Predictors of Symptomatic Change and Adherence in Internet-Based Cognitive Behaviour Therapy for Social Anxiety Disorder in Routine Psychiatric Care

Objective

A central goal of health care is to improve patient outcomes. Although several studies have demonstrated the effectiveness of therapist guided internet-based cognitive behaviour therapy (ICBT) for social anxiety disorder (SAD), a significant proportion of patients do not respond to treatment. Consequently, the aim of this study was to identify individual characteristics and treatment program related factors that could help clinicians predict treatment outcomes and adherence for individuals with SAD.

Method

The sample comprised longitudinal data collected during a 4-year period of adult individuals (N = 764) treated for SAD at a public service psychiatric clinic. Weekly self-rated Liebowitz Social Anxiety Scale (LSAS-SR) scores were provided. Rates of symptomatic change during treatment and adherence levels were analysed using multilevel modelling. The following domains of prognostic variables were examined: (a) socio-demographic variables; (b) clinical characteristics; (c) family history of mental illness; and (d) treatment-related factors.

Results

Higher treatment credibility and adherence predicted a faster rate of improvement during treatment, whereas higher overall functioning level evidenced a slower rate of improvement. Treatment credibility was the strongest predictor of greater adherence. Having a family history of SAD-like symptoms was also associated with greater adherence, whereas Attention-Deficit/Hyperactivity Disorder (ADHD)-like symptoms, male gender, and family history of minor depression predicted lower adherence. Also, the amount of therapist time spent per treatment module was negatively associated with adherence.

Conclusions

Results from a large clinical sample indicate that the credibility of ICBT is the strongest prognostic factor explaining individual differences in both adherence level and symptomatic improvement. Early screening of ADHD-like symptoms may help clinicians identify patients who might need extra support or an adjusted treatment. Therapist behaviours that promote adherence may be important for treatment response, although more research is needed in order to determine what type of support would be most beneficial.     

Rapid synthesis of antimicrobial paper under microwave irradiation

The silver-nanoparticle (AgNP) containing paper was successfully prepared. The AgNP is deposited by the in situ reduction of silver nitrate on the acrylamide grafted bagasse paper sheets in the presence of citrate molecules as stabilizing agent. In the present paper, grafting of acrylamide onto bagasse paper sheets using potassium persulfate was carried out under the influence of microwave radiations (MWR). The modified paper sheets were characterized by Fourier transform infrared spectroscopy (FTIR), UV-spectroscopy, and scanning electron microscopy (SEM). Antimicrobial activities of the prepared paper sheets were also investigated against G+ve bacterium Staphylococcus aureus, G-ve bacterium Pseudomomas aeruginosa, and yeast Candida albicans, which are model microorganisms for testing bactericidal properties. The AgNP containing paper sheets exhibited antibacterial activity.     

Supraspinatus tendon organizational and mechanical properties in a chronic rotator cuff tear animal model

Rotator cuff tears of the shoulder are a common cause of pain and disability. The successful repair of rotator cuff tendon tears depends on the time from onset of injury to the time of surgical repair. However, the effect of time from injury to repair remains poorly understood. A rat model was used to investigate the supraspinatus tendon organizational and mechanical property changes that occur with time post-injury to understand the natural injury response in the absence of repair. It was hypothesized that increased time post-injury would result in increased detrimental changes to tendon organizational and mechanical properties. Tendons were detached at the insertion on the humerus without repair and the quantitative organizational and mechanical properties were analyzed at 1, 2, 4, 8, and 16 weeks post-detachment. Tendon detachment resulted in a dramatic decrease in mechanical properties initially followed by a progressive increase with time. The quantitative collagen fiber orientation results provided corroborating support to the mechanical property data. Based on similarities in histology and mechanical properties to rotator cuff tears in humans, the animal model presented here is promising for future investigations of the tendon's natural injury response in the absence of repair.     

Roles of Arg-97 and Phe-113 in regulation of distal ligand binding to heme in the sensor domain of Ec DOS protein. Resonance Raman and mutation study

The direct oxygen sensor protein isolated from Escherichia coli (Ec DOS) is a heme-based signal transducer protein responsible for phosphodiesterase (PDE) activity. Binding of O(2), CO, or NO to a reduced heme significantly enhances the PDE activity toward 3',5'-cyclic diguanylic acid. We report stationary and time-resolved resonance Raman spectra of the wild-type and several mutants (Glu-93 --> Ile, Met-95 --> Ala, Arg-97 --> Ile, Arg-97 --> Ala, Arg-97 --> Glu, Phe-113 --> Leu, and Phe-113 --> Thr) of the heme-containing PAS domain of Ec DOS. For the CO- and NO-bound forms, both the hydrogen-bonded and non-hydrogen-bonded conformations were found, and in the former Arg-97 forms a hydrogen bond with the heme-bound external ligand. The resonance Raman results revealed significant interactions of Arg-97 and Phe-113 with a ligand bound to the sixth coordination site of the heme and profound structural changes in the heme propionates upon dissociation of CO. Mutation of Phe-113 perturbed the PDE activities, and the mutation of Arg-97 and Phe-113 significantly influenced the transient binding of Met-95 to the heme upon photodissociation of CO. This suggests that the electrostatic interaction of Arg-97 and steric interaction of Phe-113 are crucial for regulating the competitive recombination of Met-95 and CO to the heme. On the basis of these results, we propose a model for the role of the heme propionates in communicating the heme structural changes to the protein moiety.     

Assessment of atrial regional and global electromechanical function by tissue velocity echocardiography: a feasibility study on healthy individuals

Background

Myocardial contrast echocardiography and coronary flow velocity pattern with a rapid diastolic deceleration time after percutaneous coronary intervention has been reported to be useful in assessing microvascular damage in patients with acute myocardial infarction.

Aim

To evaluate myocardial contrast echocardiography with harmonic power Doppler imaging, coronary flow velocity reserve and coronary artery flow pattern in predicting functional recovery by using transthoracic echocardiography.

Methods

Thirty patients with anterior acute myocardial infarction underwent myocardial contrast echocardiography at rest and during hyperemia and were quantitatively analyzed by the peak color pixel intensity ratio of the risk area to the control area (PIR). Coronary flow pattern was measured using transthoracic echocardiography in the distal portion of left anterior descending artery within 24 hours after recanalization and we assessed deceleration time of diastolic flow velocity. Coronary flow velocity reserve was calculated two weeks after acute myocardial infarction. Left ventricular end-diastolic volumes and ejection fraction by angiography were computed.

Results

Pts were divided into 2 groups according to the deceleration time of coronary artery flow pattern (Group A; 20 pts with deceleration time ≧ 600 msec, Group B; 10 pts with deceleration time < 600 msec). In acute phase, there were no significant differences in left ventricular end-diastolic volume and ejection fraction (Left ventricular end-diastolic volume 112 ± 33 vs. 146 ± 38 ml, ejection fraction 50 ± 7 vs. 45 ± 9 %; group A vs. B). However, left ventricular end-diastolic volume in Group B was significantly larger than that in Group A (192 ± 39 vs. 114 ± 30 ml, p < 0.01), and ejection fraction in Group B was significantly lower than that in Group A (39 ± 9 vs. 52 ± 7%, p < 0.01) at 6 months. PIR and coronary flow velocity reserve of Group A were higher than Group B (PIR, at rest: 0.668 ± 0.178 vs. 0.248 ± 0.015, p < 0.0001: during hyperemia 0.725 ± 0.194 vs. 0.295 ± 0.107, p < 0.0001; coronary flow velocity reserve, 2.60 ± 0.80 vs. 1.31 ± 0.29, p = 0.0002, respectively).

Conclusion

The preserved microvasculature detecting by myocardial contrast echocardiography and coronary flow velocity reserve is related to functional recovery after acute myocardial infarction.     

The VNTR polymorphism in the human dopamine transporter gene: improved detection and absence of association of VNTR alleles with attention-deficit hyperactivity disorder

The human dopamine transporter (DAT1) gene contains a variable number tandem repeat (VNTR) in its 3'-untranslated region because of repetition of a 40-bp core sequence. Methods available for the diagnosis of this polymorphism are limited in number. We have developed a new polymerase chain reaction (PCR) test, which is similar to that described originally by Vandenbergh's group, but provides a better detection of the VNTR alleles in the human DAT1 gene. Using two independent PCR methods, we have determined the distribution of VNTR alleles in 110 healthy Omani subjects, and in 92 children with attention-deficit hyperactivity disorder (ADHD). The frequency of the risk allele (DAT1*10) was similar in the healthy subjects and ADHD cases, indicating absence of association of this allele with ADHD in Oman.     

Comprehensive Ubiquitin E2 Profiling of Ten Ubiquitin E3 Ligases

The ubiquitin pathway regulates diverse functions including protein localization and stability. The complexity of the pathway involving nearly 40 identified E2 conjugating enzymes and over 600 E3 ligases raises the issue of specificity. With the E2s and E3s fitting into a limited number of classes based on bioinformatics, structures, and proven activities, there is not a clear picture as to what would determine which E2/E3 enzyme pair would be functional. There have been many reports of limited E2/E3 activity profiling with a small number of E2s and E3s. We have expanded on this to investigate the activity of ubiquitin E2s covering the majority of the reported classes/families in concert with a number of E3s implicated in a variety of diseases. Using an ELISA-based assay we screened 10 E3 ligases against a panel of 11 E2s to determine which E2/E3 pairs exhibited E3 autoubiquitylation activity. In addition, the ubiquitin chain linkage preference by certain E2/E3 pairs was investigated. Finally, substrate ubiquitylation was assayed for the E3 ligase MuRF1 using various E2/MuRF1 pairs. These studies demonstrate the utility of identifying the correct E2/E3 pair to monitor specific substrate ubiquitylation.     

Retrotransposons in <Emphasis Type="Italic">Betula nana</Emphasis>, and interspecific relationships in the Betuloideae,based on inter-retrotransposon amplified polymorphism (IRAP) markers

The Betulaceae family comprises two subfamilies, Betuloideae and Corylaceae. The subfamily Betuloideae contains two genera, Alnus Mill. and Betula L. Twenty putative long terminal repeat (LTR) retrotransposons were mined from 171 scaffolds containing 5,208,995 bp of dwarf birch (Betula nana) genome sequences. Five retrotransposons were finally selected after filtering the retrotransposon canonical features and nucleotide similarities between left and right LTR sequences. Of the five retroelements, three elements were found to be Ty1/Copia retrotransposons; identity of the other two elements could not be ascertained due to sequence undetermined ‘N’ bases in the sequence database. Inter-retrotranposon amplified polymorphism (IRAP) analysis, based on the LTR sequences of the mined LTR-retrotransposons, produced 179 discernible IRAP bands among the Alnus and Betula genera. Sequence analysis revealed no size homoplasy among the homologous IRAP bands. Phylogenetic and principle coordinate analysis, based on the band sharing among the taxa, showed the species in two different genera were clearly separated. The subgenera in each genus of Alnus and Betula were also distinguishable from the IRAP profiles. In the genus Betula, the species in subgenus Betula showed mixed clustering between species. This is incongruent with the phylogeographical distribution of the species.     

Development of bis-locked nucleic acid (bisLNA) oligonucleotides for efficient invasion of supercoiled duplex DNA

In spite of the many developments in synthetic oligonucleotide (ON) chemistry and design, invasion into double-stranded DNA (DSI) under physiological salt and pH conditions remains a challenge. In this work, we provide a new ON tool based on locked nucleic acids (LNAs), designed for strand invasion into duplex DNA (DSI). We thus report on the development of a clamp type of LNA ON—bisLNA—with capacity to bind and invade into supercoiled double-stranded DNA. The bisLNA links a triplex-forming, Hoogsteen-binding, targeting arm with a strand-invading Watson–Crick binding arm. Optimization was carried out by varying the number and location of LNA nucleotides and the length of the triplex-forming versus strand-invading arms. Single-strand regions in target duplex DNA were mapped using chemical probing. By combining design and increase in LNA content, it was possible to achieve a 100-fold increase in potency with 30% DSI at 450 nM using a bisLNA to plasmid ratio of only 21:1. Although this first conceptual report does not address the utility of bisLNA for the targeting of DNA in a chromosomal context, it shows bisLNA as a promising candidate for interfering also with cellular genes.