Genomic Copy-Number Loss Is Rescued by Self-Limiting Production of DNA Circles.

Copy-number changes generate phenotypic variability in health and disease. Whether organisms protect against copy-number changes is largely unknown. Here, we show that Saccharomyces cerevisiae monitors the copy number of its ribosomal DNA (rDNA) and rapidly responds to copy-number loss with the clonal amplification of extrachromosomal rDNA circles (ERCs) from chromosomal repeats. ERC formation is replicative, separable from repeat loss, and reaches a dynamic steady state that responds to the addition of exogenous rDNA copies. ERC levels are also modulated by RNAPI activity and diet, suggesting that rDNA copy number is calibrated against the cellular demand for rRNA. Last, we show that ERCs reinsert into the genome in a dosage-dependent manner, indicating that they provide a reservoir for ultimately increasing rDNA array length. Our results reveal a DNA-based mechanism for rapidly restoring copy number in response to catastrophic gene loss that shares fundamental features with unscheduled copy-number amplifications in cancer cells.

Identification of pancreatic cancer risk factors from clinical notes using natural language processing.

OBJECTIVES: Screening for pancreatic ductal adenocarcinoma (PDAC) is considered in high-risk individuals (HRIs) with established PDAC risk factors, such as family history and germline mutations in PDAC susceptibility genes. Accurate assessment of risk factor status is provider knowledge-dependent and requires extensive manual chart review by experts. Natural Language Processing (NLP) has shown promise in automated data extraction from the electronic health record (EHR). We aimed to use NLP for automated extraction of PDAC risk factors from unstructured clinical notes in the EHR. METHODS: We first developed rule-based NLP algorithms to extract PDAC risk factors at the document-level, using an annotated corpus of 2091 clinical notes. Next, we further improved the NLP algorithms using a cohort of 1138 patients through patient-level training, validation, and testing, with comparison against a pre-specified reference standard. To minimize false-negative results we prioritized algorithm recall. RESULTS: In the test set (n = 807), the NLP algorithms achieved a recall of 0.933, precision of 0.790, and F1-score of 0.856 for family history of PDAC. For germline genetic mutations, the algorithm had a high recall of 0.851, while precision and F1-score were lower at 0.350 and 0.496 respectively. Most false positives for germline mutations resulted from erroneous recognition of tissue mutations. CONCLUSIONS: Rule-based NLP algorithms applied to unstructured clinical notes are highly sensitive for automated identification of PDAC risk factors. Further validation in a large primary-care patient population is warranted to assess real-world utility in identifying HRIs for pancreatic cancer screening.

Secondary osteoporosis prevention: three-year outcomes from a Fracture Liaison Service in elderly hip fracture patients.

BACKGROUND: Hip fractures are the most serious fragility fractures due to their associated disability, higher hospitalization costs and high mortality rates. Fracture Liaison Service (FLS) programs have enhanced the management of osteoporosis-related fractures and have shown their clinical effectiveness. AIMS: To analyze the effect of the implementation of a FLS model of care over the survival and mortality rates following a hip fracture. METHODS: We conducted a prospective cohort study on patients over 60 years of age who suffered a hip fracture before and after the implementation of the FLS in our center (between January 2016 and December 2019). Patients were followed for three years after the index date. Mortality, complications and refracture rates were compared between the two groups using a Multivariate Cox proportional hazard model. RESULTS: A total of 1366 patients were included in this study (353 before FLS implementation and 1013 after FLS implementation). Anti-osteoporotic drugs were more frequently prescribed after FLS implementation (79.3% vs 12.5%; p < 0.01) and there was an increase in adherence to treatment (51.7% vs 30.2%; p < 0.01). A total of 413 (40.8%) patients after FLS implementation and 141 (39.9%) individuals before (p = 0.47) died during the three-years follow-up period. A second fracture occurred in 101 (10.0%) patients after FLS implementation and 37 (10.5%) individuals before (p = 0.78). Patients after the implementation of the FLS protocol had a lower all cause one-year mortality [adjusted Hazard Ratio (HR) 0.74 (0.57-0.94)] and a decreased risk of suffering a second osteoporotic fracture [adjusted HR 0.54 (0.39-0.75) in males and adjusted HR 0.46 (0.30-0.71) in females]. CONCLUSIONS: The implementation of a FLS protocol was associated with a lower all-cause one-year mortality rate and a higher survivorship in elderly hip fracture patients. However, no three-year mortality rate differences were observed between the two groups. We also found a reduction in the complication and second-fracture rates.

Consult and procedure incidence outcomes following establishment of a fertility preservation program for children with cancer.

PURPOSE: Fertility is a quality of life outcome adversely affected by cancer therapy. Many childhood cancer patients, however, are not offered options to preserve their fertility. Providers acknowledge difficulty discussing impaired fertility to patients due to lack of knowledge of available options. Our objective was to review the impact of a pediatric multidisciplinary fertility preservation program on providers' fertility preservation counseling and discussion of options. METHODS: A retrospective medical chart review was conducted for pediatric cancer patients prior to and following program establishment. Fertility preservation discussions, consults, and incidence were noted. Following filtering and stratification, 198 and 237 patients were seen prior to and following program establishment, respectively. RESULTS: Following program establishment, provider-patient discussions of impaired fertility (p = 0.007), fertility preservation consults (p = 0.01), and incidence of fertility preservation procedures (p < 0.001) increased among patients. Furthermore, the number of patients who received fertility preservation consults after receiving gonadotoxic treatment decreased (p < 0.001). This trend was particularly noted in pre-pubertal and female patients, for whom fertility preservation options are limited without an established program. CONCLUSION: The establishment of a formal program greatly improved access to fertility preservation consults and procedures in children with cancer.

Describing pediatric hospital discharge planning care processes using the Omaha System.

PURPOSE: Although discharge planning (DP) is recognized as a critical component of hospital care, national initiatives have focused on older adults, with limited focus on pediatric patients. We aimed to describe patient problems and targeted interventions as documented by social workers or DP nurses providing specialized DP services in a children's hospital. METHODS: Text from 67 clinical notes for 28 patients was mapped to a standardized terminology (Omaha System). Data were deductively analyzed. RESULTS: A total of 517 phrases were mapped. Eleven of the 42 Omaha System problems were identified. The most frequent problem was health care supervision (297/517; 57.4%). Three Omaha System intervention categories were used (teaching, guidance, and counseling; case management; and surveillance). Intervention targets are varied by role. CONCLUSION: The findings provide a rich description of the nature of DP for complex pediatric patients and increase our understanding of the work of DP staff and the influence of the DP practice model.

Method for enhancing real-world use of a more affected arm in chronic stroke: transfer package of constraint-induced movement therapy.

BACKGROUND AND PURPOSE: Constraint-induced movement therapy is a set of treatments for rehabilitating motor function after central nervous system damage. We assessed the roles of its 2 main components. METHODS: A 2 × 2 factorial components analysis with random assignment was conducted. The 2 factors were type of training and presence/absence of a set of techniques to facilitate transfer of therapeutic gains from the laboratory to the life situation (Transfer Package; TP). Participants (N=40) were outpatients ≥ 1-year after stroke with hemiparesis. The different treatments, which in each case targeted the more affected arm, lasted 3.5 hours/d for 10 weekdays. Spontaneous use of the more affected arm in daily life and maximum motor capacity of that arm in the laboratory were assessed with the Motor Activity Log and the Wolf Motor Function Test, respectively. RESULTS: Use of the TP, regardless of the type of training received, resulted in Motor Activity Log gains that were 2.4 times as large as the gains in its absence (P<0.01). These clinical results parallel previously reported effects of the TP on neuroplastic change. Both the TP and training by shaping enhanced gains on the Wolf Motor Function Test (P<0.05). The Motor Activity Log gains were retained without loss 1 year after treatment. An additional substudy (N=10) showed that a single component of the TP, weekly telephone contact with participants for 1 month after treatment, doubled Motor Activity Log scores at 6-month follow-up. CONCLUSIONS: The TP is a method for enhancing both spontaneous use of a more affected arm after chronic stroke and its maximum motor capacity. Shaping enhances the latter.

Constraint-induced movement therapy combined with conventional neurorehabilitation techniques in chronic stroke patients with plegic hands: a case series.

OBJECTIVE: To determine whether the combination of Constraint-Induced Movement Therapy (CIMT) and conventional rehabilitation techniques can produce meaningful motor improvement in chronic stroke patients with initially fisted hands. DESIGN: Case series. SETTING: University hospital outpatient laboratory. PARTICIPANTS: Consecutive sample (N=6) >1 year poststroke with plegic hands. INTERVENTIONS: Treatment consisted of an initial period of 3 weeks (phase A) when adaptive equipment in the home, orthotics, and splints were employed to improve ability to engage in activities of daily living. This was continued in phase B, when CIMT and selected neurodevelopmental treatment techniques were added. MAIN OUTCOME MEASURES: Motor Activity Log (MAL), accelerometry, Fugl-Meyer Motor Assessment (F-M). RESULTS: Patients exhibited a large improvement in spontaneous real-world use of the more-affected arm (mean lower-functioning MAL change=1.3±0.4 points; P<.001; d'=3.0) and a similar pattern of increase in an objective measure of real-world more-affected arm movement (mean change in ratio of more- to less-affected arm accelerometer recordings=0.12±0.1 points; P=.016; d'=1.2). A large improvement in motor status was also recorded (mean F-M change=5.3±3.3 points; P=.005; d'=1.6). CONCLUSIONS: The findings of this pilot study suggest that stroke patients with plegic hands can benefit from CIMT combined with some conventional rehabilitation techniques, even long after brain injury. More research is warranted.

Nurses' attitudes, abilities and educational preference related to using family pedigrees in clinical practice.

There is growing worldwide interest in using family pedigrees to assess health risks for diseases and implementing potential preventive interventions for health promotion. Nurses have been identified as key professionals in the process of collecting family history information and constructing pedigrees, and there is a gap in the literature related to these activities. The purpose of this study was to determine nurses' knowledge about, attitudes towards, perceived ability to use, and educational preference related to inclusion of family pedigrees in clinical practice. The study utilized a survey method with 174 nurses and correlational descriptive design. Results showed 74% of the nurses were interested in learning about family pedigrees and 64% responded positively to including them in clinical practice with the belief by 88% that they are helpful for preventive health care. Findings may be used to advance education and utilization of family pedigrees for nurses in clinical practice.

Isotopic composition of serum zinc and copper in healthy children and children with autism spectrum disorder in North America.

To better understand zinc and copper regulation and their involvement in various biochemical pathways as it relates to autism spectrum disorder (ASD), isotopic composition of serum zinc and copper were evaluated in both healthy children and children with ASD in North America. No significant difference in isotopic composition of serum zinc or copper with respect to healthy controls and ASD children were identified. However, the isotopic composition of serum copper in boys was found to be enriched in 65Cu in comparison to previously published healthy adult copper isotopic composition. Furthermore, in both boys and girls, the average isotopic composition of serum zinc is heavier than previously published healthy adult isotopic zinc composition. There was also a negative association between total zinc concentrations in serum and the zinc isotopic composition of serum in boys. Finally, children with heavier isotopic composition of copper also showed a high degree of variability in their zinc isotopic composition. While numerous studies have measured the isotopic composition of serum zinc and copper in adults, this is one of the first studies which measured the isotopic composition of serum copper and zinc in children, specifically those diagnosed with ASD. The results of this study showed that age and gender specific normal ranges of isotopic composition must be established to effectively use isotopic composition analysis in studying various diseases including ASD.

Long-Term Outcomes and Risk of Pancreatic Cancer in Intraductal Papillary Mucinous Neoplasms.

Importance: Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic cysts that can give rise to pancreatic cancer (PC). Limited population data exist on their prevalence, natural history, or risk of malignant transformation (IPMN-PC). Objective: To fill knowledge gaps in epidemiology of IPMNs and associated PC risk by estimating population prevalence of IPMNs, associated PC risk, and proportion of IPMN-PC. Design, Setting, and Participants: : This retrospective cohort study was conducted in Olmsted County, Minnesota. Using the Rochester Epidemiology Project (REP), patients aged 50 years and older with abdominal computed tomography (CT) scans between 2000 and 2015 were randomly selected (CT cohort). All patients from the REP with PC between 2000 and 2019 were also selected (PC cohort). Data were analyzed from November 2021 through August 2023. Main outcomes and Measures: CIs for PC incidence estimates were calculated using exact methods with the Poisson distribution. Cox models were used to estimate age, sex, and stage-adjusted hazard ratios for time-to-event end points. Results: The CT cohort included 2114 patients (1140 females [53.9%]; mean [SD] age, 68.6 [12.1] years). IPMNs were identified in 231 patients (10.9%; 95% CI, 9.7%-12.3%), most of which were branch duct (210 branch-duct [90.9%], 16 main-duct [6.9%], and 5 mixed [2.2%] IPMNs). There were 5 Fukuoka high-risk (F-HR) IPMNs (2.2%), 39 worrisome (F-W) IPMNs (16.9%), and 187 negative (F-N) IPMNs (81.0%). After a median (IQR) follow-up of 12.0 (8.1-15.3) years, 4 patients developed PC (2 patients in F-HR and 2 patients in F-N groups). The PC incidence rate per 100 person years for F-HR IPMNs was 34.06 incidents (95% CI, 4.12-123.02 incidents) and not significantly different for patients with F-N IPMNs compared with patients without IPMNs (0.16 patients; 95% CI, 0.02-0.57 patients vs 0.11 patients; 95% CI, 0.06-0.17 patients; P = .62). The PC cohort included 320 patients (155 females [48.4%]; mean [SD] age, 72.0 [12.3] years), and 9.8% (95% CI, 7.0%-13.7%) had IPMN-PC. Compared with 284 patients with non-IPMN PC, 31 patients with IPMN-PC were older (mean [SD] age, 76.9 [9.2] vs 71.3 [12.5] years; P = .02) and more likely to undergo surgical resection (14 patients [45.2%] vs 60 patients [21.1%]; P = .003) and more-frequently had nonmetastatic PC at diagnosis (20 patients [64.5%] vs 130 patients [46.8%]; P = .047). Patients with IPMN-PC had better survival (adjusted hazard ratio, 0.62; 95% CI, 0.40-0.94; P = .03) than patients with non-IPMN PC. Conclusions and Relevance: In this study, CTs identified IPMNs in approximately 10% of patients aged 50 years or older. PC risk in patients with F-N IPMNs was low and not different compared with patients without IPMNs; approximately 10% of patients with PC had IPMN-PC, and they had better survival compared with patients with non-IPMN PC.

Nurses' perceived benefits, barriers, and educational recommendations for using family pedigrees in clinical practice.

BACKGROUND: There is growing emphasis on the use of genetics and genomics, including family pedigrees, in nursing education. This study explored nurses' perceptions of the benefits, barriers, and educational recommendations related to family pedigrees. METHODS: A qualitative design using focus group methods was used to gather data from a convenience sample of 28 nurses working at a large medical center in the Midwestern United States. RESULTS: Nurses believed that factors supporting the use of family pedigrees are clearly identified patient benefits, an electronic tool initiated in primary care, and use by multiple disciplines. Barriers include lack of ongoing support and possible ethical, legal, social, and cultural issues. Educational recommendations include clinically relevant patient and family decision making regarding care. CONCLUSION: These nurses had positive perceptions of the use of family pedigrees in clinical nursing practice. They identified a need for education and stressed the importance of specialty-specific case examples to maximize relevance.

Corrigendum: Evaluation of Zn, Cu, and Se Levels in the North American Autism Spectrum Disorder Population.

[This corrects the article DOI: 10.3389/fnmol.2021.665686.].

Biomechanical muscle stiffness measures of extensor digitorum explain potential mechanism of McArdle sign.

BACKGROUND: McArdle sign is a phenomenon of impaired gait and muscle weakness that occurs with neck flexion, immediately reversible with neck extension. A recent report measured the specificity of this sign for multiple sclerosis by measuring differences in peak torque of the extensor digitorum between neck extension and flexion. METHODS: This substudy included 73 participants (29 multiple sclerosis, 20 non-multiple sclerosis myelopathies, 5 peripheral nerve disorders, and 19 healthy controls). The effect of neck position was assessed on muscle stiffness and neuromechanical error of the extensor digitorum. FINDINGS: Patients with multiple sclerosis had greater neuromechanical error (sum of squared error of prediction) compared to controls (P = 0.023) and non-multiple sclerosis myelopathies (P = 0.003). Neuromechanical error also provided improved sensitivity/specificity of McArdle sign. Peak torque, muscle stiffness, and neuromechanical error could distinguish multiple sclerosis from other myelopathies with 80% specificity and 97% sensitivity (AUC = 0.95). INTERPRETATION: A decrease in muscle stiffness and neuromechanical error in neck flexion compared to extension are additional indicators for a diagnosis of multiple sclerosis. Analysis of muscle stiffness may provide insights into the pathophysiology of this specific clinical sign for multiple sclerosis. Furthermore, muscle stiffness may provide an additional accurate, simple assessment to evaluate multiple sclerosis therapeutic interventions and disease progression.

Evaluation of Zn, Cu, and Se Levels in the North American Autism Spectrum Disorder Population.

Metal ion dyshomeostasis and disparate levels of biometals like zinc (Zn), copper (Cu), and selenium (Se) have been implicated as a potential causative factor for Autism Spectrum Disorder (ASD). In this study, we have enrolled 129 children (aged 2-4 years) in North America, of which 64 children had a diagnosis of ASD and 65 were controls. Hair, nail, and blood samples were collected and quantitatively analyzed for Zn, Cu and Se using inductively coupled plasma mass spectrometry (ICP-MS). Of the analyzed biometals, serum Se (116.83 ± 14.84 mcg/mL) was found to be significantly lower in male ASD cases compared to male healthy controls (128.21 ± 9.11 mcg/mL; p < 0.005). A similar trend was found for nail Se levels in ASD (1.01 ± 0.15 mcg/mL) versus that of controls (1.11 ± 0.17 mcg/mL) with a p-value of 0.0132 using a stratified Wilcoxon rank sum testing. The level of Se in ASD cohort was co-analyzed for psychometric correlation and found a negative correlation between total ADOS score and serum Se levels. However, we did not observe any significant difference in Zn, Cu, and Zn/Cu ratio in ASD cases versus controls in this cohort of North American children. Further studies are recommended to better understand the biology of the relationship between Se and ASD status.

McArdle Sign: A Specific Sign of Multiple Sclerosis.

OBJECTIVE: To measure McArdle sign (rapidly reversible weakness induced by neck flexion) both qualitatively and quantitatively and to evaluate its specificity and clinical utility for diagnosis of multiple sclerosis (MS). PATIENTS AND METHODS: In this prospective study, McArdle sign was evaluated by a technician blinded to diagnosis by measuring changes in finger extensor strength in successive trials of neck extension and flexion, first clinically and then with a torque measurement device. We studied 25 healthy controls and 81 patients with finger extensor weakness. Patients were not selected for having McArdle sign. Fifty-two patients had MS, 24 had other myelopathies, and 5 had peripheral nerve lesions accounting for their weakness. The study was conducted between February 1, 2016, and June 30, 2017. RESULTS: The median clinical McArdle sign and the 2 quantitative measures of neck flexion-induced strength reduction were greater in patients with MS than in the other groups (P<.001). Baseline strength did not confound the difference. The area under the receiver operating characteristic curve was 0.84 (95% CI, 0.75-0.93) comparing patients with MS vs healthy controls and 0.84 (95% CI, 0.75-0.93) comparing MS vs patients with other myelopathies. The 2 quantitative and 1 clinical measurement of McArdle sign by the technician who performed the quantitative testing were correlated (r=.57 and r=.58; P<.001), and in turn, the technician's and unblinded referring physician's clinical assessments were correlated (r=.58; P<.001). McArdle sign was evident in some patients who had minor disability and who were in early phases of MS. CONCLUSION: McArdle sign, when defined as greater than 10% neck flexion-induced reduction in strength, is entirely specific and 65% sensitive for a diagnosis of MS when compared with other conditions that mimic MS-associated myelopathy. It may facilitate diagnosis in certain clinical situations. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03122873.

Rehabilitation of stroke patients with plegic hands: Randomized controlled trial of expanded Constraint-Induced Movement therapy.

PURPOSE: To evaluate the efficacy of an expanded form of Constraint-Induced Movement Therapy (eCIMT) that renders CIMT, originally designed for treating mild-to-moderate upper-extremity hemiparesis, suitable for treating severe hemiparesis. METHODS: Twenty-one adults ≥1 year after stroke with severe upper-extremity hemiparesis (with little or no capacity to make movements with the more-affected hand) were randomly assigned to eCIMT (n = 10), a placebo-control procedure (n = 4), or usual care (n = 7). The participants who received usual care were crossed over to eCIMT four months after enrollment. The CIMT protocol was altered to include fitting of orthotics and adaptive equipment, selected neurodevelopmental techniques, and electromyography-triggered functional electrical stimulation. Treatment was given for 15 consecutive weekdays with 6 hours of therapy scheduled daily for the immediate eCIMT group and 3.5 hours daily for the cross-over eCIMT group. RESULTS: At post-treatment, the immediate eCIMT group showed significant gains relative to the combination of the control groups on the Grade-4/5 Motor Activity Log (MAL; mean = 1.5 points, P < 0.001, f = 4.2) and a convergent measure, the Canadian Occupational Performance Measure (COPM; mean = 2.3, P = 0.014, f = 1.1; f values ≥0.4 are considered large, on the COPM changes ≥2 are considered clinically meaningful). At 1-year follow-up, the MAL gains in the immediate eCIMT group were only 13% less than at post-treatment. The short and long-term outcomes of the crossover eCIMT group were similar to those of the immediate eCIMT group. CONCLUSIONS: This small, randomized controlled trial (RCT) suggests that eCIMT produces a large, meaningful, and persistent improvement in everyday use of the more-affected arm in adults with severe upper-extremity hemiparesis long after stroke. These promising findings warrant confirmation by a large RCT.

Feasibility Testing of the Alert for AFib Intervention.

Improving early detection and treatment of atrial fibrillation (AF) is critical because untreated AF is a major contributor to stroke and heart failure. We sought to generate knowledge about the feasibility of conducting a randomized controlled trial to test the effect of the Alert for AFib intervention on knowledge, attitudes, and beliefs about treatment-seeking for signs and symptoms of AF. Adults ≥65 years old (96% White) at risk for developing AF were randomized to receive the Alert for AFib intervention ( n = 40) or an attention control session ( n = 40). Feasibility goals for recruitment, participant retention, adherence, perceived satisfaction and burden, and intervention fidelity were met. From baseline to study completion, knowledge ( p = .005) and attitudes ( p < .001) about treatment-seeking improved more in the intervention group compared with the control group. Results support testing the effectiveness of the Alert for AFib intervention in a large trial.

A treatment for a chronic stroke patient with a plegic hand combining CI therapy with conventional rehabilitation procedures: case report.

Constraint-Induced Movement therapy (CI therapy) is a recognized rehabilitation approach for persons having stroke with mild to moderately severe motor upper extremity deficits. To date, no rehabilitation treatment protocol has been proven effective that addresses both motor performance and spontaneous upper extremity use in the life situation for chronic stroke participants having severe upper extremity impairment with no active finger extension or thumb abduction. This case report describes treatment of a chronic stroke participant with a plegic hand using a CI therapy protocol that combines CI therapy with selected occupational and physical therapy techniques. Treatment consisted of six sessions of adaptive equipment and upper extremity orthotics training followed by a three-week, six-hour daily intervention of CI therapy plus neurodevelopmental treatment. Outcome measures included the Motor Activity Log for very low functioning patients (Grade 5 MAL), upper extremity portion of the Fugl-Meyer Motor Assessment, Graded Wolf Motor Function Test - for very low functioning patients (gWMFT- Grade 5), and Modified Ashworth Scale. The participant showed improvement on each outcome measure with the largest improvement on the Grade 5 MAL. In follow-up, the participant had good retention of his gains in motor performance and use of his more affected arm for real world activities after 3 months; after a one-week brush-up at 3 months, and at one year post-treatment.

Comparison of Cervical Range-of-Motion Restriction and Craniofacial Tissue-Interface Pressure With 2 Adjustable and 2 Standard Cervical Collars.

STUDY DESIGN: Randomized controlled trial. OBJECTIVE: The aim of the study was to compare and contrast the restrictiveness and tissue-interface pressure (TIP) characteristics of 2 standard and 2 adjustable cervical collars. SUMMARY OF BACKGROUND DATA: This study compared the restrictiveness and TIP of 4 commercially available cervical collars (2 standard and 2 adjustable). Adjustable collars offer potential advantages of individualized fit for patients and decreased inventory for institutions. The overall goal was to determine whether the adjustable collars provided the same benefits of cervical range-of-motion (CROM) restriction as the standard collars without increasing TIP and risk of pressure-related complications. METHODS: A total of 48 adult volunteer subjects (24 men and 24 women) were fitted with 4 collars (Aspen, Aspen Vista, Miami J, and Miami J Advanced) in random order. Data collection included assessment of CROM restrictiveness and measurement of TIP on the mandible and occiput in upright and supine positions. The experimental, repeated measures design stratified the sample by body mass index (BMI) and sex. RESULTS: All collars restricted CROM as compared with no collar (P ≤ 0.001 each). Aspen was more restrictive than Aspen Vista and Miami J in 4 movement planes (P ≤ 0.003 each), but not significantly different from Miami J Advanced. The Miami J standard collar was associated with significantly lower peak TIPs on all sites and in all positions compared with Aspen (P ≤ 0.001), Miami J Advanced (P < 0.001), and Aspen Vista (P = 0.01 for mandible site and upright position, P < 0.001 for remaining sites and positions). Increased peak TIP correlated with high BMI across all collar types, but was significantly lower for the Miami J collar than the Aspen collar. CONCLUSION: All collars, compared with no collar, significantly restricted CROM. Although the collar-to-collar comparisons were statistically significant, the differences may have little clinical significance in the acutely injured trauma patient. The Miami J standard collar had the lowest overall TIP in both sites and positions. Ongoing effort should be devoted to staff education in proper sizing and fit, particularly for patients with high BMI.

Study of MDM2 and SUMO-1 expression in actinic cheilitis and lip cancer.

Actinic cheilitis exhibits a potential of malignant transformation in 10-20 % of cases. The objective of this study was to compare the expression of MDM2 and SUMO-1 proteins between actinic cheilitis (AC) and squamous cell carcinoma (SCC) of the lip. The sample consisted of lower lip mucosa specimens obtained from cases with a clinical and histopathological diagnosis of AC (n = 26) and SCC (n = 25) and specimens of labial semi-mucosa (n = 15) without clinical alterations or inflammation. The tissue samples were stained with hematoxylin-eosin and anti-MDM2 and anti-SUMO-1 antibodies. Data were analyzed by the Kruskal-Wallis and Dunn's tests (5 %). The median expression of MDM2 (kW = 36.8565; df = 3-1 = 2; p = 0.0001) and SUMO-1 (kW = 32.7080; df = 3-1 = 2; p = 0.0001) was similar in cases of AC and SCC of the lip, but differed significantly from that observed for normal labial semi-mucosa. Despite the limitations of the present study, immunohistochemistry demonstrated the overexpression of important proteins (MDM2 and SUMO-1) related to regulatory mechanisms of apoptosis in AC and SCC of the lip, but further studies are needed.