[Translated article] A systematic review of the literature: The use of metaphyseal sleeves in revision total knee arthroplasty.

BACKGROUND AND OBJECTIVES: The purpose of this study is to analyse the indications, complications, survivorship and clinical/functional outcome of metaphyseal sleeves as a treatment option in revision total knee arthroplasty. MATERIAL AND METHOD: A systematic review was made following the PRISMA recommendations on the use of metaphyseal sleeves for revision total knee arthroplasty. We included prospective and retrospective studies published in the last 10 years looking at implant survivorship, clinical and functional outcome with a minimum follow-up of 2 years. RESULTS: The included studies showed good both functional and clinical outcomes. The overall reoperation rate was 16.2%, with an overall survival rate of 92.2% and aseptic survivorship of 98.2%. CONCLUSIONS: Metaphyseal sleeves are a good treatment option for this surgery, especially in AORI II or III type bone defects, achieving good intraoperative and primary stability of the implant, with good and rapid osseointegration.

A systematic review of the literature: The use of metaphyseal sleeves in revision total knee arthroplasty. / Una revisión sistemática de la literatura: el uso de vainas metafisarias en cirugía de revisión de artroplastia de rodilla.

BACKGROUND AND OBJECTIVES: The purpose of this study is to analyze the indications, complications, survivorship and clinical/functional outcome of metaphyseal sleeves as a treatment option in revision total knee arthroplasty. MATERIAL AND METHOD: A systematic review was made following the PRISMA recommendations on the use of metaphyseal sleeves for revision total knee arthroplasty. We included prospective and retrospective studies published in the last 10 years looking at implant survivorship, clinical and functional outcome with a minimum follow-up of 2 years. RESULTS: The included studies showed good both functional and clinical outcomes. The overall reoperation rate was 16.2%, with an overall survival rate of 92.2% and aseptic survivorship of 98.2%. CONCLUSIONS: Metaphyseal sleeves are a good treatment option for this surgery, especially in AORI II or III type bone defects, achieving good intraoperative and primary stability of the implant, with good and rapid osseointegration.

[Translated article] Has the COVID-19 lockdown influenced the mortality of hip fracture? Analysis of one-year mortality.

INTRODUCTION AND OBJECTIVES: The main objective of this study is to analyse the one-year mortality in patients with intracapsular hip fracture who were admitted during severe social confinement in the first months of the COVID-19 lockdown and compare it with previous years. MATERIAL AND METHODS: Retrospective observational study in which a cohort from March 14 to June 21, 2020 (pandemic group, n=62) was compared with a control cohort on the same dates in the years 2017, 2018 and 2019 (control group, n=172). Thirty-day-mortality and one-year-mortality, orthopaedic complications, ASA grade, comorbidities, diagnosis and treatment, time to surgery and mean stay were measured. RESULTS: No significant differences were found in 30-day mortality (p=0.156; 9.7% compared to 4.7%) or in one-year mortality (p=0.47) between the pandemic group (21%) and the control one (16.9%). A decrease in surgical delay and mean stay was observed in the pandemic group, although without statistical significance. CONCLUSION: The State of Alarm modified the distribution of the type of hip fracture with a predominance of intracapsular fracture. Maintaining the same hospital management as prior to the pandemic period made it possible not to increase 30-day mortality and one-year mortality in patients with intracapsular hip fracture.

Has the COVID-19 lockdown influenced the mortality of hip fracture? Analysis of one-year mortality. / ¿Ha influido el confinamiento social por COVID-19 en la mortalidad de la fractura de cadera? Análisis de la mortalidad al año.

INTRODUCTION AND OBJECTIVES: The main objective of this study is to analyze the one-year mortality in patients with intracapsular hip fracture who were admitted during severe social confinement in the first months of the COVID-19 lockdown and compare it with previous years. MATERIAL AND METHODS: Retrospective observational study in which a cohort from March 14 to June 21, 2020 (pandemic group, n = 62) was compared with a control cohort on the same dates in the years 2017, 2018 and 2019 (control group, n = 172). Thirty-day-mortality and one-year-mortality, orthopedic complications, ASA grade, comorbidities, diagnosis and treatment, time to surgery and mean stay were measured. RESULTS: No significant differences were found in 30-day mortality (p = 0.156; 9.7% compared to 4.7%) or in one-year mortality (p = 0.47) between the pandemic group (21%) and the control one (16.9%). A decrease in surgical delay and mean stay was observed in the pandemic group, although without statistical significance. CONCLUSIóN: The State of Alarm modified the distribution of the type of hip fracture with a predominance of intracapsular fracture. Maintaining the same hospital management as prior to the pandemic period made it possible not to increase 30-day mortality and one-year mortality in patients with intracapsular hip fracture.

Epidemiology of Bone Fractures in the Hand in Adult Population Using the ICD-10 Classification.

PURPOSE OF THE STUDY The purpose of this study was to conduct an epidemiological study of hand fractures in adult population. MATERIAL AND METHODS A retrospective observational study in a population of 470,000 habitants was performed. Over the course of three years, all patients over 16 years of age who were diagnosed with fracture or fracture-dislocation at the level of a carpal bone, metacarpal and/or phalange were included. These fractures were classified according to the International Classification of Diseases 10th edition (ICD-10). Incidence rates, along with gender and age distribution were also studied. RESULTS 1,267 patients with a total of 1,341 hand fractures were included. They represented 29.7% of all upper limb fractures and 7.6% of all traumatological emergencies involving a bone fracture during that period. The most frequent ICD-10 group was S62.3, with the fifth metacarpal as the most often affected bone (39.7%). The most frequent location at the level of the phalanges (S62.5) was the proximal third of the proximal phalanx of the fifth radius. The global incidence rate was 99 fractures per 100,000 persons/year. No seasonal variation was observed. Only 10.2% of hand fractures received surgical treatment. DISCUSSION Several epidemiological studies have been published on fractures in the hand, but none have used the ICD-10 classification. Although the distribution of our stratified sample by age and gender was similar to those previously published, the incidence rate in our study was much lower. We may possibly extrapolate our results to the rest of the Spanish population and even to the rest of the population of southern Europe, given the scarcity of epidemiological studies on this matter in these geographical areas. CONCLUSIONS The ICD-10 classification is useful for the description and classification of hand fractures. The most often affected group is that including metacarpals of the long fingers (S62.3), being the distal level of the fifth metacarpal in young male patients the most frequent one. Most fractures are treated conservatively and in case of surgical treatment, the preferred surgical techniques include K-wire fixation, interfragmentary compression screws and plate osteosynthesis. Key words: epidemiology, incidence, fracture, fracture dislocation, carpal bones, metacarpals, finger phalanges.

Prospective study about orthopaedic treatment of fifth metacarpal neck fractures. / Estudio prospectivo sobre el tratamiento conservador de las fracturas de cuello de quinto metacarpiano.

INTRODUCTION: The fifth metacarpal neck fracture is traditionally treated with closed reduction and intrinsic plus cast immobilization. Another alternative and more functional treatment is the syndactylia. The aim of our study is to compare both treatments searching for any differences in their functional outcomes. METHOD: We did a prospective, controlled, masked, randomized cohort study with patients over 18 years old attended from May 2019 to May 2020 in Vigo's Sanitary Area with this injure and an angle below 40°. The collected data was: sex, age, fracture angle, range of motion of the metacarpophalangeal articulation (MCFA), grip strength, pain, fracture consolidation, Quick DASH and comfort 4 and 6 weeks after the injury. RESULTS: 39 men and 1 woman were included in the sample. 36.1 years old as the age average. 90% of the injuries affected the right hand, being all the patients right-handed, finding statistically significant differences in MCFA flexion within 4 weeks and in grade of discomfort, both in favour of the syndactylia (p<0.05). Any of the other collected data was statistically significant. Every fracture achieved consolidation at the end of the follow-up. CONCLUSION: Following the results, we consider both immobilizations good treatment options of these fractures; nevertheless, syndactylia has proven an earlier MCFA flexion recovery and a better tolerance.

Epidemiological study of distal radius fractures in the sanitary area of Vigo. / Estudio epidemiológico de las fracturas de la extremidad distal de radio en el área sanitaria de Vigo.

INTRODUCTION: Distal radius fractures (DRF) are being a bigger burden for health resources as changes continue to happen in our population demography and in management strategies, so a precise epidemiologic comprehension is mandatory. We present a DRF epidemiology study and we compared it with other sanitary areas of the Iberian Peninsula and Europe. METHOD: Every DRF in our sanitary area registered between 2017 and 2018 in patients older than 18 years old were observational and retrospectively recorded and classified using AO-OTA classification. Age, sex, season of the year, mechanism of injury, presence of associated injuries and type of treatment were analysed. RESULTS: 1,121 DRF in 1,108 patients, 903 women (81.5%) and 205 men (18.5%), were registered. Left side was affected in 612 cases (54.6%) and right side in 509 cases (45.4%). The average age of our sample was 65.9 years old (CI95%: 65-67.9 years old). The incidence rate of DRF in our population was 158.5 fractures per 100,000 people-year; 49.2% were classified as type A of AO-OTA classification and 19% were treated surgically. CONCLUSION: Incidence of DRF had a maximum during males and women sixth decade of age. Type A fractures of AO-OTA classification were the most frequent. Most part of the fractures were treated non-surgically. The usual patient treated surgically was a woman, over 50 years old with a distal radius intraarticular complex fracture.

Influence of integrated orthogeriatric care on morbidity and mortality and length of hospital stay for hip fracture. / Influencia de la atención ortogeriátrica integrada en la morbimortalidad y el tiempo de estancia hospitalaria de la fractura de cadera.

BACKGROUND AND OBJECTIVES: Compare the morbidity and mortality, the length of hospital stay and the economic cost of the fragility fracture of the hip, in two nonconsecutive years thanks to the integrated orthogeriatric care. MATERIAL AND METHOD: Retrospective observational cohort study with 633 patients with hip fragility fracture with a mean age of 85.5 years, treated in the same Trauma and Orthopaedic Surgery service in two different years (2012 and 2017). Mean stay, surgical delay, perioperative mortality, one month and one year, and perioperative complications such as acute urine retention, pressure ulcers, and need for transfusion were measured. RESULTS: Mortality during admission decreased from 10% in 2012 to 3.6% in 2017 (P=.004 *), while mortality at thirty days (10.5% vs 7%) (P=.123) and one year (28.9% versus 24.9%) (P=.277). Hospital stay times, surgical delay, and postoperative admission time also decreased. The estimated total annual economic savings thanks to integrated orthogeriatric care amounted to €1,017,084.94. CONCLUSIONS: Integrated orthogeriatric care of the patient with fragility fracture of the hip, results in a more effective and efficient care model. Both the care and the clinical situation of patients are improved in the perioperative period, both hospital stay and mortality during admission are significantly reduced, and all this with significant associated economic savings.

Prepartum behavior changes in dry Holstein cows at risk of postpartum diseases.

The objective of this study was to identify changes in prepartum behavior associated with the incidence of postpartum diseases in dairy cows. Multiparous Holstein cows (n = 489) were monitored with accelerometers for 3 wk prepartum. Accelerometers measured steps, time at the feed bunk, frequency of meals, lying bouts, and lying time. Postpartum health was monitored from 0 to 30 d in milk and cases of metritis, mastitis, retained placenta, displaced abomasum (DA), ketosis, and hypocalcemia were recorded. A multivariate linear mixed model was used to assess differences in behavior between diseased and not diagnosed diseased cows. A multivariate logistic regression was used to predict the occurrence of diseases. Predictors were selected using a manual backward stepwise selection process of variables until all remaining predictors had a P < 0.10. Models were submitted to a leave-one-out cross-validation process, and sensitivity, specificity, false discovery rate, and false omission rate were calculated. On average, over the 3-wk prepartum period, cows not diagnosed diseased (n = 345) took 1,613 ± 38 steps, spent 181 ± 7.1 min at the feed bunk, had 8.3 ± 0.17 meals, had 9.8 ± 0.32 lying bouts, and spent 742 ± 11.3 min lying per day. Behavior of diseased cows (n = 144) did not differ from those not diagnosed diseased. However, differences for specific diseases were observed, being significant in the week prepartum. When considering changes in behavior for only the week before calving, cows with metritis had more lying bouts (+21%), cows with DA had fewer meals (-24%) and tended to take fewer steps (-18%), and cows with ketosis had fewer meals (-22%) and spent less time at the feed bunk (-40%). Prediction models with the best outcomes were found for DA and ketosis using data of the prepartum week only. The model for DA included time at the feed bunk. Cross-validation resulted in a 80% sensitivity, 58.1% specificity, 59.2% accuracy, 91.2% false discovery rate, and 1.7% false omission rate. The model for ketosis included time at the feed bunk and number of meals. Cross-validation resulted in 64.3% sensitivity, 59.3% specificity, 59.5% accuracy, 93.0% false discovery rate, and 2.8% false omission rate. Prepartum behavior of cows affected with metritis, DA, and ketosis was different from that of cows not diagnosed with diseases. Prediction equations were able to classify cows at high or low risk of ketosis and DA and can be used in taking management decisions, but the high false discovery rates requires further refinement.

Pitavastatin ameliorates autoimmune neuroinflammation by regulating the Treg/Th17 cell balance through inhibition of mevalonate metabolism.

While Treg cells are responsible for self-tolerance and immune homeostasis, pathogenic autoreactive Th17 cells produce pro-inflammatory cytokines that lead to tissue damage associated with autoimmunity, as observed in multiple sclerosis. Therefore, the immunological balance between Th17 and Treg cells may represent a promising option for immune therapy. Statin drugs are used to treat dyslipidemia; however, besides their effects on preventing cardiovascular diseases, statins also have anti-inflammatory effects. Here, we investigated the role of pitavastatin on experimental autoimmune encephalomyelitis (EAE) and the differentiation of Treg and Th17 cells. EAE was induced by immunizing C57BL/6 mice with MOG35-55. EAE severity was determined by analyzing the clinical score and inflammatory parameters in the spinal cord. Naive CD4 T cells were cultured under Treg and Th17-skewing conditions in vitro in the presence of pitavastatin. We found that pitavastatin decreased EAE development, which was accompanied by a reduction of all parameters investigated. Pitavastatin also reduced the expression of IBA1 and pSTAT3 (Y705 and S727) in the spinal cords of EAE mice. Interestingly, the reduction of Th17 cell frequency in the draining lymph nodes of EAE mice treated with pitavastatin was followed by an increase of Treg cells. Indeed, pitavastatin directly affects T cell differentiation in vitro by decreasing Th17 and increasing Treg cell differentiation. Mechanistically, pitavastatin effects are dependent on mevalonate synthesis. Thus, our data show the potential anti-inflammatory effect of pitavastatin on the pathogenesis of the experimental neuroinflammation by modulating the Th17/Treg axis.

Evaluation of the primary stability in dental implants placed in low density bone with a new drilling technique, Osseodensification: an in vitro study.

BACKGROUND: Primary stability is an important key determinant of implant osseointegration. We investigated approaches to improve primary implant stability using a new drilling technique termed osseodensification (OD), which was compared with the conventional under-drilling (UD) method utilized for low-density bones. MATERIAL AND METHODS: We placed 55 conical internal connection implants in each group, in 30 low-density sections of pig tibia. The implants were placed using twist drill bits in both groups; groups Under Drilling (UD) and Osseodensification (OD) included bone sections subjected to conventional UD and OD drilling, respectively. Before placing the implants, we randomized the bone sections that were to receive these implants to avoid sample bias. We evaluated various primary stability parameters, such as implant insertion torque and resonance frequency analysis (RFA) measurements. RESULTS: The results showed that compared with implants placed using the UD technique, those placed using the OD technique were associated with significantly higher primary stability. The mean insertion torque of the implants was 8.87±6.17 Ncm in group 1 (UD) and 21.72±17.14 Ncm in group 2 (OD). The mean RFA was 65.16±7.45 ISQ in group 1 (UD) and 69.75±6.79 ISQ in group 2 (OD). CONCLUSIONS: The implant insertion torque and RFA values were significantly higher in OD group than in UD. Therefore, compared with UD, OD improves primary stability in low-density bones (based on torque and RFA measurements).

Valor nutricional do capim-elefante verde colhido em diferentes idades de rebrota / [Nutritional value of fresh elephantgrass harvested at different regrowth ages]

Avaliou-se o valor nutricional do capim-elefante verde colhido aos 56, 84 e 112 dias de idade, por meio do consumo e da digestibilidade em ovinos, da degradabilidade in situ e da cinética da fermentação ruminal. O capim-elefante colhido aos 56 dias proporcionou maiores valores de consumo da MS (1204,81g/dia), da EB (4910,41kcal/dia), da ED (3436,21kcal/dia) e da PB (130,90g/dia). Para o capim-elefante colhido aos 56 dias, ainda foram observados os maiores valores de digestibilidade da MS (70,64%), da EB (70,11%), da PB (68,96%), da FDN (71,4%) e do conteúdo ED (2,86Mcal/kg MS). Com o avanço da idade de corte, houve redução da degradabilidade potencial da MS (77,99% x 68,33%), da PB (84,80% x 56,52%) e da FDN (72,18% x 64,33%), para as idades de corte de 56 e 112 dias, respectivamente. O capim cortado aos 56 dias apresentou maior valor de produção cumulativa de gases (210,50mL/g de MS) e de degradabilidade da matéria seca (63,9%) após 96 horas de fermentação. O capim-elefante verde deve ser colhido aos 56 dias de rebrota em razão das características nutricionais apresentadas.(AU)

The nutritional value of fresh elephant grass harvested at 56, 84 and 112 days of age was evaluated by intake and digestibility in sheep, in situ degradability, and ruminal fermentation's kinetics. The elephant grass harvested at 56 days provided higher DM intake (1204.81g/day), GE (4910.41kcal/day), DE (3436.21kcal/day), and CP (130.90g/day) values. Furthermore, the highest DM (70.64%), GE (70.11%), DE (2.86%) and CP (68.96%) digestibility values were observed at 56 days. With the increase in the harvest age there was a reduction in the DM (77.99 x 68.33%), CP (84.80 x 56.52%) and NDF (72.18 x 64.33%) potential degradability in the treatments 56 and 112 days, respectively. Higher values of cumulative gas production (210,50mL/g DM) and DM degradability for elephant grass were observed at 56 days, after 96 hours of fermentation. The fresh elephant grass should be harvested at 56 days of regrowth due to the nutritional characteristics found in this study.(AU)

Impact of asthma on children´s gustatory sensitivity, masticatory and feeding behaviors.

Asthma is a chronic inflammatory disease, in which disturbances in breathing, masticatory and swallowing functions may impact the eating behavior. The aim of the study was to evaluate the impact of asthma on taste sensitivity, masticatory behavior and feeding problems in children. The sample consisted of 91 children (6-7y) divided into two groups: asthma (n=46) and control group (n=45). Interviews were held with parents/guardians and clinical examinations were performed to gather information on medical, dental and feeding aspects. The gustatory sensitivity for sucrose and urea (sweet and bitter, respectively) were measured by staircase method designed for this age-range. The respiratory and masticatory functions were evaluated using the Orofacial Myofunctional Evaluation with Scores-expanded (OMES-e) protocol. Feeding problems were assessed using the Montreal Children's Hospital Feeding Scale, exploring oral motor, sensory, appetite, maternal concerns, child's behavior, and strategy aspects after transcultural adaptation to Brazilian Portuguese. The two groups were homogeneous relative to sociodemographic characteristics and nutritional status. Although the total OMES-e scores did not differ between groups, the frequency of changes in food incision and escape were different (p=0.007 and p=0.0011, respectively). The Asthma group required more time and higher number of masticatory cycles to eat the test-food (p<0.05). The gustatory thresholds for sweet and bitter were different, with asthmatic children requiring significantly higher concentrations to perceive the taste (p<0.001). The frequency of children classified by their parents according to feeding difficulties also differed between groups (p=0.001; Fisher's exact test). Asthmatic children showed remarkable changes in taste, chewing and eating behaviors, thereby pointing out the eating problems they may experience, which should be considered when designing and implementing therapeutic interventions.

La complejidad del entorno en la gestión de la seguridad ciudadana ante el Covid-19 / The environment complexity in the management of citizen security by Covid-19

Este artículo tiene como objetivo analizar las posibles vías de elaboración de vacunas basado en técnicas novedosas que, aunado al gran esfuerzo que se está realizando en otras áreas de la ciencia, podrían ser clave para mitigar los efectos de del COVI 19, tomando en cuenta la declaración que se hizo en Venezuela el 13 de marzo del 2020 por parte del Ejecutivo Nacional de las medidas del Aislamiento Social ante la pandemia declarada por la Organización Mundial de la Salud como consecuencia de la presencia del COVID-19. Lo anterior generó la necesidad de acceder a las cifras del índice delictivo de las cuatro semanas anteriores a la declaratoria del aislamiento social y relacionarlas al primer mes de la cuarentena social. Con estos datos centrados en el estado Miranda y aportados por la Secretaría Coordinadora de Seguridad y Paz Ciudadana de esta entidad en relación a los delitos de Homicidio, Robo y Hurto, como muestra de la realidad nacional, se realizaron comparaciones entre estos dos períodos. De este análisis se presenta como conclusión una disminución de un 79% de la incidencia delictiva acumulada en el primer mes del aislamiento social en relación con el mes anterior. Centrado en estas conclusiones se presentan las recomendaciones y aspectos de interés a ser monitoreados desde las capacidades científicas, tecnológicas y de innovación de los organismos de seguridad ciudadana(AU)

This essay seeks to provide recommendations for effective-ness and efficiency in police institutions, to make optimal use of available resources and to best adapt them to the specific realities faced in the social field where these organizations carry out their activities, under the current condition of Social Isolation, as a governance action taken to prevent the spread of COVID-19. The different environment situations to be faced by citizen security organiza-tions, determine the complexity of this, and the response mechanisms of these institu-tions constitute management models to the different varieties to be assumed and detailed in this work. The decree issued by the Venezuelan government on March 13, 2020, imposing Social Isolation because of the COVID-19 pandemic declared by the World Health Organization, created the need to access the crime rate figures of the four weeks prior to the declaration of social isolation, and link them to the first month of social quarantine. With this data focused on the Miranda State and provided by the Coordinating Secretary of Security and Citizen Peace of this entity in relation to the crimes of: Homicide, Robbery and theft, comparisons were made between these two periods. This analysis reflects a 79% decrease in the reported crime incidence in the first month of social isolation compared to the previous month, and focused on these findings, recommendations and aspects of interest are given, to be monitored from the scientific, technological and innovation capacities of citizen security agencies(AU)

Using behavior as an early predictor of sickness in veal calves.

The objective of this study was to analyze whether changes in behavior can be a good early predictor of sickness in calves. Friesian males calves (n = 325; 30 ± 9 d of age; 65 ± 15 kg) were monitored with an activity-monitoring device from 30 to 90 d of life in 4 periods corresponding to 4 seasons. The activity-monitoring device measured number of steps, number of lying bouts, lying time, and frequency and time of visits to the feed bunk. Calf health status was monitored daily and all incidences were recorded. To compare sick and healthy calves, a matched pair design was used to assign calves into the healthy group. Day 0 was defined as the day of sickness diagnosis. For each sick calf, 3 calves with no signs of sickness during the entire period (healthy calves) on the same date, in the same season, and of similar age (±4 d) and weight at entry were identified. A multivariate linear mixed model was used from d -10 to +10 relative to the sickness diagnosis to describe differences between sick and healthy calves. A multivariate logistic regression model was used for predicting sick calves on the days before the diagnosis. Significance was declared at P < 0.05. Daily, healthy calves had 1,476 ± 195 steps, spent 185 ± 32.5 min at the feed bunk, consumed 10 ± 1.1 meals, had 19.5 ± 1.8 lying bouts, and spent an average of 978 ± 30.5 min lying. The difference in behavior between sick (n = 33) and healthy calves (n = 99) began to be evident on d -10. Sick calves had fewer steps and numbers of visits to the feed bunk on d -1 and 0 and spent less time at the feed bunk on d -10 and -1 compared with healthy calves. From d -2 to d 9, sick calves had 15% fewer lying bouts, with no difference in lying time except on d -10, when sick calves spent more time lying. The best prediction model was for d -1 and included season and age at entry as qualifying variables, and frequency of visits to the feed bunk, steps, and lying time as behavior predictors (69% sensitivity, 72% specificity, 72% accuracy, 55% false discovery rate, and 12% false omission rate). However, an earlier prediction would be more useful to reduce the negative effect of sickness on production and welfare. The prediction model for d -10 had 67% sensitivity, 67% specificity, 67% accuracy, 60% false discovery rate, and 14% false omission rate. Results indicate that the occurrence of sickness can be predicted in advance, and an automated alarm system could be used to identify calves at risk of becoming sick and apply a preventive treatment.

NLRP12 Attenuates Inflammatory Bone Loss in Experimental Apical Periodontitis.

Apical periodontitis is an inflammatory disorder that results from the host immune response to microbial infection through the dental pulp, leading to alveolar bone destruction. The nod-like receptor 12 (NLRP12) is an atypical intracellular sensor of the NLR family that is involved in the negative regulation of several inflammatory conditions and also osteoclastogenesis. However, the role of NLRP12 in the regulation of immune response and bone loss induced by bacterial infection remains unclear. Here we investigated the development of apical periodontitis in wild-type (WT) and NLRP12 knockout (NLRP12-/-) mice by using micro-computed tomography together with histological, immunohistochemical, and molecular analyses. We found that NLRP12-/- mice are highly susceptible to apical periodontitis induced by bacterial infection, which is associated with an elevated infiltration of neutrophils and macrophages, periapical lesion extension, and alveolar bone destruction. Furthermore, NLRP12-/- mice showed a high expression of inflammatory cytokines ( Il1b, Il6, and Tnfa) and the osteoclastogenic markers ( Rankl and Acp5) in the periapical tissues. Consistent with this observation, NLRP12-/- mice showed an increased number of tartrate-resistant acid phosphatase-positive cells lining the apical periodontitis site, which was associated with augmented expression of the osteoclast effector genes, Ctsk and Mmp9. Mechanistically, NLRP12-deficient preosteoclasts showed elevated IκB-α degradation and p65 phosphorylation when stimulated with receptor activator of nuclear factor (NF)-κB ligand (RANKL). Similarly, increased IκB-α degradation was observed in the periapical tissue of NLRP12-/- mice. Furthermore, our in vitro study showed that preosteoclasts from NLRP12-/- mice exhibited higher RANKL-induced osteoclastogenesis, which was synergistically amplified by interleukin-1ß and tumor necrosis factor α (mimicking an inflammatory periapical milieu). In conclusion, our data show that NLRP12 exhibits a protective role in the periapical bone destruction by attenuating inflammation and osteoclastogenesis through negative regulation of the NF-κB pathway.

Effect of exercise training on ventilatory efficiency in patients with heart disease: a review.

The analysis of ventilatory efficiency in cardiopulmonary exercise testing has proven useful for assessing the presence and severity of cardiorespiratory diseases. During exercise, efficient pulmonary gas exchange is characterized by uniform matching of lung ventilation with perfusion. By contrast, mismatching is marked by inefficient pulmonary gas exchange, requiring increased ventilation for a given CO2 production. The etiology of increased and inefficient ventilatory response to exercise in heart disease is multifactorial, involving both peripheral and central mechanisms. Exercise training has been recommended as non-pharmacological treatment for patients with different chronic cardiopulmonary diseases. In this respect, previous studies have reported improvements in ventilatory efficiency after aerobic exercise training in patients with heart disease. Against this background, the primary objective of the present review was to discuss the pathophysiological mechanisms involved in abnormal ventilatory response to exercise, with an emphasis on both patients with heart failure syndrome and coronary artery disease. Secondly, special focus was dedicated to the role of aerobic exercise training in improving indices of ventilatory efficiency among these patients, as well as to the underlying mechanisms involved.

Effects of continuous vs interval exercise training on oxygen uptake efficiency slope in patients with coronary artery disease.

The oxygen uptake efficiency slope (OUES) is a submaximal index incorporating cardiovascular, peripheral, and pulmonary factors that determine the ventilatory response to exercise. The purpose of this study was to evaluate the effects of continuous exercise training and interval exercise training on the OUES in patients with coronary artery disease. Thirty-five patients (59.3±1.8 years old; 28 men, 7 women) with coronary artery disease were randomly divided into two groups: continuous exercise training (n=18) and interval exercise training (n=17). All patients performed graded exercise tests with respiratory gas analysis before and 3 months after the exercise-training program to determine ventilatory anaerobic threshold (VAT), respiratory compensation point, and peak oxygen consumption (peak VO2). The OUES was assessed based on data from the second minute of exercise until exhaustion by calculating the slope of the linear relation between oxygen uptake and the logarithm of total ventilation. After the interventions, both groups showed increased aerobic fitness (P<0.05). In addition, both the continuous exercise and interval exercise training groups demonstrated an increase in OUES (P<0.05). Significant associations were observed in both groups: 1) continuous exercise training (OUES and peak VO2 r=0.57; OUES and VO2 VAT r=0.57); 2) interval exercise training (OUES and peak VO2 r=0.80; OUES and VO2 VAT r=0.67). Continuous and interval exercise training resulted in a similar increase in OUES among patients with coronary artery disease. These findings suggest that improvements in OUES among CAD patients after aerobic exercise training may be dependent on peripheral and central mechanisms.

Effect of exercise training on ventilatory efficiency in patients with heart disease: a review

The analysis of ventilatory efficiency in cardiopulmonary exercise testing has proven useful for assessing the presence and severity of cardiorespiratory diseases. During exercise, efficient pulmonary gas exchange is characterized by uniform matching of lung ventilation with perfusion. By contrast, mismatching is marked by inefficient pulmonary gas exchange, requiring increased ventilation for a given CO2 production. The etiology of increased and inefficient ventilatory response to exercise in heart disease is multifactorial, involving both peripheral and central mechanisms. Exercise training has been recommended as non-pharmacological treatment for patients with different chronic cardiopulmonary diseases. In this respect, previous studies have reported improvements in ventilatory efficiency after aerobic exercise training in patients with heart disease. Against this background, the primary objective of the present review was to discuss the pathophysiological mechanisms involved in abnormal ventilatory response to exercise, with an emphasis on both patients with heart failure syndrome and coronary artery disease. Secondly, special focus was dedicated to the role of aerobic exercise training in improving indices of ventilatory efficiency among these patients, as well as to the underlying mechanisms involved.