CT-based radiomics analysis of different machine learning models for differentiating gnathic fibrous dysplasia and ossifying fibroma.

OBJECTIVE: In this study, our aim was to develop and validate the effectiveness of diverse radiomic models for distinguishing between gnathic fibrous dysplasia (FD) and ossifying fibroma (OF) before surgery. MATERIALS AND METHODS: We enrolled 220 patients with confirmed FD or OF. We extracted radiomic features from nonenhanced CT images. Following dimensionality reduction and feature selection, we constructed radiomic models using logistic regression, support vector machine, random forest, light gradient boosting machine, and eXtreme gradient boosting. We then identified the best radiomic model using receiver operating characteristic (ROC) curve analysis. After combining radiomics features with clinical features, we developed a comprehensive model. ROC curve and decision curve analysis (DCA) demonstrated the models' robustness and clinical value. RESULTS: We extracted 1834 radiomic features from CT images, reduced them to eight valuable features, and achieved high predictive efficiency, with area under curves (AUC) exceeding 0.95 for all the models. Ultimately, our combined model, which integrates radiomic and clinical data, displayed superior discriminatory ability (AUC: training cohort 0.970; test cohort 0.967). DCA highlighted its optimal clinical efficacy. CONCLUSION: Our combined model effectively differentiates between FD and OF, offering a noninvasive and efficient approach to clinical decision-making.

The anterior lobe of the parotid gland: a CT sialographic study.

OBJECTIVES: To investigate the imaging and anatomic features of the anterior lobe (AL) of the superficial parotid gland (SPG). METHODS: Computed tomographic sialography examinations were undertaken for 142 parotid glands in 77 patients. Whole computer tomography (CT) data were analyzed using multi-planar reformation and maximum intensity projection to generate sialographic CT images. The tributary ducts of the SPG were analyzed to classify the parotid morphology. Three-dimensional analyses were used to investigate the AL and its relationship with adjacent anatomic landmarks. RESULTS: Four major types (I-IV) and 2 minor types (V-VI) of the AL and the superficial parotid gland were observed. Type I AL (83/142) was contiguous and not separated from the retromandibular parotid gland. Type II AL (16/142) was detached from the retromandibular parotid gland with 1-4 tributary ducts. Type III AL (12/142) showed a small isolated lobe above the Stensen duct around the anterior edge of the masseter. Type IV (28/142) showed the absence of the AL. Type V (3/142) shows the absence of the retromandibular parotid gland. Type VI (3/142) showed the presence of ectopic salivary gland beneath the Stensen duct anterior to the retromandibular parotid gland. CONCLUSIONS: The AL gives rise to the morphological variations of the superficial parotid gland. AL also gives rise to the accessory parotid gland when it is detached from the retromandibular parotid gland.

Prenatal substance exposure, early-life adversity, and parenting: Associations with adolescent stress response.

We tested a conceptual model examining associations between prenatal substance exposure and adolescent cortisol reactivity profiles in response to an acute social evaluative stressor. We included cortisol reactivity in infancy, and direct and interactive effects of early-life adversity and parenting behaviors (sensitivity, harshness) from infancy to early school age on adolescent cortisol reactivity profiles in model testing. Participants were 216 families (51% female children; 116 cocaine-exposed) recruited at birth, oversampled for prenatal substance exposure, and assessed from infancy to early adolescence (EA). Majority of participants self-identified as Black (72% mothers, 57.2% adolescents), and caregivers were primarily from low-income families (76%), were single (86%), and had high school or below education (70%) at recruitment. Latent profile analyses identified three cortisol reactivity patterns including elevated (20.4%), moderate (63.1%), and blunted (16.5%) reactivity groups. Prenatal tobacco exposure was associated with higher likelihood of membership in the elevated reactivity compared to the moderate reactivity group. Higher caregiver sensitivity in early life was associated with lower likelihood of membership in the elevated reactivity group. Prenatal cocaine exposure was associated with higher maternal harshness. Interaction effects among early-life adversity and parenting indicated that caregiver sensitivity buffered, and harshness exacerbated, the likelihood that high early adversity would be associated with the elevated and blunted reactivity groups. Results highlight the potential importance of prenatal alcohol and tobacco exposure for cortisol reactivity and the role of parenting as exacerbating or buffering the impact of early-life adversity on adolescent stress response.

Effects of combined antibiotics on nitrification, bacteria and antibiotic resistance genes in activated sludge: Insights from legacy effect of antibiotics.

The effect of combined antibiotics exposure on nitrogen removal, microbial community assembly and proliferation of antibiotics resistance genes (ARGs) is a hotspot in activated sludge system. However, it is unclear that how the historical antibiotic stress affects the subsequent responses of microbes and ARGs to combined antibiotics. In this study, the effects of combined sulfamethoxazole (SMX) and trimethoprim (TMP) pollution on activated sludge under legacy of SMX or TMP stress with different doses (0.005-30 mg/L) were investigated to clarify antibiotic legacy effects. Nitrification activity was inhibited under higher level of combined exposure but a high total nitrogen removal (∼70%) occurred. Based on the full-scale classification, the legacy effect of past antibiotic stress had a marked effect on community composition of conditionally abundant taxa (CAT) and conditionally rare or abundant taxa (CRAT). Rare taxa (RT) were the keystone taxa in the microbial network, and the responses of hub genera were also affected by the legacy of antibiotic stress. Nitrifying bacteria and genes were inhibited by the antibiotics and aerobic denitrifying bacteria (Pseudomonas, Thaurea and Hydrogenophaga) were enriched under legacy of high dose, as were the key denitrifying genes (napA, nirK and norB). Furthermore, the occurrences and co-selection relationship of 94 ARGs were affected by legacy effect. While, some shared hosts (eg., Citrobacter) and hub ARGs (eg., mdtD, mdtE and acrD) were identified. Overall, antibiotic legacy could affect responses of activated sludge to combined antibiotic and the legacy effect was stronger at higher exposure levels.

Design, synthesis and anti-tumor activity studies of novel pyrido[3, 4-d]pyrimidine derivatives.

In order to find high-efficiency and low-toxic anti-tumor drugs, 29 pyrido[3,4-d]pyrimidine compounds were designed, synthesized and evaluated by MTT assay in vitro. The results presented that most of the compounds had good antitumor activities, among which compound 30 had the best anti-tumor activity on MGC803 cells (IC50 = 0.59 µM). Mechanistic studies exhibited that compound 30 inhibited migration of MGC803 and induced apoptosis. It was proved that compound 30 up-regulated expression of Bid and PARP, down-regulated expression of CycD1 by western blot experiments. This study indicated that compound 30 might be served as a lead agent for the treatment of human gastric cancers.

Heterogeneity in DSM-5 Symptom Criteria: Phenotypes of Alcohol Use Disorder in a Sample Seeking Alcohol Treatment.

AIMS: This study sought to identify phenotypic variations among individuals with alcohol use disorder (AUD) that may, in part, help improve the effectiveness of existing AUD interventions. METHODS: Latent class analysis was conducted to examine the potential heterogeneity of AUD in a sample (N = 220; Mage = 51.19 years, standard deviation = 9.94; 37.7% female) of treatment-seeking participants diagnosed with AUD using DSM-5 criteria. RESULTS AND CONCLUSIONS: Three distinct patterns of responses to the 11 DSM-5 AUD symptoms emerged: Class 1 (n = 114, 51.8%), Class 2 (n = 78, 35.5%) and Class 3 (n = 28, 12.7%). The identified profiles were further differentiated by demographics, alcohol-related constructs, individual difference characteristics and diagnostic and treatment variables. The findings have implications for refining AUD assessment as well as optimizing personalized treatment.

Alexithymia disrupts emotion regulation processes and is associated with greater negative affect and alcohol problems.

OBJECTIVE: Alexithymia is common among people who abuse alcohol, yet the mechanisms by which alexithymia exerts its influence remain unclear. This analysis tested a model whereby the three subscales of the Toronto Alexithymia Scale exert an indirect effect on alcohol problems through difficulties with emotion regulation and psychological distress. METHOD: Men and women (n = 141) seeking alcohol use disorder (AUD) treatment completed the Toronto Alexithymia Scale, the Difficulties with Emotion Regulation Scale, the Brief Symptom Inventory, the Short Inventory of Problems, and the Alcohol Dependence Scale. RESULTS: The Difficulty Identifying Feelings subscale of the Toronto Alexithymia Scale was positively associated with alcohol problems through emotion dysregulation and psychological distress. The other two subscales, Difficulty Describing Feelings and Externally oriented Thinking, were not associated with any other variables. CONCLUSION: People with alexithymia may consume alcohol to help regulate undifferentiated states of emotional arousal. Given the prevalence of alexithymia among people who abuse alcohol, treatment supplements that enhance the identification of emotions are needed.

The effect of prenatal adversity on externalizing behaviors at 24 months of age in a high-risk sample: Maternal sensitivity as a moderator.

The purpose of this study was to examine the moderating role of maternal sensitivity on the association between prenatal adversity and externalizing behaviors at 24 months of age in a diverse, high-risk sample. We hypothesized that among children with higher prenatal adversity, high maternal sensitivity would serve as a protective factor. Participants were 247 primarily low-income, diverse dyads. Results indicated a significant interaction effect of maternal sensitivity and prenatal adversity on externalizing problems. The association between prenatal adversity and externalizing behaviors was significant only among children who experienced low prenatal adversity, with higher maternal sensitivity associated with lower externalizing behaviors. These findings indicate that, in the absence of high prenatal risk, responsive and sensitive parenting can buffer children in an otherwise high-risk sample from the development of externalizing behaviors.

El propósito de este estudio fue examinar el papel moderador que la sensibilidad materna tiene sobre la asociación entre adversidad prenatal y las conductas de externalización a los 24 meses de edad en un grupo muestra diverso y de alto riesgo. Nuestra hipótesis es que entre los niños con más alta adversidad prenatal (PA), una alta sensibilidad materna serviría como un factor de protección. Participaron 247 díadas diversas, primariamente de bajos recursos económicos (173 infantes expuestos a sustancias). Los resultados indicaron un significativo efecto de interacción de la sensibilidad materna y la adversidad prenatal sobre los problemas de externalización. La asociación entre la adversidad prenatal y las conductas de externalización fue significativa sólo entre niños que habían experimentado una adversidad prenatal baja, mientras que una más alta sensibilidad materna se asoció con más bajas conductas de externalización. Estos resultados indican que, en ausencia de un riesgo prenatal alto, una crianza receptiva y sensible puede amortiguar el desarrollo de conductas de externalización en niños que, de lo contrario, están dentro de un grupo muestra de alto riesgo.

Le but de cette étude était d'examiner le rôle modérateur de la sensibilité maternelle sur l'association entre l'adversité prénatale et les comportements d'externalisation à l'âge de 24 mois chez un échantillon varié, et à haut risque. Nous avons pris comme hypothèse que chez les enfants avec une adversité prénatale élevée (PA), une sensibilité maternelle élevée servirait de facteur de protection. Les participants ont consisté en 247 dyades diverse et principalement issues de milieux défavorisés (173 bébés exposés à la toxicomanie). Les résultats indiquent un effet d'interaction important de la sensibilité maternelle et de l'adversité prénatale sur les problèmes d'externalisation. Le lien entre l'adversité prénatale et les comportements d'externalisation n'était important que chez les enfants ayant fait l'expérience d'une adversité prénatale peu élevée, avec une sensibilité maternelle plus élevée liée à des comportements d'externalisation moins élevés. Ces résultats indiquent que, en l'absence d'une risque prénatal élevé, le parentage réactif et sensible peut servir de tampon aux enfants contre le développement de comportements d'externalisation dans un échantillon qui est par ailleurs à haut risque.

The Identification of Pretreatment Trajectories of Alcohol Use and Their Relationship to Treatment Outcome in Men and Women With Alcohol Use Disorder.

BACKGROUND: Few studies have focused on behavioral changes that occur prior to entering treatment for an alcohol use disorder (AUD). In 2 studies (Psychol Addict Behav, 27, 2013, 1159; J Stud Alcohol, 66, 2005, 369), pretreatment reductions in alcohol use were associated with better treatment outcomes. Identifying patterns of pretreatment change has the potential to inform clinical decision making. METHODS: This study sought to identify pretreatment change trajectories in individuals seeking outpatient treatment for AUD (N = 205) using finite mixture modeling based on changes in number of days abstinent per week (NDA). RESULTS: The analysis identified 3 pretreatment trajectory classes. Class 1 (High Abstinence-Minimal Increase; HA-MI) (n = 64; 31.2%) reported a high level of pretreatment NDA with minimal change during an 8-week pretreatment interval. Class 2 (Low Abstinence-Steady Increase; LA-SI) (n = 73; 35.6%) reported a low level of pretreatment NDA followed by a steady increase beginning 2 weeks prior to the phone screen. Class 3 (Nonabstinent-Accelerated Increase; NA-AI) (n = 68; 33.2%) reported no or very low levels of pretreatment NDA but demonstrated an increase following the phone screen. With regard to within-treatment change, Class 1 demonstrated the least and Class 3 demonstrated the most change in NDA. From baseline to 6-month follow-up, Class 3 added 2.31 abstinent days per week, Class 2 added 0.69 days, and Class 1 added 0.63 days. The increase in NDA for Class 3 was significantly different from the other 2 classes; however, Class 3 reported fewer overall days abstinent at 6-month follow-up. CONCLUSIONS: Study results have clinical and research implications including recommended changes to treatment protocols and research designs. Understanding the impact of pretreatment trajectories of alcohol use on within-treatment and posttreatment outcomes may provide important information about adapting treatment to increase efficiency and effectiveness.

Prenatal exposure to tobacco and marijuana and child autonomic regulation and reactivity: An analysis of indirect pathways via maternal psychopathology and parenting.

We examined a conceptual model for the associations of prenatal exposure to tobacco (PTE) and marijuana with child reactivity/regulation at 16 months of age. We hypothesized that PTE would be associated with autonomic reactivity and regulation that these associations would be indirect via maternal anger/hostility, depression/stress, or harsh parenting assessed at 2 months and that these effects would be most pronounced among children exposed to both tobacco and marijuana (PTME). Participants were 247 dyads (81 PTE, 97 PTME, and 69 nonexposed) who were followed up at 2 (N = 247) and 16 months (N = 238) of child age. Results from model testing indicated an indirect association between PTME and autonomic functioning during the second year of life, which was mediated by harsh parenting during caregiver-infant interactions. This study fills an important gap in the literature on PTE, PTME, and autonomic regulation during the toddler years, highlighting the role of maternal parenting as important intervening variables.

ABIN-1 Negatively Regulates µ-Opioid Receptor Function.

The µ-opioid receptor (MOR) is a Gi/o protein-coupled receptor that mediates analgesic, euphoric, and reward effects. Using a bacterial two-hybrid screen, we reported that the carboxyl tail of the rat MOR associates with A20-binding inhibitor of nuclear factor κB (ABIN-1). This interaction was confirmed by direct protein-protein binding and coimmunoprecipitation of MOR and ABIN-1 proteins in cell lysates. Saturation binding studies showed that ABIN-1 had no effect on MOR binding. However, the interaction of ABIN-1 and MOR inhibited the activation of G proteins induced by DAMGO ([d-Ala2,N-Me-Phe4,Gly5-ol]-Enkephalin). MOR phosphorylation, ubiquitination, and internalization induced by DAMGO were decreased in Chinese hamster ovary cells that coexpressed MOR and ABIN-1. The suppression of forskolin-stimulated adenylyl cyclase by DAMGO was also inhibited by the interaction of ABIN-1 with MOR. In addition, extracellular signal-regulated kinase activation was also negatively regulated by overexpression of ABIN-1. These data suggest that ABIN-1 is a negative coregulator of MOR activation, phosphorylation, and internalization in vitro. ABIN-1 also inhibited morphine-induced hyperlocomotion in zebrafish larvae (AB strain). By utilization of an antisense morpholino oligonucleotide (MO) gene knockdown technology, the ABIN-1 MO-injected zebrafish larvae showed a significant increase (approximately 60%) in distance moved compared with control MO-injected larvae after acute morphine treatment (P < 0.01). Taken together, ABIN-1 negatively regulates MOR function in vitro and in vivo.

Mechanisms of behavior change during alcohol treatment among negative affect drinkers: A time-varying effect model analysis using 84 consecutive days of ecological momentary assessment.

OBJECTIVE: To better understand the timing and unique contribution of four potential mechanisms of behavior change (MOBC) during alcohol use disorder (AUD) treatment (negative affect, positive affect, alcohol craving, and adaptive alcohol coping), we used a time-varying effect modeling analytic approach to examine the change trajectories of alcohol abstinence, heavy drinking, the hypothesized MOBCs, and the time-varying associations between the MOBCs and alcohol outcomes. METHOD: Participants (N = 181; Mage = 50.8 years, SD = 10.6; 51% women; 93.5% Caucasian) were enrolled in a 12-week randomized clinical trial of cognitive behavioral outpatient treatment program for AUD. For 84 consecutive days, participants provided self-reports of positive and negative affect, craving, alcohol use, and adaptive alcohol coping strategies employed. RESULTS: Throughout the 84-day treatment window, higher daily average craving levels were associated with both decreased likelihood of alcohol abstinence and increased odds of heavy drinking, whereas higher adaptive alcohol coping was associated with increased odds of abstinence and decreased odds of heavy drinking. Higher negative affect was associated with decreased odds of abstinence in the first 10 days of treatment and increased odds of heavy drinking before Day 4 or Day 5. Higher positive affect was associated with decreased odds of heavy drinking during the first 4 or 5 days. CONCLUSIONS: The differential time-varying associations between negative affect, positive affect, alcohol craving, adaptive alcohol coping, and alcohol use provide insights into how and when each of the MOBCs is active during AUD treatment. These findings can help optimize the efficacy of future AUD treatments. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Negative affect variability as a potential mechanism of behavior change in alcohol use disorder treatment.

OBJECTIVE: Negative affect and affect variability figure prominently in models of addictive behaviors but are not without controversy. Negative affect variability may better capture a mechanism of behavior change in alcohol use disorder (AUD) treatment because it contains information about affect regulation, a common clinical target. The aims of this study are to examine the change in: (a) trajectory of negative affect variability, (b) association of negative affect variability and abstinence, and (c) association of negative affect variability and heavy drinking during AUD treatment. METHOD: This article is a secondary analysis of data drawn from a randomized clinical trial. N = 181 participants diagnosed with Diagnostic and Statistical Manual of Mental Disorders, fifth edition AUD (Mage = 50.8, SDage = 10.6; 51.4% female) received 12 sessions of Cognitive Behavioral Coping Skills Therapy for AUD. Participants completed one daily diary prompt per day for 84 consecutive days. Each day, participants reported on negative affect and number of alcoholic drinks consumed the previous day. Time-varying effect models examined changes in negative affect variability and its associations with abstinence and heavy drinking. RESULTS: Negative affect variability decreased throughout treatment. The positive association between negative affect variability and heavy drinking became nonsignificant (decoupled) midway through treatment. The inverse association between negative affect variability and daily abstinence became nonsignificant (decoupled) at approximately day 75 of 84. When mean levels of NA were added as a covariate, the effects were in the same direction but no longer statistically significant. CONCLUSION: Reductions in negative affect variability may capture an important change mechanism of behavioral treatments for AUD because it contains information about affect regulation as compared with mean levels of negative affect. Negative affect variability warrants further consideration as a mechanism of behavior change. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Emotion differentiation among individuals in a randomized clinical trial for alcohol use disorder: Within- and between-person associations with affect, craving, and alcohol use in daily life.

Emotion differentiation refers to cognitively distinguishing among discrete, same-valenced emotions. Negative emotion differentiation (NED) is a transdiagnostic indicator of emotional functioning. The role of positive emotion differentiation (PED) in clinical disorders, including alcohol use disorder (AUD), is less understood. Further, despite consensus that emotions are highly variable, little is known about within-person fluctuations in NED/PED. The current study leveraged 84 consecutive daily smartphone surveys from participants (N = 181) in a clinical trial of cognitive behavioral therapy for AUD to investigate whether between-person differences in overall NED/PED, or within-person variability in daily NED/PED, were associated with affect intensity, craving, drinking, and heavy drinking in daily life. Subsequent analyses explored whether associations were moderated by baseline alexithymia. At the between-persons level, greater average PED, but not NED, was associated with lower heavy drinking odds. At the within-persons level, higher-than-usual PED was associated with lower negative affect and odds of any drinking. Individuals with baseline alexithymia had stronger negative within-person associations between daily NED and both any and heavy drinking. PED is a skill linked to less alcohol use between- and within-persons irrespective of baseline alexithymia, whereas greater daily NED appears especially important for reduced alcohol use among individuals with co-morbid AUD and alexithymia.

Predictors of National Institute on Alcohol Abuse and Alcoholism (NIAAA) Alcohol Recovery among Individuals in Alcohol Treatment: Implications for Social Work.

The National Institute on Alcohol Abuse and Alcoholism's (NIAAA) definition of alcohol use disorder (AUD) recovery stipulates two criteria: remission from DSM-5 AUD and cessation of heavy drinking. Importantly, these criteria allow for consideration of nonabstinent alcohol treatment outcomes. However, researchers have yet to assess potential predictors of the NIAAA recovery outcome. The current study examined associations between mental health and coping predictors of NIAAA recovery status in an AUD treatment sample. At baseline (BL) and end-of-treatment (EOT) research interviews in a clinical trial, participants (N = 118) completed questionnaires assessing alcohol dependence, mental health, and confidence levels in reducing heavy drinking, as well as alcohol use and DSM-5 AUD symptom endorsement. Logistic regression models tested the associations between chosen predictors and the odds of achieving NIAAA recovery. Twenty-four percent of individuals (n = 28) met both criteria for NIAAA recovery at EOT. Higher levels of BL state anxiety and anxiety sensitivity predicted lower odds of achieving NIAAA recovery, while greater confidence to reduce heavy drinking predicted increased odds of NIAAA recovery. Social workers are encouraged to continue assessing and addressing mental health in AUD treatment to help individuals with alcohol problems achieve their AUD recovery goals.

Exploring causal effects of smoking and alcohol related lifestyle factors on self-report tiredness: A Mendelian randomization study.

Self-reported tiredness or low energy, often referred to as fatigue, has been linked to lifestyle factors, although data from randomized-controlled trials are lacking. We investigate whether modifiable lifestyle factors including smoking and alcohol intake related exposures (SAIEs) are causal factors for fatigue using Mendelian randomization (MR). A two-sample MR study was performed by using genome-wide association summary results from UK Biobank (UKBB), and each of the sample size is more than 100,000. We used the inverse variance weighted method, and sensitivity analyses (MR Egger, weighted median, penalized median estimators, and multivariable MR) to account for pleiotropy. The two-sample MR analyses showed inverse causal effect of never-smoking status and positive effect of current smoking status on the risk of fatigue. Similarly, genetically predicted alcoholic intake was positively associated with fatigue. The results were consistent across the different MR methods. Our Mendelian randomization analyses do support that the cessation of smoking and alcohol can decrease the risk of fatigue, and limit alcohol intake frequency can also reduce the risk.

Quantitative assessment of condylar bone resorption using fused CBCT images: differentiating and diagnosing three distinct groups based on volume and thickness decrease.

OBJECTIVES: To investigate the accuracy of fused CBCT images in diagnosing three distinct groups of bone changes characterized by volume and thickness decrease in patients with temporomandibular joint osteoarthrosis (TMJ OA) during follow-up. METHODS: In this retrospective study, 109 patients (176 TMJs) with TMJ OA were included. Two consecutive CBCT images for the same patient were registered and fused. Then, three image sets were established: without fusion, fused 2D image, and fused 3D image. Three residents randomly and independently evaluated whether there was condylar resorption with the three image sets respectively. The samples diagnosed as condylar resorption by the expert panel were divided into three subgroups according to the volume and thickness decrease calculated after segmentation. The inter- and intraobserver agreement, receiver operating characteristic (ROC), and area under the curve (AUC) evaluated the diagnostic capability for different subgroups. RESULTS: For the volume decrease more than 50 mm3 and thickness decrease more than 1 mm groups, the AUC values for fused image sets were higher than those without fusion (p < 0.01). For the volume decrease within 50 mm3 and thickness decrease within 1 mm groups, the AUC values for fused 2D image sets were higher than the image sets without fusion (p < 0.05), but there was no significant difference between the fused 3D image sets and the image sets without fusion (p = 0.48 for volume decrease, p = 0.37 for thickness decrease). CONCLUSIONS: The fused images can improve the diagnostic accuracy and repeatability for the samples with at least 50 mm3 volume decrease or 1 mm thickness decrease compared with the image groups without fusion.

Pretreatment changes in drinking: A test of a tailored treatment approach.

BACKGROUND: Pretreatment reductions in drinking are well documented and have been demonstrated to predict posttreatment drinking outcomes. Making use of the predictive value of pretreatment change has great appeal in settings that place a premium on efficient clinical decisions regarding appropriate type and intensity of treatment. METHODS: This study investigates whether different types and intensities of treatment are appropriate and beneficial for individuals entering treatment for an alcohol use disorder (AUD; N = 201) who make more vs. less pretreatment change in their drinking during a 2-month pretreatment period. Based on an algorithm derived from pilot research, we derived two independent pretreatment change arms that we called Substantial Change and Minimal Change. Each arm was a parallel, sequentially randomized design consisting of a treatment group and an active control. The Substantial Change arm compared six sessions of relapse prevention treatment (RPT) with 12 sessions of cognitive behavioral therapy for AUD (CBT) as an active control. Both CBT and RPT occurred over a 12-week period. The Minimal Change arm compared 12 sessions of an integrated motivational intervention combined with CBT (MI/CBT) with 12 sessions of CBT as an active control. The outcome variables were changes in number of days abstinent (NDA) and number of days heavy drinking (NDH) per week. RESULTS: For the Substantial Change arm, a noninferiority analysis revealed that six sessions of RPT were noninferior to 12 sessions of CBT at each posttreatment assessment for both NDA and NDH. For the Minimal Change arm, a superiority analysis failed to detect that MI/CBT was superior to CBT at any posttreatment assessment for both NDA and NDH. CONCLUSIONS: In the substantial change arm, results suggest that offering a less intensive initial treatment, like RPT, may lower costs and conserve clinical resources. In the Minimal Change arm, results indicate the need to continue searching for a treatment or treatment enhancements to improve alcohol outcomes.

Impact of ciprofloxacin and copper combined pollution on activated sludge: Abundant-rare taxa and antibiotic resistance genes.

This study aimed to explore the impacts of ciprofloxacin (CIP, 0.05-40 mg/L) and copper (3 mg/L) combined pollution on nitrification, microbial community and antibiotic resistance genes (ARGs) in activated sludge system during stress- and post-effect periods. Higher CIP concentration inhibited nitrification and an average of 50% total nitrogen removal occurred under 40 mg/L of CIP pressure. The stress- and post-effects on bacterial diversity and structure were obviously distinct. Abundant genera were more sensitive to combined pollution than rare genera based on full-scale classification and conditionally rare or abundant taxa were keystone taxa in their interactions. Ammonia oxidation genes were inhibited under high CIP level, but some aerobic denitrifying bacteria (Thauera, Comamonas and Azoarcus) and key genes increased. 96 ARG subtypes were detected with complex positive relationships and their potential hosts (abundant-rare-functional genera) changed in two periods. This study highlights the different stress- and post-effects of combined pollution on activated sludge.

[Historical Antibiotic Stress Changed the Effects of Sulfamethoxazole and Trimethoprim on Activated Sludge: ARGs and Potential Hosts].

The co-exposure of antibiotics has important effects on antibiotic resistance genes (ARGs) and microbial community aggregation in wastewater treatment plants (WWTPs). However, it is unclear whether differences in historical antibiotic exposure stress can determine responses of microbes and ARGs to combined antibiotics. By selecting a high concentration (30 mg·L-1) of sulfamethoxazole (SMX) and trimethoprim (TMP) as historical exposure stress conditions, the effects of SMX and TMP-combined pollution on ARGs, bacterial communities, and their interactions were explored in short-term experiments. Based on high-throughput quantitative PCR, a total of 13 ARGs were detected, and the absolute abundance was 2.21-5.42 copies·µL-1 (logarithm, DNA, the same below). Among them, sul2, ermB, mefA, and tetM-01 were the main subtypes in the samples, and the absolute abundance was between 2.95 and 5.40 copies·µL-1. The combined contamination of SMX and TMP could cause the enrichment of ARGs and mobile genetic elements (MGEs); however, their effects on each subtype were different, and the historical legacy effect of SMX was higher than that of TMP. Under the different exposure histories, the co-occurrence and co-exclusion patterns existed between ARGs. Moreover, MGEs (especially intI-1) were significantly correlated with sulfonamides (sul1 and sul2), tetracyclines[tet(32)], and macrolide-lincosamide-streptogramin (MLSB) resistance genes (ermB). Based on the full-scale classification of microorganisms, it was found that the microbial community structure of various groups responded differently to combined pollution, and the conditionally abundant taxa (CAT) were obviously enriched. Thauera, Pseudoxanthomonas, and Paracoccus were the dominant resistant bacterial genera. Furthermore, a total of 31 potential hosts of ARGs were identified with network analysis, which were dominated with conditionally rare taxa (CRT). Particularly, Candidatus_Alysiosphaera and Fusibacter were positively correlated with most of the ARGs, being the common protentional hosts. Importantly, some rare genera (RT, Variibacter, Aeromonas, Cloacibacterium, etc.) were potential hosts of transposon IS613, which played an important role in the proliferation and spread of ARGs. In conclusion, this study revealed the legacy effects of historical antibiotic stress on ARGs and their hosts, which could provide new ideas and theoretical basis for reducing ARGs pollution in WWTPs.