Reconfigurable DNA Nanocage for Protein Encapsulation and Regulation.

Creating nanomachines capable of precisely capturing, organizing, and regulating the activity of target biomolecules holds profound significance for advancing nanotechnology and therapeutics. Here, we develop a multistage reconfigurable DNA nanocage that can enclose and modulate proteins through multivalent interactions, activated by specific molecular signals. By strategically designing and manipulating the strut architecture of the DNA nanocages, we can achieve precise control over their reconfiguration among pyramid, square, and linear branch shapes. Additionally, we demonstrated its ability to capture thrombin and effectively inhibit its coagulation activity by incorporating two thrombin-targeting aptamers into the designed arms of the DNA nanocage. The activity of thrombin can be recovered by rearranging the conformation of the DNA nanocage and exposing the protein, thereby activating the coagulation process. This approach enriches the design toolbox for dynamic nanomachines and inspires a new strategy for protein encapsulation and regulation with potential future therapeutic applications.

Minimal residual disease assessment in transplant-eligible patients with multiple myeloma: real-world applications of multiparametric flow cytometry-DURAClone (CAREMM-2104).

Not available.

Latent triple trajectories of substance use as predictors for the onset of antisocial personality disorder among urban African American and Puerto Rican adults: A 22-year longitudinal study.

Background: Antisocial personality disorder (ASPD) incurs a high cost to society due to the high risk of violent and nonviolent offenses associated with this personality disorder, thus making the examination of the etiology and the onset of ASPD an important public health concern. Method: The present study consisted of five waves of data collection of the Harlem Longitudinal Development Study (N = 674). In the Cox proportional hazard model, latent multiple substance use trajectories from mid-adolescence to emerging adulthood (mean age 14 to mean age 24) were used as a predictor for the onset of ASPD during emerging adulthood to the mid-thirties (mean age 24 to mean age 36). The control variables were gender, ethnicity, problem behaviors, and victimization. Results: In the multiple Cox proportional hazard model, the high (HR = 2.74, p < 0.001) and the increasing frequency of (HR = 2.55, p < 0.001) use on alcohol, cigarette, and cannabis latent trajectory groups were associated with an increased hazard of ASPD onset as compared with the no or low frequency of use on alcohol, cigarette, and cannabis latent trajectory group after controlling for demographic factors and earlier problem behaviors as well as victimization. Conclusions: The implications of this study for the prediction of adult ASPD onset time may focus on the early use of alcohol, cigarette, and cannabis from mid adolescence to emerging adulthood.

Mitochondrial antiviral signaling protein is crucial for the development of pulmonary fibrosis.

Danger signals, or damage-associated molecular patterns (DAMPs), instigate mitochondrial innate immune responses wherein mitochondrial antiviral signaling protein (MAVS) functions as a key platform molecule to mediate them. The role of MAVS in the pathogenesis of idiopathic pulmonary fibrosis (IPF), however, has not yet been identified. Whether MAVS signalling can be modulated by currently existing drugs has also not been explored.We used an established model of pulmonary fibrosis to demonstrate that MAVS is a critical mediator of multiple DAMP signalling pathways and the consequent lung fibrosis after bleomycin-induced injury in vivoAfter bleomycin injury, MAVS expression was mainly observed in macrophages. Multimeric MAVS aggregation, a key event of MAVS signalling activation, was significantly increased and persisted in bleomycin-injured lungs. A proapoptotic BH3 mimetic, ABT-263, attenuated the expression of MAVS and its signalling and, consequently, the development of experimental pulmonary fibrosis. In contrast, the therapeutic effects of nintedanib and pirfenidone, two drugs approved for IPF treatment, were not related to the modulation of MAVS or its signalling. Multimeric MAVS aggregation was significantly increased in lungs from IPF patients as well.MAVS may play an important role in the development of pulmonary fibrosis, and targeting MAVS with BH3 mimetics may provide a novel and much needed therapeutic strategy for IPF.

Longitudinal predictors of male sexual partner risk among Black and Latina women in their late thirties: ethnic/racial identity commitment as a protective factor.

This study aimed to investigate predictors of male sexual partner risk among Latinas and Black women in their late thirties. We used multiple regression analysis to examine factors associated with male sexual partner risk among 296 women who participated in two waves of the Harlem Longitudinal Development Study (New York, 2011-2013 and 2014-2016). Women who experienced childhood sexual abuse had higher risk partners than those who did not [b = 0.16, 95% confidence interval (CI) = 0.06, 0.28]. Earlier marijuana use was a risk factor for partner risk in the late thirties (b = 0.12, 95% CI = 0.04, 0.27). Higher levels of ethnic/racial identity commitment mitigated this risk (b = - 0.15, 95% CI = - 0.26, - 0.04). Ethnic/racial identity commitment can be protective against male sexual partner risk among Latina and Black women who use marijuana. Further research should explore the protective role of different dimensions of ethnic/racial identity against sexually transmitted infections, including HIV.

Correlates of Cannabis Use Disorders among urban women of color: childhood abuse, relationship with spouse/partner, and media exposure.

OBJECTIVES: As the rate of cannabis use increases, it is expected that more individuals will develop a Cannabis Use Disorder (CUD). Relatively little is known, however, about the psychosocial correlates of CUDs among racial/ethnic minority women. This study, therefore, examined correlates of CUDs among a cohort of adult African American and Puerto Rican women. METHODS: The sample consisted of African American and Puerto Rican female participants (N = 343), who have been followed by the Harlem Longitudinal Development Study from mean age 14 to mean age 39 years. The bivariate and multivariate associations between CUDs at age 39 and variables from 5 domains - demographics, earlier cannabis use, childhood abuse, the relationship with the spouse/partner, and media exposure - were assessed using logistic regression analyses. RESULTS: The results showed that, with the exception of demographic factors, variables from each of the domains (e.g., sexual abuse in childhood, arguments with spouse/partner, and hours of visual media exposure) were related to CUDs at age 39. CONCLUSIONS: Findings suggest that in addition to treating CUDs, couples therapy may be indicated to strengthen the spousal/partner relationship, enlist the spouse/partner's support for cannabis use cessation. Furthermore, frequency of visual media exposure may need to be reduced.

Upfront autologous hematopoietic stem cell transplantation for high-risk patients with double-expressor diffuse large B cell lymphoma.

Although MYC and BCL2 co-expression in diffuse large B cell lymphoma (DLBCL) is associated with inferior prognosis, it remains uncertain whether upfront autologous hematopoietic stem cell transplantation (ASCT) is beneficial in this lymphoma. This study aimed to investigate whether ASCT consolidation could have a positive role for patients with MYC and BCL2 co-expression (double-expressor lymphoma, DEL). We retrospectively evaluated 67 DLBCL patients who underwent upfront ASCT following rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy. The 5-year overall survival (OS) and progression-free survival (PFS) were 82.3% and 79.2%, respectively. There were 23 (34.3%) patients with DEL and 51 (76.1%) patients with non-germinal center B cell (GCB) subtype. The 5-year OS and PFS of patients with DEL were not different from those with non-DEL (P = 0.429 and P = 0.614, respectively). No survival difference for OS and PFS was also observed between GCB and non-GCB subtypes (P = 0.950 and P = 0.901, respectively). The OS and PFS were comparable for patients with DEL and non-DEL and both GCB and non-GCB subtypes. In conclusion, MYC and BCL2 co-expression did not have a poor prognostic impact among high-risk patients with DLBCL treated with upfront ASCT regardless of molecular classification. This preliminary study suggested that the role of consolidative ASCT is needed to be evaluated in a prospective randomized clinical trial.

Correction to: Apicidin induces endoplasmic reticulum stress- and mitochondrial dysfunction-associated apoptosis via phospholipase Cγ1- and Ca2+-dependent pathway in mouse Neuro-2a neuroblastoma cells.

The original version of this article contained a mistake in the figure. The Ca2 + confocal image for the 2-APB/Apicidin-120 min in Fig. 5d is incorrect. The correction does not influence either the validity of the published data or the conclusion described in the article. The corrected Fig. 5d is given below.

Single and dual diagnoses of major depressive disorder and posttraumatic stress disorder predicted by triple comorbid trajectories of tobacco, alcohol, and marijuana use among urban adults.

Background: The adverse consequences of major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) affect a significant portion of the US population every year (i.e., 15 million for MDD; 8 million for PTSD) and are of public health concern. The current study examines tobacco, alcohol, and marijuana use as possible longitudinal predictors of MDD and/or PTSD. Methods: A community sample of 674 participants (53% African Americans and 47% Puerto Ricans; 405 females and 269 males) were recruited from the Harlem Longitudinal Development Study. We used Mplus software to obtain the triple trajectories of tobacco, alcohol, and marijuana use from mean age 14 to 36. Logistic regression analyses were then conducted to examine the associations between those triple trajectory groups and a single diagnosis of MDD or PTSD as well as a dual diagnosis of MDD with PTSD at age 36. Results: The observed percentages of MDD, PTSD, and the comorbidity of MDD and PTSD were 17%, 8%, and 5%, respectively. The heavy use of all 3 substances group was associated with an increased likelihood of having MDD (adjusted odds ratio [AOR] = 3.14, P < .01), PTSD (AOR = 3.91, P < .05), and MDD with PTSD (AOR = 6.64, P < .01), as compared with the tobacco and alcohol use group. Conclusions: Treatment programs to quit or reduce the use of tobacco, alcohol, and marijuana may help decrease the prevalence of MDD and PTSD. This could lead to improvements in individualized treatments for patients who use tobacco, alcohol, and marijuana and who have both MDD and PTSD.

Impact of Cigarette Smoke Exposure on the Lung Fibroblastic Response after Influenza Pneumonia.

Influenza viruses can result in significant lung injury with significant morbidity and mortality. In this study, we evaluated the impact of cigarette smoke (CS) exposure on the pulmonary fibroblastic response after influenza infection. We used a murine model in which animals were exposed to CS or room air and subsequently infected with H1N1 influenza virus. Inflammatory and fibrotic responses were measured at different time points after influenza infection. Primary fibroblasts were isolated from the lungs of mice and their characteristics were evaluated. Exposure to CS significantly increased the amount of collagen in the lungs of mice infected with influenza virus compared with the nonsmoking group at 30 days after infection. Furthermore, the presence of fibroblast-specific protein-positive cells increased in the lungs of influenza-infected mice that were exposed to CS compared with the infection-alone group. The smoking group also showed delays in weight recovery and higher cell counts in BAL fluid after infection. Active transforming growth factor ß1 levels in BAL fluid increased in both groups; however, CS-exposed mice had a later surge in active transforming growth factor ß1 (Day 24). Ex vivo cultures of lung-derived fibroblasts from CS-exposed mice with influenza infection showed rapid proliferation, increased expression of α-smooth muscle actin-stained stress fibers, and higher expression of growth factors compared with fibroblasts from room air-exposed lungs after infection. These results suggest that CS exposure changes the fibroblastic potential, leading to increased fibrosis after influenza infection.

Trajectories of cannabis use beginning in adolescence associated with symptoms of posttraumatic stress disorder in the mid-thirties.

BACKGROUND: Posttraumatic stress disorder (PTSD) symptoms are related to a number of adverse consequences such as substance use and general medical conditions. The present longitudinal study seeks to find the longitudinal patterns of cannabis use as precursors of PTSD symptoms. Such information will serve as a guide for intervention programs for PTSD. METHODS: Growth mixture modeling was conducted to identify the cannabis use trajectory groups using a community sample of 674 participants (53% African Americans, 47% Hispanics of Puerto Rican decent; 60% females) from the Harlem Longitudinal Development Study. Logistic regression analyses were performed to examine the association between earlier trajectories of cannabis use (ages 14 to 36) and later symptoms of PTSD (at age 36) for the full model including the entire sample (N = 674) as well as the reduced model including only participants who had experienced a traumatic event (n = 205). RESULTS: Five trajectory groups of cannabis use were obtained. The chronic use group (full model: adjusted odds ratio [AOR] = 4.68, P < .01; reduced model: AOR = 4.27, P < .05), the late quitting group (full model: AOR = 6.18, P < .01; reduced model: AOR = 6.67, P < .01), and the moderate use group (full model: AOR = 3.97, P < .01; reduced model: AOR = 3.32, P < .05) were all associated with an increased likelihood of having PTSD symptoms at age 36 compared with the no use group. CONCLUSIONS: The findings provide information that PTSD symptoms in the mid-30s can possibly be reduced by decreasing membership in the chronic cannabis use trajectory group, the late quitting trajectory group, and the moderate cannabis use trajectory group.

Clinical impact of early recovery of peripheral blood absolute lymphocyte count after frontline autologous stem cell transplantation for diffuse large B-cell lymphoma.

We conducted a retrospective study to evaluate the clinical impact of an early recovery of posttransplant absolute lymphocyte count (ALC) on the outcome of frontline autologous stem cell transplantation (ASCT) for diffuse large B-cell lymphoma (DLBCL). We reviewed 65 DLBCL patients who underwent frontline ASCT after primary chemotherapy based on cyclophosphamide, doxorubicin, vincristine, and prednisone. A receiver operating characteristic analysis was performed to determine the optimal cut point (0.4 × 109 /L) for an ALC at 15 days after ASCT (ALC-15). Both event-free survival and overall survival rates of the higher-ALC-15 group were significantly better than those of the lower-ALC-15 group (event-free survival, P = .008; overall survival, P = .013). The infused CD34+ cell count was significantly associated with the recovery of ALC-15 (>0.4 × 109 /L) after ASCT (P = .028). A multivariate analysis confirmed that a higher infused CD34+ cell dose (>5.0 × 106  cells/kg) was an independent factor affecting an early recovery of ALC after ASCT (odds ratio, 4.145; 95% confidence interval, 1.106-15.528; P = .035). In conclusion, an early recovery of ALC after ASCT can be regarded as a good prognostic marker in patients with DLBCL who have undergone frontline ASCT. We found that the infused CD34+ cell dose for ASCT was associated with the recovery of ALC.

The prognostic role of CD68 and FoxP3 expression in patients with primary central nervous system lymphoma.

The prognostic role of CD68 and FoxP3 in primary central nervous system lymphoma (PCNSL) has not been evaluated. Thus, we examined the prognostic significance of CD68 and FoxP3 expression in tumor samples of 76 newly diagnosed immunocompetent PCNSL patients. All patients were treated initially with high-dose methotrexate (HD-MTX)-based chemotherapy, and 16 (21.1%) patients received upfront autologous stem cell transplantation (ASCT) consolidation. High expression of CD68 (>55 cells/high-power field) or FoxP3 (>15 cells/high-power field) was observed in 10 patients, respectively. High CD68 expression was associated with inferior overall survival (OS) and progression-free survival (PFS) in multivariate analysis (P = 0.023 and P = 0.021, respectively). In addition, we performed subgroup analysis based on upfront ASCT. High CD68 expression was also associated with inferior OS and PFS in multivariate analysis (P = 0.013 and P < 0.001, respectively) among patients who did not receive upfront ASCT (n = 60), but not in patients who received upfront ASCT. The expression of FoxP3 was not significantly associated with survival. Therefore, we identified a prognostic significance of high CD68 expression in PCNSL, which suggests a need for further clinical trials and biological studies on the role of PCNSL tumor microenvironment.

The association between alcohol use trajectories from adolescence to adulthood and cannabis use disorder in adulthood: a 22-year longitudinal study.

BACKGROUND: Due to the increasing prevalence of cannabis use disorder (CUD), the impact of cannabis use on public health may be significant. OBJECTIVE: The present study seeks the possible precursors (e.g., alcohol use) of CUD in order to minimize the potential negative consequences of CUD such as impaired coordination and performance. METHOD: The Harlem Longitudinal Development Study included 674 participants (53% African Americans, 47% Puerto Ricans), with 60% females (n=405) from a six wave survey. We used a growth mixture model to obtain the trajectories of alcohol use from the mean ages of 14 to 36. To examine the associations between alcohol use trajectories and CUD, we used logistic regression analyses with the indicator of CUD as the dependent variable and the indicator of membership in each trajectory group as the independent variables. RESULTS: A three alcohol use trajectory group model was selected. Male gender, higher frequency of cannabis use in adolescence, and a lower educational level were associated with an increased likelihood of having CUD. Membership in the increasing alcohol use group (OR=27.44, p < .01; AOR=15.54, p < .01) and the moderate alcohol use group (OR=10.40, p < .05; AOR=8.63, p < .05) were associated with an increased likelihood of having CUD compared with the membership in the no or low alcohol use group. CONCLUSIONS: The findings of our study support the hypothesis that addressing alcohol use at an early age could impact later CUD.

The role of upfront autologous stem cell transplantation in high-risk younger patients with primary central nervous system lymphoma.

Upfront autologous stem cell transplantation (ASCT) has shown favourable outcome in patients with primary central nervous system lymphoma (PCNSL), but the role of risk-adapted upfront ASCT consolidation has not been evaluated in PCNSL. As PCNSL patients with the International Extranodal Lymphoma Study Group (IELSG) prognostic score ≥2 or those who did not achieve complete response after two courses of induction chemotherapy (non-CR1) have shown inferior outcomes, we retrospectively analysed the role of upfront ASCT in 66 high-risk (IELSG ≥2 and/or non-CR1) younger (age <65 years) immunocompetent PCNSL patients who achieved at least partial response after initial high-dose methotrexate-based chemotherapy. Nineteen patients who received upfront ASCT exhibited significantly better overall survival (OS, P = 0·021) and progression-free survival (PFS, P = 0·005) compared to 47 patients who did not. In univariate and multivariate analyses, upfront ASCT was associated with better OS (P = 0·037 and P = 0·025, respectively) and PFS (P = 0·009 and P = 0·007, respectively). In a propensity score-matched cohort (n = 36), patients who received upfront ASCT also showed better outcome (P = 0·037 for OS, P = 0·001 for PFS). Our results suggest that upfront ASCT consolidation might be especially beneficial for high-risk PCNSL patients.

Adolescent predictors of alcohol use in adulthood: A 22-year longitudinal study.

BACKGROUND AND OBJECTIVES: The excessive consumption of alcohol is a major issue in the United States and elsewhere. It is associated with a number of adverse health consequences, as well as difficulty in relationships and employment. Therefore, the present longitudinal study investigates the direct and indirect adolescent predictors of alcohol use in adulthood. METHODS: Among the 674 participants (53% African Americans, 47% Puerto Ricans), 60% were females (n = 405). Mplus software was used to perform structural equation modeling. RESULTS: Parental problems with alcohol use in the participants' late adolescence were related to low parent-child attachment in late adolescence, which in turn, was related to self delinquency in late adolescence. This was related to peer delinquency in emerging adulthood, which in turn, was associated with alcohol use in emerging adulthood and in adulthood. Low parent-child attachment in late adolescence was also related to low satisfaction with school in late adolescence, which in turn, was related to self delinquency in late adolescence. This was associated with alcohol use in emerging adulthood, which in turn, was associated with alcohol use in adulthood. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: One of the key implications of this study is that an impaired low parent-child attachment relationship is a determinant of children's engagement in delinquent behavior and ultimately the use of alcohol in adult life. Implications for social interventions from the findings of the current study were also discussed. (Am J Addict 2016;25:549-556).

Effects of Educational Interventions for Chronic Airway Disease on Primary Care.

Education has been known to essential for management of chronic airway diseases. However the real benefits remain unclear. We evaluated the effectiveness of an organized educational intervention for chronic airway diseases directed at primary care physicians and patients. The intervention was a 1-month education program of three visits, during which subjects were taught about their disease, an action plan in acute exacerbation and inhaler technique. Asthma control tests (ACT) for asthma and, chronic obstructive pulmonary disease (COPD) assessment tests (CAT) for COPD subjects were compared before and after education as an index of quality of life. Educational effectiveness was also measured associated with improvement of their knowledge for chronic airway disease itself, proper use of inhaler technique, and satisfaction of the subjects and clinicians before and after education. Among the 285 participants, 60.7% (n = 173) were men and the mean age was 62.2 ± 14.7. ACT for asthma and CAT in COPD patients were significantly improved by 49.7% (n = 79) and 51.2% (n = 65) more than MCID respectively after education (P < 0.05). In all individual items, knowledge about their disease, inhaler use and satisfaction of the patients and clinicians were also improved after education (P < 0.05). This study demonstrates the well-organized education program for primary care physicians and patients is a crucial process for management of chronic airway diseases.

Pretreatment Lymphopenia, Poor Performance Status, and Early Courses of Therapy Are Risk Factors for Severe Bacterial Infection in Patients with Multiple Myeloma during Treatment with Bortezomib-based Regimens.

The aim of this study was to identify the risk factors associated with severe bacterial infection (SBI) in multiple myeloma (MM) patients during treatment with bortezomib-based regimens. A total of 98 patients with MM were evaluated during 427 treatment courses. SBI occurred in 57.1% (56/98) of the patients and during 19.0% (81/427) of the treatment courses. In the multivariate analysis for the factors associated with the development of SBI in each treatment course, poor performance status (Eastern Cooperative Oncology Group ≥ 2, P < 0.001), early course of therapy (≤ 2 courses, P < 0.001), and pretreatment lymphopenia (absolute lymphocyte count < 1.0 × 10(9)/L, P = 0.043) were confirmed as independent risk factors. The probability of developing SBI were 5.1%, 14.9%, 23.9% and 59.5% in courses with 0, 1, 2, and 3 risk factors, respectively (P < 0.001). In conclusion, we identified three pretreatment risk factors associated with SBI in each course of bortezomib treatment. Therefore, MM patients with these risk factors should be more closely monitored for the development of SBI during bortezomib-based treatment.

Characteristics of Patients with Chronic Obstructive Pulmonary Disease at the First Visit to a Pulmonary Medical Center in Korea: The KOrea COpd Subgroup Study Team Cohort.

The Korea Chronic Obstructive Pulmonary Disorders Subgroup Study Team (Korea COPD Subgroup Study team, KOCOSS) is a multicenter observational study that includes 956 patients (mean age 69.9 ± 7.8 years) who were enrolled from 45 tertiary and university-affiliated hospitals from December 2011 to October 2014. The initial evaluation for all patients included pulmonary function tests (PFT), 6-minute walk distance (6MWD), COPD Assessment Test (CAT), modified Medical Research Council (mMRC) dyspnea scale, and the COPD-specific version of St. George's Respiratory Questionnaire (SGRQ-C). Here, we report the comparison of baseline characteristics between patients with early- (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage I and II/groups A and B) and late-stage COPD (GOLD stage III and IV/groups C and D). Among all patients, the mean post-bronchodilator FEV1 was 55.8% ± 16.7% of the predicted value, and most of the patients were in GOLD stage II (520, 56.9%) and group B (399, 42.0%). The number of exacerbations during one year prior to the first visit was significantly lower in patients with early COPD (0.4 vs. 0.9/0.1 vs. 1.2), as were the CAT score (13.9 vs. 18.3/13.5 vs. 18.1), mMRC (1.4 vs. 2.0/1.3 vs.1.9), and SGRQ-C total score (30.4 vs. 42.9/29.1 vs. 42.6) compared to late-stage COPD (all P < 0.001). Common comorbidities among all patients were hypertension (323, 37.7%), diabetes mellitus (139, 14.8%), and depression (207, 23.6%). The data from patients with early COPD will provide important information towards early detection, proper initial management, and design of future studies.