Altering Facial Movements Abolishes Neural Mirroring of Facial Expressions.

People tend to automatically imitate others' facial expressions of emotion. That reaction, termed "facial mimicry" has been linked to sensorimotor simulation-a process in which the observer's brain recreates and mirrors the emotional experience of the other person, potentially enabling empathy and deep, motivated processing of social signals. However, the neural mechanisms that underlie sensorimotor simulation remain unclear. This study tests how interfering with facial mimicry by asking participants to hold a pen in their mouth influences the activity of the human mirror neuron system, indexed by the desynchronization of the EEG mu rhythm. This response arises from sensorimotor brain areas during observed and executed movements and has been linked with empathy. We recorded EEG during passive viewing of dynamic facial expressions of anger, fear, and happiness, as well as nonbiological moving objects. We examine mu desynchronization under conditions of free versus altered facial mimicry and show that desynchronization is present when adult participants can freely move but not when their facial movements are inhibited. Our findings highlight the importance of motor activity and facial expression in emotion communication. They also have important implications for behaviors that involve occupying or hiding the lower part of the face.

A Personal Approach to Bilateral Cleft Lip Repair.

Dr Michael B. Lewis has been using his personal approach to bilateral cleft lip (BCL) repair for 30 years to achieve a loose, pouting upper lip, a 90-degree columellar-labial angle, and a projecting nasal tip. This article describes technique and results.

Increased Transmissibility of Leishmania donovani From the Mammalian Host to Vector Sand Flies After Multiple Exposures to Sand Fly Bites.

Background: Patients with active visceral leishmaniasis are important reservoirs in the anthroponotic transmission cycle of Leishmania donovani. The role of the blood or skin as a source of infection to sand flies remains unclear, and the possible effect of multiple exposures to fly bites on transmissibility has not been addressed. Methods: L. donovani-infected hamsters underwent xenodiagnoses with Lutzomyia longipalpis on the same or different sites on the abdomen on 2 consecutive days or by artificial feeding on the skin or blood. Results: The transmission of L. donovani from sick hamsters to flies was surprisingly low (mean, 24% of fed flies). New flies fed on the same site acquired significantly more infections (mean, 61%; P < .0001). By artificial feeding, flies could acquire infection from blood and skin. However, only artificial feeding on blood produced infections that correlated with the natural feeding (R = 0.792; P < .0001). Infections acquired from blood increased dramatically for blood obtained after exposure to bites, as did the parasitemia level and the number of monocytes in the circulation. Conclusions: The bites of uninfected sand flies favor the transmissibility of L. donovani by infected hosts, owing to a systemic effect that exposure to bites has on the parasitemia. Patients with active visceral leishmaniasis are important reservoirs in the anthroponotic transmission cycle of Leishmania donovani. Using the hamster model of visceral disease, we demonstrate that prior exposure to bites of uninfected sand flies potentiates their ability to transmit infection to the vector.

Antibiotic Guardians: the Role of the Dental Profession.

The increasing emergence of antibiotic resistance is a major international public health problem. As a consequence, it is essential that steps are taken to conserve the effectiveness of existing antimicrobial agents. Consumption of antibiotics is the prime contributor to the development of resistance. General dental practitioners write almost 1 out of 10 prescriptions for antibiotics in primary care within the UK and therefore the prudent prescribing of antibiotics in dentistry has never been more vital. This paper outlines the impact of antimicrobial resistance on modern healthcare, describes the current use of antibiotics in general dental practice, and recommends pragmatic ways in which dental practitioners can evaluate and optimize their prescribing. Clinical relevance: Dental professionals have a responsibility to both their patients and the wider community to prescribe antibiotics appropriately.

Modulation of Candida albicans virulence by bacterial biofilms on titanium surfaces.

Whilst Candida albicans occurs in peri-implant biofilms, its role in peri-implantitis remains unclear. This study therefore examined the virulence of C. albicans in mixed-species biofilms on titanium surfaces. Biofilms of C. albicans (Ca), C. albicans with streptococci (Streptococcus sanguinis, S. mutans) (Ca-Ss-Sm) and those incorporating Porphyromonas gingivalis (Ca-Pg and Ca-Ss-Sm-Pg) were developed. Expression of C. albicans genes associated with adhesion (ALS1, ALS3, HWP1) and hydrolytic enzymes (SAP2, SAP4, SAP6, PLD1) was measured and hyphal production by C. albicans quantified. Compared with Ca biofilms, significant (p<0.05) up-regulation of ALS3, HWP1, SAP2 and SAP6, and hyphal production occurred in biofilms containing streptococci (Ca-Ss-Sm). In Ca-Pg biofilms, down-regulation of HWP1 and SAP4 expression, with reduced hyphal production occurred. Ca-Ss-Sm-Pg biofilms had increased hyphal proportions and up-regulation of ALS3, SAP2 and SAP6. In conclusion, C. albicans expressed virulence factors in biofilms that could contribute to peri-implantitis, but this was dependent on associated bacterial species.

Synthesis and comparative biological evaluation of bifunctional ligands for radiotherapy applications of (90)Y and (177)Lu.

Zevalin® is an antibody-drug conjugate radiolabeled with a cytotoxic radioisotope ((90)Y) that was approved for radioimmunotherapy (RIT) of B-cell non-Hodgkin's lymphoma. A bifunctional ligand that displays favorable complexation kinetics and in vivo stability is required for effective RIT. New bifunctional ligands 3p-C-DE4TA and 3p-C-NE3TA for potential use in RIT were efficiently prepared by the synthetic route based on regiospecific ring opening of aziridinium ions with prealkylated triaza- or tetraaza-backboned macrocycles. The new bifunctional ligands 3p-C-DE4TA and 3p-C-NE3TA along with the known bimodal ligands 3p-C-NETA and 3p-C-DEPA were comparatively evaluated for potential use in targeted radiotherapy using ß-emitting radionuclides (90)Y and (177)Lu. The bifunctional ligands were evaluated for radiolabeling kinetics with (90)Y and (177)Lu, and the corresponding (90)Y or (177)Lu-radiolabeled complexes were studied for in vitro stability in human serum and in vivo biodistribution in mice. The results of the comparative complexation kinetic and stability studies indicate that size of macrocyclic cavity, ligand denticity, and bimodality of donor groups have a substantial impact on complexation of the bifunctional ligands with the radiolanthanides. The new promising bifunctional chelates in the DE4TA and NE3TA series were rapid in binding (90)Y and (177)Lu, and the corresponding (90)Y- and (177)Lu-radiolabeled complexes remained inert in human serum or in mice. The in vitro and in vivo data show that 3p-C-DE4TA and 3p-C-NE3TA are promising bifunctional ligands for targeted radiotherapy applications of (90)Y and (177)Lu.

Virulence and pathogenicity of Candida albicans is enhanced in biofilms containing oral bacteria.

This study examined the influence of bacteria on the virulence and pathogenicity of candidal biofilms. Mature biofilms (Candida albicans-only, bacteria-only, C. albicans with bacteria) were generated on acrylic and either analysed directly, or used to infect a reconstituted human oral epithelium (RHOE). Analyses included Candida hyphae enumeration and assessment of Candida virulence gene expression. Lactate dehydrogenase (LDH) activity and Candida tissue invasion following biofilm infection of the RHOE were also measured. Candida hyphae were more prevalent (p < 0.05) in acrylic biofilms also containing bacteria, with genes encoding secreted aspartyl-proteinases (SAP4/SAP6) and hyphal-wall protein (HWP1) up-regulated (p < 0.05). Candida adhesin genes (ALS3/EPA1), SAP6 and HWP1 were up-regulated in mixed-species biofilm infections of RHOE. Multi-species infections exhibited higher hyphal proportions (p < 0.05), up-regulation of IL-18, higher LDH activity and tissue invasion. As the presence of bacteria in acrylic biofilms promoted Candida virulence, consideration should be given to the bacterial component when managing denture biofilm associated candidoses.

Phase 2 study of neoadjuvant enzalutamide and paclitaxel for luminal androgen receptor-enriched TNBC: Trial results and insights into "ARness".

Luminal androgen receptor (LAR)-enriched triple-negative breast cancer (TNBC) is a distinct subtype. The efficacy of AR inhibitors and the relevant biomarkers in neoadjuvant therapy (NAT) are yet to be determined. We tested the combination of the AR inhibitor enzalutamide (120 mg daily by mouth) and paclitaxel (80 mg/m2 weekly intravenously) (ZT) for 12 weeks as NAT for LAR-enriched TNBC. Eligibility criteria included a percentage of cells expressing nuclear AR by immunohistochemistry (iAR) of at least 10% and a reduction in sonographic volume of less than 70% after four cycles of doxorubicin and cyclophosphamide. Twenty-four patients were enrolled. Ten achieved a pathologic complete response or residual cancer burden-I. ZT was safe, with no unexpected side effects. An iAR of at least 70% had a positive predictive value of 0.92 and a negative predictive value of 0.97 in predicting LAR-enriched TNBC according to RNA-based assays. Our data support future trials of AR blockade in early-stage LAR-enriched TNBC.

'Hubble-bubble leads to trouble'--waterpipe smoking and oral health.

UNLABELLED: Waterpipes are used to smoke tobacco by more than 100 million people worldwide. Use is not restricted to any single racial, ethnic, or cultural group, and dentists are almost certain to encounter waterpipe users amongst their patients. This article describes what the practice involves and seeks to inform members of the dental team of the significantly detrimental impacts of waterpipe smoking on both general and oral health and how'hubble-bubble really can lead to trouble'. Advising patients on ceasing waterpipe use is also discussed. CLINICAL RELEVANCE: This paper explains what smoking a waterpipe involves, the associated misconceptions of safety amongst users and the dangers to health.

A mystery wrapped in an enigma: Matrigel enhancement of mammary cell growth and morphogenesis.

The analysis of normal mammary morphogenesis is facilitated by the use of mammary fat pad transplantation. The recent experiments on analysis of normal mammary epithelial stem cell activity rely heavily on this technique. In this review, we discuss the known and unknown attributes of using Matrigel in the injection of the mammary epithelial cell suspension. Matrigel greatly increases the "take" frequency of the injected cell suspension; however, there is some uncertainty regarding the interpretation of some of the results. After consideration of these issues, our conclusion is that Matrigel is important in order to obtain rigorous and reproducible results.

Oral ulceration (Part 1).

Ulceration is probably the oral mucosal condition seen most frequently by general dental practitioners. It is almost always painful and therefore sufferers are prompt to seek advice. An important exception to this generalisation is the occurrence of oral squamous cell carcinoma, which is often painless in its early stages. Definitive diagnosis, which requires mucosal biopsy, is mandatory for any persistent area of oral ulceration.

Oral ulceration (Part 2).

Ulceration is probably the oral mucosal condition seen most frequently by general dental practitioners. It is almost always painful and therefore sufferers are prompt to seek advice. An important exception to this generalisation is the occurrence of oral squamous cell carcinoma, which is often painless in its early stages. Definitive diagnosis, which requires mucosal biopsy, is mandatory for any persistent area of oral ulceration.

Systemic interventions for recurrent aphthous stomatitis (mouth ulcers).

BACKGROUND: Recurrent aphthous stomatitis (RAS) is the most frequent form of oral ulceration, characterised by recurrent oral mucosal ulceration in an otherwise healthy individual. At its worst RAS can cause significant difficulties in eating and drinking. Treatment is primarily aimed at pain relief and the promotion of healing to reduce the duration of the disease or reduce the rate of recurrence. A variety of topical and systemic therapies have been utilised. OBJECTIVES: To determine the clinical effect of systemic interventions in the reduction of pain associated with RAS, a reduction in episode duration or frequency. SEARCH METHODS: We undertook electronic searches of: Cochrane Oral Health Group and PaPaS Trials Registers (to 6 June 2012); CENTRAL via The Cochrane Library (to Issue 4, 2012); MEDLINE via OVID (1950 to 6 June 2012); EMBASE via OVID (1980 to 6 June 2012); CINAHL via EBSCO (1980 to 6 June 2012); and AMED via PubMed (1950 to 6 June 2012). We searched reference lists from relevant articles and contacted the authors of eligible trials to identify further trials and obtain additional information. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in which the primary outcome measures assess a reduction of pain associated with RAS, a reduction in episode duration or a reduction in episode frequency. Trials were not restricted by outcome alone. We also included RCTs of a cross-over design. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data in duplicate. We contacted trial authors for details of randomisation, blindness and withdrawals. We carried out risk of bias assessment on six domains. We followed The Cochrane Collaboration statistical guidelines and risk ratio (RR) values were to be calculated using fixed-effect models (if two or three trials in each meta-analysis) or random-effects models (if four or more trials in each meta-analysis). MAIN RESULTS: A total of 25 trials were included, 22 of which were placebo controlled and eight made head-to-head comparisons (five trials had more than two treatment arms). Twenty-one different interventions were assessed. The interventions were grouped into two categories: immunomodulatory/anti-inflammatory and uncertain. Only one study was assessed as being at low risk of bias. There was insufficient evidence to support or refute the use of any intervention. AUTHORS' CONCLUSIONS: No single treatment was found to be effective and therefore the results remain inconclusive in regard to the best systemic intervention for RAS. This is likely to reflect the poor methodological rigour of trials, and lack of studies for certain drugs, rather than the true effect of the intervention. It is also recognised that in clinical practice, individual drugs appear to work for individual patients and so the interventions are likely to be complex in nature. In addition, it is acknowledged that systemic interventions are often reserved for those patients who have been unresponsive to topical treatments, and therefore may represent a select group of patients.

Droplet Sizes Emitted from Demonstration Electric Toothbrushes.

The COVID-19 pandemic has drawn attention to microbial transmission risk via aerosols in dental practice. Demonstration electric toothbrushes are used intra-orally for education. The aim of this investigation was to measure the size of droplets emitted by the brush head of two demonstration oscillating-rotating electric toothbrushes. Measurement of droplet production and size was recorded in vitro using three methods: (1) Malvern Spraytec (LASER particle size measurement device with detectable particle size of 0.1-2500 µm) and brushes mounted on a 3D-printed, two-shell form-fit fixture with a supply of tap water; (2) a DustTrak aerosol measurement device and toothpaste slurry, with brushing simulated in the oral cavity of a phantom head; (3) high-speed visualization in a simulated-use situation in the oral cavity of a phantom head, with individual evaluation of tap water, water with detergent, 70% ethanol, glycerin and toothpaste slurry. Both brushes showed the size of emitted droplets was consistently between 200 and 1200 µm, categorized as splatter (dental aerosols are <50 µm diameter). No significant incremental aerosol-sized matter was detected during toothbrush operation. The high-speed video visualization confirmed only splatter-sized droplets during operation. These findings indicate that oscillating-rotating toothbrushes do not produce aerosol-sized particles during simulated use.

Improving diagnostic specimen management systems in an oral medicine department.

Histological, haematological and microbiological investigations are essential in the field of oral medicine and are a crucial adjunct to clinical findings, often being relied on to obtain a definitive diagnosis. Importantly, in some cases, these investigations can help exclude or confirm the presence of malignancy. This project highlighted some problems regarding labelling and recording of specimens in an oral medicine department and a lack of clear specimen management processes. It aimed to improve specimen management by reducing reported incidents surrounding diagnostic tests. Quality improvement methods such as process mapping were key to understanding the journey of specimens and the departments involved at each stage of the system. Initiatives included a recording log book, staff training, information signage around the clinic and delegation of responsibilities, all of which were implemented over multiple plan, do, study, act (PDSA) cycles. The project was extremely successful and since implementation there has been a clear and sustained reduction in reported incidents. The small number of incidents which did occur all involved transportation of specimens and none involved labelling or recording. One can conclude that the change in test management systems in terms of recording and labelling of specimens in the department has been sustained. Ongoing engagement with stakeholders and senior leaders is the priority to ensure further reduction in incidents in the future and that the improvements are maintained. This project demonstrates how simple, realistic, cost-effective, quality improvement initiatives can have a significant positive impact on patient care and hospital management systems.

Focal 18F-NaF PET Prostate Activity in the Setting of Prostate Adenocarcinoma.

A 72-year-old man with a family history of prostate cancer and initial diagnosis of favorable intermediate risk prostate cancer via biopsy in 2017 elected for active surveillance. Two years later, he underwent prostate biopsy showing intermediate-risk cT1c Nx Mx lesion with Gleason score 3 + 4 = 7 (5 core positive). Transrectal ultrasound showed a prostate volume 28 mL, and the prostate-specific antigen was 8.1. Patient elected to proceed with combination radiation therapy and androgen deprivation therapy.

Comparison of genotypes, antimicrobial resistance and virulence profiles of oral and non oral Enterococcus faecalis from Brazil, Japan and the United Kingdom.

OBJECTIVES: To determine whether phenotypic and genotypic differences amongst isolates ofEnterococcus faecalis relate to geographical and clinical origin. METHODS: E. faecalis from primary endodontic infections in Brazilian patients (n = 20), oral infections in UK patients (n = 10), and non-oral infections in Japanese patients (n = 9) were studied. In addition, 20 environmental vancomycin resistant Enterococcus faecalis (VRE) isolates from a UK hospital were analysed. For all isolates, polymerase chain reaction (PCR) was used to detect genes associated with antibiotic resistance and virulence, whilst randomly amplified polymorphic DNA-PCR (RAPD-PCR) was used to produce molecular profiles. RESULTS: Gelatinase gene (gelE) was prevalent amongst isolates (77-100%) and for oral isolates, genes of aggregation substances (agg), immune evasion protein (esp), cytolysin (cylB), tetracycline resistance (tetM; tetL) and erythromycin resistance (ermB) were detected to varying extent. Japanese non-oral isolates had a similar genetic profile to oral isolates, but with higher prevalence of ermB and cylB. All VRE isolates were positive for gelE, esp, agg, vanA, ermB and tetM, 95% were positive for cylB and 17% positive for tetL. All isolates were negative for ermA, asa373 vanB, vanC1 and vanC2/3. RAPD-PCR revealed clustering of VRE isolates. CONCLUSIONS: RAPD-PCR analysis revealed extensive genetic variability among the tested isolates. Oral isolates carried antibiotic resistance genes for tetracycline and whilst they possessed genes that could contribute to pathogenicity, these were detected at lower incidence compared with non-oral and VRE isolates. RAPD-PCR proved to be a useful approach to elucidate relatedness of disparate isolates.

Molecular community profiling of the bacterial microbiota associated with denture-related stomatitis.

Denture-associated stomatitis (DS) affects over two-thirds of denture-wearers. DS presents as erythema of the palatal mucosa in areas where denture-surface associated polymicrobial biofilms containing the fungus Candida albicans exist. The contribution of the oral bacterial microbiota toward the infection is unknown. Therefore, this study characterised the bacterial microbiota of sites within the oral cavity to identify potential associations with occurrence of DS. Denture-wearing patients were recruited (denture stomatitis (DS) n = 8; non-denture stomatitis (NoDS) n = 11) and the oral bacterial microbiota of the tongue, palate and denture-fitting surface was characterised using next-generation sequencing. Operational taxonomic units (OTUs) were identified to bacterial genera and species, and presence/absence and relative abundances were examined. A significant (P = 0.007) decrease in the number of OTUs and thus, diversity of the microbiota was observed in tongue samples of DS patients (vs non-DS). The microbiota of denture-fitting surfaces and palatal mucosae were similar. Large differences in the abundance of bacterial genera and species were observed at each sample site, and unique presence/absence of bacteria was noted. Presence/absence and relative abundance of specific bacteria associated with DS warrants further in vitro and in vivo evaluation, particularly as our previous work has shown C. albicans virulence factor modulation by oral bacteria.

Denture-associated biofilm infection in three-dimensional oral mucosal tissue models.

PURPOSE: In vitro analyses of virulence, pathogenicity and associated host cell responses are important components in the study of biofilm infections. The Candida-related infection, denture-associated oral candidosis, affects up to 60 % of denture wearers and manifests as inflammation of palatal tissues contacting the denture-fitting surface. Commercially available three-dimensional tissue models can be used to study infection, but their use is limited for many academic research institutions, primarily because of the substantial purchase costs. The aim of this study was to develop and evaluate the use of in vitro tissue models to assess infections by biofilms on acrylic surfaces through tissue damage and Candida albicans virulence gene expression. METHODOLOGY: In vitro models were compared against commercially available tissue equivalents (keratinocyte-only, SkinEthic; full-thickness, MatTek Corporation). An in vitro keratinocyte-only tissue was produced using a cancer-derived cell line, TR146, and a full-thickness model incorporating primary fibroblasts and immortalised normal oral keratinocytes was also generated. The in vitro full-thickness tissues incorporated keratinocytes and fibroblasts, and have potential for future further development and analysis. RESULTS: Following polymicrobial infection with biofilms on acrylic surfaces, both in-house developed models were shown to provide equivalent results to the SkinEthic and MatTek models in terms of tissue damage: a significant (P<0.05) increase in LDH activity for mixed species biofilms compared to uninfected control, and no significant difference (P>0.05) in the expression of most C. albicans virulence genes when comparing tissue models of the same type. CONCLUSION: Our results confirm the feasibility and suitability of using these alternative in vitro tissue models for such analyses.

Community analysis of dental plaque and endotracheal tube biofilms from mechanically ventilated patients.

PURPOSE: Mechanically ventilated patients are at risk for developing ventilator-associated pneumonia, and it has been reported that dental plaque provides a reservoir of respiratory pathogens that may aspirate to the lungs and endotracheal tube (ETT) biofilms. For the first time, metataxonomics was used to simultaneously characterize the microbiome of dental plaque, ETTs, and non-directed bronchial lavages (NBLs) in mechanically ventilated patients to determine similarities in respective microbial communities and therefore likely associations. MATERIAL AND METHODS: Bacterial 16S rRNA gene sequences from 34 samples of dental plaque, NBLs, and ETTs from 12 adult mechanically ventilated patients were analyzed. RESULTS: No significant differences in the microbial communities of these samples were evident. Detected bacteria were primarily oral species (e.g., Fusobacterium nucleatum, Streptococcus salivarius, Prevotella melaninogenica) with respiratory pathogens (Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcuspneumoniae, and Haemophilus influenzae) also in high abundance. CONCLUSION: The high similarity between the microbiomes of dental plaque, NBLs, and ETTs suggests that the oral cavity is indeed an important site involved in microbial aspiration to the lower airway and ETT. As such, maintenance of good oral hygiene is likely to be highly important in limiting aspiration of bacteria in this vulnerable patient group.