Heme metabolism in Strigomonas culicis: Implications of H2O2 resistance induction and symbiont elimination.

Monoxenous trypanosomatid Strigomonas culicis harbors an endosymbiotic bacterium, which enables the protozoa to survive without heme supplementation. The impact of H2O2 resistance and symbiont elimination on intracellular heme and Fe2+ availability was analyzed through a comparison of WT strain with both WT H2O2-resistant (WTR) and aposymbiotic (Apo) protozoa. The relative quantification of the heme biosynthetic pathway through label-free parallel reaction monitoring targeted mass spectrometry revealed that H2O2 resistance does not influence the abundance of tryptic peptides. However, the Apo strain showed increased coproporphyrinogen III oxidase and ferrochelatase levels. A putative ferrous iron transporter, homologous to LIT1 and TcIT from Leishmania major and Trypanosoma cruzi, was identified for the first time. Label-free parallel reaction monitoring targeted mass spectrometry also showed that S. culicis Iron Transporter (ScIT) increased 1.6- and 16.4-fold in WTR and Apo strains compared to WT. Accordingly, antibody-mediated blockage of ScIT decreased by 28.0% and 40.0% intracellular Fe2+concentration in both WTR and Apo strains, whereas no effect was detected in WT. In a heme-depleted medium, adding 10 µM hemin decreased ScIT transcript levels in Apo, whereas 10 µM PPIX, the substrate of ferrochelatase, increased intracellular Fe2+ concentration and ferric iron reduction. Overall, the data suggest mechanisms dependent on de novo heme synthesis (and its substrates) in the Apo strain to overcome reduced heme availability. Given the importance of heme and Fe2+ as cofactors in metabolic pathways, including oxidative phosphorylation and antioxidant systems, this study provides novel mechanistic insights associated with H2O2 resistance in S. culicis.

Synthesis and activity of benzimidazole N-Acylhydrazones against Trypanosoma cruzi, Leishmania amazonensis and Leishmania infantum.

In this study, we present the design, synthesis, and cytotoxic evaluation of a series of benzimidazole N-acylhydrazones against strains of T. cruzi (Y and Tulahuen) and Leishmania species (L. amazonensis and L. infantum). Compound (E)-N'-((5-Nitrofuran-2-yl)methylene)-1H-benzo[d]imidazole-2-carbohydrazide demonstrated significant activity against both trypomastigote and amastigote forms (Tulahuen strain), with an IC50/120 h of 0.033 µM and a selectivity index (SI) of 7680. This represents a potency 46 times greater than that of benznidazole (IC50/120 h = 1.520 µM, SI = 1390). Another compound (E)-N'-(2-Hydroxybenzylidene)-1H-benzo[d]imidazole-2-carbohydrazide showed promising activity against both trypomastigote and amastigote forms (Tulahuen strain), with an IC50/120 h of 3.600 µM and an SI of 14.70. However, its efficacy against L. infantum and L. amazonensis was comparatively lower. These findings provide valuable insights for the development of more effective treatments against Trypanosoma cruzi.

Secondary bruxism: A valid diagnosis or just a coincidental finding of additional masticatory muscle activity? A narrative review of literature.

INTRODUCTION: Bruxism is defined as a repetitive masticatory muscle activity that can manifest it upon awakening (awake bruxism-AB) or during sleep (sleep bruxism-SB). Some forms of both, AB and SB can be associated to many other coexistent factors, considered of risk for the initiation and maintenance of the bruxism. Although controversial, the term 'secondary bruxism' has frequently been used to label these cases. The absence of an adequate definition of bruxism, the non-distinction between the circadian manifestations and the report of many different measurement techniques, however, are important factors to be considered when judging the literature findings. The use (and abuse) of drugs, caffeine, nicotine, alcohol and psychoactive substances, the presence of respiratory disorders during sleep, gastroesophageal reflux disorders and movement, neurological and psychiatric disorders are among these factors. The scarcity of controlled studies and the complexity and interactions among all aforementioned factors, unfortunately, does not allow to establish any causality or temporal association with SB and AB. The supposition that variables are related depends on different parameters, not clearly demonstrated in the available studies. OBJECTIVES: This narrative review aims at providing oral health care professionals with an update on the co-risk factors and disorders possibly associated with bruxism. In addition, the authors discuss the appropriateness of the term 'secondary bruxism' as a valid diagnostic category based on the available evidence. CONCLUSION: The absence of an adequate definition of bruxism, the non-distinction between the circadian manifestations and the report of many different measurement techniques found in many studies preclude any solid and convincing conclusion on the existence of the 'secondary' bruxism.

Benefits of the combination of digital and analogic tools as a strategy to control possible awake bruxism: A randomised clinical trial.

BACKGROUND: Awake Bruxism (AB) management includes cognitive and behavioural changes. Digital and analogic tools can be used to remind the individual to control/avoid AB behaviours. However, no study addressed both tools together. OBJECTIVE: To compare the efficacy of the combination of digital (smartphone application) and analogic (adhesive reminders) tools versus digital tool alone for AB management. METHODS: Seventy-two individuals diagnosed with probable AB were divided into 3 groups: Group 1 (n = 24), used both digital and analogic tools during 30 days; Group 2 (n = 24), used only a digital tool during 30 days and Group 3 (n = 24), used only a digital tool for the first 15 days and then added the analogic tool for 15 days. The AB frequency was measured in real-time with a smartphone app, which sent alerts asking the individuals if they were doing any AB behaviours (bracing, teeth contact, clenching or grinding). Groups were compared using one-way ANOVA and before-after adding an analogic tool (group 3) by paired t-test, considering α = 0.05. RESULTS: All groups showed a decrease in AB behaviours at the end of the evaluation period. Group 1 (digital and analogic tools) showed the lowest average of AB behaviours among all groups; however, statistically significant differences were found only for the comparison between groups 1 and 2. In group 3, a significantly greater reduction in AB behaviours was found after combining both approaches. CONCLUSION: The combination of digital and analogic tools showed the greatest reduction of AB frequency and can be recommended for AB control.

Association between obstructive sleep apnea and temporomandibular disorders: A meta-analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is a very common condition in patients with temporomandibular disorders (TMD). However, there is little evidence of a connection between them. OBJECTIVE: The aim of this systematic review and meta-analysis is to assess the association between OSA and TMD in adult population. METHODS: Case-control, cross-sectional and cohort studies on the association between TMD and OSA were searched in the EMBASE, LILACS, LIVIVO, PubMed/MEDLINE, Scopus, Web of Science, Google Scholar, Open Grey and Pro Quest databases. TMD should be assessed using Research Diagnostic Criteria (RDC/TMD) or Diagnostic Criteria (DC/TMD) and OSA using polysomnography (PSG) and/or a validated questionnaire. The risk of bias was evaluated using the Joanna Briggs Institute Critical Assessment Checklists; and an association meta-analysis was performed. The effect measure included the odds ratio (OR) in dichotomous variables and a 95% confidence interval (CI). Certainty of evidence was determined by analysing groups using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Out of the 1024 articles screened, 7 met the inclusion criteria for the qualitative synthesis, and 6 for quantitative analysis. All articles were classified at low risk of bias. A positive association with OSA was found in patients with TMD (OR = 2.61; 95% CI = 2.31, 2.95). A significant association was also found irrespective to the OSA diagnostic methods applied (for studies using PSG + validated questionnaires: OR = 2.74; 95% CI = 2.11, 3.57; for studies using validated questionnaires only: OR = 2.55; 95% CI = 2.22, 2.92). GRADE was moderate. CONCLUSION: Patients with TMD presented a significant association with OSA regardless of the OSA diagnostic method (PSG and/or validated questionnaires). OSA screening should be part of the TMD examination routine. Furthermore, due to the different OSA assessment methods used and the small number of studies included, there is a need to include a larger number of studies using PSG to better elucidate this association.

Assessment of awake bruxism and oral mucosa indentation in adolescents.

BACKGROUND: Oral mucosa indentations can be signs of awake bruxism (AB) in adults, but this association has not yet been verified in adolescents. OBJECTIVES: To evaluate the frequency of AB in adolescents and determine whether there is an association between AB and oral mucosa indentation. METHODS: This study enrolled 66 high school students, mean age of 16.9 (±0.54) years. Clinical inspection was performed to assess the presence or absence of tongue, cheek and lip mucosa indentation. AB was assessed by the Ecological Momentary Assessment method using the WhatsApp mobile app. Messages were sent 15 times a day, 7 days, between 8:00 AM and 7:00 PM at random times to choose one of the five oral behaviours: teeth contact, teeth clenching, teeth grinding, mandible bracing and relaxed jaw muscles. The non-parametric Mann-Whitney U-test for independent samples, Friedman test for paired samples, Friedman pairwise multiple comparisons non-parametric test, Pearson's chi-squared tests, and z-test of comparisons between two proportions were performed (p < .05). RESULTS: During the week the frequency of AB behaviours was 56.20%, teeth contact was the most frequent (37.68% ± 22.26%), significantly more frequent than other AB behaviours; there was a greater frequency of cheek indentation (27.27%) and no difference between genders in oral behaviours and indentations (p > .05). A higher frequency of AB behaviours was observed in individuals with a greater frequency of cheek indentation (p < .05). CONCLUSIONS: Teeth contact and cheek indentation were the most frequent conditions among adolescents and AB behaviours are associated with this indentation.

Cytotoxicity and Genotoxicity Evaluation of Zanthoxylum rhoifolium Lam and In Silico Studies of Its Alkaloids.

The alkaloids isolated from Zanthoxylum rhoifolium have demonstrated great pharmacological potential; however, the toxic profiles of these extracts and fractions are still not well elucidated. This study evaluated the toxicity of the ethanol extract (EEZR) and neutral (FNZR) and alkaloid (FAZR) fractions. Chemical characterization was performed by chromatographic methods: thin-layer chromatography (TLC) and high-performance liquid chromatography coupled with diode array detection (HPLC-DAD). The cytotoxicity of the samples was evaluated in human hepatocellular carcinoma (HepG2) cells using the cell viability method (MTT) and mutagenicity by the Allium cepa assay (ACA). Alkaloids isolated from the species were selected for toxicity prediction using preADMET and PROTOX. The molecular docking of the topoisomerase II protein (TOPOII) was used to investigate the mechanism of cell damage. In the EEZR, FNZR, and FAZR, the presence of alkaloids was detected in TCL and HPLC-DAD analyses. These samples showed a 50% inhibitory concentration (IC50) greater than 400 µg/mL in HepG2 cells. In ACA, time- and concentration-dependent changes were observed, with a significant reduction in the mitotic index and an increase in chromosomal aberrations for all samples. Nuclear sprouts and a micronucleus of the positive control (PC) were observed at 10 µg/mL and in the FAZR at 30 µg/mL; a chromosomal bridge in FNZR was observed at 105 µg/mL, CP at a concentration of 40 µg/mL, and nuclear bud and mitotic abnormalities in the EEZR were observed at 170 µg/mL. The alkaloids with a benzophenanthridine were selected for the in silico study, as structural alterations demonstrated certain toxic effects. Molecular docking with topo II demonstrated that all alkaloids bind to the protein. In summary, the fractionation of Z. rhoifolium did not interfere with toxicity; it seems that alkaloids with a benzophenanthridine nucleus may be involved in this toxicity.

Risk factors for non-specific low back pain in older people: a systematic review with meta-analysis.

PURPOSE: To conduct a systematic review about risk factors associated with non-specific low back pain (LBP) in older people. METHODS: The study protocol was prospectively registered with Prospero (CRD42020191619). This systematic review with meta-analysis included cohort studies that investigated risk factors for LBP in older people. The following databases were searched up to 12 December 2020: MEDLINE (Ovid), Embase, CINAHL, SCOPUS and Web of Science. Two independent reviewers appraised methodological quality using the Critical Appraisal Checklist for Cohort Studies instrument. RESULTS: We identified 3939 potentially relevant publications. After removing duplicates, screening title, and abstracts, we assessed 86 publications in full text. We included the remaining 11 publications for analysis. There is strong evidence that depressive symptoms are a risk of reporting future back pain onset (I2 = 52,7%, Odds ratio 1.4, CI 1.28-1.53). CONCLUSION: Depressive symptoms are a risk factor for LBP in older people. Due to the limitations of the literature, the role of some risk factors remains unclear. An additional high-quality prospective cohort is needed to better elucidate these relationships.

Research routes on improved sleep bruxism metrics: Toward a standardised approach.

A recent report from the European Sleep Research Society's task force "Beyond AHI" discussed an issue that has been a long-term subject of debate - what are the best metrics for obstructive sleep apnoea (OSA) diagnosis and treatment outcome assessments? In a similar way, sleep bruxism (SB) metrics have also been a recurrent issue for >30 years and there is still uncertainty in dentistry regarding their optimisation and clinical relevance. SB can occur alone or with comorbidities such as OSA, gastroesophageal reflux disorder, insomnia, headache, orofacial pain, periodic limb movement, rapid eye movement behaviour disorder, and sleep epilepsy. Classically, the diagnosis of SB is based on the patient's dental and medical history and clinical manifestations; electromyography is used in research and for complex cases. The emergence of new technologies, such as sensors and artificial intelligence, has opened new opportunities. The main objective of the present review is to stimulate the creation of a collaborative taskforce on SB metrics. Several examples are available in sleep medicine. The development of more homogenised metrics could improve the accuracy and refinement of SB assessment, while moving forward toward a personalised approach. It is time to develop SB metrics that are relevant to clinical outcomes and benefit patients who suffer from one or more possible negative consequences of SB.

Urinary symptoms in older people with low back pain: Prevalence, clinical, and functional factors associated.

AIMS: To identify the prevalence, clinical and functional factors associated with urinary symptoms (US) in community-dwelling older adults with acute low back pain (LBP). METHODS: This was a cross-sectional study of data's baseline of Back Complaints in the Elders Consortium. All elders had LPB heightened. We analyzed data on urinary symptoms, intensity of pain (Numerical Rating Scale (NRS), disability (Roland Morris [RM]), depressive symptoms (CES-D), and gait speed (m/s) in the Brazilian older adults. The sample was of 586 consecutive participants of BACE-Study. Ethical approval was obtained. In addition to the prevalence analysis, logistic regression analysis was performed. RESULTS: The prevalence of US was 18.4% and were associated with CES-D (odds ratio [OR] = 2.84; 95% confidence interval [CI] 1.66-4.86), slower gait speed (OR = 0.33; 95% CI 0.14-0.78), and LBP-related disability (OR = 1.09; 95% CI 1.04-1.13) after adjusting for radiculophaty and other confounding factors. CONCLUSIONS: In community-dwelling older people with LBP, US were associated with depressive symptoms, gait speed, and disability. Our findings may provide a new framework for US management with respect to clinical and functional capacity. Specific physical examinations should be encouraged to assess the with acute LBP and US. Others factors can be associated with US in elders with LBP.

Pain complications of oral implants: Is that an issue?

The use of oral implants as a form of replacing missing teeth in partial or total edentulous patients is considered the gold standard in oral rehabilitation. Although considered a history of success in contemporary dentistry, surgical complications may occur, as excessive bleeding, damage to the adjacent teeth and mandibular fractures. Persistent pain and abnormal somatosensory responses after the surgery ordinary healing time are also potential problems and may lead to the development of a condition named posttraumatic trigeminal neuropathic pain (PTNP). Though relatively rare, PTNP has a profound impact on patient's quality of life. Appropriated previous image techniques, effective anaesthetic procedures and caution during the surgical procedure and implant installation are recommended for the prevention of this condition. In case of the PTNP, different management modalities, including antidepressant and membrane stabilizer medications, as well as peripheral strategies, as the use of topical medication and the botulin toxin are presented and discussed.

Non-Targeted Self-Measurement of Blood Pressure: Association with Self-Medication, Unscheduled Emergency Visits and Anxiety.

Background and Objective: The routine practice of self-medication of blood pressure (BP) not oriented with pulse devices may not be precisely useful in the control of BP and can lead the patient to self-medicate in error. Thus, we need to evaluate the non-oriented self-assessment of BP in real-life circumstances in hypertensive patients. The objective of this study was to evaluate in hypertensive patients the association of BP self-measurement with its control, as well as the presence of anxiety disorders, the occurrence of unscheduled visits to the emergency room, and self-medication. Materials and Methods: An observational study was carried out with 1000 hypertensive volunteers (age: 61.0 ± 12.5). Using a questionnaire, sociodemographic and clinical data on BP control were collected. Anxiety was assessed by the State-Trait Anxiety Inventory (STAI). Results: The group that performed non-oriented self-measurement of BP, showed that they had higher frequencies of self-medication (57.9%, p < 0.05) and more unscheduled visits to the emergency room (68%, p < 0.05). In addition, a lower level of BP control (46.8%, p < 0.05) was associated with higher levels of anxiety (52.3%, p < 0.05) in the group that performed non-oriented self-measurements of BP. Conclusion: The practice of non-oriented self-assessment of BP was associated with negative factors such as high levels of anxiety and higher frequencies of self-medication and unscheduled emergency visits.

Wake-Up Headache Is Associated With Sleep Bruxism.

OBJECTIVE: To investigate the relationship between the frequency of sleep bruxism and report of morning headaches, and associations with depression and/or anxiety. BACKGROUND: The association between sleep bruxism and headaches in the morning, and between these factors and affective disorders, has been examined in several investigations. Although headache is cited by the International Classification of Sleep Disorders as a symptom associated with sleep bruxism, only a small number of studies have investigated the association between the frequencies of headaches in the morning and bruxism. METHODS: This was a cross-sectional observational study conducted between August 2017 and May 2018 in the municipality of Curitiba, Brazil. It comprised individuals of both sexes, ages between 18 and 65 years, with no restriction of race, skin color, or social group (n = 149). Structured questionnaires were used to survey demographic characteristics, sleep bruxism, depression, and anxiety. Self-reports and clinical examinations were used together to diagnose probable sleep bruxism and assess the frequency of this condition. The presence or absence of morning headaches and their frequency were evaluated using a self-report question. It was applied to people with anxiety and/or depression and to free controls of the general population by a trained dentist. RESULTS: A significant relationship (P Ë‚ .001 - Chi-square test) was found between the frequency of sleep bruxism and morning headaches. Symptoms of depression and anxiety were associated with the presence of headache (P Ë‚ .001 - One way ANOVA), but not with the frequency of sleep bruxism. CONCLUSION: The present study confirms the hypothesis of a direct relationship between the frequency of sleep bruxism and the frequency of morning headaches. It also confirmed a linear association between mean depression scores, mean anxiety scores, and morning headaches.

Meeting Physical Activity Guidelines by Walking in Older Adults From Three Middle-Income Countries: A Cross-Sectional Analysis From the International Mobility in Aging Study.

Physical activity (PA) among older adults is understudied in middle-income countries. The authors examined the associations of factors across levels of the social ecological model (individual, interpersonal, organizational, and community) with older adults meeting guidelines of 150 min of moderate- to vigorous-intensity PA per week through walking in three middle-income countries: Albania (n = 387), Colombia (n = 404), and Brazil (n = 402). Using 2012 International Mobility in Aging Study data, multivariate logistic regression models identified the following significant associations with meeting PA guidelines through walking (a) individual level: depression (odds ratio [OR] = 0.62, 95% confidence interval, CI [0.45, 0.86]), being female (OR = 0.74, 95% CI [0.56, 0.998]), and high relative education (OR = 1.79, 95% CI [1.33, 2.41]) and (b) interpersonal level: high life partner (OR = 1.38, 95% CI [1.04, 1.83]) and friend social ties (OR = 1.39, 95% CI [1.05, 1.83]). While individual and interpersonal variables were associated with meeting PA guidelines, community-level social and environmental variables were not.

Botulinum toxin type A applications for masticatory myofascial pain and trigeminal neuralgia: what is the evidence regarding adverse effects?

OBJECTIVES: The objective of the study was to conduct a systematic review of literature assessing botulinum toxin type A (BoNT-A) safety and adverse effects in the treatment of myofascial pain (MFP) and trigeminal neuralgia (TN). MATERIALS AND METHODS: The search for articles by two specific researchers involved the PubMed, EMBASE, Web of Science, and Scopus databases. Specific terms were used, and no publication time and language restrictions were applied. Clinical trials that investigated the effects of BoNT-A among participants with myofascial pain in masticatory muscles or trigeminal neuralgia were considered eligible for this systematic review. Data for each study were extracted and analyzed according to a PICO-like structured reading. RESULTS: The search strategy provided 436 citations. After analysis, 16 citations were included, seven for MFP and nine for TN. In all studies, BoNT-A was well tolerated and improved pain. The most common adverse effects were temporary regional weakness, tenderness over the injection sites, and minor discomfort during chewing. Most studies reported a spontaneous resolution of adverse effect. CONCLUSIONS: It can be concluded that BoNT-A treatment is well tolerated, since minor adverse effects were the most frequently reported; however, it is recommended that future studies aim to assess the safety and possible adverse effects of multiples applications or high doses of this treatment. CLINICAL RELEVANCE: BoNT-A has been increasingly diffused in dentistry, being used for the management of masticatory myofascial pain and trigeminal neuralgia. Nonetheless, there is no consensus about its efficacy and adverse effects that could occur when this treatment is applied.

Bruxism: An umbrella review of systematic reviews.

OBJECTIVES: To synthesise available knowledge about both sleep (SB) and awake bruxism (AB) as depicted by previous published systematic reviews (SR). METHODS: SR investigating any bruxism-related outcome were selected in a two-phase process. Searches were performed on seven main electronic databases and a partial grey literature search on three databases. Risk of bias of included SR was assessed using the "University of Bristol's tool for assessing risk of bias in SR". RESULTS: From 1038 studies, 41 SR were included. Findings from these SR suggested that (a) among adults, prevalence of AB was 22%-30%, SB (1%-15%), and SB among children and adolescents (3%-49%); (b) factors consistently associated with bruxism were use of alcohol, caffeine, tobacco, some psychotropic medications, oesophageal acidification and second-hand smoke; temporomandibular disorder signs and symptoms presented a plausible association; (c) portable diagnostic devices showed overall higher values of specificity (0.83-1.00) and sensitivity (0.40-1.00); (d) bruxism might result in biomechanical complications regarding dental implants; however, evidence was inconclusive regarding other dental restorations and periodontal impact; (e) occlusal appliances were considered effective for bruxism management, although current evidence was considered weak regarding other therapies. CONCLUSIONS: Current knowledge from SR was mostly related to SB. Higher prevalence rates were found in children and adolescents than in adults. Associated factors and bruxism effects on stomatognathic structures were considerably heterogeneous and inconsistent. Overall good accuracy regarding portable diagnostic devices was found. Interventions' effectiveness was mostly inconclusive regarding the majority of available therapies, with the exception of occlusal appliances.

Placebo and nocebo response magnitude on temporomandibular disorder-related pain: A systematic review and meta-analysis.

OBJECTIVES: The aim of this systematic review (SR) was to answer the following question: "In adult patients with temporomandibular disorder (TMD)-related pain, what is the placebo or nocebo effect of different therapies?" METHODS: A SR was performed with randomised clinical placebo-controlled trials on diagnosed painful TMD studies from five main databases and from three grey literature. Studies included must have sample older than 18 years, with painful TMD, which diagnosis was done by Research Diagnostic Criteria (RDC/TMD) or Diagnostic Criteria (DC/TMD). RESULTS: Out of 770 articles obtained, 42 met the inclusion criteria for qualitative and 26 for quantitative analysis. Meta-analysis indicated mean variation on pain intensity for placebo therapy was higher on laser acupuncture with 45.5 mm point reduction, followed by avocado soya bean extract with 36 mm and amitriptyline 25 mg with 25.2 mm. Laser showed a 29% of placebo effect, as well medicine with 19% and other therapies with 26%. Possible nocebo effect of 8% pain increase was found for intra-articular injection of Ultracain. CONCLUSIONS: Based on the available data, the placebo response could play a major effect on TMD pain management and may be responsible from 10% to 75% of pain relief. Laser acupuncture, avocado soya bean and amitriptyline promoted the higher placebo effect. Possible nocebo effect was found only for Ultracain injection with 8%. CLINICAL RELEVANCE: Clinicians could apply such evidence to optimise pain management and judgement about treatment efficacy, and researches may find it useful when designing their investigations.

Association between sleep bruxism and anxiety symptoms in adults: A systematic review.

BACKGROUND: The purpose of this systematic review was to evaluate the association between sleep bruxism (SB) and anxiety symptoms in adults. METHODS: A systematic review was performed and studies assessing SB by means of questionnaires, clinical examination and/or polysomnography (PSG), and validated questionnaires to assess anxiety, were included. Search strategies were developed for seven main electronic databases. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies, and confidence in cumulative evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation criteria. RESULTS: Eight cross-sectional studies were included, of which five were judged with low and three with moderate risk of bias. No association with SB was observed in three studies that investigated generic levels of anxiety, while other two papers that evaluated generic anxiety levels through the State-Trait Anxiety Inventory (STAI) found a positive association with probable and definite SB in both STAI-1 and STAI-2 subscales. Only one study evaluated dental anxiety in particular and an association with probable SB was observed regarding very anxious or extremely anxious scores. Two studies assessed specific symptoms of anxiety using the panic-agoraphobic spectra evaluation (PAS-SR) questionnaire. Significantly higher PAS-SR total scores were observed in both studies with regard to SB. No study with definitive assessment of SB was identified. CONCLUSION: Current literature is controversial regarding an association between SB and generic symptoms of anxiety in adults. It seems that some specific symptoms of the anxiety disorders spectrum might be associated with probable SB.

TrypanocidalActivity of Natural Sesquiterpenoids Involves Mitochondrial Dysfunction, ROS Production and Autophagic Phenotype in Trypanosomacruzi.

Chagas disease is a neglected tropical disease that is caused by the protozoan Trypanosomacruzi and represents a serious health problem, especially in Latin America. The clinical treatment of Chagas disease is based on two nitroderivatives that present severe side effects and important limitations. In folk medicine, natural products, including sesquiterpenoids, have been employed for the treatment of different parasitic diseases. In this study, the trypanocidal activity of compounds isolated from the Chilean plants Drimys winteri, Podanthus mitiquiand Maytenus boaria on three T. cruzi evolutive forms (epimastigote, trypomastigote and amastigote) was evaluated. Total extracts and seven isolated sesquiterpenoids were assayed on trypomastigotes and epimastigotes. Polygodial (Pgd) from D. winteri, total extract from P. mitiqui (PmTE) and the germacrane erioflorin (Efr) from P. mitiqui were the most bioactive substances. Pgd, Efr and PmTE also presented strong effects on intracellular amastigotes and low host toxicity. Many ultrastructural effects of these substances, including reservosome disruption, cytosolic vacuolization, autophagic phenotype and mitochondrial swelling (in the case of Pgd), were observed. Flow cytometric analysis demonstrated a reduction in mitochondrial membrane potential in treated epimastigotes and an increase in ROS production and high plasma membrane permeability after treatment with Pgd. The promising trypanocidal activity of these natural sesquiterpenoids may be a good starting point for the development of alternative treatmentsforChagas disease.

Age at First Birth, Parity and History of Hysterectomy Are Associated to Frailty Status: Cross-Sectional Analysis from the International Mobility in Aging Study -Imias.

Frailty at older ages is an adverse health condition that is more prevalent in women than men and the excess prevalence in women cannot be adequately explained by common risk factors. Reproductive history events may be among contributing factors. This study aims to examine associations between age at first childbirth, lifetime parity, and history of hysterectomy with frailty status in community dwelling older women. This is a cross-sectional study of 1047 women participating in the International Mobility in Aging Study at baseline (2012, aged between 65 and 74 years old). Fried's phenotype of frailty was used to identify frail, pre-frail and non-frail groups. Measured reproductive history variables include age at first birth (before 20 years old; 20 years old or older), lifetime parity (0; 1-2 children; 3-4 children; 5 children or more) and hysterectomy (yes/no). We constructed multinomial regression models adjusted for possible confounders to examine the relationships of interest; non frail women were the reference category. Early maternal age (before 20 years-old) was associated with increased risk of frailty (OR 2.15, 95%CI: 1.24-3.72). Compared to women who delivered five or more children, those who had 1-2 children showed significantly lower odds of pre-frail status (OR 0.54, 95%CI 0.36-0.82) and frailty (OR 0.43 95%CI 0.22-0.86). Hysterectomy was independently associated with frailty (OR 1.74 95%CI 1.04-2.89) Age at first birth, parity and hysterectomy are associated to a greater likelihood of frailty in later life. This study reinforces the importance of considering the reproductive characteristics of women as indicators of health status.