Neuroendocrine hyperplasia of infancy; a rare form of childhood interstitial lung disease: a case report.

Interstitial lung disease in infancy is rare. In this case report, we discuss the case of a six-week-old male infant who presented with persistent tachypnoea, retraction and mild hypoxaemia corrected by low-dose supplemental oxygen since the age of 2 weeks. Birth history was unremarkable. Routine workup was done which turned out to be non-contributory. The child received multiple rounds of antibiotics along with bronchodilators and corticosteroids. There was no evidence of severe gastroesophageal reflux. Computed tomography of chest showed ground glass appearance, which was especially prominent in the right middle lobe and lingula ,and accompanied with air trapping. He was managed with mild respiratory supportive care, without positive pressure ventilation and nutritional management. He was discharged home, with instructions for in clinic follow up. A distinctive topographical picture and typical clinical symptoms were consistent with neuroendocrine hyperplasia of infancy (NEHI), which has a favourable prognosis. A high index of suspicion may enable a timely diagnosis. Adequate long-term respiratory and nutritional management without lung biopsy improves the outcome.

Toward Precision Phenotyping of Multiple Sclerosis.

The classification of multiple sclerosis (MS) has been established by Lublin in 1996 and revised in 2013. The revision includes clinically isolated syndrome, relapsing-remitting, primary progressive and secondary progressive MS, and has added activity (i.e., formation of white matter lesions or clinical relapses) as a qualifier. This allows for the distinction between active and nonactive progression, which has been shown to be of clinical importance. We propose that a logical extension of this classification is the incorporation of additional key pathological processes, such as chronic perilesional inflammation, neuroaxonal degeneration, and remyelination. This will distinguish MS phenotypes that may present as clinically identical but are driven by different combinations of pathological processes. A more precise description of MS phenotypes will improve prognostication and personalized care as well as clinical trial design. Thus, our proposal provides an expanded framework for conceptualizing MS and for guiding development of biomarkers for monitoring activity along the main pathological axes in MS.

Association of redox and inflammation-related biomarkers with prognosis in IgA nephropathy: A prospective observational study.

BACKGROUND: IgA nephropathy (IGAN) has a variable prognosis. Risk stratification tools are usually based on clinical parameters combined with histologic Oxford-MEST-C score. Circulating redox- and inflammation-related biomarkers may be related to histological changes in IGAN. Therefore, we studied the performance of these biomarkers in predicting the rate of GFR-loss in IGAN. METHODS: This was an observational prospective study. Fifty-seven stable patients with IGAN were examined at baseline and after a mean observational time of 5.9 ± 1.1 years. The main outcome measure was eGFR-loss per year with predefined groups, stable (<1.5 ml/min/1,73 m2/year, intermediate (between 1.5 and 2.5), and progressive (>2.5). RESULTS: Fifteen patients were in the progressive, 11 in the intermediate, and 31 in the stable groups. Positive relationships were detected between eGFR-loss per year and baseline nitrate, oxidized free cysteine, parathyroid hormone, APRIL, TNFR1, CD30, chitinase 3, and LIF-5. The progressive group had elevated concentrations of these markers plus AOPP and osteopontin. Through ROC analysis, it was observed that AOPP, oxidized free cysteine, TNFR1, osteopontin, and LIF-5 had the best ability to identify progressive vs. non-progressive diseases. The combination of urinary albumin/creatinine ratio with AOPP and TNFR1 significantly improved the ability to identify progressive eGFR decline with ROC AUC 95% (adjusted 85%). CONCLUSIONS: We found prognostic biomarkers related to the rate of eGFR-loss in IGAN. These biomarkers may help identify patients at risk of progressive disease. AOPP, oxidized free cysteine, TNFR1, and osteopontin are promising prognostic biomarkers in IGAN, however, further validation studies are needed.

History and metrology applications of a game-changing technology: digital holography [Invited].

In digital holography (DH), information in the hologram is recorded and stored in digital format in discrete bits. Like its parent, holography, DH evolved over many years with periods of dormancy and revival. Almost abandoned, multiple times, unanticipated events or developments in separate industries revived it with explosive, quantum jumps, making it useful and popular to a wide audience. Although its history has been treated in many papers and books, the field is dynamic and constantly providing new opportunities. Having been born long before low-cost, fast, powerful digital computers and digital detectors were available, DH was confined to the academic world, where practical applications and commercial opportunities were few if any. Consumer demand that led to low-cost personal computers, high-resolution digital cameras, supporting software, and related products changed the situation drastically by providing every potential researcher affordable, powerful hardware and software needed to apply image processing algorithms and move DH to new practical application levels. In this paper, as part of the sixtieth anniversary of off-axis holography, we include a brief introduction to the fundamentals of DH and examine the history and evolution of DH during its periods of rise and fall. We summarize many new emerging techniques, applications, and potential future applications along with additional details for metrological examples from the authors' research.

National identity predicts public health support during a global pandemic.

Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = -0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.

Astrocyte Heterogeneity in Multiple Sclerosis: Current Understanding and Technical Challenges.

The emergence of single cell technologies provides the opportunity to characterize complex immune/central nervous system cell assemblies in multiple sclerosis (MS) and to study their cell population structures, network activation and dynamics at unprecedented depths. In this review, we summarize the current knowledge of astrocyte subpopulations in MS tissue and discuss the challenges associated with resolving astrocyte heterogeneity with single-nucleus RNA-sequencing (snRNA-seq). We further discuss multiplexed imaging techniques as tools for defining population clusters within a spatial context. Finally, we will provide an outlook on how these technologies may aid in answering unresolved questions in MS, such as the glial phenotypes that drive MS progression and/or neuropathological differences between different clinical MS subtypes.

Circulating inflammation-related factors are correlated with systemic redox status in IgA nephropathy; a case-control study.

BACKGROUND: IgA nephropathy (IGAN) is characterized by oxidative stress and inflammation. In the present study, we explored the relationship of redox status vs. that of circulating inflammation-related factors with other biomarkers in patients with IGAN. METHODS: This is a case-control study comparing patients with IGAN (Stage 1-4) to healthy controls. Forty patients and 40 controls were matched for age and sex. Two circulating dynamic redox parameters were analysed: oxidized free cysteine (Cys) and nitrate. Thirty-seven inflammation-related factors were measured in serum. RESULTS: The patients had elevated levels of oxidized free Cys and nitrate, indicating the presence of oxidative stress. Nine circulating inflammation-related factors were higher in the serum of patients than in that of controls. The most important factors were APRIL, MMP-3, osteopontin, TNFR1 and TWEAK. Inflammation-related factors were positively correlated with oxidized free Cys, nitrate, creatinine and parathyroid hormone (PTH) in the patients. The correlation coefficients of Latent Inflammatory Factor vs. oxidized free Cys and nitrate were r = 0.43 (p = 0.007) and r = 0.51 (p = 0.001), respectively. This finding persisted after adjusting for the glomerular filtration rate. CONCLUSIONS: Patients with IGAN had disturbed redox status. Several circulating inflammation-related factors were elevated, suggesting activation of the non-canonical NF-kB pathway. There was a positive relationship between systemic redox status and the level of inflammation-related factors, partially independent of GFR. The present findings raise the question of whether circulating oxidized free Cys and/or nitrate may be employed as prognostic biomarkers for IGAN in the future.

KLF1/EKLF expression in acute leukemia is correlated with chromosomal abnormalities.

KLF1 (EKLF) is a master regulator of erythropoiesis and controls expression of a wide array of target genes. We interrogated human tissue microarray samples via immunohistological analysis to address whether levels of KLF1 protein are associated with leukemia. We have made the unexpected findings that higher KLF1 levels are correlated with cells containing abnormal chromosomes, and that high KLF1 expression is not limited to acute myeloid leukemia (AML) associated with erythroid/megakaryoblastic differentiation. Expression of KLF1 is associated with poor survival. Further analyses reveal that KLF1 directly regulates a number of genes that play a role in chromosomal integrity. Together these results suggest that monitoring KLF1 levels may provide a new marker for risk stratification and prognosis in patients with AML.

Prosthetic rehabilitation with fixed prosthesis of a 5-year-old child with Hypohidrotic Ectodermal Dysplasia and Oligodontia: a case report.

BACKGROUND: Ectodermal dysplasia is a rare genetic disorder that affects ectodermally derived structures, including teeth, nails, hair, and sweat glands. Hypohidrotic ectodermal dysplasia is the most common type, with oligodontia being the most striking dental feature. Prosthetic rehabilitation in children with ectodermal dysplasia is an important step toward improving their overall quality of life. The fixed prosthesis has the advantages of being more stable in the mouth with good child compliance and a good aesthetic outcome. CASE PRESENTATION: Our patient was a 5-year-old Middle Eastern boy with oligodontia caused by ectodermal dysplasia. He was managed by fabrication of an upper functional space maintainer and a lower fixed partial denture to restore occlusion, masticatory function, aesthetics, and overall quality of life. CONCLUSIONS: The use of the fixed prosthesis in children is a new and evolving treatment modality that resolves many of the issues caused by removable prostheses. It accommodates jaw growth in the mandible, reduces the need to remake the prosthesis, and has an overall better aesthetic outcome.

Water entry impact dynamics of diving birds.

Some seabirds (such as northern gannets and brown boobies) can dive from heights as high as 30 m reaching speeds of up to 24 m s-1 as they impact the water surface. The physical geometry of plunge diving birds, particularly of the beak, allows them to limit high impact forces compared to non-diving birds. Numerically simulated data for one species (northern gannet) provides some insight into the impact forces experienced during diving, however, no reliable experimental data with real bird geometries exist for comparison purposes. This study utilizes eleven 3D printed diving bird models of three types of birds: plunge-diving (five), surface-diving (five) and dipper (one), with embedded accelerometers to measure water-entry impact accelerations for impact velocities ranging between 4.4-23.2 m s-1. Impact forces for all bird types are found to be comparable under similar impact conditions and well within the safe zone characterized by neck strength as found in recent studies. However, the time that each bird requires to reach maximum impact acceleration from impact is different based on its beak and head shape and so is its effect, represented here by its derivative (i.e. jerk). We show that surface diving birds have high non-dimensional jerk, which exceed a safe limit estimated from human impact analysis, whereas those by plunge divers do not.

An Expanded Synthetic Biology Toolkit for Gene Expression Control in Acetobacteraceae.

The availability of different host chassis will greatly expand the range of applications in synthetic biology. Members of the Acetobacteraceae family of Gram-negative bacteria form an attractive class of nonmodel microorganisms that can be exploited to produce industrial chemicals, food and beverage, and biomaterials. One such biomaterial is bacterial cellulose, which is a strong and ultrapure natural polymer used in tissue engineering scaffolds, wound dressings, electronics, food additives, and other products. However, despite the potential of Acetobacteraceae in biotechnology, there has been considerably little effort to fundamentally reprogram the bacteria for enhanced performance. One limiting factor is the lack of a well-characterized, comprehensive toolkit to control expression of genes in biosynthetic pathways and regulatory networks to optimize production and cell viability. Here, we address this shortcoming by building an expanded genetic toolkit for synthetic biology applications in Acetobacteraceae. We characterized the performance of multiple natural and synthetic promoters, ribosome binding sites, terminators, and degradation tags in three different strains, namely, Gluconacetobacter xylinus ATCC 700178, Gluconacetobacter hansenii ATCC 53582, and Komagataeibacter rhaeticus iGEM. Our quantitative data revealed strain-specific and common design rules for the precise control of gene expression in these industrially relevant bacterial species. We further applied our tools to synthesize a biodegradable cellulose-chitin copolymer, adjust the structure of the cellulose film produced, and implement CRISPR interference for ready down-regulation of gene expression. Collectively, our genetic parts will enable the efficient engineering of Acetobacteraceae bacteria for the biomanufacturing of cellulose-based materials and other commercially valuable products.

Systemic redox biomarkers and their relationship to prognostic risk markers in autosomal dominant polycystic kidney disease and IgA nephropathy.

BACKGROUND: Oxidative stress is evident from an early stage in chronic kidney disease (CKD). Therefore, we investigated redox biomarkers in polycystic kidney disease (ADPKD) and IgA nephropathy (IGAN). METHODS: This is a case-control study with three groups: ADPKD (n = 54), IGAN (n = 58) and healthy controls (n = 86). The major plasma aminothiols with their redox species were examined: homocysteine (Hcy), cysteinglycine (CG), cysteine (Cys) and glutathione (GSH). The redox ratio was the ratio of reduced free and oxidized aminothiols in plasma. We investigated malonedialdehyde (MDA) and advanced oxidation protein products (AOPP), and ten single nucleotide polymorphisms of antioxidant enzymes. RESULTS: Patients had elevated oxidized free Hcy and Cys with associated low redox ratios - most pronounced in IGAN. Patients with IGAN had elevated AOPP and possibly MDA. Oxidized free Hcy and Cys with redox ratios were correlated to AOPP, MDA and proteinuria. Furthermore, there was an independent relationship to parathyroid hormone (PTH). IGAN had an elevated frequency of Val16Ala SNP rs4880, which influence the function of mitochondrial superoxide dismutase 2 (p = 0.03). CONCLUSIONS: Patients with ADPKD and IGAN have evidence of oxidative stress from stage 1 to 4 - most pronounced in IGAN. In patients, aminothiol redox biomarkers were correlated to AOPP, proteinuria and PTH, which are known prognostic markers in CKD. It may be possible that oxidative stress influences PTH dysregulation in CKD. The association between IGAN and the redox related variant allele rs4880(C) might indicate a new susceptibility locus for IGAN, but this needs verification.

Self-determined shapes and velocities of giant near-zero drag gas cavities.

Minimizing the retarding force on a solid moving in liquid is the canonical problem in the quest for energy saving by friction and drag reduction. For an ideal object that cannot sustain any shear stress on its surface, theory predicts that drag force will fall to zero as its speed becomes large. However, experimental verification of this prediction has been challenging. We report the construction of a class of self-determined streamlined structures with this free-slip surface, made up of a teardrop-shaped giant gas cavity that completely encloses a metal sphere. This stable gas cavity is formed around the sphere as it plunges at a sufficiently high speed into the liquid in a deep tank, provided that the sphere is either heated initially to above the Leidenfrost temperature of the liquid or rendered superhydrophobic in water at room temperature. These sphere-in-cavity structures have residual drag coefficients that are typically less than [Formula: see text] those of solid objects of the same dimensions, which indicates that they experienced very small drag forces. The self-determined shapes of the gas cavities are shown to be consistent with the Bernoulli equation of potential flow applied on the cavity surface. The cavity fall velocity is not arbitrary but is uniquely predicted by the sphere density and cavity volume, so larger cavities have higher characteristic velocities.

In vivo effect of N-ethylmaleimide (NEM) on the measurement of nitrate in plasma.

BACKGROUND: Bioavailability of nitric oxide in the body may be estimated by measuring the concentration of nitrate in plasma. However, it has not been reported whether sequestering of aminothiols in plasma affects the concentration of nitrate in the samples. OBJECTIVE: N-ethylmaleimide (NEM) sequesters aminothiols in plasma therefore we tested the in vivo effect of NEM on the concentration nitrate in plasma. SUBJECTS AND METHODS: Blood samples were collected from 56 healthy subjects in EDTA vials, EDTA vials containing PBS (pH7.4) and EDTA vials containing NEM dissolved in PBS. Nonparametric statistical tests were used to study the effect of NEM on the concentration of nitrate in plasma measured by the Griess reagent assay and by an HPLC method. RESULTS: The concentration of nitrate in plasma containing NEM dissolved in PBS was lower than plasma containing PBS and plasma without any reagent measured by the Griess reagent assay (p<0.001 and p<0.001). Similarly, the concentration of nitrate in plasma containing NEM measured by the Griess reagent assay was significantly lower than nitrate concentration in plasma measured by the HPLC method (p<0.001). CONCLUSION: Our findings suggest that plasma, which contains NEM, may not be suitable for the measurement of nitrate by the Griess reagent assay.

Francisella philomiragia Infection and Lethality in Mammalian Tissue Culture Cell Models, Galleria mellonella, and BALB/c Mice.

Francisella (F.) philomiragia is a Gram-negative bacterium with a preference for brackish environments that has been implicated in causing bacterial infections in near-drowning victims. The purpose of this study was to characterize the ability of F. philomiragia to infect cultured mammalian cells, a commonly used invertebrate model, and, finally, to characterize the ability of F. philomiragia to infect BALB/c mice via the pulmonary (intranasal) route of infection. This study shows that F. philomiragia infects J774A.1 murine macrophage cells, HepG2 cells and A549 human Type II alveolar epithelial cells. However, replication rates vary depending on strain at 24 h. F. philomiragia infection after 24 h was found to be cytotoxic in human U937 macrophage-like cells and J774A.1 cells. This is in contrast to the findings that F. philomiragia was non-cytotoxic to human hepatocellular carcinoma cells, HepG2 cells and A549 cells. Differential cytotoxicity is a point for further study. Here, it was demonstrated that F. philomiragia grown in host-adapted conditions (BHI, pH 6.8) is sensitive to levofloxacin but shows increased resistance to the human cathelicidin LL-37 and murine cathelicidin mCRAMP when compared to related the Francisella species, F. tularensis subsp. novicida and F. tularensis subsp. LVS. Previous findings that LL-37 is strongly upregulated in A549 cells following F. tularensis subsp. novicida infection suggest that the level of antimicrobial peptide expression is not sufficient in cells to eradicate the intracellular bacteria. Finally, this study demonstrates that F. philomiragia is lethal in two in vivo models; Galleria mellonella via hemocoel injection, with a LD50 of 1.8 × 10(3), and BALB/c mice by intranasal infection, with a LD50 of 3.45 × 10(3). In conclusion, F. philomiragia may be a useful model organism to study the genus Francisella, particularly for those researchers with interest in studying microbial ecology or environmental strains of Francisella. Additionally, the Biosafety level 2 status of F. philomiragia makes it an attractive model for virulence and pathogenesis studies.

Effect of Omega-3 and Vitamins E + C Supplements on the Concentration of Serum B-Vitamins and Plasma Redox Aminothiol Antioxidant Status in Elderly Men after Strength Training for Three Months.

BACKGROUND: Data on redox plasma aminothiol status in individuals on strength training are very limited. Therefore, we studied the effect of omega-3 and vitamins E + C supplementation on the concentration of B-vitamins and redox aminothiol status in elderly men after strength training for 3 months. METHODS: Healthy men, age 60 ± 6 (mean ± SD) were randomly divided into 3 groups: group I received placebo (n = 17), group II consumed omega-3 (700 mg, n = 17), and group III consumed vitamins E + C (235 mg +1 g, n = 16) daily for 3 months. All participants completed a strength training program for the same period. RESULTS: The concentration of serum vitamin B12 decreased and the concentration of serum folate increased in group I after the intervention (p = 0.01, p = 0.009). The concentration of plasma 5-pyridoxal phosphate decreased in groups II and III (p = 0.03 and p = 0.01), whereas the concentration of serum uric acid decreased only in group II (p = 0.02). We detected an increase in the concentration of reduced form of aminothiols in all groups (p < 0.001). The red/ox plasma aminothiol status was significantly changed in all groups after the intervention (p < 0.05). CONCLUSION: Omega-3 and vitamins E + C supplementation affect the concentrations of serum B-vitamins and redox plasma aminothiol status in healthy elderly men on strength training.

Kidney donors and kidney transplants have abnormal aminothiol redox status, and are at increased risk of oxidative stress and reduced redox buffer capacity.

OBJECTIVE: Living kidney donors have been part of a successful kidney transplant programme in Norway for almost 50 years. Glomerular filtration rates (GFRs) have tended to remain stable at about 70% of pre-donation levels. Plasma total homocysteine (Hcy) has an inverse relationship to kidney function, and previous reports indicate elevated levels of Hcy in kidney donors. We wanted to examine the most important plasma aminothiols in kidney donors, i.e. Hcy, cysteine (Cys) and cysteinylglycine (CG) with their redox species. The aminothiol redox-system appears to be an integral part of the extracellular antioxidant defence system in the body. DESIGN AND METHODS: Plasma concentrations of total Hcy were obtained in 82 previous kidney donors, 82 healthy controls and 26 kidney transplants with stable and good kidney function. In a subset of 30 kidney donors, 30 matched controls and 12 kidney transplants plasma samples were analysed for Hcy, Cys, CG and their redox species. There were no differences between groups for B-vitamin status. RESULTS: Kidney donors and kidney transplants had elevated plasma concentrations of total Hcy, Cys and CG. The plasma levels of reduced Hcy species were high - with a high reduced/oxidized ratio. The plasma levels of reduced Cys species were low - with a low reduced/oxidized ratio. CONCLUSIONS: Previous kidney donors have abnormal plasma aminothiol redox status. The present findings indicate that donors may have increased risk of oxidative stress with low redox buffer capacity and disturbed cellular redox-dependent signalling pathways. Similar observations were made in the kidney transplants.

Eating patterns are associated with biomarkers in a selected population of university students and employees.

The association between diet and CVD cannot be assigned to a single nutrient, but rather to a set of nutrients and non-nutrients, and eating pattern analyses have become an important tool in investigation of this relationship. Our objective was to investigate eating patterns in relation to nutrient intake and serum concentration of folate, vitamin B12 and TAG in ninety-five healthy adult participants. Dietary information was collected by an FFQ, and eating patterns were obtained by principal components analyses of thirty-three food groups. Three eating patterns were extracted, a sweet eating pattern identified by intakes of cakes, snacks, sugar-sweetened drinks and chocolates; a prudent eating pattern identified by vegetables, fruits and olive oil; and a traditional food pattern identified by red meat, lean fish and cheese. Blood samples were collected in the morning after an overnight fast. Linear regression analyses adjusted for age, BMI and smoking showed a negative association between the sweet eating pattern scores and the serum concentration of folate (ß = -2·31 (95 % CI -4·14, -0·45)) and a positive association with serum concentration of TAG (ß = 0·35 (95 % CI 0·12, 0·57)). The prudent eating pattern scores were positively associated with the serum concentration of folate (ß = 1·69 (95 % CI 0·44, 2·92)). In conclusion, a sweet eating pattern was associated with risk factors for CVD, whereas a prudent eating pattern was associated with protective factors.

Serum folate is significantly correlated with plasma cysteine concentrations in healthy industry workers.

BACKGROUND: A low concentration of serum folate is associated with an increased risk of cardiovascular disease. Extracellular cysteine is involved in aging, cancer and cardiovascular disease. The relationship between serum folate and plasma cysteine is poorly understood. Therefore, we investigated this relationship in industry workers, whose health has economic implications. METHODS: The concentration of serum folate was determined by the Access ImmunoAssay System Sanofi Pasteur. Plasma cysteine and homocysteine were measured by an ion-pair HPLC method. The concentrations of serum triglycerides were determined by an enzymatic colorimetric method. RESULTS: We detected a positive correlation between the concentration of serum folate and plasma cysteine, whereas the concentration of serum folate was negatively correlated with plasma homocysteine and serum triglycerides. In a multiple regression analysis with adjustment for age, BMI and smoking, serum folate as the dependent variable exhibited a strong relationship with plasma cysteine, and a negative relationship with plasma homocysteine and serum triglycerides. CONCLUSION: We observed significant correlations between serum folate, plasma cysteine and serum triglyceride concentrations in industry workers, implying that folate may modulate key aspects of the body's cysteine and lipid metabolism.