Nevin Manimala

J Orthop Res. 2023 Oct 26. doi: 10.1002/jor.25720. Online ahead of print.

ABSTRACT

Rifampin has been proven to be effective in the treatment of prosthetic infections due to its ability to intercalate into biofilms. The use of rifampin in antibiotic spacers is not well described, which would be especially important in the local periprosthetic environment where parenteral doses have poor penetration. Null hypothesis tests if rifampin use in PMMA cement will show no clinically significant impact on mechanical strength at antibiotic concentrations that remain bactericidal. Test antibiotic cement samples supplemented with 0mg, 30mg, 50mg, 100mg, 150mg or 200mg of rifampin into a standard 40g bag were tested for compression to failure using published ASTM standards. The samples were then inoculated with Pseudomonas aeruginosa and either evaluated for lipo-polysacharide (LPS) presence as a marker of biofilm or tested by elution as the Kirby Bauer assay. Rifampin concentrations of 30mg, and 50mg, showed no statistically different mechanical characteristics to control PMMA (p>0.05). The 100mg sample fell within the acceptable range of compressive strength and had significantly less LPS and bacterial presence compared to control at 12 and 24 hours. The ability of PMMA with 100mg of rifampin to maintain its structural integrity and have significant bacterial inhibition at 12 and 24 hours makes it a great candidate as an antibiotic bone cement additive. PMMA loaded with up to 100mg of rifampin shows promise in the treatment and prevention of PJI for total knee and total hip arthroplasty. This article is protected by copyright. All rights reserved.

PMID:37884321 | DOI:10.1002/jor.25720

Prev Chronic Dis. 2023 Oct 26;20:E94. doi: 10.5888/pcd20.230071.

ABSTRACT

INTRODUCTION: We examined national estimates of breast, cervical, and colorectal cancer (CRC) screening test use and compared them with Healthy People 2030 national targets. Test use in 2021 was compared with prepandemic estimates.

METHODS: In 2022, we used 2021 National Health Interview Survey (NHIS) data to estimate proportions of adults up to date with US Preventive Services Task Force recommendations for breast (women aged 50-74 y), cervical (women aged 21-65 y), and CRC screening (adults aged 50-75 y) across sociodemographic and health care access variables. We compared age-standardized estimates from the 2021 and 2019 NHIS.

RESULTS: Percentages of adults up to date in 2021 were 75.7% (95% CI, 74.4%-76.9%), 75.2% (95% CI, 73.9%-76.4%), and 72.2% (95% CI, 71.2%-73.2%) for breast, cervical, and CRC screening, respectively. Estimates were below 50% among those without a wellness check in 3 years (all screening types), among those without a usual source of care or insurance (aged <65 y) (breast and CRC screening), and among those residing in the US for less than 10 years (CRC screening). Percentages of adults who were up to date with breast and cervical cancer screening and colonoscopy were similar in 2019 and 2021. Fecal occult blood/fecal immunochemical test (FOBT/FIT) use was modestly higher in 2021 (P < .001).

CONCLUSIONS: In 2021, approximately 1 in 4 adults of screening age were not up to date with breast, cervical, and CRC screening recommendations, and Healthy People 2030 national targets were not met. Disparities existed across several characteristics, particularly those related to health care access. Breast, cervical, and colonoscopy test use within recommended screening intervals approximated prepandemic levels. FOBT/FIT estimates were modestly higher in 2021.

PMID:37884318 | DOI:10.5888/pcd20.230071

AJNR Am J Neuroradiol. 2023 Oct 26. doi: 10.3174/ajnr.A8026. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: The human auditory system develops early in fetal life. This retrospective MR imaging study describes the in vivo prenatal anatomic development of the transverse temporal gyrus (Heschl gyrus) site of the primary auditory cortex.

MATERIALS AND METHODS: Two hundred seventy-two MR imaging studies of the fetal brain (19-39 weeks’ gestational age) acquired from a single institution’s 1.5T scanner were retrospectively examined by 2 neuroradiologists. MR imaging with pathologic findings and extreme motion artifacts was excluded. Postnatal Heschl gyrus landmarks were used as a reference on T2-weighted ssFSE sequences in the 3 orthogonal planes. The frequency of the Heschl gyrus was reported for gestational age, hemisphere, and planes. Descriptive statistics and a McNemar test were performed.

RESULTS: Two hundred thirty MR imaging studies were finally included. Fetal brains were divided by gestational age (in weeks) into 8 groups (parentheses indicate the number of observations): 19-21 (29), 22-23 (32), 24-25 (21), 26-27 (18), 28-29 (35), 30-31 (30), 32-33 (33) and >34 (32). The Heschl gyrus appeared on MR imaging between 24 and 25 weeks’ gestational age (14/21 fetuses, 67%) and was visible in all fetuses after the 28th week of gestation. By its appearance (24-28 weeks’ gestational age), the sagittal plane was the most sensitive in its detectability. After 28-29 weeks’ gestational age, the Heschl gyrus was evident in all acquisition planes and fetuses. Results did not differ between hemispheres.

CONCLUSIONS: The Heschl gyrus appears on MR imaging at 24-25 weeks’ gestational age, paralleling the functional activation of the auditory system. We propose the Heschl gyrus as an early additional MR imaging marker of fetal brain development.

PMID:37884303 | DOI:10.3174/ajnr.A8026

AJNR Am J Neuroradiol. 2023 Oct 26. doi: 10.3174/ajnr.A8032. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: The radiologic prevalence of superior semicircular canal dehiscence in the asymptomatic population has been widely studied, but less is known about the rates of other forms of third window dehiscence. Per the existing literature, the radiologic prevalence of cochlear-facial nerve dehiscence, for example, exceeds that seen in histologic studies, suggesting that conventional CT is unreliable for cochlear-facial dehiscence. These studies relied on nonisometric CT acquisitions, however, and underused multiplanar reformatting techniques, leading to false-positive findings. Our purpose was to determine the rate of cochlear-facial dehiscence and other non-superior semicircular canal third window dehiscences on optimized CT in asymptomatic patients.

MATERIALS AND METHODS: Sixty-four-channel temporal bone CT scans from 602 patients in emergency departments were assessed for cochlear-facial and other non-superior semicircular canal third window dehiscences by using high-resolution, multiplanar oblique reformats. Confidence intervals for dehiscence prevalence were calculated using the Newcombe 95% interval confidence method.

RESULTS: Of 602 patients, 500 were asymptomatic, while 102 had an imaging indication consistent with possible third window syndrome (symptomatic). Eight asymptomatic patients (1.6%) had cochlear-facial dehiscence, while 43 (8.4%) had jugular bulb-vestibular aqueduct dehiscence. There was no statistically significant difference between the prevalence of cochlear-facial dehiscence or jugular bulb-vestibular aqueduct dehiscence in asymptomatic patients compared with symptomatic patients. Cochlear-carotid canal, cochlear-internal auditory canal, and cochlear-petrosal sinus dehiscences were not observed.

CONCLUSIONS: Sixty-four-channel CT with multioblique reformatting is sensitive and specific for identifying cochlear-facial dehiscence, with rates similar to those in postmortem series. Jugular bulb-vestibular aqueduct dehiscence is a common incidental finding and is unlikely to produce third window physiology. Other non-superior semicircular canal third window dehiscences are rare in asymptomatic patients.

PMID:37884302 | DOI:10.3174/ajnr.A8032

AJNR Am J Neuroradiol. 2023 Oct 26. doi: 10.3174/ajnr.A8034. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: IDH-mutant gliomas are further divided on the basis of 1p/19q status: oligodendroglioma, IDH-mutant and 1p/19q-codeleted, and astrocytoma, IDH-mutant (without codeletion). Occasionally, testing may reveal single-arm 1p or 19q deletion (unideletion), which remains within the diagnosis of astrocytoma. Molecular assessment has some limitations, however, raising the possibility that some unideleted tumors could actually be codeleted. This study assessed whether unideleted tumors had MR imaging features and survival more consistent with astrocytomas or oligodendrogliomas.

MATERIALS AND METHODS: One hundred twenty-one IDH-mutant grade 2-3 gliomas with 1p/19q results were identified. Two neuroradiologists assessed the T2-FLAIR mismatch sign and calcifications, as differentiators of astrocytomas and oligodendrogliomas. MR imaging features and survival were compared among the unideleted tumors, codeleted tumors, and those without 1p or 19q deletion.

RESULTS: The cohort comprised 65 tumors without 1p or 19q deletion, 12 unideleted tumors, and 44 codeleted. The proportion of unideleted tumors demonstrating the T2-FLAIR mismatch sign (33%) was similar to that in tumors without deletion (49%; P = .39), but significantly higher than codeleted tumors (0%; P = .001). Calcifications were less frequent in unideleted tumors (0%) than in codeleted tumors (25%), but this difference did not reach statistical significance (P = .097). The median survival of patients with unideleted tumors was 7.8 years, which was similar to that in tumors without deletion (8.5 years; P = .72) but significantly shorter than that in codeleted tumors (not reaching median survival after 12 years; P = .013).

CONCLUSIONS: IDH-mutant gliomas with single-arm 1p or 19q deletion have MR imaging appearance and survival that are similar to those of astrocytomas without 1p or 19q deletion and significantly different from those of 1p/19q-codeleted oligodendrogliomas.

PMID:37884300 | DOI:10.3174/ajnr.A8034

Int J Biol Macromol. 2023 Oct 24:127654. doi: 10.1016/j.ijbiomac.2023.127654. Online ahead of print.

ABSTRACT

This work assessed the effect of different hydrolysis periods on the properties of hydrogels based on 75 % w w^-1 of N,N’-dimethyl acrylamide (DMAAm) and 25 % w w^-1 of starch-g-(glycidyl methacrylate) (^GMASt). FTIR results confirmed the conversion of ester groups into carboxylic acids and carboxylates, besides forming a keto-enol tautomer due to the peeling reaction of starch. For DMAAm, the hydrolysis mostly converted amide into carboxylate groups. The morphology, thermal stability, and the mechanical properties of the predominantly amorphous matrices (as confirmed by XRD results) did not drastically change even after 10 days of hydrolysis in alkali media. However, the thermogravimetric analysis results suggested that DMAAm partially protected ^GMASt from the hydrolysis. The swelling degree of the matrix increased from (10.1 ± 2.1) g g^-1 to (61.9 ± 2.6) g g^-1 after 1 day of hydrolysis, but no statistical differences (at 95 % of significance) were observed for the matrices hydrolyzed for longer periods, confirming that the maximum hydrolysis occurred within 24 h. The results confirmed that the hydrolysis increased the water uptake of the ^GMASt/DMAAm-based matrices, making appealing for uses as a water retentor for agricultural purposes.

PMID:37884240 | DOI:10.1016/j.ijbiomac.2023.127654

Resuscitation. 2023 Oct 24:110010. doi: 10.1016/j.resuscitation.2023.110010. Online ahead of print.

ABSTRACT

BACKGROUND: It remains unclear if percutaneous left ventricular assist device (pLVAD) reduces post-cardiac arrest myocardial dysfunction.

METHODS: This is a prespecified analysis of a subset of swine that achieved return of spontaneous circulation (ROSC) in a study comparing pLVAD, transient aortic occlusion (AO), or both during cardiopulmonary resuscitation (CPR). Devices were initiated after 24 minutes of ventricular fibrillation cardiac arrest (8 min no-flow and 16 min mechanical CPR). AO was discontinued post-ROSC, and pLVAD support or standard care were continued. Beginning 60 minutes post-ROSC, pLVAD support was weaned to <1.0 L/min and subsequently removed at 240 minutes. The primary outcome was cardiac index (CI), stroke volume index (SVI), and left ventricular ejection fraction (LVEF) at 240 minutes post-ROSC. Data are shown as mean (standard error).

RESULTS: Seventeen swine achieved ROSC without complication and were included in this analysis (pLVAD group, n = 11 and standard care group, n = 6). For the primary outcomes, the pLVAD group had significantly higher CI of 4.2(0.3) vs. 3.1(0.4) L/min/m² (p=0.043) and LVEF 60(3) vs. 49(4) % (p=0.029) at 240 minutes after ROSC when compared with the standard care group, while SVI was not statistically significantly different (32[3] vs. 23[4] mL/min/m², p=0.054). During the first 60 minutes post-ROSC, the pLVAD group had significantly higher coronary perfusion pressure, lower LV stroke work index, and total pulmonary resistance index.

CONCLUSION: These results suggest that early pLVAD support after ROSC is associated with better recovery myocardial function compared to standard care after prolonged cardiac arrest.

PMID:37884220 | DOI:10.1016/j.resuscitation.2023.110010

Brain Behav Immun. 2023 Oct 24:S0889-1591(23)00319-7. doi: 10.1016/j.bbi.2023.10.019. Online ahead of print.

ABSTRACT

BACKGROUND: Neuroinflammation and aberrant immune regulation are increasingly implicated in the pathophysiology of white matter hyperintensities (WMH), an imaging marker of cerebrovascular pathologies and predictor of cognitive impairment. The role of human leukocyte antigen (HLA) genes, critical in immunoregulation and associated with susceptibility to neurodegenerative diseases, in WMH pathophysiology remains unexplored.

METHODS: We performed association analyses between classical HLA alleles and WMH volume, derived from MRI scans of 38 302 participants in the UK Biobank. To identify independent functional alleles driving these associations, we conducted conditional forward stepwise regression and lasso regression. We further investigated whether these functional alleles showed consistent associations with WMH across subgroups characterized by varying levels of clinical determinants. Additionally, we validated the clinical relevance of the identified alleles by examining their association with cognitive function (n = 147 549) and dementia (n = 460 029) in a larger cohort.

FINDINGS: Four HLA alleles (DQB1*02:01, DRB1*03:01, C*07:01, and B*08:01) showed an association with reduced WMH volume after Bonferroni correction for multiple comparisons. Among these alleles, DQB1*02:01 exhibited the most significant association (β = -0.041, 95 % CI: -0.060 to -0.023, p = 1.04 × 10^-5). Forward selection and lasso regression analyses indicated that DQB1*02:01 and C*07:01 primarily drove this association. The protective effect against WMH conferred by DQB1*02:01 and C*07:01 persisted in clinically relevant subgroups, with a stronger effect observed in older participants. Carrying DQB1*02:01 and C*07:01 was associated with higher cognitive function, but no association with dementia was found.

INTERPRETATION: Our population-based findings support the involvement of immune-associated mechanisms, particularly both HLA class I and class II genes, in the pathogenesis of WMH and subsequent consequence of cognitive functions.

PMID:37884160 | DOI:10.1016/j.bbi.2023.10.019

Sci Total Environ. 2023 Oct 24:168065. doi: 10.1016/j.scitotenv.2023.168065. Online ahead of print.

ABSTRACT

Thorium-232 (Th-232), a naturally-occurring radioactive element with high potential of nuclear fuel is now being utilized in advanced nuclear reactors for CO₂-free energy generation. To achieve all-round capability in Th-fuel cycle for health and environment, understanding the biological effects of Th-232 at cellular and molecular level are extremely important. The present study investigated long-term effects (6 and 12 months) of Th-232 (4, 10 and 20 mg/kg) on gene expression in mice liver (major target organ). Analysis of differentially expressed genes (DEGs, ≥2.0 folds, p < 0.05) showed that with the increase of Th dose (4 to 20 mg/kg), the number of upregulated DEGs increased and the number of downregulated DEGs decreased significantly. A significant number of upregulated DEGs (10 genes in 6 months and 14 genes in 12 months) were found common between 4 and 20 mg/kg. Gene Ontology analysis revealed significant (P_adj ~ 10^-6-10^-28) enrichment of upregulated DEGs for metabolic process, signal transduction, cell death, cell cycle and cell proliferation. KEGG pathway analysis showed DEGs significantly enriched in several cancer-related pathways including hepatocellular carcinoma (HCC). Protein-protein interaction analysis further revealed statistically significant functional interaction (p-value ~10-6-10-10) among the proteins of HCC, which identified β-catenin as one of the most significant signaling nodes in association with myc, an oncogene and p53, a tumor suppressor. Importantly, these results were corroborated by quantitative real time-polymerase chain reaction and western blotting in liver tissues of animals exposed to Th-232. This study insights Wnt/β-catenin signaling network attributable to drive Th-induced liver carcinogenesis, which may have significant implications for management of long-term effects of Th-232.

PMID:37884152 | DOI:10.1016/j.scitotenv.2023.168065

Indian Heart J. 2023 Oct 24:S0019-4832(23)00167-0. doi: 10.1016/j.ihj.2023.10.003. Online ahead of print.

ABSTRACT

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is known to be associated with development of left ventricular (LV) dysfunction and heart failure (HF). The study aimed to determine the prevalence of LV dysfunction and HF in unselected out-patients with T2DM with no previous cardiac history and to correlate LV dysfunction and HF with demographic and comorbid characteristics.

METHODS: This cross-sectional study conducted at 27 centers in India captured demographic and clinical data through electronic case record forms. B-type natriuretic peptide of >105 pg/mL was used to diagnose HF and two-dimensional echocardiography was used to assess LV dysfunction.

RESULTS: Of the 615 patients, 54.3 % (n = 334) were males; mean age was 57.4 ± 10.48 years. More than one-third of the patients had T2DM duration of >10 years (n = 238; 38.7 %), with hypertension as the most prevalent comorbidity (n = 372, 78.6 %). Approximately 61.3 % of the patients had LV hypertrophy. The mean LV mass was 135.0 ± 56.16 g (95 % CI 130.28, 139.70). The prevalence of any type of LV dysfunction, including systolic or diastolic dysfunction and HF was 55 % (95 % CI 51.0, 59.0) and 10 % (95 % CI 7.0, 12.0), respectively. A negligible but statistically significant correlation was observed between LV dysfunction and T2DM duration (p = 0.011), alongside HF and age (p < 0.0001).

CONCLUSION: Real-world data from this registry from India demonstrates a substantial burden of LV dysfunction and HF in individuals with T2DM in India. It is imperative to formulate strategies for early identification of LV dysfunction in individuals with T2DM for prevention and consequent management of HF.

PMID:37884126 | DOI:10.1016/j.ihj.2023.10.003