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Genome-wide association study identifies WWC2 as a possible locus associated with persistent pulmonary hypertension of the newborn in the Thai population

Transl Pediatr. 2023 Jan 31;12(1):1-12. doi: 10.21037/tp-22-280. Epub 2023 Jan 16.

ABSTRACT

BACKGROUND: There is known to be significant genetic involvement in persistent pulmonary hypertension of the newborn (PPHN), but to date there is not a clear understanding of this situation, and clarifying that involvement would be of considerable assistance in devising effective treatments for the disease. This case-control study was undertaken to search for genetic variants associated with PPHN in the Thai population using a genome-wide association study (GWAS).

METHODS: A 659,184 single nucleotide polymorphisms from 387 participants (54 PPHN cases and 333 healthy participants) were genotyped across the human genome using an Illumina Asian Screening Array-24 v1.0 BeadChip Array. After quality control, we obtained 443,063 autosomal SNPs for the GWAS analysis. The FaST-LMM and R packages were used for all statistical analyses.

RESULTS: For the case-control analysis, the genomic inflation factor (λ) was 1.016, rs149768622 T>C in the first intron of WWC2 gene showed the strongest association with a P value of 3.76E-08 and odds ratio (OR) of 13.24 (95% CI: 3.91-44.78). The variants at the LOC102723906/LOC105377599, CADM4, GPM6A, CIT, RIMBP2, LOC105374510, LOC105375193, PTPRN2, CDK14, and LCORL loci showed suggestive evidence of associations with PPHN (P<1E-05).

CONCLUSIONS: This GWAS found that rs149768622 T>C in the WWC2 gene was possibly associated with PPHN. However, replication and functional studies are needed to validate this association and further explore the role(s) of the WWC2 gene in PPHN.

PMID:36798934 | PMC:PMC9926135 | DOI:10.21037/tp-22-280

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A dose planning study for cardiac and lung dose sparing techniques in left breast cancer radiotherapy: Can free breathing helical tomotherapy be considered as an alternative for deep inspiration breath hold?

Tech Innov Patient Support Radiat Oncol. 2023 Jan 26;25:100201. doi: 10.1016/j.tipsro.2023.100201. eCollection 2023 Mar.

ABSTRACT

PURPOSE: To investigate the possibility to be able to offer left sided breast cancer patients, not suitable for DIBH, an organ at risk saving treatment.

MATERIALS AND METHODS: Twenty patients receiving radiotherapy for left breast cancer in DIBH were enrolled in the study. Planning CT scans were acquired in the same supine treatment position in FB and DIBH. 3DCRT_DIBH plans were designed and optimized using two parallel opposed tangent beams (with some additional segments) for the breast and chest wall and anterior-posterior fields for regional lymph nodes irradiation. Additionally, FB helical tomotherapy plans were optimized to minimize heart and lung dose. All forty plans were optimized with at least 95% of the total CTV covered by the 95% of prescribed dose of 50 Gy in 25 fractions.

RESULTS: HT_FB plans showed significantly better dose homogeneity and conformity compared to the 3DCRT_DIBH specially for regional nodal irradiation. The heart mean dose was almost comparable in 3DCRT_DIBH and HT_FB while the volume (%) of the heart receiving 25 Gy had a statistically significant reduction from 7.90 ± 3.33 in 3DCRT_DIBH to 0.88 ± 0.66 in HT_FB. HT_FB was also more effective in left descending artery (LAD) mean dose reduction about 100% from 30.83 ± 9.2 Gy to 9.7 ± 3.1. The ipsilateral lung volume receiving 20 Gy has a further reduction of 43 % in HT_FB compared with 3DCRT_DIBH. For low dose comparison, 3DCRT_DIBH was superior for contralateral organ sparing compared to the HT_FB due to the limited angle for dose delivery.

CONCLUSION: For patients who cannot be a candidate for DIBH for any reason, HT in free breathing may be a good alternative and provides heart and ipsilateral lung dose sparing, however with the cost of increased dose to contralateral breast and lung.

PMID:36798947 | PMC:PMC9926227 | DOI:10.1016/j.tipsro.2023.100201

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Predictors of Mortality for Patients with ST-Elevation Myocardial Infraction after 2-Year Follow-Up: A ST-Elevation Myocardial Infarction Cohort in Isfahan Study

Adv Biomed Res. 2022 Dec 26;11:116. doi: 10.4103/abr.abr_242_21. eCollection 2022.

ABSTRACT

BACKGROUND: Mortality of ST-elevation myocardial infarction (STEMI) patients is increasing in world. This study defines predictors of mortality in patients who have STEMI.

MATERIALS AND METHODS: This study was a part of the ST-elevated myocardial infarction cohort study in Isfahan conducted on 876 acute myocardial infarction (MI) followed for 2 years that 781 patient entered. The effect of predictors of mortality includes demographic, physiological, and clinical characterizes compared in two groups alive and died patients. MACE was defined as nonfatal MI, nonfatal stroke, and atherosclerosis cardiovascular disease-related death was recorded. Univariate and multiple logistic regression analyses were performed. All analyses performed using SPSS 20.0. P < 0.05 considered statistically significant.

RESULTS: A total 781 patients, 117 (13%) that 72 (8.5%) was in-hospital died. The mean (standard deviation) age of the patients was 60.92 (12.77) years and 705 (81.3%) patients were males. Significant factors that affected mortality on analysis of demographic and physiological parameters were age (P < 0.001), sex (P = 0.004), transfusion (P = 0.010), STEMI type (P < 0.001), number epicardial territories >50% (P = 0.001), ventilation options (P < 0.001), smoker (P = 0.003), and diabetes (P = 0.026). Significant clinical factors affected mortality were ejection fraction (EF) (P < 0.001), creatinine (P < 0.001), hemoglobin (P < 0.001), low-density lipoprotein-cholesterol (LDL-C) (P = 0.019), and systolic blood pressure (P < 0.001). Multiple logistics regression model definition significant predictors for mortality were age (P < 0.001), heart rate (HR) (P = 0.007), EF (0.039), LDL-C (P = 0.002), and preangia (P = 0.022).

CONCLUSION: The set of factors can increase or decrease mortality in these patients. Significant predictors of mortality STEMI patients by 2-year follow up were age, HR, EF, LDL-C, and preangia. It seems that more articles need to be done in different parts of Iran to confirm the results.

PMID:36798920 | PMC:PMC9926029 | DOI:10.4103/abr.abr_242_21

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Association of Subclinical Hypothyroidism with Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study

Adv Biomed Res. 2022 Dec 26;11:124. doi: 10.4103/abr.abr_15_21. eCollection 2022.

ABSTRACT

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are recognized as two common health problems. Metabolic diseases, such as dyslipidemia, obesity, and hypertension are known risk factors for NAFLD. In addition to these risk factors, other risk factors have been recently suggested, such as thyroid dysfunction.

MATERIALS AND METHODS: In this study, adult patients with T2DM were recruited. Various clinical and biochemical parameters including thyroid function tests, liver function tests, and liver sonography in all participants were assessed and compared between with and without NAFLD groups.

RESULTS: Data from 926 diabetic patients were analyzed; of which, 744 (80.3%) had fatty liver. The prevalence of subclinical hypothyroidism (SCH) in patients with NAFLD was 11.6% and in patients without NAFLD was 6.0% (P = 0.029). Furthermore, the prevalence of overt hypothyroidism was higher in diabetic patients with NAFLD (3.9% vs. 1.6%); this difference was not statistically significant. In univariate logistic regression analysis, hemoglobin A1c (odds ratio [OR]: 8.13); history of insulin consumption (OR: 5.35); duration of diabetes (OR: 2.20); family history of diabetes (OR: 2.85); history of antihypertensive drug use (OR: 2.14) as well as SCH (OR: 2.03) were significant variables for NAFLD. According to the multivariate logistic model, after eliminating the confounding effect of age, sex, and body mass index; the chance of developing NAFLD in patients with SCH was 2.32 times higher than patients without SCH (P = 0.014).

CONCLUSION: NAFLD is extremely common in patients with T2DM. The relationship between hypothyroidism and NAFLD is independent of other risk factors.

PMID:36798918 | PMC:PMC9926038 | DOI:10.4103/abr.abr_15_21

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Magnetic transferrin nanoparticles (MTNs) assay as a novel isolation approach for exosomal biomarkers in neurological diseases

Biomater Res. 2023 Feb 16;27(1):12. doi: 10.1186/s40824-023-00353-2.

ABSTRACT

BACKGROUND: Brain-derived exosomes released into the blood are considered a liquid biopsy to investigate the pathophysiological state, reflecting the aberrant heterogeneous pathways of pathological progression of the brain in neurological diseases. Brain-derived blood exosomes provide promising prospects for the diagnosis of neurological diseases, with exciting possibilities for the early and sensitive diagnosis of such diseases. However, the capability of traditional exosome isolation assays to specifically isolate blood exosomes and to characterize the brain-derived blood exosomal proteins by high-throughput proteomics for clinical specimens from patients with neurological diseases cannot be assured. We report a magnetic transferrin nanoparticles (MTNs) assay, which combined transferrin and magnetic nanoparticles to isolate brain-derived blood exosomes from clinical samples.

METHODS: The principle of the MTNs assay is a ligand-receptor interaction through transferrin on MTNs and transferrin receptor on exosomes, and electrostatic interaction via positively charged MTNs and negatively charged exosomes to isolate brain-derived blood exosomes. In addition, the MTNs assay is simple and rapid (< 35 min) and does not require any large instrument. We confirmed that the MTNs assay accurately and efficiently isolated exosomes from serum samples of humans with neurodegenerative diseases, such as dementia, Parkinson’s disease (PD), and multiple sclerosis (MS). Moreover, we isolated exosomes from serum samples of 30 patients with three distinct neurodegenerative diseases and performed unbiased proteomic analysis to explore the pilot value of brain-derived blood protein profiles as biomarkers.

RESULTS: Using comparative statistical analysis, we found 21 candidate protein biomarkers that were significantly different among three groups of neurodegenerative diseases.

CONCLUSION: The MTNs assay is a convenient approach for the specific and affordable isolation of extracellular vesicles from body fluids for minimally-invasive diagnosis of neurological diseases.

PMID:36797805 | DOI:10.1186/s40824-023-00353-2

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The impact of migration-related characteristics on the risk of TORCH infections among women of childbearing age: a population-based study in southern China

BMC Public Health. 2023 Feb 16;23(1):351. doi: 10.1186/s12889-023-15238-1.

ABSTRACT

BACKGROUND: TORCH infections are the most common prenatal infections causing congenital malformation and infant mortality, especially in developing countries. Migrant women might be vulnerable to TORCH infections, but little is known about the association between migration-related characteristics and TORCH infection risk. This study aimed to investigate the impact of migrant status, migration distance, and the spouse’s migrant status on the TORCH epidemic among women of childbearing age.

METHODS: Based on the National Free Preconception Health Examination Project, we analyzed a representative dataset of TORCH infections among women of childbearing age (15-49 years old) in Guangdong Province of China (2014-2019, n = 2,451,297). The past and/or recent infection status of TORCH infections (Toxoplasma gondii [TOX], Cytomegalovirus [CMV], and Rubella virus [RV]) were identified. Demographic and migration-related characteristics were collected. We thoroughly assessed the prevalence of TORCH infections in both migrant and native women and estimated adjusted odd ratios (aOR) for migration-related characteristics using multivariable logistic regression after adjusting the other sociodemographic factors.

RESULTS: Among all 2,451,297 participants, 443,725 (18.1%) were migrant women. Migrant women presented a lower risk of past TOX infection (aOR: 0.89, 0.88-0.91) suggesting a healthy migrant effect (HME), but a higher risk of recent TOX infection (aOR: 1.88, 1.77-1.99), past CMV infection (aOR: 1.26, 1.25-1.28) and RV infection in natural ways (aOR: 1.05, 1.04-1.06). Compared with intra-provincial migrants, inter-provincial migrants had a lower past TOX infection (aOR: 0.88, 0.85-0.91), but a higher risk of recent TOX infection (aOR: 1.16, 1.05-1.27) and RV infection (aOR: 1.33, 1.31-1.36). In addition, having a migrant spouse was associated with a higher risk for all types of infection.

CONCLUSION: This study reported the association of migrant status and migration distance with TORCH infections, although the significance and directionality of these associations varied between pathogens. The spouse’s migrant status further amplified the infection risk for all types of pathogens. Our findings suggested interventions for preventing the spread of CMV and RV infection and new acquisition of TOX infection for migrants in southern China, to narrow the native-migrant health inequity and decrease the incidence of prenatal infections and related adverse outcomes.

PMID:36797787 | DOI:10.1186/s12889-023-15238-1

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Maternal hypertensive disorders during pregnancy and the risk of offspring diabetes mellitus in childhood, adolescence, and early adulthood: a nationwide population-based cohort study

BMC Med. 2023 Feb 16;21(1):59. doi: 10.1186/s12916-023-02762-5.

ABSTRACT

BACKGROUND: Maternal hypertensive disorders during pregnancy (HDP) have been suggested to contribute to the development of offspring cardiovascular disease later in life, but empirical evidence remains inconsistent. This study was aimed to assess the association of maternal overall and type-specific HDPs with diabetes in offspring from childhood to early adulthood.

METHODS: Using Danish national health registers, a total of 2,448,753 individuals born in Denmark from 1978 to 2018 were included in this study. Maternal HDP included chronic hypertension, gestational hypertension, and preeclampsia. The outcome of interest was diabetes in offspring (including type 1, type 2, and gestational diabetes). The follow-up of offspring started at birth and ended at the first diagnosis of diabetes, emigration from Denmark, death, or time end on 31 December 2018, whichever came first. Cox proportional hazards regression was used to evaluate the hazard ratios (HRs) with 95% confidence intervals (CIs) of the association between maternal HDP and diabetes (including type 1, type 2, and gestational diabetes) in offspring from birth to young adulthood (up to 41 years), with the offspring’s age as the time scale.

RESULTS: During a follow-up of up to 41 (median: 19.3) years, 1247 offspring born to mothers with HDP and 23,645 offspring born to mothers without HDP were diagnosed with diabetes. Compared with offspring born to mothers without HDP, those born to mothers with HDP had an increased risk for overall diabetes (HR=1.27, 95% CI=1.20-1.34), as well as for type 2 diabetes (HR=1.57, 95% CI=1.38-1.78) and gestational diabetes (HR=1.37, 95% CI=1.25-1.49). We did not observe obvious increased risk for type 1 diabetes (HR=1.08, 95% CI=0.98-1.18). Offspring of mothers with gestational hypertension (HR=1.37, 95% CI=1.00-1.88) or preeclampsia (HR=1.62, 95% CI=1.41-1.87) had higher risks of type 2 diabetes. The strongest association was observed for severe preeclampsia, with a 2-fold risk of type 2 diabetes (HR=2.00, 95% CI=1.42-2.82). The association between maternal HDP and type 1 diabetes did not reach statistical significance, except for maternal gestational hypertension (HR=1.41, 95%CI=1.17-1.71). In addition, we found that offspring born to mothers with any subtypes of maternal HDP had higher risk of gestational diabetes, and the corresponding HRs (95%CIs) for chronic hypertension, gestational hypertension, and preeclampsia were 1.60 (1.06-2.41), 1.29 (1.04-1.59), and 1.38 (1.24-1.53), respectively. We also observed stronger associations among offspring of mothers with HDP and comorbid diabetes (HR=4.64, 95%CI=3.85-5.60) than offspring of mothers with HDP or diabetes alone.

CONCLUSIONS: Offspring of mothers with HDP, especially mothers with comorbid diabetes, had an increased risk of diabetes later in their life. Our findings suggest that timely and effective prevention of HDP in women of childbearing age should be taken into consideration as diabetes prevention and control strategies for their generations.

PMID:36797785 | DOI:10.1186/s12916-023-02762-5

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Assessing the impact of COVID-19 interventions on influenza-like illness in Beijing and Hong Kong: an observational and modeling study

Infect Dis Poverty. 2023 Feb 16;12(1):11. doi: 10.1186/s40249-023-01061-8.

ABSTRACT

BACKGROUND: The impact of coronavirus diseases 2019 (COVID-19) related non-pharmaceutical interventions (NPIs) on influenza activity in the presence of other known seasonal driving factors is unclear, especially at the municipal scale. This study aimed to assess the impact of NPIs on outpatient influenza-like illness (ILI) consultations in Beijing and the Hong Kong Special Administrative Region (SAR) of China.

METHODS: We descriptively analyzed the temporal characteristics of the weekly ILI counts, nine NPI indicators, mean temperature, relative humidity, and absolute humidity from 2011 to 2021. Generalized additive models (GAM) using data in 2011-2019 were established to predict the weekly ILI counts under a counterfactual scenario of no COVID-19 interventions in Beijing and the Hong Kong SAR in 2020-2021, respectively. GAM models were further built to evaluate the potential impact of each individual or combined NPIs on weekly ILI counts in the presence of other seasonal driving factors in the above settings in 2020-2021.

RESULTS: The weekly ILI counts in Beijing and the Hong Kong SAR fluctuated across years and months in 2011-2019, with an obvious winter-spring seasonality in Beijing. During the 2020-2021 season, the observed weekly ILI counts in both Beijing and the Hong Kong SAR were much lower than those of the past 9 flu seasons, with a 47.5% [95% confidence interval (CI): 42.3%, 52.2%) and 60.0% (95% CI: 58.6%, 61.1%) reduction, respectively. The observed numbers for these two cities also accounted for only 40.2% (95% CI: 35.4%, 45.3%) and 58.0% (95% CI: 54.1%, 61.5%) of the GAM model estimates in the absence of COVID-19 NPIs, respectively. Our study revealed that, “Cancelling public events” and “Restrictions on internal travel” measures played an important role in the reduction of ILI in Beijing, while the “restrictions on international travel” was statistically most associated with ILI reductions in the Hong Kong SAR.

CONCLUSIONS: Our study suggests that COVID-19 NPIs had been reducing outpatient ILI consultations in the presence of other seasonal driving factors in Beijing and the Hong Kong SAR from 2020 to 2021. In cities with varying local circumstances, some NPIs with appropriate stringency may be tailored to reduce the burden of ILI caused by severe influenza strains or other respiratory infections in future.

PMID:36797765 | DOI:10.1186/s40249-023-01061-8

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Epidural lidocaine, butorphanol, and butorphanol – lidocaine combination in dromedary camels

BMC Vet Res. 2023 Feb 16;19(1):51. doi: 10.1186/s12917-023-03601-8.

ABSTRACT

BACKGROUND: The use of general anesthesia in dromedary camels is constrained by risks related to decubitus. Caudal epidural analgesia is an alternative convenient technique providing loco-regional analgesia for numerous invasive and noninvasive painful conditions. Lidocaine is probably the most commonly used local anesthetic in clinical practice, but has a relatively short duration and may not provide significant long term analgesic benefits. Epidural administration of an opioid-local anesthetic mixture would improve the quality and length of analgesia and minimizes the adverse motor effects provoked by local anesthetics. Butorphanol (potent agonist-antagonist opioid) has been used to improve the duration of epidural analgesia in some animal species, but not in camels. Therefore, our purpose was to investigate the onset and duration of analgesia as well as the clinical and hemato-biochemical effects produced by the epidural administration of butorphanol (0.04 mg/kg), lidocaine (0.22 mg/ kg), and butorphanol-lidocaine (0.04 mg/kg-0.22 mg/ kg) mixture in nine adult dromedary camels in a crossover experimental study.

RESULTS: The onset of analgesia was not statistically different between lidocaine (6.5 ± 2.3 min) and butorphanol-lidocaine (7.3 ± 1.5 min) combination. Delayed onset of analgesia was reported after butorphanol administration (14.7 ± 3.5 min). Butorphanol-lidocaine combination produced marked longer duration (175 ± 8.7 min) than lidocaine (55 ± 6.8 min) and butorphanol (158 ± 5.3 min). Mild ataxia was observed in the butorphanol-lidocaine and lidocaine treated animals and slight sedation was reported after butorphanol and butorphanol-lidocaine administration. A transient significant increase in the glucose levels was recorded after all treatments.

CONCLUSIONS: Epidural administration of butorphanol augments the analgesic effects and duration of lidocaine with minimal adverse effects.

PMID:36797763 | DOI:10.1186/s12917-023-03601-8

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Differences between the dispatch priority assessments of emergency medical dispatchers and emergency medical services: a prospective register-based study in Finland

Scand J Trauma Resusc Emerg Med. 2023 Feb 16;31(1):8. doi: 10.1186/s13049-023-01072-2.

ABSTRACT

BACKGROUND: Responsive and efficient emergency medical services (EMS) require accurate telephone triage. In Finland, such services are provided by Emergency Response Centre Agency (ERC Agency). In 2018, a new Finnish computer-assisted emergency dispatch system was introduced: the Emergency Response Integrated Common Authorities (ERICA). After the introduction of ERICA, the appropriateness of EMS dispatch has not been investigated yet. The study´s objective is to determine the consistency between the priority triage of the emergency medical dispatcher (EMD) and the on-scene priority assessment of the EMS, and whether the priority assessment consistency varied among the dispatch categories.

METHODS: This was a prospective register-based study. All EMS dispatches registered in the Tampere University Hospital area from 1 August 2021 to 31 August 2021 were analysed. The EMD’s mission priority triaged during the emergency call was compared with the on-scene EMS’s assessment of the priority, derived from the pre-set criteria. The test performance levels were measured from the crosstabulation of true or false positive and negative values of the priority assessment. Statistical significance was analysed using the chi-square test and the Kruskal-Wallis H test, and p-values < 0.05 were considered significant.

RESULTS: Of the 6416 EMS dispatches analysed in this study, 36% (2341) were urgent according to the EMD’s dispatch priority, and of these, only 29% (688) were urgent according to the EMS criteria. On the other hand, 64% (4075) of the dispatches were non-urgent according to the EMD’s dispatch priority, of which 97% (3949) were non-urgent according to the EMS criteria. Moreover, there were differences between the EMD and EMS priority assessments among the dispatch categories (p < 0.001). The overall efficiency was 72%, sensitivity 85%, specificity 71%, positive predictive value 29%, and negative predictive value 97%.

CONCLUSION: While the EMD recognised the non-urgent dispatches with high consistency with the EMS criteria, most of the EMD’s urgent dispatches were not urgent according to the same criteria. This may diminish the availability of the EMS for more urgent missions. Thus, measures are needed to ensure more accurate and therefore, more efficient use of EMS resources in the future.

PMID:36797760 | DOI:10.1186/s13049-023-01072-2