Category: Nevin Manimala

Int Endod J. 2021 Aug 29. doi: 10.1111/iej.13620. Online ahead of print.

ABSTRACT

AIM: To investigate whether TGF-β/BMP signaling participates in Jagged1-induced osteogenic differentiation in human dental pulp cells (hDPs).

METHODOLOGY: Bioinformatic analysis of publicly available RNA sequencing data of Jagged1 treated hDPs was performed using NetworkAnalyst. The mRNA expression was validated using real-time polymerase chain reaction. hDPs were seeded on Jagged1 immobilized surface in the presence or absence of TGF-β or BMP inhibitor. Osteogenic differentiation was evaluated using alkaline phosphatase staining, osteogenic marker gene expression, and mineralization assay. Statistical analyses were performed using a Kruskal Wallis test, followed by a pairwise comparison for more than three group comparison. Mann Whitney U test was employed for two group comparison. The statistical significance was considered at p< 0.05.

RESULTS: Jagged1 treatment in growth medium significantly promoted TGFB1, TGFB2, and TGFB3 while significantly inhibited BMP2, BMP4, and BMP6 mRNA expression (p<0.05). In osteogenic induction medium, Jagged1 significantly upregulated TGFB1, TGFB2, and TGFB3 at day 1 and 3 (p<0.05). Pretreatment with TGF-β1, TGF-β2, or TGF-β3 prior to osteogenic induction resulted in the significant increase of osteogenic marker gene expression, collagen type 1 protein expression, alkaline phosphatase enzymatic activity, and mineral deposition (p<0.05). However, TGF-β signaling inhibition with SB431542 (4 μM) or SB505124 (47 and 129 nM) failed to attenuate the effect of Jagged1-induced osteogenic differentiation in hDPs. Dorsomorphin (4 and 8 μM) treatment significantly abolished the effect of Jagged1 on mineralization by hDPs (p<0.05).

CONCLUSION: Notch signaling activation by Jagged1 modulated TGF-β and BMP ligand expression. Dorsomorphin, but not TGF-β receptor inhibitor, attenuated Jagged1-induced osteogenic differentiation in hDPs.

PMID:34455605 | DOI:10.1111/iej.13620

Zoo Biol. 2021 Aug 29. doi: 10.1002/zoo.21648. Online ahead of print.

ABSTRACT

Many amphibian species are threatened with extinction. Understanding their vitamin A (retinol), E (alpha-tocopherol), and carotenoid requirements is vital, as normal levels of these nutrients have a known connection to breeding success with abnormal levels leading to disease. This research examined vitamins A, E, and carotenoids (apocarotenoid, beta-carotene; beta-cryptoxanthin, lutein, zeaxanthin, and esters) concentration kinetics in the liver and plasma of 65 (57.8) cane toads (Rhinella marina) over 4 months supplemented with commercially available invertebrates in human care. Cane toads were opportunistically collected as part of a population control program for use as an amphibian model species. Toads were randomly assigned to one of two diets: treatment 1 was brown house crickets (Acheta domesticus) consuming Mazuri® Hi Calcium Gut Loading Diet without vitamin A or E supplement, plus fresh raw vegetables (carrot/sweet potato); Treatment 2 was the same diet except no vegetables. Ten toads were euthanized on Day 0 to analyze baseline free-ranging liver and plasma metabolites. Six toads consuming each treatment were euthanized on Days 22, 50, and 81, and n = 7 on Day 119 for analysis. Regardless of dietary treatment, most liver and blood metabolites were substantially higher at time 0 than all time points thereafter (p < .05); Ex: liver vitamin A at time 0 was 87.7 ± 16.12 µg/g while Day 119 for treatments 1 and 2 were 11.6 ± 1.19 and 8.2 ± 0.74, respectively. Few statistically significant differences between diets at the same time point were noted (p < .05). The results from this study indicate that additional or alternative diet supplementation may be needed for cane toads (and potentially other amphibians) to mimic their free-ranging diets.

PMID:34455629 | DOI:10.1002/zoo.21648

Adv Ther. 2021 Aug 29. doi: 10.1007/s12325-021-01897-2. Online ahead of print.

ABSTRACT

INTRODUCTION: Migraine is a debilitating neurological condition, affecting up to 15% of Americans. Recent estimates from a long-term safety study of rimegepant showed evidence of decreased monthly migraine days (MMD) in people with episodic migraine treated with rimegepant 75 mg. The objective of this study was to characterize migraine-specific quality of life version 2.1 (MSQv2) scores and corresponding mapped EuroQol-5 Dimensions-3 Level (EQ-5D-3L) utility values.

METHODS: Study participants were randomized into two treatment regimens: individuals with 2-14 MMD received rimegepant 75 mg as needed (PRN), and those with 4-14 MMD at baseline who received rimegepant on a fixed every-other-day schedule plus an as needed dose on days they did not treat (QOD + PRN). MSQv2 was mapped to EQ-5D-3L utilities using a validated algorithm. Outcomes were assessed for the PRN arm at baseline weeks 12, 24, 36, and 52 and for the QOD + PRN arm at baseline and week 12.

RESULTS: At baseline, MSQv2 data were available for 1,800 patients: 1,033 with 2-8 MMD in the PRN group, 481 with 9-14 MMD in the PRN group, and 286 with 4-14 MMD in the QOD + PRN group. For all MSQv2 domains as well as mapped utility values, outcomes improved over each study visit. At baseline, EQ-5D-3L utilities were 0.66, 0.63, and 0.65 for the 2-8 MMD PRN, 9-14 MMD PRN, and 4-14 MMD QOD + PRN groups, respectively. At end-of-study, utilities had increased by + 0.09, + 0.10, and + 0.12 for the three groups, respectively (p < 0.001 for all comparisons with baseline). Similar trends in improvement were observed across MSQv2 subdomains; all differences were statistically significant.

CONCLUSIONS: Rimegepant 75 mg, which has been shown to be associated with reduced MMD, is associated with improvement in MSQv2 domains over time, leading to estimated improvement in EQ-5D-3L utilities. While this improvement was observed in all patient-groups, it was most pronounced in those with higher MMD and those taking rimegepant QOD + PRN.

TRIAL REGISTRATION: Clinical Trials NCT03266588.

PMID:34455556 | DOI:10.1007/s12325-021-01897-2

Clin Exp Pharmacol Physiol. 2021 Aug 29. doi: 10.1111/1440-1681.13586. Online ahead of print.

ABSTRACT

The postmenopausal stage in women’s life is associated with the enhancement of inflammation that may be reduced using soy isoflavones or soy protein. The present study aimed to summarize the effect of soy isoflavones and soy protein on circulating interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in postmenopausal women. The English-language articles were identified from the databases such as Cochrane Library, clinicaltrials.gov, Web of Science, PubMed, and Scopus until December 2020. The mean change from baseline and its standard deviation (SD) for intervention and comparison groups were used to calculate the effect size. The statistical heterogeneity of the intervention effects was computing by Cochran’s Q test and I-squared statistic. Nine and seven studies were selected for systematic review and meta-analysis respectively. The results of our meta-analysis indicated a non-significant effect on the serum concentrations of IL-6 and TNF-α (weighted mean differences (WMD)=0.07 pg/mL; 95% confidence interval (CI): -0.03, 0.17 pg/mL; P=0.190; WMD=0.05 pg/mL; 95% CI: -0.01, 0.12 pg/mL; P=0.092; respectively). In subgroup analysis, soy isoflavones plus soy protein could increase the serum concentration of IL-6 in studies with soy isoflavones dose ≤87 mg/d, cross-over design, weak quality, and studies on participants who had health risk factors or diseases. The serum concentration of TNF-α increased in studies with cross-over design, intervention duration≤56 days, and body mass index (BMI)>27, and in studies which were conducted on at-risk or sick participants. In conclusion, our meta-analysis did not confirm any downward effect on serum concentration of IL-6 and TNF-α among postmenopausal women.

PMID:34455600 | DOI:10.1111/1440-1681.13586

Ann Surg Oncol. 2021 Aug 28. doi: 10.1245/s10434-021-10660-4. Online ahead of print.

ABSTRACT

INTRODUCTION: Conversion from low-grade to high-grade disease is known to occur following repeat cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC); however, the incidence rate, risk factors, and outcomes have not been studied.

METHODS: We conducted a retrospective review of multiple CRS/HIPEC cases for patients originally diagnosed with low-grade appendiceal neoplasms, and compared converted cases with non-converters. Primary outcomes were the incidence rate and risk factors for conversion, while secondary outcomes were effect on cytoreduction, overall survival (OS), and disease-free survival (DFS).

RESULTS: Overall, 65 patients undergoing 134 cases of repeat CRS/HIPEC were identified; 11 patients converted to high-grade disease, an incidence rate of 16.92%. Converted cases averaged 4.4 years between CRS/HIPEC, versus 3.7 years for non-converters. Elevated baseline carcinoembryonic antigen (CEA) level, splenectomy at index CRS/HIPEC, and adjuvant chemotherapy utilization were statistically significant with conversion. Conversion had no impact on specific cytoreductive scores at repeat CRS/HIPEC (p = 0.435). Evaluating the effect on OS from the index CRS/HIPEC conversion had no impact. Mean OS was 9.5 and 8.8 years for cases that remained low-grade compared with those that converted, respectively (p = 0.668); however, when comparing OS from the time of conversion at repeat CRS/HIPEC, patients who progressed to high-grade disease had decreased survival at 4.4 versus 5.8 years (p = 0.0317). There was no difference in DFS between non-converters and converters at 4.1 and 3.6 years, respectively (p = 0.671).

CONCLUSION: Conversion had no impact on OS from the index CRS/HIPEC but resulted in inferior survival from repeat surgery. Conversion was insignificant in regard to DFS, and should not be considered a contraindication to repeat CRS/HIPEC. Adjuvant chemotherapy should be avoided.

PMID:34455511 | DOI:10.1245/s10434-021-10660-4

J Robot Surg. 2021 Aug 29. doi: 10.1007/s11701-021-01301-9. Online ahead of print.

ABSTRACT

Older men undergoing robot-assisted radical prostatectomy (RARP) have been thought to have worse perioperative, functional and oncological outcomes than younger men. However, there is a dearth of matched studies on this subject in the currently available literature. Our study is a matched pair analysis of perioperative, oncological and functional outcomes of RARP in men < 75 years of age versus ≥ 75 years (62 in each group). There was no statistically significant difference in complications, length of stay, pathological stage, positive surgical margins (PSM) and nodal involvement. Older men were less likely to undergo nerve sparing in our study (8.0 vs 75.8% p = 0.01). Potency rates were too low to be compared. The 1-year continence rates, time to continence and the proportion of men with biochemical recurrence (BCR) were similar between the groups. Men ≥ 75 years developed BCR much earlier than < 75 years (30 versus 78 months p = 0.07). However, this was not statistically significant. Age ≥ 75 years was associated with a statistically insignificant 53.5% rise in the risk of BCR. It was also not associated with any increased risk of postoperative complications or PSM. RARP is a safe procedure in senior adults. The oncological and functional outcomes of RARP in senior adults are similar to younger men.

PMID:34455530 | DOI:10.1007/s11701-021-01301-9

Community Ment Health J. 2021 Aug 29. doi: 10.1007/s10597-021-00883-w. Online ahead of print.

ABSTRACT

Suicide among adolescents is a significant public health concern in the U.S., especially within American Indian and Alaska Native (AIAN) communities. Lack of quality of life (QoL) estimates for both suicide ideation and depression specific to the AIAN population hinders the ability to compare interventions in cost-effectiveness analysis. We surveyed 200 AI youth and young adults from the Fort Apache Indian Reservation to estimate utility weights for experiencing suicide ideation and depression. Our results indicate that, on a scale of 0-100, with higher scores indicating better health, the general community rates both suicide ideation and depression at 15.8 and 25.1, respectively. These weights are statistically significantly different and lower than for other cultures. Culturally specific QoL values will allow the comparison and identification of the most effective and feasible interventions to reduce the suicide burden among tribal communities.

PMID:34455531 | DOI:10.1007/s10597-021-00883-w

Eur Spine J. 2021 Aug 28. doi: 10.1007/s00586-021-06968-0. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the risk and predictive factors of junctional issues after conversion from Traditional growing rod (TGR) to definitive spinal fusion in Early-onset scoliosis (EOS).

METHODS: Retrospective review of a multicenter EOS database. TGR patients who received final fusion with at least two-year follow-up were included. Proximal (PJA) and Distal junctional angles (DJA) on pre-final fusion, post-final fusion (within one year of surgery), and at latest follow-up were measured on lateral upright spinal radiographs. Differences in values among designated time points and predictive factors of junctional issues were evaluated statistically.

RESULTS: Forty-six of 251 patients (28 females, 18 males and mean age at final fusion: 12 ± 2 [9-17] years) met the inclusion criteria. Mean follow-up between first postoperative measurement and latest follow-up was 49 ± 22 (24-112) months. No statistical differences in PJA and DJA values were available at pre-fusion, first post-fusion, or latest follow-up (p = 0.827, p = 0.076). Fifty percent of patients had extension of TGR instrumentation at fusion, either proximal or distal. No factor including sex and etiology, lumbar lordosis, thoracic kyphosis, major curve magnitude, PJA, and DJA at pre-fusion was found to be a predictive issue for extension of index TGR instrumentation, except the history of at least one implant-related complication during the period from index surgery to the definitive fusion.

CONCLUSION: PJA and DJA remained stable when transitioning from TGR to final posterior spinal fusion. But 50% of patients had extension of construction at fusion, either proximal or distal.

PMID:34455481 | DOI:10.1007/s00586-021-06968-0

Oral Maxillofac Surg. 2021 Aug 29. doi: 10.1007/s10006-021-00993-5. Online ahead of print.

ABSTRACT

BACKGROUND: Distally inclining posterior implants may be technically challenging in certain situations. The presence of a posterior cantilever can also exert unfavorable forces on supporting implants. The aim of the present study was to evaluate and compare peri-implant soft and hard tissues around 4 mandibular interforaminal implants having tilted posterior implants with posterior cantilevers, versus vertical implants, 2 in the interforaminal region and 2 in the first molar regions, without posterior cantilevers. All implants supported full-arch fixed detachable restorations opposing complete dentures.

MATERIAL AND METHODS: A total of 80 implants were placed flapless in the mandibles of 20 edentulous participants. Four implants were placed for every participant, who were randomly assigned into 2 equal groups. Axial group implants were vertically aligned, with 2 implants in the interforaminal area and 2 in the molar area. Tilted group implants have 2 anterior axial and 2 posterior distally inclined implants. Interim screw-retained prostheses converted from pre-existing dentures were immediately fabricated and loaded on the same day of surgery. After awaiting period of 3 months, all participants received fixed detachable metal acrylic resin definitive restorations. A follow-up protocol of 3, 6, and 12 months was scheduled to assess the modified gingival index, modified plaque index, peri-implant probing depth, implant stability, and marginal bone level and bone density changes.

RESULTS: No statistically significant differences (P > .05) were found in the modified gingival index, modified plaque index, peri-implant probing depth, implant stability, bone density, and marginal bone level between the axial and tilted implant groups after the 1-year follow-up period.

CONCLUSION: Placing 4 flapless immediately loaded implants in mandibular edentulous patients that supported full-arch fixed restorations provided high implant and prosthodontic success rates whether posterior implants were tilted with posterior cantilevers or vertically aligned without posterior cantilevers.

TRIAL REGISTRATION: Pan African Clinical Trial Registry database, PACTR201907776166846. Registered 3 July 2019, www.pactr.org .

PMID:34455503 | DOI:10.1007/s10006-021-00993-5

Abdom Radiol (NY). 2021 Aug 29. doi: 10.1007/s00261-021-03261-y. Online ahead of print.

ABSTRACT

BACKGROUND: As experience with anal fistula imaging (MRI) has increased, new pathways of fistula extension have been identified. A recently described pathway is the ‘outer-sphincteric space’ present between the external anal sphincter and its covering outer fascia. A new type of complex fistula is being described which is present in the outer-sphincteric space and continues superiorly along the lateral border of the external anal sphincter to the infero-lateral surface of the puborectalis and levator-ani. In effect, these outer-sphincteric fistulas are at the roof of the ischiorectal fossa inside the levator muscle (RIFIL). These fistulas are not transsphincteric fistulas as they remain inside the levator muscle and do not enter the ischiorectal fossa.

METHODS: The MRI scans of consecutive anal fistula patients operated over the last two years were analyzed retrospectively.

RESULTS: Of 419 operated fistula patients analyzed, 42(10%) had RIFIL and 377 non-RIFIL fistulas. Compared to non-RIFIL fistulas, there were significantly more recurrent, multiple tracts, horseshoe, supralevator, and suprasphincteric fistulas in the RIFIL group. RIFIL fistulas were significantly more complex than non-RIFIL fistulas(85.7% vs 38.5%, p < 0.00001) and the surgery failure rate was also significantly higher in the RIFIL group (30.6%) than in the non-RIFIL fistula (7.2%) group(p = 0.0001).

CONCLUSION: RIFIL are highly complex fistulas. Proper diagnosis by MRI, surgical access, and subsequent management of these fistulas is quite challenging and they are associated with poor prognosis. Missing their diagnosis would lead to higher recurrence rate. These have not been described previously and were perhaps confused with high transsphincteric infralevator fistulas in ischiorectal fossa.

PMID:34455464 | DOI:10.1007/s00261-021-03261-y