Nevin Manimala

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 ∞ (AUC_0-t and AUC_0-∞) and the maximal plasma concentration (C_max). 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 AUC_0-t were 95.4 – 100.9% and 97.8 – 103.8%, and for AUC_0-∞ 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 C_max 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 C_max 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

Alcohol Alcohol. 2022 Dec 1:agac062. doi: 10.1093/alcalc/agac062. Online ahead of print.

ABSTRACT

AIMS: To determine whether there is a difference in pituitary gland volumes in patients with alcohol use disorder compared to healthy people.

METHODS: The subjects included in the study consisted of 15 individuals who met the criteria for alcohol use disorder according to the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM 5) diagnostic criteria based on the Structured Clinical Interview for DSM 5 and were admitted to Firat University School of Medicine, Department of Psychiatry, or were hospitalized, and 17 healthy controls. The volumes of pituitary were measured in subjects.

RESULTS: Absolute pituitary gland volumes of patients with alcohol use disorder and healthy controls were compared in the analysis performed using the independent samples t-test. The mean volume of the patient group was significantly smaller than the healthy controls (58.02 ± 7.24 mm3 in patients with alcohol use disorder vs. 83.08 ± 12.11 mm3, P < 0.01), a difference which persisted after controlling for age, gender and total brain size.

CONCLUSIONS: Patients with alcohol use disorder in this study had smaller pituitary gland volumes compared to those of healthy control subjects. However, this study has limitations including small sample size and not adjusting for previous or current medication use or current anxiety and depression.

PMID:36458440 | DOI:10.1093/alcalc/agac062

J Hepatobiliary Pancreat Sci. 2022 Dec 2. doi: 10.1002/jhbp.1294. Online ahead of print.

ABSTRACT

PURPOSE: Delayed hemorrhage (DH) is a rare and yet well-known fatal complication associated with postoperative pancreatic fistula (POPF) in pancreatoduodenectomy (PD). The study aimed to investigate whether arterial reinforcement (AR) using polyglycolic acid sheets (PAS) followed by fibrin sealant (FS) to the hepatic artery could prevent DH in the setting of POPF after PD.

METHODS: A total of 345 patients underwent PD for periampullary tumors from March 2011 to March 2022. From March 2011 to March 2018, 225 patients underwent PD, and AR was not performed (non-AR group). From April 2018 to March 2022, 120 patients underwent PD, and AR was performed (AR group). AR was achieved by wrapping the proper hepatic artery all the way down to the celiac artery with PAS followed by coating with FS. Demographic profile and various outcomes including DH of these two groups were compared and analyzed retrospectively.

RESULTS: In non-AR group, 48 (21.3%) and 12 (5.3%) patients had grade B and C POPF respectively. In AR group, 26 (21.7%) and 4 (3.3%) patients had grade B and C POPF respectively. The incidence of POPF was not was not statistically significant (p = 0.702) between the groups. Among the patients with grade B or C POPF, DH occurred in 14 (23.3%) patients in non-AR group and only one patient in AR group (p = 0.016). Of the 15 patients with DH, four (26.7%) patients died.

CONCLUSION: AR using PAS and FS is effective in preventing DH in the setting of POPF.

PMID:36458401 | DOI:10.1002/jhbp.1294

J Musculoskelet Neuronal Interact. 2022 Dec 1;22(4):498-503.

ABSTRACT

OBJECTIVE: To determine the efficacy of a five-week core stability training program for collegiate athletes on upper extremity performance measures.

METHODS: Seventy healthy collegiate athletes (age 21.6±1.7years; height 175±4.63 cm; body mass 65.31±5.63 kg) were randomly allocated to experimental (n=35) and control group (n=35). The experimental group has undergone a five-week core stabilisation protocol (three days /week) and regular training, whereas the control group maintained their regular training. The upper quarter Y balance test (UQ-YBT) and Functional throwing performance index (FTPI) were assessed pre and post-training.

RESULTS: The results of mixed ANOVA show that there was a significant interaction between time and group variables on YBT (p<0.001, η_p² =0.759) and FTPI (p<0.001, η_p² =0.411) after five weeks of core stability training. Statistically, significant improvement was shown in YBT (mean change=15.2, p<0.001) and FTPI (mean change=14.4, p<0.001) in the experimental group; however, there was no significant change observed in both outcomes in the control groups.

CONCLUSION: After five weeks of core stabilisation training program, the measures of UQ-YBT and FTPI were improved, thus advocating the use of a core stabilisation training program among collegiate athletes to enhance their upper extremity performance.

PMID:36458387