Neurocognition of females with substance use disorder and comorbid personality disorder: Divergence in subjective and objective cognition.

At least one in four patients with substance use disorder (SUD) meet criteria for personality disorder and overlapping neurocognitive deficits may reflect shared neurobiological mechanisms. We studied neurocognition in females attending residential SUD treatment by comparing SUD with (n = 20) or without (n = 30) comorbid personality disorder. Neuropsychological testing included working memory, inhibition, shifting, verbal fluency, design fluency, psychomotor speed, immediate and delayed verbal memory, processing speed, premorbid functioning, cognitive screening, and self-reported executive function. As expected, whole-sample deficits included working memory (d = -.91), self-reported executive function (d = -.87), processing speed (d = -.40), delayed verbal memory recall (d = -.39), premorbid functioning (d = -.51), and cognitive screening performance (d = -.61). Importantly, the comorbid personality disorder group showed greater self-reported executive dysfunction (d = -.67) and poorer shifting performance (d = -.65). However, they also evidenced better working memory (d = .84), immediate (d = .95) and delayed (d = .83) verbal memory, premorbid functioning (d = .90), and cognitive screening performance (d = .77). Overall executive dysfunction deficits were concordant with those observed in previous SUD studies. Surprisingly, comorbid personality disorder was associated with a pattern indicating poorer subjective (self-report) but better objective performance on a number of tasks, apart from shifting deficits that may relate to emotion dysregulation. Subjective emotional dysfunction may influence the cognitive deficits observed in the personality disorder group.

Cognitive training and remediation interventions for substance use disorders: a Delphi consensus study.

AIMS: Substance use disorders (SUD) are associated with cognitive deficits that are not always addressed in current treatments, and this hampers recovery. Cognitive training and remediation interventions are well suited to fill the gap for managing cognitive deficits in SUD. We aimed to reach consensus on recommendations for developing and applying these interventions. DESIGN, SETTING AND PARTICIPANTS: We used a Delphi approach with two sequential phases: survey development and iterative surveying of experts. This was an on-line study. During survey development, we engaged a group of 15 experts from a working group of the International Society of Addiction Medicine (Steering Committee). During the surveying process, we engaged a larger pool of experts (n = 54) identified via recommendations from the Steering Committee and a systematic review. MEASUREMENTS: Survey with 67 items covering four key areas of intervention development: targets, intervention approaches, active ingredients and modes of delivery. FINDINGS: Across two iterative rounds (98% retention rate), the experts reached a consensus on 50 items including: (i) implicit biases, positive affect, arousal, executive functions and social processing as key targets of interventions; (ii) cognitive bias modification, contingency management, emotion regulation training and cognitive remediation as preferred approaches; (iii) practice, feedback, difficulty-titration, bias modification, goal-setting, strategy learning and meta-awareness as active ingredients; and (iv) both addiction treatment work-force and specialized neuropsychologists facilitating delivery, together with novel digital-based delivery modalities. CONCLUSIONS: Expert recommendations on cognitive training and remediation for substance use disorders highlight the relevance of targeting implicit biases, reward, emotion regulation and higher-order cognitive skills via well-validated intervention approaches qualified with mechanistic techniques and flexible delivery options.

Improving treatment outcomes for borderline personality disorder: what can we learn from biomarker studies of psychotherapy?

PURPOSE OF REVIEW: Borderline personality disorder (BPD) is a severe and common psychiatric disorder and though evidence-based psychotherapies are effective, rates of treatment nonresponse are as high as 50%. Treatment studies may benefit from interdisciplinary approaches from neuroscience and genetics research that could generate novel insights into treatment mechanisms and tailoring interventions to the individual. RECENT FINDINGS: We provide a timely update to the small but growing body of literature investigating neurobiological and epigenetic changes and using biomarkers to predict outcomes from evidence-based psychotherapies for BPD. Using a rapid review methodology, we identified eight new studies, updating our earlier 2018 systematic review. Across all studies, neuroimaging ( n  = 18) and genetics studies ( n  = 4) provide data from 735 participants diagnosed with BPD (mean sample size across studies = 33.4, range 2-115). SUMMARY: We report further evidence for psychotherapy-related alterations of neural activation and connectivity in regions and networks relating to executive control, emotion regulation, and self/interpersonal functioning in BPD. Emerging evidence also shows epigenetic changes following treatment. Future large-scale multisite studies may help to delineate multilevel treatment targets to inform intervention design, selection, and monitoring for the individual patient via integration of knowledge generated through clinical, neuroscience, and genetics research.

Predictive value of DNA repair gene expression for response to neoadjuvant chemotherapy in breast cancer.

Genome-wide analysis using microarrays has revolutionized breast cancer (BC) research. A substantial body of evidence supports the clinical utility of the 21-gene assay (Oncotype DX) and 70-gene assay (MammaPrint) to predict BC recurrence and the magnitude of benefit from chemotherapy. However, there is currently no genetic tool able to predict chemosensitivity and chemoresistance to neoadjuvant chemotherapy (NACT) during BC treatment. In this study, we explored the predictive value of DNA repair gene expression in the neoadjuvant setting. We selected 98 patients with BC treated with NACT. We assessed DNA repair expression in 98 formalin-fixed, paraffin-embedded core biopsy fragments used at diagnosis and in 32 formalin-fixed, paraffin-embedded post-NACT residual tumors using quantitative reverse transcription-polymerase chain reaction. The following genes were selected: BRCA1, PALB2, RAD51C, BRCA2, ATM, FANCA, MSH2, XPA, ERCC1, PARP1, and SNM1. Of 98 patients, 33 (33.7%) achieved pathologic complete response (pCR). The DNA expression of 2 genes assessed in pre-NACT biopsies (PALB2 and ERCC1) was lower in pCR than in non-pCR patients (P=0.005 and P=0.009, respectively). There was no correlation between molecular subtype and expression of DNA repair genes. The genes BRCA2 (P=0.009), ATM (P=0.004), FANCA (P=0.001), and PARP1 (P=0.011) showed a lower expression in post-NACT residual tumor samples (n=32) than in pre-NACT biopsy samples (n=98). The expression of 2 genes (PALB2 and ERCC1) was lower in pCR patients. These alterations in DNA repair could be considered suitable targets for cancer therapy.

Helping patients master core conflictual relationship themes in psychotherapy.

An important component of case formulation is to understand the patient's difficulties in the context of their relationships. The Core Conflictual Relationship Theme (CCRT) method provides a clinical guide for understanding the narratives of relationship conflicts told during therapy. We follow the case of Barbara, a 60 year old with a long history of chronic shyness. Her narratives follow a common CCRT: she wishes to feel safe, but fears that others are out to get her, which makes her withdraw. These patterns have pervasively repeated themselves in the past, present, and across different relationships (self, family, partners, colleagues). The therapist responds carefully by creating safety, tolerating her fears, and working to overcome these CCRT patterns, thus reducing her impulse to withdraw from treatment. Psychotherapists from many theoretical orientations can learn how patients mastering these repetitive negative CCRTs can lead to more adaptive relationship patterns that improve their mental health.

Predictive value of DNA repair gene expression for response to neoadjuvant chemotherapy in breast cancer

Genome-wide analysis using microarrays has revolutionized breast cancer (BC) research. A substantial body of evidence supports the clinical utility of the 21-gene assay (Oncotype DX) and 70-gene assay (MammaPrint) to predict BC recurrence and the magnitude of benefit from chemotherapy. However, there is currently no genetic tool able to predict chemosensitivity and chemoresistance to neoadjuvant chemotherapy (NACT) during BC treatment. In this study, we explored the predictive value of DNA repair gene expression in the neoadjuvant setting. We selected 98 patients with BC treated with NACT. We assessed DNA repair expression in 98 formalin-fixed, paraffin-embedded core biopsy fragments used at diagnosis and in 32 formalin-fixed, paraffin-embedded post-NACT residual tumors using quantitative reverse transcription-polymerase chain reaction. The following genes were selected: BRCA1, PALB2, RAD51C, BRCA2, ATM, FANCA, MSH2, XPA, ERCC1, PARP1, and SNM1. Of 98 patients, 33 (33.7%) achieved pathologic complete response (pCR). The DNA expression of 2 genes assessed in pre-NACT biopsies (PALB2 and ERCC1) was lower in pCR than in non-pCR patients (P=0.005 and P=0.009, respectively). There was no correlation between molecular subtype and expression of DNA repair genes. The genes BRCA2 (P=0.009), ATM (P=0.004), FANCA (P=0.001), and PARP1 (P=0.011) showed a lower expression in post-NACT residual tumor samples (n=32) than in pre-NACT biopsy samples (n=98). The expression of 2 genes (PALB2 and ERCC1) was lower in pCR patients. These alterations in DNA repair could be considered suitable targets for cancer therapy.

Now and then: a ten-year comparison of young people in residential substance use disorder treatment receiving group dialectical behaviour therapy.

BACKGROUND: Reducing substance use in youth is a global health priority. We compared two cohorts from the same 12-week residential substance use disorder (SUD) facility over a 10 year period: Cohort A (2008-2009) and Cohort B (2018-2020). The essential components of the program remained the same with the primary treatment being dialectical behaviour therapy (DBT) plus residential milieu. METHODS: Young people in the current Cohort B (N = 100) versus historical Cohort A (N = 102) had a similar ratio of males (74 vs. 70%) but were slightly older (mean 20.6 vs. 19.5 years). Linear mixed models were used to model outcome measures (global psychiatric symptoms, substance use severity, and quality of life) longitudinally up to 12 months later. RESULTS: Baseline to end-of-treatment comparisons showed that the current Cohort B had overall higher levels of global psychiatric symptoms (d = 0.70), but both groups reduced psychiatric symptoms (Cohort A: d = 1.05; Cohort B: d = 0.61), and had comparable increases in confidence to resist substance use (d = 0.95). Longitudinal data from the current Cohort B showed significant decreases in substance use severity from baseline to 6-month follow-up (d = 1.83), which were sustained at 12-month follow-up (d = 0.94), and increases in quality of life from baseline to end-of-treatment (d = 0.83). CONCLUSIONS: We demonstrate how DBT plus milieu residential care for young people continues to show positive effects in a 10-year comparison. However, youth seeking treatment today compared to 10 years ago evidenced higher acuity of psychiatric symptoms reinforcing the importance of continuous improvement of psychological treatments. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: trial ID ACTRN12618000866202 , retrospectively registered on 22/05/2018, .

Priorities for service improvement in personality disorder in Australia: Perspectives of consumers, carers and clinicians.

BACKGROUND: Improvements to service provision for personality disorder has been predominately explored through the perspectives of clinicians, with limited understanding of the views of consumers and carers. The aim of the present study was to understand the priorities for service improvement through multiple perspectives. METHOD: Twelve roundtables, with a total of 53 consumers, clinicians and carers, discussed how organizations could improve service provision for people with personality disorder and completed a questionnaire on current and optimal service provision. Inductive thematic analysis was used to identify the priorities for service improvement, and we aimed to identify differences between what participants currently receive and what they believe to be optimal. RESULTS: Four priorities were identified: (1) increasing consumer, carer and peer involvement in care, (2) re-orienting approaches to service provision, (3) improving access and accessibility of treatment and (4) building the capacity of services. Participants were more likely to receive individual or group treatment alone, yet believed combined individual and group treatment to be optimal. Significantly, more participants believed that long-term treatment was optimal. CONCLUSION: A shift in focus from establishing a consistent approach to servicing, to focusing on holistic care that involves consumers and carers in care, is required. © 2020 The Authors Personality and Mental Health Published by John Wiley & Sons Ltd.

Unprecedented generation of 3D heterostructures by mechanochemical disassembly and re-ordering of incommensurate metal chalcogenides.

Three-dimensional heterostructures are usually created either by assembling two-dimensional building blocks into hierarchical architectures or using stepwise chemical processes that sequentially deposit individual monolayers. Both approaches suffer from a number of issues, including lack of suitable precursors, limited reproducibility, and poor scalability of the preparation protocols. Therefore, development of alternative methods that enable preparation of heterostructured materials is desired. We create heterostructures with incommensurate arrangements of well-defined building blocks using a synthetic approach that comprises mechanical disassembly and simultaneous reordering of layered transition-metal dichalcogenides, MX2, and non-layered monochalcogenides, REX, where M = Ta, Nb, RE = Sm, La, and X = S, Se. We show that the discovered solid-state processes are rooted in stochastic mechanochemical transformations directed by electronic interaction between chemically and structurally dissimilar solids toward atomic-scale ordering, and offer an alternative to conventional heterostructuring. Details of composition-structure-properties relationships in the studied materials are also highlighted.

Early treatment response in psychotherapy for depression and personality disorder: links with core conflictual relationship themes.

Objective: Depressed personality disorder patients showing an early rapid response (or sudden gain) in psychotherapy have better outcomes. Early responders are five times more likely to recover, despite equivalent ratings of working alliance. We explored core conflictual relationship themes (CCRTs) of early responders compared to others to further elucidate process-outcome links. Method: Patients (N = 20) with diagnosed major depression and personality disorder received 16 weeks of psychodynamic therapy. Early response was defined as a 50% reduction in Beck Depression Inventory symptoms during the first six sessions. Transcripts of therapy session three for early responders (n = 10) and others (n = 10) were analyzed using the CCRT Leipzig/Ulm method, identifying 728 components scored by two independent judges. Results: Relationship narratives showed CCRT-wish satisfaction was lower for those not having an early response, for both CCRT "Response of Other" and "Response of Self" components. These patients told narratives of others as more unreliable, aggressive, and less supportive, with less feelings of being loved and a lower experience of being self-determined. Conclusions: Specific negative relationship patterns may inhibit the ability to benefit from both therapy and extra-therapy relationships, contributing to a slower treatment response.

Biomarker correlates of psychotherapy outcomes in borderline personality disorder: A systematic review.

Studies of neurobiological mechanisms in borderline personality disorder (BPD) have increased our understanding of the pathophysiology of its development and course. Less is known about how psychotherapy may influence these neurobiological factors, and also whether biomarkers may predict psychotherapy outcomes. We conducted a systematic review using PRISMA guidelines. Fourteen studies providing data from 467 participants diagnosed with BPD met inclusion criteria to: (a) investigate biomarkers predicting response to psychotherapy for BPD; or (b) examine neurobiological factors altered by psychotherapy. Neuroimaging studies (n = 11) used mostly functional magnetic resonance imaging methods to scope brain regions related to emotion regulation and cognitive control. Three studies examined genetic or neuroendocrine markers. The evidence suggests that psychotherapy alters neural activation and connectivity of regions subserving executive control and emotion regulation. Additionally, hypoactivation in prefrontal and cingulate regions predicted treatment response. Further work in this area may inform personalised treatment approaches in clinical practice for BPD through elucidating neural mechanisms of evidence-based psychotherapy.

The relationship between executive functions and emotion regulation in females attending therapeutic community treatment for substance use disorder.

BACKGROUND: Difficulties in emotion regulation influence the development of substance use disorder (SUD), its severity, course, treatment outcomes, and relapse. Impaired executive functions (EFs) are common in SUD populations and may relate to emotion dysregulation. The current study tested whether performance on three basic EF tasks ('working memory', 'inhibition', and 'task-switching') and/or inventory-based assessment of EF were related to difficulties in emotion regulation in females attending residential SUD therapeutic community treatment. METHODS: Cross-sectional design in which participants (N=50, all female) completed a questionnaire battery including the Difficulties in Emotion Regulation Scale (DERS) and Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) was used. Participants also completed neuropsychological assessment of EF including the Working Memory Index (WMI; Wechsler Adult Intelligence Scale), and measures of inhibition and task-switching (Color-Word Interference Test; Delis-Kaplan Executive Function System). RESULTS: Executive dysfunction, as assessed by the Global Executive Composite (GEC; BRIEF-A), and personality disorder indicators (Standardised Assessment of Personality - Abbreviated Scale; SAPAS) were positively correlated with DERS scores. Sequential hierarchical regression indicated that task-switching, GEC, and SAPAS scores statistically predicted DERS scores, while working memory and inhibition did not. Mediation analysis indicated that there was a significant indirect effect of GEC scores and task-switching performance on DERS scores, through SAPAS scores. CONCLUSIONS: Impairment of EF, particularly task-switching, is related to difficulties in emotion regulation in a female sample attending residential SUD treatment. Cognitive training interventions that improve task-switching performance may be beneficial in promoting effective emotion regulation and improved SUD treatment outcomes.

Cognitive remediation improves executive functions, self-regulation and quality of life in residents of a substance use disorder therapeutic community.

BACKGROUND: Executive dysfunction is common in substance use disorder (SUD) populations and hinders treatment. We previously found that 50% of residents in SUD therapeutic communities had been hospitalized for head injuries; this was a significant determinant of cognitive impairment. The current study aimed to establish whether cognitive remediation improves executive functions (EFs) and self-regulation in an ecologically valid sample of female residents attending SUD therapeutic community treatment, including those with past head injuries and psychiatric comorbidities. METHODS: Controlled sequential groups design with residents (N=33, all female) receiving treatment as usual (TAU). The intervention group (n=16) completed four weeks of cognitive remediation (CR) and the control, TAU only (n=17). Outcome measures assessed pre- and post-intervention included both performance- and inventory-based measures of EFs, and self-reported self-regulation and quality of life. RESULTS: CR relative to TAU significantly improved performance-based assessment of inhibition (Color-Word Interference Test; F=4.29, p=0.047), inventory-based assessment of EFs (Behavior Rating Inventory of Executive Function - Adult Version: Global Executive Composite; F=6.38, p=0.017), impulsivity (Barratt Impulsiveness Scale; F=4.61, p=0.040), self-control (Brief Self-Control Scale; F=5.53, p=0.026), and quality of life (Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form; F=7.68, p=0.010). CONCLUSIONS: Findings suggest that CR improves EFs in a heterogeneous sample of female residents in therapeutic community SUD treatment. Future research may explore the possibility of tailoring CR interventions for various SUD subgroups.

Influence of antibody immobilization strategies on the analytical performance of a magneto-elastic immunosensor for Staphylococcus aureus detection.

Magneto-elastic (ME) sensors have a great advantage in microbiology due to their ability to be queried wirelessly. Staphylococcus aureus is one of the most common bacteria widespread in the environment and a major human pathogen related to numerous illnesses. Immunosensors are affinity-based assays where the analyte is highly selective. The immobilization of antibodies (Ab) is an important step in the development of such devices. This study compared the effects of two antibody immobilization strategies on the analytical performance of a magneto-elastic immunosensor: (1) random antibody covalent immobilization (CysAb) and (2) specific-oriented antibody covalent immobilization (PrGAb). Immunosensors were exposed to solutions containing S. aureus at different concentrations (104 to 108CFU/ml) and sensor resonant frequencies were measured. In order to confirm that the frequency shifts were mainly caused by the binding of S. aureus to the sensor's surface, scanning electron microscope (SEM) and indirect immunofluorescence (IIF) images were taken after bacteria exposure at 108CFU/ml. Sensor surfaces were further monitored by non-contact topographic atomic force microscopy (AFM) images. In the covalent-oriented strategy, PrG was first bound covalently to the surface, which in turn, then binds the anti-S. aureus antibody in an oriented manner. Topographic AFM images showed different surface patterns between the two antibody immobilization strategies. Specific-oriented antibody covalent immobilization (PrGAb) strategy gave the highest anti-S. aureus antibody immobilization density. Therefore, the covalent-oriented strategy presented the best performance for S. aureus capture, detecting 104CFU/ml.

Antibody-based magneto-elastic biosensors: potential devices for detection of pathogens and associated toxins.

This work describes the design and development process of an immunosensor. The creation of such devices goes through various steps, which complement each other, and choosing an efficient immobilization method that binds to a specific target is essential to achieve satisfactory diagnostic results. In this perspective, the emphasis here is on developing biosensors based on binding antigens/antibodies on particular surfaces of magneto-elastic sensors. Different aspects leading to the improvement of these sensors, such as the antibody structure, the chemical functionalization of the surface, and cross-linking antibody reticulation were summarized and discussed. This paper deals with the progress of magneto-elastic immunosensors to detect bacterial pathogens and associated toxins. Biologically modified surface characterization methods are further considered. Thus, research opportunities and trends of future development in these areas are finally discussed.

The Montreal Cognitive Assessment (MoCA) is Sensitive to Head Injury and Cognitive Impairment in a Residential Alcohol and Other Drug Therapeutic Community.

INTRODUCTION: Retaining clients in residential alcohol and other drug (AOD) treatment is difficult and cognitive impairment has been identified as a significant predictor of treatment dropout. The application of extensive screening for cognitive impairment is cost-prohibitive for most AOD treatment services. The current study aimed to explore cognitive functioning and impairment-associated factors in a typical sample of residential AOD clients using a free brief screening tool that could be utilised by front-line AOD services. METHODS: Residents of an AOD therapeutic community (n=128) and a non-substance using control group (n=37) were administered a brief cognitive screening measure, the Montreal Cognitive Assessment (MoCA). MoCA total and domain scores were compared between these groups and within the AOD group examined in association with primary substance of misuse, severity of dependence, gender, psychological distress, and history of head injury. RESULTS: Almost half (43.8%) of the AOD sample were identified as cognitively impaired, compared to 16.2% of the control group. Furthermore, 67.2% of the AOD sample had sustained head injuries and 50% of the sample required hospitalization for head injury. History of head injury was a significant determinant of cognitive impairment, and associated with greater levels of psychological distress. CONCLUSIONS: There are high rates of inter-related cognitive impairment, head injuries, and psychological distress among clients in residential AOD treatment. Routine screening of clients at intake for cognitive impairment by means of a brief screening measure such as the MoCA, in combination with the assessment of history of head injuries and comorbid psychological disorders, could inform treatment modifications or adjunct interventions to increase retention and improve long-term outcomes.

Biocompatibility and degradation of gold-covered magneto-elastic biosensors exposed to cell culture.

Magneto-elastic materials (ME) have important advantages when applied as biosensors due to the possibility of wireless monitoring. Commercial Metglas 2826MB3™ (FeNiMoB) is widely used, however sensor stabilization is an important factor for biosensor performance. This study compared the effects of biocompatibility and degradation of the Metglas 2826MB3™ alloy, covered or not with a gold layer, when in contact with cell culture medium. Strips of amorphous Metglas 2826MB3™ were cut and coated with thin layers of Cr and Au, as verified by Rutherford Backscattering Spectroscopy (RBS). Using Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES), the presence of metals in the culture medium was quantitatively determined for up to seven days after alloy exposure. Biocompatibility of fibroblast Chinese Hamster Ovary (CHO) cultures was tested and cytotoxicity parameters were investigated by indirect means of reduction of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) at 1, 2 and 7 days. Cell death was further evaluated through in situ analysis using Acridine Orange/Ethidium Bromide (AO/EB) staining and images were processed with ImageJ software. Ions from Metglas(®) 2826MB3™ induced a degradation process in living organisms. The cytotoxicity assay showed a decrease in the percentage of live cells compared to control for the ME strip not coated with gold. AO/EB in situ staining revealed that most of the cells grown on top of the gold-covered sensor presented a normal morphology (85.46%). Covering ME sensors with a gold coating improved their effectiveness by generating protection of the transducer by reducing the release of ions and promoting a significant cell survival.

Effect of surface roughness on performance of magnetoelastic biosensors for the detection of Escherichia coli.

Escherichia coli are bacteria that must be controlled in the food industry and the hospital sector. Magnetoelastic biosensors offer the promise of rapid identification of these and other harmful antigens. In this work, strips of amorphous Metglas 2826MB3 were cut to size (5 mm × 1 mm) with a microdicing saw and were then coated with thin layers of Cr and Au, as verified by Rutherford backscattering spectroscopy (RBS). Several sensor surfaces were studied: 1) as-cast strip, wheel side; 2) as-cast strip, free surface; and 3) thinned and polished surface. A layer of cystamine was applied to the Au-covered magnetoelastic substrate, forming a self-assembledmonolayer (SAM), followed by antibodies, using a modified Hermanson protocol. The cystamine layer growth was verified by Fourier transform infrared spectroscopy (FTIR) and scanning electronmicroscopy (SEM). The biosensors were exposed to solutions of bacteria and the resonant frequency of the sensors was measured with an impedance analyzer for times up to 100 min. Reductions in the resonant frequency, corresponding to bacteria capture, were measured after optimizing the signal amplitude. For times up to 40 min, high capture rates were observed and thereafter saturation occurred. Saturation values of the frequency shifts were compared with the number of bacteria observed on the sensor using fluorescence microscopy. Parameters associated with capture kinetics were studied for different sensor surfaces. The rough surfaces were found to show a faster response, while the thinned and polished sensors showed the largest frequency shift.

O-naphthoquinone isolated from Capraria biflora L. induces selective cytotoxicity in tumor cell lines.

Biflorin is an o-naphthoquinone isolated from the roots of the plant Capraria biflora L. (Scrophulariaceae). In this study, the cytotoxic effects of biflorin were verified, and late apoptosis was detected in various cancer cell lines by in situ analysis. The cytotoxicity was further evaluated exclusively for 48 h of treatment in different tumor and non-tumor cell lines (Hep-2, HeLa, HT-29, A-375, and A-549, and HEK-293, respectively). The results indicated that biflorin induced selective cytotoxicity in tumor cells. HeLa cells were more susceptible to biflorin, followed by HT-29, A-549, A-375, and Hep-2 at all concentrations (range 5-50 µg/mL), and the highest half-maximal inhibitory concentration IC50 (56.01 ± 1.17 µg/mL) was observed in HEK-293 cells. Late apoptotic/necrotic events, observed by in situ immunostaining with Annexin V, varied with each cell line; an increase in late apoptotic events was observed corresponding to the increase in biflorin dosage. Hep-2 cells showed a greater percentage of late apoptotic events among the tumor cell lines when treated with higher concentrations of biflorin (69.63 ± 2.28%). The non-tumor HEK-293 line showed greater resistance to late apoptotic events, as well as a lower level of cytotoxicity (77.69 ± 6.68%) than the tested tumor lines. The data presented indicate that biflorin showed an important, possibly selective, cytotoxicity against tumor cell lines, thereby revealing a promising novel substance with potential anticancer activity for tumor therapy.