terminal domain (CTD, aa 245-364 ), as well as the flanking regions of NTD and CTD. NTD- or CTD-specific Abs in the plasma from COVID-19 patients were also tested by ELISA method. Cross-binding of hmAbs or plasma Abs in COVID-19 patients to other human β-CoV N proteins was determined using the capture ELISA.ResultsWe isolated five N-specific monoclonal antibodies (mAbs) from memory B cells in the peripheral blood of two convalescent COVID-19 patients. Epitope mapping revealed that three of the patient-derived mAbs (N3, N5 and N31) targeted the C-terminal domain (CTD), whereas two of the mAbs (N83 and 3B7) targeted the N-terminal domain (NTD) of SARS-CoV-2 N protein. All five patient-derived mAbs were cross-reactive to the N protein of SARS-CoV but showed little to no cross-reactivity to the N proteins of other human beta coronaviruses (β-CoVs). We also tested 52 plasma samples collected from convalescent COVID-19 patients for Abs against the N proteins of human β-CoVs and found that 78.8% of plasma samples showed detectable Abs against the N proteins of SARS-CoV-2 and SARS-CoV. No plasma sample had cross-reactive Abs to the N protein of MERS-CoV. Cross-reactive Abs to the N proteins of OC43 and HKU1 were detected in 36.5% (19/52) and 19.2% (10/52) of plasma samples, respectively.DiscussionThese results suggest that natural SARS-CoV-2 infection elicits cross-reactive Abs to the N protein of SARS-CoV and that the five patient-derived mAbs to SARS-CoV-2 N protein NTD and CTD cross-react with their counterparts of SARS-CoV, but not other human β-CoVs. Thus, these five patient-derived mAbs can potentially be used for developing the next generation of COVID-19 At-Home Test kits for rapid and specific screening of SARS-CoV-2 infection.
Samuel Lara‐Reyna, Emily A Caseley, Joanne Topping
et al.
Abstract Inflammasomes are assembled by innate immune sensors that cells employ to detect a range of danger signals and respond with pro‐inflammatory signalling. Inflammasomes activate inflammatory caspases, which trigger a cascade of molecular events with the potential to compromise cellular integrity and release the IL‐1β and IL‐18 pro‐inflammatory cytokines. Several molecular mechanisms, working in concert, ensure that inflammasome activation is tightly regulated; these include NLRP3 post‐translational modifications, ubiquitination and phosphorylation, as well as single‐domain proteins that competitively bind to key inflammasome components, such as the CARD‐only proteins (COPs) and PYD‐only proteins (POPs). These diverse regulatory systems ensure that a suitable level of inflammation is initiated to counteract any cellular insult, while simultaneously preserving tissue architecture. When inflammasomes are aberrantly activated can drive excessive production of pro‐inflammatory cytokines and cell death, leading to tissue damage. In several autoinflammatory conditions, inflammasomes are aberrantly activated with subsequent development of clinical features that reflect the degree of underlying tissue and organ damage. Several of the resulting disease complications may be successfully controlled by anti‐inflammatory drugs and/or specific cytokine inhibitors, in addition to more recently developed small‐molecule inhibitors. In this review, we will explore the molecular processes underlying the activation of several inflammasomes and highlight their role during health and disease. We also describe the detrimental effects of these inflammasome complexes, in some pathological conditions, and review current therapeutic approaches as well as future prospective treatments.
Background/Aim. Non-small-cell lung cancer (NSCLC) is the principal agent of cancer deaths globally. The goal of this study was to determine how circular RNA_0000518 (circ_0000518) regulates tumor progression. Materials/Methods. circ_0000518 was selected as a study target involved in NSCLC from GEO (Gene Expression Omnibus) database. circ_0000518 level was gauged by qRT-PCR. It was confirmed as circRNA by actinomycin D inhibition and RNase R assay. Subcellular localization of circ_0000518 was identified by FISH. Cell function was determined by CCK-8, Transwell, and western blot. Glutamine metabolic factors were detected by ELISA. The target regulation relationship between genes was clarified by dual-luciferase reporter assay. In vivo models were established to evaluate the impact of circ_0000518 on tumor growth. Immunohistochemical staining for Ki67, vimentin, and E-cadherin was used to detect cell proliferation and metastasis, respectively. Results. circ_0000518 expression was enhanced in NSCLC. si-circ_0000518 inhibited cell proliferation, invasion, and glutamine metabolism. circ_0000518 functioned as a molecular sponge for miR-330-3p, and inhibition of miR-330-3p in cells markedly reversed circ_0000518 interference-mediated antitumor effects. miR-330-3p interacted with 3′-UTR of SLC1A5. miR-330-3p inhibitor-mediated protumor effect was remarkably reversed in cells after the knockdown of SLC1A5. circ_0000518 knockdown reduced glutamine, glutamate, and α-KG by targeting miR-330-3p. Intertumoral injection of circ_0000518 shRNA adeno-associated virus effectively halted xenograft tumor growth. Conclusion. The current study revealed that circ_0000518 may have a prooncogenic function in the formation and progression of NSCLC, which might be achieved through moderating the miR-330-3p/SLC1A5 axis.
Stavroula Kanoni, Satish Kumar, Charalampia Amerikanou
et al.
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease with no therapeutic consensus. Oxidation and inflammation are hallmarks in the progression of this complex disease, which also involves interactions between the genetic background and the environment. Mastiha is a natural nutritional supplement known to possess antioxidant and anti-inflammatory properties. This study investigated how a 6-month Mastiha supplementation (2.1 g/day) could impact the antioxidant and inflammatory status of patients with NAFLD, and whether genetic variants significantly mediate these effects. We recruited 98 patients with obesity (BMI ≥ 30 kg/m2) and NAFLD and randomly allocated them to either the Mastiha or the placebo group for 6 months. The anti-oxidative and inflammatory status was assessed at baseline and post-treatment. Genome-wide genetic data was also obtained from all participants, to investigate gene-by-Mastiha interactions. NAFLD patients with severe obesity (BMI > 35kg/m2) taking the Mastiha had significantly higher total antioxidant status (TAS) compared to the corresponding placebo group (P value=0.008). We did not observe any other significant change in the investigated biomarkers as a result of Mastiha supplementation alone. We identified several novel gene-by-Mastiha interaction associations with levels of cytokines and antioxidant biomarkers. Some of the identified genetic loci are implicated in the pathological pathways of NAFLD, including the lanosterol synthase gene (LSS) associated with glutathione peroxidase activity (Gpx) levels, the mitochondrial pyruvate carrier-1 gene (MPC1) and the sphingolipid transporter-1 gene (SPNS1) associated with hemoglobin levels, the transforming growth factor‐beta‐induced gene (TGFBI) and the micro-RNA 129-1 (MIR129-1) associated with IL-6 and the granzyme B gene (GZMB) associated with IL-10 levels. Within the MAST4HEALTH randomized clinical trial (NCT03135873, www.clinicaltrials.gov) Mastiha supplementation improved the TAS levels among NAFLD patients with severe obesity. We identified several novel genome-wide significant nutrigenetic interactions, influencing the antioxidant and inflammatory status in NAFLD.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT03135873.
David W. Pittman, Alexandra M. Brantly, Alexandra L. Drobonick
et al.
Negative hedonic sensory qualities of HIV antiretroviral drugs often reduce patient adherence particularly in pediatric populations requiring oral consumption. This study examines the palatability of an innovative delivery mechanism utilizing a freeze-drying-in-blister approach to create fast-dissolving tablets (FDTs) containing a fixed-dose combination of lopinavir and ritonavir (LPV/r). Consumption patterns of solutions during brief-access and long-term testing and baby foodstuff consumption were analyzed to evaluate the orosensory detection and avoidance of placebo FDTs containing no LPV/r (FDT−) and FDTs containing LPV/r (FDT+). Rats showed no change in consumption patterns for the placebo FDT− compared with control solutions. Rats can detect but do not avoid FDT+ at body-weight-adjusted dosages in both brief-access (30-s) and long-term (23 h) consumption tests. There is an aversive response to concentrated doses of FDT+ during brief-access tests that cannot be masked by 25% sucrose. However, the strongest FDT+ concentration was not rejected when mixed with 50 g of applesauce, banana sauce, or rice cereal baby foodstuffs. The averseness of the FDT+ was associated with the presence of LPV/r and not the FDT− formulation itself. The novel FDT formulation appears to be a palatable delivery mechanism for oral antiretroviral pharmaceuticals especially when mixed with baby foodstuffs.
Britta Schiela, Sarah Bernklau, Zahra Malekshahi
et al.
Although neglected in the past, the interest on Zika virus (ZIKV) raised dramatically in the last several years. The rapid spread of the virus in Latin America and the association of the infection with microcephaly in newborns or Guillain-Barré Syndrome in adults prompted the WHO to declare the ZIKV epidemic to be an international public health emergency in 2016. As the virus gained only limited attention in the past, investigations on interactions of ZIKV with human complement are limited. This prompted us to investigate the stability of the virus to human complement. At low serum concentrations (10%) which refers to complement concentrations found on mucosal surfaces, the virus was relatively stable at 37°C, while at high complement levels (50% serum concentration) ZIKV titers were dramatically reduced, although the virus remained infectious for about 4–5 min under these conditions. The classical pathway was identified as the main actor of complement activation driven by IgM antibodies. In addition, direct binding of C1q to both envelope and NS1 proteins was observed. Formation of the MAC on the viral surface and thus complement-mediated lysis and not opsonization seems to be essential for the reduction of viral titers.