A Novel Fragment Derived from Laminin-411 Facilitates Proliferation and Differentiation of Odontoblast-Like Cells

The aim for the present study was to evaluate the in vitro effects of iMatrix-411 in odontoblast-like cells. To that end, iMatrix-411 was coated to both nontissue culture treated- (Non-PS) and tissue culture treated-polystyrene (TCPS) multiwells. MDPC-23 cells were seeded into noncoated (control) or coated wells. Optimal coating density and cell proliferation were assessed by cell counting kit-8 (CCK-8) at day two, day three, and day five. Osteo/odontogenic differentiation was evaluated by real-time RT-PCR and alkaline phosphatase (ALP) activity at days seven and eight, respectively. Calcific deposition of cells was visualized by alizarin red staining. Data were analyzed with post hoc Tukey HSD test (). Optimal coating density for iMatrix-411 was 8 μg/cm2. Exposure of MDPC-23 cells to iMatrix-411 in either non-PS or TCPS significantly enhanced proliferative activity. iMatrix-411 elevated ALP activity in both types of culture plates. iMatrix-411 significantly increased the mRNA level of OCN, BSP, OPN, ALP, and DMP-1. Meanwhile, it enhanced the expression of several integrin subunits: ITGA1, ITGA5, ITGAV, ITGB1, and ITGB5. Finally, iMatrix-411 also accelerated the mineralization at day eight in Non-PS. The results indicated iMatrix-411 stimulates proliferation and favours differentiation of odontoblast-like cells.

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Changes in Serum Electrolytes, ECG, and Baroreflex Sensitivity during Combined Pituitary Stimulation Test

The mechanisms by which hypoglycemia increases cardiovascular mortality remain unclear. The aim of the study is to investigate changes in serum electrolytes, norepinephrine concentrations, electrocardiography, and baroreflex sensitivity (BRS) and associations between corrected QT (QTc) intervals and the changes in serum electrolytes during combined pituitary stimulation test (CPST). We recruited the subjects who were admitted to the Gyeongsang National University Hospital to undergo CPST between September 2013 and December 2014. Participants were 12 patients suspected of having hypopituitarism. Among 12 patients, cardiac arrhythmia in two patients occurred during hypoglycemia. There were significant differences in serum levels of potassium (), sodium (), chloride (), and calcium () at baseline, hypoglycemia, and 30 and 120 minutes after hypoglycemia. Also, there was a significant increase in heart rate (), corrected QT (QTc) interval (), QRS duration (), and BRS () at hypoglycemia, compared to other time points during CPST. There was a positive association between QTc intervals and serum sodium levels () in 10 patients who did not develop arrhythmia during CPST. This study showed that there were significant changes in serum levels of potassium, sodium, chloride, and calcium, as well as heart rate, QTc interval, QRSd, and BRS during CPST. It was revealed that QTc intervals had a significant association with concentrations of sodium.

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Phase 1 study of seviteronel, a selective CYP17 lyase and androgen receptor inhibitor, in women with estrogen receptor-positive or triple-negative breast cancer

Abstract

Purpose

Seviteronel (INO-464) is an oral, selective cytochrome P450c17a (CYP17) 17,20-lyase (lyase) and androgen receptor inhibitor with in vitro and in vivo anti-tumor activity. This open-label phase 1 clinical study evaluated safety, tolerability, pharmacokinetics (PK), and activity of once-daily (QD) seviteronel in women with locally advanced or metastatic TNBC or ER+ breast cancer.

Methods

Seviteronel was administered in de-escalating 750, 600, and 450 mg QD 6-subject cohorts. The 750 mg QD start dose was a phase 2 dose determined for men with castration-resistant prostate cancer in (Shore et al. J Clin Oncol 34, 2016). Enrollment at lower doses was initiated in the presence of dose-limiting toxicities (DLTs). The primary objective of this study was to determine seviteronel safety, tolerability, and MTD. The secondary objectives included description of its PK in women and its initial activity, including clinical benefit rate at 4 (CBR16) and 6 months (CBR24).

Results

Nineteen women were enrolled. A majority of adverse events (AEs) were Grade (Gr) 1/2, independent of relationship; the most common were tremor (42%), nausea (42%), vomiting (37%), and fatigue (37%). Four Gr 3/4 AEs (anemia, delirium, mental status change, and confusional state) deemed possibly related to seviteronel occurred in four subjects. DLTs were observed at 750 mg (Gr 3 confusional state with paranoia) and 600 mg (Gr 3 mental status change and Gr 3 delirium) QD, with none at 450 mg QD. The recommended phase 2 dose (RP2D) was 450 mg QD, and at the RP2D, 4 of 7 subjects reached at least CBR16 (2 TNBC subjects and 2 ER+ subjects achieved CBR16 and CBR24, respectively); no objective tumor responses were reported.

Conclusions

Once-daily seviteronel was generally well tolerated in women with and 450 mg QD was chosen as the RP2D.

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Palmar Ulnar Artery Perforator Free Flap for Fingertip Reconstruction: Anatomical and Clinical Study

Background. Fingertips are a common site for hand injuries. The ideal substitute for fingertip pulp is tissue that matches texturally with minimal donor site morbidity. We described anatomical findings from cadaveric studies and the reliability of the palmar ulnar artery perforator (PUAP) free flap techniques for the reconstruction of fingertips injuries. Methods. The cadaveric study involving 8 hands was conducted to illuminate the anatomy of the hypothenar region. We investigated the emerging point of perforators, diameter of the artery at the origin, and the length of the pedicle. Forty-four patients with fingertip injuries underwent fingertip reconstruction using PUAP free flaps. Data on the baseline patient demographics, hospital courses, and flap sizes were obtained retrospectively. The 6-month postoperative sensory capacity was determined using a 2-point discrimination test. Results. The cadaveric study found that the PUAP pedicles arose from the superficial palmar arch, the mean length of pedicles, and the diameter and location of perforators were also analyzed. The PUAP flap sizes varied from 2.0 × 2.3 cm to 2.5 × 3.5 cm, and the mean operative time was 124 min. In all cases, we performed neurorrhaphy for fingertip sensory restoration. All donor sites were closed primarily, and the 2-point discrimination test result was  mm 6 months after surgery. Conclusions. We confirmed the anatomical consistency of the PUAP. Among the numerous reconstruction options available for fingertip injuries, the PUAP free flap is a useful fingertip reconstruction option.

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Growth Media Affect Assessment of Antimicrobial Activity of Plant-Derived Polyphenols

This study aimed to investigate the effects of different microbial growth media on the laboratory assessment of antimicrobial activity of natural polyphenolic compounds. The inhibition of the tea polyphenol EGCG on growth of selected oral microorganisms was evaluated in complex media and a protein-free chemically defined medium (CDM). Other antimicrobial agents (polyphenolic grape seed extract, plant alkaloid berberine, methyl salicylate, and chlorhexidine gluconate) were also tested in the study. The presence of proteins and their effects on the antimicrobial activity of EGCG were investigated by the addition of BSA to the CDM. The MICs of EGCG against test oral microorganisms were 4 to 64 times higher in complex media than in CDM. The polyphenolic grape seed extract exhibited similar discrepancies. However, the MICs of the nonpolyphenolic compounds (berberine, methyl salicylate, and chlorhexidine) were not significantly different between the two growth media. The MIC of EGCG against S. mutans UA159 in CDM with added BSA was 16 times higher than that in CDM alone. Therefore, nonproteinaceous CDM should be used to avoid interference of proteins with the active ingredients when testing the antimicrobial activity of plant-derived polyphenolic compounds against microorganisms. This will also minimize the discrepancies noted in results obtained by different investigators.

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Engaging Latino Fathers in Children’s Eating and Other Obesity-Related Behaviors: a Review

Abstract

Purpose of Review

There is a growing evidence of the important role that fathers play in influencing their children's eating and other weight-related behaviors. Latino children are at high risk for obesity and associated medical conditions. Engaging Latino fathers is a potentially important and unique way to help promote healthy lifestyles for Latino children, but doing so requires a culturally sensitive understanding both of fathers' current role and the family perceptions of this role.

Recent Findings

Here, we review recent data and argue that there are subtle but important differences between the qualitative and quantitative research conducted regarding the role Latino fathers may play in promoting healthy eating and physical activity for their children. We suggest how to synthesize these findings and also present qualitative results for ways to best engage Latino fathers in research studies with a focus on physical activity.

Summary

Results from the review support that Latino fathers are important potential targets for child obesity prevention, but our findings stress the importance of considering cultural values when trying to recruit, engage and retain Latino fathers for such research.

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Neuroendocrine Factors and Head and Neck Squamous Cell Carcinoma: An Affair to Remember

Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive malignancies. Therefore, the major goal of cancer treatment is inhibition of tumor cell growth and of metastasis development. In order to choose the best management option for HNSCC patients, we need to identify reliable prognostic factors and to develop new molecular techniques in order to obtain a better understanding of therapy resistance. By acting as neurohormones, neurotransmitters, or neuromodulators, the neuroendocrine factors are able to signal the maintenance of physiological homeostasis or progression to malignant disease. Certain neuropeptides possess strong antitumor properties acting as tumor suppressors and immunomodulators, providing additional benefits for future potential therapeutic strategies. In light of the current understanding, cancer starts as a localized disease that can be effectively treated if discovered on proper time. Unfortunately, more than often cancer cells migrate to the surrounding tissues generating distant metastases, thus making the prognosis and survival in this stage much worse. As cellular migration is mandatory for tumor invasion and metastasis development, searching for alternate controllers of these processes, such as the neuroendocrine factors, it is an active tremendous task.

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