Long-term treatment with chloroquine increases lifespan in middle-aged male mice possibly via autophagy modulation, proteasome inhibition and glycogen metabolism

Previous studies have shown that the polyamine spermidine increased the maximum life span in C. elegans and the median life span in mice. Since spermidine increases autophagy, we asked if treatment with chloroquine, an inhibitor of autophagy, would shorten the lifespan of mice. Recently, chloroquine has intensively been discussed as a treatment option for COVID-19 patients. To rule out unfavorable long-term effects on longevity, we examined the effect of chronic treatment with chloroquine given in the drinking water on the lifespan and organ pathology of male middle-aged NMRI mice. We report that, surprisingly, daily treatment with chloroquine extended the median life span by 11.4% and the maximum life span of the middle-aged male NMRI mice by 11.8%. Subsequent experiments show that the chloroquine-induced lifespan elevation is associated with dose-dependent increase in LC3B-II, a marker of autophagosomes, in the liver and heart that was confirmed by transmission electron microscopy. Quite intriguingly, chloroquine treatment was also associated with a decrease in glycogenolysis in the liver suggesting a compensatory mechanism to provide energy to the cell. Accumulation of autophagosomes was paralleled by an inhibition of proteasome-dependent proteolysis in the liver and the heart as well as with decreased serum levels of insulin growth factor binding protein-3 (IGFBP3), a protein associated with longevity. We propose that inhibition of proteasome activity in conjunction with an increased number of autophagosomes and decreased levels of IGFBP3 might play a central role in lifespan extension by chloroquine in male NMRI mice.UEFISCDI (EU Horizon 2020 Research and Innovation Programme), Consiliul National al Cercetarii Stiintifice (CNCS), Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii (UEFISCDI

Ageing, functioning patterns and their environmental determinants in the spinal cord injury (SCI) population:A comparative analysis across eleven European countries implementing the International Spinal Cord Injury Community Survey

Background As the European population with Spinal Cord Injury (SCI) is expected to become older, a better understanding of ageing with SCI using functioning, the health indicator used to model healthy ageing trajectories, is needed. We aimed to describe patterns of functioning in SCI by chronological age, age at injury and time since injury across eleven European countries using a common functioning metric, and to identify country-specific environmental determinants of functioning. Methods Data from 6’635 participants of the International Spinal Cord Injury Community Survey was used. The hierarchical version of Generalized Partial Credit Model, casted in a Bayesian framework, was used to create a common functioning metric and overall scores. For each country, linear regression was used to investigate associations between functioning, chronological age, age at SCI or time since injury for persons with para- and tetraplegia. Multiple linear regression and the proportional marginal variance decomposition technique were used to identify environmental determinants. Results In countries with representative samples older chronological age was consistently associated with a decline in functioning for paraplegia but not for tetraplegia. Age at injury and functioning level were associated, but patterns differed across countries. An association between time since injury and functioning was not observed in most countries, neither for paraplegia nor for tetraplegia. Problems with the accessibility of homes of friends and relatives, access to public places and long-distance transportation were consistently key determinants of functioning. Conclusions Functioning is a key health indicator and the fundament of ageing research. Enhancing methods traditionally used to develop metrics with Bayesian approach, we were able to create a common metric of functioning with cardinal properties and to estimate overall scores comparable across countries. Focusing on functioning, our study complements epidemiological evidence on SCI-specific mortality and morbidity in Europe and identify initial targets for evidence-informed policy-making.</p

Evaluation of the Mandibular Condyle Morphologic Relation before and after Orthognathic Surgery in Class II and III Malocclusion Patients Using Cone Beam Computed Tomography

This study aimed at evaluating the mandibular condyle position changes before and after bimaxillary orthognathic surgery in class II and III malocclusion patients. CBCT scans from patients who underwent bimaxillary orthognathic surgery were analyzed: Le Fort I osteotomy and bilateral sagittal split osteotomy (BSSO). Both condyles were independently assessed for their largest anterior and posterior joint spaces, smallest medial joint spaces, and condyle angles concerning the transverse line. In the sagittal plane, the minimum size of the anterior and posterior joint spaces was measured. In the coronal plane, the smallest medial joint space was measured. The position of the condyle within the glenoid fossa was determined before and after surgery. A total of 56 TMJs from 28 patients were studied. Following orthognathic surgery, the anterior and posterior space in class II increased. Postoperatively, the anterior joint space in class III decreased. In 42.85% of malocclusion class II patients and 57.14% of malocclusion class III patients, the pre-and post-surgical position of the condyle changed, the condyle was anteriorly positioned (42.85%) in class II patients and centrically positioned (71.4%) in class III patients. Significant changes in the joint space, condylar position, and condyle angle were found in the class II and class III subjects

Identification of Heavy Tobacco Smoking Predictors-Influence of Marijuana Consuming Peers and Truancy among College Students

Background: Poorly informed college students tend to adopt the habit of cigarette smoking. This habit often continues into their adulthoods, adversely affecting the population&rsquo;s health and increasing the burden on healthcare systems. Aim: We aimed at exploring the predictors of the avoidable habit of smoking. We performed an analysis of the correlation between the potential predictors (marijuana use among peers and truancy) and the tobacco smoking statuses of the students. Material and method: Our study sample included 2976 students from colleges in Timis County, Romania, during the 2018&ndash;2019 period. The gender distribution of the participants was 62.5% girls and 37.5% boys, between the ages 18 and 25 years. A logistic regression test was performed to determine the impact of some personal and environmental factors, which are responsible for heavy smoking in this population. Results: Our findings suggest that the degree of marijuana smoking among friends and the frequency of college truancy are meaningful predictors of heavy smoking among young adults. The students with higher cigarette smoking rates had significantly more marijuana-smoking friends when compared to the students with average smoking rates. The truancy was higher among the students with higher cigarette smoking rates, compared to the students with average smoking rates

Ageing, functioning patterns and their environmental determinants in the spinal cord injury (SCI) population: A comparative analysis across eleven European countries implementing the International Spinal Cord Injury Community Survey.

BackgroundAs the European population with Spinal Cord Injury (SCI) is expected to become older, a better understanding of ageing with SCI using functioning, the health indicator used to model healthy ageing trajectories, is needed. We aimed to describe patterns of functioning in SCI by chronological age, age at injury and time since injury across eleven European countries using a common functioning metric, and to identify country-specific environmental determinants of functioning.MethodsData from 6'635 participants of the International Spinal Cord Injury Community Survey was used. The hierarchical version of Generalized Partial Credit Model, casted in a Bayesian framework, was used to create a common functioning metric and overall scores. For each country, linear regression was used to investigate associations between functioning, chronological age, age at SCI or time since injury for persons with para- and tetraplegia. Multiple linear regression and the proportional marginal variance decomposition technique were used to identify environmental determinants.ResultsIn countries with representative samples older chronological age was consistently associated with a decline in functioning for paraplegia but not for tetraplegia. Age at injury and functioning level were associated, but patterns differed across countries. An association between time since injury and functioning was not observed in most countries, neither for paraplegia nor for tetraplegia. Problems with the accessibility of homes of friends and relatives, access to public places and long-distance transportation were consistently key determinants of functioning.ConclusionsFunctioning is a key health indicator and the fundament of ageing research. Enhancing methods traditionally used to develop metrics with Bayesian approach, we were able to create a common metric of functioning with cardinal properties and to estimate overall scores comparable across countries. Focusing on functioning, our study complements epidemiological evidence on SCI-specific mortality and morbidity in Europe and identify initial targets for evidence-informed policy-making

European Framework of Rehabilitation Services Types: the perspective of the Physical and Rehabilitation Medicine Section and Board of the European Union of Medical Specialists

BACKGROUND: Effectiveness in health services is achieved if desired clinical outcomes are reached. In rehabilitation the relevant clinical outcome is functioning, with the International Classification of Functioning, Disability and Health (ICF) as the reference system for the standardized reporting of functioning outcomes. To foster the implementation of the ICF in clinical quality management (CQM) across the rehabilitation services continuum, the UEMS-PRM Section and Board approved an ICF implementation action plan that includes the identification of types of currently provided rehabilitation services in Europe. The objective of this paper is to report on the development of a European framework of rehabilitation service types that can provide the foundation for the standardized reporting of functioning outcomes and CQM programs

Basic sociodemographic and lesion characteristics of European country study participants by collaborating country.

Basic sociodemographic and lesion characteristics of European country study participants by collaborating country.</p

Fig 5 -

a. Relative importance of each environmental factors in explaining the total variation of functioning scores in countries with representative samples, when controlling for chronological age and type of injury. For each country, the full model variation when considering EFs and chronological age and type since injury as predictors is indicated in each country figure’s title. b. Relative importance of each environmental factors in explaining the total variation of functioning scores countries with convenience samples, when controlling for chronological age and type of injury. For each country, the full model variation when considering EFs and chronological age and type since injury as predictors is indicated in each country figure’s title.</p

Fig 4 -

a. Trends of functioning scores by type since injury groups and type of injury in countries with representative samples. For each group, the mean (marked with a green x) and its 95% Confidence Interval (the box around the mean) of functioning scores are displayed. The coefficient of the regression with functioning score as outcome (y) and continuous chronological age variable as predictor (x), their correspondent p-value and used number of cases are displayed for each country and lesion level (tetraplegia in blue versus paraplegia in brown). The groups where only mean is displayed have a sample of 1 person. b. Trends of functioning scores by time since injury groups and type of injury in countries with convenience samples. For each group, the mean (marked with a green x) and its 95% Confidence Interval (the box around the mean) of functioning scores are displayed. The coefficient of the regression with functioning score as outcome (y) and continuous chronological age variable as predictor (x), their correspondent p-value and used number of cases are displayed for each country and lesion level (tetraplegia in blue versus paraplegia in brown).</p

Fig 3 -

a. Trends of functioning scores by age at SCI groups and type of injury in countries with representative samples. For each group, the mean (marked with a green x) and its 95% Confidence Interval (the box around the mean) of functioning scores are displayed. The coefficient of the regression with functioning score as outcome (y) and continuous chronological age variable as predictor (x), their correspondent p-value and used number of cases are displayed for each country and lesion level (tetraplegia in blue versus paraplegia in brown). The groups where only mean is displayed have a sample of 1 person. b. Trends of functioning scores by age at SCI groups and type of injury in countries with convenience samples. For each group, the mean (marked with a green x) and its 95% Confidence Interval (the box around the mean) of functioning scores are displayed. The coefficient of the regression with functioning score as outcome (y) and continuous chronological age variable as predictor (x), their correspondent p-value and used number of cases are displayed for each country and lesion level (tetraplegia in blue versus paraplegia in brown). The groups where only mean is displayed have a sample of 1 person.</p