Naive Subjects Research Articles

Inflammation-based markers, especially the uric acid/albumin ratio, are associated with non-dipper pattern in newly diagnosed treatment-naive hypertensive patients.

Physiologically, at night, blood pressure (BP) is expected to decrease by at least 10% in hypertensive individuals. The absence of this decrease, called non-dipper hypertension, is associated with increased end-organ damage and cardiovascular mortality and morbidity in hypertensive individuals. It is known that increased inflammatory process plays an important role in the etiopathogenesis of non-dipper hypertension pattern. In recent years, it has been shown that inflammation-based markers (IBMs) obtained by combining various inflammation-related hematological and biochemical parameters in a single fraction have stronger predictive value than single inflammatory parameters. However, until now, there has not been a study investigating the relationship of these markers with dipper/non-dipper status in newly diagnosed hypertensive patients. Based on ambulatory BP monitoring, 217 dipper and 301 non-dipper naive hypertensive subjects were included in this study. All subjects' IBM values were compared between dipper and non-dipper hypertensive individuals. IBMs [C-reactive protein/albumin ratio (CAR), monocyte/high-density lipoprotein cholesterol ratio (MHR), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio, systemic immune-inflammation index (SII), uric acid/albumin ratio (UAR)] were significantly higher in the non-dipper group. CAR, MHR, NLR, SII, and UAR were determined as independent predictors for non-dipper pattern ( P < 0.05, for all). Also, UAR's diagnostic performance for non-dipper pattern was found to be superior to other IBMs (area under the curve: 0.783, 95% confidence interval: 0.743-0.822; P < 0.001). These findings suggest an association between elevated IBMs, particularly UAR, and the non-dipper hypertension pattern observed in our study.

Strangers like me: birds respond equally to a familiar and an unfamiliar sentinel species' alarm calls, but respond less to non‐core and non‐sentinel's alarm calls

Alarm signals have evolved to communicate imminent threats to conspecifics but animals may also perceive other species' alarm displays to obtain adaptive information. In birds, mixed‐species foraging flocks are often structured around a focal sentinel species, which produces reliable alarm calls that inform eavesdropping non‐sentinel heterospecifics about predation risk. Ongoing work has revealed that several species can recognize the alarm calls of certain sentinel species even without prior encounters, including when these are from distant biogeographic regions. Similar work has yet to examine whether naive subjects' responses to unfamiliar sentinel alarm calls differ from responses to non‐sentinel alarm calls. Here we played the alarm calls of three subtropical Asian bird species that participate in mixed species flocks, to temperate North American birds. Birds responded most to the alarm call of an allopatric core sentinel and a local sympatric sentinel control species, less so to an allopatric non‐core sentinel, and least so to an allopatric non‐sentinel and a negative control stimulus. These patterns provide evidence that broad phylogenetic and geographic recognition is a pertinent aspect of sentinel alarm calls in general.

Passive antibody transfer from pregnant women to their fetus are maximized after SARS-CoV-2 vaccination irrespective of prior infection

Pregnancy is associated with a higher risk of adverse symptoms and outcomes for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for both mother and neonate. Antibodies can provide protection against SARS-CoV-2 infection and are induced in pregnant women after vaccination or infection. Passive transfer of these antibodies from mother to fetus in utero may provide protection to the neonate against infection. However, it is unclear whether the magnitude or quality and kinetics of maternally derived fetal antibodies differs in the context of maternal infection or vaccination. We aimed to determine whether antibodies transferred from maternal to fetus differed in quality or quantity between infection- or vaccination-induced humoral immune responses. We evaluated 93 paired maternal and neonatal umbilical cord blood plasma samples collected between October 2020 and February 2022 from a birth cohort of pregnant women from New Orleans, Louisiana, with histories of SARS-CoV-2 infection and/or vaccination. Plasma was profiled for the levels of spike-specific antibodies and induction of antiviral humoral immune functions, including neutralization and Fc-mediated innate immune effector functions. Responses were compared between 4 groups according to maternal infection and vaccination. We found that SARS-CoV-2 vaccination or infection during pregnancy increased the levels of antiviral antibodies compared to naive subjects. Vaccinated mothers and cord samples had the highest anti-spike antibody levels and antiviral function independent of the time of vaccination during pregnancy. These results show that the most effective passive transfer of functional antibodies against SARS-CoV-2 in utero is achieved through vaccination, highlighting the importance of vaccination in pregnant women.

Biochemical differences between high and low dose methadone clients on stable maintenance therapy

The methadone dose required to prevent withdrawal symptoms in chronic methadone users varies dramatically from 5 to 300 mg/day, which could be attributed to a number of biochemical factors, including human µ-opioid receptor (hMOR) density, down-stream desensitization, concurrent drug use or P-glycoprotein (P-gp) expression, or other, possibly genetic factors. Here we describe some biochemical changes of patients taking higher versus lower doses in chronic methadone maintenance therapy (MMT). hMOR density was measured in leukocytes from methadone-maintained patients receiving lower dose (&lt;100 mg/day) or higher dose (≥100 mg/day) and naive subjects by flow cytometry. Desensitization of receptor signaling was examined by measuring in vivo and attenuated cyclic AMP (cAMP) levels in response to increasing methadone concentrations. P-gp expression and the presence of other drugs were measured using validated methods.

Psychophysiological Parameters Predict the Performance of Naive Subjects in Sport Shooting Training.

In this study, we investigated the neural and behavioral mechanisms associated with precision visual-motor control during the learning of sport shooting. We developed an experimental paradigm adapted for naïve individuals and a multisensory experimental paradigm. We showed that in the proposed experimental paradigms, subjects trained well and significantly increased their accuracy. We also identified several psycho-physiological parameters that were associated with shooting outcomes, including EEG biomarkers. In particular, we observed an increase in head-averaged delta and right temporal alpha EEG power before missing shots, as well as a negative correlation between theta-band energies in the frontal and central brain regions and shooting success. Our findings suggest that the multimodal analysis approach has the potential to be highly informative in studying the complex processes involved in visual-motor control learning and may be useful for optimizing training processes.

Dissection of Antibody Responses of Gam-COVID-Vac-Vaccinated Subjects Suggests Involvement of Epitopes Outside RBD in SARS-CoV-2 Neutralization

Millions of people have been vaccinated with Gam-COVID-Vac but fine specificities of induced antibodies have not been fully studied. Plasma from 12 naïve and 10 coronavirus disease 2019 (COVID-19) convalescent subjects was obtained before and after two immunizations with Gam-COVID-Vac. Antibody reactivity in the plasma samples (n = 44) was studied on a panel of micro-arrayed recombinant folded and unfolded severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins and 46 peptides spanning the spike protein (S) and by immunoglobulin G (IgG) subclass enzyme-linked immunosorbent assay (ELISA). The ability of Gam-COVID-Vac-induced antibodies to inhibit binding of the receptor-binding domain (RBD) to its receptor angiotensin converting enzyme 2 (ACE2) was investigated in a molecular interaction assay (MIA). The virus-neutralizing capacity of antibodies was studied by the pseudo-typed virus neutralization test (pVNT) for Wuhan-Hu-1 and Omicron. We found that Gam-COVID-Vac vaccination induced significant increases of IgG1 but not of other IgG subclasses against folded S, spike protein subunit 1 (S1), spike protein subunit 2 (S2), and RBD in a comparable manner in naïve and convalescent subjects. Virus neutralization was highly correlated with vaccination-induced antibodies specific for folded RBD and a novel peptide (i.e., peptide 12). Peptide 12 was located close to RBD in the N-terminal part of S1 and may potentially be involved in the transition of the pre- to post-fusion conformation of the spike protein. In summary, Gam-COVID-Vac vaccination induced S-specific IgG1 antibodies in naive and convalescent subjects in a comparable manner. Besides the antibodies specific for RBD, the antibodies induced against a peptide close to the N-terminus of RBD were also associated with virus-neutralization.

A transfer learning-based feedback training motivates the performance of SMR-BCI

Objective. Feedback training is a practical approach to brain–computer interface (BCI) end-users learning to modulate their sensorimotor rhythms (SMRs). BCI self-regulation learning has been shown to be influenced by subjective psychological factors, such as motivation. However, few studies have taken into account the users’ self-motivation as additional guidance for the cognitive process involved in BCI learning. In this study we tested a transfer learning (TL) feedback method designed to increase self-motivation by providing information about past performance. Approach. Electroencephalography (EEG) signals from the previous runs were affine transformed and displayed as points on the screen, along with the newly recorded EEG signals in the current run, giving the subjects a context for self-motivation. Subjects were asked to separate the feedback points for the current run under the display of the separability of prior training. We conducted a between-subject feedback training experiment, in which 24 healthy SMR-BCI naive subjects were trained to imagine left- and right-hand movements. The participants were provided with either TL feedback or typical cursor-bar (CB) feedback (control condition), for three sessions on separate days. Main results. The behavioral results showed an increased challenge and stable mastery confidence, suggesting that subjects’ motivation grew as the feedback training went on. The EEG results showed favorable overall training effects with TL feedback in terms of the class distinctiveness and EEG discriminancy. Performance was 28.5% higher in the third session than in the first. About 41.7% of the subjects were ‘learners’ including not only low-performance subjects, but also good-performance subjects who might be affected by the ceiling effect. Subjects were able to control BCI with TL feedback with a higher performance of 60.5% during the last session compared to CB feedback. Significance. The present study demonstrated that the proposed TL feedback method boosted psychological engagement through the self-motivated context, and further allowed subjects to modulate SMR effectively. The proposed TL feedback method also provided an alternative to typical CB feedback.

Evaluation of subclinical changes in recently diagnosed pediatric hypertension patients without hypertensive retinopathy: an OCT study.

To investigate subclinical choroidal and retinal changes in recently diagnosed pediatric hypertension (HT) patients. This prospective case-control study consisted of 62 treatment naive HT patients (34 essential HT and 28 renal-induced HT) and 62 control subjects aged 10-16years. All demographic data and ocular parameters were noted. Macula and choroid measurements were acquired by spectral domain optical coherence tomography (SD-OCT). Choroidal measurements were obtained by taking the mean of the measurements taken from 3 nasal and 3 temporal locations at 500µ intervals (mean nasal, mean temporal) in addition to the subfoveal area. All choroidal thickness (ChT) values in HT subjects were significantly lower than in the healthy group (p < 0.001 for all). Also, there was no statistically significant difference between central macular thickness (CMT) and mean macular thickness (MMT) between the two groups. Subfoveal ChT, mean ChT, and CMT values were statistically lower in patients with renal-induced HT compared to essential HT subjects (p < 0.001, p = 0.04, p = 0.014, respectively). No significant correlation was observed between choroidal thicknesses and blood pressure values in essential and renal HT groups except weak correlation between mean temporal ChT and systolic blood pressure (SBP) in renal HT group (r = - 0.464, p = 0.013). This study demonstrated that choroidal thickness decreased even during the subclinical period in treatment naive pediatric HT subjects. In addition, it has been shown that the choroid is more affected in renal-induced HT compared to essential HT group.

Efficacy and Safety of 7-Day Non-Bismuth Concomitant Quadruple Therapy for First-Line Helicobacter pylori Eradication in the Elderly.

Aging may affect the efficacy of Helicobacter pylori eradication. The aim of our study was to assess the efficacy and safety of 7-day non-bismuth concomitant quadruple therapy as a first-line H. pylori infection eradication regimen in elderly individuals. We retrospectively analyzed a cohort with prospectively collected data from January 2013 to December 2019 at Chang Gung Memorial Hospital in Kaohsiung. There were 408 naive infected subjects aged 20 years or older who were treated with 7 days of concomitant therapy as a first-line H. pylori eradication regimen. We divided the patients into an elderly group (aged ≥ 65 years) and a control group (aged < 65 years). Two patients were lost during follow-up in the elderly group and 29 patients were lost in the control group, resulting in 56 in the ≥ 65-year age group and 321 in the control group. The patients were asked to perform urea breath tests 8 weeks later. The eradication rates for the elderly and control groups were 93.1% (95% confidence interval (CI): 83.3-98.1) and 84.0% (95% CI 79.7-87.7) (p = 0.070), respectively, in the intention-to-treat analysis, and 96.4% (95% CI 87.6-99.6) and 91.6% (95% CI 88.0-94.4) (p = 0.210), respectively, in the per-protocol (PP) analysis. The adverse event rates were 8.9% in the elderly group and 12.8% in the control group (p = 0.417). The compliance was 100% in both groups. No significant difference was seen in antibiotic resistance in either group. Multivariate analysis revealed that metronidazole resistance (odds ratio (OR) 6.870, 95% CI 1.182-39.919, p = 0.032) and dual-therapy resistance (OR 7.188, 95% CI 1.326-38.952, p = 0.022) were independent factors for eradication failure. The efficacy of non-bismuth concomitant quadruple therapy in the elderly cohort was comparable with that in the non-elderly cohort for first-line H. pylori eradication with acceptable adverse effects.

Intuiting machine failures

A key ingredient of effective collaborations is knowing the strengths and weaknesses of one’s collaborators. But what if one’s collaborator is a machine-classification system, of the sort increasingly appearing in semi-autonomous vehicles, radiologists’ offices, and other contexts in which visual processing is automated? Such systems have both remarkable strengths (including superhuman performance at certain classification tasks) and striking weaknesses (including susceptibility to bizarre misclassifications); can naive subjects intuit when such systems will succeed or fail? Here, five experiments (N=900) investigate whether humans can anticipate when machines will misclassify natural images. E1 showed subjects two natural images: one which reliably elicits misclassifications from multiple state-of-the-art Convolutional Neural Networks, and another image which reliably elicits correct classifications. We found that subjects could predict which image was misclassified on a majority of trials. E2 and E3 showed that subjects are sensitive to the nature of such misclassifications; subjects’ performance was better when they were told what the misclassification was (but not which image received it), and worse when the label shown was from another, randomly-chosen category. Crucially, in E4, we asked subjects to either (a) choose which image they thought was misclassified, or (b) choose the image that is the worst example of its category. While both instructions resulted in subjects choosing misclassified images above chance, subjects who were instructed to identify misclassifications performed better. In other words, humans appreciate the cues that mislead machines, beyond simply considering the prototypicality of an image. Lastly, E5 explored more naturalistic settings. Here, instead of an NAFC choice, subjects identified potential misclassifications from a stream of individual images; even in this setting, subjects were remarkably successful in anticipating machine errors. Thus, humans can anticipate when and how their machine collaborators succeed and fail, a skill that may be of great value to human-machine teams.

Assessment of a diverse panel of transmitted/founder HIV-1 infectious molecular clones in a luciferase based CD8 T-cell mediated viral inhibition assay.

Immunological protection against human immunodeficiency virus-1 (HIV-1) infection is likely to require both humoral and cell-mediated immune responses, the latter involving cytotoxic CD8 T-cells. Characterisation of CD8 T-cell mediated direct anti-viral activity would provide understanding of potential correlates of immune protection and identification of critical epitopes associated with HIV-1 control. The present report describes a functional viral inhibition assay (VIA) to assess CD8 T-cell-mediated inhibition of replication of a large and diverse panel of 45 HIV-1 infectious molecular clones (IMC) engineered with a Renilla reniformis luciferase reporter gene (LucR), referred to as IMC-LucR. HIV-1 IMC replication in CD4 T-cells and CD8 T-cell mediated inhibition was characterised in both ART naive subjects living with HIV-1 covering a broad human leukocyte antigen (HLA) distribution and compared with uninfected subjects. CD4 and CD8 T-cell lines were established from subjects vaccinated with a candidate HIV-1 vaccine and provided standard positive controls for both assay quality control and facilitating training and technology transfer. The assay was successfully established across 3 clinical research centres in Kenya, Uganda and the United Kingdom and shown to be reproducible. This IMC-LucR VIA enables characterisation of functional CD8 T-cell responses providing a tool for rational T-cell immunogen design of HIV-1 vaccine candidates and evaluation of vaccine-induced T-cell responses in HIV-1 clinical trials.

Drug resistance in children and adolescents with HIV in Panama.

The inadequacy of resistance monitoring in Latin America leads to circulation of HIV strains with drug resistance mutations (DRMs), compromising ART effectiveness. This study describes the DRM prevalence in HIV-infected paediatric patients in Panama. During 2018-19, plasma was collected from 76 HIV-infected children/adolescents (5 ART-naive, 71 treated) in Panama for HIV-1 DRM pol analysis, predicted antiretroviral (ARV) susceptibility by Stanford, and HIV-1 variant phylogenetic characterization. HIV-1 pol sequences were recovered from 67 (88.2%) of 76 children/adolescents (median age 12 years), carrying 65 subtype B, 1 subtype G and 1 unique recombinant URF_A1B. Five were ART-naive and 62 ART-treated under virological failure (viraemia >50 copies/mL) with previous exposure to NRTIs, (100%), NNRTIs (45.2%), PIs (95.2%) and integrase strand transfer inhibitors (INSTIs, 17.7%). Among the treated patients, 34 (54.8%) carried resistant strains, with major DRMs to one (40.3%), two (9.7%) or three (4.8%) ARV families. Most of them harboured DRMs to NRTIs (58.5%) or NNRTIs (39%), but also major DRMs to PIs (4.9%) and INSTIs (6.5%). We also found dual-class NRTI + NNRTI (12.2%) and NNRTI + PI (2.6%) resistance. Two naive subjects carried viruses with DRMs to NRTIs and NRTI + NNRTI, respectively. Sequenced viruses presented high/intermediate resistance mainly to emtricitabine/lamivudine (48.9% each) and efavirenz/nevirapine (33.3% each). Most participants were susceptible to PIs (91.3%) and INSTIs (88.1%). The high DRM prevalence to NRTIs and NNRTIs observed among treated HIV-infected children/adolescents in Panama justifies the need for routine resistance monitoring for optimal rescue therapy selection in this vulnerable population.

Type 2 diabetes mellitus augments Parkinson's disease risk or the other way around: Facts, challenges and future possibilities.

About 10% of the adult population is living with type 2 diabetes mellitus (T2DM) and 1% of the population over 60 years of age is suffering from Parkinson's disease (PD). A school of thought firmly believes that T2DM, an age-related disease, augments PD risk. Such relationship is reflected from the severity of PD symptoms in drug naive subjects possessing T2DM. Onset of Parkinsonian feature in case controls possessing T2DM corroborates the role of hyperglycemia in PD. A few cohort, meta-analysis and animal studies have shown an increased PD risk owing to insulin resistance. High fat diet and role of insulin signaling in the regulation of sugar metabolism, oxidative stress, α-synuclein aggregation and accumulation, inflammatory response and mitochondrial function in PD models and sporadic PD further connect the two. Although little is reported about the implication of PD in hyperglycemia and T2DM, a few studies have also contradicted. Ameliorative effect of anti-diabetic drugs on Parkinsonian symptoms and vague outcome of anti-PD medications in T2DM patients also suggest a link. The article reviews the literature supporting augmented risk of one by the other, analysis of proof of the concept, facts, challenges, future possibilities and standpoint on the subject.

The transferability of laparoscopic and open surgical skills to robotic surgery

BackgroundWithin the last decades, robotic surgery has gained popularity. Most robotic surgeons have changed their main surgical activity from open or laparoscopic without prior formal robotic training. With the current practice, it is of great interest to know whether there is a transfer of surgical skills. In visualization, motion scaling, and freedom of motion, robotic surgery resembles open surgery far more than laparoscopic surgery. Therefore, our hypothesis is that open-trained surgeons have more transfer of surgical skills to robotic surgery, compared to surgeons trained in laparoscopy.MethodsThirty-six surgically inexperienced medical students were randomized into three groups for intensive simulation training in an assigned modality: open surgery, laparoscopy, or robot-assisted laparoscopy. The training period was, for all study subjects, followed by performing a robot-assisted bowel anastomosis in a pig model. As surrogate markers of surgical quality, the anastomoses were tested for resistance to pressure, and video recordings of the procedure were evaluated by two blinded expert robotic surgeons, using a global rating scale of robotic operative performance (Global Evaluative Assessment of Robotic Skills (GEARS)).ResultsThe mean leak pressure of bowel anastomosis was 36.25 (7.62–64.89) mmHg in the laparoscopic training group and 69.01 (28.02–109.99) mmHg in the open surgery group, and the mean leak pressure for the robotic training group was 108.45 (74.96–141.94) mmHg. The same pattern was found with GEARS as surrogate markers of surgical quality. GEARS score was 15.71 (12.37–19.04) in the laparoscopic training group, 18.14 (14.70–21.58) in the open surgery group, and 22.04 (19.29–24.79) in the robotic training group. In comparison with the laparoscopic training group, the robotic training group had a statistically higher leak pressure (p = 0.0015) and GEARS score (p = 0.0023). No significant difference, for neither leak pressure nor GEARS, between the open and the robotic training group.ConclusionIn our study, training in open surgery was superior to training in laparoscopy when transitioning to robotic surgery in a simulation setting performed by surgically naive study subjects.

TLR3 polymorphisms in HIV infected individuals naïve to ART.

TLR3 polymorphisms affect the risk of HIV infection and modify the disease course. Consequently, we analyzed the association of TLR3 polymorphism (rs5743312, rs3775296, and rs3775291) with susceptilbity to HIV-1 acquisition and disease progression. This is a cross-sectional study. Genotyping of TLR3 polymorphisms were completed by the utilization of the PCR-RFLP technique in 153 HIV naive subjects and 158 healthy controls. A haplotype is a physical grouping of genomic variants that tend to be inherited together. The TCC haplotype was increased in HIV infected individuals compared with healthy controls (0.05% versus 0.03%). TLR3 rs3775291CT genotype was associated to the early stage of HIV infection (OR=2.19, P=0.04), with a higher occurrence in advance stage of HIV infection when contrasted with healthy controls (41.2% versus 32.3%). TLR3 rs3775296 CA genotype was likely to be associated with intermediate stage of HIV infection (19.5% versus 31.6%, OR=0.42, P=0.06). TLR3 rs5743312TT genotype was used to be greater prevalence in advanced stage of HIV infection compared with healthy controls (2.9% versus 1.9%). TLR3 rs3775296CA genotype was less prevalent in HIV subjects devouring tobacco when contrasted with non-users (9.1% versus 34.9%, OR=0.25, P=0.09). TLR3 rs3775296AA and rs3775291CT and TT genotypes have been overrepresented in HIV subjects using alcohol when contrasted with non-users (5.6% versus 1.1%, OR=1.83, P=0.67; 50.0% versus 42.2%, OR=1.84, P=0.31; 5.6% versus 3.3%, OR=2.70, P=0.50). In multivariate examination, rs5743312TT genotype showed a greater risk for HIV infection (OR=1.86, P=0.50). TLR3 rs3775291 C/T polymorphism may assist the risk of disease progression in alcohol consumers. TLR3 rs3775291 CT genotype may enhance the disease progression whereas the TLR3 rs3775296 CA genotype may protect for disease progression.

Humoral and cellular immune response to mRNA SARS-CoV-2 BNT162b2 vaccine in adolescents with rheumatic diseases

BackgroundData about safety and efficacy of the mRNA SARS-CoV-2 vaccine in adolescents with rheumatic diseases (RD) is scarce and whether these patients generate a sufficient immune response to the vaccine remains an outstanding question.ObjectiveTo evaluate safety and humoral and cellular immunity of the BNT162b2 vaccine in adolescents 12 to 18 years with RD and immunosuppressive treatment compared with a healthy control group.MethodsAdolescents from 12 to 18 years with RD followed at Hospital La Paz in Madrid (n = 40) receiving the BNT162b2 mRNA vaccination were assessed 3 weeks after complete vaccination. Healthy adolescents served as controls (n = 24). Humoral response was measured by IgG antiSpike antibodies, and cellular response by the quantity of IFN-γ and IL-2 present in whole blood stimulated with SARS-CoV-2 Spike and M proteins.ResultsThere were no differences in spike-specific humoral or cellular response between groups (median IFN-γ response to S specific protein; 528.80 pg/ml in controls vs. 398.44 in RD patients, p 0.78, and median IL-2 response in controls: 635.68 pg/ml vs. 497.30 in RD patients, p 0.22. The most frequent diagnosis was juvenile idiopathic arthritis (26/40, 65%) followed by Lupus (6/40, 15%). 60% of cases (23/40) received TNF inhibitors and 35% (14/40) methotrexate. 40% of patients (26/64) had previous SARS-CoV-2 infection, 9 in the control group and 17 in the RD patients without differences. Of note, 70% of infections were asymptomatic. A higher IFN-γ production was found in COVID-19 recovered individuals than in naive subjects in both groups (controls: median 859 pg/ml in recovered patients vs. 450 in naïve p 0.017, and RD patients: 850 in recovered vs. 278 in naïve p 0.024). No serious adverse events or flares were reported following vaccination.ConclusionsWe conclude that standard of care treatment for adolescents with RD including TNF inhibitors and methotrexate did not affect the humoral and the cellular immunity to BNT162b2 mRNA vaccination compared to a healthy control group. The previous contact with SARS-CoV-2 was the most relevant factor in the immune response.

Training naive subjects in using micro-phenomenological self-inquiry to investigate pain and suffering during headaches.

Micro-phenomenology is a method that generates rich and reliable reports of singular experiences in their pre-reflective dimension. Usually it is employed using a second-person interviewer. In this study we attempted to train naïve subjects in using self-inquiry version of the method. 13 subjects met twice over the course of one week, investigating their experiences of headaches, looking specifically into the pain experience itself, the experience of suffering, and the experience of absence of suffering. The analysis showed that the subject reports increase the richness of description, measured by the increase in the amount of categories described and the number of words needed to give an on target description. The analysis, informed by the participant's ideas, showed that it was possible to distinguish the experience of pain from the experience of suffering. We compare the analysis to other phenomenological studies of headaches. This reveals the strength and weakness of the micro-phenomenological method: By de-focusing on contextual factors it enables in-depth descriptions of singular moments of experience, but the bracketing of interpretations may result in overlooking overarching meaning dimensions. We conclude that micro-phenomenological self-inquiry may potentially be employed successfully in a clinical setting with initially untrained subjects for describing certain kinds of experiences and answering complex phenomenological questions.

Impact of Lacrimal Gland Extraction on the Contralateral Eye in an Animal Model for Dry Eye Disease.

PurposeAlthough there is still no consensus on the best animal model for dry eye disease research, a model based on lacrimal gland extraction (LGE) model is widely used. In this study, we aimed to investigate the histopathological changes taking place on the contralateral eye after unilateral LGE to determine whether it is useful as a control.MethodsSeven-week-old male C57BL/6 mice were divided into naive control, environmental chamber model, and LGE groups. Corneal fluorescein staining was scored to quantify the severity of damage. Morphological changes in the cornea, conjunctiva, and lacrimal gland (LG) were determined by hematoxylin and eosin staining and compared to those on naive control animals.ResultsCompared to naive subjects, the unilateral LGE model showed enhanced corneal erosion scores and loss of conjunctival goblet cells, not only on the ipsilateral but also on the contralateral side. These changes in the ocular surface became more pronounced in a time-dependent manner. Furthermore, loss of LG acinar cells and leukocyte infiltration were detected in the contralateral LGs of the LGE model.ConclusionsConsidering the changes observed in the ocular surface and LGs, the contralateral side of the LGE model may not offer proper control conditions for the experimental comparison of the effects of dry eye disease in vivo. There may be regulatory feedback or crosstalk system between both eyes activated in response to LGE.

Association of CD4 cell count and antiretroviral therapy antibody production in Human Immunodeficiency virus seropositive subjects on antiretroviral drugs in Benin City, Nigeria.

Antiretroviral therapy (ART) is widely used and subjects on ART were reported to develop antibodies against these drugs when used as monotherapy. The aim of this study was to determine the proportion of HIV-sero positive subjects on antiretroviral therapy who developed antibodies to the drugs used as combination therapy and to associate the presence of antibodies to CD4 cell count which is a marker of disease progression. A total of 300 subjects were randomly selected for the study, consisting of 100 HIV-sero positive subjects already on ART, 100 newly diagnosed HIV-sero positive ART- naive subjects and 100 HIV-sero negative individuals who were monitored as controls. CD4 cell count and complete blood count were assayed using BD FASCOUNT CD3/CD4 and Sysmex KX-21N autoanalyzer respectively. Antigen-Antibody agglutination technique was used to detect antibodies produced against antiretroviral drugs in HIV -sero positive subjects on ART. The results showed that antibodies to antiretroviral drugs (tenofovir disoproxil fumarate/lamivudine Efavirenz + lamivudine/ nevirapine/zidovudine combination) were detected in 33(33%) out of the 100 HIV-sero positive subjects on ART studied. Significantly higher CD4 cell count (p&lt;0.001), PCV (p&lt;0.001) and white blood cell count (p&lt;0.001) were recorded among control group than HIV positive subjects whether they in 33(33%) out of the 100 HIV- sero positive subjects on ART combination studied. The use of combination therapy has led to a smaller number of subjects on ART who developed antibody as against a higher percentage on monotherapy that was previously reported. Significantly lower level of platelet was observed among HIV-sero positive subjects who developed ART antibodies.

Role of plasmatic and urinary concentration of tenofovir disoproxil fumarate in a cohort of patients affected by chronic hepatitis B.

The aim of this study was to evaluate plasmatic and urinary therapeutic drug monitoring (TDM) of tenofovir disoproxil fumarate (TDF) in a cohort of patients with chronic hepatitis B (CHB). In 68 enrolled patients, the estimated glomerular filtration rate (eGFR) was 68 mL/min in naive subjects, while in adefovir dipivoxil (ADV)-pretreated patients, it was 55.5 mL/min (p < 0.001). The HBV E genotype was associated with lower TDF levels (β = -0.698, p < 0.001). The urinary TDF concentration was associated with ADV pretreatment (β = 0.829, p < 0.001). Determination of urinary concentrations of TDF may be useful in the clinical management of older CHB patients and those with previous treatment with ADV.