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Introduction: Improving patient safety and quality of care is a national healthcare priority. While changes in healthcare systems help to address some concerns in this area, the knowledge, skills, and attitudes of healthcare professionals play a role as well. Health professions education programs have a responsibility to ensure comprehensive patient safety and quality training. Objectives: This study aimed to evaluate the impact of integrating standardized safety and quality competencies from an evidence‐based framework in a patient safety and quality course within a Doctor of Pharmacy program. Methods: A gap analysis was conducted using guidelines from the Canadian Patient Safety Institute (CPSI) to explore curricular coverage of the included concepts and competencies. The course was designed to address key competencies not addressed elsewhere in the curriculum. An adapted self‐assessment survey tool was administered at the end of the course for students to retrospectively assess changes in perceived skills and attitudes. Mean retrospective pre‐ and post‐scores were compared using the paired sample t‐tests and Cohen d as a measure of effect size. Responses to an open‐ended question regarding how students could impact patient safety were qualitatively analyzed for emergent themes. Student performance on the course final exam was analyzed using descriptive statistics to assess knowledge. Results: Sixty‐three students (80.8%) completed the survey and were included in the analysis. A statistically significant change was observed in 18 of the 24 self‐assessment items, with effect sizes in the modest to moderate range. Key themes emerged regarding student professional identity development including error prevention, error management, reporting culture, learning culture, just culture, and teamwork. The mean individual student score on the final examination was 87.67% ± 4.87%. Conclusion: Findings suggest the new course using the CPSI framework had a positive impact on student knowledge, perceived skills, and attitudes in the area of patient safety. [ABSTRACT FROM AUTHOR]

Objectives: With the increasing prevalence of artificial intelligence (AI) and the significant research gap in the application of AI within dentistry, this study aimed to (1) evaluate the efficiency and accuracy of dental students in full‐mouth radiograph series (FMS) mounting with and without AI assistance, and (2) assess dental students' perceptions of AI in clinical education to address the impact of AI in dental education. Methods: An AI‐based interface for mounting radiographs on FMS templates was designed and implemented in the study. Forty third‐year dental students were randomly assigned to control and test groups. The control group manually mounted FMS radiographs, while the test group reviewed AI‐pre‐mounted radiographs for adjustments. Students' performance in efficiency and accuracy was evaluated. Pre‐ and post‐study surveys were conducted to gauge students' confidence levels and opinions regarding the usefulness of the AI‐assisted program. Results: The test group (using AI) demonstrated significantly faster radiograph mounting times than the control group (manual) (p < 0.05). Accuracy was lower in the test groups, when comparing AI‐assisted and manual mounting of FMS (p < 0.01). Self‐confidence and confidence in AI were consistent between the control and test groups, both before and after the study. Conclusion: Students with AI presented with a decreased accuracy in FMS radiograph mounting. Therefore, AI automation could potentially have negative impacts in a learning environment with inexperienced clinicians. [ABSTRACT FROM AUTHOR]

Generation Z (Gen Z) is believed to be more socially and environmentally committed. While environmentally responsible behaviour is crucial to the success of sustainable tourism, little is known about Gen Z's specific environmental behaviours in tourism settings. In this research, the roles of Gen Z's consumption emotions and environmentally friendly behaviour were explored based on cognitive appraisal and elaborated intrusion theories. The moderation impact of eco‐travel cravings was also examined. With 336 valid responses collected from Gen Z tourists, it was found that destination social responsibility significantly impacted consumption emotions, but only positive emotions had direct effects on environmentally responsible behaviour and environmentally friendly tourism behaviour. The associations of emotions with environmentally responsible behaviour were also moderated by eco‐travel cravings. The results offer theoretical and managerial implications for understanding Gen Z tourists that can help to accomplish sustainable tourism. [ABSTRACT FROM AUTHOR]

Objectives: The American Academy of Periodontology and the European Federation of Periodontology developed a new classification system for periodontal diseases in 2017. The next step in its widespread implementation involves training dental students to improve consistency in clinical decisions. This study conducted in 2020–2021 aimed to evaluate knowledge in periodontal diagnosis and treatment planning using the new classification, among first, second, third‐ and fourth‐year dental students at Indiana University School of Dentistry (IUSD), University of Texas School of Dentistry at Houston (UTSD), and University of Louisville School of Dentistry (ULSD). Methods: A minimum of 20 dental students per class year from each of the three schools participated. Ten HIPPA de‐identified case records and a questionnaire with a fixed list of answer options, comprising two demographic questions and two questions on diagnosis and treatment planning of each case, were presented to the participants. A group of three board‐certified periodontists established the answers for all cases which were used to score the appropriateness of diagnosis and treatment planning among the participants. Results: A total of 263 students participated. Overall, 22.6% of IUSD responses, 25.2% of UTSD, and 27.6% of ULSD responses were correct for diagnosis (no statistically significant differences). For the treatment plan, 64.9% of IUSD responses, 66.2% of UTSD, and 68.9% of ULSD responses were correct (no statistically significant differences). Conclusion: Based on the findings from our study, we suggest that additional training be considered to improve the understanding of the 2017 classification of periodontal and peri‐implant diseases among dental students. [ABSTRACT FROM AUTHOR]

Background: The breast reconstruction (BR) rate for women undergoing mastectomy for breast cancer management is 18% in Australia. The Australian Access to Breast Reconstruction Collaborative Group recommends that all women should have access to BR. This study presents BR uptake and outcomes from a breast surgical unit. Methods: A retrospective observational study identified women who had curative mastectomy for breast cancer between 1 January 2016 and 31 December 2021. Patient factors and surgical complications were compared between BR and no BR (NBR) patients. Results: Out of 929 women who had a curative mastectomy, 34% underwent reconstruction. Of this, 89% were immediate, and 11% were delayed. Reconstruction increased from 27% (2016) to 35% (2021). During this time, 588 women had a discussion for BR documented at their initial consultation, 58 after initial surgery and 283 were not documented. The rate of discussion prior to mastectomy increased from 38% to 74%. Women who had BR were more likely to be younger, premenopausal and less likely to be diabetic. Complications requiring return to theatre were higher in reconstructed women (13% vs. 7%). Overall, infected seroma, cellulitis requiring intravenous antibiotics and haematoma requiring drainage were comparable between both groups. Conclusion: Our unit achieved a reconstruction rate of 34%, which is higher than national and international averages. Open discussion of reconstruction is crucial for women to make an informed decision. Further prospective studies exploring barriers to timely reconstruction will improve uptake of BR surgery and allow prioritization of BR services in Australia. [ABSTRACT FROM AUTHOR]

Objective: Advances in 3-dimensional modeling have revolutionized presurgical planning for maxillofacial reconstruction, yet little is known about how this technology may affect patient education. This study was designed to evaluate the efficacy of 2-dimensional computed tomography versus 3-dimensional computed tomography for patient education in maxillofacial reconstruction. Study Design: Crossover study. Setting: General otolaryngology outpatients from a tertiary referral center were recruited. Methods: A single computed tomography data set of a zygomaticomaxillary complex fracture was used to generate 2 educational video tutorials: one in a 2-dimensional format and one in a 3-dimensional format. The tutorials were embedded into the QualtricsXM platform. Participants were randomly assigned into 2 groups. Group 1 viewed the 2-dimensional tutorial, took a self-assessment survey, took an information recall survey, viewed the 3-dimensional tutorial, and finally took a tutorial comparison survey. Group 2 followed the same sequence but viewed the 3-dimensional tutorial followed by the 2-dimensional tutorial. Results: Group 2 participants (viewing the 3-dimensional tutorial first) scored better on the self-assessment survey than their counterparts in group 1 did (P =.023). Group 2 also scored better on the recall survey (P =.042). Of all participants, 61% preferred the 3-dimensional tutorial, and 31% preferred the use of both tutorials together in the comparison survey. Conclusions: Three-dimensional patient educational tutorial regarding a zygomaticomaxillary complex fracture resulted in better knowledge retention and was preferred over the 2-dimensional format. [ABSTRACT FROM AUTHOR]

Aim: Smoking is a risk factor for periodontitis. This study aimed to evaluate the impact of smoking on clinical outcomes of non‐surgical periodontal therapy. Materials and Methods: Electronic databases were searched to screen studies published before May 2020. The included studies had to have two groups: smokers (S) and non‐smokers (NS) with periodontitis. The outcomes evaluated were differences between groups in probing depth (PD) reduction and clinical attachment level (CAL) gain after non‐surgical periodontal therapy. Meta‐regressions were conducted to evaluate correlations between outcomes and other contributing factors. Results: Seventeen studies were included. The post‐treatment PD reduction in the S group was smaller than in the NS group (weighted mean difference in PD reduction: −0.33 mm, 95% confidence interval (CI): [−0.49, −0.17], p <.01). The CAL gain in the S group was also smaller than in the NS group (weighted mean difference in CAL gain: −0.20 mm, CI: [−0.39, −0.02], p <.01). Additionally, baseline PD significantly affected the difference in PD reduction between two groups. Conclusions: Smoking negatively impacts clinical responses to non‐surgical periodontal therapy. Smokers with periodontitis have significantly less PD reduction and CAL gain than non‐smokers. [ABSTRACT FROM AUTHOR]

Acute gastric volvulus is a rare surgical emergency which can lead to severe complications such as gastric ischaemia and perforation. Gastric volvulus is classified by the axis upon which the stomach rotates into organo-axial and mesentero-axial subtypes, with the former more common in adults. We present an uncommon case of recurrent adult mesentero-axial gastric volvulus and describe the associated radiological findings. [ABSTRACT FROM AUTHOR]

Little is known about how racial/ethnic differences may influence attributions for autism spectrum disorder (ASD) and subsequent vaccine hesitancy, the latter of which refers to a continuum of concerns about vaccine safety that may lead to vaccine delays and/or refusals. Two hundred and twenty‐five parents of children with ASD who were enrolled in the SPARK cohort (Simons Foundation Powering Autism Research for Knowledge) completed the Parent Attitudes about Childhood Vaccines survey and the Revised Illness Perception Questionnaire. 28.9% of respondents (n = 65) were vaccine hesitant (PACV score ≥ 50). Significant differences were observed between proportions of vaccine‐hesitant parents (VHP) in the White sample and combined samples of color (Asian, Black, Latinx, Multiracial, and Other): 22.8% of the White sample (n = 39) versus 48.1% of the samples of color (n = 26). White, non‐hesitant parents more often agreed with the child's brain structure as a cause of their child's ASD, while White, VHP more often agreed with the deterioration of the child's immunity as a cause. All VHP (regardless of race) agreed more often with diet, their own decisions, and vaccines as causes. VHP of color more often agreed with accident or injury, environmental pollution, their own general stress, and their own emotional state as causes. Future work should examine this phenomenon in larger, diverse samples to further understand differences across specific racial/ethnic groups. Lay Summary Some parents of children with autism spectrum disorder (ASD) are vaccine hesitant, meaning they have concerns about vaccine safety and may delay/refuse vaccines. We examined possible racial/ethnic differences related to how common vaccine hesitancy is and which causes of ASD were typically endorsed among a sample of caregivers in the SPARK cohort (Simons Foundation Powering Autism Research for Knowledge). Higher proportions of parents of color were vaccine hesitant, and all vaccine‐hesitant parents agreed that "toxins in vaccines" were a cause of their child's ASD. Autism Res 2020, 13: 1790–1796. © 2020 International Society for Autism Research and Wiley Periodicals LLC [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to explore the feasibility of the use of titanium fiducial markers to minimize the metallic artifact seen with tantalum markers which causes significant distortion on postoperative orbital CT scans. Method: We designed and constructed the titanium markers in the shop of Crocker Nuclear Laboratory, UC Davis, CA. The markers were placed on an eyeball phantom. The eyeball was inserted into the Rando phantom in the orbital space. The Rando phantom was imaged with coplanar x rays on Nucletron simulator at UCSF, on digital panel on the eye beam line at CNL eye treatment facility and on CT scanner at UCSF. Results: The titanium markers can be clearly seen on the hard copy of x rays and on digital panel. The CT scan of an orbit using tantalum markers on the right eye and titanium markers on the left eye shows the metal artifact from tantalum markers. Titanium markers show very little distortion on CT images. Conclusion: The present study describes these markers and their relative benefit in comparison with tantalum marker, which has been used for localizing ocular tumor for decades. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To evaluate disparities in overall survival (OS) between Asian and non-Asian patients diagnosed with non-nasopharyngeal head and neck cancer (HNC).Study Design: This was a population-based, retrospective study of patients diagnosed with non-nasopharyngeal HNC of squamous cell carcinoma histology between 2001 and 2010 in British Columbia, Canada.Methods: Using Kaplan-Meier methods and Cox regression models, we examined the relationship between race and OS.Results: A total of 3,036 patients were included in the study. Median age was 64 years, 74% were men, and 7% were Asians. Asians had worse Eastern Cooperative Oncology Group (ECOG) status (29% vs. 23%, P = .07) and larger tumors (33% vs. 21%, P = .02), and were more likely to be diagnosed with oral cavity cancers (38% vs. 25%, P < .001) than non-Asians. Asians were also less likely to receive multimodality therapy than non-Asians (90% vs. 95%, P = .02). Asians were more likely to have never smoked (49% vs. 15%, P < .001) and to be married or with a partner (80% vs. 69%, P = .02). Multivariate models showed that Asians had better OS than non-Asians (hazard ratio [HR] = 0.50, 95% confidence interval [CI] = 0.25-0.99, P = .05). Three-year OS did not differ significantly between Asians and non-Asians (41% vs. 42%, P = .18); however, 5-year OS did (22% vs. 19% P = .03). Stratifying by treatment type, outcomes were comparable in both groups except for radiotherapy alone, where Asians showed significantly better OS (HR = 0.71, 95% CI = 0.51-0.99, P = .04). Advanced age, worse ECOG, greater tumor size, and lack of treatment also correlated with inferior OS.Conclusions: Despite several worse prognostic features and less aggressive treatment, Asians tended to exhibit better OS than non-Asians.Level Of Evidence: 2c. Laryngoscope, 127:2528-2533, 2017. [ABSTRACT FROM AUTHOR]

Objectives Optimal treatment of rectal cancer (RC) requires multidisciplinary care. We examined whether distance to treatment center or community size impacts access to multimodality care and population-based outcomes in RC. Methods Patients diagnosed with stage II/III RC from 1999 to 2009 and treated at 1 of 6 regional cancer centers in British Columbia were reviewed. Distance to treatment center was determined for each patient. Communities were classified as rural, small, medium, and large population centers. Logistic and Cox regression models assessed associations of distance and community size with treatment received as well as cancer-specific (CSS) and overall survival (OS). Results Of 3,158 patients, 93.6% underwent surgery, 86.3% received radiotherapy, and 51.3% were treated with adjuvant chemotherapy (AC). Median time from diagnosis to oncologic consultation was longer for those >100 km from a treatment center or residing in medium/rural communities. Logistic regression demonstrated no correlation between distance or community size and receipt of treatment modality. Univariate analysis showed similar CSS ( P = .18, .88) and OS ( P = .36, .47) based on community size and distance, respectively. In multivariate analysis, distance >100 km had inferior CSS (Hazard Ratio [HR] 1.39, 95% CI: 1.03-1.88; P = .031). There was no consistent trend between decreasing community size and outcomes; however, living in a small center was associated with improved OS (HR 0.58, 95% CI: 0.38-0.88; P = .011) and CSS (HR 0.42, 95% CI: 0.25-0.70; P = .001). Conclusions In this population-based study, there were no urban-rural differences in access to multidisciplinary care, but increased distance may be associated with worse cancer-specific outcomes. [ABSTRACT FROM AUTHOR]

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Background: We detected a novel imaging sign, which consists of a specific imaging pattern of diffuse susceptibility effect, delineating the cortical-subcortical junction on high-resolution susceptibility-weighted images (SWIs). We describe magnetic resonance imaging findings in 10 patients with "susceptibility etching" and possible association with their abnormal coagulation profile.Materials/methods: A retrospective case series study with a search for cases that demonstrated susceptibility effect at the cortical-subcortical junction on SWI sequences was performed. The patients' respective coagulation profiles including prothrombin time, partial thromboplastin time, fibrinogen, D-dimer values, and platelet counts were reviewed. In addition, clinical history and neurological deficits were recorded.Results: We identified 10 patients with the "susceptibility etching" pattern at the cortical-subcortical junction. All patients were acutely ill and had a significantly elevated D-dimer (4,309 mcg/L to >10,000 mcg/L) with variably reduced platelet count. Two patients had reduced fibrinogen and 5 patients had prolonged international normalized ratio. Of the 10 patients, 4 died during hospitalization, within a few days of imaging. Pathology of 1 patient at autopsy demonstrated findings suggestive of a microvascular thrombotic or embolic event without overt parenchymal microhemorrhage.Conclusion: In this preliminary case series, we describe patients with "susceptibility etching" on SWI who were also found to have profound coagulation impairment. While other comorbities may also contribute to this novel sign, we suggest that a possible etiology may be secondary to microvascular in situ formation of fine thrombi and/or emboli lodged into an area of vascular caliber reduction and maybe related to thrombotic microangiopathy. [ABSTRACT FROM AUTHOR]

Background: Prior survivorship research has largely focused on issues faced by survivors of childhood tumors, breast cancers, or hematologic malignancies. Relatively little is known about the needs of other prevalent survivor groups. Our aim was to identify the specific concerns of colorectal cancer (CRC) survivors in the key domains of physical functioning, psychological wellbeing, and social relationships.Methods: We conducted focus groups with stage II and III CRC survivors who had completed their primary active anti-cancer treatments. Patients were asked to describe how their diagnosis and treatment impacted their lives, to outline deficiencies in the care that they received, and to suggest ways of addressing any unmet needs. A content analysis was subsequently conducted to identify major themes.Results: Thirty CRC survivors participated in six focus groups. Individuals reported some degree of dissatisfaction with the amount and type of diagnostic and treatment information they received at their initial clinic visit. Distress from toxicities, such as peripheral neuropathy, was also common among the survivors. Similarly, the majority faced challenges adjusting to their lives and daily activities, especially in caring for their colostomy. Having survived CRC, many survivors expressed an interest in advocacy and health promotion of CRC.Conclusions: CRC survivors face many barriers after their cancer treatment. Issues with colostomy are unique to this survivor group. Interventions to improve CRC survivorship care should also incorporate opportunities for patient advocacy. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Study Objectives To identify subsequent therapies used after first-line therapies in patients with advanced non-small cell lung cancer ( NSCLC), compare overall survival ( OS) associated with subsequent therapies, and evaluate factors associated with OS in these patients. Methods The study was a retrospective cohort analysis of patients with advanced NSCLC (stage IIIB/ IV) who were initiated on first-line therapy from January 1, 2008, through September 30, 2013, and afterward given subsequent chemotherapy (index date). Patients had to be 18 years or older at the time of diagnosis of advanced NSCLC. Patients were followed from the index date until one of the following end points: end of the study (September 30, 2014), disenrollment from the health plan, or death-whichever came the earliest. The primary outcome was OS. Kaplan-Meier curves and Cox proportional hazard models were used to analyze OS and evaluate the factors associated with OS. Results The analysis included 1280 patients on subsequent therapies. The most common subsequent therapies were pemetrexed (284 patients [22%]), erlotinib (216 patients [17%]), and docetaxel (139 patients [11%]). Patients from the singlets group had a lower OS at 6.3 months compared with all other groups: pemetrexed based, combination of pemetrexed and bevacizumab based, bevacizumab based, doublets, and tyrosine kinase inhibitors (p<0.0001). Factors associated with greater OS included age younger than 65 years, female gender, and a longer time between initiation of first and subsequent therapies. Factors associated with a reduction in OS were pemetrexed-based or singlet regimens for subsequent therapy, diagnosis of squamous histology, and a higher number of adverse events prior to subsequent therapy. Conclusion We found that a subsequent therapy consisting of singlets is associated with reduced OS compared with other chemotherapy groups. Patient characteristics such as female gender, age younger than 65 years, diagnosis of nonsquamous histology, and/or a longer time frame between initiation of first-line and subsequent chemotherapy are associated with longer survival. [ABSTRACT FROM AUTHOR]

Apolipoprotein E receptor 2 ( Apo ER2) is an apolipoprotein E receptor involved in long-term potentiation, learning, and memory. Given its role in cognition and its association with the Alzheimer's disease ( AD) risk gene, apoE, Apo ER2 has been proposed to be involved in AD, though a role for the receptor in the disease is not clear. Apo ER2 signaling requires amino acids encoded by alternatively spliced exon 19. Here, we report that the balance of Apo ER2 exon 19 splicing is deregulated in postmortem brain tissue from AD patients and in a transgenic mouse model of AD. To test the role of deregulated Apo ER2 splicing in AD, we designed an antisense oligonucleotide ( ASO) that increases exon 19 splicing. Treatment of AD mice with a single dose of ASO corrected Apo ER2 splicing for up to 6 months and improved synaptic function and learning and memory. These results reveal an association between Apo ER2 isoform expression and AD, and provide preclinical evidence for the utility of ASOs as a therapeutic approach to mitigate Alzheimer's disease symptoms by improving Apo ER2 exon 19 splicing. [ABSTRACT FROM AUTHOR]

We examined the trends of quantitative research over the past 10 years in the Journal of Marital and Family Therapy (JMFT). Specifically, within the JMFT, we investigated the types and trends of research design and statistical analysis within the quantitative research that was published in JMFT from 2005 to 2014. We found that while the amount of peer-reviewed articles have increased over time, the percentage of quantitative research has remained constant. We discussed the types and trends of statistical analysis and the implications for clinical work and training programs in the field of marriage and family therapy. [ABSTRACT FROM AUTHOR]

Group A Streptococcus (GAS, Streptococcus pyogenes) is a human-restricted pathogen with a capacity to both colonize asymptomatically and cause illnesses ranging from pharyngitis to necrotizing fasciitis. An understanding of how and when GAS switches between genetic programs governing these different lifestyles has remained an enduring mystery and likely requires carefully tuned environmental sensors to activate and silence genetic schemes when appropriate. Herein, we describe the relationship between the Control of Virulence (CovRS, CsrRS) two-component system and the Rgg2/3 quorum-sensing pathway. We demonstrate that responses of CovRS to the stress signals Mg2+ and a fragment of the antimicrobial peptide LL-37 result in modulated activity of pheromone signaling of the Rgg2/3 pathway through a means of proteolysis of SHP peptide pheromones. This degradation is mediated by the cytoplasmic endopeptidase PepO, which is the first identified enzymatic silencer of an RRNPP-type quorum-sensing pathway. These results suggest that under conditions in which the virulence potential of GAS is elevated (i.e. enhanced virulence gene expression), cellular responses mediated by the Rgg2/3 pathway are abrogated and allow individuals to escape from group behavior. These results also indicate that Rgg2/3 signaling is instead functional during non-virulent GAS lifestyles. [ABSTRACT FROM AUTHOR]

The human-restricted pathogen S treptococcus pyogenes ( Group A Streptococcus, GAS) is responsible for wide-ranging pathologies at numerous sites in the body but has the proclivity to proliferate in individuals asymptomatically. The ability to survive in diverse tissues is undoubtedly benefited by sensory pathways that recognize environmental cues corresponding to stress and nutrient availability and thereby trigger adaptive responses. We investigated the impact that environmental signals contribute to cell-to-cell chemical communication [quorum sensing ( QS)] by monitoring activity of the Rgg2/ Rgg3 and SHP-pheromone system in GAS. We identified metal limitation and the alternate carbon source mannose as two environmental indicators likely to be encountered by GAS in the host that significantly induced the Rgg- SHP system. Disruption of the metal regulator MtsR partially accounted for the response to metal depletion, whereas pts ABCD was primarily responsible for QS induction due to mannose, but each sensory system induced Rgg- SHP signaling apparently by different mechanisms. Significantly, we found that induction of QS, regardless of the GAS serotype tested, led to enhanced resistance to the antimicrobial agent lysozyme. These results indicate the benefits for GAS to integrate environmental signals with intercellular communication pathways in protection from host defenses. [ABSTRACT FROM AUTHOR]

Clonal instability and titer loss during Chinese hamster ovary (CHO) cell line development (CLD) has several underlying causes, the most prominent of which are DNA copy number loss and DNA silencing. However, in some cases, clonal instability is due to the toxicity of the therapeutic protein(s) that clones express. Unlike DNA copy number loss, which may occur in some clones or DNA silencing that is prevalent in certain regions of the genome, the hallmark of product induced clonal instability is its manifestation in all the selected clones. To circumvent such product induced clonal instability, we have developed a vector construct that utilizes a regulated protein expression system in which the constitutive expression of the target protein(s) is prevented unless doxycycline is added to the culture. We have then successfully used this system to express, at high titers, an antibody for which constitutive expression results in clonal instability perhaps due to intracellular accumulation of the antibody. Our data shows that unlike the constitutively expressed or continuously induced clones, uninduced clones do not display instability. Furthermore, maintaining the uninduced clones in culture for months or subjecting them to freeze-thaws did not have any effects on their titers. All together, our findings suggest that a regulated expression system could be suitable for production of difficult proteins that trigger instability. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 30:1432-1440, 2014 [ABSTRACT FROM AUTHOR]

Objective In the Mexican-American population, the prevalence of Type 2 diabetes mellitus (T2 DM) is as high as 50% of the population. This randomized controlled clinical trial was designed to elucidate how treatment of periodontal disease affects HbA1c values in this population. Materials and Methods One hundred and fifty-four T2 DM patients with periodontal disease were enrolled in the study. The test group was treated with scaling and root planing ( SRP); the control group received oral hygiene instructions. At baseline and 4-6 weeks after therapy, a complete periodontal examination was performed. Blood was collected at baseline and 4 months later for HbA1c levels. Results One hundred and twenty-six individuals completed the study. Baseline mean ± SD HbA1c for the test and control groups were 9.0 ± 2.3% and 8.4 ± 2.0% respectively. Non-significant difference in HbA1c reductions (0.6 ± 2.1% and 0.3 ± 1.7%) was found between test and control groups at 4 months. Comparisons of the periodontal clinical parameters between the test and control groups found significant differences with improved results in the test subjects. Conclusions No statistically significant differences were found in the changes of HbA1c levels between test and control groups. Non-surgical periodontal therapy improved the magnitude of change in periodontal parameters as compared to the control subjects. ClinicalTrials.gov Identifier: NCT01128374 [ABSTRACT FROM AUTHOR]

Cell death due to apoptosis is frequently observed in large-scale manufacturing of therapeutic proteins, and can reduce product accumulation in bioreactors. Several different strategies that involve overexpression of antiapoptotic or downregulation of proapoptotic proteins have been designed in attempt to curb this problem in Chinese hamster ovary (CHO) cell culture. However, each of these designs has their own shortcomings and limits, rendering them ineffective for large-scale protein production. Recently, we have reported generation of a Bax and Bak deficient dhfr−/− CHO cell line using zinc-finger nucleases. Here we demonstrate that puromycin, but not methotrexate, selection can be used to generate antibody-expressing Bax and Bak deficient clones that are not only resistant to apoptosis, but that can also achieve higher titers relative to parental CHO cells due to higher cell density. Additionally, we show that Bax and Bak deficient cells have more mitochondria with healthy membrane potential, an attribute that perhaps contributes to their more potent growth compared to parental cells. Bax and Bak deficient cells do not readily apoptose, as shown by the ability to withstand high concentrations of apoptosis inducing agents, such as sodium butyrate, without a reduction in viability, growth, or titer. These traits render Bax and Bak deficient cells a potentially attractive host for production of therapeutic proteins at industrial scale. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:727-737, 2013 [ABSTRACT FROM AUTHOR]

It is often challenging to ascribe an objective measure of confidence for identifications based on surveillance imagery from a crime scene. The present work seeks to address this deficiency in the case of garment comparison evidence by developing a quantitative method for establishing a conservative lower bound on the likelihood ratio ( LR) for identifications involving patterned garments. The method is based on statistical analysis of pattern offset measurements taken from a sample of garments of the same type (manufacturer, style, and size) as the seized evidence. The developed analysis framework was demonstrated on different types of garments over a range of modeled surveillance imaging scenarios with variable image quality; the lower bounds on the LRs ranged from approximately 10-1 to over 400-1. The statistical model was tested and validated through a large-scale empirical study involving both simulated and human observer-performed garment comparisons. [ABSTRACT FROM AUTHOR]

Highly cross-linked formulations of ultrahigh-molecular-weight polyethylene (XLPE) offer exceptional wear resistance for total joint arthroplasty but are offset with a reduction in postyield and fatigue fracture properties in comparison to conventional ultrahigh-molecular-weight polyethylene (UHMWPE). Oxidation resistance is also an important property for the longevity of total joint replacements (TJRs) as formulations of UHMWPE or XLPE utilizing radiation methods are susceptible to free radical generation and subsequent embrittlement. The balance of oxidation, wear, and fracture properties is an enduring concern for orthopedic polymers used as the bearing surface in total joint arthroplasty. Optimization of material properties is further challenged in designs that make use of locking mechanisms, notches, or other stress concentrations that can render the polymer susceptible to fracture due to elevated local stresses. Clinical complications involving impingements, dislocations, or other biomechanical overloads can exacerbate stresses and negate benefits of improved wear resistance provided by XLPE. This work examines trade-offs that factor into the use of XLPE in TJR implants. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 101B: 476-484, 2013. [ABSTRACT FROM AUTHOR]

This study examined the effects of laser welding and heat treatment on the dimensional change of cast gold alloy frameworks. Pairs of cast gold alloy plates were matched, fixed in a jig, and welded in a laser-welding machine at constant welding parameters. The specimens were welded unilaterally (on one surface) or bilaterally (on two surfaces) with five spots as follows: two ends fixed/unilaterally welded (A); two ends fixed/bilaterally welded (AA); one end fixed/unilaterally welded (B); two ends fixed/welded on one surface and then one end fixed/welded on the opposite surface (AB); or one end fixed/bilaterally welded (BB). The dimensional change was determined by measuring the gap between the jig base and one end of the specimen after each welding application. Dimensional change was also measured after two different heat treatments (softening and hardening). The results were analyzed using a two-way ANOVA and Duncan's test ( p < 0.05). The dimensional change of the specimens fixed at only one end on either surface (AB, B, and BB) was higher compared with the two ends-fixed specimens (A and AA) after laser welding. The heat treatments also increased the dimensional change in all groups except for the B group. The dimensional change was similar for each fixing method between the two types of heat treatment. The method of fixing the specimens in the jig significantly affected the amount of dimensional change of the gold alloys. The heat treatments of the laser-welded specimens increased the dimensional change by releasing the residual stress. [ABSTRACT FROM AUTHOR]

Purpose: To compare pharmacokinetics and tolerability of levetiracetam (LEV) in older versus younger adults. Methods: As part of the Columbia Antiepileptic Drug Database, we retrospectively studied the pharmacokinetics and tolerability of LEV in patients who had been seen as an outpatient at our center during a 4-year period. We compared apparent clearance (CL) of LEV in the youngest (16–31 years; n = 151) and oldest (55–88 years; n = 157) quartile of 629 adult outpatients who had taken LEV. We also analyzed the frequency of adverse effects leading to dose change or discontinuation (“intolerability”) and specific adverse effects in the younger versus older adults. One-year retention was determined for younger and older adults newly started on LEV at our center. Results: Mean LEV CL differed significantly between older (46.5 ml/h/kg) and younger adults (78.3 ml/h/kg). On average, older patients had a 40% lower LEV CL than younger patients. Comedication with an enzyme-inducing antiepileptic drug (EIAED; mostly carbamazepine) was associated with a 24% higher clearance of LEV compared to those who were not on EIAEDs. This difference was 37% in a subgroup of patients whose LEV CL was compared while they were on and off EIAEDs. Stepwise linear regression identified younger age and comedication with an EIAED as significant predictors of increased LEV CL. A total of 34.3% of the 629 patients (31.7% of younger vs. 40.7% of older patients; p = 0.16) reported intolerability to LEV on at least one occasion. This difference in tolerability reached significance in the group of patients newly started on LEV (26.3% vs. 41.0%; p = 0.017). Drowsiness and psychiatric/behavioral side effects were the most common adverse effects associated with LEV use in both age groups. One-year retention was 72% in the older group vs. 54% in the younger group (not significant). Conclusion: Older adults have lower CL than younger adults and require a mean 40% lower dose of LEV to achieve the same serum level. Comedication with an EIAED increases LEV CL by 24–37%. Younger adults tolerate LEV better than older adults, but 1-year retention was (nonsignificantly) higher in the older group. [ABSTRACT FROM AUTHOR]

Group B streptococci (GBS) express a β-haemolysin/cytolysin that contributes to disease pathogenesis. We report an independent discovery and extension of a genetic locus encoding the GBS β-haemolysin/cytolysin activity. A plasmid library of GBS chromosomal DNA was cloned into Escherichia coli, and a transformant was identified as β-haemolytic on blood agar. The purified plasmid contained a 4046 bp insert of GBS DNA encoding two complete open reading frames (ORFs). A partial upstream ORF (cylB) and the first complete ORF (cylE) represent the 3′ end of a newly reported genetic locus (cyl) required for GBS haemolysin/cytolysin activity. ORF cylE is predicted to encode a 78.3 kDa protein without GenBank homologies. The GBS DNA fragment also includes a previously unreported ORF, cylF, with homology to bacterial aminomethyltransferases, and the 5′ end of cylH, with homology to 3-ketoacyl-ACP synthases. Southern analysis demonstrated that the cyl locus was conserved among GBS of all common serotypes. Targeted plasmid integrational mutagenesis was used to disrupt cylB, cylE, cylF and cylH in three wild-type GBS strains representing serotypes Ia, III and V. Targeted integrations in cylB, cylF and cylH retaining wild-type haemolytic activity were identified in all strains. In contrast, targeted integrations in cylE were invariably non-haemolytic and non-cytolytic, a finding confirmed by in frame allelic exchange of the cylE gene. The haemolytic/cytolytic activity of the cylE allelic exchange mutants could be restored by reintroduction of cylE on a plasmid vector. Inducible expression of cylE, cylF and cylEF demonstrated that it is CylE that confers haemolytic activity in E. coli. We conclude that cylE probably represents the structural gene for the GBS haemolysin/cytolysin, a novel bacterial toxin. [ABSTRACT FROM AUTHOR]