Pseudomonas syringae coffee blight is associated with the horizontal transfer of plasmid-encoded type III effectors.

The emergence of new pathogens is an ongoing threat to human health and agriculture. While zoonotic spillovers received considerable attention, the emergence of crop diseases is less well studied. Here, we identify genomic factors associated with the emergence of Pseudomonas syringae bacterial blight of coffee. Fifty-three P. syringae strains from diseased Brazilian coffee plants were sequenced. Comparative and evolutionary analyses were used to identify loci associated with coffee blight. Growth and symptomology assays were performed to validate the findings. Coffee isolates clustered in three lineages, including primary phylogroups PG3 and PG4, and secondary phylogroup PG11. Genome-wide association study of the primary PG strains identified 37 loci, including five effectors, most of which were encoded on a plasmid unique to the PG3 and PG4 coffee strains. Evolutionary analyses support the emergence of coffee blight in PG4 when the coffee-associated plasmid and associated effectors derived from a divergent plasmid carried by strains associated with other hosts. This plasmid was only recently transferred into PG3. Natural diversity and CRISPR-Cas9 plasmid curing were used to show that strains with the coffee-associated plasmid grow to higher densities and cause more severe disease symptoms in coffee. This work identifies possible evolutionary mechanisms underlying the emergence of a new lineage of coffee pathogens.

Rhodococcus erythropolis ATCC 4277 behavior against different metals and its potential use in waste biomining.

Rhodococcus erythropolis bacterium is known for its remarkable resistance characteristics that can be useful in several biotechnological processes, such as bioremediation. However, there is scarce knowledge concerning the behavior of this strain against different metals. This study sought to investigate the behavior of R. erythropolis ATCC 4277 against the residue of chalcopyrite and e-waste to verify both resistive capacities to the metals present in these residues and their potential use for biomining processes. These tests were carried out in a stirred tank bioreactor for 48 h, at 24ºC, pH 7.0, using a total volume of 2.0 L containing 2.5% (v/v) of a bacterial pre-culture. The pulp density of chalcopyrite was 5% (w/w), and agitation and oxygen flow rates were set to 250 rpm and 1.5 LO2 min-1, respectively. On the other hand, we utilized a waste of computer printed circuit board (WPCB) with a pulp density of 10% (w/w), agitation at 400 rpm, and an oxygen flow rate of 3.0 LO2 min-1. Metal concentration analyses post-fermentation showed that R. erythropolis ATCC 4277 was able to leach about 38% of the Cu present in the chalcopyrite residue (in ~ 24 h), and 49.5% of Fe, 42.3% of Ni, 27.4% of Al, and 15% Cu present in WPCB (in ~ 24 h). In addition, the strain survived well in the environment containing such metals, demonstrating the potential of using this bacterium for waste biomining processes as well as in other processes with these metals.

Sodium bicarbonate improved CrossFit® Benchmark Fran, but not subsequent 500 m rowing performance.

The aim of this study was to evaluate the influence of sodium bicarbonate (SB) supplementation on physical performance, neuromuscular and metabolic responses during CrossFit® exercise. Seventeen Advanced CrossFit®-trained athletes completed the randomized, double-blind, placebo-controlled crossover protocol consisting of four visits, including two familiarization sessions and two experimental trials separated by a 7-day washout period. Participants supplemented 0.3 g/kg body mass (BM) of SB or placebo 120-min prior to performing the CrossFit® benchmark Fran followed by 500 m of rowing. SB improved time to complete Fran compared to PLA (291.2 ± 71.1 vs. 303.3 ± 77.8 s, p = 0.047), but not 500 m rowing (112.1 s ± 7.9 vs. 113.2 s ± 8.9 s, p = 0.26). No substantial side-effects were reported during the trials. This study showed that SB improved CrossFit® benchmark Fran performance, but not subsequent 500-m rowing. These data suggest that SB might be an interesting supplementation strategy for CrossFit® athletes.

Impact of chronic pelvic pain and painful bladder syndrome on the Pittsburgh Sleep Quality Index on women with deep endometriosis: a cross-sectional study.

INTRODUCTION AND HYPOTHESIS: Painful bladder syndrome (PBS) is frequently associated with deep endometriosis (DE), and both conditions cause chronic pelvic pain (CPP), which often impairs sleep quality. This study was aimed at analyzing the impact of CPP plus PBS in women with DE on the global sleep quality index using the Pittsburgh Sleep Quality Index (PSQI) and subsequently examine each sleep dimension. METHODS: One hundred and forty women with DE were included and answered the PSQI and the O'Leary-Sant Interstitial Cystitis Symptoms and Problem Index questionnaires with or without CPP. Women were categorized into good or poor sleepers using the PSQI cutoff; subsequently, a linear regression model was used to analyze the PSQI score and a logistic regression model for each questionnaire's sleep component. RESULTS: Only 13% of women with DE had a good sleep. Approximately 20% of those with DE but no/mild pain were good sleepers; 138 women with DE (88.5%), 94% with PBS, and 90.5% with moderate/severe pain were poor sleepers. For PSQI components, CPP worsened the subjective sleep quality by more than threefold (p = 0.019), increased sleep disturbances by nearly sixfold (p = 0.03), and decreased the sleep duration by practically sevenfold (p = 0.019). Furthermore, PBS increased sleep disturbances by nearly fivefold (p < 0.01). CONCLUSIONS: The addition of PBS to CPP in women with DE is devastating for overall sleep quality, probably because it impacts some sleep dimensions unaffected by CPP and amplifies the problem in those already affected by pain.

The relationship between pain intensity and insomnia in women with deep endometriosis, a cross-sectional study.

PURPOSE: To investigate the relationship between pain intensity and insomnia frequency in women with a diagnosis of deep endometriosis. The hypothesis is that these patients with moderate or severe pain have a higher frequency of insomnia than those with mild or no pain. METHODS: We conducted a cross-sectional study of women with deep endometriosis categorized by pelvic pain intensity based on a numerical scale. Insomnia was assessed through a self-reported questionnaire, and multiple logistic regression was used to control for confounders between pain and insomnia. RESULTS: We included 234 women in the study, 39 (17%) without pelvic pain; 66 (29%) with mild pain; 53 (23%) moderate pain; and 76 (32%) severe pain. Twenty-nine (74%) pain-free women and 50 (75%) with mild pain had no insomnia; only 3 (8%) of the former and 3 (4%) of the latter group had severe insomnia. However, twenty-nine (55%) women with moderate pain and 37 (48%) with severe pain had insomnia. The logistic regression model showed that moderate to severe pain increased insomnia 2.8 times, twice for every 10 years of pain duration, and twice in women with low education levels. CONCLUSIONS: Women with moderate or severe pain had a high frequency of insomnia, increasing management complexity in patients with deep endometriosis. Pain intensity, pain duration, and low education level increased the chance of insomnia in those patients.

Combination of leukocyte and platelet-rich fibrin and demineralized bovine bone graft enhanced bone formation and healing after maxillary sinus augmentation: a randomized clinical trial.

BACKGROUND AND OBJECTIVE: The resorption of alveolar ridge bone and maxillary sinus pneumatization are challenges to implant-supported prosthetic rehabilitation. Bone regeneration using bone substitutes and growth factors are alternatives for maxillary sinus augmentation (MSA). Therefore, we sought to evaluate the effects of the association between leukocyte and platelet-rich fibrin (L-PRF) and deproteinized bovine bone mineral (DBBM) in MSA procedures. MATERIALS AND METHODS: Thirty-six maxillary sinuses from 24 individuals were included in this randomized clinical trial. The maxillary sinuses were randomly grafted with LPRF and DBBM (test group) or grafted only with DBBM (positive control). Dental implants were installed in the test group following two periods of evaluation: after 4 (DBBM+LPRF4) and 8 (DBBM+LPFR8) months of sinus graft healing, while the control group received implants only after 8 months. Cone beam computed tomography (CBCT) was taken 1 week after surgery (T1) and before implant placement (T2). Bone samples were collected during implant placement for histomorphometric and immunohistochemical (IHC) analysis. The primary implant stability was assessed by resonance frequency analysis. RESULTS: CBCT analysis demonstrated a significant decrease in bone volume from T1 to T2 in all groups without differences among them. Histologically, the test group showed significantly increase in bone neoformation in both periods of evaluation (LPRF+DBBM4: 44.70±14.01%; LPRF+DBBM8: 46.56±12.25%) compared to the control group (32.34±9.49%). The control group showed the highest percentage of residual graft. IHC analysis showed increased staining intensity of osteocalcin (OCN), vascular endothelial growth factor (VEGF), and runt related transcription factor 2 (RUNX-2) in LPRF+DBBM4 group, and osteopontin (OPN) in the L-PRF+DBBM8. Primary implant stability was successfully achieved (above 60 in implant stability quotient) in all the evaluated groups. CONCLUSION: Combination of L-PRF and DBBM increased and accelerated new bone formation allowing early implant placement probably due to the higher protein expression of RUNX2, VEGF, OCN, and OPN. These data suggest that the use of L-PRF might be an interesting alternative to use in combination with DBBM for augment the maxillary sinuses allowing the installation of appropriate length implants in shorter period of time. CLINICAL RELEVANCE: This study showed improvement in bone neoformation and accelerated healing when associating L-PRF and DBBM for maxillary sinus augmentation procedures. TRIAL REGISTRATION: This study was registered before participant recruitment in Brazilian Registry of Clinical Trials (ReBEC - RBR-95m73t).

Mutation in the MICOS subunit gene APOO (MIC26) associated with an X-linked recessive mitochondrial myopathy, lactic acidosis, cognitive impairment and autistic features.

BACKGROUND: Mitochondria provide ATP through the process of oxidative phosphorylation, physically located in the inner mitochondrial membrane (IMM). The mitochondrial contact site and organising system (MICOS) complex is known as the 'mitoskeleton' due to its role in maintaining IMM architecture. APOO encodes MIC26, a component of MICOS, whose exact function in its maintenance or assembly has still not been completely elucidated. METHODS: We have studied a family in which the most affected subject presented progressive developmental delay, lactic acidosis, muscle weakness, hypotonia, weight loss, gastrointestinal and body temperature dysautonomia, repetitive infections, cognitive impairment and autistic behaviour. Other family members showed variable phenotype presentation. Whole exome sequencing was used to screen for pathological variants. Patient-derived skin fibroblasts were used to confirm the pathogenicity of the variant found in APOO. Knockout models in Drosophila melanogaster and Saccharomyces cerevisiae were employed to validate MIC26 involvement in MICOS assembly and mitochondrial function. RESULTS: A likely pathogenic c.350T>C transition was found in APOO predicting an I117T substitution in MIC26. The mutation caused impaired processing of the protein during import and faulty insertion into the IMM. This was associated with altered MICOS assembly and cristae junction disruption. The corresponding mutation in MIC26 or complete loss was associated with mitochondrial structural and functional deficiencies in yeast and D. melanogaster models. CONCLUSION: This is the first case of pathogenic mutation in APOO, causing altered MICOS assembly and neuromuscular impairment. MIC26 is involved in the assembly or stability of MICOS in humans, yeast and flies.

Model to support intervention prioritization for the control of Aedes aegypti in Brazil: a multi-criteria approach.

BACKGROUND: Despite continuous strategic investments to mitigate the complexity involving arboviruses control, it is still necessary to further research methods and techniques to achieve in depth knowledge and shorter response times in the application of intervention activities. Consequently, the current work focused its efforts on the development of a multicriteria decision support model for the prioritization of prompt response activities for Aedes aegypti control, based on a case study in the city of Natal/RN. METHOD: The research was carried out in three stages: a) preliminary; b) modelling and choice; and c) finalization; the second stage was made possible by the Flexible and Interactive Tradeoff (FITradeoff) method for ranking problematic. Furthermore, the research encompassed ten actors who were involved in the model construction, eight internal and two external to the Natal Zoonoses Control Center (ZCC-Natal) as well as the observation of four operating scenarios for arboviruses control, based on transmission levels; and, evaluation of eleven alternatives from six different criteria perspectives. RESULTS: Rankings of the interventions evaluated in each of the four control operation scenarios present in the city of Natal/RN were obtained, considering technical criteria guided by the Pan American Health Organization (PAHO). CONCLUSIONS: As a result, it was developed a structured decision-making model that could help decision makers to minimize the effects and risks associated with the proliferation of the vector.

Classification of medicines and materials in hospital inventory management: a multi-criteria analysis.

BACKGROUND: In the hospital environment, to achieve an optimum level of operations and service, it is necessary to develop adequate inventory management system. Stocks can be managed, amongst other ways, through inputs classification, which is generally carried out based on a single criterion, such as monetary value, demand or criticality, which does not fully address the complexity of a hospital's inventory management system. Thus, the present study proposes a multi-criteria decision support model to help classify the stock of medicines and materials, enabling a more effective inventory management system for hospitals. METHODS: Methodologically, the study followed 3 stages: (1) preliminary phase; (2) modelling and choice phase; and (3) finalization phase. Each stage had a set of specific steps that were followed. The first stage identified the actors of the process, objectives, criteria and alternatives, establishing 5 criteria and 48 alternatives; the second stage was the choice and execution of the multi-criteria decision method to solve the problem. It was decided to use the Flexible and Interactive Tradeoff method for the sorting problematic. Finally, in the third stage, the sensitivity analysis for the developed model and the validation of the results with decision makers were carried out. In the study, 48 medicines and materials were included to validate the proposed model; however, the model could be used for more items. RESULTS: From the total of 48 medicines and hospital medical materials selected for the study, the classification of 34 of these alternatives to a single class was obtained through modelling and the other 14 alternatives were destined to two possible classes; moreover, the sensitivity analysis performed showed robust results. The items classified in class W should receive special attention by the stock manager; therefore, they should be monitored weekly. Items classified in class B should be monitored biweekly and finally, items classified in class M, should be monitored monthly. CONCLUSIONS: The classification of medicines and materials developed according to the inventory demands allowed more efficient purchasing decisions, optimizing the stock of materials and medicines at the hospital while optimizing the inventory manager's activities, saving time. Consequently, the proposed model can support the development of other multicriteria models in different hospital scenarios.

Priority setting in the Brazilian emergency medical service: a multi-criteria decision analysis (MCDA).

BACKGROUND: Despite the proven value of multicriteria decision analysis in the health field, there is a lack of studies focused on prioritising victims in the Emergency Medical Service, EMS. With this, and knowing that the decision maker needs a direction on which choice may be the most appropriate, based on different and often conflicting criteria. The current work developed a new model for prioritizing victims of SAMU/192, based on the multicriteria decision methodology, taking into account the scarcity of resources. METHODS: An expert panel and a discussion group were formed, which defined the limits of the problem, and identified the evaluation criteria for choosing a victim, amongst four alternatives illustrated from hypothetical scenarios of emergency situations-clinical and traumatic diseases of absolute priority. For prioritization, an additive mathematical method was used that aggregates criteria in a flexible and interactive version, FITradeoff. RESULTS: The structuring of the problem led the researchers to identify twenty-five evaluation criteria, amongst which ten were essential to guide decisions. As a result, in the simulation of prioritization of four requesting victims in view of the availability of only one ambulance, the proposed model supported the decision by suggesting the prioritization of one of the victims. CONCLUSIONS: This work contributed to the prioritization of victims using multicriteria decision support methodology. Selecting and weighing the criteria in this study indicated that the protocols that guide regulatory physicians do not consider all the criteria for prioritizing victims in an environment of scarcity of resources. Finally, the proposed model can support crucial decision based on a rational and transparent decision-making process that can be applied in other EMS.

A Systematic Review of CrossFit® Workouts and Dietary and Supplementation Interventions to Guide Nutritional Strategies and Future Research in CrossFit®.

CrossFit® is a high-intensity functional training method consisting of daily workouts called "workouts of the day." No nutritional recommendations exist for CrossFit® that are supported by scientific evidence regarding the energetic demands of this type of activity or dietary and supplement interventions. This systematic review performed in accordance with PRISMA guidelines aimed to identify studies that determined (a) the physiological and metabolic demands of CrossFit® and (b) the effects of nutritional strategies on CrossFit® performance to guide nutritional recommendations for optimal recovery, adaptations, and performance for CrossFit® athletes and direct future research in this emerging area. Three databases were searched for studies that investigated physiological responses to CrossFit® and dietary or supplementation interventions on CrossFit® performance. Various physiological measures revealed the intense nature of all CrossFit® workouts of the day, reflected in substantial muscle fatigue and damage. Dietary and supplementation studies provided an unclear insight into effective strategies to improve performance and enhance adaptations and recovery due to methodological shortcomings across studies. This systematic review showed that CrossFit® is a high-intensity sport with fairly homogenous anaerobic and aerobic characteristics, resulting in substantial metabolic stress, leading to metabolite accumulation (e.g., lactate and hydrogen ions) and increased markers of muscle damage and muscle fatigue. Limited interventional data exist on dietary and supplementation strategies to optimize CrossFit® performance, and most are moderate to very low quality with some critical methodological limitations, precluding solid conclusions on their efficacy. High-quality work is needed to confirm the ideal dietary and supplemental strategies for optimal performance and recovery for CrossFit® athletes and is an exciting avenue for further research.

Multi-criteria analysis in the health area: selection of the most appropriate triage system for the emergency care units in natal.

BACKGROUND: Multiobjective decision-making processes present a high degree of complexity in their solution, and tools such as multicriteria decision analysis appear as a way to facilitate the decision-makers' solution and ensure that the decision is made cohesively and efficiently. In the public health sector, decisions are even more delicate because they work not only with the direct influence of human needs, but also with limited financial resources. An important point for the emergency care units is the triage system, which consists of a pre-evaluation of the patients, classifying them according to the degree of life risk. Through triage, the patient can be attended more quickly and efficiently, streamlining the whole process. Thus, the present research endeavored to determine the most appropriate triage protocol for emergency healthcare units in Natal-RN city in Brazil and may help others less advanced countries to determine the most appropriate triage protocol for emergency healthcare. METHODS: In this study, we used the multicriteria analysis method known as FITradeoff. In addition, interviews and structured questionnaires applied with nurses, specialists and directors. RESULTS: Based on the questionnaires and preferences presented by the decision-makers, the Spanish Triage System was the most suitable protocol for the emergency care units, which presented with high ease of use and implementation. CONCLUSIONS: This study reached its main objective, which was to determine the most appropriate triage protocol. In addition, it was observed the possibility of new research, such as the development of a specific protocol for this emergency care units and the creation of an application software for this new protocol.

Low-Intensity Photobiomodulation Decreases Neuropathic Pain in Paw Ischemia-Reperfusion and Spared Nervus Ischiadicus Injury Experimental Models.

BACKGROUND: There is a wide range of animal models available today for studying chronic pain associated with a variety of etiologies and an extensive list of clinical manifestations of peripheral neuropathies. Photobiomodulation is a new tool for the treatment of pain in a convenient, noninvasive way. OBJECTIVE: The aim of this work is to elucidate the effects of infrared light-emitting diodes (LEDs) on behavioral responses to nociceptive stimuli in chronic pain models. METHODS: Forty-eight Swiss male mice weighing 25 to 35 g were used. Two chronic pain models, ischemia-reperfusion (IR) and spared spinal nerve injury, were performed and then treated with infrared LED irradiation (390 mW, 890 nm, 17.3 mW/cm2 , 20.8 J/cm2 , for 20 minutes). The behavioral tests used were a mechanical hypersensitivity test von Frey test) and a cold allodynia test (acetone test). RESULTS: The results showed that, in the IR model, the infrared LED had a significant effect on mechanical stimulation and cold allodynia on every day of treatment. In the spared nerve injury model, an analgesic effect was observed on every treatment day (when started on the 3rd and 7th days after the surgery). In both models, the effect was abolished when the treatment was interrupted. CONCLUSIONS: These findings suggest that photobiomodulation therapy may be a useful adjunct treatment for chronic pain.

FTO rs9939609 A allele influences anthropometric outcome in response to dietary intervention, but not in response to physical exercise program.

PURPOSE: The fat mass and obesity-associated (FTO) gene is involved in energy homeostasis. The A allele of the rs9939609 (SNP; T>A) is associated with obesity and higher food intake, while its effect in energy expenditure remains unclear. The aim of this study is to examine whether FTO rs9939609 is associated with the anthropometric outcomes of a physical exercise program and a dietary intervention. METHODS: We studied two independent samples. The first was composed by children and adolescents in which overweight and obese individuals were submitted to a physical exercise program (n = 136) and normal weight participants served as a control group (n = 172). The second sample was composed by obese women submitted to a hypocaloric dietary intervention (n = 126). RESULTS: Physical exercise and dietary intervention were effective, independently of genotype. We found no association of FTO rs9939609 with obesity in children and adolescents (p = 0.67). The rs9939609 affected the response to dietary intervention in obese women: A allele carriers reduced 2.7 cm less of abdominal circumference (AC) than homozygous TT (p = 0.04), while no effect was observed in response to physical exercise in overweight and obese children and adolescents. CONCLUSIONS: The A allele is associated with a worse outcome in response to the hypocaloric dietary intervention regarding abdominal circumference reduction; the same allele did not show interaction with any anthropometric outcomes in response to the exercise program applied.

Early Placement of Dental Implants in Maxillary Sinus Grafted With Leukocyte and Platelet-Rich Fibrin and Deproteinized Bovine Bone Mineral.

This case report aimed to describe the effects of leukocyte and platelet-rich fibrin (L-PRF) associated with demineralized bovine bone mineral (DBBM) and absorbable collagen membrane (CM) on bone regeneration in maxillary sinus augmentation. A 59-year-old male patient was referred to the Department of Periodontology for implant rehabilitation of his edentulous upper jaw. The treatment plan involved maxillary sinus augmentation followed by implant installations. A split-mouth design was employed in which the right maxillary sinus was filled using L-PRF, DBBM, and CM; the left side was filled with DBBM and CM. After 4 and 8 months postoperatively, 2 dental implants were installed in each of the right and left maxillary sinuses. Cone-beam computerized tomography (CBCT) was taken before and after sinus augmentation for evaluation of tridimensional bone volume alterations. Bone biopsies were harvested from the implant sites for histomorphometric evaluation. Resonance frequency analysis was employed immediately after implant placement and before prosthetic rehabilitation for evaluation of implant stability. Implants were loaded 10 months after sinus augmentation. CBCT analysis showed a higher resorption rate in the right side of the maxillary sinus (L-PRF + DBBM) compared to the left side (22.25% and 8.95%, respectively). Implant stability quotients were above 68 in all time-points for both groups. Histomorphometric analysis showed a high amount of newly formed bone when L-PRF was used compared with DBBM alone (2 118 102 and 975 535 mm3, respectively). Taken together, both techniques were effective for maxillary sinus augmentation, however the addition of L-PRF to the graft allowed early implant placement and accelerated bone healing in the conditions studied.

An overview of circulating cell-free microRNAs as putative biomarkers in Alzheimer's and Parkinson's Diseases.

Circulating cell-free microRNAs (miRNAs) are stable in many biological fluids and their expression profiles can suffer changes under different physiological and pathological conditions. In the last few years, miRNAs have been proposed as putative noninvasive biomarkers in diagnosis, prognosis and response to treatment for several diseases, including neurodegenerative disorders as Alzheimer's disease (AD) and Parkinson's disease (PD). Cognitive and/or motor impairments are usually considered for establishing clinical diagnosis, and at this stage, the majority of the neurons may already be lost making difficult attempts of novel therapies. In this review, we intend to survey the circulating cell-free miRNAs found as dysregulated in cerebrospinal fluid, serum and plasma samples in AD and PD patients, and show how those miRNAs can be useful for early and differential diagnosis. Beyond that, we highlighted the miRNAs that are possibly related to common molecular mechanisms in the neurodegeneration process, as well those miRNAs related to specific disease pathways.

Posterior tibial tendinopathy associated with matrix metalloproteinase 13 promoter genotype and haplotype.

BACKGROUND: Posterior tibial tendon (PTT) is particularly vulnerable and its insufficiency is recognized as the main cause of adult acquired flat foot. Some patients have a predisposition without a clinically recognized cause, suggesting that individual characteristics play an important role in tendinopathy. The present study investigated whether genetic variants in matrix metalloproteinases (MMPs) are associated with PTT dysfunction. METHODS: One hundred women who presented PTT dysfunction, with histopathological examination of the tendon and magnetic resonance imaging (MRI) confirming tendinopathy, as well as 100 asymptomatic women who presented intact PPT as assessed by MRI and constituting the control group, were evaluated for MMP-13 g.-77 A > G (rs2252070) polymorphism, individually and in haplotypes, as well as in combination with MMP-1 g.-519 A > G (rs1144393), MMP-1 g.-1607 G > GG (rs1799750) and MMP-8 g.-799 C > T (rs11225395) polymorphisms with PTT dysfunction. Genomic DNA was extracted from the saliva and genotypes were obtained by polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis of the results included a Mann-Whitney U-test, Fisher's exact test, multiple logistic regression, chi-squared and SNPstats software (http://bioinfo. iconcologia.net/snpstats/start.htm). p < 0.05 was considered statistically significant. RESULTS: The A allele frequency (MMP-13 g.-77 A > G (rs2252070) polymorphism) was significantly higher in the case group (76% and 61%, respectively; p = 0.010, odds ratio = 2.02; 95% confidence interval = 1.32-3.12). The genotype distribution was also significantly different between groups (p = 0.001, odds ratio = 2.82; 95% confidence interval = 1.58-5.02). Global haplotype analysis indicated a significant difference between both groups. CONCLUSIONS: In conclusion, these findings indicate that MMP-13 g.-77 A > G (rs2252070) polymorphism individually, as well as its haplotypes MMP-1 g.-519 A > G (rs1144393), MMP-1 g.-1607 G > GG (rs1799750) and MMP-8 g.-799 C > T (rs11225395), may contribute to PTT dysfunction.

CRF receptor type 1 (but not type 2) located within the amygdala plays a role in the modulation of anxiety in mice exposed to the elevated plus maze.

The amygdala (Amy) is an important center that processes threatening stimuli. Among the neurotransmitters implicated in the control of emotional states, the corticotrophin releasing factor (CRF) is an important modulator, acting at CRF1 and CRF2 receptors. Few studies have investigated the role of CRF and its receptors in the Amy on anxiety in mice. Here, we investigated the effects of intra-Amy (aimed at the basolateral nucleus) injections of CRF (37.5 and 75pmol/0.1µl), urocortin 3 (UCn3, a selective CRF2 agonist; 4, 8, 16 or 24pmol/0.1µl), CP376395 (a selective CRF1 antagonist; 0.375, 0.75 or 1.5nmol/0.1µl), antisauvagine-30 (ASV-30, a selective CRF2 antagonist; 1 or 3nmol/0.1µl) on the behavior of mice exposed to the elevated plus maze (EPM). Both spatiotemporal (e.g., percentage of open-arm entries and percentage of open-arm time; %OE and %OT) and complementary [e.g., frequency of protected and unprotected stretched attend postures (pSAP and uSAP) and head dips (pHD and uHD); frequency and time spent on open arm end exploration (OAEE)] measures were recorded during a 5-min test in the EPM. While intra-Amy injections of CRF decreased %OE, %OT and OAEE, suggesting an anxiogenic-like action, UCn3 (all doses) did not change any behavior. In contrast, injections of CP376395 (0.75nmol) produced an anxiolytic-like effect, by increasing %OT and OAEE and decreasing pSAP and pHD. Neither spatiotemporal nor complementary measures were changed by intra-Amy ASV-30. These results suggest that CRF plays a marked anxiogenic role at CRF1 receptors in the amygdala of mice exposed to the EPM.