miRNome profiling of extracellular vesicles in severe COVID-19 patients and identification of predictors of mortality.

BACKGROUND: Extracellular vesicles (EVs), containing microRNAs (miRNAs) and other molecules, play a central role in intercellular communication, especially in viral infections caused by SARS-CoV-2. This study explores the miRNA profiles in plasma-derived EVs from severe COVID-19 patients referred to controls, identifying potential mortality miRNA predictors. METHODS: A prospective study was carried out, including 36 severe COVID-19 patients and 33 non-COVID-19 controls. EVs-derived miRNAs were sequenced, and bioinformatics and differential expression analysis between groups were performed. The plasma miRNA profile of an additional cohort of severe COVID-19 patients (n=32) and non-COVID-19 controls (n=12) was used to compare with our data. Survival analysis was used to identify potential mortality predictors among the SDE miRNAs in EVs. RESULTS: Severe COVID-19 patients showed 50 significantly differentially expressed (SDE) miRNAs in plasma-derived EVs. These miRNAs were associated with pathways related to inflammation and cell adhesion. Fifteen of these plasma-derived EVs miRNAs were also SDE in the plasma of severe patients vs controls. Two miRNAs, hsa-miR-1469 and hsa-miR-6124, were identified as strong mortality predictors with an área under the ROC Curve (AUC) of 0.938. CONCLUSION: : This research provides insights into the role of miRNAs found within EVs in severe COVID-19 and their potential as clinical biomarkers for mortality.

Incidence of pleural effusion with dasatinib and the effect of switching therapy to a different TKI in patients with chronic phase CML.

Dasatinib is one of the second generation tyrosine kinase inhibitors (TKI) which is approved for the treatment of patients with chronic phase CML (CP-CML) both in the front line and in the second line setting. Pleural effusion (PE) is a unique toxicity associated with dasatinib use. Our aim was to study the incidence of pleural effusion in our cohort of patients who were treated with dasatinib for CP-CML and the safety upon TKI switch. A total of 390 patients were treated with dasatinib during their course of treatment for CP-CML. A total of 69 patients (17.6%) developed any grade of PE. About 33 (48%) patients developed CTCAE grade 2 PE, 34 (49%) grade 3 and only 1 patient developed grade 4 PE. Recurrence of PE was observed in 34 (49%) patients. While only 12 patients (17.3%) continued using dasatinib after development of PE, dasatinib was discontinued in the other 57 patients. Therapy was switched to bosutinib in 13 patients out of which 6 (46%) patients re-developed PE. While only 12.5% patients developed re-accumulation of pleural fluid in patients switched to imatinib, none of the patients switched to nilotinib re-developed PE. A change in TKI to bosutinib was associated with a 46% risk of recurrence of PE in patients who develop PE on dasatinib for the treatment of CP-CML. The incidence of recurrent PE was markedly lower in patient switched to imatinib or nilotinib.

Diagnostic performance of hepatitis C core antigen assay to identify active infections: A systematic review and meta-analysis.

Hepatitis C virus (HCV) core antigen (HCVcAg) assay is an alternative for diagnosing HCV infection in a single step. This meta-analysis aimed to evaluate the Abbott ARCHITECT HCV Ag assay's diagnostic performance (validity and utility) for diagnosing active hepatitis C. PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library were searched until 10 January 2023. The protocol was registered at the prospective international register of systematic reviews (PROSPERO: CRD42022337191). Abbott ARCHITECT HCV Ag assay was the test for evaluation, and nucleic acid amplification tests with a cut-off ≤50 IU/mL were the gold standard. Statistical analysis was performed using STATA with the MIDAS module and random-effects models. The bivariate analysis was conducted on 46 studies (18,116 samples). The pooled sensitivity was 0.96 (95% CI = 0.94-0.97), specificity 0.99 (95% CI = 0.99-1.00), positive likelihood ratio 141.81 (95% CI = 72.39-277.79), and negative likelihood ratio 0.04 (95% CI = 0.03-0.06). The area under the summary receiver operating characteristic curve was 1.00 (95% CI = 0.34-1.00). For active hepatitis C prevalence values of 0.1%-15%, the probability that a positive test was a true positive was 12%-96%, respectively, indicating that a confirmatory test should be necessary, particularly with a prevalence ≤5%. However, the probability that a negative test was a false negative was close to zero, indicating the absence of HCV infection. The validity (accuracy) of the Abbott ARCHITECT HCV Ag assay for screening active HCV infection in serum/plasma samples was excellent. Although the HCVcAg assay showed limited diagnostic utility in low prevalence settings (≤1%), it might help diagnose hepatitis C in high prevalence scenarios (≥5%).

The use of digital technologies in peri-implant soft tissue augmentation - A narrative review on planning, measurements, monitoring and aesthetics.

OBJECTIVE: To identify the different uses and modalities of digital technologies to diagnose, plan and monitor peri-implant soft tissue conditions and aesthetics. METHODS: A comprehensive narrative review of pertinent literature was conducted, critically appraising key digital technologies that may assist peri-implant soft tissue augmentation and assessment. An electronic search on four databases including studies published prior to 1st July 2023 was performed and supplemented by a manual search. RESULTS: Predominantly, tools such as cone beam computed tomography (CBCT), intraoral scanning (iOS), intraoral ultrasonography and digital spectrophotometry were commonly to assess and monitor peri-implant soft tissues. The main clinical and research applications included: (i) initial assessment of mucosal thickness, supra-crestal tissue height and keratinized mucosa width, (ii) evaluation of peri-implant soft tissue health and inflammation, (iii) monitoring profilometric changes and midfacial mucosal margin stability over time and (iv) aesthetic evaluation through colour assessment. While evidence for some digital tools may be limited, the integration of digital technologies into peri-implant soft tissue management holds great promise. These technologies offer improved precision, comfort and speed in assessment, benefiting both patients and clinicians. CONCLUSION: As digital technologies progress, their full potential in peri-implant soft tissue augmentation and their value will become more evident with ongoing research. Embracing these innovations and their potential benefits is recommended to ensure that during progress in implant dentistry, patient care is not hindered.

Ultrasonography-Derived Elasticity Estimation of Live Porcine Oral Mucosa.

OBJECTIVES: To investigate the biomechanical properties of porcine oral tissues with in vivo ultrasonography and to compare the difference between oral alveolar mucosa and gingival tissue concerning compressional and tensile mechanical strain. MATERIALS AND METHODS: Sinclair minipigs (6 females and 4 males, 6 to 18 months of age) were anesthetized for ultrasonography. In vivo high-frequency tissue harmonic ultrasound (12/24 MHz) cine-loops were obtained while inducing mechanical tissue stress (0 to 1 N). Post-processing strain analysis was performed in a cardiac speckle tracking software (EchoInsight®). Region of interest (ROI) was placed for gingival and alveolar mucosa tissues for longitudinal (compressional) and tensile strain analyses. A calibrated gel pad was employed to determine the absolute force (pressure) for the measured tissue strain response function. The resulting elasticity data was statistically analyzed using custom Matlab scripts. RESULTS: In total, 38 sonography cine-loops around the third premolars were included in the investigation. The longitudinal strain of alveolar mucosa ε AM L was found to be significantly (P < .05) larger than that of gingiva ε G L . Across the measured force range, ε AM L ~ 1.7 × Îµ G L . Significant differences between alveolar mucosa and gingiva tissues were found for all forces. The tensile strain of the alveolar mucosa ε AM T was found to be ~2 × Îµ G T (on the epithelial surface of the gingiva). Both were statistically significantly different for forces exceeding ~0.08 N. At depth, that is, 500 and 1000 µm below the epithelial surface, the gingiva was found to have less ability to stretch contrary to the alveolar mucosa. Gingival tissue at 500 µm depth has significantly less tensile strain than at its surface and more than at 1000 µm depth. In contrast, the tensile strain of alveolar mucosa is largely independent of depth. CONCLUSION: Ultrasonography can reveal significant differences in oral alveolar mucosal and gingival elastic properties, such as compressional and tensile strain. Under minute forces equivalent to 10 to 40 g, these differences can be observed. As dental ultrasound is a chairside, and noninvasive modality, obtaining real-time images might soon find clinical utility as a new diagnostic tool for the objective and quantitative assessment of periodontal and peri-implant soft tissues in clinical and research realms. As ultrasound is a safe modality with no known bioeffects, longitudinal monitoring of areas of concern would be particularly attractive.

Diagnostic Performance of the HCV Core Antigen Test To Identify Hepatitis C in HIV-Infected Patients: a Systematic Review and Meta-Analysis.

The standard algorithm for diagnosing hepatitis C virus (HCV) infection has two steps, an HCV antibody test for screening and a nucleic acid amplification test (NAAT) for confirmation. However, the HCV core antigen (HCVcAg) detection assay is an alternative for one-step diagnosis. We aimed to evaluate the diagnostic performance of the Abbott ARCHITECT HCV Ag assay to detect active hepatitis C in serum/plasma in people living with HIV/AIDS (PLWHA), through a systematic review and meta-analysis. PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library were searched until 20 September 2022 (PROSPERO, CRD42022348351). We included studies evaluating Abbott ARCHITECT HCV Ag assay (index assay) versus NAATs (reference test) in PLWHA coinfected with HCV who did not receive antiviral treatment for HCV. Meta-analysis was performed with the MIDAS module using Stata and random-effects models. The QUADAS-2 tool evaluated the risk of bias. The bivariate analysis was conducted on 11 studies with 2,407 samples. Pooled sensitivity was 0.95 (95% CI = 0.92 to 0.97), specificity 0.97 (95% CI = 0.93 to 0.99), positive likelihood ratio 37.76 (95% CI = 12.84 to 111.02), and negative likelihood ratio 0.06 (95% CI = 0.04 to 0.09). The area under the curve was 0.97 (95% CI = 0.20 to 1.00). For low prevalence (≤5%), the posttest probability that an individual with a positive test was a true positive ranged from 4% to 67%, whereas, at high prevalence (≥10%), the posttest probability was between 81% and 87%, indicating that a confirmatory test should be necessary, particularly with prevalence values of ≤1%. Regardless of prevalence, the probability that an individual with a negative test was a false negative was close to zero, indicating that the individual was not infected with HCV. In conclusion, the accuracy of the Abbott ARCHITECT HCV Ag assay was very good for HCV screening in serum/plasma samples from PLWHA. The clinical utility to confirm HCV infection was acceptable in high-prevalence settings (≥10%) but poor in low-prevalence settings (≤1%). Furthermore, it was excellent in excluding active HCV infection.

Relative telomere length impact on mortality of COVID-19: Sex differences.

Increasing age is associated with severity and higher mortality of COVID-19. Telomere shortening is associated with higher risk of infections and may be used to identify those patients who are more likely to die. We evaluated the association between relative telomere length (RTL) and COVID-19 mortality. RTL was measured in patients hospitalized because of COVID-19. We used Kaplan-Meier method to analyze survival probabilities, and Cox regression to investigate the association between RTL and mortality (30 and 90 days). Six hundred and eight patients were included in the analysis (mean age =72.5 years, 41.1% women, and 53.8% Caucasic). During the study period, 75 people died from COVID-19 and 533 survived. Lower RTL was associated with a higher risk of death in women either at 30 (adjusted hazard ratio [HR] (aHR) = 3.33; 95% confidence interval [CI] = 1.05-10.00; p = 0.040) and at 90 days (aHR = 3.57; 95%CI = 1.23-11.11; p = 0.019). Lower RTL was associated with a higher risk of dying of COVID-19 in women. This finding suggests that RTL has an essential role in the prognosis of this subset of the population.

HCV spontaneous clearers showed low senescence profile in people living with HIV under long ART.

Coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) increases immune activation, inflammation, and oxidative stress that could lead to premature senescence. Different HCV infections, either acute or chronic infection, could lead to distinct premature cellular senescence in people living with HIV (PLWHIV). Observational study in 116 PLWHIV under antiretroviral treatment with different HCV status: (i) n = 45 chronically infected with HCV (CHC); (ii) n = 36 individuals who spontaneously clarify HCV (SC); (iii) n = 35 HIV controls. Oxidative stress biomarkers were analyzed at lipid, DNA, protein, and nitrates levels, as well as antioxidant capacity and glutathione reductase enzyme. Replicative senescence was evaluated by relative telomere length (RTL) measurement. Additionally, 26 markers of Senescence-Associated Secretory Phenotype (SASP) were analyzed by multiplex immunoassays (Luminex xMAP technology). Differences were evaluated by generalized linear model (GLMs) adjusted by most significant covariates. The SC group had a senescence signature similar to the HIV control group and slightly lower SASP levels. However, significant differences were observed with respect to the CHC group, where an increase in the nitrate concentration [adjusted arithmetic mean ratio, aAMR = 1.73 (1.27-2.35), p < 0.001, q = 0.009] and the secretion of 13 SASP-associated factors [granulocyte macrophage colony-stimulating factor (GM-CSF), interferon-ß, interleukin (IL)-1ß, IL-2, IL-8, IL-13, tumor necrosis factor (TNF)-α, IL-1α, IL-1RA, IL-7, IL-15, C-X-C motif chemokine ligand 10 (IP-10), stem cell factor (SCF); q < 0.1)] was detected. The CHC group also showed higher values of IL-1α, IP-10, and placental growth factor 1 (PIGF-1) than HIV controls. The SC group showed a slightly lower senescence profile than the HIV group, which could indicate a more efficient control of viral-induced senescence due to their immune strengths. Chronic HCV infection in PLWHIV led to an increase in nitrate and elevated SASP biomarkers favoring the establishment of viral persistence.

Immunological and senescence biomarker profiles in patients after spontaneous clearance of hepatitis C virus: gender implications for long-term health risk.

BACKGROUND: About 25% of patients with acute hepatitis C virus (HCV) infection show spontaneous clearance within the first six months of infection but may remain at risk of inflammaging, aging, and liver and non-liver disease complications. This study evaluated the differences in the plasma levels of immune checkpoints (ICs) and senescence-associated secretory phenotype (SASP) biomarkers between patients who had spontaneously eliminated HCV infection (SC group) and individuals without evidence of HCV infection (C group). METHODS: We performed a multicenter retrospective study of 56 individuals: 32 in the SC and 24 in the C groups. ICs and SASP proteins were analyzed using a Luminex 200TM analyzer. The statistical analysis used Generalized Linear Models with gamma distribution (log-link) adjusted by significant variables and sex. RESULTS: 13 ICs (BTLA, CD137(4-1BB), CD27, CD28, CD80, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, and TIM-3) and 13 SASP proteins (EGF, Eotaxin, IL-1alpha, IL-1RA, IL-8, IL-13, IL-18, IP-10, SDF-1alpha, HGF, beta-NGF, PLGF-1, and SCF) were significantly higher in SC group after approximately more than two years of HCV clearance. After stratifying by sex, differences remained significant for males, which showed higher levels for 13 ICs and 4 SASP proteins in SC. While only PD-L2 was significantly higher in SC women, and no differences in SASP were found. CONCLUSIONS: Higher plasma levels of different IC and SASP proteins were found in individuals after more than two years of HCV clearance, mainly in men. Alterations in these molecules might be associated with an increased risk of developing liver and non-hepatic diseases.

Loss of the E2 SUMO-conjugating enzyme Ube2i in oocytes during ovarian folliculogenesis causes infertility in mice.

The number and quality of oocytes within the ovarian reserve largely determines fertility and reproductive lifespan in mammals. An oocyte-specific transcription factor cascade controls oocyte development, and some of these transcription factors, such as newborn ovary homeobox gene (NOBOX), are candidate genes for primary ovarian insufficiency in women. Transcription factors are frequently modified by the post-translational modification SUMOylation, but it is not known whether SUMOylation is required for function of the oocyte-specific transcription factors or if SUMOylation is required in oocytes during their development within the ovarian follicle. To test this, the sole E2 SUMO-conjugating enzyme, Ube2i, was ablated in mouse oocytes beginning in primordial follicles. Loss of oocyte Ube2i resulted in female infertility with major defects in stability of the primordial follicle pool, ovarian folliculogenesis, ovulation and meiosis. Transcriptomic profiling of ovaries suggests that loss of oocyte Ube2i caused defects in both oocyte- and granulosa cell-expressed genes, including NOBOX and some of its known target genes. Together, these studies show that SUMOylation is required in the mammalian oocyte during folliculogenesis for both oocyte development and communication with ovarian somatic cells.

Blood microbiome is associated with changes in portal hypertension after successful direct-acting antiviral therapy in patients with HCV-related cirrhosis.

BACKGROUND: Patients with a significant decrease in hepatic venous pressure gradient (HVPG) have a considerable reduction of liver complications and higher survival after HCV eradication. OBJECTIVES: To evaluate the association between the baseline blood microbiome and the changes in HVPG after successful direct-acting antiviral (DAA) therapy in patients with HCV-related cirrhosis. METHODS: We performed a prospective study in 32 cirrhotic patients (21 HIV positive) with clinically significant portal hypertension (HVPG ≥10 mmHg). Patients were assessed at baseline and 48 weeks after HCV treatment completion. The clinical endpoint was a decrease in HVPG of ≥20% or HVPG <12 mmHg at the end of follow-up. Bacterial 16S ribosomal DNA was sequenced using MiSeq Illumina technology, inflammatory plasma biomarkers were investigated using ProcartaPlex immunoassays and the metabolome was investigated using GC-MS. RESULTS: During the follow-up, 47% of patients reached the clinical endpoint. At baseline, those patients had a higher relative abundance of Corynebacteriales and Diplorickettsiales order, Diplorickettsiaceae family, Corynebacterium and Aquicella genus and Undibacterium parvum species organisms and a lower relative abundance of Oceanospirillales and Rhodospirillales order, Halomonadaceae family and Massilia genus organisms compared with those who did not achieve the clinical endpoint according to the LEfSe algorithm. Corynebacteriales and Massilia were consistently found within the 10 bacterial taxa with the highest differential abundance between groups. Additionally, the relative abundance of the Corynebacteriales order was inversely correlated with IFN-γ, IL-17A and TNF-α levels and the Massilia genus with glycerol and lauric acid. CONCLUSIONS: Baseline-specific bacterial taxa are related to an HVPG decrease in patients with HCV-related cirrhosis after successful DAA therapy.

Sensitized by a sea slug: Site-specific short-term and general long-term sensitization in Aplysia following Navanax attack.

Neurobiological studies of the model species, Aplysia californica (Mollusca, Gastropoda, Euopisthobranchia), have helped advance our knowledge of the neural bases of different forms of learning, including sensitization, a non-associative increase in withdrawal behaviors in response to mild innocuous stimuli. However, our understanding of the natural context for this learning has lagged behind the mechanistic studies. Previous studies, which exclusively used artificial stimuli, such as electric shock, to produce sensitization, left open the question of which stimuli might cause sensitization in nature. Our laboratory first addressed this question by testing for short and long-term sensitization after predatory attack by a natural predator, the spiny lobster. In the present study, we tested for sensitization after attack by a very different predator, the predacious sea-slug, Navanax inermis (Mollusca, Gastropoda, Euopisthobranchia). Unlike the biting and prodding action of lobster attack, Navanax uses a rapid strike that sucks and squeezes its prey in an attempt to swallow it whole. We found that Navanax attack to the head of Aplysia caused strong immediate sensitization of head withdrawal, and weaker, delayed, sensitization of tail-mantle withdrawal. By contrast, attack to the tail of Aplysia resulted in no sensitization of either reflex. We also developed an artificial attack stimulus that allowed us to mimick a more consistently strong attack. This artificial attack produced stronger but qualitatively similar sensitization: Strong immediate sensitization of head withdrawal and weaker sensitization of tail-mantle withdrawal after head attack, immediate sensitization in tail-mantle withdrawal, but no sensitization of head withdrawal after tail attack. We conclude that Navanax attack causes robust site-specific sensitization (enhanced sensitization near the site of attack), and weaker general sensitization (sensitization of responses to stimuli distal to the attack site). We also tested for long-term sensitization (lasting longer than 24 h) after temporally-spaced delivery of four natural Navanax attacks to the head of subject Aplysia. Surprisingly, these head attacks, any one of which strongly sensitizes head withdrawal in the short term, failed to sensitize head-withdrawal in the long term. Paradoxically, these repeated head attacks produced long-term sensitization in tail-mantle withdrawal. These experiments and observations confirm that Navanax attack causes short, and long-term sensitization of withdrawal reflexes of Aplysia. They add site-specific sensitization as well as paradoxical long-term sensitization of tail-mantle withdrawal to a short list of naturally induced learning phenotypes in this model species. Together with previous observations of sensitization after lobster attack, these data strongly support the premise that sensitization in Aplysia is an adaptive response to sub-lethal predator attack.

Hearing and Vestibular Loss with Misuse of Opioids and Illicit Drugs: A Review of the Literature.

BACKGROUND: The purpose of this review was to summarize the literature regarding the effects of opioids and illicit drugs on the auditory and vestibular systems. METHODS: Data were sourced from published papers reporting hearing loss (HL) and/or vestibular loss (VL) following misuse or overdose of opioids or illicit drugs. Most papers consisted of retrospective single-case reports, with few retrospective reviews or prospective cohort studies. Search terms included variations of HL, VL, opioids, and illicit drugs. Search results yielded 51 articles published between 1976 and 2021. A total of 44 articles were reviewed after excluding studies that were not available in English (n = 3), only described acute effects in healthy cohorts (n = 3) or only described general health aspects in a group on methadone maintenance (n = 1). RESULTS: Sixteen studies reported ototoxicity from illicit drugs, 27 from prescription opioids, and 1 was unspecified. This review shows that HL associated with amphetamines and cocaine was typically sudden, bilateral, and temporary. HL from cocaine/crack and heroin often presented with greatest losses in the mid-frequency range. HL associated with opioids was typically sudden, bilateral, moderately severe to profound, and in most cases permanent. The literature is sparse regarding VL from illicit drugs and opioids. CONCLUSION: Practitioners who see patients for sudden or rapidly progressive HL or VL with no apparent cause should inquire about misuse of illicit drugs and opioids, particularly when the HL does not respond to steroid treatment.

Key Characteristics and Development of Psychoceuticals: A Review.

Psychoceuticals have brought benefits to the pharmacotherapeutic management of central nervous system (CNS) illnesses since the 19th century. However, these drugs have potential side effects or lack high response rates. This review covers twenty drugs' biochemical mechanisms, benefits, risks, and clinical trial reports. For this study, medications from seven psychoceutical organizations were reviewed and evaluated. Nineteen drugs were chosen from the organizations, and one was selected from the literature. The databases used for the search were Pubmed, Google Scholar, and NIH clinical trials. In addition, information from the organizations' websites and other sources, such as news reports, were also used. From the list of drugs, the most common targets were serotonergic, opioid, and N-methyl-D-aspartate (NMDA) receptors. These drugs have shown promise in psychiatric illnesses such as substance abuse, post-traumatic stress disorder (PTSD), anxiety, depression, and neurological conditions, such as Parkinson's disease, traumatic brain injury, and neuroinflammation. Some of these drugs, however, are still early in development, so their therapeutic significance cannot be determined. These twenty drugs have promising benefits, but their clinical usage and efficacy must still be explored.

OLFM4 polymorphisms predict septic shock survival after major surgery.

BACKGROUND: Higher expression of olfactomedin-4 (OLFM4), a gene regulated by nuclear factor-kappa B (NF-κB), has been related to a higher risk of organ failure and death in patients with septic shock. We aimed to evaluate the association between OLFM4 single nucleotide polymorphisms (SNPs) and septic shock-related death in 175 patients who underwent major surgery, as well as its performance in predicting mortality. MATERIALS AND METHODS: We carried out a retrospective study. A total of seven OLFM4 SNPs were genotyped by Agena Bioscience's MassARRAY platform. Statistical analysis was performed by Kaplan-Meier and Cox regression tests. The diagnostic performance for predicting septic shock-related death was evaluated by the area under the receiver-operating characteristic (AUROC) curve. RESULTS: Patients with rs17552047 A allele and rs1891944 TT genotype had higher survival than patients with rs17552047 G allele (P-value = .024) and patients with rs1891944 CC/CT genotype (P-value = .038). However, only rs17552047 was associated with a lower risk of death under an additive inheritance model (adjusted hazard ratio [aHR] = 0.44, 95% CI = 0.27-0.71). The multivariate model with the most significant clinical variables (lactate, chronic kidney disease, peritonitis, heart disease and elective surgery) showed an AUROC of 0.776 for predicting septic shock-related death. When we added the OLFM4 rs17552047 SNP to the previous model, the AUROC was 0.811 and was close to reaching significant differences with the previous model (P-value = .065). CONCLUSION: OLFM4 rs17552047 A allele predicts septic shock survival in patients who underwent major surgery. Furthermore, rs17552047, together with clinical variables, could be useful to predict the outcome of septic shock.

HCV eradication with IFN-based therapy does not completely restore gene expression in PBMCs from HIV/HCV-coinfected patients.

OBJECTIVE: To evaluate the impact of hepatitis C virus (HCV) elimination via interferon (IFN)-based therapy on gene expression profiles related to the immune system in HIV/HCV-coinfected patients. METHODS: We conducted a prospective study in 28 HIV/HCV-coinfected patients receiving IFN-based therapy at baseline (HIV/HCV-b) and week 24 after sustained virological response (HIV/HCV-f). Twenty-seven HIV-monoinfected patients (HIV-mono) were included as a control. RNA-seq analysis was performed on peripheral blood mononuclear cells (PBMCs). Genes with a fold-change (FC) ≥ 1.5 (in either direction) and false discovery rate (FDR) ≤ 0.05 were identified as significantly differentially expressed (SDE). RESULTS: HIV/HCV-b showed six SDE genes compared to HIV-mono group, but no significantly enriched pathways were observed. For HIV/HCV-f vs. HIV/HCV-b, we found 58 SDE genes, 34 upregulated and 24 downregulated in the HIV/HCV-f group. Of these, the most overexpressed were CXCL2, PDCD6IP, ATP5B, IGSF9, RAB26, and CSRNP1, and the most downregulated were IFI44 and IFI44L. These 58 SDE genes revealed two significantly enriched pathways (FDR < 0.05), one linked to Epstein-Barr virus infection and another related to p53 signaling. For HIV/HCV-f vs. HIV-mono group, we found 44 SDE genes that revealed 31 enriched pathways (FDR < 0.05) related to inflammation, cancer/cell cycle alteration, viral and bacterial infection, and comorbidities associated with HIV/HCV-coinfection. Five genes were overrepresented in most pathways (JUN, NFKBIA, PIK3R2, CDC42, and STAT3). CONCLUSION: HIV/HCV-coinfected patients who eradicated hepatitis C with IFN-based therapy showed profound gene expression changes after achieving sustained virological response. The altered pathways were related to inflammation and liver-related complications, such as non-alcoholic fatty liver disease and hepatocellular carcinoma, underscoring the need for active surveillance for these patients.

Age Effects of Bone Conduction Vibration Vestibular-evoked Myogenic Potentials (VEMPs) Using B81 and Impulse Hammer Stimuli.

OBJECTIVE: Recently developed, the Radioear B81 bone oscillator allows for higher bone conduction vibration output; however, normative data are lacking regarding its use in vestibular-evoked myogenic potential (VEMP) testing. The purpose of this study was to examine the effect of age on cervical and ocular VEMP (c- and oVEMP) responses using the B81 and to compare with air conduction stimuli (ACS) and impulse hammer (IH) VEMP response characteristics. DESIGN: c- and oVEMP were completed with ACS, B81, and IH stimuli in healthy participants (age range = 10 to 87 years, n = 85). RESULTS: Regardless of stimulus type, c- and oVEMP amplitudes and response rates decreased with age. For cVEMP response rates, ACS performed better or equal to B81, which was superior to the IH. For cVEMP corrected amplitude, ACS had significantly higher amplitudes compared with B81 and IH. There was no difference in cVEMP corrected amplitude between B81 and IH. For oVEMP, response rates were comparable between stimuli with the largest disparity in response rates occurring in the oldest groups where IH outperformed both ACS and B81. For oVEMP amplitude, IH had significantly higher amplitudes compared with B81 and ACS. There was no difference in oVEMP amplitude between B81 and ACS. CONCLUSIONS: Age significantly affected c- and oVEMP amplitudes regardless of stimulus type (ACS, B81, IH). All stimuli are appropriate for eliciting c- and oVEMP in the young individuals. While ACS resulted in higher cVEMP corrected amplitudes, either ACS or B81 are appropriate for older individuals. However, for oVEMPs, higher response rates and larger amplitudes were noted for IH followed by B81 and ACS. Overall, the B81 performed well across the lifespan for c- and oVEMPs and may be a reasonable bone conduction vibration option for patients with absent ACS VEMPs, but at this time is not recommended as a replacement to ACS.

Bone Conduction Vibration Vestibular Evoked Myogenic Potential (VEMP) Testing: Reliability in Children, Adolescents, and Young Adults.

OBJECTIVES: Bone conduction vibration (BCV) vestibular evoked myogenic potentials (VEMP) are clinically desirable in children for multiple reasons. However, no accepted standard exists for stimulus type and the reliability of BCV devices has not been investigated in children. The objective of the current study was to determine which BCV VEMP method (B-71, impulse hammer, or Mini-shaker) yields the highest response rates and reliability in a group of adults, adolescents, and children. It was hypothesized that the Mini-shaker would yield the highest response rates and reliability because it provides frequency specificity, higher output levels without distortion, and the most consistent force output as compared to the impulse hammer and B-71. DESIGN: Participants included 10 child (ages 5 to 10), 11 adolescent (ages 11 to 18), and 11 young adult (ages 23 to 39) normal controls. Cervical VEMP (cVEMP) and ocular VEMP (oVEMP) were measured in response to suprathreshold air-conducted, 500 Hz tone bursts and 3 types of BCV (B-71, impulse hammer, and Mini-shaker) across 2 test sessions to assess reliability. RESULTS: For cVEMP, response rates were 100% for all methods in all groups with the exception of the adult group in response to the impulse hammer (95%). For oVEMP, response rates varied by group and BCV method. For cVEMP, reliability was highest in adults using the Mini-shaker, in adolescents using the impulse hammer, and in children using the B-71. For oVEMP, reliability was highest in adults using the Mini-shaker, in adolescents using the Mini-shaker or impulse hammer, and in children using the impulse hammer. Age positively correlated with air-conducted oVEMP amplitude, but not cVEMP amplitude or cVEMP corrected amplitude. Age negatively correlated with all BCV VEMP amplitudes with the exception of cVEMP corrected amplitude in response to the Mini-shaker. CONCLUSIONS: All BCV methods resulted in consistent cVEMP responses (response rates 95 to 100%) with at least moderate reliability (intraclass correlation coefficient ≥ 0.5) for all groups. Similarly, all BCV methods resulted in consistent oVEMP responses (89 to 100%) with at least moderate reliability (intraclass correlation coefficient ≥ 0.5) except for the B-71 in adults.

Plasma metabolomic fingerprint of advanced cirrhosis stages among HIV/HCV-coinfected and HCV-monoinfected patients.

BACKGROUND & AIMS: Hepatitis C virus (HCV), human immunodeficiency virus (HIV) and cirrhosis induce metabolic disorders. Here, we aimed to evaluate the association of plasma metabolites with Child-Turcotte-Pugh (CTP) score and hepatic decompensation in HIV/HCV-coinfected and HCV-monoinfected patients with advanced cirrhosis. METHODS: A cross-sectional study was carried out in 62 HIV/HCV-coinfected and 28 HCV-monoinfected patients. Metabolomics analysis was performed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The statistical association analysis was performed by partial least squares discriminant analysis (PLS-DA) and generalized linear model (GLM) with binomial distribution (to analyse HIV coinfection, high alcohol intake, treatment with statins, previous HCV therapy failure and decompensation) and ordinal logistic regression (OLR) models to analyse different stages of cirrhosis (CTP score). RESULTS: The statistical analysis identified plasma metabolites associated with HIV coinfection, high alcohol intake, CTP score and hepatic decompensation. Overall, fatty acids, bile acids, aromatic and sulphur amino acids, butyrate derivatives, oxidized phospholipids, energy-related metabolites and bacterial fermentation-related metabolites were increased in more advanced cirrhosis stages; while lysophosphatidylcholines and lysophosphatidylethanolamines, branched-chain amino acids (BCAA) and metabolites of tricarboxylic acid cycle, among others, were decreased in more advanced cirrhosis. Most of the significant metabolites displayed a similar trend after stratifying for HIV/HCV- and HCV-infected patients. Glycolic acid, LPC (16:0) and taurocholic acid had high accuracy for discriminating patients according to decompensated cirrhosis (CTP ≥ 7). CONCLUSION: Altered plasma metabolomic profile was associated with advanced stages of cirrhosis in HIV/HCV-coinfected and HCV-monoinfected patients.

DBP rs16846876 and rs12512631 polymorphisms are associated with progression to AIDS naïve HIV-infected patients: a retrospective study.

BACKGROUND: Most of the circulating Vitamin D (VitD) is transported bound to vitamin D-binding protein (DBP), and several DBP single nucleotide polymorphisms (SNPs) have been related to circulating VitD concentration and disease. In this study, we evaluated the association among DBP SNPs and AIDS progression in antiretroviral treatment (ART)-naïve-HIV-infected patients. METHODS: We performed a retrospective study in 667 patients who were classified according to their pattern of AIDS progression (183 long-term non-progressors (LTNPs), 334 moderate progressors (MPs), and 150 rapid progressors (RPs)) and 113 healthy blood donors (HIV, HCV, and HBV negative subjects). We genotyped seven DBP SNPs (rs16846876, rs12512631, rs2070741, rs2282679, rs7041, rs1155563, rs2298849) using Agena Bioscience's MassARRAY platform. The genetic association was evaluated by Generalized Linear Models adjusted by age at the moment of HIV diagnosis, gender, risk group, and VDR rs2228570 SNP. Multiple testing correction was performed by the false discovery rate (Benjamini and Hochberg procedure; q-value). RESULTS: All SNPs were in HWE (p > 0.05) and had similar genotypic frequencies for DBP SNPs in healthy-controls and HIV-infected patients. In unadjusted GLMs, we only found significant association with AIDS progression in rs16846876 and rs12512631 SNPs. In adjusted GLMs, DBP rs16846876 SNP showed significant association under the recessive inheritance model [LTNPs vs. RPs (adjusted odds ratio (aOR) = 3.53; q-value = 0.044) and LTNPs vs. MPs (aOR = 3.28; q-value = 0.030)] and codominant [LTNPs vs. RPs (aOR = 4.92; q-value = 0.030) and LTNPs vs. MPs (aOR = 3.15; q-value = 0.030)]. Also, we found DBP rs12512631 SNP showed significant association in the inheritance model dominant [LTNPs vs. RPs (aOR = 0.49; q-value = 0.031) and LTNPs vs. MPs (aOR = 0.6; q-value = 0.047)], additive [LTNPs vs. RPs (aOR = 0.61; q-value = 0.031)], overdominant [LTNPs vs. MPs (aOR = 0.55; q-value = 0.032)], and codominant [LTNPs vs. RPs (aOR = 0.52; q-value = 0.036) and LTNPs vs. MPs (aOR = 0.55; q-value = 0.032)]. Additionally, we found a significant association between DBP haplotypes (composed by rs16846876 and rs12512631) and AIDS progression (LTNPs vs RPs): DBP haplotype AC (aOR = 0.63; q-value = 0.028) and the DBP haplotype TT (aOR = 1.64; q-value = 0.028). CONCLUSIONS: DBP rs16846876 and rs12512631 SNPs are related to the patterns of clinical AIDS progression (LTNP, MP, and RP) in ART-naïve HIV-infected patients. Our findings provide new knowledge about AIDS progression that may be relevant to understanding the pathogenesis of HIV infection.