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Crosstalk Between Cholesterol, ABC Transporters, and PIP2 in Inflammation and Atherosclerosis

Adv Exp Med Biol. 2023;1422:353-377. doi: 10.1007/978-3-031-21547-6_13.

ABSTRACT

The lowering of plasma low-density lipoprotein cholesterol (LDL-C) is an easily achievable and highly reliable modifiable risk factor for preventing cardiovascular disease (CVD), as validated by the unparalleled success of statins in the last three decades. However, the 2021 American Heart Association (AHA) statistics show a worrying upward trend in CVD deaths, calling into question the widely held belief that statins and available adjuvant therapies can fully resolve the CVD problem. Human biomarker studies have shown that indicators of inflammation, such as human C-reactive protein (hCRP), can serve as a reliable risk predictor for CVD, independent of all traditional risk factors. Oxidized cholesterol mediates chronic inflammation and promotes atherosclerosis, while anti-inflammatory therapies, such as an anti-interleukin-1 beta (anti-IL-1β) antibody, can reduce CVD in humans. Cholesterol removal from artery plaques, via an athero-protective reverse cholesterol transport (RCT) pathway, can dampen inflammation. Phosphatidylinositol 4,5-bisphosphate (PIP2) plays a role in RCT by promoting adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux from arterial macrophages. Cholesterol crystals activate the nod-like receptor family pyrin domain containing 3 (Nlrp3) inflammasome in advanced atherosclerotic plaques, leading to IL-1β release in a PIP2-dependent fashion. PIP2 thus is a central player in CVD pathogenesis, serving as a critical link between cellular cholesterol levels, ATP-binding cassette (ABC) transporters, and inflammasome-induced IL-1β release.

PMID:36988888 | DOI:10.1007/978-3-031-21547-6_13

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Is radioiodine ablation with 1.1 GBq (30 mCi) 131I necessary in low-risk thyroid cancer patients? Results from a long-term follow-up prospective study

Endocrine. 2023 Mar 29. doi: 10.1007/s12020-023-03306-w. Online ahead of print.

ABSTRACT

BACKGROUND: In patients with low-risk differentiated thyroid cancer (DTC), remnant ablation with radioiodine (RA) after total thyroidectomy (TT) is controversial. No benefits have been demonstrated in terms of mortality or disease-free survival. Recent evidence found that RA did not improve mid-term outcomes.

PURPOSE: To evaluate initial response to treatment and long-term follow-up status in low-risk DTC patients after TT vs. TT + RA with 131I 1.11 GBq (30 mCi).

METHODS: Prospective multicenter non-randomized study; 174 low-risk DTC that underwent TT were recruited an divided in two groups according to RA (87 ablated and 87 non-ablated). Response to treatment was evaluated at 6-18 months after thyroidectomy and at the end of follow-up with measurements of thyroglobulin, and anti-thyroglobulin antibodies levels, and neck ultrasonography.

RESULTS: Baseline characteristics of both groups were similar. Ablated patients: median age 45.5 years, 84% females, 95.4% papillary thyroid carcinoma (PTC), mean tumor size 16 mm; non-ablated: median age 45 years, 88.5% females, 96.6% PTC, mean tumor size 14 mm. Response to initial treatment was similar between both groups, with < 2% of structural incomplete response. Final status was evaluated in 139 cases (median follow-up of 60 months). Among ablated patients, 82.8% had no evidence of disease (NED), 12% had an indeterminate response (IR) and 5% a biochemical incomplete response (BIR). Non-ablated patients had NED in 90%, IR in 8.7% and BIR in 1.2%. No statistical difference was found between groups (p = 0.29). No patient had evidence of structural disease at the end of follow-up.

CONCLUSIONS: Our findings support the recommendation against routine RA in low-risk DTC patients.

PMID:36988853 | DOI:10.1007/s12020-023-03306-w

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Instant Controlled Pressure-Drop (DIC) for Volatile Compound Extraction and Bioethanol Production from Empty Aleppo Pinecones and Eucalyptus Chips: Process Optimization and Statistical Modeling

Appl Biochem Biotechnol. 2023 Mar 29. doi: 10.1007/s12010-023-04437-6. Online ahead of print.

ABSTRACT

Several plant species contain volatile compounds extracted as “essential oils” through different technologies. After essential oil extraction, the residual solid is a lignocellulosic solid waste. This work proposes the instant controlled pressure-drop (DIC) technology to autovaporize volatile compounds and modify the lignocellulosic matrix. Indeed, DIC technology is a thermomechanical process based on short-time/high-temperature and pressure pretreatment. It enhances the saccharification and fermentation process (SSF) for bioethanol production. A 3-variable design of experiments optimized the DIC processing parameters to reach 100% efficiency (EE) of volatile compound extraction using response surface methodology (RSM). Eucalyptus chips presented 50 volatile identified compounds after 7 min of DIC treatment. 1,8-Cineole, β-phellandrene, aromadendrene, eudesmol, and spathulenol are the most important volatile compounds. The empty Aleppo pinecones delivered 32 volatile compounds in 5 min of DIC treatment, the most important of which were caryophyllene, nortricyclene, verbenol, and camphor. After the autovaporization extraction stage, solid fraction residues were hydrolyzed and fermented in the same stirred bioreactor, using SSF strategy for 72 h at 37 °C. The highest bioethanol yields reached 73.9% and 54.82% (g per 100 g DM) from eucalyptus chip and empty Aleppo pinecone, respectively.

PMID:36988842 | DOI:10.1007/s12010-023-04437-6

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Bone fragility, sarcopenia and cardiac calcifications in an elderly population: a preliminary study

Aging Clin Exp Res. 2023 Mar 29. doi: 10.1007/s40520-023-02393-z. Online ahead of print.

ABSTRACT

BACKGROUND: Cardiovascular disease, osteoporosis and sarcopenia are very common age-related conditions. This study aimed at investigating the relationships of cardiac calcifications, as assessed by using GCCS with BMD, fragility fractures and sarcopenia in elderly subjects.

METHODS: In a cohort of 106 subjects (age 70.4 ± 5.8 yrs) we measured lumbar (BMD-LS), femoral BMD (femoral neck: BMD-FN, total femur: BMD-TH) and body composition (BMD-WB) with Dual-energy X-ray Absorptiometry (DXA) method. We also evaluated the presence of sarcopenia on the basis of the EWGSOP Consensus. All subjects, simultaneously, underwent to a transthoracic color doppler echocardiography exam to assess the presence of cardiac calcifications. The degree of non coronaric cardiac calcifications was evaluated using the Global Cardiac Calcium Score (GCCS).

RESULTS: The degree of cardiac calcification assessed by GCCS was significantly higher in osteoporotic patients (p < 0.001). Furthermore, an inverse correlation emerged between BMD and GCCS, statistical significance was found at lumbar spine and femoral sub-regions in female population (p < 0.01). Moreover by dividing population according to the presence of fragility fractures, we observed that GCCS values were significantly higher in subjects with fractures in respect of non-fractured ones (p < 0.05). Multiple regression models showed that BMD-LS and BMD-FT were independently associated with cardiac calcification. GCCS values were significantly associated with BMI and ASMM in women (p < 0.01 and p < 0.05, respectively) and with handgrip strength in men (p < 0.05).

CONCLUSIONS: Our data confirm the presence of a relationship between cardiac calcifications and decreased BMD values. It’s also the first study that relates sarcopenia and valvular calcifications.

PMID:36988828 | DOI:10.1007/s40520-023-02393-z

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Can financial efficiency and environmental regulation promote R&D innovation? From the perspective of value chain decomposition

Environ Sci Pollut Res Int. 2023 Mar 29. doi: 10.1007/s11356-023-26460-0. Online ahead of print.

ABSTRACT

There is a plethora of current research on economic or financial resources for fostering innovation. These studies lack the micro-analysis and, more importantly, disregard the effect of environmental control. This study will offer a new analytical paradigm by linking financial growth, environmental regulation, and innovation growth throughout the value chain. Using the information on 30 Chinese provinces collected between 1990 and 2020, we develop a dynamic panel data model to examine the interplay between financial effectiveness, ecological regulation, and research and development (R&D) innovation. We assess the impact that the efficiency of financial organizations and the stock market have on R&D’s ability to influence R&D innovation. There are positive spillover effects for stock market efficiency, which boosts the development and conversion of R&D innovation; there are positive spillover effects for financial institution efficiency, which hurts the conversion of R&D innovation, and there is an adverse effect on environmental regulation efficiency. To what extent environmental rules affect the commercialization of research and development innovation is unclear; human capital is an effective motivator for the advancement of R&D innovation, and the volume of FDI may increase the commercialization of R&D innovation.

PMID:36988804 | DOI:10.1007/s11356-023-26460-0

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Human Papilloma Virus Knowledge Among University Students, Staff, and Faculty in the State of Indiana During 2016, 2019, and 2022

J Community Health. 2023 Mar 29. doi: 10.1007/s10900-023-01210-y. Online ahead of print.

ABSTRACT

Studies of Human Papillomavirus (HPV) knowledge among university students have previously been conducted, typically to the exclusion of faculty and staff. The study aim was to assess HPV knowledge among university students, staff, and faculty in the state of Indiana during 2016, 2019, and 2022. The three samples comprised a total of 1275, 1056, and 403 students, staff, and faculty respectively during 2016, 2019, and 2022. Ages ranged from 18 to 70 + each year of the study. A 27-item survey was administered including sociodemographic questions and quantitative HPV knowledge questions were modified from a previously validated instrument. Descriptive statistics characterized the study participants and differences in scores were reported. Among the overall sample who answered receiving the vaccine question (n = 1917), 39% had received the HPV vaccine. HPV knowledge significantly increased among students from 2016 to 2019 but decreased in 2022. Among staff, there was a significant knowledge difference between 2016 and 2022, but no significant knowledge difference among the faculty. About 86% of the total sample did not know that HPV usually does not need any treatment. Further, participants correct knowledge scores were less than average on the following items: HPV can cause throat cancer (49%); HPV can be transmitted by skin-to-skin contact (42%). More education and campus-wide efforts need to be implemented to increase awareness and accurate HPV-knowledge. Targeted and individual messaging for students, staff, and faculty may be a way to increase awareness of HPV and improve HPV knowledge.

PMID:36988774 | DOI:10.1007/s10900-023-01210-y

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CDK10, CDK11, FOXO1, and FOXO3 Gene Expression in Alzheimer’s Disease Encephalic Samples

Cell Mol Neurobiol. 2023 Mar 29. doi: 10.1007/s10571-023-01341-9. Online ahead of print.

ABSTRACT

Alzheimer’s disease (AD) is a progressive neuroinflammatory and neurodegenerative disorder that affects different regions of the brain. Its pathophysiology includes the accumulation of β-amyloid protein, formation of neurofibrillary tangles, and inflammatory processes. Genetic factors are involved in the onset of AD, but they are not fully elucidated. Identification of gene expression in encephalic tissues of patients with AD may help elucidate its development. Our objectives were to characterize and compare the gene expression of CDK10, CDK11, FOXO1, and FOXO3 in encephalic tissue samples from AD patients and elderly controls, from the auditory cortex and cerebellum. RT-qPCR was used on samples from 82 individuals (45 with AD and 37 controls). We observed a statistically significant increase in CDK10 (p = 0.029*) and CDK11 (p = 0.048*) gene expression in the AD group compared to the control, which was most evident in the cerebellum. Furthermore, the Spearman test demonstrated the presence of a positive correlation of gene expression both in the auditory cortex in the AD group (r = 0.046/p = 0.004) and control group (r = 0.454/p = 0.005); and in the cerebellum in the AD group (r = 0.654 /p < 0.001). There was no statistically significant difference and correlation in the gene expression of FOXO1 and FOXO3 in the AD group and the control. In conclusion, CDK10 and CDK11 have high expression in AD patients compared to control, and they present a positive correlation of gene expression in the analyzed groups and tissues, which suggests that they play an important role in the pathogenesis of AD.

PMID:36988771 | DOI:10.1007/s10571-023-01341-9

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Combined targeted and untargeted high-resolution mass spectrometry analyses to investigate metabolic alterations in pompe disease

Metabolomics. 2023 Mar 29;19(4):29. doi: 10.1007/s11306-023-01989-w.

ABSTRACT

INTRODUCTION: Pompe disease is a rare, lysosomal disorder, characterized by intra-lysosomal glycogen accumulation due to an impaired function of α-glucosidase enzyme. The laboratory testing for Pompe is usually performed by enzyme activity, genetic test, or urine glucose tetrasaccharide (Glc4) screening by HPLC. Despite being a good preliminary marker, the Glc4 is not specific for Pompe.

OBJECTIVE: The purpose of the present study was to develop a simple methodology using liquid chromatography-high resolution mass spectrometry (LC-HRMS) for targeted quantitative analysis of Glc4 combined with untargeted metabolic profiling in a single analytical run to search for complementary biomarkers in Pompe disease.

METHODS: We collected 21 urine specimens from 13 Pompe disease patients and compared their metabolic signatures with 21 control specimens.

RESULTS: Multivariate statistical analyses on the untargeted profiling data revealed Glc4, creatine, sorbitol/mannitol, L-phenylalanine, N-acetyl-4-aminobutanal, N-acetyl-L-aspartic acid, and 2-aminobenzoic acid as significantly altered in Pompe disease. This panel of metabolites increased sample class prediction (Pompe disease versus control) compared with a single biomarker.

CONCLUSION: This study has demonstrated the potential of combined acquisition methods in LC-HRMS for Pompe disease investigation, allowing for routine determination of an established biomarker and discovery of complementary candidate biomarkers that may increase diagnostic accuracy, or improve the risk stratification of patients with disparate clinical phenotypes.

PMID:36988742 | DOI:10.1007/s11306-023-01989-w

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Interest in the combination of antimicrobial therapy for orthopaedic device-related infections due to Enterococcus spp

Arch Orthop Trauma Surg. 2023 Mar 29. doi: 10.1007/s00402-023-04848-4. Online ahead of print.

ABSTRACT

INTRODUCTION: The objective of this study was to evaluate the management of orthopaedic device-related infections (ODRIs) due to Enterococcus spp.

MATERIALS AND METHODS: We performed a retrospective cohort study in a French tertiary university hospital. Patients with prosthetic joint- or osteosynthesis-associated infections caused by enterococci from 2013 to 2020 were included. Patients who died within 5 days after surgery; who were in palliative care; or who had osteosynthesis of the hand, foot or vertebra were excluded.

RESULTS: Thirty-six patients were included, with 24 in the arthroplasty group and 12 in the osteosynthesis material group. Most infections were polymicrobial (63.9%, n = 23). Debridement, antibiotics and implant retention (DAIR) was performed in 30.6% (n = 11), withdrawal of material in 16.7% (n = 6), one-stage exchange in 30.6% (n = 11) and two-stage exchange in 22.2% of cases (n = 8). The antibiotic regimen was amoxicillin in 41.6% (n = 15), rifampicin in 27.8% (n = 10), linezolid in 25% (n = 9) and/or fluoroquinolones in 30.6% (n = 11). Clinical success at 1 year was 67% (18/27). The only variable statistically associated with a decreased risk of clinical failure was a duration of antibiotic therapy of 12 weeks (p = 0.04). Patients with a lower body mass index and age tended to decrease the risk of clinical failure (p = 0.05 and 0.06 respectively).

CONCLUSIONS: The management of enterococcal ODRIs is complex, and ODRI patients are at high risk for relapse. In our small study, a better outcome was not demonstrated for patients with combination therapy and rifampicin use. Further studies are needed to improve the medico-surgical strategy for treating these infections.

PMID:36988713 | DOI:10.1007/s00402-023-04848-4

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HERV-K (HML-2) insertion polymorphisms in the 8q24.13 region and their potential etiological associations with acute myeloid leukemia

Arch Virol. 2023 Mar 29;168(4):125. doi: 10.1007/s00705-023-05747-0.

ABSTRACT

Human endogenous retroviruses (HERVs) are LTR retrotransposons that are present in the human genome. Among them, members of the HERV-K (HML-2) group are suspected to play a role in the development of different types of cancer, including lung, ovarian, and prostate cancer, as well as leukemia. Acute myeloid leukemia (AML) is an important disease that causes 1% of cancer deaths in the United States and has a survival rate of 28.7%. Here, we describe a method for assessing the statistical association between HERV-K (HML-2) transposable element insertion polymorphisms (or TIPs) and AML, using whole-genome sequencing and read mapping using TIP_finder software. Our results suggest that 101 polymorphisms involving HERV-K (HML-2) elements were correlated with AML, with a percentage between 44.4 to 56.6%, most of which (70) were located in the region from 8q24.13 to 8q24.21. Moreover, it was found that the TRIB1, LRATD2, POU5F1B, MYC, PCAT1, PVT1, and CCDC26 genes could be displaced or fragmented by TIPs. Furthermore, a general method was devised to facilitate analysis of the correlation between transposable element insertions and specific diseases. Finally, although the relationship between HERV-K (HML-2) TIPs and AML remains unclear, the data reported in this study indicate a statistical correlation, as supported by the χ2 test with p-values < 0.05.

PMID:36988711 | DOI:10.1007/s00705-023-05747-0