Effect of Human Amniotic Epithelial Stem Cell Transplantation on Preterm Premature Rupture of Fetal Membrane Using the Amniotic Pore Culture Technique in vitro.

OBJECTIVES: The objective of this study was to evaluate the efficacy of cell therapy using human amniotic epithelial stem cells (hAESCs) for the treatment of premature rupture of membranes (PROM) in vitro. DESIGN: Using the amniotic pore culture technique (APCT), we mimicked the environment of PROM in vitro, thus enabling the observation of the healing process of hAESC-treated amniotic membranes. MATERIALS: Amniotic membrane samples were collected from placentas of pregnant women who underwent elective cesarean sections. APCT model and isolated hAESCs were used in this study. All patients who participated in this study provided their written informed consent prior to the commencement of the study. SETTINGS: To create the APCT model in vitro, isolated amniotic membranes were punched to create 5 mm diameter circles and re-punched to form a 1-mm pore at the center. Membranes were cultured in α-minimal essential medium, and the hAESCs were collected and cultured as well. Subsequently, the APCT models were divided into two groups: hAESC treated and control. METHODS: Within the culture period, pore sizes were calculated to evaluate the degree of tissue regeneration in both groups. We then evaluated the histology, cell density, and epithelial thickness of the regenerated tissues. Statistical analyses were performed using SPSS software ver. 20.0 (IBM, Armonk, NY, USA) with repeated-measures one-way analysis of variance or paired samples t test. The significance level was set at p < 0.05. RESULTS: As per the evaluation of the APCT model in vitro, the pore size in the hAESC-treated group reduced by 62.2% on day 6 (62.2 ± 0.19, n = 24), whereas in the control group, it shrank by only 36.8% (p < 0.05) (36.8 ± 0.19, n = 24). Furthermore, the epithelial thickness in the amniotic epithelial stem cell-treated group (10.08 ± 1.26 µm, n = 8) was significantly higher than that in the control group (5.87 ± 0.94 µm, n = 8). Cell density in the regenerated tissue in the amniotic epithelial stem cell-treated group (57 ± 2.77, n = 8) was significantly higher than that in the control group (49 ± 2.23, n = 8). LIMITATIONS: In this study, we did not explore the molecular mechanisms by which hAESCs participate in membrane healing in the APCT model. Although our results showed a significant difference, this difference was not too obvious. Therefore, further research on the mechanisms of hAESCs is needed, with more amniotic tissues and APCT samples being tested. CONCLUSIONS: We developed an APCT model to investigate the PROM conditions in vitro. By implanting donor hAESCs in the pores of the APCT model, we observed that hAESCs seeding accelerated pore healing in vitro. Thus, hAESCs may be a valuable source of cells for cell therapies in regenerative medicine.

Temporal Dynamics of Transdermal Alcohol Concentration Measured via New-Generation Wrist-Worn Biosensor.

BACKGROUND: The development of a transdermal alcohol biosensor could represent a tremendous advance toward curbing problematic drinking. But several factors limit the usefulness of extant transdermal technology, including relatively lengthy delays between blood alcohol concentration (BAC) and transdermal alcohol concentration (TAC), as well as the large/bulky designs of currently available transdermal sensors (e.g., ankle monitors). The current research examined the lag time between BAC and TAC using a prototype of BACtrack Skyn-a new-generation wrist-worn transdermal sensor featuring a compact design and smartphone integration. METHODS: Participants (N = 30) received either a dose of alcohol (target BAC 0.08%) or a nonalcoholic beverage in the laboratory while wearing both the AMS SCRAM ankle monitor and a Skyn prototype. Participants were monitored in the laboratory until breath alcohol concentration (BrAC) dropped below 0.025%. RESULTS: Device failure rates for Skyn prototypes were relatively high (18 to 38%) compared with nonprototype SCRAM devices (2%). Among participants with usable data, both Skyn- and SCRAM-measured TAC showed strong correlations with BrAC, and both Skyn and SCRAM devices detected alcohol within 30 minutes of first alcohol administration. Skyn-measured TAC peaked over 1 hour earlier than SCRAM-measured TAC (54 versus 120 minutes after peak BrAC, respectively), and time-series models suggested that, on average across all measured portions of the BrAC curve, Skyn TAC lagged behind BrAC by 24 minutes, whereas SCRAM TAC lagged behind BrAC by 69 minutes-all differences statistically significant at p < 0.001. CONCLUSIONS: Results provide preliminary evidence for the validity of a new-generation wrist-worn transdermal sensor under controlled laboratory conditions and further suggest favorable properties of this sensor as they pertain to the latency of transdermal alcohol detection. The prototype version of Skyn employed here displayed a higher failure rate compared with SCRAM, and, in future, more reliable and robust Skyn prototypes will be required suitable to field testing across diverse environmental conditions.

Estimating the Distribution of Random Parameters in a Diffusion Equation Forward Model for a Transdermal Alcohol Biosensor.

We estimate the distribution of random parameters in a distributed parameter model with unbounded input and output for the transdermal transport of ethanol in humans. The model takes the form of a diffusion equation with the input being the blood alcohol concentration and the output being the transdermal alcohol concentration. Our approach is based on the idea of reformulating the underlying dynamical system in such a way that the random parameters are now treated as additional space variables. When the distribution to be estimated is assumed to be defined in terms of a joint density, estimating the distribution is equivalent to estimating the diffusivity in a multi-dimensional diffusion equation and thus well-established finite dimensional approximation schemes, functional analytic based convergence arguments, optimization techniques, and computational methods may all be employed. We use our technique to estimate a bivariate normal distribution based on data for multiple drinking episodes from a single subject.

Comparison between Slow Freezing and Vitrification for Human Ovarian Tissue Cryopreservation and Xenotransplantation.

Two methods for the cryopreservation of human ovarian tissue were compared using a xenotransplantation model to establish a safe and effective cryopreservation method. Ovarian tissues were obtained from women who underwent benign ovarian surgery in the gynecology research unit of a university hospital. The tissues were transplanted into 112 ovariectomized female severe combined immunodeficient mice 4 weeks after slow freezing or vitrification cryopreservation. Tissues were retrieved 4 weeks later. Primordial follicular counts decreased after cryopreservation and xenotransplantation, and were significantly higher in the slow freezing group than in the vitrification group (p < 0.001). Immunohistochemistry and TUNEL assay showed that the Ki-67 and CD31 markers of follicular proliferation and angiogenesis were higher in the slow freezing group (p < 0.001 and p = 0.006, respectively) and DNA damage was greater in the vitrification group (p < 0.001). Western blotting showed that vitrification increased cellular apoptosis. Anti-Müllerian hormone expression was low in transplanted samples subjected to both cryopreservation techniques. Electron microscopy revealed primordial follicle deformation in the vitrification group. Slow freezing for ovarian tissue cryopreservation is superior to vitrification in terms of follicle survival and growth after xenotransplantation. These results will be useful for fertility preservation in female cancer patients.

The Impact of Alcohol and Social Context on the Startle Eyeblink Reflex.

BACKGROUND: Researchers have long sought to understand how individuals respond to alcohol in social settings with the aim of elucidating pathways of risk for alcohol use disorder (AUD). But studies that incorporate a social context are still outnumbered by those that examine alcohol's subjective effects among participants drinking alcohol in isolation. Further, perhaps due to the challenges of capturing automatic affective processes in these settings, prior studies of alcohol response in social context have relied mainly on self-report measures, and so relatively little is known about alcohol's psychophysiological effects in social settings. METHODS: Using a novel paradigm that integrated alcohol-administration procedures, startle methodology, and social context, this study examined the impact of alcohol and social context on startle eyeblink reflex among 40 social drinkers. RESULTS: Results indicated that there was a significant effect of group presence, indicating that startle magnitude was larger when people were alone than with others. There was a significant group presence-by-alcoholic beverage interaction, with the effect of alcohol being significantly larger when people were alone versus with others. These effects were found both for the startle habituation data and during the picture-viewing task. CONCLUSIONS: Results of this study highlight the importance of considering the presence of other individuals for understanding alcohol response and mechanisms of AUD risk. Findings are discussed in light of both emotional and cognitive correlates of startle reflex magnitude. Future research should examine these effects within larger samples of participants and further explore mechanisms that might underlie these effects.

Deconvolving the input to random abstract parabolic systems: a population model-based approach to estimating blood/breath alcohol concentration from transdermal alcohol biosensor data.

The distribution of random parameters in, and the input signal to, a distributed parameter model with unbounded input and output operators for the transdermal transport of ethanol are estimated. The model takes the form of a diffusion equation with the input, which is on the boundary of the domain, being the blood or breath alcohol concentration (BAC/BrAC), and the output, also on the boundary, being the transdermal alcohol concentration (TAC). Our approach is based on the reformulation of the underlying dynamical system in such a way that the random parameters are treated as additional spatial variables. When the distribution to be estimated is assumed to be defined in terms of a joint density, estimating the distribution is equivalent to estimating a functional diffusivity in a multi-dimensional diffusion equation. The resulting system is referred to as a population model, and well-established finite dimensional approximation schemes, functional analytic based convergence arguments, optimization techniques, and computational methods can be used to fit it to population data and to analyze the resulting fit. Once the forward population model has been identified or trained based on a sample from the population, the resulting distribution can then be used to deconvolve the BAC/BrAC input signal from the biosensor observed TAC output signal formulated as either a quadratic programming or linear quadratic tracking problem. In addition, our approach allows for the direct computation of corresponding credible bands without simulation. We use our technique to estimate bivariate normal distributions and deconvolve BAC/BrAC from TAC based on data from a population that consists of multiple drinking episodes from a single subject and a population consisting of single drinking episodes from multiple subjects.

Social anxiety and alcohol consumption: The role of social context.

Research has identified social anxiety as a risk factor for the development of alcohol use disorder. However, studies have produced equivocal findings regarding the relationship between social anxiety and drinking behaviors in authentic drinking environments. This study examined how social-contextual features of real-world drinking contexts might influence the relationship between social anxiety and alcohol consumption in everyday settings. At an initial laboratory visit, heavy social drinkers (N = 48) completed the Liebowitz Social Anxiety Scale. Participants were then outfitted with a transdermal alcohol monitor individually-calibrated for each participant via laboratory alcohol-administration. Over the next seven days, participants wore this transdermal alcohol monitor and responded to random survey prompts (6x/day), during which they provided photographs of their surroundings. Participants then reported on their levels of social familiarity with individuals visible in photographs. Multilevel models indicated a significant interaction between social anxiety and social familiarity in predicting drinking, b = -0.004, p =.003 Specifically, among participants higher in social anxiety, drinking increased as social familiarity decreased b = -0.152, p <.001, whereas among those lower in social anxiety, this relationship was non-significant, b = 0.007, p =.867. Considered alongside prior research, findings suggest that the presence of strangers within a given environment may play a role in the drinking behavior of socially anxious individuals.

The effect of acute alcohol intoxication on alcohol cue salience: An event-related brain potential study.

OBJECTIVE: Alcohol cue salience is considered core to the broader understanding of drinking behaviors. In the present research, we sought to build the knowledge of alcohol cue salience by exploring P3 responses to alcohol images among social drinkers within a large-scale alcohol-administration study. METHOD: Participants (N = 246) were randomly assigned to receive either a moderate dose of alcohol (target BAC = .08%) or a nonalcoholic control beverage. Following beverage administration, participants engaged in image-viewing tasks while EEG was recorded. We examined the impact of alcohol on the amplitude of P3 responses to pictures of alcoholic versus nonalcoholic beverages, exploring both beverage-manipulation and individual-difference moderators of these effects. RESULTS: Results revealed a significant effect of acute alcohol intoxication on P3 responses across stimulus types, with the overall amplitude of P3 being significantly smaller among participants consuming alcohol versus a nonalcoholic beverage. In addition, results revealed a significant main effect of image type, such that P3 amplitude was larger for alcohol images compared to nonalcohol images. No interactions emerged between stimulus type and beverage condition or stimulus type and AUD risk level. CONCLUSIONS: With the aim of better understanding the potential influence of the broader context on responses to individual cues, the present study examined the perceived salience of alcohol cues within a drinking setting. Findings provide evidence for alcohol cue salience that is both robust and also widespread across drinkers. More generally, the present study's findings may offer new directions for understanding neurocognitive processes of alcohol cue salience across contexts. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Alcohol and Neural Dynamics: A Meta-analysis of Acute Alcohol Effects on Event-Related Brain Potentials.

BACKGROUND: An understanding of alcohol's acute neural effects could augment our knowledge of mechanisms underlying alcohol-related cognitive/motor impairment and inform interventions for addiction. Focusing on studies employing event-related brain potential methods, which offer a direct measurement of neural activity in functionally well-characterized brain networks, we present the first meta-analysis to explore acute effects of alcohol on the human brain. METHODS: Databases were searched for randomized laboratory alcohol-administration trials assessing brain activity using event-related potentials. Hedges' g coefficients were pooled using 3-level random-effects meta-regression. RESULTS: Sixty independent randomized controlled trials met inclusion (total N = 2149). Alcohol's effects varied significantly across neural systems, with alcohol leading to reductions in event-related potential components linked with attention (P3b), g = -0.40, 95% CI (-0.50, -0.29), automatic auditory processing (mismatch negativity), g = -0.44, 95% CI (-0.66, -0.22), and performance monitoring (error-related negativity), g = -0.56, 95% CI (-0.79, -0.33). These effects were moderated by alcohol dose, emerging as significant at doses as low as 0.026% blood alcohol concentration and increasing to moderate/large at 0.12%. In contrast, irrespective of dose, relatively small or nonsignificant alcohol effects emerged in other processing domains, including those linked to executive control (N2b responses) and stimulus classification (N2c responses). CONCLUSIONS: Contrary to traditional conceptualizations of alcohol as a "dirty drug" with broad central nervous system depressant effects, results instead support accounts positing targeted alcohol effects in specific processing domains. By identifying alcohol effects on brain systems involved in performance monitoring and attention, results move toward the identification of mechanisms underlying alcohol-related impairment as well as factors reinforcing addiction.

Using machine learning for real-time BAC estimation from a new-generation transdermal biosensor in the laboratory.

BACKGROUND: Transdermal biosensors offer a noninvasive, low-cost technology for the assessment of alcohol consumption with broad potential applications in addiction science. Older-generation transdermal devices feature bulky designs and sparse sampling intervals, limiting potential applications for transdermal technology. Recently a new-generation of transdermal device has become available, featuring smartphone connectivity, compact designs, and rapid sampling. Here we present initial laboratory research examining the validity of a new-generation transdermal sensor prototype. METHODS: Participants were young drinkers administered alcohol (target BAC = .08 %) or no-alcohol in the laboratory. Participants wore transdermal sensors while providing repeated breathalyzer (BrAC) readings. We assessed the association between BrAC (measured BrAC for a specific time point) and eBrAC (BrAC estimated based only on transdermal readings collected in the immediately preceding time interval). Extra-Trees machine learning algorithms, incorporating transdermal time series features as predictors, were used to create eBrAC. RESULTS: Failure rates for the new-generation prototype sensor were high (16 %-34 %). Among participants with useable new-generation sensor data, models demonstrated strong capabilities for separating drinking from non-drinking episodes, and significant (moderate) ability to differentiate BrAC levels within intoxicated participants. Differences between eBrAC and BrAC were 60 % higher for models based on data from old-generation vs new-generation devices. Model comparisons indicated that both time series analysis and machine learning contributed significantly to final model accuracy. CONCLUSIONS: Results provide favorable preliminary evidence for the accuracy of real-time BAC estimates from a new-generation sensor. Future research featuring variable alcohol doses and real-world contexts will be required to further validate these devices.

Spontaneous healing of human amnion in the premature rupture of membrane model.

INTRODUCTION: This study aimed to explore the spontaneous healing of ruptured fetal membranes experimentally in the prelabor rupture of membrane model using the amnion pore culture technique. METHODS: The human amniotic membrane was separated from the post-delivery term placenta in women with normal pregnancies who delivered by scheduled unlabored cesarean section and stained immunohistochemically with primary antibodies against SSEA-4, OCT-3/4, and TRA-1-60. The characteristics of the cultured amniotic epithelial cells were examined by fluorescence-activated cell sorting analysis. Amniotic membranes with perforations that were 1, 2, and 3 mm in diameter were cultured in αMEM containing 10% heat-inactivated FBS, 1% penicillin-streptomycin, and 10 ng/mL EGF at 37 °C in a humidified incubator with 5% CO2. Next, the pore sizes were calculated to evaluate the healing process. RESULTS: The amniotic membrane stained positive for CD49d and pluripotent stem cell markers such as SSEA-4, TRA 1-60, and OCT-4 in the stromal and epithelial cell layers. In the flow cytometry analyses, the extracted amniotic epithelial stem cells were observed to express indicator markers for stem cells such as SSEA-4, OCT-4, SOX-2, and Nanog. In the amnion pore culture technique model, the 1-mm pores healed completely, whereas the 2- and 3-mm pores did not heal substantially. DISCUSSION: The amnion pore culture technique was useful for demonstrating the natural healing process of the human amniotic membrane. Stem cells in the human amnion might facilitate the resealing of small pores in the amniotic membrane, as observed in this model.

A meta-analysis of the effect of substance use interventions on emotion outcomes.

OBJECTIVE: Emotional distress has been posited as a key underlying mechanism in the development and maintenance of substance use disorder (SUD), and patients seeking SUD treatment are often experiencing high levels of negative emotion and/or low levels of positive emotion. But the extent to which SUD interventions impact emotional outcomes among general SUD populations is yet unquantified. The current meta-analysis aims to fill this gap. METHOD: A total of 11,754 records were screened for randomized, controlled trials examining the effect of behavioral SUD interventions on emotion outcomes. Our search yielded a total of 138 effect sizes calculated based on data from 5,146 individuals enrolled in 30 independent clinical trials. Random-effects meta-analysis was used to calculate pooled effect sizes, and metaregression analyses examined study-level moderators (e.g., intervention type). RESULTS: Findings indicated a small but significant effect of SUD interventions on emotion outcomes, d = 0.157, 95% CI [0.052, 0.262] (k = 30). The effect size for negative emotion was nominally bigger, d = 0.162, 95% CI [0.056, 0.269] (k = 30), whereas the effect for positive emotion did not reach statistical significance, d = 0.062, 95% CI [-0.089, 0.213] (k = 7). Studies featuring SUD interventions designed to specifically target emotions (i.e., affect-regulation, mindfulness-based treatments) produced larger reductions in negative emotion compared with studies featuring interventions that did not contain specific emotion modules (e.g., contingency management). CONCLUSIONS: Findings suggest that SUD interventions-especially mindfulness-based and affect-regulation treatments-indeed significantly reduce negative emotion, although relatively small effect sizes indicate potential room for improvement. Conclusions regarding positive emotion should be considered preliminary because of the limited numbers of samples assessing these outcomes. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

A meta-analysis of longitudinal associations between substance use and interpersonal attachment security.

Substance use has long been associated with close relationship distress. Although the direction of influence for this association has not been established, it has often been assumed that substance use is the causal agent and that close relationship distress is the effect. But research seeking to establish temporal precedence in this link has produced mixed findings. Further, theoretical models of substance use and close relationship processes present the plausibility of the inverse pathway-that insecure close relationships may serve as a vulnerability factor for the development of later substance problems. The current review applies an attachment-theoretical framework to the association between close social bonds and substance use and substance-related problems. Targeting longitudinal studies of attachment and substance use, we examined 665 effect sizes drawn from 34 samples (total N = 56,721) spanning time frames ranging from 1 month to 20 years (M = 3.8 years). Results revealed a significant prospective correlation between earlier attachment and later substance use (r = -.11, 95% CI [-.14, -0.08]). Further, cross-lagged coefficients were calculated which parsed auto-regressive effects, indicating that lower attachment security temporally preceded increases in substance use (r = -.05, 95% CI [-.06, -.04]). Analyses further indicated that the pathway from earlier attachment to later substance use was significantly stronger than that from earlier substance use to later attachment. Results also revealed several moderators of the attachment-substance use link. These findings suggest that insecure attachment may be a vulnerability factor for substance use, and indicate close relationship quality as a promising line of inquiry in research on substance use disorder risk. (PsycINFO Database Record

A multimodal investigation of contextual effects on alcohol's emotional rewards.

Regular alcohol consumption in unfamiliar social settings has been linked to problematic drinking. A large body of indirect evidence has accumulated to suggest that alcohol's rewarding emotional effects-both negative-mood relieving and positive-mood enhancing-will be magnified when alcohol is consumed within unfamiliar versus familiar social contexts. But empirical research has never directly examined links between contextual familiarity and alcohol reward. In the current study, we mobilized novel ambulatory technology to examine the effect of social familiarity on alcohol reward in everyday drinking contexts while also examining how alcohol reward observed in these field contexts corresponds to reward observed in the laboratory. Heavy social drinking participants (N = 48, 50% male) engaged in an intensive week of ambulatory assessment. Participants wore transdermal alcohol sensors while they reported on their mood and took photographs of their social contexts in response to random prompts. Participants also attended 2 laboratory beverage-administration sessions, during which their emotional responses were assessed and transdermal sensors were calibrated to estimate breathalyzer readings (eBrACs). Results indicated a significant interaction between social familiarity and alcohol episode in everyday drinking settings, with alcohol enhancing mood to a greater extent in relatively unfamiliar versus familiar social contexts. Findings also indicated that drinking in relatively unfamiliar social settings was associated with higher eBrACs. Finally, results indicated a correspondence between some mood effects of alcohol experienced inside and outside the laboratory. This study presents a novel methodology for examining alcohol reward and indicates social familiarity as a promising direction for research seeking to explain problematic drinking. (PsycINFO Database Record