Title: An assessment of the effectiveness of Andolex-C ® mouth rinse on oral palliation in HIV-infected patients. Background: The majority of HIV-infected patients present with oral lesions associated with the disease. HIV-infected patients experience profound disorders like oral infections and ulcerations, discomfort and greater levels of social impact than non-HIV patients as a result of oral lesions. Studies have indicated that mouth pain is a significant symptom reported by HIV-infected patients. In order to relieve pain and discomfort and improve quality of life, management of HIV-infected patients should include relief of mouth pain, discomfort as well as the social and psychological distress caused by the oral lesions. Objectives: To determine the prevalence of oral lesions associated with HIV among a cohort of HIV-infected patients. To assess the effectiveness of Andolex-C® mouth rinse on oral palliation in HIV-infected patients. Methods: The intervention of Andolex C® mouth rinse plus a proven preventive oral hygiene regimen was compared to an established oral hygiene intervention. Two hundred and ninety nine patients were randomly assigned into Groups 1 and 2. Patients in Group 1 were given toothbrushes and toothpaste and oral hygiene instruction ‘routine oral hygiene package’. Those in Group 2 received Andolex-C® mouth rinse in addition to the ‘routine oral hygiene package’ given to the first group. A baseline assessment of mouth pain and/or discomfort was done via a clinical examination and an assessment of quality of life was done using the Oral Health Impact Profile (OHIP) questionnaire. The intervention was carried out over a four week period after which a follow-up assessment was done using the same tools. Comparison of baseline versus post-treatment scores was performed to determine impact of intervention in both groups. Results: The prevalence of combined candidal lesions was 71.6% of which Pseudomembranous candidiasis was 43.2%. Erythematous candidiasis and angular cheilitis were the next commonly seen, each with an equal prevalence of 14.2 %. Group 2 (Andolex-C® mouth rinse) showed a statistically significant improvement in quality of life on all subscales related to functioning, pain, psychological and social aspects when using the OHIP index. The patients demonstrated substantial reduction of [64%] of mouth pain and/or discomfort and a 73% reduction of oral lesions compared to Group 1 where there was a much smaller [22%] reduction of mouth pain and/or discomfort and a 40% reduction of the oral lesions. Conclusion: Andolex-C® mouth rinse improved the quality of life of HIV-infected patients who presented with mouth pain and/or discomfort and demonstrated that in combination with proper oral care and good hygiene habits, this regimen could be recommended for oral palliation in HIV positive patients.

The overarching goal of this dissertation is to refine methods employed for assessing neuromuscular changes and associated power/force outputs during various perturbations of fatigue, direct or perceived, induced by either exercise or nutritional interventions, with associated performance outcomes. To address this goal, we collected physiological and biomechanical data from subjects across a set of experiments designed to induce different levels of fatigue by the implementation of various exercise and nutritional interventions to cause various levels of fatigue in an ecologically valid manner. The data sets were collected during a single joint task and during cycling trials. During these experimental trials, we collected measures of kinetics (force and cycling power) as well as muscle activation (EMG) and physiological measures (heart rate, rating of perceived exertion, blood lactate, blood glucose, ventilation, oxygen uptake and carbon dioxide production) to investigate the overall performance, as well as potential mechanisms for improved performance related to the exercise and nutritional interventions. In order to substantially enhance the collection of cycling kinetics and kinematics, we have developed an innovative sensor that improved the measurement resolution (temporal and spatial) of a commercial research grade power meter. Using these improved measures alongside advanced muscle activity analysis, we could ameliorate an experimental framework that could be used to investigate changes in fatigue and coordination pattern associated with exercise and nutritional interventions. Investigation of the effects of a CHO mouth rinse vs. placebo on force and muscle activity during a very short (<3 min) neuromuscular demanding fatiguing trial demonstrated a consistent change in EMG median frequency related to increased fatigue in both experimental conditions, providing little evidence of change in neuromuscular strategy associated with CHO mouth rinse. Further investigation explored the effects of a CHO mouth rinse vs. placebo using fundamental physiological measures of neuromuscular activation and overall performance measures during an ecologically valid late endurance cycling time trial. Our results demonstrated that while there was no overall effect noticed for time to completion, there was a significant decrease in performance in the time to complete various components of the time trial during the placebo trial only. Muscle activity of the lower leg (MG and SOL) demonstrated a modification in frequency only evident during the placebo condition. Application of principal component analysis to power output and the EMG intensity profiles of the muscles of the lower leg during the pedal cycle revealed a more detailed understanding of the effect of CHO mouth rinse on performance during cycling. The average power output profile in WASH showed an earlier onset in the pedal cycle, greater duration and higher amplitude versus PLA during the TT. Additionally, only the PLA condition showed a significant increase in muscle activation throughout the time trial, which could be evidence of fatigue. This dissertation shows for the first time that CHO mouth rinse may have a substantial effect on the maintenance of power while mitigating the impact of neuromuscular fatigue, in late endurance performance, further strengthen our assertion that CHO may, in fact, minimize the changes in performance that are associated with fatigue during late endurance fatiguing events. / Graduate

O objetivo da presente tese foi verificar a influência do enxágue bucal com carboidrato (CHO) sobre o desempenho no exercício físico predominantemente aeróbio realizado após uma atividade cognitiva frequentemente utilizada para induzir a fadiga mental. Sete homens fisicamente ativos participaram do estudo (idade: 26 ± 5 anos; estatura: 176,0 ± 8,3 cm; massa corporal: 73,6 ± 7,4 kg e gordura corporal: 14,3 ± 3,7 %, VO2 pico: 43,9 ± 6,5 ml.kg-1.min-1, Wpico: 268 ± 23,8 W) realizaram o Stroop Incongruente para indução da Fadiga Mental (FM) ou assistiam a um documentário pelo mesmo período de tempo (controle, CON). Após a tarefa eles realizaram um exercício de carga constante (~55%Wpico) até exaustão. Em cada uma das condições FM e CON os voluntários utilizavam o enxágue bucal (10s) com CHO ou placebo (PLA). No pre-exercício, não houve diferença estatisticamente significante para glicose entre as diferentes condições. A frequência cardíaca apresentou aumento após todas as intervenções, assim como a fadiga percebida (P = 0,001, ES = 0,49), mas sem efeito de condição. O effect size foi moderado para essa variável, sugerindo que o aumento na fadiga percebida foi maior na condição FM (75%) quando comparado a condição CON (60%). A motivação não apresentou diferença entre as condições. Porém, houve uma tendência (0,07) a ser maior na condição DOC. Houve uma redução de 7,8% no tempo até exaustão na condição FM comparado ao CON, entretanto, essa diferença não foi estatisticamente significante. A frequência cardíaca, percepção subjetiva do esforço, fadiga percebida e eletromiografia do músculo vasto lateral aumentaram em função do tempo, sem diferença entre as condições. Com base nesses achados, pode-se concluir que a FM produz apenas um pequeno efeito deletério no exercício físico prologado e que o enxágue com CHO não era capaz de influenciar nessas condições experimentais. Possivelmente, isso se deve ao fato de ambas as intervenções estudadas (FM e enxágue com CHO) produzirem apenas pequenas alterações nas variáveis fisiológicas e perceptivas antes do exercício físico / The aim of this thesis was verify the influence of carbohydrate mouth rinse (CHO) on endurance performance after cognitive activity frequently used to induce mental fatigue. Seven health men (age: 26 ± 5 years; height: 176.0 ± 8.3 cm; weight: 73.6 ± 7.4 kg; and corporal fat: 14.3 ± 3.7%, VO2peak: 43.9 ± 6.5 ml.kg-1.min-1, Wpeak: 268.0 ± 23.8 W) performed an Incongruent Stroop to induce mental fatigue (FM) state or watched a documentary (control, CON) prior to endurance exercise. Following, they performed a workload exercise (~55%Wpeak) until exhaustion with CHO or placebo (PLA) mouth rinse (10s). In the pre-exercise, there was no significant difference for blood glucose between conditions. There was a main effect of distance for heart rate and perceived fatigue, but without interaction (P > 0.05) or condition (P > 0.05) effects. However, there was a moderate effect size for perceived fatigue (ES = 0,49), suggesting a possible relevant increase in perceived fatigue in the FM condition (75%) when compared to CON condition (60%). Although did not reach a significance level, the motivation tended (P = 0.07) to be greater in DOC condition. There was a reduction of 7.8% in time to exhaustion in FM condition compared to CON, however did not reach a significance level (P > 0.05). During exercise, the heart rate, rating perceived exertion, perception of fatigue and electromyography of the vastus lateralis increased over time (P < 0.05), but without interaction (P > 0.05) or condition (P > 0.05) effects. These results suggest that FM produce only a small deleterious effect in the prolonged physical exercise and that carbohydrate mouth rinse was not able to influence the endurance performance at all experimental conditions. Possibly, this is due to the fact of the experimental interventions (FM and carbohydrate mouth rinse) produced only discrete changes in the physiological and perceptual variables before endurance exercise

O objetivo da presente tese foi verificar a influência do enxágue bucal com carboidrato (CHO) sobre o desempenho no exercício físico predominantemente aeróbio realizado após uma atividade cognitiva frequentemente utilizada para induzir a fadiga mental. Sete homens fisicamente ativos participaram do estudo (idade: 26 ± 5 anos; estatura: 176,0 ± 8,3 cm; massa corporal: 73,6 ± 7,4 kg e gordura corporal: 14,3 ± 3,7 %, VO2 pico: 43,9 ± 6,5 ml.kg-1.min-1, Wpico: 268 ± 23,8 W) realizaram o Stroop Incongruente para indução da Fadiga Mental (FM) ou assistiam a um documentário pelo mesmo período de tempo (controle, CON). Após a tarefa eles realizaram um exercício de carga constante (~55%Wpico) até exaustão. Em cada uma das condições FM e CON os voluntários utilizavam o enxágue bucal (10s) com CHO ou placebo (PLA). No pre-exercício, não houve diferença estatisticamente significante para glicose entre as diferentes condições. A frequência cardíaca apresentou aumento após todas as intervenções, assim como a fadiga percebida (P = 0,001, ES = 0,49), mas sem efeito de condição. O effect size foi moderado para essa variável, sugerindo que o aumento na fadiga percebida foi maior na condição FM (75%) quando comparado a condição CON (60%). A motivação não apresentou diferença entre as condições. Porém, houve uma tendência (0,07) a ser maior na condição DOC. Houve uma redução de 7,8% no tempo até exaustão na condição FM comparado ao CON, entretanto, essa diferença não foi estatisticamente significante. A frequência cardíaca, percepção subjetiva do esforço, fadiga percebida e eletromiografia do músculo vasto lateral aumentaram em função do tempo, sem diferença entre as condições. Com base nesses achados, pode-se concluir que a FM produz apenas um pequeno efeito deletério no exercício físico prologado e que o enxágue com CHO não era capaz de influenciar nessas condições experimentais. Possivelmente, isso se deve ao fato de ambas as intervenções estudadas (FM e enxágue com CHO) produzirem apenas pequenas alterações nas variáveis fisiológicas e perceptivas antes do exercício físico / The aim of this thesis was verify the influence of carbohydrate mouth rinse (CHO) on endurance performance after cognitive activity frequently used to induce mental fatigue. Seven health men (age: 26 ± 5 years; height: 176.0 ± 8.3 cm; weight: 73.6 ± 7.4 kg; and corporal fat: 14.3 ± 3.7%, VO2peak: 43.9 ± 6.5 ml.kg-1.min-1, Wpeak: 268.0 ± 23.8 W) performed an Incongruent Stroop to induce mental fatigue (FM) state or watched a documentary (control, CON) prior to endurance exercise. Following, they performed a workload exercise (~55%Wpeak) until exhaustion with CHO or placebo (PLA) mouth rinse (10s). In the pre-exercise, there was no significant difference for blood glucose between conditions. There was a main effect of distance for heart rate and perceived fatigue, but without interaction (P > 0.05) or condition (P > 0.05) effects. However, there was a moderate effect size for perceived fatigue (ES = 0,49), suggesting a possible relevant increase in perceived fatigue in the FM condition (75%) when compared to CON condition (60%). Although did not reach a significance level, the motivation tended (P = 0.07) to be greater in DOC condition. There was a reduction of 7.8% in time to exhaustion in FM condition compared to CON, however did not reach a significance level (P > 0.05). During exercise, the heart rate, rating perceived exertion, perception of fatigue and electromyography of the vastus lateralis increased over time (P < 0.05), but without interaction (P > 0.05) or condition (P > 0.05) effects. These results suggest that FM produce only a small deleterious effect in the prolonged physical exercise and that carbohydrate mouth rinse was not able to influence the endurance performance at all experimental conditions. Possibly, this is due to the fact of the experimental interventions (FM and carbohydrate mouth rinse) produced only discrete changes in the physiological and perceptual variables before endurance exercise

Bakgrund:Oral mukosit (OM) är en toxisk biverkan efter högdos cytostatikabehandling (HDC) och hematopoietisk stemcellstransplantation (HSCT). OM orsakar kliniska komplikationer samt negativa följder för patienten, som längre sjukhusvistelse, oral smärta, viktförlust och parenteral nutrition (PN).Syfte:Att undersöka om det föreligger skillnad i viktförändring och nutritionsstatus hos patienter som använder munsköljmedlet, Caphosol ® i tillägg till standardbehandling i jämförelse med standardbehandling vid behandling med HDC och HSCT.Metod:En randomiserad kontrollerad öppen studie där patienter &gt; 16 år (n=40), behandlades med HDC, inför HSCT på Akademiska universitetssjukhuset, Uppsala. Patienterna randomiserades, 1:1, till oral standardbehandling och munsköljmedlet Caphosol® (EXP n=20) eller oral standardbehandling (KTR n=20). OM, oral smärta, viktförlust och dagar av PN registrerades och analyserades från baseline till 21 dagar efter avslutad HDC.Resultat:Caphosol ® hade ingen signifikant betydelse för viktförändringar mellan EXP- och KTR-grupperna. OM-smärta debuterade senare i EXP än i KTR-gruppen. KTR gruppen använde mer PN jämfört med EXP-gruppen.Konklusion:Caphosol ® hade obetydlig inverkan på förekomst, duration och svårighetsgrad av OM under HCT vid HSCT och därmed liten effekt på nutrition och vikt. Det förelåg ingen fördel att addera Caphosol ® till oral standardbehandling. / Background:Oral mucositis (OM) is a result of cytotoxic effects of high dose chemotherapy (HDCT) administered before hematopoietic stem cell transplantation (HSCT). It is a source of negative consequences for the patient, such as longer hospitalization, oral pain, weight loss, and use of parenteral nutrition (PN).Objective:To investigate whether there is differences in weight changes and nutritional status in patients receiving mouth rinse, Caphosol®, in addition to standard oral care (OC) compared to standard OC for HDCT and HSCT.Method:A randomized, controlled open study with patients &gt; 16 years, treated with HDCT before HSCT at Akademiska University Hospital, Uppsala, Sweden. Patients randomized 1:1 to standard OC and Caphosol® (EXP, n=20) or standard OC (CTR n = 20). Oral pain, weight loss and days of PN was recorded and analysed from baseline to day 21 post HDCT.Result:Caphosol ® had no significant impact on weight changes between EXP and CTR groups. OM-pain peaked later in the EXP group than in CTR. No significance in weight change between settings. CTR group had higher use of PN compared to EXP.Conclusion:Caphosol® had little effect on frequency, duration and severity of OM and thereby little effect on nutrition and weight. There was no advantage to add Caphosol ® to standard OC.

Detection of p16 through immunohistochemistry (IHC) is the standard for determining the HPV status of the tumor according the TNM eighth edition released in 2017 and has become crucial for determining the HPV status of oropharyngeal squamous cell carcinomas (OPSCC) with direct impact on staging and prognostication. In recent years, detection of HPV DNA in mouthwashes has been proposed as a noninvasive alternative, both for OPSCCs and for other head and neck squamous cell carcinomas (HNSCCs). However, the prospect of using the mouthwashes to monitor the response to therapy is unclear. To evaluate the effect of curative therapy on the detection of HPV DNA, we performed a prospective study comparing the detection frequency of high-risk HPV DNA (HR-HPV-DNA) in pre- and post-therapy mouthwashes. We collected 137 mouthwashes from 88 pathologically confirmed HNSCC patients for DNA isolation and HPV genotyping with the Inno- LiPA assay. We show that HPV DNA in pretherapeutic mouthwashes can detect HPV-driven HNSCCs with a sensitivity of 50.0% and specificity of 85.4%, alongside a high negative predictive value of 79.5% and an accuracy of 74.5%. Furthermore, we observed a notable decrease in the detection frequency of HR-HPV-DNA after successful treatment (pre-therapy 50.0% (9/18) versus post-therapy 9.7% (3/28)). However, the comparatively low sensitivity regarding detection of HPV-driven OPSCC argues against its use in clinical routine.