Nevin Manimala

Genet Epidemiol. 2022 Sep 1. doi: 10.1002/gepi.22502. Online ahead of print.

ABSTRACT

Linkage analysis maps genetic loci for a heritable trait by identifying genomic regions with excess relatedness among individuals with similar trait values. Analysis may be conducted on related individuals from families, or on samples of unrelated individuals from a population. For allelically heterogeneous traits, population-based linkage analysis can be more powerful than genotypic-association analysis. Here, we focus on linkage analysis in a population sample, but use sequences rather than individuals as our unit of observation. Earlier investigations of sequence-based linkage mapping relied on known sequence relatedness, whereas we infer relatedness from the sequence data. We propose two ways to associate similarity in relatedness of sequences with similarity in their trait values and compare the resulting linkage methods to two genotypic-association methods. We also introduce a procedure to label case sequences as potential carriers or noncarriers of causal variants after an association has been found. This post hoc labeling of case sequences is based on inferred relatedness to other case sequences. Our simulation results indicate that methods based on sequence relatedness improve localization and perform as well as genotypic-association methods for detecting rare causal variants. Sequence-based linkage analysis therefore has potential to fine-map allelically heterogeneous disease traits.

PMID:36047334 | DOI:10.1002/gepi.22502

Otolaryngol Pol. 2022 Jun 1;76(4):1-5. doi: 10.5604/01.3001.0015.8568.

ABSTRACT

PURPOSE: The aim of the study was to ascertain the risk factors of local recurrence in primary basal cell carcinoma of the head and neck Material and methods: A retrospective analysis of 545 patients with head and neck primary basal cell carcinoma treated in years 2008 – 2018 was done. The following data was recorded: age, sex, tumor site, histological subtype, greatest dimension, margin status, experience of operating surgeon and local recurrence Results: Most of the tumors were located nose (165; 30,2%) and auricle (119; 21,8%). The most common pathological subtype was nodular (119; 21,8%). Three hundred and ninety-four tumors (72,2%) were under 20mm in diameter. Positive surgical margins were noted in 107 (19,6%) cases. Local recurrence was observed in 52 (9,5%) cases, of which 29 (29/107; 27%) had positive surgical margins, in 23 (23/438; 5,2%) cases margins were free, which was the only statistically significant factor (p<0,001; OR 6,71; CI 3,69 – 12,2).

CONCLUSIONS: The results of our study have shown that positive surgical margin remains the strongest risk factor for local recurrence. With surgical excision being the gold standard of treatment the greatest emphasis should be placed on avoiding such scenario in high risk patients.

PMID:36047328 | DOI:10.5604/01.3001.0015.8568

Otolaryngol Pol. 2022 Jun 2;76(4):12-16. doi: 10.5604/01.3001.0015.8627.

ABSTRACT

<b>Introduction:</b> Patients often suffer from an elongated styloid process. This clinical entity is well known and is described as Eagle syndrome. The presence of this anatomical variation is not always associated with symptoms. However, there is a strong correlation between the elongated styloid process and Eagle syndrome </br></br> <b>Aim:</b> This study aims to calculate the incidence of elongated styloid processes in the Greek population, to analyze the morphometric characteristics of styloid processes, and to compare these among sexes. </br></br> <b>Material and methods:</b> This is a single-center retrospective study. All skulls were donated to the Department of Anatomy, the Ari-stotle University of Thessaloniki from January 2013 to May 2019 for research purposes. A styloid process longer than 30 mm was considered elongated. We used Welch’s t-test for the statistical analysis of the data. </br></br> <b>Results:</b> The prevalence of elongated styloid processes was 35%. The average diameter was 3.32 mm and the average total length was 25.02 mm. There was no statistically significant difference between male and female skulls, though the female styloid processes were slightly longer and the male ones were slightly wider. Symmetry was recorded in 31% of skulls. Average axial angle was 650 but in 4% of cases it was less than 20<sup>0</sup>. </br></br> <b>Conclusions:</b> The elongated styloid process is not a rare entity. Eagle syndrome should always be considered in the differential diagnosis when patients report chronic sore throat. Our anatomical findings add a new dimension to the etiopathogenesis of Eagle syndrome.

PMID:36047325 | DOI:10.5604/01.3001.0015.8627

Aust Occup Ther J. 2022 Sep 1. doi: 10.1111/1440-1630.12838. Online ahead of print.

ABSTRACT

INTRODUCTION: Two parallel versions (A and B) of the Oxford Cognitive Screen (OCS) were developed in the United Kingdom (UK) as a stroke-specific screen of five key cognitive domains commonly affected post-stroke. We aimed to develop the Australian versions A and B (OCS-AU), including Australian cut-scores indicative of impairment. We hypothesised there to be no difference in performance between the UK and Australian normative data cohorts.

METHODS: Our multidisciplinary expert panel used the UK pre-defined process to develop the OCS-AU versions A and B. We then conducted a cross-sectional normative study. We purposively recruited community-dwelling, Australian-born, and educated adults; with no known cognitive impairment; representative of age, sex, education level, and living location; at seven sites (four metropolitan, three regional) across four Australian states. Participants completed one or both OCS-AU versions in a randomised order. Australian cohorts were compared with the corresponding UK cohorts for demographics using Pearson’s chi-squared test for sex and education, and Welch two-sample t test for age. For the cut-scores indicating cognitive impairment, the fifth (95th) percentiles and group mean performance score for each scored item were compared using Welch two-sample t tests. The pre-defined criteria for retaining OCS cut-scores had no statistically significant difference in either percentile or group mean scores for each scored item.

RESULTS: Participants (n = 83) were recruited: fifty-eight completed version A [age (years) mean = 61,SD = 15; 62% female], 60 completed version B [age (years) mean = 62,SD = 13, 53% female], and 35 completed both [age (years) mean = 64,SD = 11, 54% female]. Education was different between the cohorts for version B (12 years, p = 0.002). Cut-scores for all 16 scored items for the OCS-AU version B and 15/16 for version A met our pre-defined criteria for retaining the OCS cut scores.

CONCLUSIONS: The OCS-AU provides clinicians with an Australian-specific, first-line cognitive screening tool for people after stroke. Early screening can guide treatment and management.

PMID:36047309 | DOI:10.1111/1440-1630.12838

Pediatrics. 2022 Sep 1:e2022056294. doi: 10.1542/peds.2022-056294. Online ahead of print.

ABSTRACT

OBJECTIVE: Congenital heart disease (CHD) is a leading cause of premature death in infants and children. Currently limited data are available regarding lesion specific mortality over time. Our study aimed to describe pediatric mortality trends by CHD lesion in the United States.

METHODS: We conducted a 19 year analysis (1999 to 2017) of publicly available, deidentified multiple cause of death data compiled and produced by the National Center for Health Statistics. Analysis was stratified by CHD diagnosis and age using 3 age categories (infants, 1 to 4 years, and 5 to 17 years). Temporal trends of CHD mortality and the effect of contributing risk factors were analyzed by using joinpoint regression.

RESULTS: Mortality was highest for in infants for all CHD lesions, in particular for total anomalous pulmonary venous return. Significant declines in infant CHD mortality occurred for most other lesions. Contributing risk factors, including prematurity, extracardiac birth defects, and genetic conditions, occurred in 19% of infant CHD deaths and demonstrated worse mortality trends in the majority of lesions. Mortality rates remained highest for single ventricle lesions in all ages, with an infant mortality rate plateau in the later half of the study and progressive increasing mortality rates for children 5 to 17 years.

CONCLUSIONS: CHD mortality is decreasing for most lesions. Because of the heterogenicity of CHD lesions, there is expected variability in mortality trends by lesion and age group. Single ventricle lesions continue to contribute most heavily to premature death because of CHD demonstrated by significant increases in mortality rate for children aged 5 to 17 years.

PMID:36047307 | DOI:10.1542/peds.2022-056294

Nucl Med Rev Cent East Eur. 2022;25(2):89-94. doi: 10.5603/NMR.a2022.0020.

ABSTRACT

BACKGROUND: Accurate preoperative localisation of the parathyroid adenoma is essential to achieve a minimally invasive parathyroidectomy. The purpose of this study was to validate and improve our single-isotope dual-phase parathyroid imaging protocol utilising 99mTechnetium-Sestamibi ([99mTc]MIBI). There has been no accepted gold standard evidence-based protocol regarding timing of single-photon emission computed tomography/computed tomography (SPECT/CT) acquisition in parathyroid imaging with resultant variation between centres. We sought to determine the optimum timing of SPECT/CT post administration of [99mTc]MIBI in the identification of parathyroid adenomas. We aimed to evaluate the efficacy of early and late SPECT/CT and to establish whether SPECT/CT demonstrates increased sensitivity over planar imaging.

MATERIAL AND METHODS: A sample of 36 patients with primary hyperparathyroidism underwent planar and SPECT/CT acquisition 15 minutes (early) and two hours (late) post [99mTc]MIBI administration. Two radionuclide radiologists reviewed the images and Fisher’s exact Chi-squared statistic was used to evaluate the diagnostic performances of early versus late SPECT/CT acquisition and SPECT/CT versus planar imaging.

RESULTS: Twenty-one likely parathyroid adenomas were identified with a statistically superior diagnosis rate in the late SPECT/CT acquisition compared with both early SPECT/CT and planar imaging (p < 0.05). All adenomas diagnosed on early SPECT/CT acquisition were also identified on late SPECT/CT images.

CONCLUSIONS: Single late phase SPECT/CT is significantly superior to early SPECT/CT in the identification of parathyroid adenomas. Late SPECT/CT improves diagnostic accuracy over planar acquisition. Imaging protocols should be revised to include late SPECT/CT acquisition. Early SPECT/CT acquisition can be eliminated from scan protocols with associated implications regarding reduced scan time and increased patient throughput.

PMID:36047295 | DOI:10.5603/NMR.a2022.0020

Catheter Cardiovasc Interv. 2022 Sep 1. doi: 10.1002/ccd.30384. Online ahead of print.

ABSTRACT

The original J-CTO score predicts the difficulty of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) lesions, but the grade of calcification has not been fully evaluated. We examined 137 patients (141 CTO lesions) who underwent coronary computed tomography angiography (CTA) pre-PCI between October 2016 and October 2021. They were randomly divided into derivation (n = 94) and validation (n = 47) groups. The degree and distribution of calcification in the occluded segment were assessed using CTA. The calcified index was defined as calcium volume divided by the length of the occluded segment. We created the J-Calc-CTO score consisting of calcification parameters associated with 30-min wire crossing in the derivation group. The validity of the J-Calc-CTO score was compared with that of the original J-CTO score using c-statistics. The procedural success rate was 96%, and 30-min wire crossing during the procedure was achieved in 29%. Dense calcification (calcified-index >12) (odds ratio [OR]: 4.63; 95% confidence interval [CI]: 1.24-22.2; p = 0.04) and calcification in the center of the lumen (OR: 7.25; 95% CI: 1.48-32.1; p = 0.02) were independently associated with 30-min wire crossing as variables evaluated using CTA. The J-Calc-CTO score was created by adding 1 point to the two parameters in place of “calcification” in the original J-CTO score. The J-Calc-CTO score showed a higher predictive value of 30-min wire crossing than the J-CTO score in the derivation (c-statistics; 0.836 vs. 0.670; p > 0.01) and validation groups (c-statistics; 0.879 vs. 0.767, p > 0.01). The degree and distribution of calcification evaluated using CTA refined the predictive value of the original J-CTO score for 30-min wire crossing.

PMID:36047294 | DOI:10.1002/ccd.30384

Med Phys. 2022 Sep 1. doi: 10.1002/mp.15919. Online ahead of print.

ABSTRACT

BACKGROUND: Routinely delineating of important skeletal growth centers is imperative to mitigate radiation-induced growth abnormalities for pediatric cancer patients treated with radiotherapy. However, it is hindered by several practical problems including difficult identification, time consumption and inter-practitioner variability.

PURPOSE: The goal of this study was to construct and evaluate a novel Triplet-Attention U-Net (TAU-Net) based auto-segmentation model for important skeletal growth centers in childhood cancer radiotherapy, concentrating on the accuracy and time efficiency.

METHODS: A total of 107 childhood cancer patients fulfilled the eligibility criteria were enrolled in the training cohort (N = 80) and test cohort (N = 27). The craniofacial growth plates, shoulder growth centers and pelvic ossification centers, with a total of 19 structures in the three groups, were manually delineated by two experienced radiation oncologists on axial, coronal, and sagittal CT images. Modified from U-Net, the proposed TAU-Net has one main branch and two bypass branches, receiving semantic information of three adjacent slices to predict the target structure. With supervised deep learning, the skeletal growth centers contouring of each group was generated by three different auto-segmentation models: U-Net, V-Net and the proposed TAU-Net. Dice Similarity Coefficient (DSC) and Hausdorff distance 95% (HD95) were used to evaluate the accuracy of three auto-segmentation models. The time spent on performing manual tasks and manually correcting auto-contouring generated by TAU-Net was recorded. The paired t-test was used to compare the statistical differences in delineation quality and time efficiency.

RESULTS: Among the 3 groups, including craniofacial growth plates, shoulder growth centers and pelvic ossification centers groups, TAU-Net had demonstrated highly acceptable performance (the average DSC = 0.77, 0.87, and 0.83 for each group; the average HD95 = 2.28 mm, 2.07 mm, and 2.86 mm for each group). In the overall evaluation of 19 ROIs in the test cohort, TAU-Net had an overwhelming advantage over U-Net (63.2% ROIs in DSC and 31.6% ROIs in HD95, P = 0.001∼0.042) and V-Net (94.7% ROIs in DSC and 36.8% ROIs in HD95, P = 0.001∼0.040). With an average time of 52.2 min for manual delineation, the average time saved to adjust TAU-Net-generated contours was 37.6 min (P<0.001), a 72% reduction.

CONCLUSIONS: Deep learning-based models have presented enormous potential for the auto-segmentation of important growth centers in pediatric skeleton, where the proposed TAU-Net outperformed than U-Net and V-Net in geometrical precision for the majority status. This article is protected by copyright. All rights reserved.

PMID:36047281 | DOI:10.1002/mp.15919

Wei Sheng Yan Jiu. 2022 Jul;51(4):632-637. doi: 10.19813/j.cnki.weishengyanjiu.2022.04.022.

ABSTRACT

OBJECTIVE: To investigate the regulation mechanism of N-acetylcysteine(NAC) on cadmium-induced apoptosis of mouse testicular interstitial cells based on protein kinase B pathway(AKT pathway).

METHODS: Mouse testicular mesenchymal cells(TM3) were divided into fourgroups according to different treatment, control group, cadmium group(Cd, 5, 10, 20, 30, 40 and 50 μmol/L), NAC group(NAC, 500 μmol/L) and NAC+Cd group(500 μmol/L NAC+20 μmol/L Cd). Cells of NAC+Cd group were pretreated with NAC for 30 min, and then combined with cadmium for 24 h. Cell viability was determined by CCK8. Hoechst staining was used to determine cell morphology. Cell apoptosis rate was analyzed by flow cytometry. Malondialdehyde(MDA) and glutathione(GSH) were measured simultaneously. Western blot was used to detect the expression levels of AKT protein, B-cell lymphoma-2(Bcl-2) and Bcl-2 associated X protein(Bax).

RESULTS: Cadmium inhibited the proliferation of TM3 cells in a dose-effect relationship. Cell morphology observation showed that with the increase of cadmium concentration, the cells shrank, became round and even fell off, and appeared dense nuclear staining. The MDA level in Cd group was(1.56±0.11) μmol/mg prot, which was significantly higher than that in control group(P&lt;0.01). Compared to the control group, the level of GSH was significantly decreased to(1.28±0.25) μmol/mg prot(P&lt;0.01). NAC pretreatment could reduce the MDA content and increase the GSH level, and the difference was statistically significant compared with the Cd group(P&lt;0.01). Western blot result showed that NAC pretreatment significantly increased levels of phosphorylated AKT and Bcl-2, the levels were 0.65±0.05 and 0.45±0.03, respectively(P&lt;0.01). The Bax/Bcl-2 ratio was 1.54±0.15, which was significantly lower than that of the Cd group(P&lt;0.01).

CONCLUSION: NAC can inhibit cadmium-mediated TM3 cell damage and apoptosis, which may be related to the improvement of oxidative stress state, activation of TM3 AKT pathway and reduction of Bax/Bcl-2 ratio.

PMID:36047270 | DOI:10.19813/j.cnki.weishengyanjiu.2022.04.022

Wei Sheng Yan Jiu. 2022 Jul;51(4):596-603. doi: 10.19813/j.cnki.weishengyanjiu.2022.04.017.

ABSTRACT

OBJECTIVE: To analyze the fat and fatty acid composition of Fujian characteristic snacks, and to evaluate their nutritional value.

METHODS: The fat and fatty acid composition of Fujian characteristic snacks were analyzed by the national standards, and analyzed by statistics such as correlation analysis, nonparametric test and cluster analysis. The nutritional value of fatty acid was evaluated by unsaturated index(UI), atherogenic index(AI), thrombosis index(TI).

RESULTS: The contents of crude fat and total fatty acid were 0.11-26.35 g/100 g and 0.08-17.85 g/100 g. The correlation coefficient r=0.915(P&lt;0.01), crude fat and total fatty acid in poultry and livestock meats were higher than those in seafood(P&lt;0.05). The main saturated fatty acids(SFA) were palmitic acid(21.80%-34.00%)and stearic acid(7.72%-21.45%), and the main unsaturated fatty acids(UFA)were oleic acid(5.38%-41.17%) and linoleic acid(2.99%-23.54%). The content of eicosapentaenoic acid(EPA) in fish noodle(0.71%) and docosahexaenoic acid(DHA) in fried fish roll, fish slide, fish noodles(0.41%, 2.12%, 1.59%)were far higher than other snacks. Polyunsaturated fatty acids/saturated fatty acids(PUFA/SFA)ratios were 0.10-0.69, there were 8 kinds of snacks with PUFA/SFA ratio value&gt;0.4. The n-3 PUFA/n-6 PUFA ratios were 0.01-0.75, n-6 PUFA/n-3 PUFA ratios were 1.33-74.31. The n-6 PUFA/n-3 PUFA ratios of fish slide(1.33) and fish noodle(2.13) conform to the ideal ratio stipulated by the British Health Organization, and the ratio of flat food(6.36) conform to the recommended ratio of Food and Agriculture Organization. The SFA∶monounsaturated fatty acids(MUFA)∶PUFA ratios were 0.8∶1.0∶0.5-2.4∶1.0∶0.2, the ratios of pork zongzi, meat yan silk, spicy meat, pressed salted duck and fried oyster(1.2∶1.1∶0.5, 0.8∶1.0∶0.6, 1.0∶1.0∶0.7, 0.8∶1.0∶0.5 and 1.1∶1.1∶0.5) were close to 1∶1∶1. The UI of 15 snacks was 48.37-90.67. The AI was 0.40-1.44, and the TI was 0.97-2.32. When the distance scale was 9, snacks were divided into three categories, namely fish noodle, fish slide and others. Fish noodle was high EPA and DHA type, and fish slide was high DHA type.

CONCLUSION: The fat and total fatty acid contents of the 15 snacks were wide, which were closely related to the raw materials and cooking style. Nutrition and health value of fish slide, fish noodles food, meat yan silk and spicy meat were high.

PMID:36047265 | DOI:10.19813/j.cnki.weishengyanjiu.2022.04.017