193 research outputs found
Measurements of the loxodromic antenna parameters
Ovaj rad se bavi loksodromskom antenom odnosno njezinim glavnim parametrima. Loksodromska antena predstavlja varijaciju helikoidne antene sa promjenjivim radijusom podloge. Napravljena su dva modela loksodromske antene u dvije varijante (antena je pričvršćena za reflektirajuću površinu i antena nije pričvršćena za reflektirajuću površinu). Ti se modeli razlikuju po broju namota te kutu nagiba dok je radijus sfere jednak za oba dva modela. Na svakom modelu antena izvršeno je po jedno mjerenje u horizontalnoj ravnini te po dva mjerenja u vertikalnoj ravnini
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ovisno o položaju antene. Mjerenjima odnosa stojnih valova VSWR, koeficijenta refleksije S11, jakosti električnog polja i impedancije antene, utvrđeno je da bolje karakteristike pokazuje model sa manjim brojem namota pa tako taj model ima veću ukupnu širinu opsega i prilagođenje impedancije. Veću usmjerenost imaju antene koje su izvedene sa reflektirajućom površinom.This paper deals with loxodromic antenna or its main parameters. Loxodromic antenna is a variation of helix antenna with a variable radius of substrate. Two models of loxodromic antenna have been made in two variants (the antenna is attached to a reflecting surface and the antenna is not attached to a reflecting surface). These models are different by the number of windings and the angle of inclination while the radius of sphere is the same for both models. The measurements of VSWR, S11 reflection coefficient, electric field strength and the input impedance of antenna show that the model with a smaller number of windings has the highest broadband and best impedance matching. Antennae attached to reflecting surface have better directivity. On each antenna model, one measurement was made in a horizontal position and two measurements were made in a vertical position depending on the positon of the antenna
Utility of CD4 cell counts for early prediction of virological failure during antiretroviral therapy in a resource-limited setting
BACKGROUND: Viral load monitoring is not available for the vast majority of patients receiving antiretroviral therapy in resource-limited settings. However, the practical utility of CD4 cell count measurements as an alternative monitoring strategy has not been rigorously assessed. METHODS: In this study, we used a novel modelling approach that accounted for all CD4 cell count and VL values measured during follow-up from the first date that VL suppression was achieved. We determined the associations between CD4 counts (absolute values and changes during ART), VL measurements and risk of virological failure (VL > 1,000 copies/ml) following initial VL suppression in 330 patients in South Africa. CD4 count changes were modelled both as the difference from baseline (DeltaCD4 count) and the difference between consecutive values (CD4 count slope) using all 3-monthly CD4 count measurements during follow-up. RESULTS: During 7093.2 patient-months of observation 3756 paired CD4 count and VL measurements were made. In patients who developed virological failure (n = 179), VL correlated significantly with absolute CD4 counts (r = - 0.08, P = 0.003), DeltaCD4 counts (r = - 0.11, P < 0.01), and most strongly with CD4 count slopes (r = - 0.30, P < 0.001). However, the distributions of the absolute CD4 counts, DeltaCD4 counts and CD4 count slopes at the time of virological failure did not differ significantly from the corresponding distributions in those without virological failure (P = 0.99, P = 0.92 and P = 0.75, respectively). Moreover, in a receiver operating characteristic (ROC) curve, the association between a negative CD4 count slope and virological failure was poor (area under the curve = 0.59; sensitivity = 53.0%; specificity = 63.6%; positive predictive value = 10.9%). CONCLUSION: CD4 count changes correlated significantly with VL at group level but had very limited utility in identifying virological failure in individual patients. CD4 count is an inadequate alternative to VL measurement for early detection of virological failure
Efficacy of broccoli and glucoraphanin in COVID-19: From hypothesis to proof-of-concept with three experimental clinical cases
COVID-19 is described in a clinical case involving a patient who proposed the hypothesis that Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-interacting nutrients may help to prevent severe COVID-19 symptoms. Capsules of broccoli seeds containing glucoraphanin were being taken before the onset of SARS-CoV-2 infection and were continued daily for over a month after the first COVID-19 symptoms. They were found to reduce many of the symptoms rapidly and for a duration of 6-12 h by repeated dosing. When the patient was stable but still suffering from cough and nasal obstruction when not taking the broccoli capsules, a double-blind induced cough challenge confirmed the speed of onset of the capsules (less than 10 min). A second clinical case with lower broccoli doses carried out during the cytokine storm confirmed the clinical benefits already observed. A third clinical case showed similar effects at the onset of symptoms. In the first clinical trial, we used a dose of under 600 mmol per day of glucoraphanin. However, such a high dose may induce pharmacologic effects that require careful examination before the performance of any study. It is likely that the fast onset of action is mediated through the TRPA1 channel. These experimental clinical cases represent a proof-of-concept confirming the hypothesis that Nrf2interacting nutrients are effective in COVID-19. However, this cannot be used in practice before the availability of further safety data, and confirmation is necessary through proper trials on efficacy and safety.Peer reviewe
CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE.
BACKGROUND: Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load.
METHODS AND FINDINGS: Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger), we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements 500 copies/µl, the first of two consecutive measurements between 50-500 copies/µl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/µl (95% CI) of: 0.35 (0.30-0.40) for counts <200 cells/µl, 0.81 (0.71-0.92) for counts 200 to <350 cells/µl, 0.74 (0.66-0.83) for counts 350 to <500 cells/µl, and 0.96 (0.92-0.99) for counts ≥500 cells/µl. A higher CD4 cell count became even more beneficial over time for patients with CD4 cell counts <200 cells/µl.
CONCLUSIONS: Despite the low mortality rate, the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression. A higher CD4 cell count was associated with the greatest benefit for patients with a CD4 cell count <200 cells/µl but still some slight benefit for those with a CD4 cell count ≥500 cells/µl
Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity
Campylobacter infection in adult patients with primary antibody deficiency
International audienceNo abstract availabl
Campylobacter infection in adult patients with primary antibody deficiency
International audiencePrimary antibody deficiency (PAD) is characterized by a defective immunoglobulin production and recurrent infections, mostly involving respiratory and gastrointestinal tracts. Chronic or recurrent diarrhea is reported in up to 23%. Campylobacter infection is a common cause of infectious diarrhea, reported in 1.2% to 7.5% of patients with common variable immunodefi-ciency (CVID), the most frequent PAD. The aim of this study was to describe Campylobacter infection in patients with PAD included in a large nationwide study and analyze factors associ-ated with susceptibility to this pathogen. The DEFI (DEFicit Immunitaire) study is an ongoing large cross-sectional French multicentric study of adults with PAD, with retrospective collection of clinical data. All patients with a history of bacteriologically documented Campylobacter infection were identified, and clinical data were collected for each episode. Factors associated with recurrent infection were assessed as oddsratio (OR) and 95% confidence interval (CI), calculated by means of simple regression analysis. In patients with available material, strains of each episode were characterized using molecular analysis and compared (Table E1, available in this article’s Online Repository at www.jaci-inpractice.org). A com-parison of immunodeficiency-related characteristics of patients with and without Campylobacter infection was performed in the homogeneous group of patients with CVID. The control group included patients with CVID from DEFI centers who confirmed that patients did not develop Campylobacter infection after enrollment (Figure E1, available in this article’s Online Repository at www.jaci-inpractice.org). After correction for multiple comparisons, P<.016 was considered significant. Since 2004, 790 patients with PAD were included in the DEFI study, and 51 presented with Campylobacter infection (6.5%). Medical chart was available for review in 45 patients. Characteristics of these patients at the time of enrollment in the DEFI study are detailed in Table E2 (available in this article’s Online Repository at www.jaci-inpractice.org). A total of 97 episodes were recorded (Table I). The overall distribution of Campylobacter species was unremarkable. Antimicrobial susceptibility testing revealed a higher resistance rate than in the general population for each antibiotic tested (see Figure E2, available in this article’s Online Repository at www.jaci-inpractice.org). A comorbidity was present in 55% of Campylobacter episodes, and a coinfection by other enteropathogens in 10%. Most patients were receiving concomitant therapy at the time of episode. One patient with end-stage cirrhosis died with Campylobacter bacteremia. Overall, bacteremia was observed in 24 episodes (13 patients) and was associated with extraintestinal complication in 10 episodes. Nineteen patients (42%) presented with recurrent (2-11) episodes. Factors associated with recurrent episodes were the presence of comorbidity (OR, 3.7 [95% CI, 1.1-13.1]) and undetectable serum IgA (OR, 8.6 [95% CI, 1.1-21.2]). None of these factors remain significant in multivariate analysis. A mo- lecular study of a subset of 18 strains from 5 patients with recurrent infections demonstrated that all strains were different, even when the antimicrobial susceptibility testing was similar and when the episodes occurred closely over time (Figure E3, available in this article’s Online Repository at www.jaci-inpractice.org). Compared with 288 patients with CVID without Campylobacter infection, patients with CVID with Campylo-bacter infection presented a higher prevalence of consanguinity and a more severe CVID phenotype, with more frequent disease- related complications, lower serum immunoglobulin levels, lower B and natural killer (NK) cells, and a trend for lower naive CD4þT cell at the time of enrollment in the DEFI study (Table II). This study is the first description of a large series of patients with PAD and Campylobacter infection. The 6.5% prevalence was probably underestimated because of the retrospective nature of the clinical data collection. In this population, symptoms were mostly restricted to an isolated, frequently severe, chronic watery diarrhea, with associated malnutrition, leading to repeated hospitalizations and impaired quality of life. Other digestive symptoms and fever were less frequent than those observed in the general population. In contrast, bacteremia and extra- digestive localizations were more frequent (25% vs 0.15% to 2%, and 22% vs 7%, respectively). Despite frequent hospitalizations, the overall prognosis was good. Recurrence rate was high (42%) compared with 1.2% in the general population, and was associated with extraintestinal comorbidity and unde- tectable IgA level in univariate analysis. Although limited by the number of available strains, molecular profiles of strains from patients with recurrent infections were all different. Thus, we could hypothesize that reinfection is more likely than persistent colonization, although colonization with multiple strains cannot be excluded. Conditions associated with the occurrence of Campylobacter infection were described in an analysis restricted to a large ho- mogeneous group of 325 patients with CVID. The present data suggest that hypochlorhydria, either proton pump inhibitor (PPI)-induced or associated with autoimmune gastritis, might play an important role in the pathogenesis of this infection. Almost all CVID-associated complications, particularly liver and gastrointestinal disease, were more frequent in patients with Campylobacter infection. A more severe immune deficiency at CVID diagnosis, with a lower serum immunoglobulin level, was also observed. Even in patients with immunoglobulin replacement therapy, IgM and IgA levels remain very low. IgA and IgM, almost absent in immunoglobulin batches, are more important than IgG in Campylobacter immunity. B-cell and specifically switch memory B-cell deficiency was also more severe in patients with CVID with Campylobacter infection than in patients without Campylobacter infection. This is in line with the high prevalence of Campylobacter infection observed in Good syndrome and X-linked agammaglobulinemia, 2 conditions associated with no circulating B cells (Figure E1, available in this article’s Online Repository at www.jaci-inpractice.org). B cells are also known to be important for the dialogue between the immune system and gut microbiota, whose composition is important for Campylobacter immunity. T cells may also play an important role, with a trend for decreased naive T cells. Indeed, 15 patients (40%) presented with a severe associated T-cell defect and could be considered as late-onset combined im-munodeficiency (data not shown). In patients with PAD, Campylobacter infection is quite frequent and seems to be related to various factors adding up together: severity of the immune deficiency, PAD complication, and associated antibiotics, immunosuppressive therapies, and PPI. It is characterized by a high frequency of recurrence and bacteremia. Recurrence is associated with the presence of comorbidity and IgA defect, and turned out to be due to rein- fection more than to persistent colonization, suggesting a specific susceptibility despite immunoglobulin substitution
Comparison of Kaposi Sarcoma risk in human immunodeficiency virus-positive adults across 5 continents: A multiregional multicohort study
Background: We compared Kaposi sarcoma (KS) risk in adults who started antiretroviral therapy (ART) across the Asia-Pacific, South Africa, Europe, Latin, and North America. Methods: We included cohort data of human immunodeficiency virus (HIV)-positive adults who started ART after 1995 within the framework of 2 large collaborations of observational HIV cohorts. We present incidence rates and adjusted hazard ratios (aHRs). Results: We included 208 140 patients from 57 countries. Over a period of 1 066 572 person-years, 2046 KS cases were diagnosed. KS incidence rates per 100 000 person-years were 52 in the Asia-Pacific and ranged between 180 and 280 in the other regions. KS risk was 5 times higher in South African women (aHR, 4.56; 95% confidence intervals [CI], 2.73-7.62) than in their European counterparts, and 2 times higher in South African men (2.21; 1.34-3.63). In Europe, Latin, and North America KS risk was 6 times higher in men who have sex with men (aHR, 5.95; 95% CI, 5.09-6.96) than in women. Comparing patients with current CD4 cell counts 65700 cells/\u3bcL with those whose counts were <50 cells/\u3bcL, the KS risk was halved in South Africa (aHR, 0.53; 95% CI, .17-1.63) but reduced by 6595% in other regions. Conclusions. Despite important ART-related declines in KS incidence, men and women in South Africa and men who have sex with men remain at increased KS risk, likely due to high human herpesvirus 8 coinfection rates. Early ART initiation and maintenance of high CD4 cell counts are essential to further reducing KS incidence worldwide, but additional measures might be needed, especially in Southern Africa
CD4/CD8 Ratio and the Risk of Kaposi Sarcoma or Non-Hodgkin Lymphoma in the Context of Efficiently Treated Human Immunodeficiency Virus (HIV) Infection: A Collaborative Analysis of 20 European Cohort Studies
BACKGROUND: A persistently low CD4/CD8 ratio has been reported to inversely correlate with the risk of non-AIDS defining cancer in people living with human immunodeficiency virus (HIV; PLWH) efficiently treated by combination antiretroviral therapy (cART). We evaluated the impact of the CD4/CD8 ratio on the risk of Kaposi sarcoma (KS) or non-Hodgkin lymphoma (NHL), still among the most frequent cancers in treated PLWH. METHODS: PLWH from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) were included if they achieved virological control (viral load ≤ 500 copies/mL) within 9 months following cART and without previous KS/LNH diagnosis. Cox models were used to identify factors associated with KS or NHL risk, in all participants and those with CD4 ≥ 500/mm3 at virological control. We analyzed the CD4/CD8 ratio, CD4 count and CD8 count as time-dependent variables, using spline transformations. RESULTS: We included 56 708 PLWH, enrolled between 2000 and 2014. At virological control, the median (interquartile range [IQR]) CD4 count, CD8 count, and CD4/CD8 ratio were 414 (296-552)/mm3, 936 (670-1304)/mm3, and 0.43 (0.28-0.65), respectively. Overall, 221 KS and 187 NHL were diagnosed 9 (2-37) and 18 (7-42) months after virological control. Low CD4/CD8 ratios were associated with KS risk (hazard ratio [HR] = 2.02 [95% confidence interval {CI } = 1.23-3.31]) when comparing CD4/CD8 = 0.3 to CD4/CD8 = 1) but not with NHL risk. High CD8 counts were associated with higher NHL risk (HR = 3.14 [95% CI = 1.58-6.22]) when comparing CD8 = 3000/mm3 to CD8 = 1000/mm3). Similar results with increased associations were found in PLWH with CD4 ≥ 500/mm3 at virological control (HR = 3.27 [95% CI = 1.60-6.56] for KS; HR = 5.28 [95% CI = 2.17-12.83] for NHL). CONCLUSIONS: Low CD4/CD8 ratios and high CD8 counts despite effective cART were associated with increased KS/NHL risks respectively, especially when CD4 ≥ 500/mm3
Symptomatic and Asymptomatic Neurological Complications of Infective Endocarditis: Impact on Surgical Management and Prognosis
International audienceObjectives:Symptomatic neurological complications (NC) are a major cause of mortality in infective endocarditis (IE) but the impact of asymptomatic complications is unknown. We aimed to assess the impact of asymptomatic NC (AsNC) on the management and prognosis of IE.Methods: From the database of cases collected for a population-based study on IE, we selected 283 patients with definite left-sided IE who had undergone at least one neuroimaging procedure (cerebral CT scan and/or MRI) performed as part of initial evaluation.Results Among those 283 patients, 100 had symptomatic neurological complications (SNC) prior to the investigation, 35 had an asymptomatic neurological complications (AsNC), and 148 had a normal cerebral imaging (NoNC). The rate of valve surgery was 43% in the 100 patients with SNC, 77% in the 35 with AsNC, and 54% in the 148 with NoNC (p<0.001). In-hospital mortality was 42% in patients with SNC, 8.6% in patients with AsNC, and 16.9% in patients with NoNC (p<0.001). Among the 135 patients with NC, 95 had an indication for valve surgery (71%), which was performed in 70 of them (mortality 20%) and not performed in 25 (mortality 68%). In a multivariate adjusted analysis of the 135 patients with NC, age, renal failure, septic shock, and IE caused by S. aureus were independently associated with in-hospital and 1-year mortality. In addition SNC was an independent predictor of 1-year mortality.Conclusions The presence of NC was associated with a poorer prognosis when symptomatic. Patients with AsNC had the highest rate of valve surgery and the lowest mortality rate, which suggests a protective role of surgery guided by systematic neuroimaging results
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