ABSTRACT
OBJECTIVE: To evaluate the association of the rs11125908 polymorphism in the COMMD1 gene in the Cuban population with rheumatoid arthritis (RA). METHODS: In this case-control study, 161 RA patients and 150 control subjects were genotyped for rs11125908 by the allele-specific polymerase chain reaction method. DNA sequencing was used to verify the assignation of the polymorphism. The odds ratios (OR) and their 95% confidence interval were calculated by logistic regression to determine the associations between genotypes and RA using the SNPStats software. RESULTS: An association of the single nucleotide polymorphism with the disease was found in the overdominant model (p=0.025; OR=1.91) for the AG genotype. Our analyses revealed an association between rs11125908 and the subgroup of patients with swollen joints < median under the codominant model for AG (p=0.034; OR=2.30) and GG genotype (p=0.034; OR=0.82) and with the overdominant model (p=0.01; OR=2.38). The subgroup of patients with an age of onset lower than the mean and AG genotype showed an association in the overdominant model (p=0.027; OR=2.27). Disease activity score 28 with erythrocyte sedimentation rate and disease duration variables were not associated with the rs11125908 polymorphism. CONCLUSIONS: rs11125908 was associated with RA and with the number of swollen joints and age of onset subgroup analyses. We provide concepts for treatments for RA, based on pharmacological management of COMMD1 expression.
Subject(s)
Arthritis, Rheumatoid , Polymorphism, Single Nucleotide , Adult , Aged , Female , Humans , Male , Middle Aged , Adaptor Proteins, Signal Transducing/genetics , Arthritis, Rheumatoid/genetics , Case-Control Studies , Cuba , Genetic Predisposition to Disease , GenotypeABSTRACT
Curdlan, a ß-1,3/1,6-glucan found in Alcaligenes faecalis (A. faecalis) wall, activates innate and humoral immunity. The aim of this study is to evaluate whether pretreated rats with A. faecalis A12C could prevent sepsis disturbances and identify the immunomodulatory mechanisms involved. Experiments occurred in two stages: a survival study with 16 rats randomly divided into septic (SC) (n = 8) and septic pretreated (SA) (n = 8) groups and 45 rats divided into four groups: healthy (AGUSAN) (n = 9), septic (AGUIC) (n = 13), septic pretreated (AGUIA) (n = 14), and healthy pretreated (AGUSTO) (n = 9). Sepsis was induced by cecal ligation and puncture after 30 days of A. faecalis A12C pretreatment or without. SA group had a higher survival rate of 58% vs. 16% for SC group (P < 0.05). Overall, AGUIA showed better status than AGUIC (P < 0.01). Higher monocytosis was found in AGUIA and AGUSTO vs. AGUIC and AGUSAN, respectively (P < 0.05). A gradual increase in curdlan fecal concentration was observed in AGUIA during pretreatment. Fecal concentrations of Escherichia coli significantly decreased in AGUIA and AGUSTO. Bacterial load in urine, peritoneal lavage fluid (PLF), and bronchoalveolar lavage fluid (BALF) decreased (P < 0.05) in AGUIA vs. AGUIC. Finally, lower inflammation was observed in serum, BALF, and PLF, with reduced IL-6, IL-10, IL-1ß, and TNF-α, along with less damage in lungs and peritoneum in AGUIA vs. AGUIC. These findings suggest the connection between curdlan-produced by A. faecalis A12C-with the immune system and the reduction in severity of experimental sepsis.
ABSTRACT
In this work, we present a novel approach for improving the energy resolution from particles impinging on the interstrip regions of silicon strip detectors. We employed three double-sided strip detectors from the GRIT array and a triple α-source under laboratory conditions. The results showed that the interstrip resolution depends not only on the impinging side but also on whether it is a P- or an N-interstrip. We obtained the interstrip energy resolution down to 0.4%, and, depending on the scenario, the resolution was enhanced by a factor of 2. We believe that this new rotation method allows for the possibility of applying particle identification methods on interstrip events, which in most cases are dismissed during data recording.
ABSTRACT
Magnetic resonance imaging (MRI) plays a pivotal role in primary staging of rectal cancer, enabling the determination of appropriate management strategies and prediction of patient outcomes. However, inconsistencies and pitfalls exist in various aspects, including rectal anatomy, MRI protocols and strategies for artifact resolution, as well as in T- and N-staging, all of which limit the diagnostic value of MRI. This narrative and pictorial review offers a comprehensive overview of factors influencing primary staging of rectal cancer and the role of MRI in assessing them. It highlights the significance of the circumferential resection margin and its relationship with the mesorectal fascia, as well as the prognostic role of extramural venous invasion and tumor deposits. Special attention is given to tumors of the lower rectum due to their complex anatomy and the challenges they pose in MRI staging. The review also addresses current controversies in rectal cancer staging and the need for personalized risk stratification. In summary, this review provides valuable insights into the role of MRI in the primary staging of rectal cancer, emphasizing key aspects for accurate assessment to enhance patient outcomes.
Subject(s)
Magnetic Resonance Imaging , Neoplasm Staging , Rectal Neoplasms , Humans , Magnetic Resonance Imaging/methods , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/pathologyABSTRACT
Urban sewage sludge (SL) is a major concern due to the number of environmental problems it causes. Its application for different purposes is strictly regulated, limiting the possibilities of recycling and reusing this material. Thus, in this work, a complete study of a simple method to convert SL into activated carbon (AC) was carried out. The comprehensive study involves an evaluation of the main process parameters, such as the activating agent (AA) content (25 %, 33 %, 50 %), using the lowest amount of AA as novelty, different pyrolysis temperatures (600 and 800 °C), and purification conditions (6 M HCl:AC ratio, v:w). Under controlled and optimised conditions and through a single combined activation and pyrolysis step followed by acid purification, ACs with well-developed porosity can be obtained. Surface area values of around 870 m2/g and over 60 % carbon content were achieved, demonstrating that the prepared ACs could have applications in a wide variety of fields as high-value products. As an innovative aspect in this research, the gases streams and liquid effluents generated during the global process were analysed, achieving elimination of over 63 % of the concentration of the chemical elements contained in the SL during the chemical purification stage. Finally, mass, energy, and economic balances were carried out to estimate the production cost of AC derived from SL (< 8/kg AC).
Subject(s)
Charcoal , Sewage , Sewage/chemistry , Porosity , Charcoal/chemistry , Gases , RecyclingABSTRACT
This work deals with the characteristics of highly segmented double-sided silicon detectors. These are fundamental parts in many new state-of-the-art particle detection systems, and therefore they must perform optimally. We propose a test bench that can handle 256 electronic channels with off-the-shelf equipment, as well as a detector quality control protocol to ensure that the detectors meet the requirements. Detectors with a large number of strips bring new technological challenges and issues that need to be carefully monitored and understood. One of the standard 500 µm thick detectors of the GRIT array was investigated, undergoing studies that revealed its IV curve, charge collection efficiency, and energy resolution. From the data obtained, we calculated, among other things, the depletion voltage (110 V), the resistivity of the bulk material (9 kΩ·cm), and the electronic noise contribution (8 keV). We present, for the first time, a methodology called "the energy triangle'' to visualize the effect of charge sharing between two adjacent strips and to study the hit distribution with the interstrip-to-strip hit ratio (ISR).
Subject(s)
Silicon , Quality ControlABSTRACT
BACKGROUND: Neurodegeneration in Alzheimer's disease (AD) is typically assessed through brain MRI. Although proprietary software can provide normative estimates of regional atrophy, such tools can be cost-prohibitive for research settings. Free software for generating normative estimates has recently been released but has yet to be validated in the context of amnestic mild cognitive impairment (aMCI). OBJECTIVES: Determine whether normative morphometric estimates generated from open-source software replicate established patterns of neurodegeneration in aMCI, and whether these metrics correlate with episodic memory performance. DESIGN: Observational study of brain MRI and cognition in aging and aMCI with two identical study visits occurring approximately 1.2 years apart. SETTING: Participants were recruited from the local community and outpatient clinical settings. PARTICIPANTS: Adults ages 60-85 with aMCI (n = 25) and cognitively normal controls (CN; n = 74). A subset returned for follow-up (aMCI n = 11, CN n = 52). MEASUREMENTS: Participants completed brain MRI and two neuropsychological tests of verbal episodic memory. FreeSurfer v6.0 and Normative Morphometry Image Statistics were used to generate normative morphometric estimates for AD-relevant regions (hippocampus, parahippocampus, entorhinal cortex, amygdala) and control regions (cuneus, lingual gyrus, pericalcarine gyrus), adjusting for age, sex, head size, scanner manufacturer, and field strength. We tested for baseline group differences in ROI volumes and memory and assessed their within-group associations. We also evaluated changes in ROI volumes over time and tested whether these changes corresponded to declines in memory. RESULTS: At baseline, the aMCI group exhibited poorer memory and smaller volumes in AD-relevant regions than the CN group. There were no group differences in control region volumes. Memory was associated with volumes in AD-relevant regions in the aMCI group only. The aMCI group exhibited greater declines than the CN group in hippocampal volume (17% vs. 8% annual decline) and entorhinal volume (54% vs. 5% annual decline). Decrease in hippocampal volume was marginally associated with decline in memory for the aMCI group. CONCLUSIONS: Normative morphometric values generated from freely available software demonstrated expected patterns of group differences in AD-related volumes and associations with memory. Significant effects were localized to AD-relevant brain regions and only occurred in the aMCI group. These findings support the validity of these free tools as reliable and cost-effective alternatives to proprietary software for use in research settings.
Subject(s)
Alzheimer Disease , Cognition Disorders , Cognitive Dysfunction , Memory, Episodic , Humans , Middle Aged , Aged , Aged, 80 and over , Access to Information , Cognitive Dysfunction/psychology , Brain/diagnostic imaging , Cognition Disorders/complications , Alzheimer Disease/psychologyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Solanum sisymbriifolium Lam., is used in Paraguayan folk medicine claiming antihypertensive and diuretic properties. AIM OF THE STUDY: This study aimed to determine the influence of chronic oral administration of the crude root extract and saponins obtained from S. sisymbriifolium Lam., on the blood pressure of male and female rats with hypertension induced by L-NAME, and its consequences on diuresis, the body weight, blood glucose, and level of serum parameters of liver and kidney functionality. MATERIALS AND METHODS: Wistar rats were randomly divided into seven male, and seven female groups (8 animals each), which received as 6-week pretreatment, 0.9% saline solution (two groups; 0.1mL/10 g of b.w.), L-arginine (100.0 mg/kg/day), enalapril (15.0 mg/kg/day), crude extract (CESs 100.0 mg/kg/day), and saponin purified fraction (1.0, and 10.0 mg/kg/day), and treated with L-NAME (20 mg/kg/day/i.p.) twice, 1, and 6 h after pre-treatment. The animals' body weight, glycemia, and blood pressure were recorded weekly, while serum, hepatic, renal, and histological parameters were analyzed at the end of 6-week of treatment. RESULTS: A protective effect of CESs (100.0 mg/kg/day), and saponins (1.0, and 10.0 mg/kg/day) against hypertension induced by L-NAME was verified in the systolic, diastolic, and mean blood pressure values, which were significantly lower than the positive L-NAME-hypertensive control group (male and female) at the end of the 6-week treatment. Also, pretreatment with enalapril (15.0 mg/kg/day) induced an efficient protective activity, which validates the method used. Likewise, the volume of urine, creatinine, uric acid, urea, and electrolyte excretion was enhanced at the end of 6-week of treatment in concordance with the reduction in serum level of the same parameters, compatible with the improvement of the diuretic activity. The glycemia, body weight, heart rate, and functional hepato-renal parameters were not modified after a 6-week of treatment, in comparison to the control group, indicating relatively acceptable harmless properties of CESs and saponins. Interestingly, the HDL level in females was increased in contrast to male rats by chronic saponins treatment when compared with the negative control group. CONCLUSIONS: It can be concluded that either the increment in blood pressure (systolic, diastolic, and median) or cardiorenal remodeling effects in male and female rats submitted to L-NAME-induced hypertensive condition, were prevented and well-preserved without a significant variation during a period of 6-week of pretreatment with CESs and saponins pretreatments. Likewise, an important diuretic effect was revealed after this period of treatment.
Subject(s)
Hypertension , Saponins , Solanum , Animals , Antihypertensive Agents , Blood Pressure , Body Weight , Diuretics/pharmacology , Enalapril , Female , Hypertension/chemically induced , Hypertension/drug therapy , Male , NG-Nitroarginine Methyl Ester/pharmacology , Plant Extracts , Rats , Rats, Wistar , Saponins/pharmacology , Saponins/therapeutic useABSTRACT
BACKGROUND: Oral squamous cell carcinoma (OSCC) and potentially malignant oral disorders (OPMDs) could be associated with low levels of vitamin D. This systematic review aimed to determine the relationship between serum levels of vitamin D with OPMDs and OSCC. MATERIAL AND METHODS: This review was conducted according to Cochrane guidelines (PROSPERO CRD42020207382) on literature retrieved from the PubMed, Cochrane, and Web of Science databases. The antecedents extracted were study design, methodology, sample (country, number of patients, age, and sex), oral manifestations (type of lesion, location, prevalence, and follow-up), serum vitamin D levels or use of vitamin D supplements, results, and conclusions. RESULTS: Twelve articles were selected. Some of the most relevant findings were alterations in vitamin D could favor the progress of OPMDs to OSCC. Higher levels of vitamin D can increase levels of anti-inflammatory mediators, CD4+ T lymphocytes and CD8+ T lymphocytes and CD3+ T lymphocytes in intratumoral tissue. The normalization of vitamin D levels in patients with OSCC can increased cytotoxic activity of natural killer cells, favoring antitumor immune response. Vitamin D supplemented can lower adverse effects associated with chemotherapy like mucositis and pain. Tobacco can increase risk of developing OSCC altering vitamin D levels. CONCLUSIONS: Hypovitaminosis D could increase risk of developing OSCC from OPMDs, thus altering the immune response and it is associated with a lower survival rate in patients with OSCC, a greater recurrence of tumors in patients who underwent surgical treatment, and an increase in adverse reactions to chemotherapy. The use of vitamin D supplements can be a complement to primary therapy to prevent the recurrence of lesions and reduce adverse events associated with treatment.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Vitamin D Deficiency , Carcinoma, Squamous Cell/etiology , Carcinoma, Squamous Cell/pathology , Humans , Mouth Neoplasms/etiology , Mouth Neoplasms/pathology , Squamous Cell Carcinoma of Head and Neck , Vitamin D Deficiency/complicationsABSTRACT
Los queratoquistes maxilares son frecuentes en pacientes con síndrome de Gorlin. Su tratamiento es debatido por su alta tendencia a la recidiva. En los últimos años la cirugía endoscópica nasosinusal ha adquirido importancia en el manejo de esta patología. Exponemos en caso de un varón de 16 años afecto de este síndrome con queratoquistes maxilares donde se realiza un abordaje combinado, endonasal y transoral.
Maxillary keratocysts are frequent in Gorlin Syndrome patients. Its treatment is discussed due to the high tendency to recurrence. In the last years the sinonasal endoscopic surgery has become an important tool in the management of this pathology. We report a 16 years old boy with Gorlin Syndrome and maxillary keratocysts treated with a trans-nasal endoscopic and intra-oral combined approach.
Subject(s)
Humans , Male , Adolescent , Basal Cell Nevus Syndrome/surgery , Maxillary Diseases/surgery , Odontogenic Cysts/surgery , Basal Cell Nevus Syndrome/diagnostic imaging , Maxillary Diseases/diagnostic imaging , Odontogenic Cysts/diagnostic imaging , Tomography, X-Ray Computed/methods , Endoscopy/methodsABSTRACT
A strain of Alcaligenes faecalis A12C (A. faecalis A12C) isolated from Argyrosomus regius is a probiotic in fish. Previous experiments showed that A. faecalis A12C had inhibitory effects on the growth of multidrug-resistant bacteria. We aimed to confirm whether A. faecalis A12C is safe and has adequate intestinal colonization in experimental rats, and evaluate its efficacy in an animal model of peritonitis. We used 30 male rats, randomly divided into 6 groups (n = 5): three groups (HA7, HA15, HA30) received A. faecalis A12C in drinking water (6 × 108 CFU/mL) for 7 days, and three control groups received drinking water only. All groups were evaluated at 7, 15, and 30 days. Survival after A. faecalis A12C administration was 100% in all groups. Mild eosinophilia (1.5%, p < 0.01) and increased aspartate aminotransferase (86 IU/L, p < 0.05) were observed in HA7, followed by progressive normalization. No histological signs of organ injury were found. We observed significant E. coli decline in faeces, parallel to an increase in A. faecalis A12C at 7 days. E. coli had a tendency to recover initial values, while A. faecalis A12C disappeared from the intestinal microbiota at 30 days. To evaluate its efficacy against peritonitis, we studied two additional groups of animals: IA group pretreated with A. faecalis A12C before E. coli intra-abdominal inoculation, and IC group inoculated with no A. faecalis A12C. We found an increase in C-reactive protein, alanine aminotransferase, urea, and eosinophils in IC animals when compared with IA. Peritonitis was more evident in IC than in IA animals. Our findings suggest that A. faecalis A12C altered clinically relevant parameters in sepsis and was associated with a lesser spread of infection.
Subject(s)
Alcaligenes faecalis , Peritonitis , Probiotics , Animals , Drinking Water , Escherichia coli/pathogenicity , Male , Peritonitis/therapy , RatsABSTRACT
Aethina tumida Murray is currently a worldwide emergent pest of Apis mellifera L. hives. Although the damaging effect on the colony stores and brood is well known, the possible role of these beetles as a disease carrier is not clear. This is the first report of DNA presence of the trypanosome honeybee parasite Lotmaria passim and Crithidia bombi, and the Apis mellifera filamentous virus (AmFV) in A. tumida. Further studies will be needed to determine if A. tumida is indeed a mechanical or biological vector of these pathogens.
Subject(s)
Bees , Coleoptera , Trypanosoma/isolation & purification , Animals , Coleoptera/parasitologyABSTRACT
Odor emissions from wastewater treatment plants (WWTPs) have always been a public concern. In this work, the physico-chemical, olfactometric and textural characterization of granular active carbon (GAC) used by an urban WWTP as a deodorization system, as well as the chromatographic quantification of the retained odoriferous compounds, have been carried out. These techniques have allowed an integral evaluation of the contaminated GAC and the characterization of the retained gaseous emission from four different stages of the wastewater treatment (pretreatment header: GAC-1; sand and fat removal: GAC-2; sludge thickening: GAC-3; sludge dehydration: GAC-4). A larger amount and variety of retained odoriferous compounds were found in GAC samples from the wastewater line deodorization (GAC-1 and GAC-2) after the same operation time (one year), GAC-1 being the adsorbent bed that retained the highest mass of volatile compounds (approximately 150µg/g GAC). Furthermore, some variables such as the removed specific odor concentration and free micropore volume were inversely correlated (R2=0.9945). The analysis of odor contribution showed that sulfur-containing compounds were the major odor contributors (61-97%). However, hydrogen sulfide cannot be considered a key odorant in this particular WWTP, since the elimination of this compound does not reduce the significant contribution of other (organic) sulfur compounds to the global odor (especially dimethyl disulfide). Consequently, multi-technical analysis might be a suitable alternative to better understand odor removal by GAC adsorption.
Subject(s)
Anesthesiology/statistics & numerical data , Cataract Extraction , Preoperative Care/statistics & numerical data , Radiography, Thoracic/statistics & numerical data , Unnecessary Procedures/statistics & numerical data , Adult , Age Factors , Ambulatory Surgical Procedures/statistics & numerical data , Hospitals, Public , Humans , Practice Guidelines as Topic , Retrospective Studies , Societies, Medical , Spain , Surgical Procedures, Operative/statistics & numerical dataABSTRACT
Microalgae cultivation has been receiving increasing interest in wastewater remediation due to their ability to assimilate nutrients present in wastewater streams. In this respect, cultivating microalgae in membrane photobioreactors (MPBRs) allows decoupling the solid retention time (SRT) from the hydraulic retention time (HRT), which enables to increase the nutrient load to the photobioreactors (PBRs) while avoiding the wash out of the microalgae biomass. The reduction of the PBR light path from 25 to 10 cm increased the nitrogen and phosphorus recovery rates, microalgae biomass productivity and photosynthetic efficiency by 150, 103, 194 and 67%, respectively.The areal biomass productivity (aBP) also increased when the light path was reduced, reflecting the better use of light in the 10-cm MPBR plant. The capital and operating operational expenditures (CAPEX and OPEX) of the 10-cm MPBR plant were also reduced by 27 and 49%, respectively. Discharge limits were met when the 10-cm MPBR plant was operated at SRTs of 3-4.5 d and HRTs of 1.25-1.5 d. At these SRT/HRT ranges, the process could be operated without a high fouling propensity with gross permeate flux (J20) of 15 LMH and specific gas demand (SGDp) between 16 and 20 Nm3air·m-3permeate, which highlights the potential of membrane filtration in MPBRs. When the continuous operation of the MPBR plant was evaluated, an optical density of 680 nm (OD680) and soluble chemical oxygen demand (sCOD) were found to be good indicators of microalgae cell and algal organic matter (AOM) concentrations, while dissolved oxygen appeared to be directly related to MPBR performance. Nitrite and nitrate (NOx) concentration and the soluble chemical oxygen demand:volatile suspended solids ratio (sCOD:VSS) were used as indicators of nitrifying bacteria activity and the stress on the culture, respectively. These parameters were inversely related to nitrogen recovery rates and biomass productivity and could thus help to prevent possible culture deterioration.
Subject(s)
Microalgae , Photobioreactors , Biomass , Phosphorus , WastewaterABSTRACT
This data in brief (DIB) article is related to a Research article entitled 'Optimising an outdoor membrane photobioreactor for tertiary sewage treatment' [1]. Data related to the effect of substrate turbidity, the ammonium concentration at which the culture reaches nitrogen-deplete conditions and the microalgae growth rate under outdoor conditions is provided. Microalgae growth rates under different substrate turbidity were obtained to assess the reduction of the culture's light availability. Lab-scale experiments showed growth rates reductions of 22-44%. Respirometric tests were carried to know the limiting ammonium concentration in this microalgae-based wastewater treatment system. Growth rates (µ) of green microalgae Scenedesmus and Chlorella obtained under outdoor conditions; i.e. 0.40 d-1 (R2 = 0.993) and 0.43 d-1 (R2 = 0.995), respectively, can be useful to obtain optimum operating conditions of membrane photobioreactor (MPBR).
ABSTRACT
OBJECTIVE: To perform an epidemiologic profile of pancreatic cancer (PC) in Puerto Rico (PR) with data gathered from 2001 to 2015. METHODS: Using data from the PR Central Cancer Registry we estimated incidence and mortality rates and trends of PC in PR, and performed survival analyses. We also compared the age-standardized incidence and mortality rates of PC in people in PR with those of Hispanics, non-Hispanic whites, and non Hispanic blacks in the United States (US). RESULTS: From 2011 to 2015, 7.8 per 100,000 persons were diagnosed with PC in PR; higher rates were observed in men than in women (9.2 vs. 6.7 per 100,000, respectively) and in persons 65 years old and older (42.7 per 100,000 persons). For the same period, 6.7 per 100,000 persons died from PC; men and persons 65 years and older had higher mortality rates. Incidence and mortality trends of PC in PR increased from 2001-2015 (annual percent change [APC] = 3.8% and 1.9%, respectively (p<0.05). Lower risk of being diagnosed with and dying from PC was seen in PR than in members of several racial/ethnic groups in the US. The median survival time for PC cases diagnosed in PR during the period of 2008 to 2012 was 5.3 months. CONCLUSION: We observed increasing mortality rates and low survival in PC patients in PR. Research on access and response to treatment is needed to elucidate the reasons for the observed results and have a positive impact on PC burden and survival.
Subject(s)
Black or African American/statistics & numerical data , Hispanic or Latino/statistics & numerical data , Pancreatic Neoplasms/epidemiology , White People/statistics & numerical data , Aged , Female , Humans , Incidence , Male , Middle Aged , Puerto Rico/epidemiology , Registries , Survival RateABSTRACT
The most remote isotope from the proton dripline (by 4 atomic mass units) has been observed: ^{31}K. It is unbound with respect to three-proton (3p) emission, and its decays have been detected in flight by measuring the trajectories of all decay products using microstrip detectors. The 3p emission processes have been studied by the means of angular correlations of ^{28}S+3p and the respective decay vertices. The energies of the previously unknown ground and excited states of ^{31}K have been determined. This provides its 3p separation energy value S_{3p} of -4.6(2) MeV. Upper half-life limits of 10 ps of the observed ^{31}K states have been derived from distributions of the measured decay vertices.
ABSTRACT
OBJECTIVE: We evaluated the effects of the B-cell activating factor (BAFF)-targeting antibody Belimumab on human nonmemory B-cell pools. Human B-cell pools were identified using surface markers adapted from mouse studies that specifically assessed reductions in immature B cells due to BAFF depletion. Patients with systemic lupus erythematosus (SLE) have high levels of both BAFF and immature B cells. Mechanistic mouse studies provide a framework for understanding human responses to therapies that target B cells. METHODS: Peripheral blood mononuclear cells were isolated from healthy donors and SLE patients on Belimumab or standard-of-care therapy (SCT). Cells were stained for flow cytometry to identify B-cell subsets based on CD21/CD24. Differences in subset proportions were determined by one-way ANOVA and Tukey's post hoc test. RESULTS: Patients treated with Belimumab show alterations in the nonmemory B-cell pool characterized by a decrease in the Transitional 2 (T2) subset (p = 0.002), and an increase in the proportion of Transitional 1 (T1) cells (p = 0.005) as compared with healthy donors and SCT patients. The naïve B-cell compartment showed no significant differences between the groups (p = 0.293). CONCLUSION: Using a translational approach, we show that Belimumab-mediated BAFF depletion reduces the T2 subset in patients, similar to observations in mouse models with BAFF depletion.