Nevin Manimala

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

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

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

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

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

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

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

J Cancer Res Clin Oncol. 2023 Mar 29. doi: 10.1007/s00432-023-04700-7. Online ahead of print.

ABSTRACT

PURPOSE: Renal cell carcinoma belongs among the deadliest malignancies despite great progress in therapy and accessibility of primary care. One of the main unmet medical needs remains the possibility of early diagnosis before the tumor dissemination and prediction of early relapse and disease progression after a successful nephrectomy. In our study, we aimed to identify novel diagnostic and prognostic biomarkers using next-generation sequencing on a novel cohort of RCC patients.

METHODS: Global expression profiles have been obtained using next-generation sequencing of paired tumor and non-tumor tissue of 48 RCC patients. Twenty candidate lncRNA have been selected for further validation on an independent cohort of paired tumor and non-tumor tissue of 198 RCC patients.

RESULTS: Sequencing data analysis showed significant dysregulation of more than 2800 lncRNAs. Out of 20 candidate lncRNAs selected for validation, we confirmed that 14 of them are statistically significantly dysregulated. In order to yield better discriminatory results, we combined several best performing lncRNAs into diagnostic and prognostic models. A diagnostic model consisting of AZGP1P1, CDKN2B-AS1, COL18A1, and RMST achieved AUC 0.9808, sensitivity 95.96%, and specificity 90.4%. The model for prediction of early relapse after nephrectomy consists of COLCA1, RMST, SNHG3, and ZNF667-AS1 and achieved AUC 0.9241 with sensitivity 93.75% and specificity 71.07%. Notably, no combination has outperformed COLCA1 alone. Lastly, a model for stage consists of ZNF667-AS1, PVT1, RMST, LINC00955, and TCL6 and achieves AUC 0.812, sensitivity 85.71%, and specificity 69.41%.

CONCLUSION: In our work, we identified several lncRNAs as potential biomarkers and developed models for diagnosis and prognostication in relation to stage and early relapse after nephrectomy.

PMID:36988708 | DOI:10.1007/s00432-023-04700-7

Pediatr Nephrol. 2023 Mar 29. doi: 10.1007/s00467-023-05947-5. Online ahead of print.

ABSTRACT

BACKGROUND: Uromodulin is the most abundant protein in the urine of healthy adults, and higher urine concentrations mark better tubular health. Greater kidney size and function are predictors of higher uromodulin levels in adults. Urine uromodulin has not yet been studied in children with chronic kidney disease (CKD). Thus, we sought to determine the relationship between age and kidney function with urine uromodulin levels in children with CKD.

METHODS: In the CKD in Children (CKiD) cohort, we utilized multivariable linear regression to evaluate the relationship of age and eGFR with urine uromodulin levels. The primary outcome was uromodulin indexed to urine creatinine (Umod/Cr, mg/g), which was log₂-transformed given its skewed distribution.

RESULTS: Among 677 CKiD participants, the median age was 11.8 years (8.2-15.3), the median eGFR was 49 ml/min/1.73 m² (37-63), the etiology of CKD was glomerular disease in 31%, and the median Umod/Cr level was 0.114 mg/g (0.045-0.226). In the multivariable models, each one-year older age was associated with 0.18 (12%) lower log₂(Umod/Cr) and 0.20 (13%) lower log₂(Umod/Cr) among those with non-glomerular and glomerular disease, respectively (p < 0.001). However, we did not find a statistically significant association between eGFR and Umod/Cr in either participants with non-glomerular or glomerular disease (p = 0.13 and p = 0.58, respectively).

CONCLUSIONS: Among children with CKD, older age is significantly associated with lower Umod/Cr, independent of eGFR. Further studies are needed to comprehensively evaluate age-specific reference ranges for urine uromodulin and to evaluate the longitudinal relationship of uromodulin with both age and eGFR in children with CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

PMID:36988691 | DOI:10.1007/s00467-023-05947-5

Eur J Pediatr. 2023 Mar 29. doi: 10.1007/s00431-023-04947-9. Online ahead of print.

ABSTRACT

Congenital cryptorchidism is a well-established risk factor of testicular malignancies. However, there is still remarkable variability in the measures of associations between of these two clinical entities. The current meta-analysis investigates the up-to-date risk of testicular cancer in adults with a history of surgically corrected congenital cryptorchidism until adolescence. The meta-analysis was conducted with strict criteria for the identification of the congenital cryptorchidism cases that underwent surgery before adulthood. The study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search of the PubMed and the Scopus databases was conducted, using a defined strategy, from inception to February 2023. Two independent authors screened the literature and extracted the data, using inclusion and exclusion criteria. Of the 2176 articles identified, 93 articles were fully retrieved, and 6 articles met all the inclusion criteria. The Newcastle-Ottawa scale was applied for the studies’ quality assessment. The random-effects model in RevMan 5.4 program was used for the meta-analysis. Three case-control studies and three cohort studies were selected. They included 371,681 patients and 1786 incidents of testicular cancer. The pooled odds ratio (OR) was 3.99 (95% confidence intervals (CI): 2.80-5.71). The heterogeneity was moderate and estimated at 51% with the I-squared statistic. A forest plot and a funnel plot were produced to evaluate the ORs and the probable publication bias, respectively. The mean Newcastle-Ottawa score was 8/9 for all the included reports. Conclusion: This systematic review and meta-analysis verifies, with an updated estimate, the increased risk of testicular cancer in adults with an orchidopexy history. New evidence on the maldescent laterality supports that the cancer risk remains increased and for the contralateral, unaffected testicle, although to a lesser extent. The orchidopexy in the first year of life prevents the testicular damage and decreases the overall cancer risk. What is Known: • Congenital cryptorchidism is the commonest genitourinary abnormality and a risk factor for testicular cancer. • The most recent meta-analysis reporting this association was in 2013. What is New: • After reviewing literature until February 2023, the association of congenital cryptorchidism with testicular cancer risk in adulthood was verified: odds ratio=3.99 [2.80-5.71], 95% CI. • The meta-analysis highlights the protective role of early orchidopexy and the controversial data about maldescent and testicular cancer laterality.

PMID:36988678 | DOI:10.1007/s00431-023-04947-9