Nevin Manimala

Nat Commun. 2022 Sep 12;13(1):5350. doi: 10.1038/s41467-022-33093-3.

ABSTRACT

Age-related changes to the genome-wide DNA methylation (DNAm) pattern observed in blood are well-documented. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by the age-related acquisition and expansion of leukemogenic mutations in hematopoietic stem cells (HSCs), is associated with blood cancer and coronary artery disease (CAD). Epigenetic regulators DNMT3A and TET2 are the two most frequently mutated CHIP genes. Here, we present results from an epigenome-wide association study for CHIP in 582 Cardiovascular Health Study (CHS) participants, with replication in 2655 Atherosclerosis Risk in Communities (ARIC) Study participants. We show that DNMT3A and TET2 CHIP have distinct and directionally opposing genome-wide DNAm association patterns consistent with their regulatory roles, albeit both promoting self-renewal of HSCs. Mendelian randomization analyses indicate that a subset of DNAm alterations associated with these two leading CHIP genes may promote the risk for CAD.

PMID:36097025 | DOI:10.1038/s41467-022-33093-3

Nat Commun. 2022 Sep 12;13(1):5239. doi: 10.1038/s41467-022-32848-2.

ABSTRACT

The blood and lymphatic vasculature networks are not yet fully understood even in mouse because of the inherent limitations of imaging systems and quantification methods. This study aims to evaluate the usefulness of the tissue-clearing technology for visualizing blood and lymphatic vessels in adult mouse. Clear, unobstructed brain/body imaging cocktails and computational analysis (CUBIC) enables us to capture the high-resolution 3D images of organ- or area-specific vascular structures. To evaluate these 3D structural images, signals are first classified from the original captured images by machine learning at pixel base. Then, these classified target signals are subjected to topological data analysis and non-homogeneous Poisson process model to extract geometric features. Consequently, the structural difference of vasculatures is successfully evaluated in mouse disease models. In conclusion, this study demonstrates the utility of CUBIC for analysis of vascular structures and presents its feasibility as an analysis modality in combination with 3D images and mathematical frameworks.

PMID:36097010 | DOI:10.1038/s41467-022-32848-2

Womens Health Issues. 2022 Sep 9:S1049-3867(22)00082-2. doi: 10.1016/j.whi.2022.07.004. Online ahead of print.

ABSTRACT

OBJECTIVE: Women incarcerated in local jails have pregnancy and sexual health needs, yet little information is available about what services are provided and how jail administrators prioritize this care. Our objective was to document jails’ provision of pregnancy and sexual health services in four states in the Midwest.

METHODS: We invited all jail administrators (N = 347) in Kansas, Missouri, Iowa, and Nebraska to participate in a web-based survey conducted from November 2017 to October 2018. We asked administrators which pregnancy and sexual health services they offered and to rate the importance of offering services. Results were analyzed using descriptive statistics and logistic regression.

RESULTS: The survey response rate was 55% (192/347). Jails most often provided pregnancy testing (n = 116 [60%]) and distribution of prenatal vitamins (n = 85 [44%]). Sexually transmitted infection treatment was offered at 23% of jails (n = 45). Larger, accredited jails located in urban areas and with high numbers of clinical providers on staff were more likely to provide sexual health services. Jails with privately contracted health care were more likely to provide pregnancy services compared with other entities providing medical care. The most prioritized sexual health service was sexually transmitted infection testing, with 39% of administrators believing it was important. Only 6% of administrators responded that contraception was important.

CONCLUSIONS: Local jails in the Midwest do not meet the basic reproductive and sexual health needs of women. Provision of these services is not a priority for jail administrators. Appropriate partnerships could engage administrators and increase the availability of services to meet the needs of women in jail.

PMID:36096980 | DOI:10.1016/j.whi.2022.07.004

Vaccine. 2022 Sep 9:S0264-410X(22)01077-5. doi: 10.1016/j.vaccine.2022.08.069. Online ahead of print.

ABSTRACT

BACKGROUND: Japan currently lacks a data platform that can support quantitative assessments of the causal relationships between vaccines and adverse events. This study describes the development and application of the Vaccine Effectiveness, Networking, and Universal Safety (VENUS) Study to facilitate such assessments.

METHODS: A database was created by linking public insurance enrollees’ claims data with vaccination records acquired from participating municipalities. To provide an overview of the study data, we produced descriptive statistics of sex, age, and vaccinations. We also conducted a pilot study using the database to assess influenza vaccine safety during the 2018/2019 season among older persons (≥65 years) residing in a single municipality.

RESULTS: Our database was created using data from approximately 1.12 million individuals in 7 municipalities between 2013 and 2020. The data during fiscal year 2018 included 853,016 individuals (male: 363,079, female: 489,937) with a median age of 70 years (interquartile range: 52-79). We obtained information on 17 vaccine types, including the pneumococcal vaccine and influenza vaccine. In the pilot study, we analyzed 48,723 vaccinated persons matched with 48,723 unvaccinated persons. The only adverse event that occurred in both groups was Bell’s palsy, which had an adjusted incidence rate ratio of 1.21 (95 % confidence interval: 0.48-3.07).

CONCLUSIONS: The VENUS Study is Japan’s first healthcare data platform that enables comparative assessments of vaccinated and unvaccinated persons in large samples covering all age groups. Efforts are underway to increase the number of participating municipalities and to generate evidence on vaccine effectiveness and safety.

PMID:36096969 | DOI:10.1016/j.vaccine.2022.08.069

J Emerg Med. 2022 Sep 9:S0736-4679(22)00279-7. doi: 10.1016/j.jemermed.2022.04.006. Online ahead of print.

ABSTRACT

BACKGROUND: D-dimer testing rules out deep vein thrombosis (DVT) and pulmonary embolism (PE) in low-risk emergency department (ED) patients. Most research has measured fibrin-equivalent units (FEUs), however, many laboratories measure D-dimer units (DDUs).

OBJECTIVE: Our aim was to determine whether either DDU measurements or FEU measurements can rule out DVT/PE using traditional or age-related cutoff values.

METHODS: We performed a de-identified multicenter retrospective evaluation of D-dimer in nonpregnant adult ED patients to evaluate for DVT/PE. DDUs were multiplied by 2 to determine equivalent FEUs prior to analysis. Sensitivity measurements for D-dimer were calculated for FEUs, DDUs, combined FEU/DDUs, and multiple age-adjusted values.

RESULTS: We identified 47,088 ED patients with a D-dimer laboratory value (27,307 FEUs/19,781 DDUs) and 1623 DVT/PEs. The median combined FEU/DDU D-dimer was 400 ng/mL FEUs (interquartile range [IQR] 300-900 ng/mL FEUs) for patients without a DVT/PE vs 2530 ng/mL FEU (IQR 1094-6000 ng/mL FEUs) with a DVT/PE (p < 0.001), overall sensitivity of 87.3% (95% confidence interval [CI] 87.0-87.6%) and negative predictive value of 99.3% (95% CI 99.2-99.4%). Individually, FEUs performed better than DDUs, with sensitivities of 88.0% (95% CI 85.8-89.9%) and 86.1% (95% CI 83.1-88.7%), respectively; however, this difference was not statistically significant. Combined age-adjusted performance had a sensitivity of 90.3% (95% CI 88.3-92.0%); however, a new DDU-only age-adjusted criteria had the highest sensitivity of 91.1% (95% CI 87.9-93.6%).

CONCLUSIONS: Our undifferentiated D-dimer measurements had a slightly lower sensitivity to rule out DVT/PE than reported previously. Our data support using either DDU or FEU measurements for all ages or when using various age-adjusted criteria to rule out DVT/PE.

PMID:36096961 | DOI:10.1016/j.jemermed.2022.04.006

Prog Retin Eye Res. 2022 Sep 9:101115. doi: 10.1016/j.preteyeres.2022.101115. Online ahead of print.

ABSTRACT

Retinal gene supplementation therapy such as the first approved one, voretigene neparvovec, delivers a functioning copy of the missing gene enabling the protein transcription in retinal cells and restore visual functions. After gene supplementation for the genetic defect, a complex network of functional regeneration is the consequence, whereas the extent is very individualized. Diagnostic and functional testings that have been used routinely by ophthalmologists so far to define the correct diagnosis, cannot be applied in the new context of defining small, sometimes subtle changes in visual functions. New view on retinal diagnostics is needed to understand this processes that define safety and efficacy of the treatment. Not only does vision have many aspects that must be addressed by specific evaluations and imaging techniques, but objective readouts of local retinal function for rods and cones separately have been an unmet need until recently. A reliable test-retest variability is necessary in rare diseases such as inherited retinal dystrophies, because statistics are often not applicable due to a low number of participants. Methods for a reliable individual evaluation of the therapy success are needed. In this manuscript we present an elaboration on retinal diagnostics combining psychophysics (eg. full-field stimulus threshold or dark adapted perimetry) as well as objective measures for local retinal function (eg. photopic and scotopic chromatic pupil campimetry) and retinal imaging for a meaningful workflow to apply in evaluation of the individual success in patients receiving gene therapy for photoreceptor diseases.

PMID:36096933 | DOI:10.1016/j.preteyeres.2022.101115

Asian J Surg. 2022 Sep 9:S1015-9584(22)01199-X. doi: 10.1016/j.asjsur.2022.08.085. Online ahead of print.

ABSTRACT

OBJECTIVE: We aimed to evaluate associations between abdominal fat distribution (AFD) parameters and incisional hernia (IH) in patients who underwent transumbilical single-port laparoscopic surgery (SPLS) for gynecological disease.

METHODS: Medical records of 2116 patients who underwent SPLS for gynecological disease at Daejeon St. Mary’s Hospital between March 2014 and February 2021 were reviewed. Among 21 (1.0%) patients who developed IH requiring surgical treatment after SPLS, 18 had preoperative abdominopelvic computed tomography (CT) images. As a control group, we randomly selected 72 patients who did not develop IH and who had undergone preoperative abdominopelvic CT scan, matched to test patients by type of surgery. Total fat area (TFA), visceral fat area (VFA), subcutaneous fat area (SFA), visceral-to-subcutaneous fat ratio (VSR), and waist circumference (WC) were measured at the level of the third lumbar vertebral body on the preoperative abdominopelvic CT images, using National Institutes of Health (NIH) ImageJ version 1.53 k.

RESULTS: Receiver operating curve analysis showed that VFA has the highest predictive value for IH among AFD parameters (AUC = 0.749, 95% CI 0.630-0.869, p < 0.001). Univariate analysis showed that age, BMI, hypertension, dyslipidemia, TFA, VFA, VSR and WC were significant factors for IH. In multivariate analysis, only high VFA was identified as an independent risk factor for IH (HR 6.18, 95% CI 1.13-33.87, p = 0.04), whereas BMI, TFA, SFA, VSR, and WC failed to show statistical significance.

CONCLUSION: We could find high VFA as an independent risk factor of IH in patients who underwent SPLS for gynecologic disease.

PMID:36096929 | DOI:10.1016/j.asjsur.2022.08.085

Sci Rep. 2022 Sep 12;12(1):15347. doi: 10.1038/s41598-022-18894-2.

ABSTRACT

Saliva is rich in proteins, DNA, RNA and microorganisms, and can be regarded as a biomarker library. In order to explore a noninvasive and simple means of early screening for liver cancer, proteomics was used to screen salivary markers of hepatitis B associated liver cancer. We used mass spectrometry coupled isobaric tags for relative and absolute quantitation (iTRAQ)-technology to identify differentially expressed proteins (DEPs). Western blot, immunohistochemistry and enzyme linked immunosorbent assay were used to detect marker expression of in tissues and saliva. Statistical analysis was used to analyze the diagnostic efficacy of the markers was analyzed through statistical analyses. By comparing the hepatocellular carcinoma (HCC) group with non-HCC groups, we screened out 152 salivary DEPs. We found orosomucoid 1(ORM1) had significantly higher expression in saliva of HCC patients compared with non-HCC groups (p < 0.001) and the expression of ORM1 in liver cancer tissues was significantly higher than that in adjacent normal tissues (p < 0.001). The combination of salivary ORM1 and alpha-fetoprotein (AFP) showed reasonable specificities and sensitivities for detecting HCC. In a word, salivary ORM1 as a new biomarker of hepatitis B associated hepatocellular carcinoma, combination of salivary ORM1 and AFP as an improved diagnostic tool for hepatocellular carcinoma.

PMID:36096917 | DOI:10.1038/s41598-022-18894-2

Sci Rep. 2022 Sep 12;12(1):15325. doi: 10.1038/s41598-022-19412-0.

NO ABSTRACT

PMID:36096916 | DOI:10.1038/s41598-022-19412-0

J Prosthet Dent. 2022 Sep 9:S0022-3913(22)00466-8. doi: 10.1016/j.prosdent.2022.07.005. Online ahead of print.

ABSTRACT

STATEMENT OF PROBLEM: When an abutment screw fractures, there is no standardized technique for retrieving it from the intaglio of the dental implant.

PURPOSE: The purpose of this in vitro study was to assess the relative efficacy of a commercially available screw fragment retrieval kit with a range of standard dental instruments in regard to success and retrieval time. In addition, the effects of other variables on the success rate of screw fragment retrieval and the retrieval time required were also investigated. Finally, the integrity of the intaglio screw channel of the dental implant was also assessed following retrieval.

MATERIAL AND METHODS: The abutment screws from 4 dental implant systems: Osseotite Certain, Ø4.1 mm (Zimmer Biomet); Osseotite External hexagonal connection micromini, Ø3.25 mm (Zimmer Biomet); Standard Plus Tissue Level, Ø4.8 mm (Institut Straumann AG); and Brånemark Mark III TiUnite, Ø4.1 mm (Nobel Biocare) had notches placed between the first and second coronal threads before being placed in their respective abutments, positioned in the dental implants (n=128), and tightened until the screws fractured. The dental implant specimens were placed in maxillary and mandibular casts at the lateral incisor and first molar sites on both sides. The casts were placed in mannequin heads on a dental chair and assigned to 2 experienced and 2 inexperienced operators who used 2 different retrieval kits to retrieve the screw fragments. Chisquared tests were used to determine the association between the success rate of screw fragment retrieval and the other factors recorded (α=.05), and a binary logistic regression was used to determine the association between the retrieval event and all of the independent variables. Regression models were developed to determine the factors effecting retrieval time.

RESULTS: An overall success rate of 88.3% was achieved for screw fragment retrieval. No statistically significant difference (P=1) was found in the relative efficacy of the retrieval kits. Univariate analysis identified a statistically significant association (P<.01) in the success of abutment screw fragment retrieval between the Osseotite Certain and the Osseotite External hexagonal connection micromini implant systems. Gamma regression analysis identified significant differences between the time taken to retrieve the screw fragments and the type of dental implant (P<.001), (P<.01). The time taken to retrieve screw fragments in the maxillary arch was significantly longer than for the mandibular arch (P<.05).

CONCLUSIONS: The commercially available screw fragment retrieval kit and the standard dental instruments were equally effective in retrieving the screw fragments. Less time was required to retrieve screw fragments in the mandibular arch than the maxillary arch. The level of experience of the operator had no effect on the ability to successfully retrieve fractured abutment screws.

PMID:36096913 | DOI:10.1016/j.prosdent.2022.07.005