Red blood cell distribution width as a surrogate biomarker of damage and disease activity in patients with systemic lupus erythematosus.

OBJECTIVES: Red blood cell distribution width (RDW) is a measure of variability in mean corpuscular volume. Alterations in RDW can be observed in a variety of human disorders, including inflammatory, cardiovascular, and hepatic or renal diseases. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect virtually any organ in the body. In this work, our objective was to analyse how a complete characterisation of disease characteristics in a large series of patients with SLE is related to RDW values. METHODS: 284 patients with SLE and 181 age- and sex-matched healthy controls were recruited. Complete blood count including RDW was assessed. Multivariable analysis was performed to analyse the relationship between RDW and SLE disease characteristics, including composite scores of disease activity and damage. RESULTS: After multivariable adjustment, RDW was higher in patients with SLE compared to controls (beta coefficient 0.8 [95% confidence interval: 0.3-1] %, p=0.003). Several disease characteristics, such as the presence of extractable nuclear antibodies and antiphospholipid syndrome, and the use of prednisone and azathioprine, were significantly associated with higher levels of RDW after adjustment for confounders. Of note, cumulative disease damage and disease activity scores were associated with higher RDW values after controlling for covariates. CONCLUSIONS: RDW may serve as a surrogate biomarker of accrual disease damage and activity in patients with SLE.

Validating the usefulness of Sudoscan in ATTRv: a single centre experience.

BACKGROUND: Variant transthyretin amyloidosis (ATTRv) can cause sensorimotor and autonomic neuropathy. Objective quantification of sudomotor function may be essential for early diagnosis and early initiation of treatment. The aim of this study is to evaluate the diagnostic value of the Sudoscan® in ATTRv. METHODS: Electrochemical skin conductance (ESC) was measured in V30M ATTRv patients, asymtomatic V30M carriers and healthy controls. Comparisons between the three groups were made using the Kruskal-Wallis test, and ROC curves were used to estimate the discriminatory power of ESC values between groups. RESULTS: ESC was measured in 52 ATTRv patients, 107 asymptomatic carriers and 40 healthy controls. ESC was significantly lower in ATTRv patients compared to asymptomatic carriers and healthy controls in both feet and hands; median values are as follows: 40 µS, 78 µS and 81 µS, respectively (p < 0.001), and 53 µS, 69 µS and 74 µS, respectively (p < 0.001). ESC in feet < 70.5 µS had a sensitivity of 89.7% and specificity of 84.6% to discriminate asymptomatic carriers from patients with ATTRv. CONCLUSION: The determination of ESC by Sudoscan® is a rapid, noninvasive and easily reproducible technique capable of discriminating patients with ATTRv from asymptomatic carriers and healthy controls with adequate sensitivity and specificity.

Elevated complement C3 and increased CD8 and type 1 helper lymphocyte T populations in patients with post-COVID-19 condition.

BACKGROUND: Biological markers associated to post-COVID-19 condition (PCC) have not been clearly identified. METHODS: Eighty-two patients attending our post-COVID-19 outpatient clinic were recruited and classified as fully recovered (40.2%) or presenting with PCC (59.8%). Clinical and radiological data, laboratory markers, cytokines, and lymphocyte populations were analyzed. RESULTS: Median number of days after hospitalization was 78.5 [p25-p75: 60-93] days. PCC was significantly more frequent in women, in patients with a previously critical COVID-19, and in those with two or more comorbidities. No differences were found in lymphocyte counts, ferritin, C-reactive protein, D-dimer or sCD25, IL-1ß, IL-1Ra, IL-6, CXCL8, IL-17A, IL-18, IL-22, IFN-γ, TNF-α, and IL-10 cytokines levels. PCC patients showed significantly higher levels of complement factor C3 than fully recovered patients: median C3 128 mg/dL [p25-p75:107-135] vs 111 mg/dL [p25-p75: 100-125] (p =.005), respectively. In the flow cytometry assessment of peripheral blood lymphocyte subpopulations, PCC patients showed significantly increased CD8 populations compared to fully recovered patients: median CD8: 529 [p25-p75: 384-683] vs 370/mm3 [p25-p75:280-523], p =.007. When type 1, 2, 17/22, and 17.1 helper and follicular T lymphocyte subpopulations were analyzed, the frequency of Th1 was significantly higher in PCC patients compared to fully recovered patients (30% vs 38.5%, p =.028). CONCLUSION: Patients with a post-COVID-19 condition showed significantly increased immunological parameters of inflammation (complement factor C3 and CD8 and Th1 T lymphocyte populations) compared to fully recovered patients. These parameters could be used as biological markers of this condition.

Patterns and drivers of climatic niche dynamics during biological invasions of island-endemic amphibians, reptiles, and birds.

Shifts between native and alien climatic niches pose a major challenge for predicting biological invasions. This is particularly true for insular species because geophysical barriers could constrain the realization of their fundamental niches, which may lead to underestimates of their invasion potential. To investigate this idea, we estimated the frequency of shifts between native and alien climatic niches and the magnitude of climatic mismatches using 80,148 alien occurrences of 46 endemic insular amphibian, reptile, and bird species. Then, we assessed the influence of nine potential predictors on climatic mismatches across taxa, based on species' characteristics, native range physical characteristics, and alien range properties. We found that climatic mismatch is common during invasions of endemic insular birds and reptiles: 78.3% and 55.1% of their respective alien records occurred outside of the environmental space of species' native climatic niche. In comparison, climatic mismatch was evident for only 16.2% of the amphibian invasions analyzed. Several predictors significantly explained climatic mismatch, and these varied among taxonomic groups. For amphibians, only native range size was associated with climatic mismatch. For reptiles, the magnitude of climatic mismatch was higher for species with narrow native altitudinal ranges, occurring in topographically complex or less remote islands, as well as for species with larger distances between their native and alien ranges. For birds, climatic mismatch was significantly larger for invasions on continents with higher phylogenetic diversity of the recipient community, and when the invader was more evolutionarily distinct. Our findings highlight that apparently common niche shifts of insular species may jeopardize our ability to forecast their potential invasions using correlative methods based on climatic variables. Also, we show which factors provide additional insights on the actual invasion potential of insular endemic amphibians, reptiles, and birds.

Depression and anxiety in systemic lupus erythematosus: A case-control study on prevalence and associated factors in a single-center cohort.

OBJECTIVES: To evaluate the prevalence of self-perceived depression and anxiety in patients with systemic lupus erythematosus (SLE) and to explore associated factors. METHODS: Cross-sectional study of unselected patients with SLE (ACR-97 criteria) and controls with chronic inflammatory rheumatic diseases. Both completed the Hospital Anxiety and Depression Scale (HADS). Demographic and clinical characteristics, comorbidity, and treatments were collected, and a multivariate analysis was performed to explore factors associated with depression and anxiety in SLE. RESULTS: The study population comprised 172 patients and 215 controls. Women accounted for 93% of the patients with SLE. Fibromyalgia was recorded in 12.8% and a history of depression in 17%. According to HADS, 37.2% fulfilled the diagnostic criteria for depression and 58.7% those for anxiety; prevalence was similar in the controls (32.6% and 55.1%, respectively). Up to a third of patients with self-perceived depression were not receiving antidepressants. There was no concordance between a previous history of depression and current depression. In the multivariate model, current depression was associated with single marital status (OR 2.69; 95% CI: 1.17-6.42; p = .022), fibromyalgia (7.69; 2.35-30.72; p = .001), smoking (3.12; 1.24-8.07; p = .016), severity of SLE (0.76; 0.6-0.94; p = .016), and organ damage (1.27; 1.01-1.61; p = .042). Current anxiety was only associated with fibromyalgia (3.97; 1.21-17.98; p = .036). CONCLUSIONS: Depression and anxiety are most likely underdiagnosed in SLE. Prevalence appears to be similar to that of other chronic inflammatory rheumatic diseases. Anxiety is associated with fibromyalgia, while depression is also associated with single marital status, smoking, organ damage, and severity of SLE.

SLAMF1 is expressed and secreted by hepatocytes and the liver in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent forms of chronic liver disease in the United States and worldwide. Nonalcoholic steatohepatitis (NASH), the most advanced form of NAFLD, is characterized by hepatic steatosis associated with inflammation and hepatocyte death. No treatments are currently available for NASH other than lifestyle changes, and the disease lacks specific biomarkers. The signaling lymphocytic activation molecule family 1 (SLAMF1) protein is a self-ligand receptor that plays a role in orchestrating an immune response to some pathogens and cancers. We found that livers from humans and mice with NASH showed a more prominent immunohistochemistry staining for SLAMF1 than non-NASH controls. Furthermore, SLAMF1 levels are significantly increased in NASH plasma samples from mice and humans compared with their respective controls. In mice, the levels of SLAMF1 correlated significantly with the severity of the NASH phenotype. To test whether SLAMF 1 is expressed by hepatocytes, HepG2 cells and primary murine hepatocytes were treated with palmitic acid (PA) to induce a state of lipotoxicity mimicking NASH. We found that PA treatments of HepG2 cells and primary hepatocytes lead to significant increases in SLAMF1 levels. The downregulation of SLAMF1 in HepG2 cells improved the cell viability and reduced cytotoxicity. The in vivo data using mouse and human NASH samples suggests a potential role for this protein as a noninvasive biomarker for NASH. The in vitro data suggest a role for SLAMF1 as a potential therapeutic target to prevent hepatocyte death in response to lipotoxicity.NEW & NOTEWORTHY This study identified for the first time SLAMF1 as a mediator of hepatocyte death in nonalcoholic fatty liver disease (NASH) and as a marker of NASH in humans. There are no pharmacological treatments available for NASH, and diagnostic tools are limited to invasive liver biopsies. Therefore, since SLAMF1 levels correlate with disease progression and SLAMF1 mediates cytotoxic effects, this protein can be used as a therapeutic target and a clinical biomarker of NASH.

Prior Distribution and Entropy in Computer Adaptive Testing Ability Estimation through MAP or EAP.

To derive a latent trait (for instance ability) in a computer adaptive testing (CAT) framework, the obtained results from a model must have a direct relationship to the examinees' response to a set of items presented. The set of items is previously calibrated to decide which item to present to the examinee in the next evaluation question. Some useful models are more naturally based on conditional probability in order to involve previously obtained hits/misses. In this paper, we integrate an experimental part, obtaining the information related to the examinee's academic performance, with a theoretical contribution of maximum entropy. Some academic performance index functions are built to support the experimental part and then explain under what conditions one can use constrained prior distributions. Additionally, we highlight that heuristic prior distributions might not properly work in all likely cases, and when to use personalized prior distributions instead. Finally, the inclusion of the performance index functions, arising from current experimental studies and historical records, are integrated into a theoretical part based on entropy maximization and its relationship with a CAT process.

Amphibian Speciation Rates Support a General Role of Mountains as Biodiversity Pumps.

AbstractContinental mountain areas cover <15% of global land surface, yet these regions concentrate >80% of global terrestrial diversity. One prominent hypothesis to explain this pattern proposes that high mountain diversities could be explained by higher diversification rates in regions of high topographic complexity (HTC). While high speciation in mountains has been detected for particular clades and regions, the global extent to which lineages experience faster speciation in mountains remains unknown. Here we addressed this issue using amphibians as a model system (>7,000 species), and we found that families showing high speciation rates contain a high proportion of species distributed in mountains. Moreover, we found that lineages inhabiting areas of HTC speciate faster than lineages occupying areas that are topographically less complex. When comparing across regions, we identified the same pattern in five biogeographical realms where higher speciation rates are associated with higher levels of complex topography. Low-magnitude differences in speciation rates between some low and high complex topographies suggest that high mountain diversity is also affected by low extinction and/or high colonization rates. Nevertheless, our results bolster the importance of mountains as engines of speciation at different geographical scales and highlight their importance for the conservation of global biodiversity.

Idiosyncratic responses to drivers of genetic differentiation in the complex landscapes of Isthmian Central America.

Isthmian Central America (ICA) is one of the most biodiverse regions in the world, hosting an exceptionally high number of species per unit area. ICA was formed <25 million years ago and, consequently, its biotic assemblage is relatively young and derived from both colonization and in situ diversification. Despite intensive taxonomic work on the local fauna, the potential forces driving genetic divergences and ultimately speciation in ICA remain poorly studied. Here, we used a landscape genetics approach to test whether isolation by distance, topography, habitat suitability, or environment drive the genetic diversity of the regional frog assemblage. To this end, we combined data on landscape features and mitochondrial DNA sequence variation for nine codistributed amphibian species with disparate life histories. In five species, we found that at least one of the factors tested explained patterns of genetic divergence. However, rather than finding a general pattern, our results revealed idiosyncratic responses to historical and ecological processes, indicating that intrinsic life-history characteristics may determine the effect of different drivers of isolation on genetic divergence in ICA. Our work also suggests that the convergence of several factors promoting isolation among populations over a heterogeneous landscape might maximize genetic differentiation, despite short geographical distances. In conclusion, abiotic factors and geographical features have differentially affected the genetic diversity across the regional frog assemblage. Much more complex models (i.e., considering multiple drivers), beyond simple vicariance of Caribbean and Pacific lineages, are needed to better understand the evolutionary history of ICA's diverse biotas.

Pulmonary nodular lymphoid hyperplasia and Sjögren's syndrome: a case report and literature review.

Pulmonary nodular lymphoid hyperplasia, also known as pseudolymphoma, is an uncommon reactive lymphoproliferative disorder of unknown etiology that can be found in Sjögren's syndrome patients. Here, we present a case of a previously healthy woman in which the incidental finding of a lung mass compatible with nodular lymphoid hyperplasia led to the subsequent diagnosis of Sjögren's syndrome. We also performed a literature review for the association between both entities and described the main clinical aspects of the reported cases. Although its rarity, we consider that pulmonary nodular lymphoid hyperplasia should be considered in the differential diagnosis of lung nodules or masses among Sjögren's syndrome patients.

Predictive Immunological, Virological, and Routine Laboratory Markers for Critical COVID-19 on Admission.

BACKGROUND: Early identification of COVID-19 patients at risk of critical illness is a challenging endeavor for clinicians. We aimed to establish immunological, virological, and routine laboratory markers, which, in combination with clinical information, may allow identifying such patients. METHODS: Blood tests to measure neutrophil/lymphocyte ratio (NLR) and levels of ferritin, CRP, D-dimer, complement components (C3 and C4), cytokines, and lymphocyte subsets, as well as SARS-Cov-2 RT-PCR tests, were performed in COVID-19-confirmed cases within 48 hours of admission. RT-PCR cycle threshold (Ct) values from oropharyngeal or nasopharyngeal swabs were determined on the day of admission. Symptom severity was categorized as mild (grade 1), severe (grade 2), or critical (grade 3). RESULTS: Of 120 patients who were included, 49 had mild, 32 severe, and 39 critical COVID-19. Levels of ferritin >370 ng/mL (OR 16.4, 95% CI 5.3-50.8), D-dimer >440 ng/mL (OR 5.45, 95% CI 2.36-12.61), CRP >7.65 mg/dL (OR 11.54, 95% CI 4.3-30.8), NLR >3.77 (OR 13.4, 95% CI 4.3-41.1), IL-6 >142.5 pg/mL (OR 8.76, 95% CI 3.56-21.54), IL-10 >10.8 pg/mL (OR 16.45, 95% CI 5.32-50.81), sIL-2rα (sCD25) >804.5 pg/mL (OR 14.06, 95% CI 4.56-43.28), IL-1Ra >88.4 pg/mL (OR 4.54, 95% CI 2.03-10.17), and IL-18 >144 pg/mL (OR 17.85, 95% CI 6.54-48.78) were associated with critical COVID-19 in the univariate age-adjusted analysis. This association was confirmed in the multivariate age-adjusted analysis only for ferritin, CRP, NLR, IL-10, sIL-2rα, and IL-18. T, B, and NK cells were significantly decreased in critical patients. SARS-CoV-2 was not detected in blood except in 3 patients who had indeterminate results. RT-PCR Ct values from oropharyngeal or nasopharyngeal swabs on admission were not related to symptom severity. CONCLUSION: Ferritin, D-dimer, CRP, NLR, cytokine (IL-18 and IL-10), and cytokine receptor (IL-6, IL1-Ra, and sCD25) test results combined with clinical data can contribute to the early identification of critical COVID-19 patients.

Walking Recognition in Mobile Devices.

Presently, smartphones are used more and more for purposes that have nothing to do withphone calls or simple data transfers. One example is the recognition of human activity, which isrelevant information for many applications in the domains of medical diagnosis, elderly assistance,indoor localization, and navigation. The information captured by the inertial sensors of the phone(accelerometer, gyroscope, and magnetometer) can be analyzed to determine the activity performedby the person who is carrying the device, in particular in the activity of walking. Nevertheless,the development of a standalone application able to detect the walking activity starting only fromthe data provided by these inertial sensors is a complex task. This complexity lies in the hardwaredisparity, noise on data, and mostly the many movements that the smartphone can experience andwhich have nothing to do with the physical displacement of the owner. In this work, we exploreand compare several approaches for identifying the walking activity. We categorize them into twomain groups: the first one uses features extracted from the inertial data, whereas the second oneanalyzes the characteristic shape of the time series made up of the sensors readings. Due to the lackof public datasets of inertial data from smartphones for the recognition of human activity underno constraints, we collected data from 77 different people who were not connected to this research.Using this dataset, which we published online, we performed an extensive experimental validationand comparison of our proposals.

Urinary phytate concentration and risk of fracture determined by the FRAX index in a group of postmenopausal women

Background/aim: This study was designed to evaluate the relationship between urinary phytate concentration and risk of fracture at 10 years, determined by using the FRAX model, in women who had undergone menopause within 5 years of the time of enrollment. Materials and methods: Of the 212 postmenopausal women evaluated, 69 were excluded because they had urinary phytate concentrations between 0.51 and 0.99 mg/L. Of the remaining 143 women, 91 had low (≤0.50 mg/L) and 52 had high (≥1.0 mg/L) urinary phytate concentrations. The 10-year risk of fracture was calculated by using the FRAX model. Results: The risks of major osteoporotic fracture and hip fracture were higher in women with low urinary phytate levels (P < 0.001 in both cases). Evaluation of the risk of hip fracture in women with and without risk factors for osteoporosis (e.g., tobacco, alcohol, and drug consumption) and according to urinary phytate concentrations indicated that, among women with no risk factors, those with low and high urinary phytate levels had a range of risks of 0%­0.6% and 0%­0.3%, respectively (P = 0.098). Moreover, among women with at least one risk factor, those with low and high urinary phytate had a range of risks of 0.1%­0.8% and 0.1%­0.4%, respectively (P = 0.002). Similar results were observed when the risks of major osteoporotic fracture were analyzed. Conclusion: These results indicate the relationship of phytate with the risks of major osteoporotic fracture and hip fracture, with these differences being more marked in women with risk factors for osteoporosis. From this study follows the importance of the consumption of phytate-rich products (nuts, legumes, whole cereals) to protect against the risk of fracture in 10 years, mainly in women with risk factors for osteoporosis.

Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD.

OBJECTIVE: Bile acids are regulators of lipid and glucose metabolism, and modulate inflammation in the liver and other tissues. Primary bile acids such as cholic acid and chenodeoxycholic acid (CDCA) are produced in the liver, and converted into secondary bile acids such as deoxycholic acid (DCA) and lithocholic acid by gut microbiota. Here we investigated the possible roles of bile acids in non-alcoholic fatty liver disease (NAFLD) pathogenesis and the impact of the gut microbiome on bile acid signalling in NAFLD. DESIGN: Serum bile acid levels and fibroblast growth factor 19 (FGF19), liver gene expression profiles and gut microbiome compositions were determined in patients with NAFLD, high-fat diet-fed rats and their controls. RESULTS: Serum concentrations of primary and secondary bile acids were increased in patients with NAFLD. In per cent, the farnesoid X receptor (FXR) antagonistic DCA was increased, while the agonistic CDCA was decreased in NAFLD. Increased mRNA expression for cytochrome P450 7A1, Na+-taurocholate cotransporting polypeptide and paraoxonase 1, no change in mRNA expression for small heterodimer partner and bile salt export pump, and reduced serum FGF19 were evidence of impaired FXR and fibroblast growth factor receptor 4 (FGFR4)-mediated signalling in NAFLD. Taurine and glycine metabolising bacteria were increased in the gut of patients with NAFLD, reflecting increased secondary bile acid production. Similar changes in liver gene expression and the gut microbiome were observed in high-fat diet-fed rats. CONCLUSIONS: The serum bile acid profile, the hepatic gene expression pattern and the gut microbiome composition consistently support an elevated bile acid production in NAFLD. The increased proportion of FXR antagonistic bile acid explains, at least in part, the suppression of hepatic FXR-mediated and FGFR4-mediated signalling. Our study suggests that future NAFLD intervention may target the components of FXR signalling, including the bile acid converting gut microbiome.

Poor Agreement Between Imaging and Histologic and Colonoscopy Findings in Pediatric Patients.

BACKGROUND: Computed tomography scans (CTs), more recently magnetic resonance imaging, are often used to assess the gastrointestinal tract in patients complaining of abdominal pain. We aim to determine the strength of agreement among abdominal imaging, endoscopic, and histologic findings. METHODS: Retrospective chart review of pediatric patients who underwent colonoscopy between January 1, 2012, and December 31, 2014, at Women and Children's Hospital of Buffalo. Patients who had abdominal and pelvic CTs or magnetic resonance imaging within 30 days before or after a colonoscopy were included. RESULTS: One hundred two patients were included: mean age 12.7 ±â€Š3.8 years, 66% girls. A total of 109 imaging studies were performed. Overall 61% of imaging studies were abnormal. The most frequent intestinal radiological findings were colonic wall thickening (CWT) (55%) and colonic wall enhancement (CWH) (24%). Free fluid (20%) and fat stranding (18%) were the most common extra-intestinal findings. Imaging studies agreed with histology in 81% and with colonoscopy in 75% with a moderate strength of agreement (k: 0.59 and 0.466, respectively). CWT agreed with histology in 74% with a moderate strength of agreement (k: 0.47). History of weight loss (OR 5.35, P = 0.041), chronic diarrhea (OR 4.22, P = 0.014), a positive lactoferrin (OR 7.00, P = 0.011), and presence of CWT on imaging study (OR 5.20, P = 0.001) were predictive of having abnormal histology. CONCLUSIONS: The strength of agreement among imaging, endoscopic, and histologic findings was suboptimal. Colonoscopy and imaging are both likely to be necessary in patients with suspected inflammatory bowel disease. Although colonoscopy may be superior in diagnosis of colitis, imaging may provide more information regarding small bowel disease.

Effect of sample time on urinary lithogenic risk indexes in healthy and stone-forming adults and children.

BACKGROUND: The diagnosis and follow-up of stone forming patients is usually performed by analysis of 24-h urine samples. However, crystallization risk varies throughout the day, being higher at night. The main objective of this study is to evaluate the urinary crystallization risk in adults and children by calculating risk indexes based on different collection periods. METHODS: The study included 149 adults (82 healthy and 67 stone-formers) and 108 children (87 healthy and 21 stone-formers). 24-h urine was collected, divided into 12-h daytime sample (8 am to 8 pm), and 12-h overnight sample (8 pm to 8 am next morning). Solute concentrations, the calcium to citrate ratio (Ca/Cit), and the ion activity product of calcium oxalate (AP[CaOx]) and calcium phosphate (AP[CaP]) were calculated in each 12-h sample and in overall 24-h urine. Assessments were also related to stone type. RESULTS: Ca/Cit and AP(CaOx) were significantly higher in stone forming patients than in healthy subjects. The 12-h overnight samples had the highest values for both risk indexes, confirming a greater risk for crystallization at night. The AP(CaP) index was significantly higher in patients with pure hydroxyapatite stones than healthy controls, but was not significantly different between stone-formers overall and healthy controls. CONCLUSIONS: The calculation of risk indexes is a simple method that clinicians can use to estimate crystallization risk. For this purpose, the use of 12-h overnight urine may be a reliable alternative to 24-h collections.

The Use of Fecal Calprotectin Levels in the Fontan population.

The Fontan procedure was first performed in the seventies as a palliation for patients with single ventricle physiology. A feared complication after a Fontan procedure is the development of protein losing enteropathy (PLE). Systemic inflammation has a negative effect on the intestinal barrier integrity, which has supported the use of steroids in this setting. To the best of our knowledge there are no studies linking intestinal inflammation in patients with PLE after Fontan. The objective of this study was to identify the presence of intestinal inflammation measured by FC in patients with PLE after a Fontan procedure. A cross-sectional analysis was performed examining 23 stool samples from 23 Fontan patients for both Fecal alpha-1-antitrypsin (FA1AT) and FC with and without PLE. The median FC was 21 mcg/gm of stool (IQR: 15.7-241 mcg/gm of stool), and the median FA1AT was 40 mg/dL (IQR: 30-220 mg/dL). The median FC and FA1AT were significantly higher in the PLE group than in the Non-PLE group (p = 0.002 and p < 0.0001, respectively). Significantly elevated levels of FC were demonstrated in Fontan patients with PLE, which correlated with the elevated levels of FA1AT. Inversely, levels of FC in Fontan patients without suspected PLE were within the normal range. To our knowledge, this is the first study to demonstrate intestinal inflammation using FC in the setting of PLE within this cohort, and may prove to be useful as a diagnostic tool in its treatment.

Biomachining: metal etching via microorganisms.

The use of microorganisms to remove metal from a workpiece is known as biological machining or biomachining, and it has gained in both importance and scientific relevance over the past decade. Conversely to mechanical methods, the use of readily available microorganisms is low-energy consuming, and no thermal damage is caused during biomachining. The performance of this sustainable process is assessed by the material removal rate, and certain parameters have to be controlled for manufacturing the machined part with the desired surface finish. Although the variety of microorganisms is scarce, cell concentration or density plays an important role in the process. There is a need to control the temperature to maintain microorganism activity at its optimum, and a suitable shaking rate provides an efficient contact between the workpiece and the biological medium. The system's tolerance to the sharp changes in pH is quite limited, and in many cases, an acid medium has to be maintained for effective performance. This process is highly dependent on the type of metal being removed. Consequently, the operating parameters need to be determined on a case-by-case basis. The biomachining time is another variable with a direct impact on the removal rate. This biological technique can be used for machining simple and complex shapes, such as series of linear, circular, and square micropatterns on different metal surfaces. The optimal biomachining process should be fast enough to ensure high production, a smooth and homogenous surface finish and, in sum, a high-quality piece. As a result of the high global demand for micro-components, biomachining provides an effective and sustainable alternative. However, its industrial-scale implementation is still pending.

Efficacy of Mixtures of Magnesium, Citrate and Phytate as Calcium Oxalate Crystallization Inhibitors in Urine.

PURPOSE: The main aim of the current study was to evaluate the effectiveness of mixtures of magnesium, citrate and phytate as calcium oxalate crystallization inhibitors. MATERIALS AND METHODS: A turbidimetric assay in synthetic urine was performed to obtain induction times for calcium oxalate crystallization in the absence and presence of different mixtures of inhibitors. The morphology of calcium oxalate crystals in the absence or presence of inhibitors and mixtures of the inhibitors was evaluated in 2 crystallization experiments at low and high calcium oxalate supersaturation. The crystals formed were examined using scanning electron microscopy. RESULTS: Examination of crystallization induction times revealed clear inhibitory effects of magnesium, citrate and phytate on calcium oxalate crystallization, supporting usefulness in the treatment and prevention of calcium oxalate nephrolithiasis. Significant synergistic effects between magnesium and phytate were observed. Scanning electron microscopy images revealed that phytate is a powerful crystal growth inhibitor of calcium oxalate, totally preventing the formation of trihydrate and monohydrate. In addition to crystallization inhibition capacity, citrate and magnesium avoided calcium oxalate crystallization by decreasing its supersaturation. CONCLUSIONS: The synergistic effect between magnesium and phytate on calcium oxalate crystallization suggests that a combination of these 2 compounds may be highly useful as antilithiasis therapy.