Micro-autologous Fat Transplantation (MAFT) for Forehead Volumizing and Contouring.

BACKGROUND: Frontal fullness in Asians is often considered to indicate one's public popularity and leadership skills. Numerous materials and techniques have been applied clinically to recontour or volumize the frontal area, with variable results. The micro-autologous fat transplantation (MAFT) technique proposed by Lin et al. (2nd academic congress of Taiwan Cosmetic Association Taipei, Taiwan) in 2007 has demonstrated its feasibility in facial rejuvenation. In the present study, we used an innovative instrument to apply the MAFT technique to frontal augmentation with fat grafting and reported the results. METHODS: MAFT was performed on 178 patients (167 female, 11 male) during a 5-year period starting in January 2010. Fat was harvested by liposuction, processed and refined by centrifugation at 1200×g for 3 min. The purified fat was micro-transplanted for frontal contouring with the assistance of an instrument, the MAFT-GUN. The patients were followed up regularly, and photographs were taken for comparison. RESULTS: On average, the MAFT procedure took 52 min to complete. The average amount of delivered fat was 10.2 mL. The follow-up period was 34 months on average. No complications, including neurovascular injury, skin necrosis, abscess, nodulation, calcification or irregularity, were noted. A patient-rated satisfaction 5-point Likert scale demonstrated that 83.1% of all patients had favorable results (48.3% were satisfied, and 34.8% were very satisfied). CONCLUSION: The concept and technique of MAFT has changed fat grafting from an operation with unpredictable clinical results to an easy, reliable and consistent procedure. Furthermore, the use of a precisely controlled instrument enabled surgeons to perform highly accurate micro-fat grafting. In comparison with other strategies for volume restoration, the MAFT procedure demonstrated high patient satisfaction with the long-term results. Therefore, the use of MAFT as an alternative approach to forehead contouring and volumizing was addressed. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A need to provide explanations for observed biological effects of radiofrequency exposure.

Although there is scientific consensus that radiofrequency (RF) exposure at high intensity can cause thermal effects, including well-established adverse health effects, there is still considerable controversy on whether low-intensity RF exposure can cause biological effects, especially adverse health effects. The objective of this paper is to describe several reported "non-thermal" effects that were later shown to be due to a weak thermal effect or an experimental artifact by properly conducted and thorough follow-on scientific research. First, the multiple factors that can cause different RF energy absorption in biological tissues are reviewed and second, several examples of experimental artifacts in published papers are described to demonstrate the importance of paying attention to dosimetry and temperature control. For example, isolated nerve response studies show that when temperature of the RF-exposed tissues is controlled, effects disappeared. During RF exposure, conductive electrodes routinely used in physiological studies have been shown to cause field intensification at the tips or contacts of the electrodes with biological tissue; thus, the RF exposure at the site of measurement could be much higher than the incident field. In some in vitro studies, a lack of temperature uniformity in RF-exposed cell cultures and rate of heating explain changes originally reported to be due to low-level RF exposure. In other studies, detailed dosimetry studies have identified artifacts that explain the reasons why so-called "non-thermal" effects were mistakenly reported. Researchers should look for explanations for their own findings, and not expect others to figure out what was the reason for their observed effects.

Allotransplantation of transgenic mouse ovaries expressing enhanced green fluorescent protein under the control of the murine phosphoglycerate kinase 1 promoter.

The aim of this study was to generate a transgenic mouse that ubiquitously expressed enhanced green fluorescent protein (EGFP) under the control of the murine phosphoglycerate kinase 1 promoter by allotransplantation of transgenic mouse ovaries. The EGFP transgenic mice expressed green fluorescence in many organs, and the fluorescence was detected as early as the embryonic stage. Ovaries from the EGFP transgenic mice were allotransplanted into recipients and these mice were mated with normal male mice. Histological sections of EGFP-allotransplanted ovaries from the recipient mice showed the well development and formation at follicles and corpora lutea. The green fluorescence was clearly detectable at the allotransplanted section of the ovaries, which had fused with the normal ovary. The average size of the first litter from these mice was 6.8 ± 1.2 pups per recipient, and 17.8% of the pups expressed EGFP. These results demonstrated that allotransplantation of transgenic ovaries can restore a normal reproductive lifespan and can be used to generate a ubiquitously expressing EGFP animal model.

IEEE Committee on Man and Radiation-COMAR Technical Information Statement: Health and Safety Issues Concerning Exposure of the General Public to Electromagnetic Energy from 5G Wireless Communications Networks.

This COMAR Technical Information Statement (TIS) addresses health and safety issues concerning exposure of the general public to radiofrequency (RF) fields from 5G wireless communications networks, the expansion of which started on a large scale in 2018 to 2019. 5G technology can transmit much greater amounts of data at much higher speeds for a vastly expanded array of applications compared with preceding 2-4G systems; this is due, in part, to using the greater bandwidth available at much higher frequencies than those used by most existing networks. Although the 5G engineering standard may be deployed for operating networks currently using frequencies extending from 100s to 1,000s of MHz, it can also operate in the 10s of GHz where the wavelengths are 10 mm or less, the so-called millimeter wave (MMW) band. Until now, such fields were found in a limited number of applications (e.g., airport scanners, automotive collision avoidance systems, perimeter surveillance radar), but the rapid expansion of 5G will produce a more ubiquitous presence of MMW in the environment. While some 5G signals will originate from small antennas placed on existing base stations, most will be deployed with some key differences relative to typical transmissions from 2-4G base stations. Because MMW do not penetrate foliage and building materials as well as signals at lower frequencies, the networks will require "densification," the installation of many lower power transmitters (often called "small cells" located mainly on buildings and utility poles) to provide for effective indoor coverage. Also, "beamforming" antennas on some 5G systems will transmit one or more signals directed to individual users as they move about, thus limiting exposures to non-users. In this paper, COMAR notes the following perspectives to address concerns expressed about possible health effects of RF field exposure from 5G technology. First, unlike lower frequency fields, MMW do not penetrate beyond the outer skin layers and thus do not expose inner tissues to MMW. Second, current research indicates that overall levels of exposure to RF are unlikely to be significantly altered by 5G, and exposure will continue to originate mostly from the "uplink" signals from one's own device (as they do now). Third, exposure levels in publicly accessible spaces will remain well below exposure limits established by international guideline and standard setting organizations, including ICNIRP and IEEE. Finally, so long as exposures remain below established guidelines, the research results to date do not support a determination that adverse health effects are associated with RF exposures, including those from 5G systems. While it is acknowledged that the scientific literature on MMW biological effect research is more limited than that for lower frequencies, we also note that it is of mixed quality and stress that future research should use appropriate precautions to enhance validity. The authorship of this paper includes a physician/biologist, epidemiologist, engineers, and physical scientists working voluntarily and collaboratively on a consensus basis.

FLJ10540-elicited cell transformation is through the activation of PI3-kinase/AKT pathway.

A significant challenge in the post-genomic era is how to prioritize differentially expressed and uncharacterized novel genes found in hepatocellular carcinoma (HCC) microarray profiling. One such category is cell cycle regulated genes that have only evolved in higher organisms but not in lower eukaryotic cells. Characterization of these genes may reveal some novel human cancer-specific abnormalities. A novel transcript, FLJ10540 was identified. FLJ10540 is overexpressed in HCC as examined by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. The patients with higher FLJ10540 expression had a poor survival than those with lower FLJ10540 expression. Functional characterization indicates that FLJ10540 displays a number of characteristics associated with an oncogene, including anchorage-independent growth, enhanced cell growth at low serum levels and induction of tumorigenesis in nude mice. FLJ10540-elicited cell transformation is mediated by activation of the phosphatidylinositol 3'-kinase (PI3K)/AKT pathway. Moreover, FLJ10540 forms a complex with PI3K and can activate PI3K activity, which provides a mechanistic basis for FLJ10540-mediated oncogenesis. Together, using a combination of bioinformatics searches and empirical data, we have identified a novel oncogene, FLJ10540, which is conserved only in higher organisms. The finding raises the possibility that FLJ10540 is a potential new therapeutic target for HCC treatment. These findings may contribute to the development of new therapeutic strategies that are able to block the PI3K/AKT pathway in cancer cells.

The fabrication and testing of electrospun silica nanofiber membranes for the detection of proteins.

In this study, we fabricated electrospun silica nanofiber membranes and investigated their use in biomolecular sensing. The diameter, porosity and surface-to-volume ratio of nanofiber membranes were investigated under different fabrication conditions. Using this type of nanofiber membrane, enzyme-linked immunosorbent assay (ELISA) was performed, and the results were compared with those obtained with conventional ELISA using polystyrene well plates. The minimum detectable concentration was determined as 0.19 ng ml(-1) (1.6 pM), which is 32 times lower than that of conventional ELISA. In addition, the detection time for all processes for the nanofiber membrane was reduced to 1 h, compared with 1 day for conventional ELISA. The increased sensitivity, faster reaction time, and affordability of the nanofiber membrane make it well suited for bio-chip use.

Early and late endophthalmitis following trabeculectomy in a Chinese population.

PURPOSE: To investigate the rate of bleb-related endophthalmitis over 5 years in a Chinese population. METHODS.:Retrospective chart review. RESULTS: Of 988 trabeculectomies performed over 5 years, one case (0.1%) developed early endophthalmitis caused by Morganella morganii, which was rarely reported in the literature. Six cases (0.6%) developed late-onset endophthalmitis. Mitomycin C significantly increased the risk of late-onset endophthalmitis (p=0.0002). CONCLUSIONS: Physicians should weigh the benefits against the risks of mitomycin C application in performing trabeculectomies.

Expression of class I and class II major histocompatibility antigens on human hepatocellular carcinoma.

Previous reports indicate that human hepatocytes do not express class I and class II MHC antigens. Our analyses on 10 human hepatocellular carcinoma (HCC) cell lines by immunofluorescence tests and RIA, demonstrate that all the human HCC cell lines tested express class I MHC antigens and among them, three poorly differentiated human HCC cell lines also express class II MHC antigens. Results of immunoprecipitation and/or Western blotting experiments indicate similarity in the chemical nature of both the class I and class II MHC antigens expressed by the human HCC cell lines and by a human B lymphoblastoid cell line Raji. Furthermore, a new variant form of class I antigen was detected in some of these HCC cell lines. Immunohistochemical studies of HCC tissues using the peroxidase-antiperoxidase staining method indicated that class I and class II antigens were detectable in 7 out of 11 and 3 out of 11 HCC tissues from patients, respectively. The availability of MHC class I antigen-positive cultured HCC cell lines, including the poorly differentiated lines that also express MHC class II antigen, has provided us with interesting models to study the relationship between expression of MHC antigen and transformation and differentiation of human hepatocytes. These studies will also allow us some insight into the role of MHC class I and class II antigen in the immunosensitivity and immunogenicity of HCC cells to the host-immune response.

Selective suppression of insulin-induced proliferation of cultured human hepatoma cells by somatostatin.

The effects of somatostatin (SRIF), insulin, and triiodothyronine (T3) on the growth of human hepatoma cells were investigated on the well-differentiated human hepatoma cell line Hep3B. Results showed that both insulin and T3 can stimulate cell growth of serum starved Hep3B cells at physiological concentrations. SRIF alone showed little growth-promoting activity. When added concurrently with insulin, however, SRIF suppressed the insulin-induced cell proliferation in a dose-dependent manner. On the other hand, SRIF had no inhibitory effect on T3-induced cell proliferation. SRIF is labile in the medium, with a half-life of about 2 h during culture incubation. SRIF did not disturb the insulin binding to its surface receptors nor inhibit the insulin-dependent receptor kinase activity of Hep3B cells in vitro. These results suggest that postreceptor regulation may be involved. The selective suppression by SRIF of insulin-induced cell growth provides an unique approach to the study of insulin actions on proliferation of human hepatoma cells.

Induction of plasma protein secretion in a newly established human hepatoma cell line.

To study the expression and the regulation of hepatocyte markers, we have undertaken to establish human hepatoma cell lines of various phenotypes. We now report the establishment of a new human hepatoma cell line, HA22T/VGH. This cell line has many of the properties of human hepatocellular carcinoma. Only 5 of 15 plasma proteins investigated were detected in the medium of a 10-day-old HA22T/VGH culture. However, when the HA22T/VGH cells and a clonal derivative, C5, were cultured in an aggregated form, all 15 plasma proteins were found in the culture medium. These results indicate that hepatoma cell lines with different phenotypes can be established, and they provide a good experimental framework to investigate differentiation of human hepatocytes.

mcl-1 is an immediate-early gene activated by the granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling pathway and is one component of the GM-CSF viability response.

mcl-1, a bcl-2 family member, was originally identified as an early gene induced during differentiation of ML-1 myeloid leukemia cells. In the present study, we demonstrate that Mcl-1 is tightly regulated by the granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling pathway. Upon deprivation of survival factor from TF-1 myeloid progenitor cells, Mcl-1 levels quickly dropped prior to visible detection of apoptosis of these cells. Upon restimulation of these deprived cells with GM-CSF, the mcl-1 mRNA was immediately induced and its protein product was accordingly resynthesized. Analysis with Ba/F3 cells expressing various truncation mutants of the GM-CSF receptor revealed that the membrane distal region between amino acids 573 and 755 of the receptor beta chain was required for mcl-1 induction. Transient-transfection assays with luciferase reporter genes driven by various regions of the mcl-1 promoter demonstrated that the upstream sequence between -197 and -69 is responsible for cytokine activation of the mcl-1 gene. Overexpression of mcl-1 delayed but did not completely prevent apoptosis of cells triggered by cytokine withdrawal. Its down regulation by antisense constructs overcame, at least partially, the survival activity of GM-CSF and induced the apoptosis of TF-1 cells. Taken together, these results suggest that mcl-1 is an immediate-early gene activated by the cytokine receptor signaling pathway and is one component of the GM-CSF viability response.

An attenuated Salmonella oral DNA vaccine prevents the growth of hepatocellular carcinoma and colon cancer that express alpha-fetoprotein.

Antitumor vaccination therapies using attenuated Salmonella typhimurium carrying plasmid DNA encoding tumor-associated antigens are currently under preclinical development. In the present study, we first established a useful method to facilitate in vivo monitoring of attenuated S. typhimurium uptake using a bioluminescent lux gene operon plasmid. Following transformation with the lux gene operon construct, mice were fed with various amounts of attenuated S. typhimurium-lux to monitor in vivo clearance over a period of 24 h. We found that the ingested attenuated S. typhimurium-lux cells were almost cleared out 9 h postfeeding, as judged by a significant decrease in bioluminescence. We further examined the therapeutic efficacy of vaccination using attenuated S. typhimurium carrying the mouse alpha-fetoprotein (AFP) gene against a cancer line CT26-murine alpha-feto protein (mAFP) that stably expresses AFP and mouse hepatocellular carcinoma (HCC) Hepa1-6. Attenuated S. typhimurium oral DNA vaccine was found to promote protective immunity against both CT26-mAFP and Hepa1-6 tumor cells growth. The oral DNA vaccine significantly increased the life span of tumor-challenged mice in both tumor models. Together, these results suggest that vaccination with the attenuated S. typhimurium oral DNA vaccine that carries the AFP gene could be a promising strategy to prevent HCC development.

In vitro apoptosis in the human hepatoma cell line induced by transforming growth factor beta 1.

The effect of transforming growth factor beta 1 (TGF-beta 1) on human hepatoma cells (Hep 3B) was studied. Cell death was observed when the serum starved Hep 3B cells were exposed to a very low concentration of TGF-beta 1. The half-maximal cytocidal concentration of TGF-beta 1 was around 20 pM. Cell death began approximately 24 h following treatment, with more than 80% of the cells dying after 48 h. In contrast, the control cells, which were cultured in serum-free condition, still gradually proliferated. Furthermore, the cytocidal effect of TGF-beta 1 on Hep 3B cells was not altered by either cycloheximide or actinomycin D. It was discovered, using diphenylamine assay, that TGF-beta 1 induced DNA fragmentation in Hep 3B cells. Using gel electrophoresis, the fragmented DNA could be displayed, and showed a characteristic stepladder pattern. Thus, it appeared that TGF-beta 1 induced a particular pathway in Hep 3B cells in which de novo protein synthesis was not actively involved, but endogenous nuclease was activated which cleaves cellular DNA and induces cell death.

Overexpression of epidermal growth factor and insulin-like growth factor-I receptors and autocrine stimulation in human esophageal carcinoma cells.

The growth-stimulatory effects of epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and insulin-like growth factor-I (IGF-I) on the human esophageal carcinoma cell line CE48T/VGH were evaluated. Under serum-free conditions, EGF, TGF-alpha, and IGF-I promoted 3.6- to 4.1-fold increased cell proliferation. Scatchard analyses and Northern blot hybridization revealed that both the EGF/TGF-alpha receptor and the IGF-I receptor were overexpressed in CE48T/VGH cells. Furthermore, ligand-dependent autophosphorylation of the EGF receptor and the IGF-I receptor was clearly detected using antireceptor and antiphosphotyrosine antibodies. Autocrine regulation was strongly indicated by the following evidence: (a) CE48T/VGH cells were found to express TGF-alpha and IGF-I genes, (b) serum-free conditioned medium promoted the growth of CE48T/VGH cells and stimulated the autophosphorylation of the EGF/TGF-alpha receptor and the IGF-I receptor, and (c) the addition of IGF-I receptor antibodies significantly suppressed CE48T/VGH cell growth under serum-free conditions. Our studies suggest that the overexpression of EGF and IGF-I receptors and autocrine growth regulation may concertedly control the proliferation of esophageal carcinoma cells.

Transcripts of the insulin-like growth factors I and II in human hepatoma.

Using complementary DNAs of human insulin-like growth factors as probes, expressions of the insulin-like growth factors I and II mRNA were examined in seven human hepatoma tissues and their adjacent nontumorous livers. The level of insulin-like growth factor I mRNA in hepatoma was lower than that in the nontumorous liver control. This phenomenon was probably caused by the low expression of human growth hormone receptor in hepatoma tissues. The levels of insulin-like growth factor II mRNA vary among hepatomas. Some show elevated expression; some have diminished expression compared to their nontumorous liver counterparts. In four of the seven hepatomas, expression of fetal forms of insulin-like growth factor II transcripts was observed and may represent dedifferentiation of insulin-like growth factor II expression during hepatocarcinogenesis.

Systematic review with meta-analysis: the efficacy of levofloxacin triple therapy as the first- or second-line treatments of Helicobacter pylori infection.

BACKGROUND: Levofloxacin triple therapy has been used for the first-line and second-line treatment of Helicobacter pylori infection for more than 10 years. AIMS: To systematically review the efficacy of levofloxacin triple therapy in the first- and second-line treatment, and to assess the time trend and factors that might affect its efficacy. METHODS: Prospective trials reporting the efficacy of levofloxacin triple therapy in either the first-line or second-line treatment of H. pylori infection in adults were searched from the PubMed and Cochrane database from January 2000 to September 2015. Meta-analysis was performed to calculate the cumulative eradication rate and the efficacies in subgroups. RESULTS: Of the 322 articles identified, a total of 4574 patients from 41 trials, including 16 trials in the first-line treatment and 25 trials in the second-line treatment were eligible for analysis. The cumulative eradication rate was 77.3% (95% confidence intervals, CI: 74.7-79.6) and was 80.7% (95% CI 77.1-83.7) in the first-line treatment and 74.5% (95% CI: 70.9-77.8) in the second-line treatment. The efficacies of levofloxacin triple therapy before 2008, between 2009 and 2011, and after 2012 were 77.4%, 79.6% and 74.8% respectively. The eradication rate was higher when levofloxacin was given once daily (80.6%, 95% CI: 77.1-83.7) than twice daily (73.6%, 95% CI: 69.7-77.2). The efficacy was significantly higher in levofloxacin-susceptible strains than resistant strains (81.1% vs. 36.3%, risk ratio 2.18, 95% CI: 1.6-3, P < 0.001). CONCLUSION: The efficacy of levofloxacin triple therapy has been lower than 80% in many countries and it is not recommended when the levofloxacin resistance is higher than 5-10%.

Cloning and characterization of a novel human ninein protein that interacts with the glycogen synthase kinase 3beta.

Using human glycogen synthase kinase 3beta (GSK-3beta) as bait in the yeast two-hybrid system, we identified a novel human centrosome associated protein, hNinein. When the full length cDNA of hNinein was sequenced, it showed that an open reading frame encoded a protein consisting of 2047 amino acids with a predicted molecular mass of 239 kDa. The features of this protein include a potential GTP binding site, a large coiled-coil domain together with four leucine zipper domains and a GSK-3beta binding site. Fluorescence microscopy experiment showed that hNinein is localized in the pericentriolar matrix of the centrosome. In addition, hNinein also showed to react with centrosomal autoantibody sera. Our findings suggest that hNinein may be involved in the formation of centrosome matrix and interacts with the GSK-3beta, implying that it may also be regulated by GSK-3beta phosphorylation signaling.

Genomic structure of carp mitogen-activated protein kinase kinase 1 gene.

Carp mitogen-activated protein kinase kinase 1 (cMKK1) gene was isolated from a liver genomic library. The sequence around the exon-intron boundaries and 2 kb of the promoter region were determined. Our data indicate that this gene is composed of 11 exons and 10 introns spanning about 9 kb. Multiple potential transcription initiation sites were located by primer extension analysis. Examination of 2 kb of 5'-flanking sequence revealed potential binding sites for a variety of transcription factors such as E2F, Ets-1, GATA-1, Myb, NF-IL6, Sp1, and NF-kB.

Genomic organization and characterization of the promoter region of the round-spotted pufferfish (Tetraodon fluviatilis) JAK1 kinase gene.

Seventeen kilobases of genomic DNA containing the promoter and the coding region of the round-spotted pufferfish JAK1 gene was isolated and completely sequenced. This gene consists of 25 exons and 24 introns spanning about 13.5 kb, compared to > 30kb in carp JAK1 gene. Primer extension analysis revealed one transcription initiation site which was 376 bp upstream of the translation initiation site. The sequence of the 2.9 kb region upstream of the transcription initiation site contains numerous potential binding sites for transcription factors including HNF-5, GCF, Sp1, CRE, AP2, GATA, GAGA, E2A, p53, and NF-IL6. When this region was placed upstream of the chloramphenicol acetyltransferase (CAT) reporter gene and transfected into a carp CF cell line, it could drive the synthesis of CAT enzyme three times more efficiently than could the common carp JAK1 promoter.