Tag: pubmed

Kidney Int. 2023 Jul 4:S0085-2538(23)00472-6. doi: 10.1016/j.kint.2023.06.018. Online ahead of print.

ABSTRACT

Multiple genome-wide association studies (GWASs) have reproducibly identified the MTMR3/HORMAD2/LIF/OSM locus to be associated with IgA nephropathy (IgAN). However, the causal variant(s), implicated gene(s), and altered mechanisms remain poorly understood. Here, we performed fine-mapping analyses based on GWAS datasets encompassing 2762 IgAN cases and 5803 control individuals, and identified rs4823074 as the candidate causal variant that intersects the MTMR3 promoter in B-lymphoblastoid cells. Mendelian randomization studies suggested the risk allele may modulate disease susceptibility by affecting serum IgA levels through increased MTMR3 expression. Consistently, elevated MTMR3 expression in peripheral blood mononuclear cells was observed in patients with IgAN. Further mechanistic studies in vitro demonstrated that MTMR3 increased IgA production dependent upon its phosphatidylinositol 3-phosphate binding domain. Moreover, our study provided the in vivo functional evidence that Mtmr3-/- mice exhibited defective Toll Like Receptor 9-induced IgA production, glomerular IgA deposition, as well as mesangial cell proliferation. RNA-seq and pathway analyses showed that MTMR3 deficiency resulted in an impaired intestinal immune network for IgA production. Thus, our results support the role of MTMR3 in IgAN pathogenesis by enhancing Toll Like Receptor 9-induced IgA immunity.

PMID:37414396 | DOI:10.1016/j.kint.2023.06.018

J Dent. 2023 Jul 4:104603. doi: 10.1016/j.jdent.2023.104603. Online ahead of print.

ABSTRACT

OBJECTIVES: Adequate reporting of limitations is crucial to enable clinicians to accurately interpret the clinical trial findings. This meta-epidemiological study aimed to evaluate whether study limitations are reported in full-text articles of randomized controlled trials (RCTs) published in the leading dental journals. Associations between the trial characteristics and the reporting of limitations were also explored.

METHODS: RCTs published between 1^st January and 31^st December in the years 2011, 2016 and 2021 were identified from the 12 high impact factor dental journals (general and specialty). RCT characteristics were extracted, and reporting of limitations was recorded for the selected studies. Descriptive statistics were calculated for trial and limitations related characteristics. Univariable ordinal logistic regression models were fit to explore univariable associations between trial characteristics and reporting of limitations.

RESULTS: Two hundred and sixty-seven trials were included and analyzed. Most RCTs were published in 2021 (40.8%), had authors based in Europe (50.2%), did not have a statistician involved (88.8%) and assessed a procedure/method intervention type (40.5%). The reporting of trial limitations was generally sub-optimal. More recent trials and studies with a published protocol were associated with better reporting of limitations. The type of journal was a significant predictor for limitation reporting.

CONCLUSIONS: Within this study, the clear reporting of study limitations in the manuscripts of dental RCTs is sub-optimal and requires improvement.

CLINICAL SIGNIFICANCE: The reporting of limitations should not be viewed as a weakness of a trial but due diligence, so clinicians can fully interpret the impact of these limitations on both the validity and generalisability of the results.

PMID:37414393 | DOI:10.1016/j.jdent.2023.104603

J Thorac Oncol. 2023 Jul 4:S1556-0864(23)00639-1. doi: 10.1016/j.jtho.2023.06.018. Online ahead of print.

ABSTRACT

BACKGROUND: The role of family history of lung cancer (LCFH) in screening using low-dose computed tomography (LDCT) has not been prospectively investigated and with long-term follow-up.

METHODS: A multicenter prospective study with up to three rounds of annual LDCT screening was conducted to determine the detection rate of LC in asymptomatic first or second-degree relatives of LCFH.

RESULTS: From 2007 to 2011, there were 1,102 participants enrolled, including 805 and 297 from simplex (SF) and multiplex families (MF), respectively (54.2% female, and 70.0% never-smokers). Last follow-up date was May 05, 2021. The overall LC detection rate was 4.5% (50/1102). The detection rate in MF was 9.4% (19/202) and 4.4% (4/91) in never-smokers and who smoked, respectively. The corresponding rates for SF were 3.7% (21/569) and 2.7% (6/223), respectively. Of them, 68.0% and 22.0% of cases with stage I and IV diseases, respectively. LC diagnoses within a 3-year interval from initial screening were younger, higher detection rate, and more stage I disease; thereafter, more stage III/IV disease and 66.7% (16/24) with negative or semi-positive nodules in initial CT scans. Within the 6-year interval, only maternal (modified rate ratio [RR]=4.46, 95% confidence interval [CI]=2.32-8.56) or maternal relative history of LC (modified RR=5.41, 95% CI=2.84-10.30) increased the risk of LC.

CONCLUSION: LCFH is a risk factor for LC, more in MF history, never-smokers, younger adults, and those with maternal relatives with LC. Randomized controlled trials are needed to confirm mortality benefit of LDCT screening in those with LCFH.

PMID:37414358 | DOI:10.1016/j.jtho.2023.06.018

Gynecol Obstet Fertil Senol. 2023 Jul 4:S2468-7189(23)00153-8. doi: 10.1016/j.gofs.2023.06.005. Online ahead of print.

NO ABSTRACT

PMID:37414341 | DOI:10.1016/j.gofs.2023.06.005

Chest. 2023 Jul 4:S0012-3692(23)00945-5. doi: 10.1016/j.chest.2023.06.038. Online ahead of print.

ABSTRACT

Developing and evaluating statistical prediction models is challenging, and many pitfalls can arise. This article identifies what the authors feel are some common methodological concerns that may be encountered. We describe each problem and make suggestions on how to address them. The hope is that this manuscript will result in higher quality publications of statistical prediction models.

PMID:37414333 | DOI:10.1016/j.chest.2023.06.038

Chemosphere. 2023 Jul 4:139362. doi: 10.1016/j.chemosphere.2023.139362. Online ahead of print.

ABSTRACT

BACKGROUND: The association between long-term air pollution exposure and the development of idiopathic pulmonary fibrosis (IPF) has been established, but the evidence regarding the effect of low levels of air pollution, especially ambient sulfur dioxide (SO₂), is limited. Besides, the combined effect and interaction between genetic susceptibility and ambient SO₂ on IPF remain uncertain.

METHODS: This study retrieved data from 402,042 participants who were free of IPF at baseline in the UK Biobank. The annual mean concentration of ambient SO₂ was estimated for each participant based on their residential addresses using a bilinear interpolation method. Cox proportional hazard models were used to examine the relationship between ambient SO₂ and incident IPF. We further generated a polygenic risk score (PRS) for IPF and estimated the combined effects of genetic susceptibility and ambient SO₂ on incident IPF.

RESULTS: After a median follow-up of 11.78 years, 2562 cases of IPF were identified. The results indicated that each 1 μg/m³ increase in ambient SO₂ was associated with a hazard ratio (HR) (95% confidence interval [CI]) of 1.67 (1.58, 1.76) for incident IPF. The study found statistically significant synergistic additive interaction between genetic susceptibility and ambient SO₂. Individuals with high genetic risk and high ambient SO₂ exposure had a higher risk of developing IPF (HR = 7.48, 95% CI:5.66, 9.90).

CONCLUSION: The study suggests that long-term exposure to ambient SO₂, even at concentrations lower than current air quality guidelines set by the Word Health Organization and European Union, may be an important risk factor for IPF. This risk is more pronounced among people with a high genetic risk. Therefore, these findings emphasize the need to consider the potential health effects of SO₂ exposure and the necessity for stricter air quality standards.

PMID:37414299 | DOI:10.1016/j.chemosphere.2023.139362

J Food Prot. 2023 Jul 4:100126. doi: 10.1016/j.jfp.2023.100126. Online ahead of print.

ABSTRACT

Previous environmental monitoring projects in food production facilities have revealed inconsistencies in how produce brush washer machines are cleaned after use; thus, study of effective sanitation procedures for these machines is needed. Four chlorine solution treatments (ranging from 25-200ppm), as well as a water-only treatment, were tested for efficacy in reducing bacterial loads for a selected small brush washer machine. Results indicate that rinsing with the machine’s power and water alone, a frequent practice among some produce processors, yielded a reduction of 0.91-1.96 log CFU per brush roller in bacterial counts, which was not statistically significant (p>0.05). However, the chlorine treatments were found to be effective in reducing bacterial loads significantly, with higher concentrations being the most effective. The 200ppm and 100ppm chlorine treatments yielded bacterial reductions of 4.08 and 3.95 log CFU per brush roller respectively, leaving bacterial levels statistically similar to the levels at post-process decontamination, meaning these are the most effective at killing bacteria of all the chlorine concentrations tested. These data suggest the use of at least 100ppm chlorine sanitizer solution is a good method to sanitize hard-to-clean produce washing machines, yielding an approximate 4 log CFU reduction of the inoculated bacteria.

PMID:37414285 | DOI:10.1016/j.jfp.2023.100126

J Am Pharm Assoc (2003). 2023 Jul 4:S1544-3191(23)00237-6. doi: 10.1016/j.japh.2023.06.024. Online ahead of print.

ABSTRACT

BACKGROUND: The growing population demand and the epidemic lead of Coronavirus Disease 2019 (COVID-19) have highlighted the critical importance of patient access to compounded formulations, including for special purposes such as pediatrics, geriatrics, and other uses. However, there are many potential risks, including quality issues and 503A facilities have not received valid prescriptions for individually-identified patients for a portion of the drug products they produce.

OBJECTIVE: The aim is to analyze the (503A facilities) warning letters and identify the problem of compounding medicines not meeting the USP specifications.

METHODS: Content analysis and descriptive statistics methods were used to analyze the violations of compounding warning letters from 2017 to 2021. The content of warning letter violations was analyzed in terms of both the compounding environment and 503A facilities that did not received valid prescriptions for individually-identified patients for a portion of the drug products they produced.

RESULTS: A total of 113 compounding warning letters (503A facilities, N=112) from 2017 to 2021 were analyzed in this study. The percentage of 503A facilities involved in sterile compounding environmental issues was 79.46%, with facility design and environmental controls (73/89, 82.02%), cleaning and disinfecting the compounding area (59/89, 66.29%), and personnel cleansing and garbing (44/89, 49.44%) being the top three issues. Seventy-two (72/112, 64.29%) 503A facilities that did not received valid prescriptions for individually-identified patients for a portion of the drug products they produced. Fifty-one (51/72, 70.83%) of these warning letters were related to sterile environment issues, and 28 warning letters identified specific drugs that did not qualify for Section 503A exemptions.

CONCLUSION: The warning letter of compounding drugs issued by FDA can be used as a learning tool for compounders. Compounders can learn from the experience and lessons, improve compounding operations and reduce mistakes.

PMID:37414280 | DOI:10.1016/j.japh.2023.06.024

Hear Res. 2023 Jun 20;436:108837. doi: 10.1016/j.heares.2023.108837. Online ahead of print.

ABSTRACT

Sensitivity to changes in the stimulus level at one or at both ears and to changes in the interaural level difference (ILD) between the two ears has been studied widely. Several different definitions of threshold and, for one of them, two different ways of averaging single-listener thresholds have been used (i.e., arithmetically and geometrically), but it is unclear which definition and which way of averaging is most suitable. Here, we addressed this issue by examining which of the differently defined thresholds yielded the highest degree of homoscedasticity (homogeneity of the variance). We also examined how closely the differently defined thresholds followed the normal distribution. We measured thresholds from a large number of human listeners as a function of stimulus duration in six experimental conditions, using an adaptive two-alternative forced-choice paradigm. Thresholds defined as the logarithm of the ratio of the intensities or amplitudes of the target and the reference stimulus (i.e., as the difference in their levels or ILDs; the most commonly used definition) were clearly heteroscedastic. Log-transformation of these latter thresholds, as sometimes performed, did not result in homoscedasticity. Thresholds defined as the logarithm of the Weber fraction for stimulus intensity and thresholds defined as the logarithm of the Weber fraction for stimulus amplitude (the most rarely used definition) were consistent with homoscedasticity, but the latter were closer to the ideal case. Thresholds defined as the logarithm of the Weber fraction for stimulus amplitude also followed the normal distribution most closely. The discrimination thresholds should therefore be expressed as the logarithm of the Weber fraction for stimulus amplitude and be averaged arithmetically across listeners. Other implications are discussed, and the obtained differences between the thresholds in different conditions are compared to the literature.

PMID:37413706 | DOI:10.1016/j.heares.2023.108837

Chic Med J. 1875 Aug;32(8):639-640.

NO ABSTRACT

PMID:37413629 | PMC:PMC9812181