Oral medicine in regional oral and maxillofacial surgery units: a five-year review.

Introduction This study looks at the amount of oral medicine activity in oral and maxillofacial surgery (OMFS) units in both South East Wales and South West England, and to consider the development of training programmes in oral medicine and OMFS, to determine how to best deliver a service which would benefit patients with oral medicine diagnoses.Materials and methods Following institutional approvals, local OMFS units in South East Wales and South West England collected data from OMFS outpatient clinics to determine what proportion of patient diagnoses fell within the scope of practice of oral medicine.Results In South East Wales in 2017, patients with oral medicine diagnoses formed 45% of total outpatient activity in OMFS outpatient clinics compared to 37% of patients in the South West of England in 2021. Patients with oral medicine diagnoses were predominantly female and in the older age groups.Discussion and conclusions Changing age demographics suggest that the demand for specialist oral medicine services will continue to rise. Outside of the university dental hospital setting, where all UK oral medicine units are currently located, there is a growing need for specialists in oral medicine to work alongside colleagues in OMFS in district general hospitals to provide specialist oral medicine care to an increasingly large and complex patient group, ideally as part of a managed clinical network.

An opioid receptor-independent mechanism underlies motility dysfunction and visceral hyperalgesia in opioid-induced bowel dysfunction.

Constipation and abdominal pain are commonly encountered in opioid-induced bowel dysfunction (OBD). The underlying mechanisms are incompletely understood, and treatments are not satisfactory. As patients with OBD often have fecal retention, we aimed to determine whether fecal retention plays a pathogenic role in the development of constipation and abdominal pain in OBD, and if so to investigate the mechanisms. A rodent model of OBD was established by daily morphine treatment at 10 mg/kg for 7 days. Bowel movements, colonic muscle contractility, visceromotor response to colorectal distention, and cell excitability of colon-projecting dorsal root ganglion neurons were determined in rats fed with normal pellet food, or with clear liquid diet. Morphine treatment (Mor) reduced fecal outputs starting on day 1, and caused fecal retention afterward. Compared with controls, Mor rats demonstrated suppressed muscle contractility, increased neuronal excitability, and visceral hypersensitivity. Expression of cyclooxygenase-2 (COX-2) and nerve growth factor (NGF) was upregulated in the smooth muscle of the distended colon in Mor rats. However, prevention of fecal retention by feeding rats with clear liquid diet blocked upregulation of COX-2 and NGF, restored muscle contractility, and attenuated visceral hypersensitivity in Mor rats. Moreover, inhibition of COX-2 improved smooth muscle function and fecal outputs, whereas anti-NGF antibody administration attenuated visceral hypersensitivity in Mor rats. Morphine-induced fecal retention is an independent pathogenic factor for motility dysfunction and visceral hypersensitivity in rats with OBD. Liquid diet may have therapeutic potential for OBD by preventing fecal retention-induced mechanotranscription of COX-2 and NGF.NEW & NOTEWORTHY Our preclinical study shows that fecal retention is a pathogenic factor in opioid-induced bowel dysfunction, as prevention of fecal retention with liquid diet improved motility and attenuated visceral hyperalgesia in morphine-treated animals by blocking expression of cyclooxygenase-2 and nerve growth factor in the colon.

Evaluating the role of interpersonal hopelessness in the interpersonal theory of suicide.

To further inclusion of interpersonal hopelessness within the interpersonal theory of suicide, we evaluated the Interpersonal Hopelessness Scale's (IHS) factor structure, and compared its relation to suicide ideation to that of the Interpersonal Needs Questionnaire's. Participants were 591 attentive US adults who completed surveys online. Exploratory factor analyses supported a single IHS factor, which accounted for about 70% of the total variance. Both measures statistically predicted suicide ideation; the IHS explained slightly more variation in suicide ideation scores. Including interpersonal hopelessness within measures of the interpersonal theory's constructs may prove important in developing suicide risk assessment and treatment.

Postacute inpatient rehabilitation for COVID-19.

This case describes the successful pulmonary rehabilitation of a premorbidly independent female in the early 80s who was admitted for acute respiratory distress syndrome secondary to COVID-19 requiring 14 days of intubation. Patient was admitted to the acute rehabilitation unit 1 month after hospitalisation. Patient initially had poor endurance and was only able to ambulate with a front wheel walker for 150 feet, and also had tachycardia and decreased oxygen saturation after ambulation. During patient's rehabilitation course, therapy was focused on improving activity tolerance. Ten days after admission, patient was able to ambulate without an assistive device for 250 feet and with a rollator for over 900 feet. Patient also showed improvement in gait speed, heart rate, oxygen saturation after ambulation and incentive spirometer volume. This case demonstrates that pulmonary rehabilitation is an important component of inpatient care for patients with COVID-19 to improve functional exercise capacity and aerobic capacity.

Efficacy, Safety, and Feasibility of the Morphine Microdose Method in Community-Based Clinics.

Objectives: The goal of this study was to assess the success of the morphine microdose method in a community pain clinic setting by monitoring follow-up frequency, dose escalation, and monotherapy/polytherapy ratio. The morphine microdose method involves a pretrial reduction or elimination of systemic opioids followed by a period of abstinence. Intrathecal (IT) morphine is then started at doses of less than 0.2 mg per day. Systemic opioid abstinence is then continued after pump implant and IT morphine monotherapy. Design: Retrospective review of medical records. Setting: Private and academic pain clinic practices. Subjects: Chronic noncancer pain patients. Methods: We reviewed the charts of 60 patients who had completed a microdose regimen and had an IT pump implanted between June 11, 2008, and October 11, 2014. During IT therapy, dose change over time, pain scores, side effects, max dose, and duration were recorded. Results: The majority of patients (35/60, 58%) were successfully managed solely on morphine microdose monotherapy. These patients did not require additional oral therapy. There was a significant reduction in mean pain scores, from 7.4 ± 0.32 before microdose therapy to 4.8 ± 0.3 after microdose therapy. Conclusions: Microdose therapy achieved analgesia, improved safety, and avoided systemic side effects. The safety of IT therapy was increased by using a lower concentration (2 mg/mL) and lower daily doses (<3 mg/d) of morphine. Furthermore, microdose therapy was feasible, safe, and cost-effective in the outpatient setting.

A simple and fast method to image calcium activity of neurons from intact dorsal root ganglia using fluorescent chemical Ca2+ indicators.

Chemical calcium indicators have been commonly used to monitor calcium (Ca2+) activity in cell bodies, i.e., somata, of isolated dorsal root ganglion neurons. Recent studies have shown that dorsal root ganglion somata play an essential role in soma-glia interactions and actively participate in the transmission of nociceptive signals. It is therefore desirable to develop methods to study Ca2+ activity in neurons and glia in intact dorsal root ganglia. In our previous studies, we found that incubation of intact dorsal root ganglia with acetoxymethyl dye resulted in efficient Ca2+ dye loading into glial cells but limited dye loading into neurons. Here, we introduce a useful method to load Ca2+ dyes in intact dorsal root ganglion neurons through electroporation. We found that electroporation greatly facilitated loading of Fluo-4 acetoxymethyl, Oregon green bapta-1-488 acetoxymethyl, and Fluo-4 pentapotassium salt into dorsal root ganglion neurons. In contrast, electroporation did not further facilitate dye loading into glia. Using electroporation followed by incubation of acetoxymethyl form Ca2+ dye, we can load acetoxymethyl Ca2+ dye well in both neurons and glia. With this approach, we found that inflammation induced by complete Freund's adjuvant significantly increased the incidence of neuron-glia interactions in dorsal root ganglia. We also confirmed the actions of capsaicin and morphine on Ca2+ responses in dorsal root ganglion neurons. Thus, by promoting the loading of Ca2+ dye in neurons and glia through electroporation and incubation, Ca2+ activities in neurons and neuron-glia interactions can be well studied in intact dorsal root ganglia.

QT Interval Shortening With Isavuconazole: In Vitro and In Vivo Effects on Cardiac Repolarization.

The effects of isavuconazole (active moiety of isavuconazonium sulfate) on cardiac ion channels in vitro and cardiac repolarization clinically were assessed in a phase I, randomized, double-blind study in healthy individuals who received isavuconazole (after 2-day loading dose), at therapeutic or supratherapeutic doses daily for 11 days, moxifloxacin (400 mg q.d.), or placebo. A post-hoc analysis of the phase III SECURE trial assessed effects on cardiac safety. L-type Ca2+ channels were most sensitive to inhibition by isavuconazole. The 50% inhibitory concentrations for ion channels were higher than maximum serum concentrations of nonprotein-bound isavuconazole in vivo. In the phase I study (n = 161), isavuconazole shortened the QT interval in a dose- and plasma concentration-related manner. There were no serious treatment-emergent adverse events; palpitations and tachycardia were observed in placebo and supratherapeutic isavuconazole groups; no cardiac safety signals were detected in the SECURE study (n = 257). Isavuconazole was associated with a shortened cardiac QT interval.

Pathogenesis of abdominal pain in bowel obstruction: role of mechanical stress-induced upregulation of nerve growth factor in gut smooth muscle cells.

Abdominal pain is one of the major symptoms in bowel obstruction (BO); its cellular mechanisms remain incompletely understood. We tested the hypothesis that mechanical stress in obstruction upregulates expression of nociception mediator nerve growth factor (NGF) in gut smooth muscle cells (SMCs), and NGF sensitizes primary sensory nerve to contribute to pain in BO. Partial colon obstruction was induced with a silicon band implanted in the distal bowel of Sprague-Dawley rats. Colon-projecting sensory neurons in the dorsal root ganglia (T13 to L2) were identified for patch-clamp and gene expression studies. Referred visceral sensitivity was assessed by measuring withdrawal response to stimulation by von Frey filaments in the lower abdomen. Membrane excitability of colon-projecting dorsal root ganglia neurons was significantly enhanced, and the withdrawal response to von Frey filament stimulation markedly increased in BO rats. The expression of NGF mRNA and protein was increased in a time-dependent manner (day 1-day 7) in colonic SMC but not in mucosa/submucosa of the obstructed colon. Mechanical stretch in vitro caused robust NGF mRNA and protein expression in colonic SMC. Treatment with anti-NGF antibody attenuated colon neuron hyperexcitability and referred hypersensitivity in BO rats. Obstruction led to significant increases of tetrodotoxin-resistant Na currents and mRNA expression of Nav1.8 but not Nav1.6 and Nav1.7 in colon neurons; these changes were abolished by anti-NGF treatment. In conclusion, mechanical stress-induced upregulation of NGF in colon SMC underlies the visceral hypersensitivity in BO through increased gene expression and activity of tetrodotoxin-resistant Na channels in sensory neurons.

Stabilization of the Activated hERG Channel Voltage Sensor by Depolarization Involves the S4-S5 Linker.

Slow deactivation of hERG channels is critical for preventing cardiac arrhythmia yet the mechanistic basis for the slow gating transition is unclear. Here, we characterized the temporal sequence of events leading to voltage sensor stabilization upon membrane depolarization. Progressive increase in step depolarization duration slowed voltage-sensor return in a biphasic manner (τfast = 34 ms, τslow = 2.5 s). The faster phase of voltage-sensor return slowing correlated with the kinetics of pore opening. The slower component occurred over durations that exceeded channel activation and was consistent with voltage sensor relaxation. The S4-S5 linker mutation, G546L, impeded the faster phase of voltage sensor stabilization without attenuating the slower phase, suggesting that the S4-S5 linker is important for communications between the pore gate and the voltage sensor during deactivation. These data also demonstrate that the mechanisms of pore gate-opening-induced and relaxation-induced voltage-sensor stabilization are separable. Deletion of the distal N-terminus (Δ2-135) accelerated off-gating current, but did not influence the relative contribution of either mechanism of stabilization of the voltage sensor. Lastly, we characterized mode-shift behavior in hERG channels, which results from stabilization of activated channel states. The apparent mode-shift depended greatly on recording conditions. By measuring slow activation and deactivation at steady state we found the "true" mode-shift to be ∼15 mV. Interestingly, the "true" mode-shift of gating currents was ∼40 mV, much greater than that of the pore gate. This demonstrates that voltage sensor return is less energetically favorable upon repolarization than pore gate closure. We interpret this to indicate that stabilization of the activated voltage sensor limits the return of hERG channels to rest. The data suggest that this stabilization occurs as a result of reconfiguration of the pore gate upon opening by a mechanism that is influenced by the S4-S5 linker, and by a separable voltage-sensor intrinsic relaxation mechanism.

Evaluating Community Health Advisor (CHA) Core Competencies: The CHA Core Competency Retrospective Pretest/Posttest (CCCRP).

Health care and academic systems are increasingly collaborating with community health advisors (CHAs) to provide culturally relevant health interventions that promote sustained community transformation. Little attention has been placed on CHA training evaluation, including core competency attainment. This study identified common CHA core competencies, generated a theoretically based measure of those competencies, and explored psychometric properties of that measure. A concept synthesis revealed five CHA core competencies (leadership, translation, guidance, advocacy, and caring). The CHA Core Competency Retrospective Pretest/Posttest (CCCRP) resulted from that synthesis, which was administered using multiple approaches to individuals who previously received CHA training (N= 142). Exploratory factor analyses revealed a two-factor structure underlying the posttraining data, and Cronbach's alpha indicated high internal consistency. This study suggested some CHA core competencies might be more interrelated than previously thought, and two major competencies exist rather than five and supported the CCCRP's use to evaluate core competency attainment resulting from training.

A home-based training programme improves family caregivers' oral care practices with stroke survivors: a randomized controlled trial.

OBJECTIVES: Stroke survivors experience poor oral health when discharged from the hospital to the community. The aim of this study was to evaluate the effectiveness of a home-based oral care training programme on knowledge, attitude, self-efficacy and practice behaviour of family caregivers. METHODS: A randomized controlled trial was conducted. The experimental group consisted of 48 family caregivers who received the home-based oral care training programme, and the control group consisted of 46 family caregivers who received routine oral care education. The outcomes were measured by the Knowledge of Oral Care, Attitude towards Oral Care, Self-Efficacy of Oral Care and Behaviour of Oral Care before the training programme, and at one and two months afterwards. The data were analysed using mixed model anova to determine differences in the outcomes between the two groups. RESULTS: The findings demonstrated that the intervention group had more knowledge (t = 8.80, P < 0. 001), greater self-efficacy (t = 3.53, P < 0.01) and better oral care behaviour (t = 11.93, P < 0.001) than the control group at one and two months, with statistically significant differences in oral care knowledge, self-efficacy and behaviour outcome over time. The attitude of the intervention group towards oral care practice was generally positive (mean of baseline and two month = 12.9 and 14.7), but no significant difference in attitude change between the control and intervention groups (t = 1.56, P = 0.12). The treatment interaction effect was significant for the family caregivers' behaviour of oral care at one and two months of the intervention for both groups. CONCLUSION: Our individualized home-based oral care education can achieve significant improvements in oral care knowledge and self-efficacy among family caregivers of stroke survivors, and it can sufficiently empower them to modify their oral care practices in a home-based healthcare environment.

Effect of family caregiver oral care training on stroke survivor oral and respiratory health in Taiwan: a randomised controlled trial.

OBJECTIVE: To evaluate the effectiveness of home-based oral care training programs on tongue coating (TC), dental plaque (DP), and symptoms of respiratory infection (SRI) in stroke survivors. METHODS: A single-blind, randomised, controlled trial conducted in a home-based setting over 2 months. Stroke survivors (n=48, experimental group) and their family caregivers received home-based oral care training programme while a control group of 46 stroke survivors and family caregivers received routine oral care education with swabs. TC, DP, and SRI were assessed at baseline and after one and two months, with results analysed using Mixed Model ANOVA. RESULTS: Poor oral hygiene and overall neglect of home oral care practices were observed at baseline. TC and DP scores were significantly reduced in the experimental group receiving the home-base oral care training program compared to the control group, who received only routine oral care education (P<0.001). The groupxtime interaction was significant, with decreased TC and DP scores for both groups at one month and at two months of additional care (when compared to baseline). The SRI scores were not significantly different between groups (P>0.05). The groupxtime interaction did not correlate with SRI for either group when compared to the baseline and to one month and two months of additional care. No adverse events were encountered and there was no external funding. CONCLUSIONS: Home-based oral care training programme had a beneficial effect on oral health as measured by TC and DP scores. The effect on SRI requires further longitudinal study.

DNA vaccine elicits an efficient antitumor response by targeting the mutant Kras in a transgenic mouse lung cancer model.

Mutant Kras (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) is observed in more than 20% of non-small-cell lung cancers; however, no effective Kras target therapy is available at present. The Kras DNA vaccine may represent as a novel immunotherapeutic agent in lung cancer. In this study, we investigated the antitumor efficacy of the Kras DNA vaccine in a genetically engineered inducible mouse lung tumor model driven by Kras(G12D). Lung tumors were induced by doxycycline, and the therapeutic effects of Kras DNA vaccine were evaluated with delivery of Kras(G12D) plasmids. Mutant Kras(G12D) DNA vaccine significantly decreased the tumor nodules. A dominant-negative mutant Kras(G12D)N17, devoid of oncogenic activity, achieved similar therapeutic effects. The T-helper 1 immune response was enhanced in mice treated with Kras DNA vaccine. Splenocytes from mice receiving Kras DNA vaccine presented an antigen-specific response by treatment with peptides of Kras but not Hras or OVA. The number of tumor-infiltrating CD8(+) T cells increased after Kras vaccination. In contrast, Kras DNA vaccine was not effective in the lung tumor in transgenic mice, which was induced by mutant L858R epidermal growth factor receptor. Overall, these results indicate that Kras DNA vaccine produces an effective antitumor response in transgenic mice, and may be useful in treating lung cancer-carrying Ras mutation.

From SARS in 2003 to H1N1 in 2009: lessons learned from Taiwan in preparation for the next pandemic.

In anticipation of a future pandemic potentially arising from H5N1, H7N9 avian influenza or Middle East Respiratory Syndrome, and in large part in response to severe acute respiratory syndrome (SARS) in 2003, the city of Taipei, Taiwan, has developed extensive new strategies to manage pandemics. These strategies were tested during the 2009 H1N1 outbreak. This article assesses pandemic preparedness in Taipei in the wake of recent pandemic experiences in order to draw lessons relevant to the broader international public health community. Drawing on Taiwan and Taipei Centers for Disease Control data on pandemic response and control, we evaluated the effectiveness of the changes in pandemic response policies developed by these governments over time, emphasizing hospital and medical interventions with particular attention paid to Traffic Control Bundling. SARS and H1N1 2009 catalysed the Taiwan and Taipei CDCs to continuously improve and adjust their strategies for a future pandemic. These new strategies for pandemic response and control have been largely effective at providing interim pandemic containment and control, while development and implementation of an effective vaccination programme is underway. As Taipei's experiences with these cases illustrate, in mitigating moderate or severe pandemic influenza, a graduated process including Traffic Control Bundles accompanied by hospital and medical interventions, as well as school- and community-focused interventions, provides an effective interim response while awaiting vaccine development. Once a vaccine is developed, to maximize pandemic control effectiveness, it should be allocated with priority given to vulnerable groups, healthcare workers and school children.

Proline scan of the HERG channel S6 helix reveals the location of the intracellular pore gate.

In Shaker-like channels, the activation gate is formed at the bundle crossing by the convergence of the inner S6 helices near a conserved proline-valine-proline motif, which introduces a kink that allows for electromechanical coupling with voltage sensor motions via the S4-S5 linker. Human ether-a-go-go-related gene (hERG) channels lack the proline-valine-proline motif and the location of the intracellular pore gate and how it is coupled to S4 movement is less clear. Here, we show that proline substitutions within the S6 of hERG perturbed pore gate closure, trapping channels in the open state. Performing a proline scan of the inner S6 helix, from Ile(655) to Tyr(667) revealed that gate perturbation occurred with proximal (I655P-Q664P), but not distal (R665P-Y667P) substitutions, suggesting that Gln(664) marks the position of the intracellular gate in hERG channels. Using voltage-clamp fluorimetry and gating current analysis, we demonstrate that proline substitutions trap the activation gate open by disrupting the coupling between the voltage-sensing unit and the pore of the channel. We characterize voltage sensor movement in one such trapped-open mutant channel and demonstrate the kinetics of what we interpret to be intrinsic hERG voltage sensor movement.

Smoking increases risk of recurrence after successful anti-tuberculosis treatment: a population-based study.

OBJECTIVE: To investigate whether tobacco smoking increases the risk of tuberculosis (TB) recurrence and identify factors associated with TB recurrence among adults who had successfully completed anti-tuberculosis treatment in Taipei, Taiwan. METHODS: Recurrence was defined as a new clinical or microbiological diagnosis of TB requiring the start of a new course of treatment in a patient who had satisfactorily completed treatment for a previous TB episode. Cox proportional hazard models were used to calculate adjusted hazard ratios (aHRs) for recurrence. RESULTS: We followed 5567 adults for recurrence after successful anti-tuberculosis treatment. The mean age was 58.5 years; 62.9% were male. Overall, 84 (1.5%) had a recurrence of TB during follow-up. The incidence of TB recurrence was 4.9 episodes/1000 person-years of follow-up. Cox proportional hazards regression showed that after controlling for other variables, the risk of TB recurrence among subjects who smoked >10 cigarettes a day was double that of never/former smokers. Other independent risk factors significantly associated with TB recurrence were homelessness (aHR 3.75, 95%CI 1.17-12.07), presence of comorbidities (aHR 2.66, 95%CI 1.22-5.79) and a positive acid-fast bacilli smear (aHR 2.27, 95%CI 1.47-3.49). CONCLUSION: Smoking >10 cigarettes a day was significantly associated with TB recurrence. To reduce the risk of recurrence, we recommend including effective measures of smoking cessation in TB control programmes, as recommended by the World Health Organization Stop TB Strategy.

Bacteria killing nanotechnology Bio-Kil effectively reduces bacterial burden in intensive care units.

A contaminated hospital environment has been identified as an important reservoir of pathogens causing healthcare-associated infections. This study is to evaluate the efficacy of bacteria killing nanotechnology Bio-Kil on reducing bacterial counts in an intensive care unit (ICU). Two single-bed rooms (S-19 and S-20) in the ICU were selected from 7 April to 27 May 2011. Ten sets of new textiles (pillow cases, bed sheets, duvet cover, and patient clothing) used by patients in the two single-bed rooms were provided by the sponsors. In the room S-20, the 10 sets of new textiles were washed with Bio-Kil; the room walls, ceiling, and air-conditioning filters were treated with Bio-Kil; and the surfaces of instruments (respirator, telephone, and computer) were covered with Bio-Kil-embedded silicon pads. Room S-19 served as the control. We compared the bacterial count on textiles and environment surfaces as well as air samples between the two rooms. A total of 1,364 samples from 22 different sites in each room were collected. The mean bacterial count on textiles and environmental surfaces in room S-20 was significantly lower than that in room S-19 (10.4 vs 49.6 colony-forming units [CFU]/100 cm(2); P < 0.001). Room S-20 had lower bacterial counts in air samples than room S-19 (33.4-37.6 vs 21.6-25.7 CFU/hour/plate; P < 0.001). The density of microbial isolations was significantly greater among patients admitted to room S-19 than those to room S-20 (9.15 vs 5.88 isolates per 100 patient-days, P < 0.05). Bio-Kil can significantly reduce bacterial burden in the environment of the ICU.