Acquired thrombotic thrombocytopenic purpura (TTP) in children is a rare but severe disease, which is caused by Immunoglobulin G antibodies, which inactivate a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). Daily high-volume plasma exchange (PEX) and immunosuppression with glucocorticoids and rituximab is the current standard of treatment for TTP. We report two females aged 5 and 12 years, with TTP, induced by anti-ADAMTS13 inhibitory antibodies who relapsed very shortly after PEX, rituximab and glucocorticoids, in whom long-term remission with disappearance of ADAMTS13 inhibitors was achieved after one course of bortezomib.

A 56-year-old male presented to an emergency dental service with multiple intra-oral swellings.The intraoral swellings were seen radiographically as punched out radiolucencies in the upper right first molar region and the lower left second molar region. These were indicative of browns tumours.

Background and Purpose: The activation of the defense reaction inhibits the baroreflex response through the B3 and nucleus tractus solitarius (NTS) regions. Our aim was to determine whether and how baroreflex inhibition induced by the disinhibition of the rostral cuneiform nucleus, part of the defense pathway, involves serotonin cells in B3 and 5-HT3 receptors in the NTS. Experimental Approach: We performed immunohistochemistry and anatomical experiments to determine whether raphe serotonin cells expressing Fos were directly targeted by the rostral cuneiform nucleus. The effect of blocking raphe serotonin transmission and NTS 5-HT3 receptors, on cuneiform-induced inhibition of the baroreflex cardiac response, were also analyzed. Key Results: Bicuculline microinjected into the rostral cuneiform nucleus induced an increase of double labeled Fos-5-HT IR cells in both the LPGi and Raphe Magnus. The anterograde tracer Phaseolus vulgaris leucoaggutinin into the rostral cuneiform nucleus revealed a dense projection to the LPGi but not Raphe Magnus. Cuneiform-induced baroreflex inhibition was prevented by B3 injection of 8-OH-DPAT, a specific agonist for 5-HT1A receptors. Cuneiform disinhibition also failed to inhibit the baroreflex bradycardia after microinjection of a 5-HT3 receptor antagonist (granisetron) into the NTS or in 5-HT3 receptor knock-out mice. Conclusion and Implications: In conclusion, the rostral cuneiform nucleus participates in the defense inhibition of the baroreflex bradycardia via direct activation of the LPGi and a relay to the Raphe Magnus, to activate NTS 5-HT3 receptors and inhibit second-order baroreflex neurons. These data bring new insights in primary and secondary mechanisms involved in vital baroreflex prevention during stress.

Cytoreg is an ionic therapeutic agent comprising a mixture of hydrochloric, sulfuric, phosphoric, hydrofluoric, oxalic, and citric acids. In diluted form, it has demonstrated efficacy against human cancers in vitro and in vivo. Although Cytoreg is well tolerated in mice, rats, rabbits, and dogs by oral and intravenous administration, its mechanism of action is not understood. The acidic nature of Cytoreg could potentially disrupt the pH and levels of ions and dissolved gases in the blood. Here, we report the effects of the intravenous administration of Cytoreg on the arterial pH, oxygen and carbon dioxide pressures, and bicarbonate, sodium, potassium, and chloride concentrations. Our results demonstrate that Cytoreg increases oxygen levels and can be used from a therapeutic point of view.

Background and Purpose: Cocaine addiction causes serious health problems and no effective treatment is available yet. We previously identified a genetic risk variant for cocaine addiction in the PLCB1 gene and found this gene upregulated in postmortem brains of cocaine abusers and in human dopaminergic neuron-like cells after an acute cocaine exposure. Here, we functionally tested the contribution of PLCB1 gene to cocaine addictive properties in mice. Experimental approach: We used heterozygous Plcb1 knockout mice (Plcb1+/-) and characterized their behavioral phenotype. Subsequently, mice were trained for operant conditioning and self-administered cocaine for 10 days. Plcb1+/- mice were assessed for cocaine motivation, followed by 26 days of extinction and finally evaluated for cue-induced reinstatement of cocaine seeking. Gene expression alterations after reinstatement were assessed in medial prefrontal cortex (mPFC) and hippocampus (HPC) by RNAseq. Key Results: Plcb1+/- mice showed normal behavior, although they had increased anxiety and impaired short-term memory. Importantly, after cocaine self-administration and extinction, we found a reduction in the cue-induced reinstatement of cocaine-seeking behavior in Plcb1+/- mice. After reinstatement, we identified transcriptomic alterations in the medial prefrontal cortex of Plcb1+/- mice, mostly related to pathways relevant to addiction like the dopaminergic synapse and long-term potentiation. Conclusions and Implications: To conclude, we found that heterozygous deletion of the Plcb1 gene decreases cue-induced reinstatement of cocaine seeking, pointing at PLCB1 as a possible therapeutic target for preventing relapse and treating cocaine addiction.

Objective: The aim of this study is to find out the potential risk factors including Charlson Comorbidity index (CCI) score associated with death in COVID-19 cases hospitalized due to pneumonia and try to find a novel COVID-19 mortality score for daily use. Methods: All patients diagnosed as confirmed or probable COVID-19 pneumonia whom hospitalized in our Chest Diseases Education and Research Hospital between March 11, 2020 and May 15,2020 were enrolled. The optimal cut-off values, sensitivity and specificity values and odds ratios to be used in mortality prediction of the novel scoring system created from these parameters were calculated by ROC analysis according to the area under the curve and Youden index. Results: Over 383 patients (n:33 deceased, n:350 survivors) univariate and multivariate regression analysis showed that CCI and lymphocyte ratio were prognostic factors for COVID-19 related mortality. Using this analysis, a novel scoring model CoLACD (CoVID-19 Lymphocyte ratio, Age, CCI score, Dyspnea) was established. The cut-off value of this scoring system, which determines the mortality risk in patients, was 2.5 points with 82% sensitivity and 73% specificity (AUC = 0.802, 95% CI 0.777-0.886, p <0.001). The risk of mortality was 11.8 times higher in patients with a CoLACD mortality score higher than 2.5 points than patients with a score lower than 2.5 (OR = 11.8 95% CI 4.7-29.3 p <0.001). Conclusion: This study showed that by using the CoLACD mortality score, clinicians may achieve a prediction of mortality in COVID-19 patients hospitalized for pneumonia.

This present study has employed the hedonic pricing technique to calculate the value of marginal changes in the characteristic of treated industrial wastewater irrigated farm land in Tamil Nadu, India. A sample of 240 farmers was selected through multistage random sampling technique. The major findings of the analysis revealed that, the additional income obtained from agricultural land value in sample farms using treated wastewater was higher by INR 13.34 lakh while compared to control farm. As one would expect, agricultural attributes are very important determinants of agricultural land prices followed by environmental attributes and location attributes. Implicit values for transport facility, number of irrigation, bore and open well availability, land quality index and vegetative cover are embedded in agricultural land prices and there is evidence that the use of treated wastewater reuse for agriculture can improve the fit of the hedonic price regression. Distance between cisterns to farm significantly reduces the land value. In this present study emphasized that the use of treated industrial wastewater for agriculture is high potential for increasing the agricultural land value in the Tamil Nadu.

Analytical methods involving electronic tongue technique combined with chemometrics analysis was proposed to discriminate oil variety and predict oil quality parameters. All the studied Camellia oil samples from pressing, n-hexane extraction and scCO2 extraction, were successfully discriminated by principal component analysis (PCA) and hierarchical cluster analysis (HCA). Furthermore, Multi Factor Linear Regression Model (MLRM) was established allowing predictive capacity of oil quality indicators, such as acid value (AV) and peroxide value (POV). The practical potential of e-tongue for the discrimination and assessment of Camellia oils has shown promising application in the characterization of Camellia oils in the oil quality evaluation.

Our results indicated that 64 % (38/59) of small mammals (Apodemus flavicolis, A. sylvaticus, Myodes glareolus, Microtus agrestris, M. arvalis, Sorex araneus and S. minutus) studied in 2015 were infected with Syphacia, Trichuris, Aonchotheca, Heligmosomidae and tapeworms, and 64 % (27/42) of animals investigated in 2018 were infected with Syphacia, Trichuris, Aonchotheca, Heligmosomidae and tapeworms. In 2018, prevalence of infection was 83 % (15/18) in autumn in NW Bohemia and 50 % (12/24) in autumn 2018 in South-East Bohemia. Regarding locality, total prevalence of infection and species richness were higher in North-West Bohemia. Total prevalence of infection according to season was 72 % (18/25) in spring and 62 % (47/76) in autumn. In NW Bohemia in 2015, 72 % (18/25) of animals were infected in spring and 59 % (20/34) in autumn. Statistically significant differences in parasite infection of Murinae and Arvicolinae were evident when comparing years and seasons.

Rawadanau, located in Serang, Banten, is the main water supply for the Cilegon industrial area, West Coast of Java, Indonesia, has geothermal potential. Understanding groundwater origin and quality is an essential factor in determining appropriate actions to save water supply sources. This paper aims to answer the groundwater origin that fills the Rawadanau, whose rocks are composed of volcanic products with evidence of the main elements of water chemistry and stable isotopes (δ2H and δ18O). Analysis of pH, temperature, EC, HCO3ˉ is carried out in the field, while other chemical elements and stable isotopes are analyzed in the laboratory. Groundwater found consists of hot springs, cold springs, dug wells, river water. Hierarchical analysis clusters based on water chemistry and stable isotopes can be grouped into two, cluster K (K1 and K2) and clusters L, respectively. Data of δ2H and δ18O of the spring waters in the Rawadanau indicate that they are of meteoric origin, and there has been evaporation from several springs. Water comes from meteoric water with stable isotopes content of δ18O between -6.39 to -4.82 ‰ and δ2H between - 41.35 to -31.30 ‰, which has been controlled by two main mechanisms, namely rock dominance, and evaporation dominance. Aquifers are composed of product volcanic with the dominant composition rock of porphyritic andesite, basaltic andesite, and andesite. The multivariate statistical analysis results besides pH and SO4, all parameters (cation and anions) showed significant correlation. There are four groundwater facies, namely Ca-HCO3, Ca-Mg-HCO3, Mg-Ca-HCO3, and Na-Cl.

Rationale The end of life (EOL) experience in the intensive care unit (ICU) can be psychologically distressing. The 3 Wishes Project (3WP) personalizes the EOL experience by carrying out wishes for dying patients and their families. While the 3WP has been integrated in academic, tertiary care ICUs, implementing this project in a community ICU has yet to be described. Objectives To examine facilitators of, and barriers to, implementing the 3WP in a community ICU from the clinician and key-stakeholder perspective. Methods This mixed-method study evaluated the implementation of the 3WP in a 20-bed community ICU in Southern Ontario, Canada. Patients were considered for the 3WP if they had a high likelihood of imminent death or planned withdrawal of life-sustaining therapy. Quantitative data include patient demographic data and wishes implemented. Following the qualitative descriptive approach, semi-structured interviews were conducted with purposively sampled clinicians and key-stakeholders. Data from transcribed interviews were analyzed in triplicate through qualitative content analysis. Results During the 10-month period, 66 of 67 wishes were completed, with a median of 4.5 wishes per patient-family dyad. Interviews with 12 participants indicated that the 3WP personalized and enriched the EOL experience for patients, families and clinicians. Interviewees indicated higher intensity education strategies were needed to enable spread as the project grew. Clinicians described many physical resources for the project but required more non-clinical project support for orientation, continuing education and data collection. Instead, these roles were completed by clinicians with saturated work capacity which may have inhibited the spread of the project. Conclusions In this community hospital, ICU clinicians and key stakeholders reported the 3WP improved EOL care for patients, families, and clinicians. Project implementation in a community ICU requires investigators take into account project characteristics and adapt the intervention to the community hospital context.

The Maximum Entropy Theory of Ecology (METE) predicts the shapes of macroecological metrics in relatively static ecosystems using constraints imposed by static state variables. In disturbed ecosystems, however, with time-varying state variables, its predictions often fail. We extend macroecological theory from static to dynamic by combining the MaxEnt inference procedure with explicit mechanisms governing disturbance. In the static limit, the resulting theory, DynaMETE, reduces to METE but also predicts new scaling relationships among static state variables. Under disturbances, expressed as shifts in demographic, ontogenic growth, or migration rates, DynaMETE predicts the time trajectories of the state variables as well as the time-varying shapes of macroecological metrics such as the species abundance distribution and the distribution of metabolic rates over individuals. An iterative procedure for completely solving the dynamic theory is presented. In a lowest-order iteration, characteristic signatures of the deviation from static predictions of macroecolgoical patterns are shown to result from different kinds of disturbance. Because DynaMETE combines MaxEnt inference with explicit dynamical mechanisms, but does not assume any specific trait distributions over species or individuals, it is widely applicable across diverse ecosystems. This makes it a promising theory of macroecology for ecosystems responding to anthropogenic or natural disturbances.

Duchenne Muscular Dystrophy is an X-linked inherited disorder and the most common fatal degenerative muscle disease in pediatric patients. Its first symptoms usually manifest at an early age, with weakness, psychomotor developmental delay, evolving to cardiac and ventilatory muscle impairment. The involvement of the pulmonary musculature is demonstrated by the frequent episodes of obstruction and aspirations, sleep-disordered breathing, and by the development of a chronic restrictive breathing pattern. Failure of respiratory mechanics is a major cause of mortality in Duchenne Muscular Dystrophy, and the beginning of lung function deterioration is not always accompanied by symptoms, which reinforces the need for serial evaluations for early initiation of a ventilatory support. The present article is thought to provide a synthesized overview of the assessment and management of Duchenne Muscular Dystrophy ventilatory disturbances.

CircRNA expression profile and circRNA-miRNA-mRNA crosstalk in allergic rhinitisTo the Editor,Allergic rhinitis (AR) is a chronic multi-factorial inflammatory disease, with a prevalence on the rise in China1. CircRNAs, a newly discovered family of endogenous non-coding RNAs, function in various biological processes2. For instance, circRNAs are involved in neuronal activities, tumor development, and innate immune responses, inflammatory diseases3-4. However, the roles of circRNAs in AR remain unclear. In this study, using high-throughput sequencing (HTS), we explored the circRNA, miRNA, and mRNA expression profiles in nasal mucosa from AR patients, and constructed a differentially expressed (DE) circRNA-DEmiRNA-DEmRNA network to illustrate the molecular mechanism in AR.This study was approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University and each patient provided written informed consent. Patients and methods are detailed as online data.

Purpose Tear fluid N-Glycome from patients affected with vernal (VKC) and atopic keratoconjunctivitis (AKC) was investigated to identify specific changes in tears and to recognize possible glyco-biomarkers. Methods The analysis of N-glycans was performed using matrix-assisted laser desorption ionization mass spectrometry on single tear samples. Tears from control normal subjects (CTRL), VKC and AKC patients were processed and treated with peptide N-glycosidase F (PNGase F) to deglycosylate N-glycoproteins. Released N-glycans were purified, permethylated and analyzed by Matrix-Assisted Laser Desorption/Ionization-Time Of Flight Mass Spectrometry and tandem Mass Spectrometry (MALDI-TOF MS and MALDI-TOF MS/MS). Results More than 150 complex N-glycans, including highly fucosylated biantennary, triantennary, tetraantennary and bisecting species, were observed in our spectra. Three distinct patterns for CTRL, VKC and AKC patients were identified in terms of relative intensities for some N-glycans structures. Major variations involved bisecting and hyperfucosylated glycoforms. The most intense ions were associated to species at m/z 1907.0 (asialo, agalacto, bisected, biantennary structure – NGA2B) in CTRL MS profiles, at m/z 2605.3 and 2966.5 in VKC, and at m/z 2792.4 in AKC corresponding to a well-known biantennary, disialylated N-glycan. Several peaks were associated to structures bearing one or two Lewis X epitopes. Structures were confirmed by MS/MS analysis. Quantitative differences among the three groups were statistically significant. Conclusions Tear MS profiles are rich in specific glycoforms, particularly those with a high fucosylation degree, indicating both core and peripheral decoration. Tear N-glycome analysis provided important information for a better comprehension of VKC and AKC alterations at the molecular level

Background: Cardiovascular disease (CVD) is the primary cause of mortality and morbidity in chronic kidney disease (CKD) patients. Aortic propagation velocity (APV), epicardial fat thickness (EFT), and carotid intima-media thickness (CIMT) measurements could provide additional information on assessing renal decline in CKD patients. The study aimed to evaluate EFT, AVP, and CIMT in CKD patients and then investigate the association among those parameters. Methods and Results: A total of 170 CKD consecutive subjects were enrolled in the study. Patients were divided into five groups according to their GFR values. Each patient underwent complete transthoracic echocardiography examination. APV, EFT and CIMT were measured for analyses. A multivariate linear regression model was used for analysis to determine the independent predictors of GFR. The lowest APV was observed in stage IV-V, and the highest APV was observed in stage I-II (p<0.001). Stage IV-V patients had the highest EFT, and stage I-II patients had the lowest EFT (p<0.001). Moreover, the lowest CIMT was observed in stage III, and the highest APV was observed in stage V (p<0.001). GFR was significantly and positively correlated with APV and negatively correlated with EFT and CIMT. In multivariate analyses, APV (OR: 0.289, p<0.001), EFT (OR: -0.135, p<0.001) and CIMT (OR: -0.388, p<0.001) were independent predictors of GFR. Conclusion: We found that APV decreased, and EFT and CIMT increased as CKD progress. The present study suggests that APV, EFT, and CIMT might be incorporated with the examination of CKD patients in daily practice.

To explore the association between pulmonary artery systolic pressure (PASP) and success to wean from mechanical ventilation in COVID-19 patients.Thirty-four critically ill COVID-19 patients who had been placed on ventilator support were enrolled in this retrospective study and were divided into two groups: the weaning success group (group I) and the weaning failure group (group II). Physical examination, echocardiography, and routine laboratory test data were collected. The levels of troponin I, myoglobin, interleukin 6, and D-dimer were significantly lower in group I than in group II. The interventricular septum end-diastolic thickness (IVSd) was thicker (14.00 [13.50‒15.00] mm) and the PASP was higher (61.63 ± 13.53 mmHg) in group II. Logistic regression analysis showed that D-dimer and IVSd were factors associated with ventilator weaning. The odds ratio (OR) of D-dimer was 0.81 (95% CI 0.69‒0.95) and the OR of IVSd was 0.16 (95% CI 0.045‒0.59). Cox analysis revealed that the adjusted hazard ratio (HR) for a 1-mmHg increase in PASP was 0.94 (95% CI 0.90‒0.97) for weaning events (P < 0.001). PASP was negatively correlated with the PaO2:FiO2 (r = -0.48, P < 0.01). A receiver operating characteristic curve showed that the best cutoff value of PASP for ventilator weaning was 39.50 mmHg, with a sensitivity of 100% and a specificity of 96.15% PASP was an independent risk factor for the difficulty of weaning severely ill COVID-19 patients off mechanical ventilation. PASP can be used as one of the indicators for evaluating the condition of COVID-19 patients.

Global declines in structurally complex habitats are reshaping both land and seascapes in directions that affect biological communities’ responses to warming. Here, we test whether widespread loss of kelp habitats through sea urchin overgrazing systematically changes warming sensitivity of fish communities. Community thermal affinity shifts related to habitat were assessed by simulating and comparing fish communities from 2,271 surveys across 15 ecoregions. We find that fishes in kelp and urchin barrens differ in realized thermal affinities and range sizes, but only in regions where species pools have high variability in species’ thermal affinities. Barrens on warm-temperate reefs host relatively more warm-affinity fish species than neighbouring kelp beds, highlighting acceleration of tropicalization processes facilitated by urchin herbivory. By contrast, proportionally more cool-affinity fishes colonize barrens at high temperate latitudes, contributing to community lags with ocean warming in these regions. Our findings implicate urchins as drivers of ecological change, in part by affecting biological resilience to warming.

The Ocean Barcode Atlas (OBA) is a user friendly web service designed for biologists who wish to explore the biodiversity and biogeography of marine organisms locked in otherwise difficult to mine planetary scale DNA metabarcode datasets. Using just a web browser, a comprehensive picture of the diversity of a taxon or a barcode sequence is visualized graphically on world maps and interactive charts. Interactive results panels allow dynamic threshold adjustments and the display of diversity results in their environmental context measured at the time of sampling (temperature, oxygen, latitude, etc.). Ecological analyses such as alpha and beta-diversity plots are produced via publication quality vector graphics representations. Currently, the Ocean Barcode Altas is deployed online with the i) Tara Oceans eukaryotic 18S-V9 rDNA metabarcodes, ii) Tara Oceans 16S/18S rRNA miTags, and iii) 16S-V4V5 metabarcodes collected during the Malaspina-2010 expedition. Additional prokaryotic or eukaryotic plankton barcode datasets will be added upon availability, given they provide the required complement of barcodes (including raw reads to compute barcode abundance) associated with their contextual environmental variables. Ocean Barcode Atlas is a freely-available web service at: http://oba.mio.osupytheas.fr/ocean-atlas/.

CD26, acting as a co-stimulator of T cell activation, plays an important role in the immune system. However, the role of CD26 in the differentiation of T cell subsets, especially of new paradigms of T cells, such as Th17 and Tregs, is not fully clarified. In the present study, the role of CD26 in T cell differentiation was investigated in vitro. CD26 expression was analysed in the different subsets of human peripheral blood T lymphocytes after antigen stimulation. Here, the percentage of CD4+ cells significantly increased and most of these cells were co-expressed with CD26, suggesting a close correlation of CD26 expression with the proliferation of CD4+ cells. Subsequently, after antigen stimulation, CD26 high-expressing cells (CD26high) were separated from CD26 low-expressing cells (CD26low) by magnetic cell sorting. We found that the percentages of cells secreting Th1-typical cytokines (IL-2, IFN-γ), Th17-typical cytokines (IL-6, IL-17, IL-22) or expressing Th17-typical biomarkers (IL-23R, CD161, CD196) in the CD26high group were markedly higher than in the CD26low group. In addition, a co-expression of CD26 with IL-2, IFN-γ, IL-17, IL-22, and IL-23R in lymphocytes was demonstrated by fluorescence microscopy. These results provide direct evidence that the high expression of CD26 is accompanied by the differentiation of T lymphocytes into Th1 and Th17, indicating that CD26 plays a crucial role in regulating the immune response.

Background: Differences in cardiac remodeling after mitral valve (MV) surgery between the sexes is poorly understood. Inferior outcomes for females undergoing MV surgery compared to males have been suggested in the literature, although causative factors behind this discrepancy have not been identified. Materials and Methods: In this propensity-matched, retrospective, single-center study, we sought to identify the impact that sex may have on cardiac remodeling and long-term outcomes to better inform clinical decision making in MV surgical intervention. Outcomes were compared between males and females undergoing MV replacement (MVR) between 2004 and 2018. The primary outcome was cardiac remodeling 1 year postoperatively. Secondary outcomes included mortality, stroke, myocardial infarction (MI), reoperation of the MV, and rehospitalization. Results: 314 males and 314 females were included after propensity matching. Males demonstrated a significant degree of improved left ventricular remodeling while females did not, and females showed a significant degree of left atrial remodeling while males did not. Mortality rates were relatively equivalent between the two groups, although males were more likely to develop sepsis and require rehospitalization due to MI. Conclusions: There has been little research exploring the differences in cardiac remodeling between the sexes after MVR. The results of this study have suggested that MVR is equally safe for both sexes and has demonstrated a difference in the heart’s ability to remodel after MVR. The significance of this difference has the potential to result in largely different clinical outcomes for males and females. Further study is necessary to fully elucidate this relationship.

Inadvertent endocardial lead malposition is recognised as a rare incident which is usually underreported and if recognised during implantation can be easily corrected. This phenomenon is caused by the ventricular lead unintentionally crossing a pre-existing patent foremen ovale, septal defects (atrial or ventricular) or directly from the aorta via an accidental subclavian puncture resulting in the lead implanting into the left ventricle. While this is a rare occurrence we report the incidental finding of pacemaker lead malposition during a routine follow-up transthoracic echocardiogram and the benefits of three dimensional transoesophageal echocardiography in this patient prior to lead extraction.

Evidence suggest soy isoflavones might reduce inflammatory biomarkers, therefore; the objective of this study is to conduct a systematic review and meta-analysis on randomized controlled trials (RCTs) that assessed the effect of soy isoflavones on serum concentration of C-reactive protein (CRP) among postmenopausal women. Literature search was conducted by searching PubMed, Scopus, ISI Web of Science, Cochrane Library, and Clinicaltrials.gov up to January 2020. The mean change from baseline in the CRP concentrations and its SD for both intervention and comparison groups were used to compute the effect size. The summary of the overall effects and heterogeneity was estimated by using the DerSimonian and Laird random effects model. The protocol was registered with PROSPERO (No. CRD42020166053). This article considered 23 articles for systematic review and 19 articles for meta-analysis. The overall effect suggested a non-significant effect of soy isoflavones on serum CRP concentrations (WMD= 0.08 mg/L, 95% CI: -0.08, 0.24; p=0.302) and the overall effect of the combination of soy isoflavones plus soy protein indicated non-significant effect in serum levels of CRP (WMD= -0.02 mg/L 95% CI: -0.12, 0.08; p=0.715). There was no significant change in serum levels of CRP in subgroup analysis based on dose, age, intervention duration, baseline CRP level, sample size, region, quality assessment, publication year, and health status. Dose response analysis revealed no association of higher dose of soy isoflavones with isoflavones effect on CRP levels.

Objective To determine the efficacy of fractional carbon dioxide laser (FXCO2) therapy for vulvar lichen sclerosus (VLS). Design Prospective, double-blind, sham-controlled, randomized trial. Setting Clinic specializing in vulvovaginal disorders. Population Forty women with active VLS confirmed with biopsy who abstaining from topical and/or systemic treatments for at least 4 weeks. Methods Women were randomized in a 1:1 ratio to receive either five sham laser treatments or five FXCO2 treatments in a 24-week period. Pre- and post-treatment biopsies were obtained on all participants. Study participants, treating clinicians, and evaluating pathologist were blinded. Main Outcome Measures Primary: pre- and post-treatment biopsy Histopathologic Scale (HS) findings. Secondary: Clinical Scoring System for Vulvar Lichen Sclerosus (CSS) Results There was a 0.12 reduction (improvement) in HS from baseline in the active treatment group (95%CI = -1.01, 0.78, p=0.79) and a 0.06 increase from baseline in the sham treatment group (95%CI - -0.81, 0.92, p=0.90). The change in HS between the active and sham arm was not statistically significant (-0.17; 95%CI = -1.14, 1.06, p=0.78). There was a 6.82-point reduction (improvement) in the patients’ CSS from baseline in the active (95% CI = -11.28, -2.37, p= 0.004) and a 4.83-point reduction in the sham treatment group (95% CI = -9.16, -0.51, p=0.03). In the clinicians’ CSS, there was a 0.82 increase (worsening) in the active (95% CI = -0.46, 2.11, p=0.20) and a 0.28 reduction in the sham treatment group (95% CI = -1.53, 0.97, p=0.65). Conclusions. FXCO2 is not an effective monotherapy treatment for VLS