Categories
Nevin Manimala Statistics

Identification of potentially common loci between childhood obesity and coronary artery disease using pleiotropic approaches

Sci Rep. 2022 Nov 14;12(1):19513. doi: 10.1038/s41598-022-24009-8.

ABSTRACT

Childhood obesity remains one of the most important issues in global health, which is implicated in many chronic diseases. Converging evidence suggests that a higher body mass index during childhood (CBMI) is significantly associated with increased coronary artery disease (CAD) susceptibility in adulthood, which may partly arise from the shared genetic determination. Despite genome-wide association studies (GWASs) have successfully identified some loci associated with CBMI and CAD individually, the genetic overlap and common biological mechanism between them remains largely unexplored. Here, relying on the results from the two large-scale GWASs (n = 35,668 for CBMI and n = 547,261 for CAD), linkage disequilibrium score regression (LDSC) was used to estimate the genetic correlation of CBMI and CAD in the first step. Then, we applied different pleiotropy-informed methods including conditional false discovery rate ([Formula: see text]) and genetic analysis incorporating pleiotropy and annotation (GPA) to detect potentially common loci for childhood obesity and CAD. By integrating the genetic information from the existing GWASs summary statistics, we found a significant positive genetic correlation ([Formula: see text] = 0.127, p = 2E-4) and strong pleiotropic enrichment between CBMI and CAD (LRT = 79.352, p = 5.2E-19). Importantly, 28 loci were simultaneously discovered to be associated with CBMI, and 13 of them were identified as potentially pleiotropic loci by [Formula: see text] and GPA. Those corresponding pleiotropic genes were enriched in trait-associated gene ontology (GO) terms “amino sugar catabolic process”, “regulation of fat cell differentiation” and “synaptic transmission”. Overall, the findings of the pleiotropic loci will help to further elucidate the common molecular mechanisms underlying the association of childhood obesity and CAD, and provide a theoretical direction for early disease prevention and potential therapeutic targets.

PMID:36376549 | DOI:10.1038/s41598-022-24009-8

Categories
Nevin Manimala Statistics

Zinc-modified phosphate-based glass micro-filler improves Candida albicans resistance of auto-polymerized acrylic resin without altering mechanical performance

Sci Rep. 2022 Nov 14;12(1):19456. doi: 10.1038/s41598-022-24172-y.

ABSTRACT

Colonization of auto-polymerized acrylic resin by pathogenic Candida albicans is a common problem for denture users. In this study, zinc-modified phosphate-based glass was introduced into an auto-polymerized acrylic resin at concentrations of 3, 5, and 7 wt.%. The mechanical or physical properties (flexural strength, elastic modulus, microhardness, and contact angle), surface morphology of the resultant materials, and the antimicrobial effect on C. albicans were investigated. There were no statistical differences in the mechanical properties between the control and the zinc-modified phosphate-based glass samples (p > 0.05); however, the number of C. albicans colony-forming units was significantly lower in the control group (p < 0.05). Scanning electron microscopy revealed that C. albicans tended not to adhere to the zinc-modified-phosphate-based glass samples. Thus, the zinc-modified materials retained the advantageous mechanical properties of unaltered acrylic resins, while simultaneously exhibiting a strong antimicrobial effect in vitro.

PMID:36376540 | DOI:10.1038/s41598-022-24172-y

Categories
Nevin Manimala Statistics

Publisher Correction: Stroke genetics informs drug discovery and risk prediction across ancestries

Nature. 2022 Nov 14. doi: 10.1038/s41586-022-05492-5. Online ahead of print.

NO ABSTRACT

PMID:36376532 | DOI:10.1038/s41586-022-05492-5

Categories
Nevin Manimala Statistics

Regional cortical hypoperfusion and atrophy correlate with striatal dopaminergic loss in Parkinson’s disease: a study using arterial spin labeling MR perfusion

Neuroradiology. 2022 Nov 14. doi: 10.1007/s00234-022-03085-7. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the relationship of the striatal dopamine transporter density to changes in the gray matter (GM) volume and cerebral perfusion in patients with Parkinson’s disease (PD).

METHODS: We evaluated the regional cerebral blood flow (CBF) and GM volume, concurrently measured using arterial spin labeling and T1-weighted magnetic resonance imaging, respectively, as well as the striatal specific binding ratio (SBR) in 123I-N-ω-fluoropropyl-2β-carboxymethoxy-3β-(4-iodophenyl)nortropane (123I-FP-CIT) single-photon emission computed tomography in 30 non-demented patients with PD (15 men and 15 women; mean age, 67.2 ± 8.8 years; mean Hoehn-Yahr stage, 2.2 ± 0.9). Voxel-wise regression analyses using statistical parametric mapping (SPM) were performed to explore the brain regions that showed correlations of the striatal SBR to the GM volume and CBF, respectively, with a height threshold of p < 0.0005 at the voxel level and p < 0.05 family-wise error-corrected at the cluster level.

RESULTS: SPM analysis showed a significant positive correlation between the SBR and GM volume in the inferior frontal gyrus (IFG). Whereas, a positive correlation between the SBR and CBF was widely found in the frontotemporal and parietotemporal regions, including the IFG. Notably, the opercular part of the IFG showed significant correlations in both SPM analyses of the GM volume (r2 = 0.90, p < 0.0001) and CBF (r2 = 0.88, p < 0.0001).

CONCLUSION: The voxel-wise analyses revealed the brain regions, mainly the IFG, that showed hypoperfusion and atrophy related to dopaminergic loss, which suggests that the progression of dopaminergic neurodegeneration leads to regional cortical dysfunction in PD.

PMID:36376524 | DOI:10.1007/s00234-022-03085-7

Categories
Nevin Manimala Statistics

Association of sex steroid hormones and new bone formation rate after iliac onlay grafting: a prospective clinical pilot study

Int J Implant Dent. 2022 Nov 15;8(1):53. doi: 10.1186/s40729-022-00447-x.

ABSTRACT

PURPOSE: The present prospective study evaluates the association between new bone formation rate in the iliac onlay graft and sex steroid hormone serum levels.

METHODS: A total of 15 partially or completely edentulous postmenopausal females and 9 males with less than 5 mm height of the remaining alveolar bone underwent iliac onlay grafting followed by dental implant placement using a two-stage approach. Sex hormone binding globulin and 17β-estradiol serum levels were investigated by electrochemiluminescence immunoassay, while total testosterone level was analyzed using radioimmunoassay. At the time of implant placement, 12 weeks after grafting, bone biopsies were obtained and analyzed histomorphometrically. Statistical analysis was performed using linear mixed models.

RESULTS: Grafting procedure was successfully performed in all patients. The mean new bone formation rate was 32.5% (116 samples). In men the mean new bone formation rate (38.1%) was significantly higher (p < 0.01) than in women (27.6%). Independent of gender 17β-estradiol and testosterone were positively associated to overall new bone formation rate, albeit a significant influence was only seen for 17β-estradiol in men (p = 0.020). Sex hormone binding globulin had no influence on new bone formation rate (p = 0.897). There was no significant association between new bone formation rate and age (p = 0.353) or new bone formation rate and body mass index (p = 0.248).

CONCLUSION: Positive association of 17ß-estradiol as well as testosterone with new bone formation rate after iliac onlay grafting indicates a role of sex steroid hormones in alveolar bone regeneration, although the observed influence was only significant for 17ß-estradiol in men.

PMID:36376517 | DOI:10.1186/s40729-022-00447-x

Categories
Nevin Manimala Statistics

Early skin-to-skin contact and risk of late-onset-sepsis in very and extremely preterm infants

Pediatr Res. 2022 Nov 14. doi: 10.1038/s41390-022-02383-3. Online ahead of print.

ABSTRACT

BACKGROUND: To evaluate the association between exposure to early skin-to-skin contact (SSC) and incidence of late-onset sepsis (LOS) in extremely and very preterm infants.

METHODS: Observational study using the national population-based EPIPAGE-2 cohort in 2011. A propensity score for SSC exposure was used to match infants with and without exposure to SSC before day 4 of life and binomial log regression used to estimate risk ratios and CIs in the matched cohort. The primary outcome was at least one episode of LOS during hospitalization. Secondary outcomes were the occurrence of any late-onset neonatal infection (LONI), LOS with Staphylococcus or Staphylococcus aureus, incidence of LOS and LONI per 1000 central venous catheter days.

RESULTS: Among the 3422 included infants, 919 were exposed to early SSC. The risk ratio (RR) for LOS was 0.86 (95% CI, 0.67-1.10), for LONI was 1.00 (95% CI, 0.83-1.21), and for LOS with Coagulase-negative Staphylococcus or Staphylococcus aureus infection was 0.91 (95% CI, 0.68-1.21) and 0.77 (95% CI, 0.31-1.87). The incidence RR for LOS per-catheter day was 0.87 (95% CI, 0.64-1.18).

CONCLUSION: Early SSC exposure was not associated with LOS or LONI risk. Thus, their prevention should not be a barrier to a wider use of SSC.

IMPACT: Kangaroo Mother Care decreased neonatal infection rates in middle-income countries. Skin-to-skin contact is beneficial for vulnerable preterm infants but barriers exist to its implementation. In a large population-based study using a propensity score methods, we found that skin-to-skin contact before day 4 of life was not associated with a decreased risk of late-onset-sepsis in very and extremely preterm infants. Early skin-to-skin contact was not associated with an increased risk of any late-onset-neonatal-infection, in particular with staphylococcus. The fear of neonatal infection should not be a barrier to a wider use of early skin-to-skin contact in this population.

PMID:36376509 | DOI:10.1038/s41390-022-02383-3

Categories
Nevin Manimala Statistics

Identifying the optimal conditioning intensity for stem cell transplantation in patients with myelodysplastic syndrome: a machine learning analysis

Bone Marrow Transplant. 2022 Nov 14. doi: 10.1038/s41409-022-01871-8. Online ahead of print.

ABSTRACT

A conditioning regimen is an essential prerequisite of allogeneic hematopoietic stem cell transplantation for patients with myelodysplastic syndrome (MDS). However, the optimal conditioning intensity for a patient may be difficult to establish. This study aimed to identify optimal conditioning intensity (reduced-intensity conditioning regimen [RIC] or myeloablative conditioning regimen [MAC]) for patients with MDS. Overall, 2567 patients with MDS who received their first HCT between 2009 and 2019 were retrospectively analyzed. They were divided into a training cohort and a validation cohort. Using a machine learning-based model, we developed a benefit score for RIC in the training cohort. The validation cohort was divided into a high-score and a low-score group, based on the median benefit score. The endpoint was progression-free survival (PFS). The benefit score for RIC was developed from nine baseline variables in the training cohort. In the validation cohort, the hazard ratios of the PFS in the RIC group compared to the MAC group were 0.65 (95% confidence interval [CI]: 0.48-0.90, P = 0.009) in the high-score group and 1.36 (95% CI: 1.06-1.75, P = 0.017) in the low-score group (P for interaction < 0.001). Machine-learning-based scoring can be useful for the identification of optimal conditioning regimens for patients with MDS.

PMID:36376472 | DOI:10.1038/s41409-022-01871-8

Categories
Nevin Manimala Statistics

Sexual function of adult long-term survivors and their partners after allogeneic hematopoietic cell transplantation in Europe (S-FAST): a study from the Transplant Complications Working Party and Nurses Group of the EBMT

Bone Marrow Transplant. 2022 Nov 14. doi: 10.1038/s41409-022-01869-2. Online ahead of print.

ABSTRACT

Sexual dysfunction after allogeneic hematopoietic cell transplantation (allo-HCT) is a common long-term complication. We conducted a European multicenter cross-sectional study of adult allo-HCT recipients who had survived >2 years and their partners to investigate sexual functioning after HCT and to evaluate whether discussion about sexual functioning between the transplant team and the survivor and partner was perceived to have taken place. In total, 136 survivors (77 males, 59 females) and 81 partners (34 males, 47 females) participated. Median age was 56 and 54 years in male and female survivors, respectively. Forty-seven percent of male and 65% of female survivors and 57% of male and 59% of female partners reported clinically relevant sexual problems. Sixty-two percent of survivors and 79% of partners reported that sexual functioning had not been discussed with them during transplant. Standardized sexual functioning scores were correlated with self-reported health status in survivors (rho = 0.24, p = 0.009). The high prevalence of sexual dysfunction warrants additional studies focusing on the impact of changes in sexuality for patients as well as their partners. Future studies should also investigate which methods that are effective in preventing or treating sexual problems after allo-HCT.

PMID:36376470 | DOI:10.1038/s41409-022-01869-2

Categories
Nevin Manimala Statistics

Disrupted White Matter Microstructure in Patients With Fibromyalgia Owing Predominantly to Psychological Factors: A Diffusion Tensor Imaging Study

Pain Physician. 2022 Nov;25(8):E1305-E1313.

ABSTRACT

BACKGROUND: Neuroimaging investigations have already uncovered alterations to cerebral microstructural integrity in patients with fibromyalgia (FM). In the meantime, these patients commonly suffer from depression and anxiety.

OBJECTIVE: In this study, microstructure changes within white matter were examined in patients with FM with consideration of concurrent physiological factors.

STUDY DESIGN: A cross-sectional case-control study.

SETTING: A university hospital.

METHODS: Diffusion tensor imaging was performed on 20 patients with FM and 20 healthy controls. The 4 diffusional indices, namely, fractional anisotropy (FA), mean, radial, and axial diffusivity (MD, RD, AD) were calculated using tract-based spatial statistics. The relationships between the diffusional parameters and pain scales were also examined.

RESULTS: The patients with FM exhibited enhanced FA, reduced MD, RD, and AD in numerous white matter tracts, including the corpus callosum, corona radiata, internal capsule, corticospinal tract, posterior thalamic radiation, cerebellar peduncle, sagittal stratum, and superior fronto-occipital fasciculus. When depression and anxiety were added as covariates, most between-group diffusional difference disappeared except for AD reduction in the corona radiate, internal capsule, and cerebellar peduncle (P < 0.05, threshold-free cluster enhancement corrected). The diffusion tensor imaging measures were not correlated with clinical variables.

LIMITATION: A relatively small sample size.

CONCLUSION: Our results demonstrate that disrupted white matter microstructure in patients with FM is mainly restricted to tracts associated with pain sensory processing and motor control, adjusting for psychosocial factors. A considerable degree of difference in white matter characteristics may be explained by the patients with FM group’s greater level of psychological distress.

PMID:36375204

Categories
Nevin Manimala Statistics

Use of High-Resolution Ultrasound to Guide Alcohol Neurolysis for Chronic Pain

Pain Physician. 2022 Nov;25(8):E1297-E1303.

ABSTRACT

BACKGROUND: The diagnosis and treatment of neuropathic pain is often clinically challenging, with many patients requiring treatments beyond oral medications. To improve our percutaneous treatments, we established a clinical pathway that utilized ultrasound (US) guidance for steroid injection and alcohol ablation for patients with painful neuropathy.

OBJECTIVES: To describe a collaborative neuropathy treatment pathway developed by a neurosurgeon, pain physicians, and a sonologist, describing early clinical experiences and patient-reported outcomes.

STUDY DESIGN: A retrospective case series was performed.

METHODS: Patients that received percutaneous alcohol ablation with US guidance for neuropathy were identified through a retrospective review of a single provider’s case log. Demographics and treatment information were collected from the electronic medical record. Patients were surveyed about their symptoms and treatment efficacy. Descriptive statistics were expressed as medians and the interquartile range ([IQR]; 25th and 75th data percentiles). Differences in the median follow-up pain scores were assessed using a Wilcoxon signed-rank test.

RESULTS: Thirty-five patients underwent US-guided alcohol ablation, with the average patient receiving one treatment (range: 1 to 2), having a median duration of 4.8 months until reinjection (IQR: 2.9 to 13.1). The median number of steroid injections that individuals received before US-guided alcohol ablation was 2 (IQR: 1 to 3), and the median interval between steroid injections was 3.7 months (IQR: 2.0 to 9.6). Most (20/35 [57%]) patients responded to the survey, and the median pain scores decreased by 3 units (median: -3, IQR: -6 to 0; P < 0.001) one week following the alcohol ablation. This pain reduction remained significant at one month (P < 0.001) and one year (P = 0.002) following ablation. Most (12/20 [60%]) patients reported that alcohol ablation was more effective in improving their pain than oral pain medications.

LIMITATIONS: Given the small sample size, treatment efficacy for alcohol neurolysis cannot be generalized to the broader population.

CONCLUSIONS: US-guided percutaneous treatments for neuropathic pain present a growing opportunity for interprofessional collaboration between neurosurgery, clinicians who treat chronic pain, and sonologists. US can provide valuable diagnostic information and guide accurate percutaneous treatments in skilled hands. Further studies are warranted to determine whether a US-guided treatment pathway can prevent unnecessary open surgical management.

PMID:36375203