Category: Nevin Manimala

Eur J Hum Genet. 2023 Feb 15. doi: 10.1038/s41431-023-01302-2. Online ahead of print.

ABSTRACT

Age-related (AR) hearing loss (HL) is a prevalent sensory deficit in the elderly population. Several studies showed that common variants increase ARHL susceptibility. Here, we demonstrate that rare-variants play a crucial role in ARHL etiology. We analyzed exome and imputed data from white-European UK Biobank volunteers, performing both single-variant and rare-variant aggregate association analyses using self-reported ARHL phenotypes. We identified and replicated associations between ARHL and rare-variants in KLHDC7B, PDCD6, MYO6, SYNJ2, and TECTA. PUS7L and EYA4 also revealed rare-variant associations with ARHL. EYA4, MYO6, and TECTA are all known to underline Mendelian nonsyndromic HL. PDCD6, a new HL gene, plays an important role in apoptosis and has widespread inner ear expression, particularly in the inner hair cells. An unreplicated common variant association was previously observed for KHLDC7B, here we demonstrate that rare-variants in this gene also play a role in ARHL etiology. Additionally, the first replicated association between SYNJ2 and ARHL was detected. Analysis of common variants revealed several previously reported, i.e., ARHGEF28, and new, i.e., PIK3R3, ARHL associations, as well as ones we replicate here for the first time, i.e., BAIAP2L2, CRIP3, KLHDC7B, MAST2, and SLC22A7. It was also observed that the odds ratios for rare-variant ARHL associations, were higher than those for common variants. In conclusion, we demonstrate the vital role rare-variants, including those in Mendelian nonsyndromic HL genes, play in the etiology of ARHL.

PMID:36788145 | DOI:10.1038/s41431-023-01302-2

Health Commun. 2023 Feb 14:1-14. doi: 10.1080/10410236.2023.2175407. Online ahead of print.

ABSTRACT

This meta-analysis investigated the persuasive effects of temporal framing in health messaging. Our analysis included 39 message pairs from 22 studies in 20 articles (N = 4,998) that examined the effects of temporal framing (i.e. present-oriented messages vs. future-oriented messages) on attitudes, intentions, and behaviors in health contexts. We found that present-oriented messages were significantly more persuasive than future-oriented messages in terms of intentions and integrated persuasive outcomes. Effects of temporal framing on attitudes and behaviors were not statistically significant. We tested six moderators of temporal framing effects (gain vs. loss framing, temporal framing operationalization, behavior type, timing of effect assessment, age, CFC levels) but none of them was statistically significant. Implications for future temporal framing research are discussed.

PMID:36788142 | DOI:10.1080/10410236.2023.2175407

Mod Pathol. 2023 Jan 10;36(3):100051. doi: 10.1016/j.modpat.2022.100051. Online ahead of print.

ABSTRACT

An epithelial odontogenic tumor called adenoid ameloblastoma (AA) has recently been included in the new WHO classification. However, AA has considerable overlapping features with a preexisting entity, dentinogenic ghost cell tumor (DGCT). This study compared the clinical, histologic, and molecular characteristics of AA and DGCT. Eight cases of odontogenic tumors initially diagnosed as AA or DGCT were included in this study. Quantitative histologic analysis, β-catenin immunohistochemistry, and molecular profiling using next generation sequencing were performed. Additionally, accumulated clinical data of AA and DGCT were statistically analyzed. Nuclear β-catenin accumulation was detected in all cases in common, although the tumors studied histologically consisted of varying combinations of the AA-like phenotype, ghost cells, and dentinoid. However, CTNNB1 hotspot mutations were not found in any case. Instead, loss-of-function mutations in tumor suppressor genes involved in the WNT pathway, including the APC, SMURF1, and NEDD4L genes, were found regardless of histologic type. In addition, KRT13 mutations were detected in 2 cases with a high proportion of ghost cells. Finally, a literature analysis revealed clinical similarities between the previously reported cases of AA and DGCT. These findings suggest that from a clinical and molecular point of view, AA and DGCT represent a histologic spectrum of WNT pathway-altered benign odontogenic tumors rather than 2 distinct tumors. Moreover, previously unidentified keratin mutations may be associated with ghost cell formation found in specific types of odontogenic lesions.

PMID:36788106 | DOI:10.1016/j.modpat.2022.100051

Mod Pathol. 2023 Jan 10;36(3):100069. doi: 10.1016/j.modpat.2022.100069. Online ahead of print.

ABSTRACT

Dedifferentiated chondrosarcoma is rare, aggressive, and microscopically bimorphic. How pathologic features such as the amounts of dedifferentiation affect prognosis remains unclear. We evaluated the percentages and sizes of dedifferentiation in a consecutive institutional series of dedifferentiated chondrosarcomas from 1999 to 2021. The statistical analysis included cox proportional hazard models and log-rank tests. Of the 67 patients (26 women, 41 men; age, 39 to >89 [median 61] years; 2 with Ollier disease), 58 presented de novo; 9 were identified with conventional chondrosarcomas 0.6-13.2 years (median, 5.5 years) prior. Pathologic fracture and distant metastases were noted in 27 and 7 patients at presentation. The tumors involved the femur (n = 27), pelvis (n = 22), humerus (n = 7), tibia (n = 4), scapula/ribs (n = 4), spine (n = 2), and clivus (n = 1). In the 56 resections, the tumors ranged in size from 3.5 to 46.0 cm (median, 11.5 cm) and contained 1%-99.5% (median, 70%) dedifferentiated components that ranged in size from 0.6 to 24.0 cm (median, 7.3 cm). No correlation was noted between total size and percentage of dedifferentiation. The dedifferentiated components were typically fibrosarcomatous or osteosarcomatous, whereas the associated cartilaginous components were predominantly grade 1-2, rarely enchondromas or grade 3. The entire cohort’s median overall survival and progression-free survival were 11.8 and 5.4 months, respectively. In the resected cohort, although the total size was not prognostic, the percentage of dedifferentiation ≥20% and size of dedifferentiation >3.0 cm each predicted worse overall survival (9.9 vs 72.5 months; HR, 3.76; 95% CI, 1.27-11.14; P = .02; 8.7 vs 58.9 months; HR, 3.03; 95% CI, 1.21-7.57; P = .02, respectively) and progression-free survival (5.3 vs 62.1 months; HR, 3.05; 95% CI, 1.13-8.28; P = .03; 5.3 vs 56.6 months; HR, 2.50; 95% CI, 1.06-5.88; P = .04, respectively). In conclusion, both the percentages and sizes of dedifferentiation were better prognostic predictors than total tumor sizes in dedifferentiated chondrosarcomas, highlighting the utility of their pathologic evaluations.

PMID:36788104 | DOI:10.1016/j.modpat.2022.100069

Mod Pathol. 2023 Jan 11;36(4):100100. doi: 10.1016/j.modpat.2023.100100. Online ahead of print.

ABSTRACT

TP53 mutation is associated with primary endocrine resistance in luminal breast cancer (BC). Nuclear accumulation of p53, as determined by immunohistochemistry (IHC), is a surrogate marker for TP53 mutation. The immunohistochemical p53 index that defines a p53-positive status is not well established. This study determined the optimal p53 index cutoff to identify luminal BCs harboring TP53 mutations. In total, 364 luminal BCs from the West German Study Group ADAPT trial (NCT01779206) were analyzed for TP53 mutations by next-generation sequencing and for p53 expression by IHC (DO-7 antibody). P53 indices were determined by automated image analysis. All tumors were from patients treated with short-term preoperative endocrine therapy (pET; tamoxifen or aromatase inhibitor) before tumor resection. IHC evaluation included needle biopsies before therapy (baseline) and resections specimens after therapy (post-pET). Optimal p53 index cutoffs were defined with Youden statistics. TP53 mutations were detected in 16.3% of BC cases. The median p53 indices were significantly higher in TP53-mutated BCs compared to BCs harboring wild-type TP53 (baseline: 47.0% vs 6.4%, P < .001; post-pET: 50.1% vs 1.1%, P < .001). Short-term pET decreased p53 indices in BCs harboring wild-type TP53 (P < .001) but not in TP53-mutated BCs (P = .102). For baseline biopsies, the optimal p53 index cutoff was ≥34.6% (specificity 0.92, sensitivity 0.63, Youden index 0.54, accuracy: 0.87). For post-pET specimens, the optimal cutoff was ≥25.3% (specificity 0.95, sensitivity 0.65, Youden index 0.60, accuracy: 0.90). Using these cutoffs to define the p53 status, p53-positive BCs were >2-fold more common in pET nonresponders compared to pET responders (baseline: 37/162, 22.8% vs 18/162, 11.1%, P = .007; post-pET: 36/179, 20.1% vs 16/179, 8.9%, P = .004). In summary, IHC for p53 identifies TP53-mutated luminal BCs with high specificity and accuracy. Optimal cutoffs are ≥35% and ≥25% for treatment-naïve and endocrine-pretreated patients, respectively.

PMID:36788081 | DOI:10.1016/j.modpat.2023.100100

Mod Pathol. 2023 Jan;36(1):100037. doi: 10.1016/j.modpat.2022.100037.

NO ABSTRACT

PMID:36788072 | DOI:10.1016/j.modpat.2022.100037

Addiction. 2023 Feb 14. doi: 10.1111/add.16167. Online ahead of print.

ABSTRACT

AIMS: To estimate the efficacy of multiple psychosocial interventions for opioid dependent persons receiving methadone maintenance treatment (MMT).

METHODS: Systematic review and network meta-analysis of randomized controlled trials (RCTs) reporting the effect of psychosocial intervention for opioid dependent persons receiving MMT in outpatient clinics. We searched multiple data sources (Medline, Embase, Web of Science, PsycINFO and Cochrane Library) from inception to January 2022, finding 21 RCTs evaluating a total of 2862 persons with opioid dependence receiving MMT. The primary outcome was the opioid positive rate (assessed by urinalysis) and the secondary outcome was treatment discontinuation (the number of patients who terminated the study for any reason). We performed random effects Bayesian meta-analysis. We used relative ranking using surface under the cumulative ranking method and certainty of evidence using grading of recommendations, assessment, development, and evaluations.

RESULTS: Cognitive-behavioral therapy (CBT) [Odds Ratio (OR): 0.66, 95% Credibility Interval (CI): 0.66 to 0.96; low certainty] and educational and behavioral counseling (EBC) (OR: 0.28, 95% CI: 0.12 to 0.25; high certainty) were more effective than treatment as usual (TAU) in efficacy. In terms of treatment discontinuation, at the end of the follow-up period there was no statistical significance among psychosocial interventions. According to the ranking probabilities, EBC might be the best treatment in terms of efficacy and behavioral couple therapy (BCT) might be the best treatment in terms of treatment discontinuation.

CONCLUSIONS: Educational and behavioral counseling and cognitive-behavioral therapy appear to be the most effective psychosocial interventions for opioid dependent persons receiving methadone maintenance treatment.

PMID:36787637 | DOI:10.1111/add.16167

Physiol Meas. 2023 Feb 14. doi: 10.1088/1361-6579/acbc07. Online ahead of print.

ABSTRACT

Assessment of heartbeat dynamics provides a promising framework for non-invasive monitoring of cardiovascular and autonomic states. Nevertheless, the non-specificity of such measurements among clinical populations and healthy conditions associated with different autonomic states severely limits their applicability and exploitation in naturalistic conditions. This limitation arises specially when pathological or postural change-related sympathetic hyperactivity is compared to autonomic changes across age and experimental conditions. In this frame, we investigate the intrinsic irregularity and complexity of cardiac sympathetic and vagal activity series in different populations, which are associated with different cardiac autonomic dynamics. Sample entropy, fuzzy entropy, and distribution entropy are calculated on the recently proposed sympathetic and parasympathetic activity indices (SAI and PAI) series, which are derived from publicly available heartbeat series of congestive heart failure patients, elderly and young subjects watching a movie in the supine position, and healthy subjects undergoing slow postural changes. Results show statistically significant differences between pathological/old subjects and young subjects in the resting state and during slow tilt, with interesting trends in SAI- and PAI-related entropy values. Moreover, while CHF patients and healthy subjects in upright position show the higher cardiac sympathetic activity, elderly and young subjects in resting state showed higher vagal activity. We conclude that quantification of intrinsic cardiac complexity from sympathetic and vagal dynamics may provide new physiology insights and improve on the non-specificity of heartbeat-derived biomarkers.

PMID:36787644 | DOI:10.1088/1361-6579/acbc07

Cir Cir. 2023;91(1):28-33. doi: 10.24875/CIRU.21000624.

ABSTRACT

BACKGROUND: Management of breast cancer is increased by late diagnoses.

OBJECTIVE: To analyse direct costs of breast cancer in early and advanced stage in a third level medical facility at Mexican Social Security Institute.

METHOD: Observational study, direct costs of care in breast cancer in initial and advanced clinical stages are compared. Variables analysed were laboratory and diagnostic imaging studies, drugs, as well as hospitalization costs. The evaluated period included from the first care to the completion of the treatment. Costs were determined according to the table of Unit Costs by Level of Medical Care for the year 2019 of the Mexican Social Security Institute. Student’s t test was used to determinate differences between groups, as well as descriptive statistics.

RESULTS: The advanced stage compared to the initial stage, causes a greater number of laboratory-cabinet studies, surgeries, day/bed and interconsultations. The average cost of breast cancer care per patient is $99,280.36 (US$5,230.78) and $148,023.60 (US$7,789.92) for the initial and advanced stages, respectively (p = 0.024).

CONCLUSIONS: Cost of medical attention in the initial stage is lower than that of the advanced stage.

PMID:36787613 | DOI:10.24875/CIRU.21000624

Cir Cir. 2023;91(1):9-14. doi: 10.24875/CIRU.22000490.

ABSTRACT

OBJECTIVE: The present study aims to investigate the relationship between bile reflux (BR) and diameter of the common bile duct (CBD) in patients after cholecystectomy.

MATERIALS AND METHODS: In our case series analysis, according to the endoscopy results, the patients who underwent cholecystectomy were divided into two groups as those with BR and those non-BR. Age, sex, CBD diameter measured on ultrasonography, computed tomography, magnetic resonance cholangiopancreatography, and endoscopic biopsy results of the patients were statistically analyzed.

RESULTS: In a total of 188 patients included in the study, BR was detected in 93 patients, it was not observed in 95 patients. The CBD diameter of the patients was observed to be 7 mm or less in 70.9% (n = 66) in the BR group, and 23% (n = 22) in the non-BR group. The statistical analysis revealed that while there was a significant difference between the two groups in terms of CBD diameter and intestinal metaplasia, the results were similar in both groups in terms of inflammation, activity, atrophy, and Helicobacter pylori.

CONCLUSION: We believe that CBD diameter may be a predictive factor in the detection of BR after cholecystectomy.

PMID:36787612 | DOI:10.24875/CIRU.22000490