Genetic variation in S-nitrosoglutathione reductase (GSNOR) and childhood asthma

BACKGROUND: S-nitrosothiols are potent endogenous bronchodilators depleted in asthmatic airway lining fluid. S-nitrosoglutathione reductase (GSNOR; also known as alcohol dehydrogenase 5 or formaldehyde dehydrogenase) catalyzes the metabolism of S-nitrosoglutathione (GSNO) and controls intracellular levels of S-nitrosothiols. GSNOR knockout mice have increased lung S-nitrosothiol levels and are therefore protected from airway hyperresponsiveness after methacholine or allergen challenge. OBJECTIVE: We sought to investigate whether genetic variation in GSNOR is associated with childhood asthma and atopy. METHODS: We genotyped 5 tagging and 2 additional single nucleotide polymorphisms (SNPs) in GSNOR in 532 nuclear families consisting of asthmatic children aged 4 to 17 years and both parents in Mexico City. Atopy was determined by means of skin prick testing. RESULTS: Carrying 1 or 2 copies of the minor allele of SNP rs1,154,404 was associated with decreased risk of asthma (relative risk [RR], 0.77; 95% CI, 0.61-0.97; P = .028 for 1 copy and RR, 0.66; 95% CI, 0.44-0.99; P = .046 for 2 copies). Homozygosity for the minor allele of SNP rs28,730,619 was associated with increased risk of asthma (RR, 1.60; 95% CI, 1.13-2.26; P = .0077). Haplotype analyses supported the single SNP findings. GSNOR SNPs were not associated with the degree of atopy. CONCLUSION: This is the first study of genetic polymorphisms in GSNOR and asthma. These data suggest that genetic variation in GSNOR might play a role in asthma susceptibility. CLINICAL IMPLICATIONS: The association of GSNOR polymorphisms with asthma suggests a potential therapeutic target.     

Dairy-Based and Energy-Enriched Berry-Based Snacks Improve or Maintain Nutritional and Functional Status in Older People in Home Care

Objective

Consumption of energy- and nutrient-dense snacks are recommended for older people to maintain adequate nutrition. We evaluated the effects of dairy-based and energy-enriched berry products consumed as snacks on nutritional and functional status among vulnerable older people receiving home care services.

Design

Randomised controlled study.

Setting and participants

The study sample consisted of 85 home care clients, with mean age of 81.9 (SD 7.1) years in the intervention group (n=50) and 83.7 (SD 8.1) years in the control group (n=35), and 72% women in both groups.

Intervention

In the intervention group, the participants consumed both high-protein dairy-based products and energy-enriched berry purées for three months. The snack products provided nearly 300 kcal and 14 g protein per day.

Measurements

The Mini Nutritional Assessment (MNA), body mass index (BMI), mid-arm muscular area (MAMA) and concentrations of plasma albumin and prealbumin and blood haemoglobin were used to determine nutritional status, and handgrip strength was used to determine functional status at baseline and after the intervention. Results: After adjustment for age and gender, the intervention showed a significant effect on MNA scores (2.1, 95% [CI]: 1.0 to 3.3) (p=0.003), albumin concentration (2.0 g/L, 95% [CI]: 1.1 to 3.2) (p=0.006) and handgrip strength of the right hand in women (2.4 kg, 95% [CI]: 1.2 to 3.3) (p=0.007). The MNA scores improved in the intervention group, while albumin concentration and handgrip strength decreased in the control group.

Conclusions

Regular use of dairy- and energy-enriched berry-based snacks may improve or maintain nutritional and functional status among older people in home care.

     

Repeated metal ion measurements in patients with high risk metal-on-metal hip replacement

Purpose

Conventional follow-up methods are not sufficient to identify adverse soft tissue reactions in patients with metal-on-metal hip replacements. The national guidelines regarding metal ion measurements are debatable. The aims of our study were to investigate (1) if there is a clinically significant change in whole blood (WB) cobalt (Co) or chrome (Cr) levels in repeated WB assessment in patients operated on with ASR hip replacements, and (2) what proportion of patients has WB Co or Cr level below the previously established safe upper limits (SUL) in the repeated WB metal ion assessment.

Methods

We identified all patients (n = 254) with unilateral ASR implants who had second blood sample taken eight to 16 months after the first.

Results

WB Co and Cr levels remained below SUL and within their initial values during a mean one-year measurement interval in the majority of patients with a high risk HR device. In contrast to this, 50 % of patients with THRs had metal ion levels exceeding the SUL in the first measurement. WB Co values significantly increased over the measurement interval in the THR group.

Conclusion

In patients with a high risk HR, repeated metal ion measurement did not provide useful information for clinical decision-making. In patients with a LD MoM THR repeated measurements revealed a large number of patients with metal ion levels exceeding SUL and might thus be clinically beneficial.     

3D Non-Fluoroscopic Cryoablation of Right-Sided Accessory Pathways in Children: Monocentric Study and Literature Review

Background: Cryoablation of accessory pathways (APs) is effective and very safe in children, as previously reported by our group. The aim of this retrospective study was to evaluate the current efficacy of 3D non-fluoroscopic cryoablation of right sided APs in children, comparing results obtained with the Ensite Velocity^TM and the more recent Ensite Precision^TM 3D mapping systems. Methods and Results: From January 2016 to December 2019, 102 pediatric patients [mean age 12.5 ± 2.8, 62 males (61% of total cohort)] with right APs underwent 3D non-fluoroscopic transcatheter cryoablation at our Institution. Fifteen (14.7%) patients had previously undergone catheter ablation. Acute procedural success rate was 95.1% (n = 97). No significant differences were detected in acute success rates achieved with Ensite Velocity^TM or Ensite PrecisionTM systems nor between manifest (94%) and concealed APs (100%). No permanent complications occurred. During follow-up (428 ± 286 days, median 396 days [interquartile range 179-713]), 19 patients (19.6%) had recurrences. Recurrences were more frequent for parahissian/anterior APs compared to midseptal/posterior and lateral APs (p = 0.043). Recurrences were not related to the Ensite system used. A redo ablation procedure was attempted in 13 cases, 11 cryoablation and 2 radiofrequency ablations: the former was successful in 10 cases out of 11 (90.9%). Conclusion: 3D cryoablation of right-sided APs is associated with a very high acute success rate with limited use of fluoroscopy, resulting in great benefit to the children. Recurrence rates are not high and patients can be retreated with cryo-energy with higher success rates.     

Association of calcium channel blocker use with clinical outcome of COVID-19: A meta-analysis

AimsThis meta-analysis aims to analyze the association of calcium channel blocker (CCB) use with COVID-19 clinical outcomes.MethodsPubMed, ProQuest, Science Direct, Scopus, and medRxiv databases were searched systematically in a limited period. The primary outcome was mortality.ResultsA total of 119,298 patients from 31 eligible studies were included. Pooled analysis of the random-effect model revealed CCB was not associated with reduced mortality (OR = 1.21 [95%CI: 0.98–1.49], p = 0.08). Interestingly, subgroup analysis in hypertensive patients revealed significantly reduced mortality (OR = 0.69 [95%CI: 0.52–0.91], p = 0.009).ConclusionCCB usage was not associated with the outcome of COVID-19. However, CCB was associated with a decreased mortality rate in hypertensive COVID-19 patients.     

PRERECORDED HYPNOTIC PERI-SURGICAL INTERVENTION TO ALLEVIATE RISK OF CHRONIC POSTSURGICAL PAIN IN TOTAL KNEE REPLACEMENT: A RANDOMIZED CONTROLLED PILOT STUDY

This pilot study evaluated the effect sizes associated with prerecorded hypnotic interventions provided during the perisurgical period for reducing risk factors associated with chronic postsurgical pain, including acute postsurgical pain, anxiety, depression, and pain catastrophizing. A total of 25 participants (N = –25) were randomly assigned to receive a hypnotic intervention (n = 8), minimal-effect treatment (n = 8), or treatment as usual (n = 9) during their hospital stay for total knee replacement (TKR). Participants were followed for 6 months after hospital discharge. Results indicate that prerecorded hypnotic intervention exerted medium effects for reducing acute postsurgical pain and large effects for reducing perisurgical anxiety and pain catastrophizing. The findings indicate that a fully powered clinical trial to evaluate the beneficial effects of prerecorded hypnosis to manage pain and psychological distress in patients undergoing TKR is warranted.     

Genotoxicity of steroidal estrogens.

The molecular mechanisms underlying the development of breast cancer in general, and estrogen-associated breast carcinogenesis in particular, are not completely understood. There are three mechanisms considered responsible for the carcinogenicity of estrogens in the human breast: (i) receptor-mediated hormonal activity, which stimulates cellular proliferation, resulting in more opportunities for accumulation of the genetic damage that leads to carcinogenesis; (ii) a cytochrome P450-mediated metabolic activation, which elicits direct genotoxic effects by increasing mutation rates; and (iii) the induction of aneuploidy by estrogen. In this article, we concentrate on discussing the role of estrogen receptors and the metabolic activation of 17beta-estradiol (E(2)) as mechanisms of breast cancer initiation.     

Films based on the biopolymer poly(3-hydroxybutyrate) as platforms for the controlled release of dexamethasone

Controlled drug delivery aims to achieve an effective drug concentration in the action site for a desired period of time, while minimizing side effects. In this contribution, biodegradable poly(3-hydroxybutyrate) films were evaluated as a reservoir platform for dexamethasone controlled release. These systems were morphological and physicochemically characterized. In vitro release assays were performed for five different percentages of drug in the films and data were fitted by a mathematical model developed and validated by our research group. When the profiles were normalized, a single curve properly fitted all the experimental data. Using this unique curve, the dissolution efficiency (DE), the time to release a given amount of drug (t_X%), and the mean dissolution time were calculated. Furthermore, the dissolution rate, the initial dissolution rate (a%) and the intrinsic dissolution rate were determined. The a% mean value was 1.968 × 10^?2% released/min, t_80% was about 14 days, and the DE was 59.6% at 14 days and 66.5% at 20 days. After 2 days, when approximately 40% of the drug was released, the dissolution rate decreased about 60% respect to the initial value. The poly(3-hydroxybutyrate) platforms behaved as an appropriate system to release and control the dexamethasone delivery, suggesting that they could be an alternative to improve drug therapy.     

Exploiting pre‐rRNA processing in Diamond Blackfan anemia gene discovery and diagnosis

Diamond Blackfan anemia (DBA), a syndrome primarily characterized by anemia and physical abnormalities, is one among a group of related inherited bone marrow failure syndromes (IBMFS) which share overlapping clinical features. Heterozygous mutations or single‐copy deletions have been identified in 12 ribosomal protein genes in approximately 60% of DBA cases, with the genetic etiology unexplained in most remaining patients. Unlike many IBMFS, for which functional screening assays complement clinical and genetic findings, suspected DBA in the absence of typical alterations of the known genes must frequently be diagnosed after exclusion of other IBMFS. We report here a novel deletion in a child that presented such a diagnostic challenge and prompted development of a novel functional assay that can assist in the diagnosis of a significant fraction of patients with DBA. The ribosomal proteins affected in DBA are required for pre‐rRNA processing, a process which can be interrogated to monitor steps in the maturation of 40S and 60S ribosomal subunits. In contrast to prior methods used to assess pre‐rRNA processing, the assay reported here, based on capillary electrophoresis measurement of the maturation of rRNA in pre‐60S ribosomal subunits, would be readily amenable to use in diagnostic laboratories. In addition to utility as a diagnostic tool, we applied this technique to gene discovery in DBA, resulting in the identification of RPL31 as a novel DBA gene. Am. J. Hematol. 89:985–991, 2014. © 2014 Wiley Periodicals, Inc.