Tag: nevin manimala

Hum Reprod. 2023 Oct 9:dead201. doi: 10.1093/humrep/dead201. Online ahead of print.

ABSTRACT

STUDY QUESTION: In oocytes of advanced maternal age (AMA) women, what are the mechanisms leading to aneuploidy and what is the association of aneuploidy with embryo development?

SUMMARY ANSWER: Known chromosome segregation errors such as precocious separation of sister chromatids explained 90.4% of abnormal chromosome copy numbers in polar bodies (PBs), underlying impaired embryo development.

WHAT IS KNOWN ALREADY: Meiotic chromosomal aneuploidies in oocytes correlate with AMA (>35 years) and can affect over halfof oocytes in this age group. This underlies the rationale for PB biopsy as a form of early preimplantation genetic testing for aneuploidy(PGT-A), as performed in the ‘ESHRE STudy into the Evaluation of oocyte Euploidy by Microarray analysis’ (ESTEEM) randomizedcontrolled trial (RCT). So far, chromosome analysis of oocytes and PBs has shown that precocious separation of sister chromatids (PSSC), Meiosis II (MII) non-disjunction (ND), and reverse segregation (RS) are the main mechanisms leading to aneuploidyin oocytes.

STUDY DESIGN, SIZE, DURATION: Data were sourced from the ESTEEM study, a multicentre RCT from seven European centres to assessthe clinical utility of PGT-A on PBs using array comparative genomic hybridization (aCGH) in patients of AMA (36-40 years). This included data on the chromosome complement in PB pairs (PGT-A group), and on embryo morphology in a subset of embryos, up to Day 6 post-insemination, from both the intervention (PB biopsy and PGT-A) and control groups.

PARTICIPANTS/MATERIALS, SETTING, METHODS: ESTEEM recruited 396 AMA patients: 205 in the intervention group and 191 in the control group. Complete genetic data from 693 PB pairs were analysed. Additionally, the morphology from 1034 embryos generated from fertilized oocytes (two pronuclei) in the PB biopsy group and 1082 in the control group were used for statistical analysis.

MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 461/693 PB pairs showed abnormal segregation in 1162/10 810 chromosomes. The main observed abnormal segregations were compatible with PSSC in Meiosis I (MI) (n = 568/1162; 48.9%), ND of chromatids in MII or RS (n = 417/1162; 35.9%), and less frequently ND in MI (n = 65/1162; 5.6%). For 112 chromosomes (112/1162; 9.6%), we observed a chromosome copy number in the first PB (PB1) and second PB (PB2) that is not explained by any of the known mechanisms causing aneuploidy in oocytes. We observed that embryos in the PGT-A arm of the RCT did not have a significantly different morphology between2and 6 days post-insemination compared to the control group, indicating that PB biopsy did not affect embryo quality.Following age-adjusted multilevel mixed-effect ordinal logistic regression models performed for each embryo evaluation day, aneuploidy was associated with a decrease in embryo quality on Day 3 (adjusted odds ratio (aOR) 0.62, 95% CI 0.43-0.90), Day 4 (aOR 0.15, 95% CI 0.06-0.39), and Day 5 (aOR 0.28, 95% CI 0.14-0.58).

LIMITATIONS, REASON FOR CAUTION: RS cannot be distinguished from normal segregation or MII ND using aCGH. The observed segregations were based on the detected copy number of PB1 and PB2 only and were not confirmed by the analysis of embryos. The embryo morphology assessment was static and single observer.

WIDER IMPLICATIONS OF THE FINDINGS: Our finding of frequent unexplained chromosome copy numbers in PBs indicates that our knowledge of the mechanisms causing aneuploidy in oocytes is incomplete. It challenges the dogma that aneuploidy in oocytes is exclusively caused by mis-segregation of chromosomes during MI and MII.

STUDY FUNDING/COMPETING INTEREST(S): Data were mined from a study funded by ESHRE. Illumina provided microarrays and other consumables necessary for aCGH testing of PBs. None of the authors have competing interests.

TRIAL REGISTRATION NUMBER: Data were mined from the ESTEEM study (ClinicalTrials.gov Identifier NCT01532284).

PMID:37814912 | DOI:10.1093/humrep/dead201

Nan Fang Yi Ke Da Xue Xue Bao. 2023 Sep 20;43(9):1629-1635. doi: 10.12122/j.issn.1673-4254.2023.09.22.

ABSTRACT

OBJECTIVE: To analyze the changes of brain small-world and node function network properties in patients with insomnia following radiotherapy for cervical cancer based on graph theory analysis and explore the correlation between functional networks and the clinical efficacy of individual-target transcranial magnetic stimulation (IT-TMS) for treatment of insomnia.

METHODS: The resting state functional magnetic resonance imaging (rs-fMRI) data were collected from 30 patients with insomnia following radiotherapy for cervical cancer and 30 matched healthy individuals. All the patients received accelerated intelligent neuromodulation TMS therapy. Using graph theory analysis and GRETNA software, the functional connectivity matrices were constructed and the attribute features were extracted. The scores on the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) of the participants were collected before and after IT-TMS, and the correlation between improvement in insomnia and the functional network was investigated.

RESULTS: The two groups matched for age, gender, and education level (P>0.05) showed significant differences in PSQI, ISI, SAS and SDS scores (P<0.05). Both groups showed attributes of the small-world network. Compared with the healthy individuals, the patients showed significantly decreased σ, EI, Cp and Lp (P<0.05) and increased Eg (P<0.05) at baseline, which, along with insomnia symptoms, were all improved after IT-TMS treatment. The patients showed reduced functional connections of the node network at follow-up compared with the baseline, and the low functional connectivity between the right insula and left superior frontal gyrus was correlated with the improvement of ISI scores.

CONCLUSION: The patients with insomnia following radiotherapy for cervical cancer have impaired information integration ability of the brain network, IT-TMS can significantly improve insomnia symptoms by reducing the hyperconnectivity between the default mode network and the salience network.

PMID:37814879 | DOI:10.12122/j.issn.1673-4254.2023.09.22

Arkh Patol. 2023;85(5):60-64. doi: 10.17116/patol20238505160.

ABSTRACT

A study was made of the structure of mortality of the population of the Penza region from diseases of the liver and biliary tract in 2021-2022. Data on registered deaths were analyzed, the main cause of which was non-tumor diseases of the liver and biliary tract (excluding hepatitis B, C). Statistical calculations were carried out using the STATISTICA program. Between April 2021 and April 2022, 285 deaths from diseases of the liver and biliary tract were identified. The proportion of the male population prevails over the female and is 57.5%. The largest number of deaths occurs in persons aged 45 to 59 years, the smallest – in people over the age of 90 years. There were no deaths from diseases of the liver and bile ducts among minors. Among the initial causes of death in the studied sample, cirrhosis of the liver (K74.6) is in the lead – 75.4%, in second place are gallbladder stones with acute cholecystitis (K80.0) – 4.9%, then – chronic hepatitis (K73.8) – 4.2%. The categories of the population that are at risk for mortality from diseases of the liver and biliary tract have been identified. Among males, the risk group is people aged 45-59 years, among women – 18-44 years. The risk of death among men is 14% higher than among women. The most likely cause of death is cirrhosis of the liver (the terminal stage of chronic liver pathology).

PMID:37814852 | DOI:10.17116/patol20238505160

Arkh Patol. 2023;85(5):5-12. doi: 10.17116/patol2023850515.

ABSTRACT

OBJECTIVE: Study of PD-L1 expression in squamous and adenosquamous cell cervical cancer (CC) by immunohistochemical (IHC) method, assessment of the relationship between PD-L1 tumor status and its clinical and morphological characteristics, TILs, MSI/dMMR, and HPV tumor status.

MATERIAL AND METHODS: Surgical material was obtained from 41 patients with CC, on which the expression of PD-L1, proteins of the MMR system and p16 was studied by the IHC method, the TILs index was determined.

RESULTS: Positive PD-L1 status was found in 51.2% of the studied CC samples. In the study sample, the level of PD-L1 expression depended on the severity of lymphoid infiltration of the tumor (p=0.038), it was shown that a positive PD-L1 status of CC can be expected with a TILs value greater than or equal to 50%. The age of the patients, the histological variant of the tumor, the pT and pN stage, the presence of lymphovascular invasion, and the HPV status did not statistically significantly affect the level of PD-L1 expression, however, there was an association between the PD-L1 status and the grade of CC malignancy (p=0.027). The presence of the MSI/dMMR phenomenon was detected in a small percentage of carcinomas (4.9%), the PD-L1 status of these tumors was determined as positive.

CONCLUSION: A positive PD-L1 status is determined in a significant number of cases of CC, regardless of most of the studied clinical and morphological characteristics; there is a statistically significant relationship between PD-L1 expression and the degree of tumor differentiation and TILs. It has been shown that CC with the MSI/dMMR phenomenon is characterized by a positive PD-L1 status. The authors consider it necessary to study the expression of PD-L1 in patients with cervical carcinomas in order to determine the possibility of prescribing personalized therapy with immune checkpoint inhibitors.

PMID:37814844 | DOI:10.17116/patol2023850515

J Antimicrob Chemother. 2023 Oct 10:dkad301. doi: 10.1093/jac/dkad301. Online ahead of print.

ABSTRACT

OBJECTIVES: Community-acquired pneumonia (CAP) is a significant source of hospital admissions and mortality. Atypical organisms are implicated in up to 40% of cases of CAP diagnoses. We studied the difference in outcomes of severe CAP patients treated with doxycycline versus azithromycin in addition to β-lactam therapy.

PATIENTS AND METHODS: This was a prospective observational cohort study from March 2020 to July 2022 in a medical ICU (MICU) of an academic quaternary medical center. Adults ≥18 years admitted to the MICU receiving doxycycline or azithromycin in addition to β-lactam therapy for the treatment of CAP were included for analysis. The primary outcomes were in-hospital and 30 day mortality. Secondary outcomes were ICU and hospital length-of-stay, 30 day readmission, days of mechanical ventilation, escalation and duration of antibiotics, adverse effects such as Clostridioides difficile infection and QTc prolongation.

RESULTS: Sixty-three patients were in the azithromycin group and eighty-six patients in the doxycycline group. Both groups had similar APACHE IV and CURB-65 scores. The mean Charlson Comorbidity Index score was higher for the doxycycline group compared with the azithromycin group (P = 0.04). There was no statistically significant difference in in-hospital and 30 day mortality between the groups (P = 0.53, P = 0.57). There were no significant differences in any of the secondary outcomes.

CONCLUSIONS: MICU patients with severe CAP who received doxycycline versus azithromycin in addition to β-lactam treatment showed no significant differences in outcomes. These data offer support for inclusion of doxycycline as an alternative regimen in current IDSA recommendations.

PMID:37814829 | DOI:10.1093/jac/dkad301

Anthropol Anz. 2023 Oct 9. doi: 10.1127/anthranz/2023/1755. Online ahead of print.

ABSTRACT

Manufacturers aim to design implants fitting for the broadest possible population segment. Due to the scarcity of available morphological data of intact long bones, anatomical collections of historical bone specimens may represent valuable additional sources. Previous work on femoral morphology measurements suggests that historical specimens are widely consistent with data from present-day populations. This study aimed to investigate whether this also applies to the anatomical fitting of a clinically used femoral nail. Nail fit was computer-graphically quantified through virtual implantation into CT-based 3D models of 52 femora, comprising a subset representative of the present-day Caucasian population (n = 31), a subset from a historical medieval European bone collection (n = 20), and additionally, a dataset from a natural ice mummy from the Neolithic period. Nail fit was assessed by nail protrusion (area and distance) to the inner cortex surface and the distal nail tip’s position in the medullary canal. Assessed measurements and parameters of the present-day Caucasian subset were mostly consistent with those of the medieval European subset. After adjusting for multiple testing, only the distance from lateral nail entry point to shaft axis remained significantly (p = 0.03) different when comparing our modern and medieval subsets. Subsequent bivariate (Spearman) correlation analyses for both subsets (modern and medieval) combined showed that of the three variables representing basic demographic parameters, individual age, biological sex, and femur length, most statistically significant associations to the examined nail fit measurements were found for age (six measurements at a level of p < 0.05), however, with a relatively weak monotonic correlation (rho values ranging between ±0.31 and ±0.37). The measurements for the Iceman’s femur lie within the range of the modern and historical subgroups, but in some cases, differ by more than one standard deviation from the mean. Our results confirm previous findings, suggesting that more recent historical bone specimen collections may indeed be a convenient and easily accessible source of new 3D morphological data and complement existing data to be used for the development of femoral nails.

PMID:37814806 | DOI:10.1127/anthranz/2023/1755

Anthropol Anz. 2023 Oct 9. doi: 10.1127/anthranz/2023/1734. Online ahead of print.

ABSTRACT

The body mass index (BMI) is used as the most common and simplest measure to predict obesity. The aim of the study was to compare the BMI method and % BF (body fat) determined by bioimpedance analysis for obesity screening and to evaluate the correlation between these methods. 200 women aged 18-25 years were included in the study. BMI ≥ 25/ ≥ 30 kg/m² was the criterion for assessment of overweight/obesity. Body fat (BF) in % and kg was determined by bioimpedance analysis. For assessment of obesity by % BF, the criterion was ≥ 30% fat. Based on BMI, 4.5% of women were obese, 14.5% were overweight. According to % BF, up to 30% of women were obese. The largest differences between BMI and % BF categorization were found in the underweight and overweight groups. According to the BMI 43% of women in the underweight category and 34.5% in the overweight category had a % BF in the normal range. By correlation analysis, we found a strong positive statistically significant correlation in women between BMI and BF (%) (rs = 0.782, p < 0.01) and also between BMI and BF (kg) (rs = 0.880, p < 0.01). Both of these methods assess body composition in their own specific way, complement each other, and other combining them, we achieve more accurate results for determining the overall health status of an individual.

PMID:37814802 | DOI:10.1127/anthranz/2023/1734

J Magn Reson Imaging. 2023 Oct 10. doi: 10.1002/jmri.29024. Online ahead of print.

ABSTRACT

BACKGROUND: The clinical presentation of juvenile myoclonic epilepsy (JME) and epilepsy with generalized tonic-clonic seizures alone (GTCA) is similar, and MRI scans are often perceptually normal in both conditions making them challenging to differentiate.

PURPOSE: To develop and validate an MRI-based radiomics model to accurately diagnose JME and GTCA, as well as to classify prognostic groups.

STUDY TYPE: Retrospective.

POPULATION: 164 patients (127 with JME and 37 with GTCA) patients (age 24.0 ± 9.6; 50% male), divided into training (n = 114) and test (n = 50) sets in a 7:3 ratio with the same proportion of JME and GTCA patients kept in both sets.

FIELD STRENGTH/SEQUENCE: 3T; 3D T1-weighted spoiled gradient-echo.

ASSESSMENT: A total of 17 region-of-interest in the brain were identified as having clinical evidence of association with JME and GTCA, from where 1581 radiomics features were extracted for each subject. Forty-eight machine-learning combinations of oversampling, feature selection, and classification algorithms were explored to develop an optimal radiomics model. The performance of the best radiomics models for diagnosis and for classification of the favorable outcome group were evaluated in the test set.

STATISTICAL TESTS: Model performance measured using area under the curve (AUC) of receiver operating characteristic (ROC) curve. Shapley additive explanations (SHAP) analysis to estimate the contribution of each radiomics feature.

RESULTS: The AUC (95% confidence interval) of the best radiomics models for diagnosis and for classification of favorable outcome group were 0.767 (0.591-0.943) and 0.717 (0.563-0.871), respectively. SHAP analysis revealed that the first-order and textural features of the caudate, cerebral white matter, thalamus proper, and putamen had the highest importance in the best radiomics model.

CONCLUSION: The proposed MRI-based radiomics model demonstrated the potential to diagnose JME and GTCA, as well as to classify prognostic groups. MRI regions associated with JME, such as the basal ganglia, thalamus, and cerebral white matter, appeared to be important for constructing radiomics models.

LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.

PMID:37814782 | DOI:10.1002/jmri.29024

Cureus. 2023 Sep 8;15(9):e44894. doi: 10.7759/cureus.44894. eCollection 2023 Sep.

ABSTRACT

Background Advances in imaging techniques have led to increased utilization of imaging devices in catheterization laboratories. Invasive surgical procedures for cardiac disorders have been largely replaced by fluoroscopic cardiac catheterization. With this increase, concerns and risks associated with exposure to ionizing radiation among interventional cardiologists are growing. This study aims to measure and compare the occupational doses to the eye lens and thyroid of pediatric interventional cardiologists during different procedures in the catheterization laboratory and its significance. Methodology In this study, cardiologists wore bandanas with attached dosimeters to measure the absorbed doses to the eyes and thyroid gland. The dosimeters were collected for reading. The procedure types were also collected. In addition, the total fluoroscopy time and tube voltage of the biplane machine were measured. SPSS version 23 (IBM Corp., Armonk, NY, USA) was used to analyze the data. The characteristics of the study sample were described using simple counts and percentages, whereas means and standard deviations were used for continuous variables. Statistical significance was set at p-values <0.05. Results A total of 93 procedures were evaluated. The mean absorbed doses for all 93 procedures in both eyes and thyroid were 0.09 mGy and 0.08 mGy, respectively. A significant difference was found between the left and right eye measurements (p = 0.034), with higher doses administered to the left eye. However, no significant difference was observed between the right and left thyroid doses (p = 0.281). Significant correlations were found between the eye and thyroid doses and the procedure type (p = 0.02 and p = 0.009, respectively). Conclusions A significant amount of radiation was measured in the measurements of both organs. In addition, radiation dose measurements varied between different types of procedures. Our current results indicate the importance and necessity of applying the radiation protection concept of dose optimization.

PMID:37814769 | PMC:PMC10560443 | DOI:10.7759/cureus.44894

Cureus. 2023 Sep 8;15(9):e44887. doi: 10.7759/cureus.44887. eCollection 2023 Sep.

ABSTRACT

Background Artificial intelligence (AI) is increasingly used in healthcare, but more data are needed about the knowledge, perceptions, attitudes, and preparedness of medical students in Oman towards this technology. This study aimed to investigate these aspects among clinical-year medical students at Sultan Qaboos University. Methodology A web-based validated exploratory questionnaire adapted from a study conducted at the University of Toronto was distributed to all clinical year (phase III) medical students at Sultan Qaboos University. The questionnaire collected demographic and background information, tested students’ knowledge of AI, and assessed their perceptions and attitudes toward it. The data were analyzed using the Statistical Package for Social Sciences (SPSS, IBM Corp., Armonk, NY). Results A total of 221 out of 368 clinical-year medical students (60%) completed the survey. Most respondents were in their junior clerkship year (n = 94, 42.5%). Most students (n = 167, 75.4%) had no prior exposure to AI in healthcare, with a median knowledge score of 3.25 out of 5 in AI, and showed no improvement over the years. However, they overall had positive perceptions and attitudes towards AI. Students also had concerns about the impact of AI on employment prospects and ethical issues but were generally receptive to incorporating AI into medical school curricula, as 174 students (78.7%) believed every medical trainee should receive training on AI competencies. Conclusion This study provides valuable insights into the knowledge, perceptions, attitudes, and preparedness of medical students in Oman toward AI in healthcare. Medical educators in Oman should consider incorporating AI into medical school curricula to prepare future physicians for using this technology in healthcare.

PMID:37814766 | PMC:PMC10560391 | DOI:10.7759/cureus.44887