Steven Poser
Jun 1, 2003; 23:4420-4427
Cellular

Atherosclerotic cardiovascular diseases have roots in childhood. Modification of dietary fat intake influences serum lipid and lipoprotein concentrations. Reduction of saturated fat intake is recommended to promote cardiovascular health.

Dietary counseling had a beneficial effect on saturated fat intake from ages 7 months to 19 years. The counseling reduced serum low-density lipoprotein cholesterol concentrations in both genders. It also decreased computationally estimated concentrations of intermediate-density lipoprotein cholesterol, very low-density lipoprotein–triglycerides and apolipoprotein B in boys. (Read the full article)

Vitamin D levels in the general population have decreased considerably over the past decade. The implications of maternal vitamin D insufficiency during pregnancy for offspring neurocognitive development remain unclear.

Studying a large sample and using a prospective longitudinal design, this study demonstrates a link between maternal vitamin D insufficiency during pregnancy and offspring language impairment. There was no association with childhood behavioral or emotional problems. (Read the full article)

Neonatal hyperbilirubinemia may progress to bilirubin encephalopathy. Findings from previous studies on long-term development of neonatal hyperbilirubinemia are conflicting.

Using Ages and Stages Questionnaire, we observed no association between bilirubin exposure and overall development in 1- to 5-year-old children who in the neonatal period had total serum bilirubin level ≥25 mg/dL and no or only minor neurologic symptoms. (Read the full article)

Uric acid (UA) is associated with hypertension in children, after body weight adjustment. Whether the whole spectrum of variables, such as visceral adiposity, insulin resistance, puberty, and renal function, influence the relationship between UA and blood pressure is unknown.

In a cohort of children at relatively high cardiovascular risk, the association between UA and blood pressure levels is independent of several well-known factors implicated in the development of hypertension, such as insulin resistance, pubertal status, and renal function. (Read the full article)

Preterm infants are born with low serum levels and low body stores of tocopherol. Serum levels ≥0.5 mg/dL are required for protection against lipid peroxidation. Previous studies have shown good intestinal absorption of vitamin E given intragastrically to preterm infants.

Serum α-tocopherol increases after a single 50-IU/kg dose of vitamin E as dl-α-tocopheryl acetate given intragastrically to very preterm infants soon after birth; however, 30% of infants still have serum α-tocopherol level <0.5 mg/dL 24 hours after dosing. (Read the full article)

A serum 25-hydroxyvitamin D (25(OH)D) concentration of 20 ng/mL meets the requirements of at least 97.5% of the population older than 1 year. A recommended dietary intake to achieve this serum 25(OH)D concentration has not been established during infancy.

Daily maternal (during pregnancy) and then infant vitamin supplementation with 1000/400 IU or 2000/800 IU increases the proportion of infants with 25(OH)D ≥20 ng/mL during infancy with the higher dose sustaining this increase for longer. (Read the full article)

Jaundiced newborns without additional risk factors rarely develop kernicterus if the total serum bilirubin is <25 mg/dL. Measuring the bilirubin/albumin ratio might improve risk assessment, but the relationships of both indicators to advancing stages of neurotoxicity are poorly documented.

Both total serum bilirubin and bilirubin/albumin ratio are strong predictors of advancing stages of acute and post-treatment auditory and neurologic impairment. However, bilirubin/albumin ratio, adjusted to the same sensitivity, does not improve prediction over total serum bilirubin alone. (Read the full article)

Poverty is prevalent among children in the United States, and it has a clear association with negative health outcomes. Smoking and passive smoke exposure are both more common among socioeconomically disadvantaged populations and are associated with asthma morbidity.

Reported family hardships were common among children admitted for asthma or wheezing, and most were associated with detectable tobacco smoke exposure. The cumulative number of hardships was also associated with greater odds of tobacco smoke exposure. (Read the full article)

In most previous studies, transcutaneous bilirubin measurement has been found to provide an accurate estimate of total serum bilirubin levels. However, most of these studies were conducted in settings that optimized accuracy.

This study provides a "real-world" assessment of the accuracy of transcutaneous bilirubin measurements in multiple clinical settings and identification of sources of discrepancy between transcutaneous and total serum bilirubin measurements. (Read the full article)

Diabetic ketoacidosis (DKA) is a common and serious first manifestation of diabetes mellitus in children. During initial evaluation, the venous blood pH is frequently used to make the diagnosis and classify the severity of DKA.

This study demonstrates that the serum bicarbonate concentration is a simple and accurate predictor of DKA and its severity and can be used in lieu of venous pH measurement, especially in resource-poor settings where access to pH measurement is limited. (Read the full article)

Antimicrobial peptides and proteins play critical roles in the host defense against invading pathogens. We recently discovered that recombinantly expressed human and mouse serum amyloid A1 (rhSAA1 and rmSAA1) proteins have potent antifungal activities against the major human fungal pathogen Candida albicans. At high concentrations, rhSAA1 disrupts C. albicans membrane integrity and induces rapid fungal cell death. In the current study, we find that rhSAA1 promotes cell aggregation and targets the C. albicans cell wall adhesin Als3. Inactivation of ALS3 in C. albicans leads to a striking decrease in cell aggregation and cell death upon rhSAA1 treatment, suggesting that Als3 plays a critical role in SAA1 sensing. We further demonstrate that deletion of the transcriptional regulators controlling the expression of ALS3, such as AHR1, BCR1, and EFG1 in C. albicans results in similar effects to that of the als3/als3 mutant upon rhSAA1 treatment. Global gene expression profiling indicates that rhSAA1 has a discernible impact on the expression of cell wall- and metabolism-related genes, suggesting that rhSAA1 treatment could lead to a nutrient starvation effect on C. albicans cells.

Vinod K. Bhutani
Jan 1, 1999; 103:6-14
ARTICLES

Once the clinical trials are over and successful, SII will release its vaccine. If the clinical trials by Oxford are not successful then the loss will be of SII. Some limited clinical trials will be done by SII also.

ABSTRACT

A large portion of biological iron is found in the form of an iron-protoporphyrin IX complex, or heme. In the human host environment, which is exceptionally poor in free iron, heme iron, particularly from hemoglobin, constitutes a major source of iron for invading microbial pathogens. Several fungi were shown to utilize free heme, and Candida albicans, a major opportunistic pathogen, is able both to capture free heme and to extract heme from hemoglobin using a network of extracellular hemophores. Human serum albumin (HSA) is the most abundant host heme-scavenging protein. Tight binding of heme by HSA restricts its toxic chemical reactivity and could diminish its availability as an iron source for pathogenic microbes. We found, however, that rather than inhibiting heme utilization, HSA greatly increases availability of heme as an iron source for C. albicans and other fungi. In contrast, hemopexin, a low-abundance but high-affinity heme-scavenging serum protein, does inhibit heme utilization by C. albicans. However, inhibition by hemopexin is mitigated in the presence of HSA. Utilization of albumin-bound heme requires the same hemophore cascade as that which mediates hemoglobin-iron utilization. Accordingly, we found that the C. albicans hemophores are able to extract heme bound to HSA in vitro. Since many common drugs are known to bind to HSA, we tested whether they could interfere with heme-iron utilization. We show that utilization of albumin-bound heme by C. albicans can be inhibited by the anti-inflammatory drugs naproxen and salicylic acid.

IMPORTANCE Heme constitutes a major iron source for microorganisms and particularly for pathogenic microbes; to overcome the iron scarcity in the animal host, many pathogenic bacteria and fungi have developed systems to extract and take up heme from host proteins such as hemoglobin. Microbial heme uptake mechanisms are usually studied using growth media containing free heme or hemoglobin as a sole iron source. However, the animal host contains heme-scavenging proteins that could prevent this uptake. In the human host in particular, the most abundant serum heme-binding protein is albumin. Surprisingly, however, we found that in the case of fungi of the Candida species family, albumin promoted rather than prevented heme utilization. Albumin thus constitutes a human-specific factor that can affect heme-iron utilization and could serve as target for preventing heme-iron utilization by fungal pathogens. As a proof of principle, we identify two drugs that can inhibit albumin-stimulated heme utilization.

Bovine tuberculosis (TB), caused by Mycobacterium bovis, remains an important zoonotic disease posing a serious threat to livestock and wildlife. The current TB tests relying on cell-mediated and humoral immune responses in cattle have performance limitations. To identify new serodiagnostic markers of bovine TB, we screened a panel of 101 recombinant proteins, including 10 polyepitope fusions, by a multiantigen print immunoassay (MAPIA) with well-characterized serum samples serially collected from cattle with experimental or naturally acquired M. bovis infection. A novel set of 12 seroreactive antigens was established. Evaluation of selected proteins in the dual-path platform (DPP) assay showed that the highest diagnostic accuracy (~95%) was achieved with a cocktail of five best-performing antigens, thus demonstrating the potential for development of an improved and more practical serodiagnostic test for bovine TB.

Objective

To determine whether serum neurofilament light chain (sNfL) levels are associated with recent MRI activity in patients with relapsing-remitting MS (RRMS).

Methods

This observational study included 163 patients (405 samples) with early RRMS from the Study of Early interferon-beta1a (IFN-β1a) Treatment (SET) cohort and 179 patients (664 samples) with more advanced RRMS from the Genome-Wide Association Study of Multiple Sclerosis (GeneMSA) cohort. Based on annual brain MRI, we assessed the ability of sNfL cutoffs to reflect the presence of combined unique active lesions, defined as new/enlarging lesion compared with MRI in the preceding year or contrast-enhancing lesion. The probability of active MRI lesions among patients with different sNfL levels was estimated with generalized estimating equations models.

Results

From the sNfL samples ≥90th percentile, 81.6% of the SET (OR = 3.4, 95% CI = 1.8-6.4) and 48.9% of the GeneMSA cohort samples (OR = 2.6, 95% CI = 1.7-3.9) was associated with radiological disease activity on MRI. The sNfL level between the 10th and 30th percentile was reflective of negligible MRI activity: 1.4% (SET) and 6.5% (GeneMSA) of patients developed ≥3 active lesions, 5.8% (SET) and 6.5% (GeneMSA) developed ≥2 active lesions, and 34.8% (SET) and 11.8% (GeneMSA) showed ≥1 active lesion on brain MRI. The sNfL level <10th percentile was associated with even lower MRI activity. Similar results were found in a subgroup of clinically stable patients.

Conclusions

Low sNfL levels (≤30th percentile) help identify patients with MS with very low probability of recent radiologic disease activity during the preceding year. This result suggests that in future, sNfL assessment may substitute the need for annual brain MRI monitoring in considerable number (23.1%–36.4%) of visits in clinically stable patients.

OBJECTIVE

Type 2 diabetes is characterized by increased death rate. In order to tackle this dramatic event, it becomes essential to discover novel biomarkers capable of identifying high-risk patients to be exposed to more aggressive preventive and treatment strategies. hs-CRP and serum amyloid P component (SAP) are two acute-phase inflammation proteins, which interact physically and share structural and functional features. We investigated their combined role in associating with and improving prediction of mortality in type 2 diabetes.

RESEARCH DESIGN AND METHODS

Four cohorts comprising 2,499 patients with diabetes (643 all-cause deaths) were analyzed. The improvement of mortality prediction was addressed using two well-established prediction models, namely, EstimatioN oF mORtality risk in type 2 diabetiC patiEnts (ENFORCE) and Risk Equations for Complications of Type 2 Diabetes (RECODe).

RESULTS

Both hs-CRP and SAP were independently associated with all-cause mortality (hazard ratios [HRs] [95% CIs]: 1.46 [1.34–1.58] [P < 0.001] and 0.82 [0.76–0.89] [P < 0.001], respectively). Patients with SAP ≤33 mg/L were at increased risk of death versus those with SAP >33 mg/L only if hs-CRP was relatively high (>2 mg/L) (HR 1.96 [95% CI 1.52–2.54] [P < 0.001] and 1.20 [0.91–1.57] [P = 0.20] in hs-CRP >2 and ≤2 mg/L subgroups, respectively; hs-CRP-by-SAP strata interaction P < 0.001). The addition of hs-CRP and SAP significantly (all P < 0.05) improved several discrimination and reclassification measures of both ENFORCE and RECODe all-cause mortality prediction models.

CONCLUSIONS

In type 2 diabetes, hs-CRP and SAP show opposite and synergic associations with all-cause mortality. The use of both markers, possibly in combination with others yet to be unraveled, might improve the ability to predict the risk of death in the real-life setting.

Background and objectives

Uromodulin is exclusively produced by tubular epithelial cells and released into urine and serum. Higher serum uromodulin has been associated with lower risk for kidney failure in Chinese patients with CKD and with lower risk for mortality in the elderly and in patients undergoing coronary angiography. We hypothesized that lower serum uromodulin is associated with mortality, cardiovascular events, and kidney failure in white patients with CKD.

Design, setting, participants, & measurements

We measured serum uromodulin in 5143 participants enrolled in the German CKD (GCKD) study. The associations of baseline serum uromodulin with all-cause mortality, major adverse cardiovascular events (MACE; a composite of cardiovascular mortality, nonfatal myocardial infarction or stroke, or incident peripheral vascular disease), and kidney failure (dialysis or transplantation) were evaluated using multivariable Cox proportional hazard regression analyses in a cohort study design, adjusting for demographics, eGFR, albuminuria, cardiovascular risk factors, and medication.

Results

The mean age of participants was 60±12 years, 60% were male. Mean serum uromodulin concentration was 98±60 ng/ml, eGFR was 49±18 ml/min per 1.73 m², and 78% had eGFR <60 ml/min per 1.73 m². Participants in lower serum uromodulin quartiles had lower eGFR and higher albuminuria, prevalence of diabetes, hypertension, coronary artery disease, and more frequent history of stroke at baseline. During a follow-up of 4 years, 335 participants died, 417 developed MACE, and 229 developed kidney failure. In multivariable analysis, the highest serum uromodulin quartile was associated with lower hazard for mortality (hazard ratio [HR], 0.57; 95% CI, 0.38 to 0.87), MACE (HR, 0.63; 95% CI, 0.45 to 0.90), and kidney failure (HR, 0.24; 95% CI, 0.10 to 0.55) compared with the lowest quartile.

Conclusions

Higher serum uromodulin is independently associated with lower risk for mortality, cardiovascular events, and kidney failure in white patients with CKD.

Clinical Trial registry name and registration number

Deutsches Register für Klinische Studien (DRKS; German national database of clinical studies), DRKS00003971.

Background and objectives

This study aimed to investigate the association between in-hospital trajectories of serum sodium and risk of in-hospital and 1-year mortality in patients in hospital.

Design, setting, participants, & measurements

This is a single-center cohort study. All adult patients who were hospitalized from years 2011 through 2013 who had available admission serum sodium and at least three serum sodium measurements during hospitalization were included. The trend of serum sodium during hospitalization was analyzed using group-based trajectory modeling; the five main trajectories were grouped as follows: (1) stable normonatremia, (2) uncorrected hyponatremia, (3) borderline high serum sodium, (4) corrected hyponatremia, and (5) fluctuating serum sodium. The outcome of interest was in-hospital mortality and 1-year mortality. Stable normonatremia was used as the reference group for outcome comparison.

Results

A total of 43,539 patients were analyzed. Of these, 47% had stable normonatremia, 15% had uncorrected hyponatremia, 31% had borderline high serum sodium, 3% had corrected hyponatremia, and 5% had fluctuating serum sodium trajectory. In adjusted analysis, there was a higher in-hospital mortality among those with uncorrected hyponatremia (odds ratio [OR], 1.33; 95% CI, 1.06 to 1.67), borderline high serum sodium (OR, 1.66; 95% CI, 1.38 to 2.00), corrected hyponatremia (OR, 1.50; 95% CI, 1.02 to 2.20), and fluctuating serum sodium (OR, 4.61; 95% CI, 3.61 to 5.88), compared with those with the normonatremia trajectory. One-year mortality was higher among those with uncorrected hyponatremia (hazard ratio [HR], 1.28; 95% CI, 1.19 to 1.38), borderline high serum sodium (HR, 1.18; 95% CI, 1.11 to 1.26), corrected hyponatremia (HR, 1.24; 95% CI, 1.08 to 1.42), and fluctuating serum sodium (HR, 2.10; 95% CI, 1.89 to 2.33) compared with those with the normonatremia trajectory.

Conclusions

More than half of patients who had been hospitalized had an abnormal serum sodium trajectory during hospitalization. This study demonstrated that not only the absolute serum sodium levels but also their in-hospital trajectories were significantly associated with in-hospital and 1-year mortality. The highest in-hospital and 1-year mortality risk was associated with the fluctuating serum sodium trajectory.

Podcast

This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_03_25_CJN.12281019.mp3

The measurement of neuron-specific enolase (NSE) in serum is frequently requested for diagnosis, risk stratification, and treatment monitoring of neuroblastoma (NB) in the pediatric population. However, authoritative clinical practice guidelines advise about the poor diagnostic performance of NSE.We critically appraised the available literature evaluating the diagnostic and prognostic value of NSE in the management of NB, paying special attention to the definition of appropriate threshold levels. In addition, we discuss the interfering conditions causing artifactual increases of NSE concentrations in serum and potentially influencing the clinical evaluation of patients with suspected NB.No definitive evidence supports the use of serum NSE for diagnosis and monitoring of NB. The risk of obtaining false-positive NSE results associated with confounders (e.g., sample hemolysis) and other pathophysiologic conditions (e.g., inflammation) is remarkable and hampers the diagnostic value of this test. NSE may be helpful to define the risk of death of patients with NB, mainly in the advanced stages of disease. However, further studies validating currently marketed immunoassays and defining threshold values useful for this scope are warranted.

Background:

Early diagnosis can significantly reduce colorectal cancer deaths. We sought to identify serum PIWI-interacting RNAs (piRNAs) that could serve as sensitive and specific noninvasive biomarkers for early colorectal cancer detection.

Methods:

We screened the piRNA expression profile in sera from 7 patients with colorectal cancer and 7 normal controls using small RNA sequencing. Differentially expressed piRNAs were measured in a training cohort of 140 patients with colorectal cancer and 140 normal controls using reverse transcription quantitative PCR. The identified piRNAs were evaluated in two independent validation cohorts of 180 patients with colorectal cancer and 180 normal controls. Finally, the diagnostic value of the identified piRNAs for colorectal adenoma (CRA) was assessed, and their expression was measured in 50 patients with lung cancer, 50 with breast cancer, and 50 with gastric cancer.

Results:

The piRNAs piR-020619 and piR-020450 were consistently elevated in sera of patients with colorectal cancer as compared with controls. A predicative panel based on the two piRNAs was established that displayed high diagnostic accuracy for colorectal cancer detection. The two-piRNA panel could detect small-size and early-stage colorectal cancer with an area under the ROC curve of 0.863 and 0.839, respectively. Combined use of the two piRNAs could effectively distinguish CRA from controls. Aberrant elevation of the two piRNAs was not observed in sera of patients with lung, breast, and gastric cancer.

Conclusions:

Serum piR-020619 and piR-020450 show a strong potential as colorectal cancer-specific early detection biomarkers.

Impact:

The field of circulating piRNAs could allow for novel tumor biomarker development.

Forever Youth Liberator Serum Video

Forever Youth Liberator Serum Video

Adar Poonawala, CEO of Serum Institute of India, says he is taking the risk of initiating production even before the vaccine has reached advanced clinical trials

The latest product promising to work miracles has arrived in the shape of a face serum which claims to achieve smoother skin in minutes with just a few gentle dabs.

The active ingredient in an anti-ageing lotion launched this week won its developers a Nobel Prize but unsurprisingly Bioeffect EGF Serum doesn’t come cheap.

The fashion designer, 45, took to Instagram to share a make-up free video of herself after applying the serum to her face to show her fans the results.

Beauty pro Frankie Boyd revealed that he used skincare from The Inkey List in order to 'hydrate and prep' Scarlett's skin for the award ceremony.

Serum, the world’s largest maker of vaccines by volume, is mass-producing the vaccine candidate developed by the University of Oxford.

Interview with David J. A. Jenkins, MD, author of Effect of a Dietary Portfolio of Cholesterol-Lowering Foods Given at 2 Levels of Intensity of Dietary Advice on Serum Lipids in Hyperlipidemia: A Randomized Controlled Trial

Interview with Brian K. Kit, MD, MPH, author of Trends in Serum Lipids Among US Youths Aged 6 to 19 Years, 1988-2010