Background/Objectives
The risk of chronic kidney disease (CKD) in patients who regularly drink soda is controversial. The objective of this meta‐analysis was to evaluate the associations between ...consumption of sugar‐sweetened and artificially sweetened soda and CKD.
Methods
A literature search was performed using MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews from inception until 30 June 2014. Studies that reported odds ratios or hazard ratios comparing the risk of CKD in patients consuming significant amounts of either sugar‐sweetened or artificially sweetened soda versus those who did not consume soda were included. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random‐effects, generic inverse variance method.
Results
Five studies were included in our analysis of the association between consumption of sugar‐sweetened soda and CKD. The pooled RR of CKD in patients consuming sugar‐sweetened soda was 1.58 (95% CI 1.00–2.49). Four studies were selected to assess the association between consumption of artificially sweetened soda and CKD. The pooled RR of CKD in patients consuming artificially sweetened soda was 1.33 (95% CI 0.82–2.15).
Conclusions
Our study demonstrates statistically significant increased risks of CKD in patients consuming sugar‐sweetened soda, but not in patients consuming artificially sweetened soda. This finding suggests that sugar‐sweetened soda consumption is associated with CKD and may impact clinical management and primary prevention of CKD in high‐risk patients.
Summary at a Glance
This review suggests that long‐term consumption of sugar‐sweetened, but not artificially sweetened, carbonated drinks increases the risk of chronic kidney disease.
Immunoconjugates targeting cell-surface antigens have demonstrated clinical activity to enable regulatory approval in several solid and hematologic malignancies. We hypothesize that a rigorous and ...comprehensive surfaceome profiling approach to identify osteosarcoma-specific cell-surface antigens can similarly enable development of effective therapeutics in this disease. Herein, we describe an integrated proteomic and transcriptomic surfaceome profiling approach to identify cell-surface proteins that are highly expressed in osteosarcoma but minimally expressed on normal tissues. Using this approach, we identified targets that are highly expressed in osteosarcoma. Three targets, MT1-MMP, CD276, and MRC2, were validated as overexpressed in osteosarcoma. Furthermore, we tested BT1769, an MT1-MMP-targeted Bicycle toxin conjugate, in osteosarcoma patient-derived xenograft models. The results showed that BT1769 had encouraging antitumor activity, high affinity for its target, and a favorable pharmacokinetic profile. This confirms the hypothesis that our approach identifies novel targets with significant therapeutic potential in osteosarcoma.
Purpose: Preterm infants undergoing Retinopathy of Prematurity Eye Exams (ROPEE) may experience adverse events, possibly from systemic absorption of cyclopentolate. The purpose of this study was to ...analyze the association between adverse events and drug levels found in neonates undergoing ROPEE.
Materials and Methods: 25 infants were randomized into two groups during routine ROP screening: 5 infants for blood collection before mydriatic drops and 20 for blood collection 1 h after eye drops. Blood was collected onto dried blood spot cards, extracted, and analyzed for cyclopentolate and phenylephrine using liquid chromatography and mass spectrometry. Relationships between drug levels and adverse events were assessed.
Results: Cyclopentolate (range 6-53 ng/ml) was observed in 15 of 18 infants, while phenylephrine was not detected. Levels of cyclopentolate were significantly higher in infants who were on oxygen (p = 0.01). There was a significant association between cyclopentolate levels and gastric residuals in tube-fed infants not receiving oxygen (p = 0.01).
Conclusions: Cyclopentolate levels varied among preterm infants after ROPEE. Cyclopentolate was positively associated with increased gastric residuals. Underlying medical conditions requiring oxygen administration may affect absorption and metabolism of cyclopentolate. There is a need to predict infants at risk for high blood levels of cyclopentolate in order to prevent or treat adverse events after ROPEE.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
OBI-3424 is a highly selective prodrug that is converted by aldo-keto reductase family 1 member C3 (AKR1C3) to a potent DNA-alkylating agent. OBI-3424 has entered clinical testing for hepatocellular ...carcinoma and castrate-resistant prostate cancer, and it represents a potentially novel treatment for acute lymphoblastic leukemia (ALL).
We assessed AKR1C3 expression by RNA-Seq and immunoblotting, and evaluated the
cytotoxicity of OBI-3424. We investigated the pharmacokinetics of OBI-3424 in mice and nonhuman primates, and assessed the
efficacy of OBI-3424 against a large panel of patient-derived xenografts (PDX).
AKR1C3 mRNA expression was significantly higher in primary T-lineage ALL (T-ALL;
= 264) than B-lineage ALL (B-ALL;
= 1,740;
< 0.0001), and OBI-3424 exerted potent cytotoxicity against T-ALL cell lines and PDXs.
, OBI-3424 significantly prolonged the event-free survival (EFS) of nine of nine ALL PDXs by 17.1-77.8 days (treated/control values 2.5-14.0), and disease regression was observed in eight of nine PDXs. A significant reduction (
< 0.0001) in bone marrow infiltration at day 28 was observed in four of six evaluable T-ALL PDXs. The importance of AKR1C3 in the
response to OBI-3424 was verified using a B-ALL PDX that had been lentivirally transduced to stably overexpress AKR1C3. OBI-3424 combined with nelarabine resulted in prolongation of mouse EFS compared with each single agent alone in two T-ALL PDXs.
OBI-3424 exerted profound
efficacy against T-ALL PDXs derived predominantly from aggressive and fatal disease, and therefore may represent a novel treatment for aggressive and chemoresistant T-ALL in an AKR1C3 biomarker-driven clinical trial.
Engineered bacteriophages (phages) can be effective diagnostic reporters for detecting a variety of bacterial pathogens. Although a promising biotechnology, the large-scale use of these reporters may ...result in the unintentional release of genetically modified viruses. In order to limit the potential environmental impact, the ability of these phages to propagate outside the laboratory was targeted. The phage SEA1 has been previously engineered to facilitate food safety as an accurate and sensitive reporter for
contamination. In this study, homologous recombination was used to replace the expression of an essential baseplate wedge subunit (gp141) in SEA1 with a luciferase, NanoLuc
. This reporter, referred to as SEA1Δgp141.NL, demonstrated a loss of plaque formation and a failure to increase in titer following infection of
. SEA1Δgp141.NL was thus incapable of producing infectious progeny in the absence of gp141. In contrast, production of high titer stocks was possible when gp141 was artificially supplied in trans during infection. As a reporter, SEA1Δgp141.NL facilitated rapid, sensitive, and robust detection of
despite an inability to replicate. These results suggest that replication-deficient reporter phages are an effective method to obtain improved containment without sacrificing significant performance or the ease of production associated with many phage-based diagnostic methods.
Conotruncal heart defects (CTDs) are among the most severe birth defects worldwide. Studies of CTDs indicate both lifestyle behaviors and genetic variation contribute to the risk of CTDs. Based on a ...hybrid design using data from 616 case-parental and 1645 control-parental triads recruited for the National Birth Defects Prevention Study between 1997 and 2008, we investigated whether the occurrence of CTDs is associated with interactions between 921 maternal and/or fetal single nucleotide polymorphisms (SNPs) and maternal obesity and tobacco use. The maternal genotypes of the variants in the glutamate-cysteine ligase, catalytic subunit (GCLC) gene and the fetal genotypes of the variants in the glutathione S-transferase alpha 3 (GSTA3) gene were associated with an elevated risk of CTDs among obese mothers. The risk of delivering infants with CTDs among obese mothers carrying AC genotype for a variant in the GCLC gene (rs6458939) was 2.00 times the risk among those carrying CC genotype (95% confidence interval: 1.41, 2.38). The maternal genotypes of several variants in the glutathione-S-transferase (GST) family of genes and the fetal genotypes of the variants in the GCLC gene interacted with tobacco exposures to increase the risk of CTDs. Our study suggests that the genetic basis underlying susceptibility of the developing heart to the adverse effects of maternal obesity and tobacco use involve both maternal and embryonic genetic variants. These results may provide insights into the underlying pathophysiology of CTDs, and ultimately lead to novel prevention strategies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
With rising prevalence of morbid obesity, the number of bariatric surgeries performed each year has been increasing worldwide. The objective of this meta-analysis was to assess the risk of kidney ...stones following bariatric surgery.
A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from inception through July 2015. Only studies reporting relative risks, odd ratios or hazard ratios (HRs) to compare risk of kidney stones in patients who underwent bariatric surgery versus no surgery were included. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method.
Four studies (One randomized controlled trial and three cohort studies) with 11,348 patients were included in analysis to assess the risk of kidney stones following bariatric surgery. The pooled RR of kidney stones in patients undergoing bariatric surgery was 1.22 (95% CI, 0.63-2.35). The type of bariatric surgery subgroup analysis demonstrated an increased risk of kidney stones in patients following Roux-en-Y gastric bypass (RYGB) with the pooled RR of 1.73 (95% CI, 1.30-2.30) and a decreased risk of kidney stones in patients following restrictive procedures including laparoscopic banding or sleeve gastrectomy with the pooled RR of 0.37 (95% CI, 0.16-0.85).
Our meta-analysis demonstrates an association between RYGB and increased risk of kidney stones. Restrictive bariatric surgery, on the other hand, may decrease kidney stone risk. Future study with long-term follow-up data is needed to confirm this potential benefit of restrictive bariatric surgery.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Host range is a major determinant in the industrial utility of a bacteriophage. A model host range permits broad recognition across serovars of a target bacterium while avoiding cross-reactivity with ...commensal microbiota. Searching for a naturally occurring bacteriophage with ideal host ranges is challenging, time-consuming, and restrictive. To address this, SPTD1.NL, a previously published luciferase reporter bacteriophage for
, was used to investigate manipulation of host range through receptor-binding protein engineering. Similar to related members of the
bacteriophage family, SPTD1.NL possessed a receptor-binding protein gene cluster encoding four tailspike proteins, TSP1-4. Investigation of the native gene cluster through chimeric proteins identified TSP3 as the tailspike protein responsible for
detection. Further analysis of chimeric phages revealed that TSP2 contributed off-target
recognition, whereas TSP1 and TSP4 were not essential for activity against any known host. To improve the host range of SPTD1.NL, TSP1 and TSP2 were sequentially replaced with chimeric receptor-binding proteins targeting
. This engineered construct, called RBP-SPTD1-3, was a superior diagnostic reporter, sensitively detecting additional
serovars while also demonstrating improved specificity. For industrial applications, bacteriophages of the
family are thus uniquely versatile and may be engineered with multiple chimeric receptor-binding proteins to achieve a custom-tailored host range.
We aimed to determine the optimal range of discharge serum magnesium in hospitalized patients by evaluating one-year mortality risk according to discharge serum magnesium.
This was a single-center ...cohort study of hospitalized adult patients who survived until hospital discharge. We classified discharge serum magnesium, defined as the last serum magnesium within 48 hours of hospital discharge, into ≤1.6, 1.7-1.8, 1.9-2.0, 2.1-2.2, and ≥2.3 mg/dL. We assessed one-year mortality risk after hospital discharge based on discharge serum magnesium, using discharge magnesium of 2.1-2.2 mg/dL as the reference group.
Of 39,193 eligible patients, 8%, 23%, 34%, 23%, and 12% had a serum magnesium of ≤1.6, 1.7-1.8, 1.9-2.0, 2.1-2.2, and ≥2.3 mg/dL, respectively, at hospital discharge. After the adjustment for several confounders, discharge serum magnesium of ≤1.6, 1.7-1.8, and ≥2.3 mg/dL were associated with higher one-year mortality with hazard ratio of 1.35 (95% CI 1.21-1.50), 1.14 (95% CI 1.06-1.24), and 1.17 (95% CI 1.07-1.28), respectively, compared to discharge serum magnesium of 2.1-2.2 mg/dL. There was no significant difference in one-year mortality between patients with discharge serum magnesium of 1.9-2.0 and 2.1-2.2 mg/dL.
The optimal range of serum magnesium at discharge was 1.9-2.2 mg/dL. Both hypomagnesemia and hypermagnesemia at discharge were associated with higher one-year mortality.
The prognosis for children diagnosed with high-risk acute lymphoblastic leukemia (ALL) remains suboptimal, and more potent and less toxic treatments are urgently needed. We investigated the efficacy ...of a novel nicotinamide phosphoribosyltransferase inhibitor, OT-82, against a panel of patient-derived xenografts (PDXs) established from high-risk and poor outcome pediatric ALL cases. OT-82 was well-tolerated and demonstrated impressive single agent in vivo efficacy, achieving significant leukemia growth delay in 95% (20/21) and disease regression in 86% (18/21) of PDXs. In addition, OT-82 enhanced the efficacy of the established drugs cytarabine and dasatinib and, as a single agent, showed similar efficacy as an induction-type regimen combining three drugs used to treat pediatric ALL. OT-82 exerted its antileukemic action by depleting NAD
and ATP, inhibiting the NAD
-requiring DNA damage repair enzyme PARP-1, increasing mitochondrial ROS levels and inducing DNA damage, culminating in apoptosis induction. OT-82 sensitivity was associated with the occurrence of mutations in major DNA damage response genes, while OT-82 resistance was characterized by high expression levels of CD38. In conclusion, our study provides evidence that OT-82, as a single agent, and in combination with established drugs, is a promising new therapeutic strategy for a broad spectrum of high-risk pediatric ALL for which improved therapies are urgently needed.
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