Category: Nevin Manimala

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

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Prevalence and significance of large granular lymphocytes in patients with immune thrombocytopenia

Post author By Nevin Manimala
Post date December 2, 2022

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

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Circulating CD133+/- CD34- progenitors have increased c-MYC expressions in Myeloproliferative Neoplasms

Post author By Nevin Manimala
Post date December 2, 2022

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

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Screening of functionalized collagen membranes with a porcine periodontal regeneration model

Post author By Nevin Manimala
Post date December 2, 2022

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

Tags nevin manimala, pubmed, statistics