Skull Abnormalities in Cadavers in the Gross Anatomy Lab.

BACKGROUND: The skull encompasses and houses one of the most important organs in the body-the brain-and like all tissues in the body, it is comprised of living cells that are constantly remodeling as this maintains the strength and homeostasis of the bone. In the present study, abnormal bone growth patterns were observed and the possible causes of said findings were investigated in multiple cadaver skulls dissected during head and neck anatomy courses at Detroit Mercy Dental over the past year. There are many factors, both intrinsic and extrinsic, with differences in stimulation to the skull resulting in skull abnormalities. Materials and Methods. For this study, skull abnormalities were examined from 65 formalin-embalmed cadaver heads, obtained from the Gross Anatomy Laboratory at the University of Detroit Mercy School of Dentistry between the years 2016 and 2019. We have recorded the age, sex, and previous chief medical issues of all lab specimens used in the study. Skulls were later evaluated for possible indications of bone disease such as hypertosis frontalis interna (HFI) or Paget's disease. RESULTS: Among the sixty-five specimens provided to the Detroit Mercy Dental cadaver lab, 19 specimens (29%) were found to present with irregular, undulating, thickening of the frontal bone internal surface. The findings located on the skulls closely resembled the gross anatomic appearance of HFI or Paget's disease; however, a conclusive diagnosis of these skull abnormalities cannot be made without a pathologist biopsy and radiological examination. Twelve of the nineteen specimens that displayed possible bone disease, approximating 63% prevalence, were females; their ages ranged from 68 to 95 years old. Thus, seven of the nineteen specimens exhibiting features of skull abnormalities, approximating 36% prevalence, were males with ages ranging from 70 to 103 years old. In addition, five of these nineteen specimens collected (26% prevalence) had been diagnosed with neurological disorders, including Alzheimer's, dementia, depression, and Parkinson's disease. In the current study, the proportion of specimens exhibiting skull abnormalities was higher compared to the overall prevalence observed in previous studies. CONCLUSION: Possible causes of observed anatomical abnormalities in the skull of cadavers of a gross anatomy laboratory were investigated, and it was determined that hypertosis frontalis interna (HFI) may contribute to such abnormalities. This is a condition that affects bone growth in the frontal skull. Our numbers of skull abnormalities were higher than previous studies and might be due to the fact that HFI was predominately present as an incidental finding during imaging of postmenopausal females or observed postmortem in cadavers. In addition, Paget's disease or hormonal imbalances could also result in similar features, and thus cannot be ruled out as a plausible cause. Paget's disease causes the bone to deposit at a faster rate than normal, which will result in thick and brittle bone. Studies that will involve further examination of new cadavers for the presence of HFI is needed, either using biopsy specimens and/or radiological examination to explore possible causes for the abnormal bone growth in the frontal bone.

A Quasi-experimental Evaluation of Performance Improvement Teams in the Safety-Net: A Labor-Management Partnership Model for Engaging Frontline Staff.

BACKGROUND: Unit-based teams (UBTs), initially developed by Kaiser Permanente and affiliated unions, are natural work groups of clinicians, managers, and frontline staff who work collaboratively to identify areas for improvement and implement solutions. OBJECTIVE: We evaluated the UBT model implemented by the Los Angeles County Department of Health Services in partnership with its union to engage frontline staff in improving patient care. DESIGN: We conducted a quasi-experimental study, comparing surveys at baseline and 6 months, among personnel in 10 clinics who received UBT training to personnel in 5 control clinics. We also interviewed staff from 5 clinics that received UBT training and 3 control clinics. PARTICIPANTS: We conducted 330 surveys and 38 individual, semi-structured interviews with staff at an outpatient facility in South Los Angeles. INTERVENTIONS: Each UBT leader received an 8-hour training in basic performance improvement methods, and each UBT was assigned a team "coach." MAIN MEASURES: Our outcome measure was 6-month change in the "adaptive reserve" score, the units' self-reported ability to make and sustain change. We analyzed transcripts of the interviews to find common themes regarding the UBT intervention. KEY RESULTS: The survey response rate was 63% (158/252) at baseline and 75% (172/231) at 6 months. There was a significant difference-in-change in adaptive reserve between UBTs and non-UBTs at 6 months (+0.11 vs -0.13; P = .02). Nine of the 10 UBTs reported increases in adaptive reserve and 8 UBTs reported decreased no-show rates or patient length of stay in clinic. Staff overwhelmingly felt the UBTs were a positive intervention because it allowed all levels of staff to have a voice in improvement. CONCLUSIONS: Our results indicate that partnership between management and unions to engage frontline staff in teams may be a useful tool to improve delivery of health care in a safety-net setting.

DNA Three-Way Junctions Stabilized by Hydrophobic Interactions for Creation of Functional Nanostructures.

The construction of nanomaterials from oligonucleotides by modular assembly invariably requires the use of branched nucleic acid architectures such as three- and four-way junctions (3WJ and 4WJ). We describe the stabilization of DNA 3WJ by using non-nucleotide lipophilic spacers to create a hydrophobic pocket within the junction space. Stabilization of nucleic acid junctions is of particular importance when constructing nanostructures in the "ultra-nano" size range (<20 nm) with shorter double-stranded regions. UV thermal melting studies show that lipophilic spacers strategically placed within the junction space significantly increased thermal stability. For a 3WJ with eight base pair arms, thermal stability was increased from 30.5 °C for the unmodified junction to a maximum stability of 55.0 °C. The stability of the junction can be modulated within this temperature range by using the appropriate combinations of spacers.

Direct oligonucleotide-photosensitizer conjugates for photochemical delivery of antisense oligonucleotides.

Activation of photosensitizers in endosomes enables release of therapeutic macromolecules into the cytosol of the target cells for pharmacological actions. In this study, we demonstrate that direct conjugation of photosensitizers to oligonucleotides (ONs) allows spatial and temporal co-localization of the two modalities in the target cells, and thus leads to superior functional delivery of ONs. Further, light-activated delivery of an anticancer ON caused cancer cell killing via modulation of an oncogene and photodynamic therapy.

Bioconjugates for targeted delivery of therapeutic oligonucleotides.

Bioconjugates have been used to deliver therapeutic oligonucleotides to their pharmacological targets in diseased cells. Molecular-scale conjugates can be prepared by directly linking targeting ligands with oligonucleotides and the resultant conjugates can selectively bind to cell surface receptors in target cells in diseased tissues. Besides targeted delivery, additional functionality can be incorporated in the conjugates by utilization of carrier molecules, and these larger conjugates are called carrier-associated conjugates. Both molecular and carrier-associated conjugates have achieved initial successes in clinical trials for treating liver diseases; therefore, currently the greater challenge is to deliver oligonucleotides to extrahepatic tissues such as tumors. This review will provide an update on the application of oligonucleotide conjugates for targeted delivery during the last decade. By identifying key elements for successful delivery, it is suggested that oligonucleotide conjugates with intermediate size, cell targeting ability, and endosomal release functionality are superior systems to advance oligonucleotides to achieve their full therapeutic potentials.

Effectiveness of a smartphone application for weight loss compared with usual care in overweight primary care patients: a randomized, controlled trial.

BACKGROUND: Many smartphone applications (apps) for weight loss are available, but little is known about their effectiveness. OBJECTIVE: To evaluate the effect of introducing primary care patients to a free smartphone app for weight loss. DESIGN: Randomized, controlled trial. (ClinicalTrials.gov: NCT01650337). SETTING: 2 academic primary care clinics. PATIENTS: 212 primary care patients with body mass index of 25 kg/m2 or greater. INTERVENTION: 6 months of usual care without (n = 107) or with (n = 105) assistance in downloading the MyFitnessPal app (MyFitnessPal). MEASUREMENTS: Weight loss at 6 months (primary outcome) and changes in systolic blood pressure and behaviors, frequency of app use, and satisfaction (secondary outcomes). RESULTS: After 6 months, weight change was minimal, with no difference between groups (mean between-group difference, -0.30 kg [95% CI, -1.50 to 0.95 kg]; P = 0.63). Change in systolic blood pressure also did not differ between groups (mean between-group difference, -1.7 mm Hg [CI, -7.1 to 3.8 mm Hg]; P = 0.55). Compared with patients in the control group, those in the intervention group increased use of a personal calorie goal (mean between-group difference, 2.0 d/wk [CI, 1.1 to 2.9 d/wk]; P < 0.001), although other self-reported behaviors did not differ between groups. Most users reported high satisfaction with MyFitnessPal, but logins decreased sharply after the first month. LIMITATIONS: Despite being blinded to the name of the app, 14 control group participants (13%) used MyFitnessPal. In addition, 32% of intervention group participants and 19% of control group participants were lost to follow-up at 6 months. The app was given to patients by research assistants, not by physicians. CONCLUSION: Smartphone apps for weight loss may be useful for persons who are ready to self-monitor calories, but introducing a smartphone app is unlikely to produce substantial weight change for most patients. PRIMARY FUNDING SOURCE: Robert Wood Johnson Foundation Clinical Scholars Program, National Institutes of Health/National Center for Advancing Translational Sciences for the UCLA Clinical and Translational Science Institute, and the Resource Centers for Minority Aging Research Center for Health Improvement of Minority Elderly under the National Institutes of Health/National Institute on Aging.

Cellular uptake and intracellular trafficking of oligonucleotides: implications for oligonucleotide pharmacology.

One of the major constraints on the therapeutic use of oligonucleotides is inefficient delivery to their sites of action in the cytosol or nucleus. Recently it has become evident that the pathways of cellular uptake and intracellular trafficking of oligonucleotides can strongly influence their pharmacological actions. Here we provide background information on the basic processes of endocytosis and trafficking and then review recent literature on targeted delivery and subcellular trafficking of oligonucleotides in that context. A variety of approaches including molecular scale ligand-oligonucleotide conjugates, ligand-targeted nanocarriers, and the use of small molecules to enhance oligonucleotide effects are discussed.

Mobile applications for weight management: theory-based content analysis.

BACKGROUND: The use of smartphone applications (apps) to assist with weight management is increasingly prevalent, but the quality of these apps is not well characterized. PURPOSE: The goal of the study was to evaluate diet/nutrition and anthropometric tracking apps based on incorporation of features consistent with theories of behavior change. METHODS: A comparative, descriptive assessment was conducted of the top-rated free apps in the Health and Fitness category available in the iTunes App Store. Health and Fitness apps (N=200) were evaluated using predetermined inclusion/exclusion criteria and categorized based on commonality in functionality, features, and developer description. Four researchers then evaluated the two most popular apps in each category using two instruments: one based on traditional behavioral theory (score range: 0-100) and the other on the Fogg Behavioral Model (score range: 0-6). Data collection and analysis occurred in November 2012. RESULTS: Eligible apps (n=23) were divided into five categories: (1) diet tracking; (2) healthy cooking; (3) weight/anthropometric tracking; (4) grocery decision making; and (5) restaurant decision making. The mean behavioral theory score was 8.1 (SD=4.2); the mean persuasive technology score was 1.9 (SD=1.7). The top-rated app on both scales was Lose It! by Fitnow Inc. CONCLUSIONS: All apps received low overall scores for inclusion of behavioral theory-based strategies.

Evaluation of end-capped DNA modules for pRNA capture and functionalization.

The ability of packaging RNA (pRNA) from the phi29 DNA packaging motor to form nanoassemblies and nanostructures has been exploited for the development of the nascent field of RNA nanotechnology and subsequent applications in nanomedicine. For applications in nanomedicine, it is necessary to modify the pRNA structure for the conjugation of active molecules. We have investigated end-capped double-stranded DNA segments as reversible capture reagents for pRNA. These capture agents can be designed to allow the conjugation of any desired molecule for pRNA functionalization. The results of model studies presented in this report show that 5- to 7-nucleotide overhangs on a target RNA can provide efficient handles for the high-affinity association to capped double-stranded DNA.

Are e-health web users looking for different symptom information than callers to triage centers?

INTRODUCTION: Telemedicine options for symptom assessment include both telephonic means (call centers) and Internet sites. Although symptom assessment call centers have been available for decades, symptom assessment over the Internet is relatively new. It is not well known what types of symptoms Internet users are seeking assessment for and whether extant telephone triage algorithms would be applicable to Internet users. METHODS: Symptom assessments on a heavily used Internet site (MayoClinic.com) were compared with symptom calls to a U.S. call center (Ask Mayo Clinic). RESULTS: Internet users sought symptom assessments about adult symptoms 13 times more often than children's symptoms. In contrast, over the telephone, adult symptoms were addressed 2.1 times more frequently than children's symptoms. Despite the differences in frequencies of adult and child symptom assessments, users of the Internet and telephone callers asked about specific symptoms with similar relative frequencies. Analysis of 20 adult symptom types shared by the Web and call center revealed that by excluding only 2 assessments (nasal symptoms and leg pain) the remaining 18 showed a significant correlation in counts of use (r(2) = 0.68, p < 0.001 for linear trend). CONCLUSIONS: Internet users have symptoms assessed in similar proportions to callers, with a few exceptions. Compared with callers, Web users are much more likely looking for information about adult symptoms. Callers are proportionally asking more about acute symptoms, whereas Internet users appear more interested in symptom assessment of chronic conditions.

Optimized method for the synthesis and purification of adenosine--folic acid conjugates for use as transcription initiators in the preparation of modified RNA.

We present an optimized synthetic strategy for the attachment of molecules to 5'-adenosine monophosphate (AMP), which can then be used to label the 5'-end of RNA by T7 RNA polymerase mediated in vitro transcription. Through the use of a boronate affinity gel, we have developed an efficient route to the preparation of folate conjugated AMP with high yields and purity. Affi-Gel boronate is an affinity resin that selectively binds nucleoside and nucleoside derivatives at pH>7.5 and releases them at pH<6.5. This resin is used to efficiently bind and purify ribonucleotides such as AMP. This allows for the addition of a large excess of reactants and reagents in order to drive the reaction to completion and then allow easy purification without HPLC. The synthesis can be successfully scaled up to produce large quantities of AMP conjugates.

Properties of double-stranded oligonucleotides modified with lipophilic substituents.

We have synthesized a series of short, self-complementary oligonucleotide sequences modified at their 5'- and/or 3'- termini with a lipophilic dodecane (C12); these systems serve as models to assess the biophysical properties of double-stranded DNA (dsDNA) equipped with potentially stabilizing lipophilic substituents. Addition of C12 to the 5'-termini of self-complementary 10 nucleotide sequences increased their duplex melting temperatures (T(m)) by approximately 4-8 degrees C over their corresponding unmodified sequences. C12 functionalities added to both the 3'- and 5'-termini increased T(m) values by approximately 10-12 degrees C. The observed increases in T(m) correlated with greater duplex stabilities as determined by the free energy values (DeltaG) derived from T(m) plots. There is a greater degree of stabilization when C12 is positioned with a C.G base pair at the termini, and the stabilizing effect of lipophilic groups far exceeds the effect seen in adding an additional base pair to both ends of DNA. Stable, short dsDNA sequences are of potential interest in the development of transcription factor decoy oligonucleotides as possible therapeutic agents and/or biological tools. These results suggest that the stability of short dsDNA sequences are improved by lipophilic substituents and can be used as the basis for the design of dsDNAs with improved biological stabilities and function under physiological conditions.

Synthesis and evaluation of new spacers for use as dsDNA end-caps.

A series of aliphatic and aromatic spacer molecules designed to cap the ends of DNA duplexes have been synthesized. The spacers were converted into dimethoxytrityl-protected phosphoramidites as synthons for oligonucleotides synthesis. The effect of the spacers on the stability of short DNA duplexes was assessed by melting temperature studies. End-caps containing amide groups were found to be less stabilizing than the hexaethylene glycol spacer. End-caps containing either a terthiophene or a naphthalene tetracarboxylic acid diimide were found to be significantly more stabilizing. The former showed a preference for stacking above an A*T base pair. Spacers containing only methylene (-CH(2)-) and amide (-CONH-) groups interact weakly with DNA and consequently may be optimal for applications that require minimal influence on DNA structure but require a way to hold the ends of double-stranded DNA together.

Primary care's eroding earnings: is congress concerned?

PURPOSE: Despite increasing data demonstrating the positive impact primary care has on quality of care and costs, our specialty faces uncertainty. Its popularity among medical students is declining, and the income gap is growing between primary care and other specialties. Congress has the power to intervene in this impending crisis. If we want to influence lawmakers' actions, we need to know how they are thinking about these issues. METHODS: Using a set of questions covering several physician payment topics, we interviewed 14 congressional staff aides (5 aides on Medicare-oversight committees, 9 general staff aides) and one representative from each of 3 governmental agencies: the Medicare Payment Advisory Commission, Congressional Budget Office, and Government Accountability Office. RESULTS: Interviewees revealed that issues in primary care are not high on the congressional agenda, and that Medicare's Sustainable Growth Rate (SGR) is the physician-payment issue on the minds of congressional staff members. CONCLUSION: Attempts to solve primary care's reimbursement difficulties should be tied to SGR reform.

Introducing the "teamlet": initiating a primary care innovation at san francisco general hospital.

CONTEXT: The 15-minute office visit to primary care clinicians cannot meet the health care needs of patients. Innovation is needed to address this limitation, but practice redesign is challenging in clinical settings. OBJECTIVE: Here we describe the implementation of a practice innovation, the teamlet model, in a San Francisco safety-net clinic. The teamlet consists of a clinician and "health coach" who expand the traditional medical visit into previsit, visit, postvisit, and between-visit care. DESIGN: Teamlet implementation is occurring in phases. Phase 1 is evaluated using plan-do-study-act improvement cycles and interviews with a few patients, clinicians, and coaches. Phase 2 is evaluated using a pre- and postevent questionnaire, focused interviews, and focus groups with patients, faculty, clinicians, and coaches. MAIN OUTCOME MEASURES: Phase 1: Plan-do-study-act cycles generate ideas to improve implementation. Phase 2 evaluation will query demographics, satisfaction, knowledge of self-management support, access, teamwork, and benefits/challenges of the teamlet model. Future research would measure objective clinical outcomes. RESULTS: Phase 1 of the teamlet project led to useful adaptations, with anecdotal evidence that patients and clinicians were satisfied overall with practice improvements. Logistic problems made implementation of the innovation challenging. Phase 2 is currently underway, with results expected in 2008. CONCLUSIONS: Primary care innovation requires multiple perspectives and constant revision. Traditional randomized controlled trials and quantitative evaluation designs are not appropriate for assessing practice-improvement pilot projects because projects must change and develop in their early stages. Despite numerous challenges, the teamlet practice redesign has the potential for improving on the traditional 15-minute physician's office visit.

The teamlet model of primary care.

The 15-minute visit does not allow the physician sufficient time to provide the variety of services expected of primary care. A teamlet (little team) model of care is proposed to extend the 15-minute physician visit. The teamlet consists of 1 clinician and 2 health coaches. A clinical encounter includes 4 parts: a previsit by the coach, a visit by the clinician together with the coach, a postvisit by the coach, and between-visit care by the coach. Medical assistants or other practice personnel would require retraining to assume the health coach role. Some organizations have instituted aspects of the teamlet model. Primary care practices interested in trying out the teamlet concept need to train 2 health coaches for each full-time equivalent clinician to ensure smooth patient flow.