Significant Posttreatment Changes Research Articles

Effect of orthodontic premolar extraction on maxillary teeth angulation and arch dimensions in adolescent patients: A 3-D digital model analysis.

Therapeutic orthodontic premolar extraction is a common orthodontic treatment, yet the extent of its impact on the upper dental arch dimensions and teeth angulations is still under exploration. Hypothesis: We postulated that the therapeutic extraction of orthodontic premolars significantly alters the orientation of teeth and the dimensions of the dental arch. Objective: This study assessed the impact of therapeutic orthodontic premolar extraction on dental arch dimensions and tooth angulations. We conducted a retrospective cohort study involving 30 patients who underwent bilateral upper premolar extraction and fixed appliance treatment. Pre and post-treatment dental casts were scanned, and changes in tooth angulations and arch dimensions were evaluated using 3D digital maxillary models. Statistical analyses encompassed the application of paired samples t-test. Significant post-treatment changes were observed, including distal tipping in anterior teeth, minor mesial tipping in first molars, and a reduction in torque for central incisors and canines. Dental arch dimensions were also influenced, with increased width and depth between the canines and decreased width between the second premolars while inter-molar width and overall arch depth significantly reduced post-treatment. Therapeutic orthodontic premolar extraction significantly affects dental arch dimensions and tooth angulations. These findings have implications for treatment planning and predicting changes associated with orthodontic treatments involving premolar extraction. Key words:3D digital models - orthodontic premolar extraction - teeth angulation - dental arch dimensions.

Evaluation of efficacy and safety of Amarantha footcare cream in subjects suffering from cracked heels (xerosis of the feet): A randomized, open labeled, multi-centric, comparative, interventional, prospective, clinical study

Xerosis of the foot can lead to cracks in plantar surface with discomfort, pain, and predisposition to infection. This study was conducted to evaluate the comparative efficacy and safety of Amarantha footcare cream (AFC) in subjects suffering from cracked heels (xerosis of feet). A total of 95 subjects (32 in AFC group, 31 in marketed cracked heal cream [MCHC] group, and 32 in Amarantha wound healing cream [AWHC] group) were completed the study. All trial subjects were advised to apply sufficient quantity of given creams, twice daily for 28 days or till complete clearance of the cracked heel, whichever was earlier. Study subjects were called for follow-up visits on days 7, 14, 21, and 28. Clinical trial registry of India registration number is CTRI/2020/11/028829. The mean days required for complete healing of cracked heel were 16.69, 22.96, and 25.74 in AFC, MCHC, and AWHC groups. The mean xerosis score was significantly reduced (P < 0.01) in AFC group than other groups from baseline to end of study. Majority of the patients showed a significant (P < 0.01) improvement in xerosis assessment scale (normal skin) along with a significant (P < 0.01) reduction in skin roughness score, mean hyperkeratosis score, and mean overall clinical cutaneous score at the end of the study. Almost all the patients showed a significant overall improvement after the completion of the study. No significant posttreatment changes were observed in any of the vital or laboratory parameters. AFC is safe and effective for the treatment of cracked heels (planter xerosis).

Outcomes of an interprofessional intensive comprehensive aphasia program’s first five years

ABSTRACT Background and Objectives This ICAP program is a collaboration between an institute of health professions and a rehabilitation hospital. It was a 6-week intensive treatment program for people with post-stroke aphasia designed to maximize recovery and return to activities. This retrospective study investigated outcomes of this program offered annually from 2015 to 2019. Methods This is an analysis of existing data collected for other purposes. While conducting a therapeutic program for people with aphasia, data were not collected for the purpose of conducting research. The treatment components addressed the activity participation goals of 35 participants. Programming consisted of individual and group speech-language and occupational therapy, adaptive sports, swimming, music therapy, and a wellness mindfulness group.. Participants received a comprehensive evaluation and a treatment plan addressing their individual participation goals, delivered primarily by SLP and OT graduate students under faculty supervision. Pre- and post-treatment outcomes were measured within four WHO ICF domains: impairment, participation, environment, person. Each cohort consisted of seven or eight community-dwelling participants seen four days/week. Results Significant post-treatment changes were observed on measures within the impairment domain and on self-perception measures of participation, functional communication, and communication confidence. Subsequent analyses found a subset of 15 responders (WAB Aphasia Quotient change of ≥5) drove most significant effects seen on performance-based impairment measures, but that patient-reported self-perception measures showed significant changes in both responders and non-responders. Conclusions Results support research indicating that short-term intensive, interprofessional comprehensive aphasia programs (ICAPs) are effective treatment options for people with moderate-to-severe aphasia.

Effectiveness of Aromatherapy and Music Distraction in Managing Pediatric Dental Anxiety: A Comparative Study.

BackgroundManaging a child's anxiety is most critical for the success of treatment in the pediatric dental setup. Present trend advocates the use of non-aversive behavior management techniques.Aim and objectiveTo compare and evaluate the efficacy of aromatherapy using orange essential oil with that of music distraction in the management of anxious pediatric dental patients.DesignOne hundred and fifty children of the age 6–8 years were divided into three groups of 50 each and performed restorative treatment under aromatherapy, with music distraction, without aromatherapy, or music distraction, respectively. Venham's picture test and facial image scale (FIS), pulse rate, respiratory rate, and oxygen saturation were recorded before and after the procedure.ResultsCompared with controls, both the aromatherapy group and music distraction group showed significant posttreatment change in anxiety levels with respect to Venham's picture test and FIS, along with the reduction in pulse rate and respiratory rate. When compared between music distraction and aromatherapy, it did not yield statistical significance, though music distraction showed better results compared to aromatherapy.ConclusionBoth music distraction and aromatherapy using orange essential oil are effective in anxiety management of which music distraction presents a comparatively better result. Either these non-invasive techniques alone or a combination of both may be employed in the dental setup of pediatric dentists for molding cooperative patients.How to cite this articleJames J, Retnakumari N, Vadakkepurayil K, et al. Effectiveness of Aromatherapy and Music Distraction in Managing Pediatric Dental Anxiety: A Comparative Study. Int J Clin Pediatr Dent 2021;14(2):249–253.

One-Year Stability of LeFort I Advancement in Patients With Complete Cleft Lip and Palate Using a Standardized Clinical and Surgical Protocol.

To assess treatment outcome and 1-year stability of LeFort I advancement in patients with complete cleft lip and palate. Thirty-five patients (age 20.65 ± 2.20 years) with unilateral (n = 25) or bilateral (n = 10) complete cleft lip and palate who underwent LeFort I advancement were included.Lateral cephalograms before surgery (T1), immediately postsurgery (T2), and at 1-year follow-up (T3) were superimposed, and the position of anterior nasal spine (ANS), A-point, and U1 Tip assessed using an x, y coordinate system. Differences between landmark positions at the 3-time points were analyzed using paired sample t-tests, with a significance defined as α ≤ 0.05. The mean surgical advancement in the horizontal direction (T2-T1) was 6.50 ± 2.62 mm at ANS (P < 0.001) and 7.05 ± 2.51 mm at A-point (P < 0.001). At a 1-year follow-up (T3-T2), the mean horizontal relapse at ANS was -1.41 ± 1.89 mm (P < 0.001) and -0.79 ± 1.48 mm at A-point (P 0.003). Mean horizontal relapse was 21.7% and 11% of surgical advancement when assessed at ANS and A-point, respectively. The central incisor tip position remained stable during the postsurgical period (0.12 ± 2.11 mm, P 0.732). At A-point, the mean vertical surgical change (T2-T1) was -0.96 ± 2.57 mm (P < 0.001). No significant post-treatment (T3-T2) vertical changes were detected at ANS or A-point. Phenotypic stability was excellent, with all patients maintaining positive overjet at 1-year follow-up. LeFort I advancement in complete cleft lip and palate is stable, with less than a 2 mm relapse after 1-year. Surgical overcorrection by 10% to 20% is recommended to compensate for the expected skeletal relapse.

LSVT LOUD® Applied to an Adult With Cerebral Palsy: Acoustic Findings

A 36-year-old female with severe spastic dysarthria participated in this study. She received 4 weeks of individual, intensive voice-focused treatment. Voice recordings were conducted at three baseline points, immediately posttreatment, and at a 4-month follow-up. The primary outcome variables were selected acoustic measures of vocal function: sound pressure level (SPL), mean fundamental frequency (F0), maximum phonation time (MPT), jitter, shimmer, noise-to-harmonics ratio (NHR), and maximum phonation frequency range (MPFR). Significant pre-to-posttreatment changes ( p &lt; .05) were found for most acoustic variables. All acoustic gains, except for MPFR, were maintained at the 4-month follow-up. The significant posttreatment changes in the majority of the acoustic measures analyzed suggest that intensive voice-focused treatment may have the potential to improve vocal function in adults with severe spastic dysarthria secondary to cerebral palsy (CP). Evidence-based treatment options for voice disorders in adults with CP are limited. Results emphasize the need for more studies with this population.

Considering tumour volume for motion corrected DWI of colorectal liver metastases increases sensitivity of ADC to detect treatment-induced changes

ADC is a potential post treatment imaging biomarker in colorectal liver metastasis however measurements are affected by respiratory motion. This is compounded by increased statistical uncertainty in ADC measurement with decreasing tumour volume. In this prospective study we applied a retrospective motion correction method to improve the image quality of 15 tumour data sets from 11 patients. We compared repeatability of ADC measurements corrected for motion artefact against non-motion corrected acquisition of the same data set. We then applied an error model that estimated the uncertainty in ADC repeatability measurements therefore taking into consideration tumour volume. Test-retest differences in ADC for each tumour, was scaled to their estimated measurement uncertainty, and 95% confidence limits were calculated, with a null hypothesis that there is no difference between the model distribution and the data. An early post treatment scan (within 7 days of starting treatment) was acquired for 12 tumours from 8 patients. When accounting for both motion artefact and statistical uncertainty due to tumour volumes, the threshold for detecting significant post treatment changes for an individual tumour in this data set, reduced from 30.3% to 1.7% (95% limits of agreement). Applying these constraints, a significant change in ADC (5th and 20th percentiles of the ADC histogram) was observed in 5 patients post treatment. For smaller studies, motion correcting data for small tumour volumes increased statistical efficiency to detect post treatment changes in ADC. Lower percentiles may be more sensitive than mean ADC for colorectal metastases.

The Effect of Panretinal Photocoagulation (PRP) versus Intravitreal Bevacizumab (IVB) Plus PRP on Peripapillary Retinal Nerve Fiber Layer (RNFL) Thickness Analyzed by Optical Coherence Tomography in Patients with Proliferative Diabetic Retinopathy.

Purpose:The current study aimed to evaluate changes in peripapillary retinal nerve fiber layer (RNFL) thickness in diabetic patients with bilateral proliferative diabetic retinopathy (PDR) after receiving panretinal photocoagulation (PRP) or intravitreal bevacizumab (IVB) with PRP.Methods:Ocular examination and peripapillary optical coherent tomography (OCT) were performed for each patient at baseline, 1, 3, 6, and 10 months after treatment. Both eyes of each patient were randomized into either PRP or PRP + IVB group.Results:Sixty-four eyes (32 patients) were enrolled in this randomized clinical trial. In the PRP group, global RNFL thickness initially increased and reached statistical significance in the third month (from 105.9 ± 21.4μm at baseline to 119 ± 41.6μm at 3 months, P = 0.03). Subsequent decline was observed with no significant difference from baseline at 10 months (106 ± 19.3μm, P = 0.914). There were no statistically significant changes in the PRP + IVB group (from 101.7 ± 22.2μm at baseline to 109.3 ± 26.9μm at 3 months, P = 0.996 and 101.9 ± 16.5μm at 10 months, P = 0.999). In the latter group, slight increase in RNFL thickness was observed in the first month (107.7 ± 21.1μm). RNFL thickness was similar to baseline in the two groups at month 10, with the exception of significant increase in superior-temporal sector in the PRP group (145.3 ± 13.4μm vs. 127.2 ± 17.3μm, P = 0.045).Conclusion:Compared to eyes treated with PRP, eyes treated with adjunctive IVB showed less significant post-treatment changes in RNFL thickness.

Safety and initial efficacy of radiation segmentectomy for the treatment of hepatic metastases​.

Hepatic metastatectomy and ablation are associated with prolonged survival, but not all lesions are anatomically amenable to these therapies. We evaluated safety and initial efficacy of segmental ablative transarterial radioembolization, or radiation segmentectomy (RS), as a treatment for hepatic metastases. A single institution retrospective analysis was performed of patients with hepatic metastases, determined unamenable to resection by a multidisciplinary tumor board, treated with RS from 2015-2017. Safety parameters evaluated were pre and post procedure liver chemistry, MELD score, ALBI grade, platelet count, and adverse events using both Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 and Clavien Dindo (CD) classifications. Initial efficacy was evaluated using RECIST, mRECIST, and PERCIST criteria. Ten patients underwent between 1-3 RS treatments. There was no clinical treatment toxicity or significant post-treatment change in liver chemistry, MELD, or ALBI score. One patient had a CTCAE Grade 1/CD Grade 1 adverse event. All patients showed partial or complete imaging response at initial assessment (1-3 months). Seven patients demonstrated disease control at a mean of 7.1 months post treatment. Three patients developed out of field disease progression. One RS was technically unsuccessful. Early evaluation of segmental radioembolization suggests a safe treatment option for select patients with hepatic metastases. Initial efficacy as definitive radiotherapy with minimal toxicity is promising in anatomic locations unamenable to resection or alternative means of ablation.

TYPE 2 DIABETES;

Background: The data among vitamin D supplementation on glycemic control isvariable and contradictory in various clinical studies. Objectives: To determine the efficacy of vitD supplementation on glycemic control in type 2 diabetic patients. Study Design: Case controlstudy. Setting: Private Clinical Set up of District, Rahim Yar Khan. Period: August to October2016. Patients and methods: 100 cases of type 2 diabetes were randomly divided into groupA and group B each contained 50 patients .The cases in group A were treated with vitamin D3at the dose of 50,000 units per week orally while cases in group B were treated with placeboalong with the standard doses of anti-diabetic drugs. The value of HbA1c and Vit D wereassayed pre and post treatment by high performance liquid chromatography. Results: Therewas significant post treatment changes observed in vitamin D level in group A vs group B inmales 20.46±2.45 vs 15.16±1.47 (p= 0.001) and females 18.32±1.44 vs 13.95±2.48 (p= 0.09)There was significant post treatment changes in HbA1c in males 6.65±0.12 vs 8.34±0.71 (p=0.01) and in females 6.81±0.43 vs 8.04±0.71 (p= 0.03) in group A and group B respectively.Similarly better improvement in vitamin D and HbA1c level was seen with respect to aged group30-50 years and duration of diabetes less than 5 years. Conclusion: Vitamin D is deficient in ourpopulation and its supplementation not only improves its own level but also glycemic control intype 2 diabetic patients.

English

Background: The data among vitamin D supplementation on glycemic control isvariable and contradictory in various clinical studies. Objectives: To determine the efficacy of vitD supplementation on glycemic control in type 2 diabetic patients. Study Design: Case controlstudy. Setting: Private Clinical Set up of District, Rahim Yar Khan. Period: August to October2016. Patients and methods: 100 cases of type 2 diabetes were randomly divided into groupA and group B each contained 50 patients .The cases in group A were treated with vitamin D3at the dose of 50,000 units per week orally while cases in group B were treated with placeboalong with the standard doses of anti-diabetic drugs. The value of HbA1c and Vit D wereassayed pre and post treatment by high performance liquid chromatography. Results: Therewas significant post treatment changes observed in vitamin D level in group A vs group B inmales 20.46±2.45 vs 15.16±1.47 (p= 0.001) and females 18.32±1.44 vs 13.95±2.48 (p= 0.09)There was significant post treatment changes in HbA1c in males 6.65±0.12 vs 8.34±0.71 (p=0.01) and in females 6.81±0.43 vs 8.04±0.71 (p= 0.03) in group A and group B respectively.Similarly better improvement in vitamin D and HbA1c level was seen with respect to aged group30-50 years and duration of diabetes less than 5 years. Conclusion: Vitamin D is deficient in ourpopulation and its supplementation not only improves its own level but also glycemic control intype 2 diabetic patients.

Potential Interest in Circulating miR-BART17-5p As a Post-Treatment Biomarker for Prediction of Recurrence in Epstein-Barr Virus-Related Nasopharyngeal Carcinoma.

ObjectivesEpstein-Barr virus (EBV)-related micoRNAs (miRNAs), BamHI-A rightward transcripts (BART)-miRNAs, are released in a stable form from viable cells, which are abundant in patients with EBV-positive nasopharyngeal carcinoma (NPC). We estimated copy numbers of circulating miR-BART2-5p, miR-BART17-5p, and miR-BART18-5p as well as BamHI-W DNA as biomarkers.Materials and MethodsSerums from 31 EBV-positive (confirmed by in situ hybridization for EBV-encoded small RNAs) NPC patients and 40 non-NPC controls were analyzed. Among the 31 NPC patients, serums at the initial diagnosis and three months after treatment were obtained from 20 patients, and serums only at three months after treatment were obtained from 11 patients.ResultsThe sensitivity/specificity of circulating BamHI-W DNA, miR-BART2-5p, miR-BART17-5p, and miR-BART18-5p for the diagnosis of NPC before treatment were 100 / 100, 85 / 85, 60 / 95, and 25 / 100%, respectively. For BamHI-W DNA, NPC patients with stage IV disease had significantly higher copy numbers than those with I-III. Copy numbers decreased significantly post-treatment. In contrast, copy numbers of the three BART-miRNAs showed no significant correlation with the clinical stage at diagnosis or any significant post-treatment change. After treatment, BamHI-W DNA and miR-BART17-5p were detected in 5 and 6 cases out of 11 patients with recurrent or residual tumors, respectively. However, BamHI-W DNA and miR-BART17-5p were absent in all 20 patients without relapse or residual tumors.ConclusionThe copy number of circulating BamHI-W DNA is a more useful biomarker for the initial diagnosis of NPC than the three BART-miRNAs examined. Post-treatment detection of miR-BART17-5p is a potential biomarker of a poor prognosis.

A three-year evaluation of triclopyr for selective whole-bay management of Eurasian watermilfoil on Lake Minnetonka, Minnesota

Impact of whole-bay, low-dose triclopyr applications for selective control of Eurasian watermilfoil (Myriophyllum spicatum: EWM) was evaluated on Lake Minnetonka, Minnesota, from 2011 to 2013. To assess invasive and native plant frequency and abundance over multiple seasons following management, we collected plant frequency, herbicide concentration, biomass, and hydroacoustic data. Two enclosed bays, St. Albans (64 ha) and Grays (64 ha), were treated at 300 μg/L. St. Albans was treated in late May 2011 and 2013 and Grays was treated in late May 2012. Triclopyr half-lives ranged from 8.6 to 12.1 days. A larger, more open bay, Gideons (133 ha), was treated by targeting 50 ha of EWM beds at 1500 μg/L in early June 2011. Triclopyr half-lives in Gideons treatment blocks averaged 3.7 days with a bay-wide half-life of 9.4 days. Near complete loss of EWM in the 3 bays was observed the year of treatment. Increased EWM frequency was observed the following June and August; however, EWM remained a minor component of bay-wide biomass (<2%). Number of points with native plants, mean native species per point, and native species richness in the bays were not reduced following treatment. Native species decreasing in frequency included Myriophyllum sibiricum, Zosterella dubia, Elodea canadensis, and Potamogeton zosteriformis. Most native plants showed no significant posttreatment change in frequency. Hydroacoustic data did not indicate bay-wide decreases in percent coverage or biovolume. Treatments provided up to 2 seasons of EWM control without reducing the overall distribution and abundance of native plants.

Abstract 1307: Assessment of gene expression in peripheral blood from patients with advanced melanoma using RNA-seq before and after treatment with anti-PD-1 therapy with pembrolizumab (MK-3475)

Abstract Pembrolizumab (MK-3475) is a humanized monoclonal IgG4 antibody against programmed death receptor 1 (PD-1) that is currently being studied in clinical trials across more than 30 types of cancer. Gene expression profiling was used to explore a less invasive method for gaining new insights into the pembrolizumab mechanism of action and to assess the potential for blood-based predictive biomarkers. RNA-seq data were obtained from the whole blood of 44 patients with advanced melanoma enrolled in the phase 1 KEYNOTE-001 clinical study before and after the first cycle of treatment with pembrolizumab. Objective response rates (ORR) were assessed per RECIST v1.1 by independent central review. The pembrolizumab dose and treatment schedule varied among the patients studied and included 10 mg/kg given once every 3 weeks (Q3W) (n = 21), 10 mg/kg Q2W (n = 12), and 2 mg/kg Q3W (n = 11). Among the 44 patients with melanoma included in the analysis, 75% received previous ipilimumab treatment. The ORR was 32%. Significant posttreatment changes in gene expression were confirmed for the target, PD-1, and its key ligand, programmed death ligand 1 (PD-L1). Changes in PD-1 and PD-L1 gene expression did not, however, show a significant association with ORR. Statistically significant posttreatment changes for an interferon-gamma (IFNG)-related 10-gene signature were observed (P &amp;lt; 0.002, upregulated in 70% of patients), and these changes were also associated with improved clinical outcome in terms of ORR (P = 0.042) and progression-free survival (P = 0.010). There appeared to be a possible association between IFNG gene signature posttreatment changes in blood in tumors with higher PD-L1 expression at baseline. There were no clear differences between posttreatment changes in the IFNG gene signature according to previous ipilimumab treatment. Baseline blood expression levels for PD-1, PD-L1, and the IFNG 10-gene signature were not found to be associated with clinical outcome. Additional post hoc analyses of baseline expression in combination with pathway analysis showed that the more highly ranked genes were linked to oxidative phosphorylation, suggesting that for patients whose tumors are not responding to pembrolizumab, their T cells may not be engaged with glycolysis, which is important for the transcriptional regulation of IFNG. The observation that nonresponders showed a lack of ability to induce activation of IFNG signaling suggests a possible link to defective T-cell effector function and may provide a means by which to monitor patient response to anti-PD-1 therapy. Citation Format: Mark D. Ayers, Michael Nebozhyn, Heather A. Hirsch, Razvan Cristescu, Erin E. Murphy, S. Peter Kang, Scot W. Ebbinghaus, Terrill K. McClanahan, Andrey Loboda, Jared K. Lunceford. Assessment of gene expression in peripheral blood from patients with advanced melanoma using RNA-seq before and after treatment with anti-PD-1 therapy with pembrolizumab (MK-3475). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1307. doi:10.1158/1538-7445.AM2015-1307

Preventing addiction related suicide: A pilot study

Persons addicted to alcohol and drugs are at 5–10 times higher risk for suicide as compared to the general population. To address the need for improved suicide prevention strategies in this population, the Preventing Addiction Related Suicide (PARS) module was developed. Pilot testing of 78 patients demonstrated significant post-treatment changes in knowledge [t(66)=12.07, p=.000] and attitudes [t(75)=6.82, p=.000] toward suicide prevention issues. Significant gains were maintained at 1-month follow-up for changes in knowledge [t(55)=6.33, p=.000] and attitudes [t(61)=3.37, p=.0001], with changes in positive help seeking behaviors in dealing with suicidal issues in friends [χ2(1) =10.49, p=.007], family [χ2(1)=9.81, p=.015], and self [χ2(1)=19.62, p=.008] also observed. The PARS was also highly rated by treatment staff as feasible within their standard clinical practice.

Effects of an early intervention on perceived stress and diurnal cortisol in pregnant women with elevated stress, anxiety, and depressive symptomatology

The goal of the present investigation was to examine effects of a cognitive-behavioral group intervention for pregnant women with subclinically elevated stress, anxiety and/or depression on perceived stress and salivary cortisol levels. Expectant mothers were recruited in gynaecologist practices. They participated in a screening, a standardized diagnostic interview (Munich-Composite Diagnostic Interview, M-CIDI), and were randomly assigned to an intervention (N = 21) and treatment as usual control group (N = 40). The intervention consisted of a manualized cognitive-behavioral group program for expectant mothers with subclinically elevated stress, depression, and/or anxiety symptoms. Stress questionnaire (prenatal distress (PDQ), perceived stress (PSS)) as well as diurnal salivary cortisol assessment took place at T1 (antenatal, preintervention), at T2 (antenatal, post-intervention) and T3 (3-month postpartum). Subjects that participated in the intervention exhibited a significant post-treatment change in morning cortisol (cortisol awakening response, CAR) in contrast to control subjects, F(8,51) = 2.300, p = 0.047. Intervention participants showed a smaller CAR subsequent to the intervention, displaying a lessened stress reaction. This effect was not observed in the control group. In contrast, we failed in discovering a significant difference between the research groups regarding the cortisol area under curve parameter (AUC) and the applied subjective stress questionnaires. Evaluation results were thus heterogeneous. Nevertheless, intervention effects on the CAR are promising. Our results suggest that a cognitive-behavioral intervention might lead to an improvement in the biological stress response of pregnant women with subclinically elevated stress, anxiety, or depressive symptoms.

Phase I Clinical Trial of Systemically Administered TUSC2(FUS1)-Nanoparticles Mediating Functional Gene Transfer in Humans

BackgroundTumor suppressor gene TUSC2/FUS1 (TUSC2) is frequently inactivated early in lung cancer development. TUSC2 mediates apoptosis in cancer cells but not normal cells by upregulation of the intrinsic apoptotic pathway. No drug strategies currently exist targeting loss-of–function genetic abnormalities. We report the first in-human systemic gene therapy clinical trial of tumor suppressor gene TUSC2.MethodsPatients with recurrent and/or metastatic lung cancer previously treated with platinum-based chemotherapy were treated with escalating doses of intravenous N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTAP):cholesterol nanoparticles encapsulating a TUSC2 expression plasmid (DOTAP:chol-TUSC2) every 3 weeks.ResultsThirty-one patients were treated at 6 dose levels (range 0.01 to 0.09 milligrams per kilogram). The MTD was determined to be 0.06 mg/kg. Five patients achieved stable disease (2.6–10.8 months, including 2 minor responses). One patient had a metabolic response on positron emission tomography (PET) imaging. RT-PCR analysis detected TUSC2 plasmid expression in 7 of 8 post-treatment tumor specimens but not in pretreatment specimens and peripheral blood lymphocyte controls. Proximity ligation assay, performed on paired biopsies from 3 patients, demonstrated low background TUSC2 protein staining in pretreatment tissues compared with intense (10–25 fold increase) TUSC2 protein staining in post-treatment tissues. RT-PCR gene expression profiling analysis of apoptotic pathway genes in two patients with high post-treatment levels of TUSC2 mRNA and protein showed significant post-treatment changes in the intrinsic apoptotic pathway. Twenty-nine genes of the 82 tested in the apoptosis array were identified by Igenuity Pathway Analysis to be significantly altered post-treatment in both patients (Pearson correlation coefficient 0.519; p<0.01).ConclusionsDOTAP:chol-TUSC2 can be safely administered intravenously in lung cancer patients and results in uptake of the gene by human primary and metastatic tumors, transgene and gene product expression, specific alterations in TUSC2-regulated pathways, and anti-tumor effects (to our knowledge for the first time for systemic DOTAP:cholesterol nanoparticle gene therapy).Trial RegistrationClinicalTrials.gov NCT00059605

Multiple-allergen and single-allergen immunotherapy strategies in polysensitized patients: Looking at the published evidence

In allergen immunotherapy there is debate as to whether polysensitized patients are best treated with many allergens simultaneously (chosen according to the sensitization profile, a predominantly North American approach) or a single allergen (chosen according to the most clinically problematic allergy, a predominantly European approach). In patients seeking treatment for moderate-to-severe respiratory allergies, polysensitization is more prevalent (range, 50% to 80%) than monosensitization in both the United States and Europe. Safe, effective, single-allergen preparations will most likely have been tested in polysensitized patients. In robust, large-scale clinical trials of grass pollen sublingual tablets, polysensitized patients benefited at least as much from allergen immunotherapy as monosensitized patients. A recent review of multiallergen immunotherapy concluded that simultaneous delivery of multiple unrelated allergens can be clinically effective but that there was a need for additional investigation of therapy with more than 2 allergen extracts (particularly in sublingual allergen immunotherapy). More work is also required to determine whether single-allergen and multiallergen immunotherapy protocols elicit distinct immune responses in monosensitized and polysensitized patients. Sublingual and subcutaneous multiallergen immunotherapy in polysensitized patients requires more supporting data to validate its efficacy in practice.

Perception of Threat in Children With Social Phobia: Comparison to Nonsocially Anxious Children Before and After Treatment

The present study investigated interpretation bias and reduced evidence for danger (RED) bias in 49 children with social phobia and 49 nonsocially anxious children between the ages of 8 and 14 years, using an ambiguous stories task. A posttreatment and follow-up measure was included for 26 of the socially phobic children to examine whether there would be a change in interpretation and RED bias after a 12-week behavior therapy program. Ambiguous scenarios were presented sentence by sentence. Participants gave interpretations and fear ratings after each sentence, and they rated negative emotions after each complete scenario. Compared to the nonsocially anxious children, children with social phobia displayed both a RED bias and an interpretation bias. After the treatment program, the children with social phobia displayed a reduced tendency to make biased interpretations, but there were no significant posttreatment changes in the RED bias. At 1 year follow-up there was a significant reduction in both interpretation and RED bias and clinical children no longer differed from nonsocially anxious controls.

Efficacy of second molar to achieve anchorage control in maximum anchorage cases

Background: The aim of the study was to assess the efficacy of inclusion of second molar in treatment at the outset to reinforce anchorage. Methods: A comparative study comprising of 30 maximum anchorage cases to quantify anchorage loss in two situations was undertaken. Group I consisted of cases in which only first molars were banded and Group II consisted of cases where both first and second molars were banded. A total of seven landmarks were marked and six measurements were recorded on to the pre-treatment and post-treatment lateral cephalogram. Result: The difference in pre-treatment and post-treatment values of all the variables were statistically significant (p<0.05) except maxillary central incisor vertical movement (U1 VER), implying a significant post-treatment change. Thus in both the treatment approaches U6 and U1 showed a considerable amount of movement in horizontal and vertical direction and there was rotation which brought about change in angular values. Conclusion: The study has successfully quantified the anchorage loss and brought out the advantages of including second molar in treatment at the outset. Not only the anchorage loss is minimized but inclusion of second molar also helps to maximize incisor retraction and helps control angular movement of molar and incisor. Extra time required for second molar banding is well spent, as the benefits are overwhelming.