RESUMEN
BACKGROUND: The use of serious games in medical education provides a bridge between rapidly developing technology and traditional health-care teaching. Building on a promising web-based serious game for reviewing and acquiring factual knowledge in dental education, the present study investigated the benefits of a dual-player mode and various game options for enhancing knowledge gain and study motivation. METHODS: Before the intervention, students' dental knowledge and game experience were assessed using a pre-knowledge test and questionnaire-based self-assessment. Students in the clinical study phase (n = 57) were stratified based on prior knowledge and gender and then randomly assigned to two groups, with two player modes: single player (SP) and dual player (DP). In the SP group, each participant played alone, whereas in the DP group, the participants played against a previously determined peer. For a period of 4 weeks, the students were able to playfully acquire knowledge from the field of operative dentistry using METIS, a serious game application with three different game options (Marathon, Sprint, and Time). After the intervention phase, both groups completed a post-knowledge test. The usability of the serious game was evaluated with a self-assessment questionnaire. RESULTS: The competitive game mode (DP mode; M = 8.92, SD = 1.85) resulted in an increase in the factual knowledge test that was a mean of 2.49 points higher than the SP mode (M = 5.89, SD = 2.19; p < 0.001). The DP group also found the game significantly more helpful for learning (p = 0.04) and engaged more with the teaching content because of the app (p = 0.04). Overall, the usability of METIS was rated as excellent, and students successfully improved their knowledge of dentistry after game play with both game modes (SP, DP, p < 0.001), with the game option "Marathon," which involves playing the largest number of questions, being the most preferred. CONCLUSIONS: These results suggest that serious games such as METIS are a suitable educational medium for increasing students' knowledge and interest in the field, and that competition with peers provides even greater motivation to engage with the learning content.
Asunto(s)
Educación en Odontología , Estudiantes de Odontología , Juegos de Video , Humanos , Masculino , Estudiantes de Odontología/psicología , Femenino , Educación en Odontología/métodos , Evaluación Educacional , Adulto Joven , Encuestas y Cuestionarios , Motivación , Aprendizaje , AdultoRESUMEN
INTRODUCTION: We present a systematic review of phenotypes of McLeod syndrome (MLS) and a case of a 73-year-old female carrier of the genetic alteration leading to MLS with the typical progressive supranuclear palsy (PSP) phenotype. METHODS: To facilitate clinical reasoning and enable targeted diagnosis, we conducted a systematic review of the papers describing symptomatic cases of confirmed McLeod syndrome. This review follows the PRISMA 2020 statement: an updated guideline for reporting systematic reviews (Page et al in Syst Rev 10(1):89, 2021). RESULTS: The average onset of MLS was at 40.2 years of age with chorea (46%), seizures and psychiatric changes (each 13%). Very common are weakened Kell antigen (100%), changes in muscle biopsy (100%), genetic alterations in XK (100%), elevated creatine kinase (97%), acanthocytes (96%), MRI changes (95%), chorea (84%) and hyporeflexia (82%). CONCLUSION: This review of 65 males and 11 females gives a concise overview of clinical phenotypes in MLS, reinforcing our view that this female patient had PSP independent of MLS carrier status. This report highlights the pitfalls of anchoring in medical decision-making, particularly the possible diagnostic bias of a known genetic carrier status of a very rare disease.
Asunto(s)
Fenotipo , Parálisis Supranuclear Progresiva , Humanos , Femenino , Anciano , Parálisis Supranuclear Progresiva/genética , Parálisis Supranuclear Progresiva/patología , Neuroacantocitosis/genética , Neuroacantocitosis/patología , Neuroacantocitosis/diagnóstico , MasculinoRESUMEN
Objectives: Photochemical systems are frequently recommended as an adjuvant treatment option in peri-implantitis therapy. The aim of the present study was to evaluate the efficacy of these treatment options, as well as a novel curcumin-based option, in a biofilm model on implants. Methods: Eighty dental implants were inoculated with an artificial biofilm of periodontal pathogens and placed in peri-implant pocket models. The following groups were analyzed: I, photodynamic therapy (PDT); II, PDT dye; III, curcumin/DMSO + laser; IV, curcumin/DMSO only; V, dimethyl sulfoxide (DMSO) only; VI, photothermal therapy (PTT); VII, PTT dye; VIII, control. After treatment, remaining bacterial loads were assessed microbiologically using quantitative real-time polymerase chain reaction analysis. Results: The PDT, PTT, and DMSO treatment methods were associated with statistically significant (p < 0.05) improvements in germ reduction in comparison with the other methods and the untreated control group. The mean percentage reductions were as follows: I (PDT) 93.9%, II (PDT dye) 62.9%, III (curcumin/DMSO + laser) 74.8%, IV (curcumin/DMSO only) 67.9%, V (DMSO) 89.4%, VI (PTT) 86.8%, and VII (PTT dye) 66.3%. Conclusions: The commercially available PDT and PTT adjuvant treatment systems were associated with the largest statistically significant reduction in periopathogenic bacteria on implant surfaces. However, activation with laser light at a suitable wavelength is necessary to achieve the bactericidal effects. The use of curcumin as a photosensitizer for 445 nm laser irradiation did not lead to any improvement in antibacterial efficacy in comparison with rinsing with DMSO solution alone.
RESUMEN
BACKGROUND: The introduction of tyrosine kinase inhibitors (TKI) has greatly improved the management of metastatic melanoma. Recent studies have uncovered a relationship between the body mass index (BMI) and outcome of patients with metastatic melanoma. However, conflicting results have challenged the relevance of this finding. In the current work, we aim to dissect body composition features of melanoma patients treated with TKI to evaluate their value as biomarkers. PATIENTS AND METHODS: We analyze body composition features via CT scans in a retrospective cohort of 57 patients with non-resectable stage III/IV melanoma receiving first-line treatment with TKI in our department, focusing on the impact of body composition on treatment efficacy and occurrence of adverse events. RESULTS: In uni- and multivariate analyses, we identify an association between the visceral adipose tissue gauge index (VATGI) and survival. We furthermore profile additional body composition features including sarcopenia, which was also associated with a shorter overall survival. Finally, we detected an enrichment of cases with fatigue in patients with low VATGI. CONCLUSIONS: Our study represents the first exploratory study evaluating the suitability of body composition measurements as biomarkers for melanoma patients treated with TKI. Our data suggest a putative use of VATGI as a biomarker predicting patient outcome.
Asunto(s)
Composición Corporal , Melanoma , Inhibidores de Proteínas Quinasas , Neoplasias Cutáneas , Humanos , Melanoma/tratamiento farmacológico , Melanoma/patología , Composición Corporal/efectos de los fármacos , Masculino , Femenino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Estudios Retrospectivos , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Anciano , Índice de Masa Corporal , Adulto , Resultado del Tratamiento , Tomografía Computarizada por Rayos X , Estadificación de Neoplasias , Grasa Intraabdominal/diagnóstico por imagen , Grasa Intraabdominal/efectos de los fármacosRESUMEN
PURPOSE: Adjuvant immunotherapy with immune checkpoint blockade(ICB) has greatly reduced the risk of recurrence and metastatic spread in early and advanced melanoma. However, not all patients benefit from adjuvant treatment: many patients show disease recurrence despite therapy, while those without recurrence harbor the risk for potentially irreversible adverse events. Biomarkers to select patients benefitting most from adjuvant therapy are currently lacking. As body composition assessment using CT images has shown promising results as a prognostic biomarker in stage IV melanoma, we aim to study the applicability of body composition parameters also in adjuvant melanoma treatment. METHODS: We analyze body composition features via CT scans in a retrospective cohort of 109 patients with resected stage IIB-IV melanoma receiving an adjuvant first-line treatment with ICB in our department. In this analysis, we focus on the impact of body composition, especially the presence of low skeletal muscle mass (LSMM), on patients' survival and occurrence of adverse events (AEs). RESULTS: In uni- and multivariate analyses, we identify an association between CT-measured LSMM and melanoma-specific survival in patients treated with adjuvant ICB. Furthermore, LSMM is associated with a lower risk for therapy-related AEs, especially hypothyroidism, fatigue, and xerostomia. Conventional serological biomarkers e.g. S100 and LDH and measures of adipose tissue compartments did not show a correlation with survival or the occurrence of AEs. CONCLUSIONS: LSMM constitutes a novel biomarker for melanoma-specific survival in patients treated with adjuvant ICB.
Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Melanoma , Músculo Esquelético , Humanos , Melanoma/mortalidad , Melanoma/tratamiento farmacológico , Melanoma/patología , Melanoma/terapia , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Anciano , Músculo Esquelético/patología , Músculo Esquelético/diagnóstico por imagen , Adulto , Composición Corporal , Quimioterapia Adyuvante/métodos , Pronóstico , Anciano de 80 o más Años , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/inmunología , Tomografía Computarizada por Rayos XRESUMEN
Background In the current cosmetics industry, bleaching is often associated with lasers. However, such treatment also harbors risks. Tooth death is observed at pulpal temperature increases ≥5.6 °C. Therefore, it seems important to investigate the effects of using different lasers. The aim of this study was to determine pulpal temperature increases at different laser parameters during bleaching by modeling a realistic environment and to compare the temperature recording using a thermocouple and thermal camera. The authors assumed that there are laser settings for the lasers used at which the pulpal temperature increases are <5.6 °C and that the temperature recordings with thermocouples and thermal cameras differ only minimally. Methods Human teeth were used, which were extracted for dental reasons. During experiment, teeth were bleached conventionally and by laser activation at 940 nm, 445 nm, and 970 nm. The temperature in the pulp was recorded using thermocouples. In a second setup, longitudinally halved teeth were bleached, while the temperature in the pulp was recorded with a thermocouple and thermal camera. Descriptive statistics were used. The significance level is 0.05. Results In addition to conventional bleaching, temperature increases <5.6 °C were observed for bleaching at 940 nm 1.5 W, at 445 nm 0.3 W, and at 970 nm 0.5 W. For bleaching procedures using 940 nm 7 W, 940 nm 2 W, 445 nm 0.5 W, and 970 nm 1 W, the temperature increase was ≥5.6 °C. Significant differences (p < 0.05) were found in the maximum temperature increases (°C) between all groups. Temperature recordings using a thermocouple and thermal camera differed by about 2.3 °C. The working hypotheses were confirmed. Conclusion With laser bleaching, attention must be paid to the type of laser, its power, and the time in order to avoid excessive overheating of the dental pulp.
RESUMEN
STUDY OBJECTIVES: Wearable devices that monitor sleep stages and heart rate offer the potential for longitudinal sleep monitoring in patients with neurodegenerative diseases. Sleep quality reduces with disease progression in Huntington's disease (HD). However, the involuntary movements characteristic of HD may affect the accuracy of wrist-worn devices. This study compares sleep stage and heart rate data from the Fitbit Charge 4 (FB) against polysomnography (PSG) in participants with HD. METHODS: Ten participants with manifest HD wore an FB during overnight hospital-based PSG, and 9 of these participants continued to wear the FB for 7 nights at home. Sleep stages (30-second epochs) and minute-by-minute heart rate were extracted and compared against PSG data. RESULTS: FB-estimated total sleep and wake times and sleep stage times were in good agreement with PSG, with intraclass correlations of 0.79-0.96. However, poor agreement was observed for wake after sleep onset and the number of awakenings. FB detected waking with 68.6 ± 15.5% sensitivity and 93.7 ± 2.5% specificity, rapid eye movement sleep with high sensitivity and specificity (78.7 ± 31.9%, 95.6 ± 2.3%), and deep sleep with lower sensitivity but high specificity (56.4 ± 28.8%, 95.0 ± 4.8%). FB heart rate was strongly correlated with PSG, and the mean absolute error between FB and PSG heart rate data was 1.16 ± 0.42 beats/min. At home, longer sleep and shorter wake times were observed compared with hospital data, whereas percentage sleep stage times were consistent with hospital data. CONCLUSIONS: Results suggest the potential for long-term monitoring of sleep patterns using wrist-worn wearable devices as part of symptom management in HD. CITATION: Doheny EP, Renerts K, Braun A, et al. Assessment of Fitbit Charge 4 for sleep stage and heart rate monitoring against polysomnography and during home monitoring in Huntington's disease. J Clin Sleep Med. 2024;20(7):1163-1171.
Asunto(s)
Frecuencia Cardíaca , Enfermedad de Huntington , Polisomnografía , Fases del Sueño , Dispositivos Electrónicos Vestibles , Humanos , Polisomnografía/métodos , Polisomnografía/instrumentación , Masculino , Enfermedad de Huntington/fisiopatología , Enfermedad de Huntington/complicaciones , Femenino , Frecuencia Cardíaca/fisiología , Persona de Mediana Edad , Fases del Sueño/fisiología , Adulto , Monitoreo Ambulatorio/instrumentación , Monitoreo Ambulatorio/métodosRESUMEN
The aim of this in vitro study was to evaluate the efficiency of diode laser-activated bleaching systems for color change of teeth. 75 extracted teeth were studied in five different bleaching protocols. Group 1: diode laser 445 nm, 320 µm fiber, 0.5W, continuous wave mode, dose 53 J/cm2. Group 2: diode laser 970 nm, 320 µm fiber, 1W, continuous wave mode, dose 106.10 J/cm2. Group 3: diode laser 940 nm, bleaching handpiece, 7W, continuous wave mode, dose 105 J/cm2. Group 4: diode laser 940 nm, 300 µm fiber, 2W, continuous wave mode, dose 47.16 J/cm2. Group 5: bleaching process without laser activation. In groups 1, 2 and 5, teeth were bleached with Perfect Bleach Office + and in groups 3 and 4, LaserWhite20 bleaching gel was used. Tooth color was determined immediately after the bleaching process using a spectrophotometer. Color change data on the CIE L * a * b* system was analyzed statistically by the one-way ANOVA and Tukey's HSD test. All bleaching procedures resulted in a change of color. All laser groups (∆E * ab > 3) have statistically larger ∆E * ab values than the control group (∆E * ab = 0.73) (p < 0.05). The diode laser 445 nm has the largest ∆E * ab value (∆E * ab = 4.65) and results in a significantly higher color difference than all other groups. In terms of color score difference in VITA Shades, all laser-activated groups lead to a lightening effect while the control group leads to only a slight lightening effect. The diode laser 445 nm produced the greatest color difference. Laser-activated bleaching is more effective than conventional bleaching without light activation. The diode laser 445 nm performs best in this in vitro study.
Asunto(s)
Láseres de Semiconductores , Espectrofotometría , Blanqueadores Dentales , Blanqueamiento de Dientes , Blanqueamiento de Dientes/métodos , Humanos , Láseres de Semiconductores/uso terapéutico , Técnicas In Vitro , Decoloración de Dientes/terapia , ColorRESUMEN
Recent pan-cancer genomic analyses have identified numerous oncogenic driver mutations that occur in a cell-type and tissue-specific distribution. For example, oncogenic mutations in Braf and Nras genes arise predominantly in melanocytic neoplasms of the epidermis, while oncogenic mutations in Gnaq/11 genes arise mostly in melanocytic lesions of the dermis or the uvea. The mechanisms promoting cell-type and tissue-specific oncogenic events currently remain poorly understood. Here, we report that Gnaq/11 hotspot mutations occur as early oncogenic drivers during the evolution of primary melanomas in Hgf-Cdk4 mice. Additional single base substitutions in the Trp53 gene and structural chromosomal aberrations favoring amplifications of the chromosomal region containing the Met receptor gene accumulate during serial tumor transplantation and in cell lines established in vitro. Mechanistically, we found that the GnaqQ209L mutation transactivates the Met receptor. Overexpression of oncogenic GnaqQ209L in the immortalized melanocyte cell line promoted in vivo growth that was enhanced by transgenic Hgf expression in the tumor microenvironment. This cross-signaling mechanism explains the selection of oncogenic Gnaq/11 in primary Hgf-Cdk4 melanomas and provides an example of how oncogenic driver mutations, intracellular signaling cascades, and microenvironmental cues cooperate to drive cancer development in a tissue-specific fashion.
Asunto(s)
Quinasa 4 Dependiente de la Ciclina , Subunidades alfa de la Proteína de Unión al GTP Gq-G11 , Factor de Crecimiento de Hepatocito , Melanoma , Proteínas Proto-Oncogénicas c-met , Transducción de Señal , Animales , Ratones , Proteínas Proto-Oncogénicas c-met/genética , Proteínas Proto-Oncogénicas c-met/metabolismo , Quinasa 4 Dependiente de la Ciclina/genética , Quinasa 4 Dependiente de la Ciclina/metabolismo , Factor de Crecimiento de Hepatocito/genética , Factor de Crecimiento de Hepatocito/metabolismo , Humanos , Melanoma/genética , Melanoma/metabolismo , Melanoma/patología , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/metabolismo , Activación Transcripcional , Mutación , Línea Celular Tumoral , Ratones Transgénicos , Microambiente Tumoral/genéticaRESUMEN
Elimination of microbes in the root canal system is crucial for achieving long-term success in endodontic treatment. Further efforts in study design and standardization are needed in order to improve the validity and comparability of in vitro results on endodontic disinfection procedures, in turn improving clinical outcomes. This study optimizes two models at all steps: tooth selection, pretreatment, inoculation method (by growth or centrifugation), and confocal laser scanning microscopy (CLSM)-guided imaging of LIVE/DEAD-stained specimens. Individual anatomical conditions lead to substantial differences in penetration depth. Sclerosis grading (SCG), a classification system introduced in this study, provides information about the sclerosis status of the dentine and is helpful for careful, specific, and comparable tooth selection in in vitro studies. Sonically activated EDTA for the pretreatment of roots, inoculation of Enterococcus faecalis in an overflow model, 3-4 weeks of incubation, as well as polishing of dentine slices before staining, led to advances in the visualization of bacterial penetration and irrigation depths. In contrast, NaOCl pretreatment negatively affected performance reproducibility and should be avoided in any pretreatment. Nonsclerotized teeth (SCG0) can be used for microbial semilunar-shaped inoculation by centrifugation as a "quick-and-dirty" model for initial orientation. In conclusion, CLSM-guided imaging for quantifying endodontic infection/disinfection is a very powerful method after the fine-tuning of materials and methods.
RESUMEN
Successful bacterial inactivation or elimination is essential for successful outcomes in endodontics. This study investigated the efficacy of a calcium hydroxide paste (Ca(OH)2) as a temporary medical dressing for 1 week after chemomechanical root canal treatment (CMRCT). Microbiological samples from 26 patients were collected after endodontic emergency treatment as follows: (1) removal of the provisional filling material; (2) CMRCT; (3) irrigation with sodium hypochlorite I (3%); (4) medicinal insertion of Ca(OH)2; and (5) irrigation with sodium hypochlorite II (3%). A microbiological examination was carried out after the specimens had been taken from the root canals via saline and sterile paper points. CMRCT resulted in a significant reduction in total bacterial load (TBL) in the root canal (p < 0.05). Additional irrigation (3) resulted in a further significant reduction in TBL (p < 0.05). In contrast, Ca(OH)2 medication did not prevent the bacterial load from returning to the previous level immediately after CMRCT, but did not increase above that level either (p < 0.05). However, the increase in TBL was significant (p < 0.05) in comparison with the disinfection groups (I/II). Administration of Ca(OH)2 for 1 week shows that in combination with an additional disinfection procedure, an increase in TBL must be expected, but not above the level of conditions after CMRCT.
RESUMEN
OBJECTIVES: Oral potentially malignant disorders (OPMDs) are the most clinically relevant precursor lesions of the oral squamous cell carcinoma (OSCC). OSCC is one of the 15 most common cancers worldwide. OSCC is with its high rate of mortality an important cause of death worldwide. The diagnosis and therapy of clinically relevant precursor lesions of the OSCC is one of the main parts of prevention of this malignant disease. Targeted therapy is one of the main challenges concerning an oncologically safe tissue removal without overwhelming functional and aesthetic impairment. MATERIALS AND METHODS: In this randomized controlled trial, a newly introduced intraoral 445-nm semiconductor laser (2W; cw-mode; SIROLaser Blue, Dentsply Sirona, Bensheim, Germany) was used in the therapy of OPMDs. Duration and course of wound healing, pain, and scar tissue formation were compared to classical cold blade removal with primary suture by measuring remaining wound area, tissue colorimetry, and visual analogue scale. The study includes 40 patients randomized using a random spreadsheet sequence in two groups (n1 = 20; n2 = 20). RESULTS: This comparative analysis revealed a significantly reduced remaining wound area after 1, 2, and 4 weeks in the laser group compared to the cold blade group (p < 0.05). In the laser group, a significantly reduced postoperative pain after 1 week was measured (p < 0.05). CONCLUSION: Laser coagulation of OPMDs with the investigated 445-nm semiconductor laser is a safe, gentle, and predictable surgical procedure with beneficial wound healing and reduced postoperative discomfort. CLINICAL RELEVANCE: Compared to the more invasive and bloody cold blade removal with scalpel, the 445-nm semiconductor laser could be a new functional less traumatic tool in the therapy of OPMDs. The method should be further investigated with regard to the identification of further possible indications. TRAIL REGISTRATION: German Clinical Trials Register No: DRKS00032626.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Láseres de Semiconductores/uso terapéutico , Neoplasias de la Boca/radioterapia , Neoplasias de la Boca/cirugía , Estética Dental , Cicatrización de Heridas , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
Over the past decade, dramatic progress has been made in dental research areas involving laser therapy. The photobiomodulatory effect of laser light regulates the behavior of periodontal tissues and promotes damaged tissues to heal faster. Additionally, photobiomodulation therapy (PBMT), a non-invasive treatment, when applied in orthodontics, contributes to alleviating pain and reducing inflammation induced by orthodontic forces, along with improving tissue healing processes. Moreover, PBMT is attracting more attention as a possible approach to prevent the incidence of orthodontically induced inflammatory root resorption (OIIRR) during orthodontic treatment (OT) due to its capacity to modulate inflammatory, apoptotic, and anti-antioxidant responses. However, a systematic review revealed that PBMT has only a moderate grade of evidence-based effectiveness during orthodontic tooth movement (OTM) in relation to OIIRR, casting doubt on its beneficial effects. In PBMT-assisted orthodontics, delivering sufficient energy to the tooth root to achieve optimal stimulation is challenging due to the exponential attenuation of light penetration in periodontal tissues. The penetration of light to the root surface is another crucial unknown factor. Both the penetration depth and distribution of light in periodontal tissues are unknown. Thus, advanced approaches specific to orthodontic application of PBMT need to be established to overcome these limitations. This review explores possibilities for improving the application and effectiveness of PBMT during OTM. The aim was to investigate the current evidence related to the underlying mechanisms of action of PBMT on various periodontal tissues and cells, with a special focus on immunomodulatory effects during OTM.
Asunto(s)
Terapia por Luz de Baja Intensidad , Ortodoncia , Resorción Radicular , Humanos , Inflamación , Terapia por Luz de Baja Intensidad/efectos adversos , Resorción Radicular/etiología , Resorción Radicular/terapia , Técnicas de Movimiento DentalRESUMEN
The link between periodontitis and systemic diseases has increasingly become a focus of research in recent years. In this context, it is reasonable-especially in vulnerable patient groups-to minimize bacteremia during periodontal treatment. The aim of the present in vivo feasibility study was to investigate the possibility of laser-based bacteremia prevention. Patients with stage III, grade B generalized periodontitis were therefore treated in a split-mouth design either with prior 445 nm laser irradiation before nonsurgical periodontal therapy or without. During the treatments, clinical (periodontal measures, pain sensation, and body temperature), microbiological (sulcus samples and blood cultures before, 25 min after the start, and 10 min after the end of treatment), and immunological parameters (CRP, IL-6, and TNF-α) were obtained. It was shown that periodontal treatment-related bacteremia was detectable in both patients with the study design used. The species isolated were Schaalia georgiae, Granulicatella adiacens, and Parvimonas micra. The immunological parameters increased only slightly and occasionally. In the laser-assisted treatments, all blood cultures remained negative, demonstrating treatment-related bacteremia prevention. Within the limitations of this feasibility study, it can be concluded that prior laser disinfection can reduce bacteremia risk during periodontal therapy. Follow-up studies with larger patient numbers are needed to further investigate this effect, using the study design presented here.
RESUMEN
Over the past decade, dramatic progress has been made in dental research areas involving laser therapy. The photobiomodulatory effect of laser light regulates the behavior of periodontal tissues and promotes damaged tissues to heal faster. Additionally, photobiomodulation therapy (PBMT), a non-invasive treatment, when applied in orthodontics, contributes to alleviating pain and reducing inflammation induced by orthodontic forces, along with improving tissue healing processes. Moreover, PBMT is attracting more attention as a possible approach to prevent the incidence of orthodontically induced inflammatory root resorption (OIIRR) during orthodontic treatment (OT) due to its capacity to modulate inflammatory, apoptotic, and anti-antioxidant responses. However, a systematic review revealed that PBMT has only a moderate grade of evidence-based effectiveness during orthodontic tooth movement (OTM) in relation to OIIRR, casting doubt on its beneficial effects. In PBMT-assisted orthodontics, delivering sufficient energy to the tooth root to achieve optimal stimulation is challenging due to the exponential attenuation of light penetration in periodontal tissues. The penetration of light to the root surface is another crucial unknown factor. Both the penetration depth and distribution of light in periodontal tissues are unknown. Thus, advanced approaches specific to orthodontic application of PBMT need to be established to overcome these limitations. This review explores possibilities for improving the application and effectiveness of PBMT during OTM. The aim was to investigate the current evidence related to the underlying mechanisms of action of PBMT on various periodontal tissues and cells, with a special focus on immunomodulatory effects during OTM.
RESUMEN
BACKGROUND: Migratory insects are important for the provision of ecosystem services both at the origin and destination sites but - apart from some iconic species - the migration routes of many insect species have not been assessed. Coastlines serve as a funnel where migrating animals including insects accumulate. Migratory behaviour and captures of dragonflies in bird traps suggest autumn migration of dragonflies along coastlines while the origin and regularity of this migration remain unclear. METHODS: Dragonfly species were caught at the bird observatory Kabli at the Baltic coast in Estonia in 2009, 2010 and 2015. For the 2015 data set, we used a stable hydrogen (H) approach to trace the potential natal origin of the migrant hawker (Aeshna mixta). RESULTS: 1079 (2009), 701 (2010) and 88 (2015) A. mixta individuals were caught during the study periods (35, 37 and 11 days in 2009, 2010 and 2015, respectively). The migration period lasted from end of August to end of September. Based on the results from our stable isotope analysis, we identified two populations of A. mixta: One (range of isotope signatures of non-exchangeable H [δ2Hn wing]: -78 to -112) had a local likely origin while the other (δ2Hn wing: -113 to -147) migrated from northerly directions even in headwind from the South. The former showed an even sex ratio whereas the actively migrating population was dominated by males. CONCLUSIONS: Our results suggest a regular southbound autumn migration of A. mixta along the Baltic coast. However, nearly half of the sampled individuals originated from the surroundings suggesting either no, partial or "leap-frog" migration. Contrary to our expectation, A. mixta did not select favourable wind conditions but continued the southbound autumn migration in the flight boundary layer even in case of headwinds. The dominance of males might indicate migration as a result of competition for resources. Further repeated, large-scale studies along the Baltic coast are necessary to pinpoint the migratory pattern and the reason for migration of A. mixta. Such studies should also comprise locations north of the known species range of A. mixta because of the rapid climate-change induced range expansion.
RESUMEN
Most clinically applied cancer immunotherapies rely on the ability of CD8+ cytolytic T cells to directly recognize and kill tumour cells1-3. These strategies are limited by the emergence of major histocompatibility complex (MHC)-deficient tumour cells and the formation of an immunosuppressive tumour microenvironment4-6. The ability of CD4+ effector cells to contribute to antitumour immunity independently of CD8+ T cells is increasingly recognized, but strategies to unleash their full potential remain to be identified7-10. Here, we describe a mechanism whereby a small number of CD4+ T cells is sufficient to eradicate MHC-deficient tumours that escape direct CD8+ T cell targeting. The CD4+ effector T cells preferentially cluster at tumour invasive margins where they interact with MHC-II+CD11c+ antigen-presenting cells. We show that T helper type 1 cell-directed CD4+ T cells and innate immune stimulation reprogramme the tumour-associated myeloid cell network towards interferon-activated antigen-presenting and iNOS-expressing tumouricidal effector phenotypes. Together, CD4+ T cells and tumouricidal myeloid cells orchestrate the induction of remote inflammatory cell death that indirectly eradicates interferon-unresponsive and MHC-deficient tumours. These results warrant the clinical exploitation of this ability of CD4+ T cells and innate immune stimulators in a strategy to complement the direct cytolytic activity of CD8+ T cells and natural killer cells and advance cancer immunotherapies.
Asunto(s)
Linfocitos T CD4-Positivos , Muerte Celular , Inmunoterapia , Inflamación , Neoplasias , Microambiente Tumoral , Humanos , Células Presentadoras de Antígenos/inmunología , Antígeno CD11c/inmunología , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Muerte Celular/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Inmunidad Innata , Inflamación/inmunología , Interferones/inmunología , Complejo Mayor de Histocompatibilidad/inmunología , Neoplasias/inmunología , Neoplasias/patología , Neoplasias/terapia , Microambiente Tumoral/inmunología , Inmunoterapia/métodos , Células Asesinas Naturales/inmunología , Células Mieloides/inmunología , Células TH1/citología , Células TH1/inmunologíaRESUMEN
RATIONALE AND OBJECTIVES: Despite the impressive efficacy of immune checkpoint inhibitors (ICIs) in the treatment of metastatic melanoma, not all patients respond to therapy. In addition, ICI harbors the risk for serious adverse events (AEs), highlighting the need for novel biomarkers predicting treatment response and occurrence of AEs. Recently, the identification of enhanced response to ICI in obese patients has indicated that body composition might influence treatment efficacy. The aim of the current study is to assess radiologic measurements of body composition as biomarkers for treatment response and AEs to ICI in melanoma. MATERIALS AND METHODS: In the current work, we analyze adipose tissue abundance and density, as well as muscle mass via computed tomography scans in a retrospective cohort of 100 patients with non-resectable stage III/IV melanoma receiving first-line treatment with ICI in our department. From these, we investigate the impact of the subcutaneous adipose tissue gauge index (SATGI) and other parameters of body composition on treatment efficacy and occurrence of AEs. RESULTS: Low SATGI was associated with prolonged progression-free survival (PFS) in univariate and multivariate analyses (hazard ratio 2.56 [95% CI 1.18-5.55], Pâ¯=â¯.02), as well as an enhanced objective response rate (50.0% vs 27.1%; Pâ¯=â¯.02). Further analysis with a random forest survival model highlighted a nonlinear relationship between SATGI and PFS with a clear separation into high- and low-risk cohorts separated by the median. Finally, a significant enrichment of cases with vitiligo, but no other AEs, was observed in the SATGI-low cohort (11.5% vs 0%; P = .03). CONCLUSION: We identify SATGI as a biomarker predicting treatment response to ICI without increased risk for severe AEs in melanoma.