Category: Nevin Manimala

Brain. 2024 Feb 22:awae058. doi: 10.1093/brain/awae058. Online ahead of print.

ABSTRACT

Neurodevelopmental disorders are major indications for genetic referral and have been linked to more than 1,500 loci including genes encoding transcriptional regulators. The dysfunction of transcription factors often results in characteristic syndromic presentations, however, at least half of these patients lack a genetic diagnosis. The implementation of machine learning approaches has the potential to aid in the identification of new disease genes and delineate associated phenotypes. Next generation sequencing was performed in seven affected individuals with neurodevelopmental delay and dysmorphic features. Clinical characterization included reanalysis of available neuroimaging datasets and 2D portrait image analysis with GestaltMatcher. The functional consequences of ZSCAN10 loss were modelled in mouse embryonic stem cells (mESC), including a knock-out and a representative ZSCAN10 protein truncating variant. These models were characterized by gene expression and Western blot analyses, chromatin immunoprecipitation and quantitative PCR (ChIP-qPCR), and immunofluorescence staining. Zscan10 knockout mouse embryos were generated and phenotyped. We prioritized bi-allelic ZSCAN10 loss-of-function variants in seven affected individuals from five unrelated families as the underlying molecular cause. RNA-Seq analyses in Zscan10-/- mESCs indicated dysregulation of genes related to stem cell pluripotency. In addition, we established in mESCs the loss-of-function mechanism for a representative human ZSCAN10 protein truncating variant by showing alteration of its expression levels and subcellular localization, interfering with its binding to DNA enhancer targets. Deep phenotyping revealed global developmental delay, facial asymmetry, and malformations of the outer ear as consistent clinical features. Cerebral MRI showed dysplasia of the semicircular canals as an anatomical correlate of sensorineural hearing loss. Facial asymmetry was confirmed as a clinical feature by GestaltMatcher and was recapitulated in the Zscan10 mouse model along with inner and outer ear malformations. Our findings provide evidence of a novel syndromic neurodevelopmental disorder caused by bi-allelic loss-of-function variants in ZSCAN10.

PMID:38386308 | DOI:10.1093/brain/awae058

Curr Environ Health Rep. 2024 Feb 22. doi: 10.1007/s40572-024-00430-1. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Airway inflammation is a common biological response to many types of environmental exposures and can lead to increased nitric oxide (NO) concentrations in exhaled breath. In recent years, several studies have evaluated airway inflammation using fractional exhaled nitric oxide (FeNO) as a biomarker of exposures to a range of air pollutants. This systematic review aims to summarize the studies that collected personal-level air pollution data to assess the air pollution-induced FeNO responses and to determine if utilizing personal-level data resulted in an improved characterization of the relationship between air pollution exposures and FeNO compared to using only ambient air pollution exposure data.

RECENT FINDINGS: Thirty-six eligible studies were identified. Overall, the studies included in this review establish that an increase in personal exposure to particulate and gaseous air pollutants can significantly increase FeNO. Nine out of the 12 studies reported statistically significant FeNO increases with increasing personal PM_2.5 exposures, and up to 11.5% increase in FeNO per IQR increase in exposure has also been reported between FeNO and exposure to gas-phase pollutants, such as ozone, NO_2, and benzene. Furthermore, factors such as chronic respiratory diseases, allergies, and medication use were found to be effect modifiers for air pollution-induced FeNO responses. About half of the studies that compared the effect estimates using both personal and ambient air pollution exposure methods reported that only personal exposure yielded significant associations with FeNO response. The evidence from the reviewed studies confirms that FeNO is a sensitive biomarker for air pollutant-induced airway inflammation. Personal air pollution exposure assessment is recommended to accurately assess the air pollution-induced FeNO responses. Furthermore, comprehensive adjustments for the potential confounding factors including the personal exposures of the co-pollutants, respiratory disease status, allergy status, and usage of medications for asthma and allergies are recommended while assessing the air pollution-induced FeNO responses.

PMID:38386269 | DOI:10.1007/s40572-024-00430-1

Braz J Microbiol. 2024 Feb 22. doi: 10.1007/s42770-024-01285-2. Online ahead of print.

ABSTRACT

The objective of this work was to carry out a systematic review on the effectiveness of local anesthetics as antimicrobial agents against Staphylococcus spp. Searches were performed in the PubMed, Web of science, Scopus, Embase and Lilacs databases. As inclusion criteria, complete original articles, with in vitro experimental tests with the application of selected anesthetics and bacteria of the genus Staphylococcus spp. This review followed the methodological checklist for writing papers reporting systematic reviews by the PRISMA statement. The risk of bias was assessed according to the JBI critical appraisal checklist. Analysis was performed using an anesthetic-moderated simple linear regression model. This systematic review was registered by the Open Science Framework-OSF ( https://doi.org/10.17605/OSF.IO/C5JM7 ). Initially, 1141 articles were found, of which, after careful selection, 52 articles were analyzed. Lidocaine was the most commonly used anesthetic, being evaluated in 35 of the articles. S. aureus ATCC 25923 was the standard microorganism in 17 articles. The impact of the anesthetic concentration in relation to the antimicrobial effect was evaluated and the results showed that there was no statistically significant difference. (F [5, 12] = 0.688 p = 0.642), even when taking into account the moderator effect of anesthetics individually. Therefore, although the antimicrobial effect of local anesthetics was demonstrated in 82.7% of the studies evaluated, great heterogeneity of the results was found, which made it impossible to carry out a meta-analysis and make recommendations based on the evidence.

PMID:38386261 | DOI:10.1007/s42770-024-01285-2

Biol Trace Elem Res. 2024 Feb 22. doi: 10.1007/s12011-024-04097-5. Online ahead of print.

ABSTRACT

In this study, the concentrations of heavy metals such as cadmium (Cd), chromium (Cr), and lead (Pb) in the two groups of cigarette smokers and non-smokers in five age range groups were measured. Heavy metal concentrations were collected in participants’ urine samples and analyzed using atomic absorption spectrophotometry (AAS). The results showed that the concentrations of these metals in the urine of smokers were higher than in non-smoker subjects. The mean concentration of Cd, Cr, and Pb for smokers were 1.188 ± 0.931, 1.929 ± 0.940, and 0.069 ± 0.023, respectively, while the mean concentration of Cd, Cr, and Pb for non-smokers were 0.151 ± 0.165, 0.203 ± 0.218, and 0.037 ± 0.030, respectively. The results revealed statistically significant differences when comparing the samples of smokers to the control group in all heavy metals in the present study. Also, the results revealed statistically significant differences in Cd, Cr, and Pb when comparing the samples of smokers to age groups. The trend of metals in urine samples in two groups (smokers and non-smokers) is as follows: Cd > Cr > Pb. The concentration of Cd, Cr, and Pb in all samples of the present study was higher than the biological limit, according to ACGIH. Therefore, Cd, Cr, and Pb were the most critical metals accumulated in the urine of cigarette smokers.

PMID:38386229 | DOI:10.1007/s12011-024-04097-5

J Robot Surg. 2024 Feb 22;18(1):89. doi: 10.1007/s11701-024-01845-6.

ABSTRACT

The aim of this study was to report our single-center experience of the da Vinci robotic surgery system in the management of endometrial cancer (EC) patients during 2019-2023. We descriptively summarized the preoperative, intraoperative, and postoperative outcomes. Moreover, we conducted subgroup analyses based on obesity (BMI ≥ 30 kg/m²) and the intraoperative use of indocyanine green dye (ICG). Overall, 100 patients were analyzed. Eighty-five patients (85%) were obese. The mean operative time and estimated blood loss (EBL) were 240.84 ± 70.08 min (range: 110-720) and 104.2 ± 80.3 ml (range: 20-500), respectively. The mean number of retrieved pelvic LNs was 3.01 ± 3.06 (range: 0-15). The use of ICG was employed in 58 (58%). Only a single patient (1%) underwent conversion to laparotomy. Besides, only three (3%) patients experienced vaginal laceration intraoperatively, respectively. The mean hospital stay was 1.34 ± 0.69 days (range: 1-5). No patient experienced postoperative complications. Most tumors had endometrioid histology (82%), grade-1 tumor (49%), and stage-1A disease (67%). At 3-year follow-up, only two patients (2%) developed recurrence. Patients who received the ICG had significantly lower operative time (225.86 vs. 261.52 min, p = 0.011), estimated blood loss (90 vs. 123.81 ml, p = 0.037), and hospital stay (1.12 vs. 1.64 days, p < 0.001) compared with patients who did not receive it. However, there was no significant difference between both groups regarding the number of retrieved pelvic LNs. Obesity had no significant impact on the rates of intraoperative complications, postoperative complications, and 3-year recurrence incidence. In conclusion, robotic surgery was technically feasible and safe. The use of ICG was statistically linked to favorable outcomes, in terms of decreased operative time, EBL, and hospital stay. Obesity did not impact the perioperative surgical outcomes.

PMID:38386227 | DOI:10.1007/s11701-024-01845-6

J Robot Surg. 2024 Feb 22;18(1):90. doi: 10.1007/s11701-024-01841-w.

ABSTRACT

The influence of Medicaid or being uninsured is prevailingly thought to negatively impact a patient’s socioeconomic and postoperative course, yet little has been published to support this claim specifically in reference to robotic pancreaticoduodenectomy. This study was undertaken to determine impact of health insurance type on perioperative outcomes in patients undergoing robotic pancreaticoduodenectomy. Following IRB approval, we prospectively followed 364 patients who underwent robotic pancreaticoduodenectomy. Patients were stratified by insurance status (i.e., Private, Medicare, and Medicaid/Uninsured); 100 patients were 2:2:1 propensity-score matched by age, BMI, ASA class, pathology, 8th edition AJCC staging, and tumor size. Perioperative variables were compared utilizing contingency testing and ANOVA. Statistical significance was accepted at a p-value ≤ 0.05 and data are presented as median (mean ± SD). The 100 patients undergoing propensity-score matching were 64 (65 ± 9.1) years old with a BMI of 27 (27 ± 4.9) kg/m² and ASA class of 3 (3 ± 0.5). Operative duration was 421 (428 ± 105.9) minutes and estimated blood loss was 200 (385 ± 795.0) mL. There were 4 in-hospital deaths and 8 readmissions within 30 days of discharge. Total hospital cost was $32,064 (38,014 ± 22,205.94). After matching, no differences were found in pre-, intra-, and short-term postoperative variables among patients with different insurances, including hospital cost and time to initiate adjuvant treatment, which was 8 (9 ± 7.9) weeks for patients with malignant disease. In our hepatopancreaticobiliary program, health insurance status did not impact perioperative outcomes or hospital costs. These findings highlight that financial coverage does not influence quality of perioperative care, reinforcing the equity of robotic surgery.

PMID:38386222 | DOI:10.1007/s11701-024-01841-w

Cell Tissue Bank. 2024 Feb 22. doi: 10.1007/s10561-024-10134-3. Online ahead of print.

ABSTRACT

Allografts are the second most transplanted tissue in medicine after blood and are now increasingly used for both primary and revision surgery. Allografts have the advantages of lower donor site morbidity, availability of multiple grafts, and shorter operative time. The Banks represents the bridge between Donor and Recipient and guarantees the quality and safety of the distributed allografts Given the increasing interest in these tissues, a retrospective analysis of data collected from the Regional Musculoskeletal Tissue Bank registry over an 11-year period (2009-2019) was conducted. The statistical analyses used were the Shapiro-Wilk normality test and a Poisson regression model. From January 2009 to December 2019, a total of 14,199 musculoskeletal tissues stored in the Regional Musculoskeletal Tissue Bank were provided for surgical allograft procedures. In 2009, the number of allografts performed was 925; this figure has steadily increased to 1599 in 2019. Epiphyses were taken as the reference tissue with an almost constant trend over the period, while a significant increase was denoted for extensor mechanism allograft, ligaments, tendons and long bone corticals (p < 0.001), processed bone tissues had no change in trend (p = 0.841). There was also a gradual decrease in the rate of microbiological positivity, as determined by bacteriological and serological tests performed on the collected tissues. This phenomenon is due to improved sampling techniques and the training of a dedicated team. Thus, we have seen how the use of allografts in orthopedic surgery has increased over the past 11 years, uniformly in terms of tissue type, except for the noticeable increase in ligamentous tissue.

PMID:38386210 | DOI:10.1007/s10561-024-10134-3

Int J Comput Assist Radiol Surg. 2024 Feb 22. doi: 10.1007/s11548-024-03069-3. Online ahead of print.

ABSTRACT

PURPOSE: Intracardiac transcatheter interventions allow for reducing trauma and hospitalization stays as compared to standard surgery. In the treatment of mitral regurgitation, the most widely adopted transcatheter approach consists in deploying a clip on the mitral valve leaflets by means of a catheter that is run through veins from a peripheral access to the left atrium. However, precise manipulation of the catheter from outside the body while copying with the path constraints imposed by the vessels remains challenging.

METHODS: We proposed a path tracking control framework that provides adequate motion commands to the robotic steerable catheter for autonomous navigation through vascular lumens. The proposed work implements a catheter kinematic model featuring nonholonomic constraints. Relying on the real-time measurements from an electromagnetic sensor and a fiber Bragg grating sensor, a two-level feedback controller was designed to control the catheter.

RESULTS: The proposed method was tested in a patient-specific vessel phantom. A median position error between the center line of the vessel and the catheter tip trajectory was found to be below 2 mm, with a maximum error below 3 mm. Statistical testing confirmed that the performance of the proposed method exhibited no significant difference in both free space and the contact region.

CONCLUSION: The preliminary in vitro studies presented in this paper showed promising accuracy in navigating the catheter within the vessel. The proposed approach enables autonomous control of a steerable catheter for transcatheter cardiology interventions without the request of calibrating the intuitive parameters or acquiring a training dataset.

PMID:38386176 | DOI:10.1007/s11548-024-03069-3

World J Urol. 2024 Feb 22;42(1):95. doi: 10.1007/s00345-024-04787-8.

ABSTRACT

PURPOSE: The primary objective was to establish whether blood-based leucine-rich alpha-2-glycoprotein (LRG1) can predict outcomes in patients with locally advanced prostate cancer undergoing androgen-deprivation therapy (ADT) and radiotherapy (RT) and to determine how it may relate to 92 immune-oncology (I-O)-related proteins in this setting.

METHODS: Baseline blood level of LRG1 from patients treated with ADT and RT enrolled in the CuPCa (n = 128) and IMRT (n = 81) studies was measured using ELISA. A longitudinal cohort with matched blood samples from start of ADT, start of RT, and end of RT protocol from 47 patients from the IMRT cohort was used to establish levels of I-O proteins by high-multiplexing Proximal Extension Assay by Olink Proteomics. Statistical analyses using Kaplan-Meier, Cox regression, and LIMMA analyses were applied to predict the prognostic value of LRG1 and its correlation to I-O proteins.

RESULTS: High baseline levels of LRG1 predicted a low frequency of treatment failure in patients undergoing ADT + RT in both the CuPCa and the IMRT cohorts. LRG1 was moderately correlated with CD4, IL6, and CSF1. We identified I-O proteins predicting metastatic failure (MF) at different timepoints.

CONCLUSION: LRG1 biomarker is associated with I-O proteins and can be used to improve stratification and monitoring of prostate cancer patients undergoing ADT + RT. This work will require further in-depth analyses in independent cohorts with treatment outcome data.

PMID:38386171 | DOI:10.1007/s00345-024-04787-8

Invest New Drugs. 2024 Feb 22. doi: 10.1007/s10637-024-01424-4. Online ahead of print.

ABSTRACT

Patients with metastatic lung adenocarcinoma (MLA) and malignant pleural effusion (MPE) without driver gene mutations have a poor prognosis. None of the standard treatment strategies is recommended for such patients. We retrospectively analyzed the efficacy of the first-line treatment for this specific population: standard platinum-based doublet chemotherapy (CT), CT plus an immune checkpoint inhibitor (CT plus ICI), and CT plus bevacizumab (CT plus Bev). A total of 323 eligible patients were enrolled: CT alone (n = 166), CT plus Bev (n = 72), and CT plus ICI (n = 85). Treatment efficacy assessments were performed every two cycles according to the RECIST guidelines. The endpoints were overall survival (OS) and progression-free survival (PFS). Kaplan-Meier (K‒M) curves and the log-rank test were used to compare OS and PFS. p < 0.05 was the threshold of significance (statistical software: SPSS). The median follow-up was 11.4 months (range, 2.1-49.6 months). PFS and OS in the CT plus ICI/CT plus Bev cohort were significantly longer than those in the CT group (PFS: 7.8/6.4/3.9 months, p < 0.0001; OS: 16.4/15.6/9.6 months, p < 0.0001, respectively). CT plus Bev had better PFS and OS than CT plus ICI/CT in PD-L1 < 1% patients (PFS: 8.4/5.0/3.8 months, p < 0.0001; OS: 15.6/12.9/9.3 months, p < 0.0001). Among patients with PD-L1 1-49%, CT plus ICI led to a longer PFS and OS (PFS: 8.9/5.8/4.2 months, p = 0.009; OS: 24.2/18.8/11.5 months, p = 0.03). In the cohort with PD-L1 ≥ 50%, CT plus ICI was still the best first-line treatment (PFS: 19.7/13.8/9.6 months, p = 0.033; OS: 27.2/19.6/14.9 months, p = 0.047). In driver gene-negative MLA with MPE, CT plus Bev or ICI better controlled MPE and significantly prolonged survival compared to CT alone. PD-L1 expression (negative/positive) may be a key factor influencing the choice of CT plus Bev or ICI.

PMID:38386170 | DOI:10.1007/s10637-024-01424-4