Pain Relief with Combination Acetaminophen/Codeine or Ibuprofen following Third-Molar Extraction: A Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of our study was to perform a systematic review and meta-analysis of randomized, blinded, placebo-controlled studies that, following third-molar extraction, utilized either a combination of acetaminophen (600 mg) with codeine (60 mg) or ibuprofen (400 mg) for pain management. DESIGN: We searched PubMed, and the trial registry ClinicalTrials.gov databases with the keywords "molar or molars," "tooth or teeth," "extraction," and "pain." Selected studies were: (1) randomized, blinded, placebo controlled, (2) utilized either a single-dose combination acetaminophen (600 mg) with codeine (60 mg) (A/C) or ibuprofen, and (3) recorded standardized pain relief (PR) at 6 hours, or summed total pain relief over 6 hours (TOTPAR6). Of the 2,949 articles that were identified, 79 were retrieved for full-text analysis, and 20 of these studies met our inclusion criteria. RESULTS: For A/C, the weighted, standardized mean difference (SMD) for TOTPAR6 was 0.796 (95% confidence interval [CI], 0.597-0.995), P < .001, and for PR at 6 hours, the SMD was 0.0186 (0.007 to 0.378; P = .059), whereas for ibuprofen the SMD for TOTPAR6 was 3.009 (1.283 to 4.735; P = .001), and for PR at 6 hours, the SMD was 0.854 (95% CI, 0.712-0.996; P < .001). A SMD of 0.8 or larger is indicative of a large effect. CONCLUSIONS: Our data indicate that single dose of ibuprofen (400 mg) is an effective pain reducer for post third molar extraction pain.

Rapid Transition to a Virtual Multiple Mini-Interview Admissions Process: A New Medical School's Experience During the COVID-19 Pandemic.

PROBLEM: The University of Houston College of Medicine (UH COM) began its first admissions cycle after receiving preliminary accreditation in February 2020. With the advent of remote learning in response to the COVID-19 pandemic, the school moved its admissions process, including multiple mini-interview (MMI), from an in-person to online format in mid-March 2020. APPROACH: The UH COM selected Zoom as the video conferencing platform for its virtual admissions process, including MMI. On each interview day (3-4 hours), 14-16 applicants joined administrators, faculty, and staff in a virtual meeting room. Applicants were divided into 2 groups: one viewed short presentations about the school, curriculum, and departments, while the other participated in 7 MMI stations (one-on-one interactions with interviewers) via virtual breakout rooms; the groups then switched. The MMI stations were the same as those used in-person in early March. Applicants were able to ask questions at multiple points during the day. Technical support was provided for participants with connectivity issues or unfamiliar with Zoom. OUTCOMES: Of the 180 applicants interviewed in March-April 2020, 134 (74%) participated in the virtual process and 46 (26%) in the on-site process. Twenty-five (83%) of the 30 members of the inaugural class of 2024 interviewed virtually. Advantages of the virtual format included ease of access for faculty and more flexibility and less expense for applicants. Challenges included the need for applicants to decide whether to accept an offer of admission from a new school without visiting and missed opportunities for faculty to have relatively unstructured interactions with applicants. NEXT STEPS: This virtual admissions process was a feasible alternative for the inaugural class but is not sustainable. UH COM plans to leverage lessons learned to refine the virtual format for use in future admissions cycles, even when in-person interviews are possible.

Reducing relative response factor variation using a multidetector approach for extractables and leachables (E&L) analysis to mitigate the need for uncertainty factors.

Characterization of Extractables and Leachables (E&Ls) is an important aspect of product quality in important fields such as pharmaceuticals, medical devices and food contact materials. The main goal of an E&L study is identification and quantification of those species which may leach from packaging materials used to contain pharmaceuticals or which may leach directly out of a medical device or food contact material and thus may result in patient exposure. It is common practice to perform relative quantitation of extractables and leachables using surrogate standards due to the large diversity of species observed and the lack of available reference standards. A key problem in obtaining accurate E&L results arises due to response factor (RF) variation. Different compounds at the same concentration give different signal intensities and thus have different RF values. Two key aspects of study quality are affected by this problem. First, the evaluation of the number of compounds which are above the toxicologically relevant threshold (analytical evaluation threshold, (AET)) can be affected (RF Problem 1: AET Underreporting). Second, quantitative accuracy is affected which can reduce the reliability of the margin of safety (MOS) calculations which serves as the basis of the toxicological evaluation (RF Problem 2: Quantitative Error). RF databases have been the main solution proposed for solving these problems but do not reduce the underlying RF variation and lack the scope required to address quantitative error for compounds not contained in the database. In the absence of other solutions, large uncertainty factors (UF) have been applied in the AET calculations to account for RF Problem 1: AET Underreporting. These UF factors have been assigned values of 4 for GCMS and up to 10 for LCMS. Large uncertainty factors have a number of unintended negative consequences including the need for large amounts of sample concentration (>10X) prior to analysis resulting in potential compound loss or degradation and increased matrix effects. To overcome these problems, this publication demonstrates a multidetector approach using an HPLC system coupled with a Quadrupole Time of Flight Liquid Chromatography Mass Spectrometer (QTOF-LCMS), Charged Aerosol Detector (CAD) and an Ultraviolet-Visible Detector (UV) and a dual detection Gas Chromatography Mass Spectrometry (GCMS) system using a Polyarc Reactor system with Flame Ionization Detection (FID). Herein, it is demonstrated that this combination of methods (the multidetector approach) allowed detection and accurate surrogate standard quantitation of 217 unique extractables spanning a wide range of chemical properties (Mw, logP, pKa and boiling point). The combination of optimized detector selection with appropriate standard selection was verified to provide positive detection for 94% of the compounds at the AET level and a high level of quantitative accuracy (± 20% for 85% of the compounds and ±40% for 91% of the compounds) while using only a UF of 2. Unlike the RF database approach, the multidetector approach is not limited to only those compounds contained in the database but is applicable to the majority of extractables.

Persistent Post-Mastectomy Pain: Risk Factors and Current Approaches to Treatment.

Persistent Post-Mastectomy Pain (PPMP) is a common condition that can follow surgeries for breast cancer, the most common cancer in women. Because of the frequency of PPMP and its potential severity, it has received increasing research attention. This manuscript reviews the recent research literature, beginning with a brief history and then relevant medical, surgical, demographic, and psychosocial risk factors. Subsequently, social, psychological, and functional sequelae that have been linked to PPMPS are considered, as is research on current pharmacological, psychological, and rehabilitative approaches to treatment. The review concludes with a discussion of directions for future research and treatment that might reduce the incidence and impact of PPMP on breast cancer survivors. PERSPECTIVE: This article describes current research literature involving mechanisms, risks, and treatments related to persistent post-mastectomy pain. Implications of research findings also are discussed for pre- and post-surgical approaches to pain management, current treatments, and promising research directions.

Rethinking Dental School Admission Criteria: Correlation Between Pre-Admission Variables and First-Year Performance for Six Classes at One Dental School.

Admissions committees in dental schools are charged with the responsibility of selecting candidates who will succeed in school and become successful members of the profession. Identifying students who will have academic difficulty is challenging. The aim of this study was to determine the predictive value of pre-admission variables for the first-year performance of six classes at one U.S. dental school. The authors hypothesized that the variables undergraduate grade point average (GPA), undergraduate science GPA (biology, chemistry, and physics), and Dental Admission Test (DAT) scores would predict the level of performance achieved in the first year of dental school, measured by year-end GPA. Data were collected in 2015 from school records for all 297 students in the six cohorts who completed the first year (Classes of 2007 through 2013). In the results, statistically significant correlations existed between all pre-admission variables and first-year GPA, but the associations were only weak to moderate. Lower performing students at the end of the first year (lowest 10% of GPA) had, on average, lower pre-admission variables than the other students, but the differences were small (≤10.8% in all categories). When all the pre-admission variables were considered together in a multiple regression analysis, a significant association was found between pre-admission variables and first-year GPA, but the association was weak (adjusted R2=0.238). This weak association suggests that these students' first-year dental school GPAs were mostly determined by factors other than the pre-admission variables studied and has resulted in the school's placing greater emphasis on other factors for admission decisions.

Multiple modes of water quality impairment by fecal contamination in a rapidly developing coastal area: southwest Brunswick County, North Carolina.

Fecal contamination of surface waters is a significant problem, particularly in rapidly developing coastal watersheds. Data from a water quality monitoring program in southwest Brunswick County, North Carolina, gathered in support of a regional wastewater and stormwater management program were used to examine likely modes and sources of fecal contamination. Sampling was conducted at 42 locations at 3-4-week intervals between 1996 and 2003, including streams, ponds, and estuarine waters in a variety of land use settings. Expected fecal sources included human wastewater systems (on-site and central), stormwater runoff, and direct deposition by animals. Fecal coliform levels were positively associated with rainfall measures, but frequent high fecal coliform concentrations at times of no rain indicated other modes of contamination as well. Fecal coliform levels were also positively associated with silicate levels, a groundwater source signal, indicating that flux of fecal-contaminated groundwater was a mode of contamination, potentially elevating FC levels in impacted waters independent of stormwater runoff. Fecal contamination by failing septic or sewer systems at many locations was significant and in addition to effects of stormwater runoff. Rainfall was also linked to fecal contamination by central sewage treatment system failures. These results highlight the importance of considering multiple modes of water pollution and different ways in which human activities cause water quality degradation. Management of water quality in coastal regions must therefore recognize diverse drivers of fecal contamination to surface waters.

Corticotropin releasing factor receptor expression in painful human dental pulp.

BACKGROUND: Our objective was to correlate the presence of symptoms and dental pulp injury with the amount of a subtype of corticotropin releasing factor receptor (CRF-R) in symptomatic and asymptomatic human teeth. We hypothesized that patients diagnosed with irreversible pulpitis have increased levels of CRF-R. MATERIALS AND METHODS: Dental history, diagnosis and radiographs were obtained from treatment records following extractions. Teeth were diagnosed as asymptomatic or symptomatic demonstrated by clinical and radiographic evaluation. Tissue sections from tooth pulp were immunoreacted with antibodies directed against CRF receptor 2 (CRF-R2) and neurofilament protein and examined to correlate CRF-R expression with pulpal diagnosis. RESULTS: Our results indicated that symptomatic pulps demonstrated significantly greater expression of CRF-R2. The increased expression was localized on distinct cellular profiles throughout the pulp and was not directly correlated with neurofilament expression. CONCLUSIONS: Our findings suggest that the analgesic effects of endogenously produced CRF may be enhanced via upregulation of CRF-R2 expression, and may explain the occurrence of reduced pain symptoms in some patients with irreversible pulpitis. The application of CRF-R agonists may be a feasible strategy in reducing pain associated with irreversible pulpitis.

The gross anatomy laboratory: a novel venue for critical thinking and interdisciplinary teaching in dental education.

Reports on the status of dental education have concluded that there is a need for various types of curricular reform, making recommendations that include better integration of basic, behavioral, and clinical sciences, increased case-based teaching, emphasis on student-driven learning, and creation of lifelong learners. Dental schools faced with decreasing contact hours, increasing teaching material, and technological advancements have experimented with alternate curricular strategies. At Southern Illinois University School of Dental Medicine, curricular changes have begun with a series of integrated biomedical sciences courses. During the process of planning and implementing the integrated courses, a novel venue-the gross anatomy laboratory-was used to introduce all Year 1 students to critical thinking, self-directed learning, and the scientific method. The venture included student-driven documentation of anatomical variations encountered in the laboratory using robust scientific methods, thorough literature review, and subsequent presentation of findings in peer review settings. Students responded positively, with over 75% agreeing the experience intellectually challenged them. This article describes the process of re-envisioning the gross anatomy laboratory as an effective venue for small group-based, student-driven projects that focus on key pedagogical concepts to encourage the development of lifelong learners.

A comparative analysis of adhesive resin removal methods.

The objective was to determine which bracket adhesive removal method was the most effective. Four different techniques were investigated: adhesive removing pliers, 12-fluted carbide, white stone, and Sof-Lex discs. Scanning electron microscopy was used for microanalysis and photographing. Sof-Lex discs was the best removal method, similar to the negative control.

Tooth injury increases expression of the cold sensitive TRP channel TRPA1 in trigeminal neurons.

OBJECTIVE: Transient receptor potential (TRP) channels, a family of structurally related proteins have been implicated in the sensation of pain and hyperalgesia caused by exogenous and endogenous agonists, as well as touch, pH, and temperature. The objective of this study was to determine the effects of tooth injury on the expression of the cold sensitive channel TRPA1, in the trigeminal ganglion, the primary source of sensory and nociceptive innervation of teeth. DESIGN: We analyzed TRPA1 expression in a rodent model of tooth injury, by Western blot analyses of proteins extracted from trigeminal ganglia. RESULTS: We found that TRPA1 was selectively increased in trigeminal ganglia innervating injured teeth when compared to TRPA1 expression in trigeminal ganglia innervating healthy teeth. CONCLUSIONS: Our results provide the first evidence of increased expression of a cold-sensitive TRP channel in trigeminal ganglia after pulp exposure, and are consistent with the possibility that increased expression and function of TRPA1 in trigeminal neurons contributes to hyperalgesia and allodynia following tooth injury.

Localized increases in corticotropin-releasing factor receptors in pulp after dental injury.

Corticotropin-releasing factor (CRF) binds to membrane-bound CRF receptors (CRF-Rs). Among the actions mediated by activated CRF-Rs is beta-endorphin (END) release from immune cells, increasing peripheral antinociception. For assessment of inflammatory regulation of CRF-R expression, rats underwent pulp exposure of left, first mandibular molars and recovered for 6 days. Control pulpal tissue consisted of contralateral, uninjured molars and left, first mandibular molars of uninjured animals. Pulp tissue specimens were incubated with antibodies directed against CRF-R (both isoforms), neurofilament, CD45, and END. We observed (1) increases in pulp CRF-R immunoreactivity after injury, (2) increased CRF-R immunoreactivity expressed in 3 distinct zones in relation to the injury, and (3) increased CD45 and END immunoreactivity in regions surrounding the pulpal abscess. CRF-Rs might provide an additional target for novel analgesics to treat pulpal pain.

Kv1.4 subunit expression is decreased in neurons of painful human pulp.

Kv1.4, a subunit of voltage-gated K(+) channels, plays a large role in regulating neuronal excitability. The level of Kv1.4 expression is unknown in human sensory neurons innervating healthy or painful tissue. Therefore, we examined Kv1.4 immunoreactivity in axons innervating both clinically diagnosed asymptomatic and painful symptomatic human tooth pulp. Antibodies directed against Kv1.4 and PGP9.5, a protein marker for axons, was used to determine the proportion of PGP9.5 immunopositive tissue that was also immunopositive for Kv1.4. We report that on pulpal axons innervating symptomatic teeth Kv1.4 immunoreactivity, a correlate of decreased Kv1.4 expression, is significantly decreased (p < 0.0001), suggestive of a factor responsible for facilitating chronic dental pain and decreases in currents produced, such as I(A), in neurons innervating painful pulp.

Expression of Nav1.9 channels in human dental pulp and trigeminal ganglion.

There is a higher incidence of local anesthetic failure in endodontic patients experiencing pulpal hyperalgesia. Up-regulation of Nav1.9, a voltage-gated sodium channel isoform, might play a key role in local anesthetic failure because Nav1.9 channels increase neuronal excitability and have low sensitivity to blockade by local anesthetics. Immunocytochemistry was used to examine Nav1.9 channel expression in axons of symptomatic (painful) versus asymptomatic human dental pulp and to determine Nav1.9 expression levels in neuronal somata of the human trigeminal ganglion. Nav1.9 channel immunoreactivity on pulpal axons was significantly increased in painful teeth. Nav1.9 channels were expressed in membranes and cytoplasm of human trigeminal ganglion neurons, with the highest expression in small neuronal somata. Nav1.9 expression in the trigeminal ganglion coupled with increased expression in symptomatic pulp might contribute to hypersensitivity of inflamed pulps and local anesthetic failure. Furthermore, the present study suggests that Nav1.9 channels are potential targets for novel anesthetics.

Development of gerbil medial superior olive: integration of temporally delayed excitation and inhibition at physiological temperature.

The sensitivity of medial superior olive (MSO) neurons to tens of microsecond differences in interaural temporal delay (ITD) derives in part from their membrane electrical characteristics, kinetics and timing of excitatory and inhibitory inputs, and dendrite structure. However, maturation of these physiological and structural characteristics are little studied, especially in relationship to the onset of auditory experience. We showed, using brain slices at physiological temperature, that MSO neurons exhibited sensitivity to simulated temporally delayed (TD) EPSCs (simEPSC), injected through the recording electrode, by the initial phase of hearing onset at P10, and TD sensitivity was reduced by block of low threshold potassium channels. The spike generation mechanism matured between P10 and P16 to support TD sensitivity to adult-like excitatory stimuli (1-4 ms duration) by P14. IPSP duration was shorter at physiological temperature than reported for lower temperatures, was longer than EPSP duration at young ages, but approached the duration of EPSPs by P16, when hearing thresholds neared maturity. Dendrite branching became less complex over a more restricted time frame between P10 and P12. Because many physiological and structural properties approximated mature values between P14 and P16, we studied temporal integration of simEPSCs and IPSPs at P15. Only a narrow range of relative onset times (< 1 ms) yielded responses showing sensitivity to TD. We propose that shaping of excitatory circuitry to mediate TD sensitivity can begin before airborne sound is detectable, and that inhibitory inputs having suboptimal neural delays may then be pruned by cellular mechanisms activated by sensitivity to ITD.

Coordination polymer gels: synthesis, structure and mechanical properties of amorphous coordination polymers.

The synthesis and mechanical properties of a new class of coordination polymer based materials, amorphous coordination polymer sol-gels and xerogels, is presented.

TRPM2 immunoreactivity is increased in fibroblasts, but not nerves, of symptomatic human dental pulp.

Transient receptor potential (TRP) channels function in diverse processes such as acting as second messenger systems, regulating of ionic concentrations, and aiding in thermoception. TRPM2 channels, members of the melastatin subfamily, mediate calcium influx in response to oxidative stress but during pathological states facilitate hyperexcitability and cellular necrosis via calcium excitotoxicity. We hypothesized that TRPM2 channel expression is upregulated in pulpal tissue of symptomatic teeth with signs of irreversible pulpitis. TRPM2 channel expression was significantly increased in pulp from clinically diagnosed symptomatic teeth compared with pulp from asymptomatic teeth. Additionally, increased TRPM2 expression in symptomatic pulp was the result of increased immunoreactivity in fibroblasts, whereas neural expression of TRPM2 was absent. We provide a possible mechanism explaining the association between TRPM2 channel expression with pain and necrosis. We suggest that TRPM2 channel antagonists could be administered in attempts to inhibit the progression of or even reverse pulpal degradation.

Optimizing synaptic architecture and efficiency for high-frequency transmission.

Bursts of neuronal activity are transmitted more effectively as synapses mature. However, the mechanisms that control synaptic efficiency during development are poorly understood. Here, we study postnatal changes in synaptic ultrastructure and exocytosis in a calyx-type nerve terminal. Vesicle pool size, exocytotic efficiency (amount of exocytosis per Ca influx), Ca current facilitation, and the number of active zones (AZs) increased with age, whereas AZ area, number of docked vesicles per AZ, and release probability decreased with age. These changes led to AZs that are less prone to multivesicular release, resulting in reduced AMPA receptor saturation and desensitization. A greater multiplicity of small AZs with few docked vesicles, a larger pool of releasable vesicles, and a higher efficiency of release thus promote prolonged high-frequency firing in mature synapses.