Eur Spine J. 2022 Dec 2. doi: 10.1007/s00586-022-07471-w. Online ahead of print.
NO ABSTRACT
PMID:36459201 | DOI:10.1007/s00586-022-07471-w
Br J Health Psychol. 2022 Dec 2. doi: 10.1111/bjhp.12638. Online ahead of print.
ABSTRACT
OBJECTIVES: Blunted cardiovascular reactivity is associated with a distinct behavioural profile of greater exposure to early life adversity, coupled with higher levels of behavioural disengagement and symptoms of depression. The present study sought to extend on this work by investigating if behavioural clusters with distinct patterns of reactivity were related to health and behavioural outcomes at baseline and at a 4-year follow-up.
METHODS: Hierarchical cluster analyses were conducted using longitudinal data drawn from the Midlife Development in the United States (MIDUS 2) Biomarker Project and the MIDUS 3 follow-up 4 years later. During MIDUS, 2 participants (N = 513) underwent a standardized stress testing protocol and had their blood pressure and heart rate monitored throughout. In addition, hierarchical cluster analyses were conducted on responses from measures of early life adversity, behavioural disengagement and depression. Binary logistic regressions were conducted to determine whether cluster membership was related to health and behavioural outcomes which were taken at both time points.
RESULTS: Three behavioural clusters emerged with statistically different blood pressure reactivity patterns. The cluster characterized by greater exposure to early life adversity, higher levels of behavioural disengagement and depressive symptoms, had relatively lower blood pressure reactivity patterns compared with both the exaggerated reactivity cluster and the cluster similar to the sample mean. In fully adjusted models, this cluster was associated with hypertension (p = .050) and depressed affect (p = .033), while Cluster 1 characteristic of an exaggerated blood pressure reactivity profile was associated with depressed affect (p < .001). Cluster membership did not significantly predict future health status.
CONCLUSION: This study extends research on behavioural clusters characteristic of reactivity profiles to demonstrate how they relate to health and behavioural outcomes during MIDUS 2.
PMID:36458587 | DOI:10.1111/bjhp.12638
Platelets. 2023 Dec;34(1):2144194. doi: 10.1080/09537104.2022.2144194.
ABSTRACT
The association between T-cell large granular lymphocytes (T-LGL) and ITP is uncertain. The aims of this study were to determine the prevalence of T-LGL in patients with ITP and to describe its association with ITP disease severity. We analyzed flow cytometry results for T-LGL (using a threshold of 0.3 x109 or greater cells/L) or positive T-cell receptor clonality in patients with ITP and nonimmune thrombocytopenia. Descriptive statistics were used to characterize the association between T-LGL and ITP, response to ITP treatments (rituximab and splenectomy) and response to T-LGL treatment. Among ITP patients, 14.3% (13/91) had evidence of a T-LGL population compared to 10.3% (3/29) of patients with non-immune thrombocytopenia. ITP patients with T-LGL had lower nadir platelet counts (2 vs. 47 × 109/L) and received more ITP treatments (median 6 vs. 3) than ITP patients without T-LGL. Response to rituximab was observed in 14.3% (1/7) of ITP patients with T-LGL and 54.5% (6/11) without T-LGL. Response to splenectomy was observed in 25% (2/8) with T-LGL and 56.2% (9/16) without T-LGL. Four patients with ITP and T-LGL received treatment for T-LGL with methotrexate; none had an improvement in platelet count levels. T-LGL may appear in patients with ITP, and the meaning of this finding remains unclear; however, for some patients, the presence of abnormal T-LGL may indicate a more severe form of ITP that tends to be less responsive to therapy. In this cohort, treatment of T-LGL with methotrexate did not improve platelet counts in the few patients who were treated.
PMID:36458562 | DOI:10.1080/09537104.2022.2144194
Turk J Haematol. 2022 Dec 2. doi: 10.4274/tjh.galenos.2022.2022.0343. Online ahead of print.
ABSTRACT
OBJECTIVE: Myeloproliferative neoplasms (MPNs) are hematopoietic stem cell (HSC)-originated diseases with clonal myeloproliferation. The constitutive activation of JAK/STAT pathway is frequently detected in patients with Philadelphia chromosome negative (Ph-) MPNs with an acquired mutation JAK2V617F. Proto-oncogene, c-MYC is associated with malignant growth and cellular transformation, and previously, JAK2V617F has been shown to induce a constitutive expression of c-MYC. This study examines the expressional profile of c-MYC in Ph-MPNs with JAK2V617F and highlights its hierarchical level of activation in circulating hematopoietic stem/progenitor cell (HSPC) subgroups.
MATERIALS AND METHODS: Mononuclear cells(MNCs) of Ph-MPNs were fluorochrome-labeled in situ with wild-type(wt)-JAK2 or JAK2V617F mRNA gold nanoparticle technology and sorted simultaneously. The isolated populations of JAK2wt or JAK2V617F were evaluated for their c-MYC expressions. MNCs of fourteen Ph-MPNs were further isolated for HSPC subgroups regarding to their CD34 and CD133 expressions, evaluated for the presence of JAK2V617F, and compared to cord blood (CB) counterparts for the expression of c-MYC.
RESULTS: The mRNA-labeled gold nanoparticle-treated MNCs were determined to have the highest ratio of c-MYC relative fold-change expression in biallelic-JAK2V617F compartment compared to JAK2wt. The relative c-MYC expression in MNCs of MPN revealed significant increase compared to CB(p=0.01). The circulating HSPC of MPN in CD133+/-CD34- have revealed a statistically significant elevated c-MYC expression compared to CB.
CONCLUSION: This is the first study of circulating CD133+/-CD34- in Ph-MPNs, and reveals an elevated c-MYC expression level in the HSC/endothelial progenitor cells (HSC/EPC) and EPC. Furthermore, the steady increase in the expression of c-MYC within the MNCs carrying no mutation, monoallelic, or biallelic-JAK2V617F transcripts was notable. The presence of JAK2V617F with respect to c-MYC expression in the circulating in HSC/EPC and EPC of MPN might provide some evidence for the initiation of JAK2V617F and propagation of disease. Further studies are required to highlight the implication of increased c-MYC expression in such populations.
PMID:36458557 | DOI:10.4274/tjh.galenos.2022.2022.0343
Oral Dis. 2022 Dec 2. doi: 10.1111/odi.14445. Online ahead of print.
ABSTRACT
OBJECTIVES: Current methods for periodontal regeneration do not promote collagen fiber insertions into new bone and cementum. We used a pig wound model to screen different functionalized collagen membranes in promoting periodontal reattachment to root surfaces.
METHODS: Treatment groups included (1) control with no membranes, (2) collagen-coated membranes, (3) membranes with insulin-like growth factor-1 (IGF-1), (4) membranes with amelotin, or (5) membranes attached with calcium phosphate cement (CPC), or with CPC combined with IGF-1. Flap procedures were performed on mandibular and maxillary premolars of each pig.
RESULTS: Histomorphometric, micro-CT, and clinical measurements obtained at 4 and 12 weeks after surgery showed cementum formation on denuded roots and reformation of alveolar bone, indicating that the pig model can model healing responses in periodontal regeneration. Calcium phosphate cement simplified procedures by eliminating the need for sutures and improved regeneration of alveolar bone (p < 0.05) compared with other treatments. There was a reduction (p < 0.05) of PD only for the IGF group. Large observed variances between treatment groups indicated that a priori power analyses should be conducted to optimize statistical analysis.
CONCLUSIONS: Pigs can model discrete elements of periodontal healing using collagen-based, functionalized membranes. Screening indicates that membrane anchorage with calcium phosphate cements improve regeneration of alveolar bone.
PMID:36458549 | DOI:10.1111/odi.14445
Pediatr Blood Cancer. 2022 Dec 2:e30115. doi: 10.1002/pbc.30115. Online ahead of print.
ABSTRACT
BACKGROUND: Palliative care (PC) provides numerous benefits for children with cancer. Pediatric patients with high-grade glioma (HGG) are particularly well suited for early PC involvement given their high symptom burden and poor prognosis. However, studies continue to reveal that children with cancer, including HGG, have delayed PC involvement. We hypothesized that clinical trial enrollment may lead to a lack of or delay in PC involvement in this population.
PROCEDURE: For each patient in our cohort of 43 pediatric patients with HGG, demographic, diagnostic, therapeutic, clinical trial enrollment, and PC information were collected. Statistical analysis was performed comparing PC characteristics between patients who did and did not enroll in a clinical trial.
RESULTS: Seventy-two percent of patients had at least one visit with a PC provider. Fifty-six percent of patients enrolled in a clinical trial with HGG-directed therapy. Seventy-one percent of patients who enrolled in a clinical trial received specialty PC compared to 74% of non-trial participants (p = 1.000). Patients who enrolled in clinical trials received PC earlier in their disease course measured in days before death (mean = 177 days) compared to those who did not enroll (mean = 113 days, p = .180), though not statistically significant.
CONCLUSIONS: The prevalence of clinical trial enrollment is high in patients with HGG and will likely increase as the genomic/epigenomic landscape of these tumors is better understood. As such, our data reassuringly suggest that trial participation does not interfere with the receipt of specialty PC in this population.
PMID:36458446 | DOI:10.1002/pbc.30115
Brief Bioinform. 2022 Dec 1:bbac494. doi: 10.1093/bib/bbac494. Online ahead of print.
ABSTRACT
Deciphering 3D genome conformation is important for understanding gene regulation and cellular function at a spatial level. The recent advances of single cell Hi-C technologies have enabled the profiling of the 3D architecture of DNA within individual cell, which allows us to study the cell-to-cell variability of 3D chromatin organization. Computational approaches are in urgent need to comprehensively analyze the sparse and heterogeneous single cell Hi-C data. Here, we proposed scDEC-Hi-C, a new framework for single cell Hi-C analysis with deep generative neural networks. scDEC-Hi-C outperforms existing methods in terms of single cell Hi-C data clustering and imputation. Moreover, the generative power of scDEC-Hi-C could help unveil the differences of chromatin architecture across cell types. We expect that scDEC-Hi-C could shed light on deepening our understanding of the complex mechanism underlying the formation of chromatin contacts.
PMID:36458445 | DOI:10.1093/bib/bbac494
Orthop Surg. 2022 Dec 2. doi: 10.1111/os.13561. Online ahead of print.
ABSTRACT
OBJECTIVE: The percutaneous IS screws and the minimally invasive percutaneous plate are the most popular internal methods for Zone II unstable sacral fractures. However, the choice of fixation remains controversial for orthopaedic surgeons. The purpose of study was to evaluate and compare the clinical results of percutaneous iliosacral (IS) screw fixation under three-dimensional (3D) navigation and minimally invasive percutaneous plate fixation in the treatment of Zone II unstable sacral fractures.
METHODS: A retrospective study was performed, including 64 patients with Zone II unstable sacral fractures who underwent percutaneous IS screw fixation under 3D navigation (navigation group) and minimally invasive percutaneous plate fixation (plate group) from January 2011 and March 2021 in our department. The age, gender, fracture type, mechanism of injury, injury severity score (ISS), time from admission to operation, operative time, intraoperative blood loss, hospital stay, incision length, follow-up time, time to clinical healing, and complications were recorded and analyzed. Matta standard was used to assess fracture reduction outcomes. The Majeed function system assessed functional outcomes at the last follow-up.
RESULTS: The average follow-up time was (14.42 ± 1.57) months in the navigation group and (14.79 ± 1.37) months in the plate group. No statistical difference between the two groups in age, gender, fracture type, mechanism of injury, ISS, time from admission to operation, and time to clinical healing. However, significant differences were detected in operative time, intraoperative blood loss, hospital stay, and incision length (p < 0.001). According to Matta standard at 2 days postoperatively, the excellent and good rate was 91.42% in the navigation group, and it was 93.10% in the plate group. There was no significant difference between the two groups (p = 0.961). According to Majeed function system at the follow-up, the excellent and good rate was 97.14% in the navigation group, and 93.10% in the plate group. The difference between the two groups was not statistically significant (p = 0.748). There were no neurovascular injuries associated with this procedure. The incidence of complications was 44.82% (13/29) in the plate group, while 14.28% (5/35) in the navigation group (p = 0.007).
CONCLUSION: This study found that compared with minimally invasive percutaneous plate fixation, percutaneous IS screw fixation under 3D navigation is a suitable option for the treatment of Zone II unstable sacral fractures. This approach is characterized by its shorter operation time, less surgical trauma, less bleeding, less hospital time, and fewer complications.
PMID:36458444 | DOI:10.1111/os.13561
Int J Clin Pharmacol Ther. 2022 Dec 2. doi: 10.5414/CP204299. Online ahead of print.
ABSTRACT
OBJECTIVE: To evaluate the pharmacokinetics (PK), safety, and bioequivalence of two formulations of apixaban in healthy Chinese subjects under fasting and fed conditions.
MATERIALS AND METHODS: A single-center, randomized, open, single-dose, two-period crossover PK study was carried out under fasting and fed conditions in 64 healthy subjects enrolled in either the fasting (36 subjects) or the fed (28 subjects) arms of the study. Subjects received a single oral dose of 2.5 mg apixaban tablets as test (T) or reference (R) formulation. The primary PK parameters determined were the area under the plasma concentration-time curve from zero to t and ∞ (AUC0-t and AUC0-∞) and the maximal plasma concentration (Cmax). Safety was assessed mainly from the occurrence of adverse events (AEs).
RESULTS: A single drop-out in the fed arm of the trial was excluded from the statistical evaluation. The 90% confidence intervals (CIs) for the geometric mean ratio (GMR) for T/R using AUC0-t were 95.4 – 100.9% and 97.8 – 103.8%, and for AUC0-∞ were 95.3 – 100.6% and 98.3 – 104.3% under fasting (36 subjects) and fed (27 subjects) conditions, respectively. Similarly, the 90% CIs for Cmax were 94.6 – 103.1% and 88.8 – 102.0% under fasting (36 subjects) and the fed (27 subjects) conditions, respectively. Therefore, the 90% CIs for the T/R AUC and Cmax ratios were within the standard range for bioequivalence (80.0 – 125.0%). There were no serious adverse events (SAEs).
CONCLUSION: The test and reference 2.5 mg apixaban tablets were bioequivalent and both showed good tolerability and safety.
PMID:36458443 | DOI:10.5414/CP204299
Int J Clin Pharmacol Ther. 2022 Dec 2. doi: 10.5414/CP204300. Online ahead of print.
ABSTRACT
PURPOSE: To evaluate the rate and determinants of non-adherence to antipsychotic medications in Saudi Arabia.
MATERIALS AND METHODS: This was a cross-sectional study that included a questionnaire, interview, and data extraction from medical records of adult patients on antipsychotic medications. The study was conducted at outpatient clinics at the psychological care department at King Fahad Medical City, Riyadh, Saudi Arabia, between October 25 and November 26, 2020. Data collection included three parts: patients’ sociodemographic characteristics; antipsychotic medications used and patients’ clinical characteristics; and adherence to antipsychotic medications measured by the Medication Adherence Rating Scale (MARS).
RESULTS: Out of 220 patients, 122 (55.5%) were considered non-adherent (MARS scores 6 or less). The MARS items contributing most to non-adherence were “the medication makes me feel tired and sluggish” and “forget to take the medication”, 55 and 40.9%, respectively. Additionally, adverse drug effect significantly increased the risk of poor adherence in regression analysis (odds ratio = 1.97, p = 0.028). The model also showed that female sex, low income, cigarette smoking, substance abuse, uncontrolled disease, comorbidity, and use of Ruqyah religious therapy were associated with increased risk of poor adherence, but were however not statistically significant (p < 0.05).
CONCLUSION: This study showed high non-adherence rate to antipsychotic medications. Adverse drug effects and forgetting to take medications were the main patient-reported barriers to adherence. Likewise, sociodemographic, clinical, and spiritual factors affected medication adherence. Knowing these predictors helps in early identification of patients who are predisposed to medication non-adherence and allows personalized interventions that improve adherence and treatment outcomes.
PMID:36458442 | DOI:10.5414/CP204300