Vaping Transitions and Incident Depressive Symptoms among Young Adults: A Marginal Structural Model Analysis.

The extent to which vaping influences depression is unclear, but could be estimated through application of novel epidemiologic methods. Among a prospective cohort of young adults from California who screened negative for depression, we estimated repeated measures marginal structural models to examine the association of four vaping transitions from time T to T+1 (persistent use, discontinuation, initiation, persistent nonuse) with risk of clinically significant depressive symptoms at T+1, simultaneously across three ~1.5 year time-intervals between 2017-2021. Stabilized inverse probability of treatment and censoring weights adjusted for time-dependent confounders and selection bias. Among n=3,496 observations (1,806 participants, mean pooled baseline age=19.5), 8.1% reported persistent vaping from T to T+1, 6.2% reported discontinuation (i.e., use at T and no use at T+1), 6.5% initiated e-cigarettes (i.e., no use at T and use at T+1), and 79.2% reported persistent nonuse at both time-points. Compared to persistent vaping at two waves, persistent nonuse (RR=0.76, 95%CI:0.62-0.93) and discontinuation (RR=0.71, 95%CI:0.52-0.96) were associated with lower risk of depression. Associations were robust to sensitivity analyses, including restricting to tobacco naïve participants and varying temporal assumptions to reduce potential for reverse causation. Young adults who consistently avoid or discontinue vaping may be protected from depressive symptom occurrence.

Longitudinal Transitions Between Use of Combustible, Noncombustible, and Multiple Cannabis Products From Adolescence to Young Adulthood and Intersections With Nicotine Use.

Understanding transitions across use of different types of cannabis products and multiple cannabis products and how they intersect with nicotine use in young people can inform etiology and prevention. In this study, we examined transitions across use of combustible and noncombustible forms of cannabis and multiple types of cannabis from adolescence to young adulthood and the role of nicotine use in transitions. In a Southern California longitudinal cohort study (n = 3,298; baseline mean age = 16.1 (standard deviation, 0.4) years) with 9 semiannual survey waves (2015-2021), we used Markov multistate transition modeling to estimate short-term (2-wave) and long-term (9-wave) probabilities of transition across 5 cannabis use states: never use of any product, prior use with no past-6-month (P6M) use of any product, and P6M use of exclusively noncombustible products, exclusively combustible products, and multiple (noncombustible + combustible) products. Sizable transition probabilities from prior and exclusive P6M noncombustible or combustible cannabis use to P6M poly-cannabis-product use were observed in short-term (10.7%-38.9%) and long-term (43.4%-43.8%) analyses. P6M nicotine use increased risk of transitioning from never and prior use to exclusive P6M noncombustible and combustible cannabis use. Cannabis use in any form, even temporary use, during midadolescence may often be followed by poly-cannabis-product use. Nicotine use may amplify the probability of future cannabis use onset or recurrence.

Parenting practices, mental health, and electronic cigarette use among U.S. young adolescents: A longitudinal panel analysis, 2013-2018.

PURPOSE: This study examined prospective association of parenting practices related to tobacco use with adolescent e-cigarette use and the moderating role of mental health among U.S. young adolescents. METHODS: We study used multi-wave longitudinal data (2013-2018) drawn from the Population Assessment of Tobacco and Health Study. A total of 5114 young adolescents (12-14 years) who were not lost to follow-ups across four waves (Wave 1-4) comprised the study sample. Weighted logistic regression models along with generalized linear mixed modeling assessed the within-subject associations of parenting practices related to tobacco use (tobacco availability at parent/guardian's home, past-year parent talk about tobacco use, and rules about non-combustible tobacco use at home) with adolescent current e-cigarette use. RESULTS: Prevalence of having home rules about non-combustible tobacco use increased (74.5%-80.2%) and that of parent talk about tobacco use decreased (52.0%-33.9%) over time while tobacco availability at home did not show a specific trend. Tobacco availability at home was associated with increased odds of adolescent e-cigarette use (adjusted odd ratio[OR] = 2.25, 95% confidence interval[CI] = 1.72-2.95), and having home rules about non-combustible tobacco use was linked to decreased likelihood of e-cigarette use (adjusted OR = 0.72, 95% CI = 0.55-0.92). The magnitude of negative association between having rules about non-combustible tobacco and adolescent e-cigarette use was stronger among adolescents with internalizing problems but weaker among those with externalizing problems. CONCLUSIONS: Our findings highlight the important role of home-based interventions in discouraging young adolescents from e-cigarette use. Parents/guardians should consider adolescents' mental health to provide more efficient home- and/or clinical-based e-cigarette use prevention.

Association of over the counter "hangover remedy" use with alcohol use problems and consumption patterns among young adults.

This cross-sectional study of young adults examined associations of hangover remedy use with alcohol use problems. Results suggest that ever-use of hangover remedy products was positively associated with alcohol use problem score, drinks per typical drinking day, and alcohol use disorder symptom count. Use of hangover remedies among young adults merits further scientific and regulatory attention.

Prevalence of and disparities in adolescents' susceptibility to novel oral nicotine products marketed as "tobacco-free".

Non-therapeutic, novel oral nicotine products are convenient, discreet to use, and flavored, with increasing sales in the United States. It is unclear whether these products appeal predominantly to adolescents already susceptible to inhalable nicotine products, or whether they attract adolescents who would not otherwise use nicotine. This study examined prevalence and correlates of susceptibility to inhalable and oral nicotine product use among adolescents. Ninth- and tenth-grade students from Southern California who had never used any nicotine product (N = 3129) completed an online survey in Fall 2021 assessing susceptibility to inhalable (i.e., cigarettes, e-cigarettes) and oral (e.g., pouches, gum, gummies) nicotine products. Multinomial logistic regression analyses estimated associations of demographic characteristics with odds of susceptibility to oral, inhalable, or both products. Susceptibility was highest for e-cigarettes (19.7%), followed by cigarettes (15.0%) and nicotine gum, lozenges, tablets and/or gummies (15.0%), and nicotine pouches (8.7%). Dual susceptibility to oral and inhalable products (vs. neither product type) was higher in cisgender female and non-cisgender (vs. cisgender male) adolescents (odds ratios [ORs] = 1.36-2.02; ps < 0.05). Hispanic adolescents (vs. Asian) were more susceptible to both products (OR = 1.47; p < .05). Lower-socioeconomic status (SES) and sexual minority adolescents were more susceptible to oral (ORs = 1.76-1.87; ps < 0.05) and both products (ORs = 1.32-1.88; ps < 0.05), compared to higher-SES and heterosexual adolescents. Adolescents in Southern California may be more susceptible to e-cigarettes than other nicotine/tobacco products. However, appreciable numbers may be susceptible to oral nicotine products, including some youth who might not otherwise use nicotine and youth from populations historically impacted by tobacco-related health disparities.

Statewide vaping product excise tax policy and use of electronic nicotine delivery systems among US young adults, 2014-2019.

OBJECTIVES: An increasing number of US states have required a tax on electronic nicotine delivery systems (ENDS) in the past few years. This study evaluated the effect of statewide vaping product excise tax policy on ENDS use among young adults. METHODS: We used the two recent waves (2014-2019) of the Tobacco Use Supplement to the Current Population Survey. A total of 17 896 US young adults were analysed. Difference-in-differences approach along with weighted multilevel logistic regressions was used to evaluate the association of vaping product excise tax policy adoption with current ENDS use, accounting for the clustering of respondents within the same states. RESULTS: There was an increase in current ENDS use prevalence from 2014-2015 (3.4%) to 2018-2019 (5.4%). Respondents living in states with vaping product excise tax policy showed significantly lower increase in ENDS use prevalence during the study period (interaction between within-state changes and between-state differences: adjusted OR (AOR)=0.57, 95% CI=0.35 to 0.91), controlling for other state-level policies and sociodemographic characteristics. Additional stratified analysis with state-fixed effects by vaping product excise tax policy implementation status showed consistent findings. CONCLUSIONS: Our findings suggest that adopting a vaping product excise tax policy may help reduce ENDS use and suppress the increase of ENDS use prevalence among young adults. Considering that there are still a number of US states that have not implemented vaping product excise tax policy, wider adoption of such policy across the nation would likely help mitigate ENDS use prevalence.

Dose-response effects of two nicotine salt formulations on electronic cigarette appeal and sensory attributes.

OBJECTIVES: Various organic acids are used to create nicotine salt formulations, which may improve the appeal and sensory experience of vaping electronic cigarettes (e-cigarettes). This clinical experiment examined the effects of partially and highly protonated forms of two nicotine salt formulations (nicotine lactate and benzoate) versus free-base (no acid additive) on the appeal and sensory attributes of e-cigarettes. METHODS: Current adult tobacco product users (n=116) participated in an online remote double-blind within-subject randomised experiment involving standardised self-administration of e-cigarette solutions varying in nicotine formulation (free-base, 50% nicotine lactate -1:2 lactic acid to nicotine molar ratio, 100% nicotine lactate - 1:1 ratio, 50% nicotine benzoate and 100% nicotine benzoate). Each formulation had equivalent nicotine concentrations (27.0-33.0 mg/mL) and was administered in four flavours in a pod-style device. After each administration, participants rated appeal (liking, disliking and willingness to use again) and sensory attributes (0-100 scale). RESULTS: Compared with free-base nicotine, 50% and 100% nicotine lactate and benzoate yielded higher appeal, smoothness and sweetness and lower harshness and bitterness. Dose-response analyses found 100% vs 50% nicotine salt improved appeal, smoothness, bitterness and harshness for nicotine lactate and sweetness, smoothness and harshness for nicotine benzoate. Solutions with higher pH were associated with worse appeal and sensory attributes across nicotine formulations. Nicotine formulation effects did not differ by tobacco use status and flavours. CONCLUSION: Restricting benzoic acid or lactic acid additives or setting minimal pHs in e-cigarettes merits consideration in regulations designed to reduce vaping among populations deterred from using e-cigarettes with aversive sensory properties. TRIAL REGISTRATION NUMBER: This study was registered under ClinicalTrials.gov Identifier: NCT03742817 under the title 'Effects of e-Cigarettes on Perceptions and Behavior'.

Dendritic cell expression of the signaling molecule TRAF6 is critical for gut microbiota-dependent immune tolerance.

The intracellular signaling molecule TRAF6 is critical for Toll-like receptor (TLR)-mediated activation of dendritic cells (DCs). We now report that DC-specific deletion of TRAF6 (TRAF6ΔDC) resulted, unexpectedly, in loss of mucosal tolerance, characterized by spontaneous development of T helper 2 (Th2) cells in the lamina propria and eosinophilic enteritis and fibrosis in the small intestine. Loss of tolerance required the presence of gut commensal microbiota but was independent of DC-expressed MyD88. Further, TRAF6ΔDC mice exhibited decreased regulatory T (Treg) cell numbers in the small intestine and diminished induction of iTreg cells in response to model antigen. Evidence suggested that this defect was associated with diminished DC expression of interleukin-2 (IL-2). Finally, we demonstrate that aberrant Th2 cell-associated responses in TRAF6ΔDC mice could be mitigated via restoration of Treg cell activity. Collectively, our findings reveal a role for TRAF6 in directing DC maintenance of intestinal immune tolerance through balanced induction of Treg versus Th2 cell immunity.

Within-Person Longitudinal Associations Between Electronic Nicotine Delivery Systems Use and Smoking Cessation Efforts Among US Continuing Adult Cigarette Smokers.

OBJECTIVES: Prior studies that examined the role of electronic nicotine delivery systems (ENDS) use in smoking cessation have shown divergent conclusions. This study examined the time-course of ENDS-associated smoking abstinent behaviors among continuing cigarette smokers who were willing but unable to quit smoking. METHODS: Data were drawn from the four waves of the Population Assessment of Tobacco and Health Study. Of the 1684 smokers who tried to quit smoking completely at Wave 1, a total of 1094 who were continuing smokers until Wave 4 and were not lost to follow-ups comprised the sample. Using generalized linear mixed modeling, we fitted weighted negative binomial regression models to examine within-person associations of ENDS use with quit attempts and number of days abstinent from smoking. RESULTS: Quit attempt frequency and smoking abstinent days were highest at Wave 1, dropped at Wave 2, and then either increased a little or remained stagnant in later waves. ENDS use to quit smoking was associated with more frequent quit attempts (aIRR = 1.67, 95% CI = 1.42-1.95) and more abstinent days (aIRR = 3.28, 95% CI = 2.43-4.44), and the magnitude of such associations became stronger over time. ENDS use was associated with becoming a nondaily smoker among baseline daily smokers. CONCLUSIONS: ENDS use among continuing smokers may help increase the number of quit attempts and smoking abstinent days. Given that the study sample is continuing smokers who failed in complete smoking cessation, future research would be desirable that evaluates whether such abstinent behaviors sustain and manifest harm reduction with improved health outcomes. IMPLICATIONS: Smokers increasingly adopt electronic nicotine delivery systems (ENDS) to quit smoking. However, the association of ENDS use with smoking cessation efforts among continuing cigarette smokers who were willing but unable to quit smoking is largely unknown. This study found that quit attempts and smoking abstinent days increased with ENDS use to quit smoking by following up with population-representative continuing smokers. Additionally, this study assessed whether cigarette smokers' abstinent behaviors vary with their use of ENDS by estimating within-person associations with frequent assessments of both exposures and outcomes in a long-term perspective.

Benzotriazole-Based Nonfused Ring Acceptors for Efficient and Thermally Stable Organic Solar Cells.

Nonfused ring acceptors (NFRAs) have attracted significant attention for nonfullerene organic solar cells (OSCs) owing to their chemical tunability and facile synthesis. In this study, a benzotriazole-based NFRA with chlorinated end groups (Triazole-4Cl) is developed to realize highly efficient and thermally stable NFRA-based OSCs; an analogous NFRA with nonchlorinated end groups (Triazole-H) is synthesized for comparison. Triazole-4Cl film exhibits the high-order packing structure and the near-infrared absorption capability, which are advantageous in charge transport and light harvesting of the resulting OSCs. In particular, the strong crystalline behavior of Triazole-4Cl results in enhanced self-aggregation, leading to high charge carrier mobility. Owing to these properties, a PBDB-T (polymer donor):Triazole-4Cl OSC demonstrates a high short-circuit current, fill factor, and power conversion efficiency (PCE = 10.46%), outperforming a PBDB-T:Triazole-H OSC (PCE = 7.65%). In addition, the thermal stability of a PBDB-T:Triazole-4Cl OSC at an elevated temperature of 120 °C exceeds that of a PBDB-T:Triazole-H OSC. This is mainly attributed to the significantly higher cold crystallization temperature of Triazole-4Cl (205.9 °C). This work provides useful guidelines for the design of NFRAs to achieve efficient and thermally stable NFRA-based OSCs.

Unregulated antigen-presenting cell activation by T cells breaks self tolerance.

T cells proliferate vigorously following acute depletion of CD4+ Foxp3+ T regulatory cells [natural Tregs (nTregs)] and also when naive T cells are transferred to syngeneic, nTreg-deficient Rag1-/- hosts. Here, using mice raised in an antigen-free (AF) environment, we show that proliferation in these two situations is directed to self ligands rather than food or commensal antigens. In both situations, the absence of nTregs elevates B7 expression on host dendritic cells (DCs) and enables a small subset of naive CD4 T cells with high self affinity to respond overtly to host DCs: bidirectional T/DC interaction ensues, leading to progressive DC activation and reciprocal strong proliferation of T cells accompanied by peripheral Treg (pTreg) formation. Likewise, high-affinity CD4 T cells proliferate vigorously and form pTregs when cultured with autologous DCs in vitro in the absence of nTregs: this anti-self response is MHCII/peptide dependent and elicited by the raised level of B7 on cultured DCs. The data support a model in which self tolerance is imposed via modulation of CD28 signaling and explains the pathological effects of superagonistic CD28 antibodies.

Identifying emerging predictors for adolescent electronic nicotine delivery systems use: A machine learning analysis of the Population Assessment of Tobacco and Health Study.

Intervention strategies to prevent adolescents from using electronic nicotine delivery systems (ENDS) should be based on robust predictors of ENDS use that may differ from predictors of conventional cigarette use. Literature points to the need for uncovering emerging predictors of ENDS use. This study identified emerging predictors of adolescent ENDS use using machine learning (ML) techniques. We analyzed nationally representative multi-wave longitudinal survey data (2013-2018) drawn from the Population Assessment of Tobacco and Health Study. A sample of adolescents (12-17 years) who never used any tobacco products at baseline and completed Wave 2 (n = 7958), Wave 3 (n = 6260) and Wave 4 (n = 4544) were analyzed. We developed a supervised ML prediction model using the penalized logistic regression to assess self-reported past-month ENDS use (i.e., current use) at Waves 2-4 based on the variables measured at the previous wave. We then extracted important predictors from each model. The penalized logistic regression models showed suitable capability to discriminate between ENDS uses and non-uses at each wave based on the area under the receiver operating characteristic curve and the area under the precision-recall curve. Interestingly, social media use emerged as an important variable in predicting adolescent ENDS use. ML models appear to be a promising method to identify unique population-level predictors for U.S. adolescent ENDS use behaviors. More research is warranted to investigate emerging predictors of ENDS use and experimentally examine the mechanism by which these emerging predictors affect ENDS use behavior across different spectrum of populations.

Using machine learning to predict opioid misuse among U.S. adolescents.

This study evaluated prediction performance of three different machine learning (ML) techniques in predicting opioid misuse among U.S. adolescents. Data were drawn from the 2015-2017 National Survey on Drug Use and Health (N = 41,579 adolescents, ages 12-17 years) and analyzed in 2019. Prediction models were developed using three ML algorithms, including artificial neural networks, distributed random forest, and gradient boosting machine. The performance of the ML prediction models was compared with performance of the penalized logistic regression. The area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC) were used as metrics of prediction performance. We used the AUPRC as the primary measure of prediction performance given that it is considered more informative for assessing binary classifiers on imbalanced outcome variable than AUROC. The overall rate of opioid misuse among U.S. adolescents was 3.7% (n = 1521). Prediction performance was similar across the four models (AUROC values range from 0.809 to 0.815). In terms of the AUPRC, the distributed random forest showed the best performance in prediction (0.172) followed by penalized logistic regression (0.162), gradient boosting machine (0.160), and artificial neural networks (0.157). Findings suggest that machine learning techniques can be a promising technique especially in the prediction of outcomes with rare cases (i.e., when the binary outcome variable is heavily lopsided) such as adolescent opioid misuse.

Predicting opioid misuse at the population level is different from identifying opioid misuse in individual patients.

Tumin and Bhalla mentioned challenges associated with the use of population-based survey and machine learning (ML) results on adolescent opioid misuse to clinical settings. In a clinical setting, medical providers do know patient's identity. So, it is not surprising that drug misuse is rarely identified through patient's self-report especially if it involves illicit drug. Even though self-report is susceptible to bias, it is a valid and affordable tool to gather data on illicit drug use at the population level. Use of audio computer-assisted self-interviewing (ACASI) and computer-assisted personal interviewing (CAPI) in NSDUH provides the respondent with a highly private and confidential mode for responding to questions, which helps increase the level of honest reporting of illicit drug use and other sensitive behaviors. As acknowledged in the paper, opioid misuse should not be inferred at the individual level from our ML models. Such interpretations may lead to ecological fallacy. Predicting opioid misuse at the population level is different from identifying opioid misuse in individual patients. Nonetheless, we believe that coordinated multisectoral collaborations that leverage the expertise and resources of both public health and clinical sectors would offer a promising model for addressing the opioid crisis.

Decreased Neuron Number and Synaptic Plasticity in SIRT3-Knockout Mice with Poor Remote Memory.

The sirtuin family of proteins consists of nicotinamide adenine dinucleotide-dependent deacetylases that are involved in the response to calorie restriction and various physiological phenomena, such as aging and cognition. One of these proteins, sirtuin 3 (SIRT3), is localized in the mitochondria and protects the cell against oxidative or metabolic stress. Sirtuin protein deficiencies have been shown to accelerate neurodegeneration in neurotoxic conditions. The mechanisms underlying the involvement of SIRT3 in cognition remain unclear. Interestingly, SIRT1, another member of the sirtuin family, has been reported to modulate synaptic plasticity and memory formation. To learn more about these proteins, we examined the behavior and cognitive functions of Sirt3-knockout mice. The mice exhibited poor remote memory. Consistent with this, long-term potentiation was impaired in the Sirt3-knockout mice, and they exhibited decreased neuronal number in the anterior cingulate cortex, which seemed to contribute to their memory deficiencies.

Transcription-independent expression of PKMζ in the anterior cingulate cortex contributes to chronically maintained neuropathic pain.

Protein kinase M ζ is well known for its role in maintaining memory and pain. Previously, we revealed that the activation of protein kinase M ζ in the anterior cingulate cortex plays a role in sustaining neuropathic pain. However, the mechanism by which protein kinase M ζ is expressed in the anterior cingulate cortex by peripheral nerve injury, and whether blocking of protein kinase M ζ using its inhibitor, zeta inhibitory peptide, produces analgesic effects in neuropathic pain maintained chronically after injury, have not previously been resolved. In this study, we show that protein kinase M ζ expression in the anterior cingulate cortex is enhanced by peripheral nerve injury in a transcription-independent manner. We also reveal that the inhibition of protein kinase M ζ through zeta inhibitory peptide treatment is enough to reduce mechanical allodynia responses in mice with one-month-old nerve injuries. However, the zeta inhibitory peptide treatment was only effective for a limited time.

Dendritic cell expression of the signaling molecule TRAF6 is required for immune tolerance in the lung.

Immune tolerance in the lung is important for preventing hypersensitivity, such as allergic asthma. Maintenance of tolerance in the lung is established by coordinated activities of poorly understood cellular and molecular mechanisms, including participation of dendritic cells (DCs). We have previously identified DC expression of the signaling molecule TRAF6 as a non-redundant requirement for the maintenance of immune tolerance in the small intestine of mice. Because mucosal tissues share similarities in how they interact with exogenous antigens, we examined the role of DC-expressed TRAF6 in the lung. As with the intestine, we found that the absence TRAF6 expression by DCs led to spontaneous generation of Th2-associated immune responses and increased susceptibility to model antigen-induced asthma. To examine the role of commensal microbiota, mice deficient in TRAF6 in DCs were treated with broad-spectrum antibiotics and/or re-derived on a germ-free (GF) background. Interestingly, we found that antibiotics-treated specific pathogen-free, but not GF, mice showed restored immune tolerance in the absence of DC-expressed TRAF6. We further found that antibiotics mediate microbiota-independent effects on lung T cells to promote immune tolerance in the lung. This work provides both a novel tool for studying immune tolerance in the lung and an advance in our conceptual understanding of potentially common molecular mechanisms of immune tolerance in both the intestine and the lung.

An Ultrahigh Mobility in Isomorphic Fluorobenzo[c][1,2,5]thiadiazole-Based Polymers.

To understand the effects rendered on the relevant basic physical properties and device function by controlling the regiochemistry of the cyclopenta[1,2-b:5,4-b']dithiophene-fluorobenzo[c][1,2,5]thiadiazole polymer (hereafter referred to as the CDT-FBT polymer), two polymers, the regiorandom polymer (RA) and regioregular version (RR), respectively, are synthesized and characterized. In addition, an efficient route for synthesizing a key monomer for RR using various synthesis scope and optimizing the reaction conditions is discussed. Although RA exhibits optical, electrochemical, and morphological properties similar to RR, it shows better field-effect transistor (FET) performance. Surprisingly, by employing a capillarity-mediated sandwich-casting process on a nanogrooved substrate, an unprecedented mobility of 17.8 cm2 V-1 s-1 is obtained for RA-based FETs; this mobility value is almost twofold greater than those of the corresponding RR-based FETs. For the first time, this study challenges previously reported results in that high carrier mobility is related to the high degree of polymer order induced by the backbone regioregularity.

The anti-aging properties of a human placental hydrolysate combined with dieckol isolated from Ecklonia cava.

BACKGROUNDS: In the present study, we aimed to examine the anti-aging properties of human placental hydrolysate (HPE) and dieckol (DE) from Ecklonia cava against free radical scavenging, muscle hypertrophy-related follistatin mRNA expression, amelioration of cognition-related genes and proteins, inhibition of collagenase-regulating genes, and elastinase activity. METHODS: The anti-aging effects were examined in human fibroblast (CCD986sk), mouse myoblast (C2C12), and neuroblastoma (N2a) cell models, by employing various assays such as 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH) scavenging, hydroxyl radical-mediated oxidation, quantitative real-time polymerase chain reaction, enzyme activity, and immunocytochemistry observation. RESULTS: Our results show that HPE combined with DE (HPE:DE) strongly scavenged DPPH radicals and protected proteins against degradation by hydroxyl radical attack. HPE:DE effectively inhibited matrix metalloproteinase-1 expression, protein kinase C alpha expression, and elastinase activity. Furthermore, HPE:DE improved the expression of cognition-related genes (choline acetyltransferase and vesicular acetylcholine transporter). These events may proactively contribute to retard the aging processes and the abrupt physiological changes probably induced by mitochondrial dysfunction with aging. CONCLUSIONS: Based on these findings, we conclude that the combined treatment of HPE:DE may be useful for anti-aging therapy in which the accumulation of oxidative damage is the main driving force.

Continuous high-pressure negative suction drain: new powerful tool for closed wound management: clinical experience.

BACKGROUND: Although various reconstructive flap surgeries have been successfully performed, there still are difficult wound complications, such as seroma formation, wound margin necrosis, delayed wound healing, and even flap failures. The negative-pressure wound therapy has been described in detail in the literature to assist open chronic/complex wound closure in reconstructive surgery. However, the negative-pressure wound therapy was difficult to be applied under the incisional closed wounds. METHODS: A total of 23 patients underwent the various reconstructive flap surgeries with continuous high-pressure negative suction drain. Instead of using regular suction units, Barovac (50-90 mm Hg, Sewoon Medical, Seoul, Republic of Korea) drainage tubes were connected to the wall suction unit, providing continuous high-powered negative pressure. In addition, continuous subatmospheric suction pressure (100-300 mm Hg) was applied. Outcome of the measures was obtained from the incidence of seroma, volume of postoperative drainage, hospitalization period, and incidence of other typical wound complications. Dead space was evaluated postoperatively with ultrasonography. RESULTS: Using continuous high-pressure negative suction drain, successful management of seroma was obtained without any major complication such as wound infection, flap loss, and wound margin necrosis, except for only 1 case of seroma after discharge from the hospital. The indwelling time of the drain in the latissimus dorsi donor site was significantly reduced in comparison with the authors' previous data (P = 0.047). The volume of drainage and hospitalization period were also reduced; however, these were not statistically significant. The dead space with continuous high-pressure negative suction drain was more reduced than in the control group in the immediate postoperative period and confirmed with ultrasonography. CONCLUSIONS: Continuous high-pressure negative suction drain might be the simple and powerful solution in the management of challenging closed wounds.