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Michelangelo's marble sculpture of David is one of the most admired works of art in the world. It is the most iconic symbol of the Florentine Renaissance, and a representation of the idealized human form in its perfection and proportion. The statue was examined in 2004 by two anatomists who observed the apparent absence of a single muscle. Our re-examination of the statue, from our perspective as clinical geneticists, shows unexpected and hitherto unpublished details of variations and disproportions within the overall context of exceptional harmony and beauty. This apparent contradiction raises the question as to what is considered to be morphologically "normal" and what "is not". [ABSTRACT FROM AUTHOR]

The vertical jump is frequently used for the functional evaluation of athletes and non-sporting subjects. The jump height is often used as an indicator of lower limbs strength. The aim of this study was to verify the presence of a relationship between the maximum height reached and muscle parameters expressed during the vertical jump. In 22 healthy males practicing recreational physical activity (age, mean ± standard deviation: 22.5±1.2 years; body mass: 72.8±13.2 kg; body height: 177.1±7.0 cm) and in 15 female volley players (age: 16.5±0.4 years; body mass: 64.4± 8.4 kg; body height: 175.5±7.9 cm), Jump Height (cm), Muscle Strength (N/kg) and Power (W/kg) were recorded during the jump tests. In the healthy males group, jump height was correlated with muscle power: r = 0.33, p>0.05; a higher correlation resulted between muscle strength and power: r = 0.62, p<0.01. In the female volleyball players group, only the muscle strength and power showed a correlation: r = 0.54, p<0.05. It is therefore possible to confirm that the jump height reached during a vertical jump does not provide clear information on the strength of the lower limbs. At the same time, an improvement in muscular strength of the lower limbs does not guarantee an increase in jump height. Several parameters should be evaluated at the same time for a correct functional assessment of athletes and healthy non-sporting subjects. [ABSTRACT FROM AUTHOR]

Even if physical activity plays a key role within diabetic foot treatment its use and the results obtained from this treatment seem to be still limited. Nowadays, new and even more advanced technologies for the long term daily physical activity monitoring are available and they are radically changing some aspects of physical activity such as its amount, features and monitoring. In spite of the past, the several electronic devices that are currently available can be integrated into routine care and provide essential information for management to both the healthcare providers and patients. In particular, since the end of the last century, an increasing number of studies have applied the movement monitoring to patients at risk or with history of ulceration. The questionnaires have been progressively replaced with modern technologies such as accelerometers or complex multisensory devices able to objectively measure the physical activity performed. The data collected through the use of such devices can allow a better assessment of patient's condition and provide useful information for the definition of a more complete treatment protocol. Daily physical activity monitoring devices provide to the Diabetes Units information on the typology, quantity, distribution and intensity of the daily physical activity performed by each patient concurring to the prevention of foot ulcers that represent the most dreadful diabetes complications. The different functions and modes of operation of monitoring devices can be integrated to provide a more comprehensive and intelligent monitoring system that provide valuable information on patients' ongoing health status and the physical activity performed during daily life. These devices can manage in real time or even in remote the physical activity performed in addition to calculate that to be performed in the following hours. As a result, they contribute to improve patients' lifestyle and reduce the costs for the treatment of such complications. The aim of this review is to define and emphasize the role of a long term daily physical activity monitoring in the prevention of diabetic foot ulcers. [ABSTRACT FROM AUTHOR]

Variations in the branching pattern of the aortic arch are clinically relevant because of the direct influence that their presence can have on the success of cardio-vascular procedures, neck or thorax surgery, trauma management or intensive care. In most cases these anatomical variations are asymptomatic and considered clinically benign, but some particular aortic branching patterns have been associated with surgical complications or with vascular diseases in non-surgical patients. The main objective of this work was to study the frequency of variation of the aortic arch branching pattern in a wide and varied population on the basis of literature reports. The aortic arch branching pattern of 20,030 cases reported by 40 anatomical or radiological studies were analyzed. 84,52% of the studied population had a three branches pattern and 14,65% had a two branches pattern. The four primary arteries were seen arising directly from the aortic arch in 0,81% of the cases and only 0,02% had them all arising from a common trunk. [ABSTRACT FROM AUTHOR]

Objective. The impairment of glycemic control can induce limited joint mobility even in young type 1 diabetic (T1DM) patients. The aims of this study were to verify the presence of ankle joint mobility (AJM) deficits in young T1DM subjects and define a mathematical model of diabetes mellitus long-term effects on AJM. Methods. AJM was evaluated using an inclinometer in 37 patients and 53 healthy, sex- BMI- and age-matched controls. To set up the mathematical model, we assumed that reduced metabolic control affects AJM according to a lognormal function: requiring some time for development of a reduction of joint mobility, which then persists for a long period, before fading out over time (if glycemic control has been recovered). A non-linear optimization determined the model parameters to achieve the best fit for a series of patients. Results. Both plantar and dorsiflexion AJM was significantly lower in diabetic subjects than in controls (plantarflexion: 28.5°±7.5 vs 35.2°±6.5; dorsiflexion: 93.9°±16.0 vs 104.7±12.8; p<0.01). The defined model approximates the experimental data with good accuracy; after optimization, the lognormal curve obtained is in line with empirical estimates: lack of glycemic control needs to persist for at least a few months before producing a significant effect, that lasts up until one year. The fitting procedure indicated the optimal solution is p = (37; 30; 3:5; 6:7; 137); thus, the optimal _im(t) corresponds to the curve reported. Conclusion. AJM was significantly reduced in young T1DM patients. The mathematical model represents the experimental data accurately. [ABSTRACT FROM AUTHOR]

Objective: Hand muscle strength assessment is widespread and can be a useful marker in the evaluation and monitoring of subjects at different ages and health conditions. This study aimed at validating and determining the reliability of a new digital device for evaluation of hand pinch strength by comparing it with a well-validated hand strength assessment device, the Jamar hydraulic hand dynamometer. Methods: In 65 healthy subjects, (males / females: 29 / 36), mean age 40.3±18.0 (range: 19.3 - 76.5) years, hand pinch strength and hydraulic hand dynamometer were used to assess hand strength following a testing protocol. Only the dominant hand was tested. Evaluations were performed considering gender, hand dominance, body mass index and age, according to the standardized testing protocol. The mean of three consecutive grip tests and lateral pinch tests was recorded. Results: There was a strong correlation (p<0.0001) between the hydraulic hand dynamometer and hand pinch strength tests. Both mean strengths measured by hydraulic hand dynamometer and hand pinch strength in females were significantly lower than in males (P<0.001), the grip strength being 34.75% and the lateral pinch test 27.83% weaker than in males. Multivariate analysis indicated that the strength expressed by the hand pinch strength pinch test remained significantly associated with the results of hydraulic hand dynamometer (p<0,001), independent of age and body weight. Conclusions: hand pinch strength and hydraulic hand dynamometer have been shown to be significantly correlated with each other in subjects of different ages, sex and body mass index.The hand pinch strength device has been proven to be a reliable tool for measuring maximal isometric strength by lateral pinch test. This device can be used for quick and inexpensive numerical evaluation of muscular strength in cases as the elderly in communities, bedridden patients, and during drug therapies presumed to be strength affecting. [ABSTRACT FROM AUTHOR]

The article focuses on studying the blood-brain barrier (BBB) and the crucial role of astrocytes in its formation and function, highlighting their influence on the expression and correct distribution of tight junction proteins like claudin 5 in brain endothelial cells.

The article offers information on morphological features of rat brain vascular pericytes (RBVP) during toxic insult and their role in blood-brain barrier characterization. Topics include information on pericytes which are fibroblast like cells; information on extensive cytoplasmic elongation; and different cell types of central nervous system.

The article discusses a study conducted to evaluate in the human cerebellum the presence of an intrinsic serotonergic neuronal subpopulation. The immunoreactions were revealed by streptavidin-biotin-peroxidase and 3,3-diaminobenzidine tetrahydrochloride technique; for positive controls were used duodenum and brainstem fragments of rat subjected to the same experimental protocol.

C Cadmium is a toxic heavy metal known as environmental pollutant world-wide distributed. Its toxicity, predominantly due to its long half-life of 15-20 years, affects many organs and tissues including kidney, lung, liver, heart, bone, muscles and the central nervous system (CNS) as well [1]. Our research group previously demonstrated that cadmium is able to alter the blood-brain barrier by modifying the tight junction sealing morphology and to induce oxidative stress, thus leading to neuronal degeneration mainly by oxidative stress [2]. Among the cellular population of the CNS, glial cells own a pivotal role in maintaining the physiological brain homeostasis and their alteration has been demonstrated to indirectly affect neurons [3]. The aim of the present research is to evaluate cadmium toxicity in two glial cell lines (astrocyte DITNC1 and microglia BV-2), at different time and increasing concentration of metal exposure. Cadmium increasing concentrations (0.1-100 µM) were administered in starvation medium for 8, 24 and 48 hours. Cell viability assay, western blotting analysis, and immunofluorescent staining were employed in order to evaluate the molecular and morphological alterations induced by the heavy metal. Our results clearly demonstrated that Cd is able to affect the cell viability even at the lowest concentrations and in a time-dependent manner, by altering the oxidative balance (ROS production, cytochrome C expression) and inducing an endoplasmic reticulum stress (GRP78 upregulation). Moreover, Cd is able to induce glial morphological alterations as well as an overexpression of activation glial markers, such as GFAP, S100ß, CD86, and Iba1. In conclusion, the data obtained clearly demonstrated that Cd toxicity occurs even at low doses and for very short exposure times Further experiments should be performed in order to evaluate the mechanisms underlying the Cd-dependent activation of glial cells and how this, in turn, induces a neuronal homeostasis alteration. [ABSTRACT FROM AUTHOR]

The study of the relationships between the different structures of the human locomotor system still to date raises great interest. In fact, the human body networks and in particular the myofascial system "myofascial system network" underlie posture and movement and new knowledge could be useful and applied to many fields such as medicine and prosthetics. The hypothesis of this study was to verify the possibility of creating a structural network representing the human locomotor system as well as to study and describe the relationship between the different structures considered. The graph theory was applied to a network of 2339 body parts (nodes) and 7310 links, representing the locomotor system. The open source platform software Cytoscape was used for data entry (nodes and links) as well as for debugging. In addition, the "Network Analyzer" plugin was used for the descriptive statistics of the network obtained. In order to achieve a better rendering, the results of the network parameters gained were then imported into Gephi (www.Gephi.org). At the end of this procedure, we obtained a image of a human being in an orthostatic position with a precise distribution of the nodes and links. By simulating the common amputations at the level of the foot and leg (as for necrotic complications of diabetes) the balance between the parts and the whole structure of the graph are profoundly modified. [ABSTRACT FROM AUTHOR]

Interaction between intestinal epithelial cells (IECs) and the underlying immune systems is critical for maintaining intestinal immune homeostasis and mounting appropriate immune responses. We have previously showed that the T helper type 1 (TH1) cytokine IL-12 plays a key role in the delicate immunological balance in the gut and the lack of appropriate levels of IL-12 had important consequences for health and disease, particularly with regard to food allergy. Here we sought to understand the role of IL-12 in the regulation of lympho-epithelial cross talk and how this interaction affects immune responses locally and systemically. Using a combination of microscopy and flow cytometry techniques we observed that freshly isolated IECs expressed an incomplete, yet functional IL-12 receptor (IL-12R) formed solely by the IL-12Rb2 chain that albeit the lack of the complementary IL-12b1 chain responded to ex-vivo challenge with IL-12. Furthermore, the expression of IL-12Rb2 on IECs is strategically located at the interface between epithelial and immune cells of the lamina propria (lp) and using in vitro co-culture models and primary intestinal organoids we showed that immune-derived signals were required for the expression of IL-12Rb2 on IECs. The in vivo biological relevance of the IEC-associated IL-12Rb2 was assessed in vivo in a mouse model of food allergy characterized by allergy-associated diminished intestinal levels of IL-12 and in chimeric mice that lack the IL-12Rb2 chain on IECs. These experimental models enabled us to show that the anti-allergic properties of orally delivered recombinant Lactococcus lactis secreting bioactive IL-12 (rLc- IL12) were reduced in mice lacking the IL-12b2 chain on IECs. Finally, we observed that the oral delivery of IL-12 was accompanied by the down-regulation of the production of the IECderived pro-allergic cytokine thymic stromal lymphopoietin (TSLP). However, further analysis of intestinal levels of TSLP in IL-12Rb2-/- mice suggested that this event was not directly linked to the IEC-associated IL-12Rb2 chain. We interpreted these data as showing that IECassociated IL12Rb2 is a component of the cytokine network operating at the interface between the intestinal epithelium and immune system that plays a role in immune regulation. [ABSTRACT FROM AUTHOR]

It is known that joint mobility (JM), flexibility, muscle strength and posture can determine the quality of movement and could also adversely affect the body development of young subjects practicing sport. The aim of this study was to investigate how the practice of different sports affects these parameters. We enrolled 109 young subjects practicing different sports: soccer (M/F:22/10), mean age 12,6±1,4 yrs, BMI:18,3±2,3 kg/m2; volleyball (M/F:13/14), mean age 12,0±1,3 yrs, BMI 17,4±2,2 kg/m2; basketball (M/F:20/2), mean age 11,1±0,8 yrs, BMI 20,9±4,4 kg/m2; gymnastics (M/F:0/11), mean age 14,5±1,1 yrs, BMI 18,9±2,1 kg/m2 and dance (M/F:0/17), mean age 11,7±3,1 yrs, BMI 18,3±2,8 kg/m2. In these subjects we evaluated ankle JM (inclinometer), trunk flexibility (sit & reach test), muscle strength (standing long jump, vertical jump and Jamar hand grip), posture (images on the sagittal plane) and lifestyle (IPAQ-C, IPAQ-A). The individual sporting history was investigated by a specific questionnaire. The tests performed showed a significantly higher ankle JM in young dancers (155,8±10,3°) compared to all other groups excluding volleyball players (p<0,001). In particular, the subjects practicing soccer showed a significant reduction of the ankle JM (125,2±22,3°) compared to all the other groups of subjects investigated (p<0,01). Gymnasts showed a greater flexibility of the trunk than that measured in all other groups (18,3±3,5 cm; p<0,001), while basketball players showed lower trunk flexibility (-7.7 ± 7.0 cm). In the muscle-strength tests performed the dancers showed the following results (hand grip: 18.7 ± 6.6 kg, long-jump standing 119.8 ± 29.2 cm) that are significantly reduced compared to the gymnasts (hand grip: 26.0 ± 4, 2 kg: p <0.005, long jump standing 163.8 ± 12.7 cm: p <0.001) and to volleyball players (standing long jump 152.5 ± 27.9 cm: p <0.001). The practice of specific sports can significantly modify the ankle JM and the flexibility of the trunk as well as affect muscle strength even in young subjects. It is not entirely clear whether these effects may induce negative consequences on health and development of the anatomical structures involved; therefore, further studies are needed to verify the conclusions and the possible usefulness of APA programmes in the prevention or recovery of such significant effects. [ABSTRACT FROM AUTHOR]

Exercise is generally recommended for elderly subjects although the effects of the different programmes used in the adapted physical activity (APA) centers are not always properly verified. The aim of this study was to evaluate the response of elderly subjects attending classes of APA to a moderate aerobic physical activity. In 15 subjects (2/13 M/F), mean age 67,8±13,8 yrs, body mass index 23,7±3,5 Kg/m2 attending an APA class we evaluated ankle joint mobility (inclinometer), hand strength (Jamar hand grip), walking speed and step length (10 and 20 meters), aerobic capacity and endurance (6 Minute Walk Test- 6MWT), lower extremity function (SPPB: short physical performance battery), posture (sagittal images), and peripheral microcirculation (Laser doppler flowmetry). The subjects were evaluated in the following 3 stages: at the end of a 8-months APA period, after 4 months of inactivity and 4 months after recommencing of a new period of the same programme. All the subjects included in the study performed a training programme of APA twice a week for 1 hour each. The training programme consisted in 10 minutes of organic activation, 30 minutes of moderate physical activity at 45-65% of VO2 peak and toning, 20 minutes of exercises on the floor: breathing and stretching. After 4 months of inactivity, the subjects investigated showed a significant and widespread reduction of the gait parameters investigated: 6MWT (446.5 ± 91.4 vs 429 ± 89.4 mt, p <0.01); 10 meters (step length: 0.67 ± 0.09 vs 0.63 ± 0.08 mt - time: 7.6 ± 1.7 vs 8.5 ± 1.7''); 20 meters (step length: 0.71 ± 0.08 vs 0.67 ± 0.06 mt - time: 14.0 ± 2.1 vs 15.4 ± 2.0''). After 4 months of training there was a significant, even if partial recovery of the parameters investigated in comparison to the results achieved after the inactivity period,: 6MWT (438.05 ± 92.3 mt, p <0.01); 10 meters (step length: 0.65 ± 0.07 mt - time: 8.0 ± 1.7'', p <0.01); 20 meters (step length: 0.68 ± 0.07 mt, p = 0.15 - time: 14.6 ± 2.1'', p <0.01). The 4 meter walking speed (SPPB) evaluated in the subjects investigated was correlated with 10 mt (r = 0.69, p <0.01) and 20 mt (r = 0.6, p <0, 05). The length of the step measured in the 10 and 20 meters tests was correlated with the ankle mobility (10 mt: r = 0.7, p <0.01; 20 mt: r = 0.62, p <0.5). The results of this study show that in a population of elderly subjects a programme of APA, as scheduled and performed in this study, significantly improves the gait parameters. However, a short interruption of the APA training significantly reduced the walking speed and step length. This study, in addition to underlining the importance of the APA programmes, also shows that it is necessary to reduce or avoid interruptions of these physical activities. [ABSTRACT FROM AUTHOR]

Degenerative diseases of the central nervous system are significant causes of mortality among aging population in industrialized countries, as well as expensive for the national health systems and caregivers [1]. Nowadays, pharmacological therapies are still not decisive because they are hindered by the blood brain barrier (BBB) [2]. Although in the last decades many researchers have conducted in vivo experiments to better identify a therapeutic approach of ultrasound (US) in neurodegenerative diseases, little is known about their role in increasing the BBB permeability [3,4]. The present study aims to identify, the effect of focused US on a rat brain endothelial cell line (RBE4). After ultrasound stimulation (10-20-30 min.), MTT and western blotting assay were conducted to demonstrate the non-toxic effects of US. Furthermore, immunostaining of stimulated cells was performed to detect changes in cytoskeletal F-actin fibers and Zonula occludens-1 (ZO1) tight juntion. BBB opening was evaluated by measuring the extent of the intercellular space, in Papanicolaou stained cells. The results evidenced an ultrasonic-dependent mechanical action on F-actin fibers that altered their distribution within the cells showing the formation of numerous stress fibers. F-actin alterations were accompanied by an alteration of the ZO-1 distribution, exhibiting a "zipper-like" staining pattern and holes that became visible between cells. Papanicolaou staining confirm the opening of the BBB evidencing many wider areas of intercellular space. All these structural changes on RBE4 cell line occurred without significant alterations in metabolic activity as well as in absence of apoptotic or endoplasmic reticulum stress markers. In conclusion, these results confirm and highlight the potential role of ultrasound in the permeabilization of the BBB, thus suggesting new ways for drugs administration. [ABSTRACT FROM AUTHOR]

Quality of life into later life is influenced by multiple factors. The physical abilityto perform common everyday activities represents a key factor to maintain a healthy and independent lifestyle. Moreover, aging is a process characterized by physiological alterations resulting in a progressive decline in biological functions, decreased resistance to stress, and increased susceptibility to diseases. Especially in elderly people, alterations such as imbalance between pro and antioxidant activity and/or hormonal dysregulation negatively affect the physical capacity, the emotionalstatus and the overall general health and quality of life [1]. On the other hand, regular physical activity is considered an effective strategy for older adults to prevent and reduce the risk of developing those negative conditions arising from aging. A 24-week regular physical activity program (twice weekly, 1 hour per session) focused on functional fitness exercises was performed by 20 older adults (aged 55 years or more). A set of anthropometric (height, weight, BMI and body fat percentage) and physical measurements (grip strength, chair sit to stand, sit and reach and back scratch) assessing the functional fitness performance [2] were evaluated. Moreover, biochemical markers (d-ROMs and BAP tests as assessment of oxidative stress and antioxidant potential; salivary cortisol levels) were measured before and after the intervention program. The results confirm the benefits of a regular physical activity in older adults resulting in improved physical strength and flexibility in the functional fitness parameters, and in regulating pro and antioxidant activity and cortisol levels. [ABSTRACT FROM AUTHOR]

During infection intestinal CX3CR1+ cells can either extend transepithelial cellular processes to sample luminal bacteria or, very early after infection migrate into the intestinal lumen to capture bacteria. However, up to date, the biological relevance of the intraluminal migration of CX3CR1+ cells remained to be determined. We addressed this by using a combination of mouse strains differing in their ability to carry out CX3CR1-mediated sampling and intraluminal migration. We observed that, the number of S. Typhimurium traversing the epithelium did not differ between sampling-competent/migration-competent C57BL/6 and sampling deficient/migration- competent Balb/c mice. By contrast, in sampling-deficient/migration deficient CX3CR1-/- mice the numbers of S. Typhimurium penetrating the epithelium were significantly higher. However, in these mice the number of invading S. Typhimurium was significantly reduced after the adoptive transfer of CX3CR1+ cells directly into the intestinal lumen, consistent with intraluminal CX3CR1+ cells preventing S. Typhimurium from infecting the host. This interpretation was also supported by a higher bacterial faecal load in CX3CR1+/gfp compared to CX3CR1gfp/gfp mice following oral infection. Furthermore, by using real time in vivo imaging we observed that CX3CR1+ cells migrated into the lumen moving through paracellular channels within the epithelium. Also, we reported that the absence of CX3CR1 mediated sampling did not affect antibody responses to a non-invasive S. Typhimurium strain that specifically targeted the CX3CR1-mediated entry route. These data showed that the rapidly deployed CX3CR1+ cell-based mechanism of immune-exclusion is a defence mechanism against pathogens that complements the mucous and secretory (s)IgA antibodymediated system in the protection of intestinal mucosal surface. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a worldwide occupational and environmental pollutant [1]. Cd toxicity is widely known and studied in many tissues and organs such as testis, kidney, liver, lung and brain [2,3]. On the other hand, zinc (Zn) is a trace element known as coenzyme for many proteins such as methallothionein [4]. To date, very little is known about the role of Cd and Zn in BBB permeability. To study their effects in BBB permeability in vitro, the RBE4 cell line was used and different concentrations of CdCl2 and ZnCl2 were tested. Metabolic activity (MTT assay) was performed to test the protective and preventive role of ZnCl2 on CdCl2 toxicity. Western blotting analysis was used to better investigate the molecular pathway involved in Cd-induced BBB permeability evaluating GRP78 (ER stress marker) and caspase-3 protein expression levels. Furthermore, ZO-1 and F-actin immunofluorescent staining was performed to better understand the morphological alterations and BBB permeability achieved by Cd treatment. Our preliminary data highlight the role of Cd in evoking BBB permeability by F-actin and ZO1 dislocations, triggering the caspase-3 molecular pathway activation induced by GRP78-ER stress increase. Moreover, the data clearly show how Zn is able to counteract the metabolic impairment induced by Cd treatment. Taken together these data point out the possible role of Zn in counteracting the Cd-induced BBB impairment. [ABSTRACT FROM AUTHOR]

Due to its high permeability to blood-brain barrier (BBB), cadmium (Cd) has been regarded as a possible etiological factor for human neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, and Huntington's disease [1]. However, the mechanism underlying cadmium-induced BBB permeability remains unclear. In this study, we investigated the effect of Cd in RBE4 cells (rat brain endothelial cells) and delineated the signaling pathway that, triggering endoplasmic reticulum (ER) stress and caspase 3 activation, leads to cytoskeleton disorganization and tight junctions disassembly. Our results demonstrate a possible downstream pathway mediated through the Cd-dependent ER stress, assessed by the cytoplasmic expression of an ER protein GRP78, and the consequent caspase-3 activation that results in an extracellular ATP increase, which in turns induces a dislocation, evaluated by immunofluorescent staining, of Zonula Occludens-1 (ZO-1), a tight junction protein, and F-actin. These findings, whereby Cd-induced permeabilization of BBB through a ER stressdependent pathway on endothelial cells represent a possible novel mechanism of action for Cd that could explain, at least in part, the Cd-related central effects. [ABSTRACT FROM AUTHOR]