Nevin Manimala

Eur J Med Res. 2022 Oct 10;27(1):199. doi: 10.1186/s40001-022-00828-3.

ABSTRACT

OBJECTIVES: The aim of this study was to investigate serum biomarkers linked to primary Sjögren’s syndrome (pSS)-associated interstitial lung disease (ILD).

METHODS: 69 pSS patients were consecutively enrolled and evaluated via quantitative ILD scoring based on high-resolution computed tomography (HRCT). Biomarkers of interest were assessed by multiplex enzyme-linked immunosorbent assays (ELISAs).

RESULTS: Among consecutively enrolled patients with pSS, the presence of pSS-ILD was 50% based on the presence of radiographically defined interstitial lung abnormalities (ILA) meeting specified criteria for mild/moderate (ILA 2) or severe (ILA 3) disease. Age, immunoglobulin M (IgM), C-reactive protein (CRP), and serum levels of eotaxin/CCL11, Krebs von den Lungen-6 (KL-6), TNFα, and TGFα were significantly higher in the combined pSS-ILD group (ILA 2 + ILA 3) than in the pSS-no-ILD and pSS-indeterminate ILD groups (ILA 0 and ILA 1, respectively) in unadjusted analyses (p < 0.05 for all variables). A binary logistic regression model revealed that disease duration and KL-6 levels were associated with the presence of pSS-ILD (p < 0.05). Complementary least absolute shrinkage and selection operator (LASSO) modeling showed that age, KL-6, and TNF-α effectively differentiated pSS-ILD (ILA 2 + ILA3) from pSS without ILD (ILA 0 + ILA 1), with an area under the curve (AUC) of 0.883 (p value < 0.0001).

CONCLUSIONS: Patient age, disease duration, and serum levels of both KL-6 and TNFα were the most discriminating factors associated with the presence of ILD in our pSS patients. Higher levels of CRP, IgM, eotaxin, TGFα, and TNFα should also prompt the search for occult as well as clinically evident lung involvement based on statistically significant univariate associations with pSS-ILD.

CLINICAL TRIAL REGISTRATION: None.

PMID:36217184 | DOI:10.1186/s40001-022-00828-3

Mol Cancer. 2022 Oct 10;21(1):195. doi: 10.1186/s12943-022-01665-y.

ABSTRACT

BACKGROUND: Papillary thyroid carcinoma (PTC) is one of the most common forms of thyroid cancer with a cure rate of over 90% after surgery. However, aggressive forms may still occur, and personalized therapeutic strategies are increasingly required.

METHODS: We performed integrated genomic and proteomic analysis of PTC tumor samples from patients who did not harbor BRAF or RAS mutations. We validate the analysis and present in-depth molecular analysis of the identified genetic rearrangement by employing biochemical and cell biological assays. Finally, we employ 3D spheroid models, loss of function studies and chemical inhibitors to target the hitherto upregulated factors. The data are analysed with appropriate statistical tests which are mentioned in the legends section.

RESULTS: In a 23-year-old patient with thyroiditis, we identified a novel rearrangement leading to a BAIAP2L1-BRAF fusion that transforms immortalized human thyroid cells in a kinase and CC-domain dependent manner. Moreover, quantitative proteomic analysis of the same patient samples revealed the upregulation of several proteins including the Ubiquitin E3 ligase TRIM25, PDE5A, and PKCδ. Further, in a cohort of PTC patients, we observed higher expression of TRIM25 and PKCδ in the tumor and metastatic lesions, when compared to the matched normal tissue. Inhibition of TRIM25, PDE5A and PKCδ with small molecules or RNA interference affected not only viability and proliferation of BAIAP2L1-BRAF transformed cells, but also the viability, growth and invasion of corresponding 3D spheroid cultures.

CONCLUSIONS: Apart from unveiling a novel oncogenic BRAF fusion in PTCs, our data may open a novel avenue of therapeutic targeting in human PTCs.

PMID:36217175 | DOI:10.1186/s12943-022-01665-y

Clin Epigenetics. 2022 Oct 10;14(1):125. doi: 10.1186/s13148-022-01345-0.

ABSTRACT

BACKGROUND: Phthalates and bisphenols are non-persistent endocrine disrupting chemicals that are ubiquitously present in our environment and may have long-lasting health effects following fetal exposure. A potential mechanism underlying these exposure-outcome relationships is differential DNA methylation. Our objective was to examine the associations of maternal phthalate and bisphenol concentrations during pregnancy with DNA methylation in cord blood using a chemical mixtures approach.

METHODS: This study was embedded in a prospective birth cohort study in the Netherlands and included 306 participants. We measured urine phthalates and bisphenols concentrations in the first, second and third trimester. Cord blood DNA methylation in their children was processed using the Illumina Infinium HumanMethylation450 BeadChip using an epigenome-wide association approach. Using quantile g-computation, we examined the association of increasing all mixture components by one quartile with cord blood DNA methylation.

RESULTS: We did not find evidence for statistically significant associations of a maternal mixture of phthalates and bisphenols during any of the trimesters of pregnancy with DNA methylation in cord blood (all p values > 4.01 * 10^-8). However, we identified one suggestive association (p value < 1.0 * 10^-6) of the first trimester maternal mixture of phthalates and bisphenols and three suggestive associations of the second trimester maternal mixture of phthalates and bisphenols with DNA methylation in cord blood.

CONCLUSIONS: Although we did not identify genome-wide significant results, we identified some suggestive associations of exposure to a maternal mixture of phthalates and bisphenols in the first and second trimester with DNA methylation in cord blood that need further exploration in larger study samples.

PMID:36217170 | DOI:10.1186/s13148-022-01345-0

BMC Nurs. 2022 Oct 10;21(1):275. doi: 10.1186/s12912-022-01049-z.

ABSTRACT

INTRODUCTION: Older adults with Alzheimer’s disease (AD) experience drastic changes in their physical and mental abilities. AD patients became heavily dependent on their caregivers for everyday functions, which have significant implications not only for them but also for their caregivers. So, many AD caregivers experienced an increased level of depression and anxiety symptoms, lower perceived control, and higher burden compared to non-AD caregivers. Therefore, psychological first aid (PFA) and educational interventions are designed to enable those caregivers to meet the daily requirements of their patient care and to cope with its challenges.

AIM: Determine the effect of psychological first aid program on stress level and psychological well-being among caregivers of older adults with Alzheimer’s disease.

DESIGN: One group pre-test post-test was followed.

SUBJECTS: A convenience sample of one hundred (100) caregivers of older adults with AD.

SETTING: All online groups concerned with the care of Alzheimer’s disease patients on Facebook.

TOOLS: Socio-demographic and clinical data of older adults with Alzheimer’s disease and their caregivers’ questionnaire, Alzheimer’s disease knowledge scale, Kingston caregiver stress scale, and authentic identity measures (AIM) scale of psychological well-being RESULTS: The psychological first aid program has highly statistically significant effect on the AD caregivers’ knowledge, stress level and psychological well-being as (t=-30.707, P = 0.000, t = 8.500, P = 0.000 & t= -4.763, P = 0.000 respectively).

CONCLUSION: Psychological first aid program is considered an effective intervention in decreasing the AD caregivers’ stress and increasing their psychological wellbeing and knowledge regarding delivering care for AD patients.

PMID:36217138 | DOI:10.1186/s12912-022-01049-z

BMC Oral Health. 2022 Oct 10;22(1):441. doi: 10.1186/s12903-022-02483-w.

ABSTRACT

BACKGROUND: The aim of the present study was to compare the effects on vertical dentoskeletal dimension produced by Pendulum appliance and Clear Aligners in patients with Class II malocclusion.

TRIAL DESIGN: This is a prospective two-arm parallel group randomized clinical trial with 1:1 allocation ratio.

METHODS: The Pendulum Group (PG) consisted of 20 patients (15F, 5 M) with a mean age of 17.2 ± 4.3 years. The Clear Aligners Group (CAG) comprised 20 patients (13F, 7 M) with a mean age of 17.2 ± 3.2 years. Distalization’s protocol in PG involved the activation of TMA wires till the achievement of Class I molar relationship. A protocol of sequential distalization was applied in the CAG. For each subject lateral cephalograms have been analyzed before treatment (T1) and at the end of the therapy (T2). Descriptive statistics and statistical between-group comparisons (PG vs CAG) were calculated for the craniofacial starting forms at T1 and for the T2-T1 changes. Statistical between-group comparisons for the T2-T1 changes were performed with independent samples t-tests (P < 0.05).

RESULTS: The PG showed significantly greater increases in SN^GoGn° when compared with CAG (+ 2.1 and – 0.3 degrees, respectively). Clockwise rotation of the occlusal plane with significantly greater increase of SN^POccl angle was observed in PG (+ 2.8 degrees) when compared with CAG (- 4.2 degrees). The PG revealed a significant increase in the N-Me variable with a mean change of + 4.4 mm compared to the CAG with mean values of – 1.2 mm. The PG showed an increase in the ArGo^GoMe angle (+ 0.7° degrees) compared to the CAG (- 3.4° degrees). The PG showed significantly greater increases in both maxillary and mandibular first molar to palatal plane (+ 1.3 and + 2.1 mm, respectively) when compared with CAG (- 0.9 and – 0.2 mm, respectively).

CONCLUSIONS: Upper molar distalization with clear aligners represents a valid alternative to non-extraction treatment of Class II malocclusion, reducing the extrusion of maxillary first molars and improving the management of the occlusal plane and vertical dimension.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT05298280. Registered 28 March 2022-Retrospectively registered, https://clinicaltrials.gov .

PMID:36217134 | DOI:10.1186/s12903-022-02483-w

BMC Med. 2022 Oct 11;20(1):330. doi: 10.1186/s12916-022-02540-9.

ABSTRACT

BACKGROUND: Instruments to critically appraise randomised controlled trials (RCTs) are based on evidence from meta-epidemiological studies. We aim to conduct a meta-epidemiological study on the average bias associated with reported methodological trial characteristics such as random sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and compliance of RCTs in nutrition research.

METHODS: We searched the Cochrane Database of Systematic Reviews, for systematic reviews of RCTs, published between 01 January 2010 and 31 December 2019. We combined the estimates of the average bias (e.g. ratio of risk ratios [RRR] or differences in standardised mean differences) in meta-analyses using the random-effects model. Subgroup analyses were conducted to investigate the potential differences among the RCTs with low versus high/unclear risk of bias with respect to the different types of interventions (e.g. micronutrients, fatty acids, dietary approach), outcomes (e.g. mortality, pregnancy outcomes), and type of outcome (objective, subjective). Heterogeneity was assessed through I² and τ², and prediction intervals were calculated.

RESULTS: We included 27 Cochrane nutrition reviews with 77 meta-analyses (n = 927 RCTs). The available evidence suggests that intervention effect estimates may not be exaggerated in RCTs with high/unclear risk of bias (versus low) judgement for sequence generation (RRR 0.97, 95% CI 0.93 to 1.02; I² = 28%; τ² = 0.002), allocation concealment (RRR 1.00, 95% CI 0.96 to 1.04; I² = 27%; τ² = 0.001), blinding of participants and personnel (RRR 0.95, 95% CI 0.91 to 1.00; I² = 23%; τ² = 0), selective reporting (RRR 0.97, 95% CI 0.92 to 1.02; I² = 24%; τ² = 0), and compliance (RRR 0.95, 95% CI 0.89 to 1.02; I² = 0%; τ² = 0). Intervention effect estimates seemed to be exaggerated in RCTs with a high/unclear risk of bias judgement for blinding of outcome assessment (RRR 0.81, 95% CI 0.70 to 0.94; I² = 26%; τ² = 0.03), which was predominately driven by subjective outcomes, and incomplete outcome data (RRR 0.92, 95% CI 0.88 to 0.97; I² = 22%; τ² = 0.001). For continuous outcomes, no differences were observed, except for selective reporting.

CONCLUSIONS: On average, most characteristics of nutrition RCTs may not exaggerate intervention effect estimates, but the average bias appears to be greatest in trials of subjective outcomes. Replication of this study is suggested in this field to keep this conclusion updated.

PMID:36217133 | DOI:10.1186/s12916-022-02540-9

Adv Exp Med Biol. 2022;1384:219-239. doi: 10.1007/978-3-031-06413-5_13.

ABSTRACT

Obstructive sleep apnea (OSA) is a multidimensional disease often underdiagnosed due to the complexity and unavailability of its standard diagnostic method: the polysomnography. Among the alternative abbreviated tests searching for a compromise between simplicity and accurateness, oximetry is probably the most popular. The blood oxygen saturation (SpO₂) signal is characterized by a near-constant profile in healthy subjects breathing normally, while marked drops (desaturations) are linked to respiratory events. Parameterization of the desaturations has led to a great number of indices of severity assessment commonly used to assist in OSA diagnosis. In this chapter, the main methodologies used to characterize the overnight oximetry profile are reviewed, from visual inspection and simple statistics to complex measures involving signal processing and pattern recognition techniques. We focus on the individual performance of each approach, but also on the complementarity among the great amount of indices existing in the state of the art, looking for the most relevant oximetric feature subset. Finally, a quick overview of SpO₂-based deep learning applications for OSA management is carried out, where the raw oximetry signal is analyzed without previous parameterization. Our research allows us to conclude that all the methodologies (conventional, time, frequency, nonlinear, and hypoxemia-based) demonstrate high ability to provide relevant oximetric indices, but only a reduced set provide non-redundant complementary information leading to a significant performance increase. Finally, although oximetry is a robust tool, greater standardization and prospective validation of the measures derived from complex signal processing techniques are still needed to homogenize interpretation and increase generalizability.

PMID:36217087 | DOI:10.1007/978-3-031-06413-5_13

Ir J Med Sci. 2022 Oct 10. doi: 10.1007/s11845-022-03182-9. Online ahead of print.

ABSTRACT

INTRODUCTION: The brief rise in blood glucose level during acute physiological stress in patients with no previous symptoms of diabetes mellitus is called stress hyperglycemia.

METHODS: This study is conducted with 1033 patients over the age of 18 who are diagnosed with STEMI and who did not meet the exclusion criteria for 1 year. Patients were divided into 2 groups as DM and non-DM and their blood glucose levels, demographic data (age, sex, cardiovascular risk factors, DM, HT presence/absence, history of smoking), vital signs, fatal arrhythmia requiring intervention (ventricular tachycardia and ventricular fibrillation), cardiac insufficiency development according to Killip score, length of hospital stay, mortality and cardiogenic shock conditions were evaluated. Statistical analysis was made using SPSS 23.0 for Windows^® (IBM Inc. Chicago, IL, USA). Results were considered significant at p < 0.05, with a 95% confidence interval.

RESULTS: In non-DM group, BG has been found to be significantly higher in mortal cases compared to surviving cases (289.25 ± 106.35 mg/dL for mortal cases; whereas 156.99 ± 58.60 mg/dL for surviving cases; p < 0.001). Likewise, in DM group BG has been found to be higher in mortal cases compared to surviving cases. (328.38 ± 77.13 mg/dL for mortal cases while 237.16 ± 95.00 mg/dL for surviving cases; p < 0.001).

CONCLUSIONS: For patients who are admitted to the hospital with STEMI, stress hyperglycemia in the non-DM group and hyperglycemia in the DM group are associated with both mortality and adverse conditions; thereby, glucose levels of those patients must be evaluated.

PMID:36217074 | DOI:10.1007/s11845-022-03182-9

J Cancer Surviv. 2022 Oct 10. doi: 10.1007/s11764-022-01258-0. Online ahead of print.

ABSTRACT

PURPOSE: To examine whether sociodemographic characteristics, access to care, risk behavior factors, and chronic health conditions were associated with colorectal cancer (CRC) screening utilization among breast, cervical, prostate, skin, and lung cancer survivors.

METHODS: We analyzed the 2020 Behavioral Risk Factor Surveillance System (BRFSS) data on 9780 eligible cancer survivors. Descriptive statistics and multivariable logistic regression models were applied to assess the association between guideline-concordant CRC screening and the mentioned characteristics.

RESULTS: Overall, 81.9%, 65%, 88%,78.1%, and 80.1% of breast, cervical, prostate, skin, and lung cancer survivors received CRC screening, respectively (p-value < 0.001). In multivariable analysis, breast, cervical, and skin cancer survivors aged 60 years or older were associated with higher odds of receiving CRC screening. Respondents that had their recency of routine checkup two or more years before had lower odds of having CRC screening among cervical (OR = 0.06; 95% CI, 0.02-0.22), prostate (OR = 0.26; 95% CI, 0.14-0.49), and skin cancer (OR = 0.50; 95% CI, 0.36-0.70) survivors. The presence of chronic diseases was also associated with guideline-concordant CRC screening among breast, prostate, and skin cancer survivors.

CONCLUSIONS: Our findings provide important evidence on potential factors that are associated with guideline-concordant CRC screening utilization across different cancer survivors, which include older age, recency of routine checkup, and multiple chronic diseases. Moreover, variation in CRC screening utilization across cancer survivors may highlight missed opportunities for secondary cancer prevention.

IMPLICATIONS FOR CANCER SURVIVORS: Establishing clear CRC screening guidelines and including patient-provider communication on recommendation in cancer survivorship care may increase adherence to CRC screening.

PMID:36217067 | DOI:10.1007/s11764-022-01258-0

Matern Child Health J. 2022 Oct 10. doi: 10.1007/s10995-022-03514-2. Online ahead of print.

ABSTRACT

INTRODUCTION: Children who are deaf or hard of hearing (DHH) are at risk for poor developmental outcomes related to incomplete language access. Evidence based interventions are available to improve early access to language. With a better understanding of caring for DHH children, pediatricians will be more prepared to work with families in improving outcomes for this population. To date, there are no formal curricula on educating pediatric trainees on childhood hearing differences.

METHODS: The authors designed a novel pilot curriculum to educate pediatric trainees on caring for DHH children, including screening, diagnosis, signed languages, and hearing technologies. The curriculum was delivered to pediatric interns in a 1-hour seminar. Pre-lecture, immediate post-lecture, and 6-month post-lecture surveys were developed and conducted to evaluate the effectiveness of the curriculum. Descriptive statistics were used to determine differences in understanding concepts before and after the curricular intervention.

RESULTS: A total of 55 residents participated in the curriculum over a 14-month study period from 2018 to 2019. There were significant differences in responses between the pre- and post- surveys related to residents’ understanding of childhood deafness and their confidence in their ability to care for DHH children.

CONCLUSION: Pediatric trainees gained an understanding of the challenges faced by DHH children and of the interventions that aim to provide them with access to language during the critical period of development. As a result, trainees will be in a better position to care for patients and their families after a new diagnosis of a hearing difference and guide them through early language-based interventions.

PMID:36217055 | DOI:10.1007/s10995-022-03514-2