Controlled Rate Research Articles

Botulinum Toxin Therapy in Writer's Cramp and Musician's Dystonia.

Task-specific focal dystonia is characterized by muscle contraction(s) during a specific task, resulting in abnormal postures or movements. Specifically, writer’s cramp involves the upper extremity during the act of writing. Musician’s dystonia has a highly variable presentation, and thus makes therapeutic options more limited. Treatments include oral pharmacologic agents, neuromodulation, surgery and, most often, botulinum toxin (BoNT) injection. Selection of target muscles for toxin injection continues to be an area of active research for these task-specific movements. We present a review of the literature selected from a predefined search of the MEDLINE and ClinicalTrials.gov databases. We include six controlled studies of botulinum toxin for the management of writer’s cramp and focal task-specific dystonia (FTSD), including musician’s dystonia. Overall, 139 patients were included across all studies, with 99 individuals injected for writer’s cramp and the remaining 40 individuals with FTSD. The age range of all patients was 18–80 years old. We included studies that utilized only the BoNT-A serotype. These studies utilized various severity scales to quantify response to toxin injection, with ratings of instrument or pen control included as subjective ratings. Of the included 139 patients in this review, pooled data for toxin response show that 73% of patients who received the drug demonstrated improvement. Specific techniques for muscle localization and targeting were difficult to study as variable methods were employed. This remains an area of ongoing exploration.

Automated Dispensing Cabinet Functionality Expansion to Reduce Controlled Substance Inventory Discrepancies.

Automated dispensing cabinets have the potential to create technology-induced errors that can arise during controlled substance medication dispensing. Despite enhancements made to the medication use process, the impact of ADC functionality on technology-induced controlled substance discrepancies have yet to be described. To evaluate the impact of ADC functionality expansion on technology-induced errors such as controlled substance discrepancies created during "blind inventory counts" and cassette dispensing errors. This quasi-experimental study was conducted over 18 months that evaluated the expanded use of dispensing cassettes within 8 ADCs at the University of Chicago Medicine. Unit-dose controlled substances with high usage were directed for inventory reassignment to cassettes. Controlled substance dispenses, blind inventory counts discrepancies and cassette dispensing errors were evaluated before and after cassette expansion. ADC discrepancy and Cassette Dispensing Error rates were calculated using 1-week segments across the study period. Of the 64 040 dispenses during the study period, the proportion of cassette dispenses increased from 16% to 72% after cassette expansion. Controlled substance discrepancies decreased from 11 to 7 discrepancies for every 1000 dispenses (P < .0001). After cassette expansion, cassette dispensing errors increased to roughly 28 errors for every 1000 dispenses (P < .0001). Expansion of ADC functionality created opportunities for reduced technology-induced controlled substance discrepancy rates at the expense of increased cassette dispensing errors.

The effect of a mindfulness‐based versus health self‐management intervention on cognitive performance in older adults with subjective cognitive decline (SCD): The SCD‐Well randomized controlled trial

AbstractBackgroundSubjective cognitive decline (SCD) denotes self‐reported cognitive concerns in the absence of objective cognitive impairment. Individuals with SCD convert to dementia at twice the annual rate of healthy controls, with relatively poorer cognition in SCD conferring additional risk. Non‐pharmacological interventions are currently undergoing intensive evaluation for promoting cognitive function in SCD.MethodThis study utilized data from the SCD‐Well randomized controlled trial. One hundred forty‐seven older adults with SCD, recruited from clinics in four European countries, were randomized to one of two 8‐week non‐pharmacological interventions: the Caring Mindfulness‐Based Approach for Seniors (CMBAS), or a Health Self‐Management Program (HSMP). Participants’ objective cognitive performance was assessed at baseline, post‐intervention, and 24‐weeks follow‐up using a battery of tests. Four of these (RAVLT, WAIS‐IV Coding, Mattis DRS‐2 and Category Fluency) were combined to yield an abridged version of the Preclinical Alzheimer’s Cognitive Composite 5 (PACC5Abridged). Linear mixed models estimated the change in outcome measures (the PACC5Abridged and its constituents) within and between arms. All models were adjusted for country and participant demographics (sex, age, and education), as well as the time‐varying effect of participants’ repeated practice with the outcome measures.ResultThere was a statistically significant improvement in the PACC5Abridged in both arms of the trial (p&lt;.001), which did not differ between groups. The mean change in PACC5Abridged from baseline to 24‐weeks was 0.28 for CMBAS, and 0.22 for HSMP (pooled baseline SD 0.72). The effect of participants’ repeated practice on the PACC5Abridged was non‐significant, ruling out retest effects as a substantive explanation for results. Amongst the PACC5Abridged constituent tests, significant improvement was observed in the RAVLT and WAIS‐IV Coding.ConclusionThis clinical trial evaluated the effect of two 8‐week non‐pharmacological interventions on objective cognitive performance in SCD. Scores on a composite measure of early Alzheimer’s disease related cognitive dysfunction improved in both arms, even after accounting for practice effects. These results paralleled those of the primary outcome measure (trait anxiety), for which scores also improved in both arms. This work adds to the growing body of evidence that non‐pharmacological interventions can impact cognition in individuals at increased risk of dementia.

Control Release Coating for Urinary Catheters with Enhanced Released Profile for Sustained Antimicrobial Protection.

Catheter-associated urinary tract infections (CAUTIs) are common and pose significant costs to healthcare systems. To date, this problem is largely unsolved as commercially available antimicrobial catheters are still lacking in functionality and performance. A prior study by Lim et al. ( Biotechnol. Bioeng. 2018, 115 (8), 2000-2012) reported the development of a novel anhydrous polycaprolactone (PCL) polymer formulation with controlled-release functionality for antimicrobial peptides. In this follow-up study, we developed an improved antimicrobial peptide (AMP)-impregnated poly(ethylene glycol) (PEG)-polycaprolactone (PCL) anhydrous polymer coating for enhanced sustained controlled-release functionality to provide catheters with effective antimicrobial properties. Varying the ratio of PEG and PEG-PCL copolymers resulted in polymers with different morphologies, consequently affecting the AMP release profiles. The optimal coating, formulated with 10% (w/w) PEG-PCL in PCL, achieved a controlled AMP release rate of 31.65 ± 6.85 μg/mL daily for up to 19 days, with a moderate initial burst release. Such profile is desired for antimicrobial coating as the initial burst release acts as a sterilizer to kill the bacteria present in the urinary tract upon insertion, and the subsequent linear release functions as a prophylaxis to deter opportunistic microbial infections. As a proof-of-concept application, our optimized coating was then applied to a commercial silicone catheter for further antibacterial tests. Preliminary results revealed that our coated catheters outperformed commercial silver-based antimicrobial catheters in terms of antimicrobial performance and sustainability, lasting for 4 days. Application of the controlled-release coating also aids in retarding biofilm formation, showing a lower extent of biofilm formation at the end of seven inoculation cycles.

Mixed Class I/Class II post-peak curves of mortar models of rock samples

A comparative analysis of post-peak tests in uniaxial compression under different methods of load control is presented. The majority of the samples showed mixed Class I / II curves: the post-peak curves start with Class I curve which then turns into Class II. This mixed curve is observed under all types of loading control we tested. However the extent of the initial, Class I curve depends upon the pre-defined lateral strain rate in lateral strain control. The Class II curve obtained under lateral strain control is attributed to the unloading of the loading frame attempting to maintain the pre-defined lateral strain rate, but is not the real Class II behaviour. The sample failure pattern depends upon the mortar compositions and reveals the presence of either sub-vertical fractures (the loading direction is vertical) or inclined (oblique) fractures of vertical fractures with inclined segments. In many samples spallation was also observed. The type of loading control affects the growth of internal cracks/fractures and the failure pattern. Yet, both types of loading control (the lateral strain and failure control) stabilise the crack growth to the extent sufficient for investigating the mechanics of fracturing of mortar/rock samples in uniaxial compression.

Cortical Thinning and White Matter Loss in Sickle Cell Anemia Despite Chronic Exchange Transfusion Therapy

Neurovascular complications are a common and major cause of morbidity and mortality in patients with sickle cell disease (SCD). Prior studies have demonstrated cortical thinness (Kim et al. 2016) as well as reduced cerebral volume in children with SCD (Kawadler et al. 2013) when compared to age-matched controls. There is very limited data regarding cerebral volume in adults with SCD. Recently, our group showed that adults with SCD have reduced cerebral volumes when compared to race and age-matched controls (Santini et al. 2021a). A prior prospective study by Nitkunan et al. 2011. demonstrated brain atrophy rate of −0.914%±0.8% in older adults (mean 68 years old) with Small Vessels Disease, which is about twice the rate of healthy controls. Transfusion therapy has been effective in the primary and secondary prevention of strokes and silent infarcts in SCD. Automated erythrocytapheresis (exchange transfusion), in particular, is the most aggressive disease modifying-treatment in SCD, by rapidly diluting sickle hemoglobin and replacing it with normal hemoglobin. We hereby present a case of a 42 -year-old woman with sickle cell anemia (HbSS) who developed accelerated loss of cerebral volume within a three-year period despite chronic exchange transfusion therapy. The patient underwent brain MRI in 2016 and 2019 as part of an NIH-funded, prospective, longitudinal study of the neuroradiological correlates of cognitive dysfunction in SCD. Past medical history is notable for prior right hemispheric stroke for which she was placed on chronic exchange transfusion monthly with the goal of reducing HbS to <30%. T1-weighted images were acquired at 7T MRI using a customized RF coil (Santini et al. 2021b) and with the following parameters: 3D MPRAGE, TE/TI/TR = 2.17/1200/3000 ms, resolution 0.75 mm isotropic, total acquisition time = 5 min. The extent of atrophy was estimated using the longitudinal analysis as part of the Freesurfer package (version 7.1.1) and ITK-snap (version 3.8.0). The pre-exchange HbS was reliably maintained <30% throughout the observation period, during which the patient did not develop new strokes or neurological complications. Unfortunately, in spite of the patient's excellent adherence with the treatment and the achievement of the target HbS values, we observed progression of cerebral atrophy of 2.47% in volume in the hemisphere contralateral to the stroke between the two time points. The differences are also visible in the raw data (Figure 1). Chronic exchange transfusion is the most aggressive preventive treatment for the neurological sequelae of sickle cell disease. This case demonstrates an accelerated brain atrophy, suggesting that this treatment may not be fully protective against progressive cerebral atrophy. Unfortunately, the mechanism of brain atrophy in SCD is not fully understood. More longitudinal studies are needed to assess cortical changes and cerebral volume changes as this can lead to further understanding of their pathophysiology and to the development of therapeutic options to arrest the progression of cerebrovascular disease in this population. [Display omitted] DisclosuresNovelli: Novartis Pharmaceuticals: Consultancy.

Social Robots for Evaluating Attention State in Older Adults.

Sustained attention is essential for older adults to maintain an active lifestyle, and the deficiency of this function is often associated with health-related risks such as falling and frailty. The present study examined whether the well-established age-effect on reducing mind-wandering, the drift to internal thoughts that are seen to be detrimental to attentional control, could be replicated by using a robotic experimenter for older adults who are not as familiar with online technologies. A total of 28 younger and 22 older adults performed a Sustained Attention to Response Task (SART) by answering thought probes regarding their attention states and providing confidence ratings for their own task performances. The indices from the modified SART suggested a well-documented conservative response strategy endorsed by older adults, which were represented by slower responses and increased omission errors. Moreover, the slower responses and increased omissions were found to be associated with less self-reported mind-wandering, thus showing consistency with their higher subjective ratings of attentional control. Overall, this study demonstrates the potential of constructing age-related cognitive profiles with attention evaluation instruction based on a social companion robot for older adults at home.

Weekly Paclitaxel, Carboplatin, and Cetuximab as First-Line Treatment of Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma for Patients Ineligible to Cisplatin-Based Chemotherapy: A Retrospective Monocentric Study in 60 Patients.

ObjectiveFor most patients suffering from recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC), chemotherapy is the main option after considering surgery and reirradiation. Cetuximab combined with a platinum-fluorouracil regimen (EXTREME) has been the standard of care for over a decade. Nevertheless, a significant number of patients remain unfit for this regimen because of age, severe comorbidities, or poor performance status. The aim of this study is to investigate an alternative regimen with sufficient efficacy and safety.MethodsWe reviewed retrospectively the medical charts of all patients treated with paclitaxel, carboplatin, and cetuximab (PCC) at our institution. Eligibility criteria were as follows: first-line R/M-HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx not suitable for local therapy, cisplatin, and/or 5-FU ineligibility, ECOG-PS: 0–2. PCC consisted of paclitaxel 80 mg/m2, carboplatin AUC 2, and cetuximab at an initial dose of 400 mg/m2 then 250 mg/m2, for 16 weekly administrations followed by cetuximab maintenance for patients for whom a disease control was obtained. The primary endpoint was overall survival (OS), and secondary endpoints were overall response rate (ORR), progression free survival (PFS), and safety.ResultsWe identified 60 consecutive patients treated with PCC between 2010 and 2016 at our institution. Thirty-one patients (52%) were ECOG-PS 2. Fifty-five patients (92%) were cisplatin ineligible. ORR was 43.3% (95% CI, 30.8–55.8), and disease control rate was 65% (95% CI, 52.9–77.1). With a median follow-up of 35.7 months (IQR 28.6–48.8), median PFS was 5.8 months (95% CI, 4.5–7.2), and median OS was 11.7 months (95% CI, 7.5-14.8). For ECOG-PS 0–1 patients, median OS was 14.8 months (95% CI, 12.2–21.7) while it was only 7.5 months (95%CI: 5.5-12.7) for ECOG-PS 2 patients (p < 0.04). Grades III–IV toxicities occurred in 30 patients (50%). Most toxicities were hematologic. Six patients (10%) had febrile neutropenia. Nonhematologic toxicities were reported such as cutaneous toxicities, neuropathy, infusion-related reactions, or electrolyte disorders.ConclusionThe weekly PCC regimen seems to be an interesting option in cisplatin-unfit patients. This study shows favorable PFS and OS when compared with what is achieved with the EXTREME regimen and a high controlled disease rate with predictable and manageable toxicities even in the more fragile population.

Quantification of Target Volume Changes on Radiation Planning MRI in IDH-Wildtype Glioblastoma

IDH-wildtype glioblastoma (GBM) has an exceptionally poor prognosis due to its rapid growth. Delaying post-operative radiation therapy (RT) more than 6 weeks after surgery negatively impacts prognosis. Post-operative magnetic resonance imaging (MRI) is commonly used to assess the extent of surgical resection followed by a delayed MRI for RT planning. In a heterogeneous population of high-grade gliomas treated in the pre-molecular era, significant resolution of edema and a trend towards increase in surgical cavity sizes were observed. Post-operative volumetric changes in IDH-wildtype GBM have not been described and we suspect these tumors may demonstrate higher rates of recurrence or regrowth during the latent period before the initiation of RT.30 patients with IDH-wildtype GBM treated with post-operative RT from our institution were identified. Patients with RT planning MRIs obtained between 3-6 weeks after biopsy or surgical resection were included. RT target volumes were contoured and compared between post-operative and RT planning MRIs. Volumetric changes in GTV2 (surgical cavity + residual enhancing disease) and GTV1 (edema + GTV2) were calculated. Progression-free survival (PFS) and overall survival (OS) were measured.The mean time between post-operative and RT planning MRI was 29.4 days (range: 21-42 days). When comparing post-operative and RT planning MRIs, the mean decrease in GTV1 was 25.8cc or 14.7% (P = 0.011) and the mean increase in GTV2 was 10.21cc or 39.6% (P = 0.0013). GTV1 decreased at an average rate of 0.5% per day and GTV2 increased at an average rate of 1.4% per day. The proportional growth was similar to a rate of historical controls of mixed high-grade gliomas. Median PFS and OS in our group were 5.6 and 11.2 months, respectively. A delay of more than one month between post-operative and planning MRI was associated with worse median OS of 8.0 months compared with 11.5 months (P = 0.044).To our knowledge, this is the largest volumetric study of the impact of post-operative MRIs in a uniform group of IDH-wildtype GBM. RT planning MRIs performed 3-6 weeks after biopsy or surgical resection of IDH-wildtype GBM demonstrate significant volumetric changes. Similar to previously published data on a heterogenous population of high-grade gliomas, decreases in GTV1 signify a resolution of edema, however, increases in GTV2 imply recurrence or regrowth of disease over a relatively short time. While this was not statistically significant in a previously published analysis of a heterogeneous population of high-grade gliomas, our analysis of a homogeneous population of IDH-wildtype GBM demonstrates a statistically significant increase in GTV2. Delaying planning MRI more than one month post-operatively was associated with worse OS. These findings support the need for RT planning MRIs and confirm the association between delayed treatment and worse survival. Radiomic analysis of cavity regression vs. tumor regrowth is forthcoming.J.B. Bell: None. B.J. Rich: None. I.B. Mihaylov: Research Grant; Philips Radiation Oncology Systems, NIH.C. Benjamin: None. E.A. Mellon: None. M.C. Abramowitz: None. G. Azzam: None. M. Guillermo Prieto Ei: None. M. De La Fuente: None. M. Butkus: None. T. Diwanji: None.

Nondetrimental impact of two concomitant entomopathogenic fungi on life history parameters of a generalist predator, Coccinella septempunctata (Coleoptera: Coccinellidae)

The non-persistent impact of biocontrol agents can be revealed for pest control when associated entomopathogenic fungi (EPFs) negatively affect the natural enemies. In this assay, impacts of Beauvaria bassiana (Balsamo) Vuillemin, and Metarhizium anisopliae (Metschnikoff) Sorokin were studied for their compatibility or side effects on life table parameters of an important generalist predator, Coccinella septempunctata L. The results indicated non-significant impacts of both EPFs on life table parameters of C. septempunctata. The development time (egg-adult) was not significantly different in control (69.79 days) and EPFs treated C. septempunctata (69.35–80.07 days). Both fungi did not induce any significant changes in the fecundity, adult pre-oviposition period (APOP), total preoviposition period (TPOP), and mean generation time (T) as compared to control treatment. Similarly, no difference in fecundity rate of C. septempunctata was observed after EPFs treatment (287.7–288.5) compared to control (290.0). The highest net reproductive rate (R0) occurred in control (87.05 offspring individual−1) and M. anisopliae (86.31 offspring individual−1) as compared to B. bassiana treated beetles (76.97 offspring individual−1). The age-specific fecundity curves indicated that the C. septempunctata had a similar fecundity rate in both EPFs treatments and control. This study demonstrates no significant side effects of B. bassiana and M. anispoliae on the performance and biology of C. septempunctata. Considering the compatibility of both EPFs with C. septempunctata, their combinations can be recommended in various integrated pest management programs.

Hepatotoxicity during legacy cancer chemotherapy in patients infected with hepatitis C virus: A retrospective cohort study.

The rates and causes of significant hepatotoxicity with cancer chemotherapy (CCT) in patients infected with hepatitis C virus (HCV) are incompletely characterized. We compared rates of grade 3 or 4 hepatotoxicity, defined as elevated transaminases, during CCT in patients who are mono-infected with HCV compared with rates in controls matched on demographics, diagnosis, and rituximab use. We excluded patients with hepatobiliary cancers, hepatitis B virus or human immunodeficiency virus infection. Hepatotoxicity was attributed to a medical cause, cancer progression, or CCT, including HCV flare. Patients with HCV (n = 196) had a higher rate of cirrhosis than the 1,130 matched controls (21.9% versus 4%; P <0.001). Their higher rate of overall hepatotoxicity (8.7% versus 4.5% of controls, P = 0.01) was due to higher rate of CCT-related hepatotoxicity (4.1% versus 1.2%, P = 0.01). On multivariable analysis, the largest risk factor for overall hepatotoxicity was cirrhosis, and the only risk factor for CCT-related hepatotoxicity was HCV infection. Among those with HCV, the only significant risk factor for hepatotoxicity was rituximab use. Hepatotoxicity caused by CCT delayed or altered treatment in only 3 HCV patients and 1 control (1.5% versus 0.1%, P = 0.01). Most patients with HCV can safely be treated with cancer chemotherapy. Cirrhosis and HCV infection contributed to increased hepatotoxicity in subjects on CCT. Among HCV patients, rituximab use was the major risk factor for increased hepatotoxicity. Hepatotoxicity due to CCT itself rarely altered or delayed CCT. Nonetheless, HCV-positive patients should be monitored carefully during CCT.

Beneficial Microbes and Basal Fertilization in Antagonism of Banana Fusarium Wilt

Fusarium Wilt Tropical Race 4 (TR4) is spreading rapidly all over the world and threatens banana production, especially the Cavendish variety, which is the main commercial cultivar in Asia. This work aims to use beneficial microbes and fertilizers to control TR4. Both Bacillus mycoides NP02 (BM) and Bacillus amyloliquefaciens BaPD1 (BA) antagonized TR4 growth in plate tests. In addition, basal nutrients (BN) in combination with BM and BA were used to treat 1-month-old banana seedlings infected by Fusarium Wilt; plant growth and nutrients of leaves were investigated after 6-month cultivation in the field. The seedling survival rates for uninfected and infected controls without the microbes were 89.4 ± 14.8% and 50 ± 10.7%, respectively. In contrast, the corresponding rates for 2BM, 5BM, 1BA, F1 (5BM + 4BN + 1BA) and G1 (1BM + 4BN + 1BA) in the infected plants were 80 ± 9.4%, 83 ± 4.3%, 85 ± 14.2%, 96.7 ± 1.9% and 96.7 ± 3.3%, respectively. The 2BM treatment promoted the growth of both uninfected and infected banana plants and the 5BA treatment significantly reduced the severity index by 1.45-fold. Plants infected with TR4 showed significantly reduced contents of nitrogen and potassium, but the contents of iron, copper and zinc were higher than those of healthy plants. Additionally, 1BM treatment stimulated the accumulation of nitrogen and zinc ions in the leaves of uninfected plants. Both the 1BA and 2BN treatments increased the iron (Fe) and nickel (Ni) metal ion levels of TR4 infected plants. The F2 (5BM + 2BN + 1BA) treatment significantly maintained the growth of banana plants under TR4 stress with increased contents of nickel and zinc in banana leaves, suggesting that these ions may play a key role in stimulating the growth of banana plants under the threat of TR4. This work shows the potential of applying BM, BN and BA in the control of Fusarium wilt in field conditions.

Impaired transcriptional compensation for oxidative damage in a porcine model of ischaemic cardiomyopathy

Abstract Background The prognosis of heart failure remains poor. Energetic imbalances related to mitochondrial dysfunction, impaired oxidative phosphorylation and oxidative damage have been implicated in the pathogenesis or worsening of heart failure (1,2). Improved understanding of the metabolic alterations in heart failure may provide new biomarkers or therapeutic targets. Purpose We explored mutation rate, mitochondrial copy number and regional mitochondrial gene transcription in a porcine model of ischaemic cardiomyopathy. Specifically, we investigated the Dloop region – a promotor for mitochondrial DNA- in which mutations have been implicated in many cancers. We hypothesised that there may be differences in mutation rate and oxidative damage within the mitochondrial genome. Methods 15 female Yorkshire pigs were studied. 7 animals underwent percutaneous balloon catheter myocardial infarction followed by termination at 4 weeks. A group of 8 healthy animals served as controls. Reverse transcription quantitative PCR (RT-qPCR) assays were performed to determine the gene expression levels of mitochondrial DNA codified genes (ND1, ND2, ND4, ATP6 and ND6). Quantitative PCR (qPCR) methodology was modified to obtain the relative mitochondrial copy number, mutation rate, and oxidative damage according to established methods (3–5). Results Significant mitochondrial transcriptional activity of the genes studied was seen in both groups (see Table 1 and 2). When examining the ND2-ND6 region (excluding the Dloop) in control animals, we note an inverse correlation with increased oxidative damage corresponding to a significantly lower mutation rate (p=0.017). There was no correlation between the mutation rate and oxidative damage in the ND6-ND2- including Dloop- region. However, when examining the Dloop specifically, there was a marked inverse correlation between oxidative damage and mutation rate (p=0.007). This suggests that in controls, there is regional variation in the susceptibility to damage within the mitochondrial genome which may trigger repair mechanisms. Indeed, the relative mitochondrial copy number was inversely associated to the mutation rate (p=0.08) in controls. In contrast, in the chronic animals, we noted no correlation with the level of oxidative damage in the ND2-ND6, D-loop, or ND6–2 regions compared to mutation rate (p=0.52, p=0.53 and p=0.17 respectively). This indicates that there is a loss in the ability to instigate repair mechanisms in the setting of ischaemic cardiomyopathy. Conclusions This study demonstrates that in control animals, there appears to be regional variation in the ability to mitigate against mutations in response to oxidative damage within the mitochondrial genome. In contrast, this protection and/or the effectiveness of repair mechanisms appear to be impaired in the setting of ischaemic cardiomyopathy. This may be a driver, and in turn a therapeutic target, for adverse remodelling in this setting. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): This research work was supported by grants awarded to Professor Ascione: the British Heart Foundation (BHF) (BHF IG/14/2/30991, BHF RM/13/2/30158), and the Medical Research Council (MRC) (MRC MR/L012723/1).

Introducing a flexible drug delivery system based on poly(glycerol sebacate)-urethane and its nanocomposite: potential application in the prevention and treatment of oral diseases

In this study, a novel biopolymer based on poly(glycerol sebacic)-urethane (PGS-U) and its nanocomposites containing Cloisite@30B were synthesized by facile approach in which the crosslinking was created by aliphatic hexamethylene diisocyanate (HDI) at room temperature and 80 °C. Moreover, metronidazole and tetracycline drugs were selected as target drugs and loaded into PGSU based nanocomposites. A uniform and continuous microstructure with smooth surface is observed in the case of pristine PGS-U sample. The continuity of microstructure is observed in the case of all bionanocomposites. XRD result confirmed an intercalated morphology for PGSU containing 5 wt% of clay nanoparticles with a d-spacing 3.4 nm. The increment of nanoclay content up to 5%, the ultimate tensile stress and elastic modulus were obtained nearly 0.32 and 0.83 MPa, which the latter was more than eight-fold than that of pristine PGS-U. A sustained release for both dugs was observed by 200 h. The slowest and controlled drug release rate was determined in the case of PGSU containing 5 wt% clay and cured at 80 °C. A non-Fickian diffusion can be concluded in the case of tetracycline release via PGS-U/nanoclay bionanocomposites, while a Fickian process was detected in the case of metronidazole release by PGS-U/nanoclay bionanocomposites. As a result, the designed scaffold showed high flexibility, which makes it an appropriate option for utilization in the treatment of periodontal disease.

Neoadjuvant Concurrent Radiotherapy and Chemotherapy in Early Breast Cancer Patients: Long-Term Results of a Prospective Phase II Trial.

Simple SummaryThe originality of this prospective study is to use radiation therapy in association with chemotherapy before surgery and permit patients to preserve their breasts or to undergo immediate reconstruction. This neoadjuvant strategy can therefore allow one-stage breast reconstructive surgery, the so-called “reverse technique”.Background: Neoadjuvant concurrent radiochemotherapy makes it possible to increase the breast conservation rate. This study reports the long term outcome of this treatment. Methods: From 2001 to 2003, 59 women with T2–3 N0–2 M0 invasive breast cancer (BC) not amenable to upfront breast conserving treatment (BCS) were included in this prospective, non-randomized phase II study. Chemotherapy (CT) consisted of four cycles of continuous 5-FU infusion and Vinorelbine. Starting concurrently with the second CT cycle, normofractionated RT was delivered to the breast and LN. Breast surgery was then performed. Results: Median follow-up (FU) was 13 years [3–18]. BCS was performed in 41 (69%) patients and mastectomy in 18 patients, with pathological complete response rate of 27%. Overall and distant-disease free survivals rates at 13 years were 70.9% [95% CI 59.6–84.2] and 71.5% [95% CI 60.5–84.5] respectively. Loco regional and local controls rates were 83.4% [95% CI 73.2–95.0] and 92.1% [95% CI 83.7–100], respectively. Late toxicity (CTCAE-V3) was assessed in 51 patients (86%) with a median follow-up of 13 years. Fifteen presented grade 2 fibrosis (29.4%), 8 (15.7%) had telangiectasia, and 1 had radiodermatitis. Conclusions: This combined treatment provided high long-term local control rates with limited side-effects.

Child neurocognitive functioning influences the effectiveness of specific techniques in behavioral teacher training for ADHD: Moderator analyses from a randomized controlled microtrial.

Childhood attention-deficit/hyperactivity disorder (ADHD) is associated with several neurocognitive impairments. Whether these impairments influence the effectiveness of techniques that are commonly used in behavioral teacher training for ADHD has not been investigated so far. In this microtrial, teachers of 90 children with ADHD symptoms (6-12years) were randomly assigned to a short intervention consisting of either antecedent-based (stimulus-control) techniques or consequent-based (contingency management) techniques, or to a waitlist control condition. Primary outcome was the daily assessment of individually selected problem behavior, assessed pre- and post-intervention. Potential neurocognitive moderators of treatment effect included teacher ratings of cognitive control, reward, and punishment sensitivity, and measures derived from computerized neurocognitive tasks, including attentional lapses, interference control, visuospatial working memory, and emotional functioning. Intervention condition by moderator interactions were assessed in separate multilevel mixed models. Lapses of attention, working memory, and emotional functioning interacted with intervention effectiveness. Antecedent-based techniques were effective independent of these neurocognitive functions; consequent-based techniques were (more) effective when these functions were more impaired. The effectiveness of techniques was neither related to interference control nor to teacher-rated neurocognitive functioning. This study showed that child neurocognitive functioning influences the effectiveness of behavioral teacher techniques for children with ADHD symptoms. Findings suggest that antecedent-based techniques may be effective for all children, while consequent-based techniques have added value particularly for children who suffer from low visuospatial working memory, low emotional functioning, and/or large numbers of attentional lapses.

Investigation of the effect of non-uniform heat distribution of microwave on the mortality rates of some plants

Weeds, cause significant losses in agricultural production and are mostly controlled by herbicides, which are harmful to the environment. An alternative method that can be applied instead of these chemicals that pollute the soil and water is the microwave weed control method. But, one of the main problems with the microwave weed control method is the non-uniform heat distribution. This study aims to investigate the effect of non-uniform heat distribution on the mortality rate in the microwave weed control method by the NDVI (Normalized Difference Vegetation Index) technique. The NDVI technique has been used for the first time in this study to determine the mortality rate in microwave weed control. Mortality rates in one-week germinated Lepidium sativum (cress) and Hordeum vulgare (barley) grasses that were exposed to microwave energy for 10, 20, and 30 seconds were measured. It was determined that a higher rate of mortality occurred in the uniform heat distribution condition, compared to the non-uniform heat distribution (p &amp;lt;0.05). Mortality rates in both Hordeum vulgare (barley) and Lepidium sativum (cress) grasses increased as the microwave application time increased. The highest mortality rate occurred in Lepidium sativum (cress) grass (69.81%) and Hordeum vulgare (barley) grass (61.01%) with uniform heat distribution for 30 seconds. In the non-uniform heat distribution for 10 seconds, an increase was observed in Hordeum vulgare (barley) grass compared to the control group (7.01%). As a result, it can be said that weed control with microwave energy has the potential to be a good “environmentally friendly alternative method” to chemical weed control methods.

Exploration of dynamic text presentations in bilateral central vision loss.

Dynamic text presentation methods may improve reading ability in patients with central vision loss (CVL) by eliminating the need for accurate eye movements. We compared rapid serial visual presentation (RSVP) and horizontal scrolling text presentation (scrolling) on reading rate and reading acuity in CVL observers and normally-sighted controls with simulated CVL (simCVL). CVL observers' (n=11) central scotomas and preferred retinal loci (PRL) for each eye were determined with MAIA microperimetry and fixation analysis. SimCVL controls (n=16) used 4° inferior eccentric viewing, enforced with an Eyelink eye-tracker. Observers read aloud 4-word phrases randomly drawn from the MNREAD sentences. Six font sizes (0.50-1.30logMAR) were tested with the better near acuity eye and both eyes of CVL observers. Three font sizes (0.50-1.00logMAR) were tested binocularly in simCVL controls. Text presentation duration of each word for RSVP or drift speed for scrolling was varied to determine reading rate, defined as 50% of words read correctly. In a subset of CVL observers (n=7), relationships between PRL eccentricity, reading threshold and rate were explored. SimCVL controls demonstrated significantly faster reading rates for RSVP than scrolling text (p<0.0001), and there was a significant main effect of font size (p<0.0001). CVL patients demonstrated no significant differences in binocular reading rate between font sizes (p=0.12) and text presentation (p=0.25). Similar results were seen under monocular conditions. Readingacuity for RSVP and scrolling worsened with increasing PRL eccentricity (μ=4.5°, p=0.07). RSVP reading rate decreased significantly with increasing eccentricity (p=0.02). Consistent with previous work, reading acuity worsened with increasing PRL eccentricity. RSVP and scrolling text presentations significantly affected reading rate in simCVL, but not in CVL observers, suggesting that simCVL results may not generalise to pathological CVL.

Here I sit, making men in my own image: how learning disorder labels affect teacher student’s expectancies

Teacher’s evaluation of students is sometimes negatively affected by diagnostic labels. We explored such negative effects caused by the labels “dyscalculia”, “dyslexia”, and “ADHD” in teacher students. In Experiment 1, we varied the presence of the dyscalculia and dyslexia label in vignettes between participants. The dyslexia but not the dyscalculia label had a negative effect on participant’s academic expectations. In our preregistered Experiment 2, the presence of the ADHD label in vignettes was manipulated within participants. To understand the cognitive mechanisms driving label effects, we explored participants’ attributions regarding the students’ problems. Furthermore, a short dissonance-based intervention for counteracting negative label effects was implemented. Unexpectedly, we found both negative and positive label effects. The label led to more positive performance expectations and to more negative ratings of problem stability and problem control. The dissonance-based intervention led to more positive evaluations regardless of whether the ADHD label was mentioned or not. Overall, our findings suggest that learning-disorder labels affect teachers’ expectations in different ways.

The choice levels modulate outcome processing during outcome independent of behavior selection: Evidence from event-related potentials

Having a choice is a basic demand to influence human behavior. However, how various choice levels modulate outcome processing when the outcome is independent of the choices remains unclear. In this event-related potential (ERP) study, thirty-seven participants were instructed to perform a one-person choice task in which they were required to choose one card from 1 (no-choice level), 2 (medium-choice level), and 8 cards (high-choice level) to win a reward, with a 50% chance. Behavioral results indicated that pleasure and perceived control rating scores were linearly promoted with increased choice levels. ERP results revealed that having choices (medium- and high-choice level) elicited greater original-RewP and PCA-RewP amplitudes than having no choice (no-choice level), suggesting the amplification of the reward prediction error by quickly detecting whether there is a choice or not. Moreover, ERP results revealed that the original-P300 amplitudes were linearly enhanced with increased choice levels, suggesting the increased attentional allocation based on the motivational and emotional significance, due to advanced processing of the value of choice levels. Therefore, these results suggest that choice levels can modulate outcome processing, even when the outcome is independent of the choices, and provide further evidence to support the intrinsic value of having choices.