Mechanics of tensegrity cell units incorporating asymmetry and insights into mollitaxis.

The mechanical response of a contractile cell anchored to the substrate through focal adhesions is studied by means of an asymmetric pre-strained tensegrity structure obeying a neo-Hookean stress-strain law. The aim is to assess the influence of overall asymmetric contraction on the cell durotaxis and on the growth of the focal adhesion plaque. The asymmetric kinematics of the system is obtained in two ways, that is by assuming a gradient of the substrate stiffness and through asymmetric buckling. Equivalent springs are purposely considered to represent the stiffness of the ensemble formed by the substrate, the focal adhesion plaque and the integrin ligands. Then, contraction results from elastic strains induced by competing polymerization and actomyosin contraction. The cell mechanical response in terms of durotaxis and its coupling with focal adhesion plaque growth is finally analysed with respect to the effects of asymmetry, gaining some insights into how this asymmetry could participate to redirect cell migration, both in terms of durotaxis and mollitaxis.

Pre-strains and buckling in mechanosensitivity of contractile cells and focal adhesions: A tensegrity model.

We demonstrate that several key aspects of the contractile activity of a cell interacting with the substrate can be captured by means of a non linear elastic tensegrity mechanical system made of a tensile element in parallel with a buckling-prone component, and exchanging forces with the surroundings through an extracellular matrix-focal adhesion complex. Mechanosensitivity of the focal adhesion plaque is triggered by pre-strain-driven buckling of the system induced either by pre-contraction or pre-polymerization of the constituents. The impact of pre-polymerization on the mechanical force and the implications of using linear and nonlinear elasticity for the focal adhesion plaque are assessed.

Actomyosin contractility and buckling of microtubules in nucleation, growth and disassembling of focal adhesions.

Building up and maintenance of cytoskeletal structure in living cells are force-dependent processes involving a dynamic chain of polymerization and depolymerization events, which are also at the basis of cells' remodelling and locomotion. All these phenomena develop by establishing cell-matrix interfaces made of protein complexes, known as focal adhesions, which govern mechanosensing and mechanotransduction mechanisms mediated by stress transmission between cell interior and external environment. Within this framework, by starting from a work by Cao et al. (Biophys J 109:1807-1817, 2015), we here investigate the role played by actomyosin contractility of stress fibres in nucleation, growth and disassembling of focal adhesions. In particular, we propose a tensegrity model of an adherent cell incorporating nonlinear elasticity and unstable behaviours, which provides a new kinematical interpretation of cellular contractile forces and describes how stress fibres, microtubules and adhesion plaques interact mechanobiologically. The results confirm some experimental evidences and suggest how the actomyosin contraction level could be exploited by cells to actively control their adhesion, eventually triggering cytoskeleton reconfigurations and migration processes observed in both physiological conditions and diseases.

Preliminary comparative serological evaluation of Histamine H2 receptors in dogs with an acute onset of vomiting treated with Ranitidine and healthy dogs.

Despite the lack of evidence of the ability to suppress gastric acid secretion in dogs, ranitidine (RT) is often used to control clinical signs in dogs with acute vomiting even if the way it happens it is still largely unknown. The aim of this study was thus to evaluate the therapeutic effect of ranitidine on H2 receptors in dogs with acute vomiting. To investigate the RT activity a preliminary study was performed in dogs which underwent gastroscopy analyses, demonstrating that the level of H2R observed in the serum and gastric wall tissue was the same [1.473(1.30; 1.79) ng/ml and 1.498 (1.33; 1.85) ng/ml, respectively]. After that H2R levels in the serum of 22 healthy dogs (Group 1) and in a group of 22 dogs with acute vomiting (Group 2) were compared both before (T0), after 7-10 days (T1) of 2 mg/kg twice a day ranitidine administration and after 11 days since the drug was discontinued (T2). Significant differences (p<0.001) were detected between the level of circulating H2R among Group 1: 0.41 ng/ml (0.28;0.54) and Group 2: 2.27 ng/ml (2.11;2.49) at T0. In Group 2, no difference in the level of H2R was detected in samples collected at T0 compared to those at T1 [T1: 2.32 ng/ml (2.14; 2.49)] and T2 [T2: 2.30 ng/ml (1.99;2.69)]. In Group 2 all patients but one displayed remission of symptoms attributable to inflammatory gastropathy at the first withdrawal (T1: 7-10 days), while at the second withdrawal (T2: after 21 days), remission was detected in all dogs. Our preliminary hypothesis is that the clinical efficacy of ranitidine is related to the greater expression of H2 receptors in patients with acute vomiting. This increased expression may be due to continuous pathological stimulus at the gastric level. Further studies with a wider population are needed to better investigate the activity of RT in dogs with acute onset of vomiting.

Engineering of keratin functionality for the realization of bendable all-biopolymeric micro-electrode array as humidity sensor.

The technological quest for flexible devices to be interfaced with the biological world has driven the recent reinvention of bioderived polymers as multifunctional active and passive constituent elements for electronic and photonic devices to use in the biomedical field. Keratin is one of the most important structural proteins in nature to be used as biomaterial platform in view of the recently reported advances in the extraction and processing from hair and wool fibers. In this article we report for the first time the simultaneous use of naturally extracted keratin as both active ionic electrolyte for water ions sensing and as bendable and insoluble substrate into the same multielectrode array-based device. We implemented the multifunctional system exclusively made by keratin as a bendable sensor for monitoring the humidity flow. The enhancement of the functional and structural properties of keratin such as bendability and insolubility were obtained by unprecedented selective chemical doping. The mechanisms at the basis of the sensing of humidity in the device were investigated by cyclic voltammetry and rationalized by reversible binding and extraction of water ions from the volume of the keratin active layer, while the figures of merit of the biopolymer such as the ionic conductivity and relaxation time were determined by means of electrical impedance and dielectric relaxation spectroscopy. A reliable linear correlation between the controlled-humidity level and the amperometric output signal together with the assessment on measure variance are demonstrated. Collectively, the fine-tuned ionic-electrical characterization and the validation in controlled conditions of the free-standing insoluble all-keratin made microelectrode array ionic sensor pave the way for the effective use of keratin biopolymer in wearable or edible electronics where conformability, reliability and biocompatibility are key-enabling features.

Early post-surgical cognitive dysfunction is a risk factor for mortality among hip fracture hospitalized older persons.

This study investigates the relationship between cognitive dysfunction or delirium detected in the early post-surgical phase and the 1-year mortality among 514 hip fracture hospitalized older persons. Patients with early cognitive dysfunction or delirium experienced a 2-fold increased mortality risk. Early post-operative cognitive dysfunction and delirium are negative prognostic factors for mortality. BACKGROUND AND PURPOSE: Premorbid cognitive impairment and dementia in older individuals negatively affect functional recovery after hip fracture. Additionally, post-operative delirium is an established risk factor for negative outcomes among hip fracture patients. While the majority of hip fracture patients experience minor post-surgical cognitive dysfunction, the prognostic value of this phenomenon is unknown. Therefore, we investigated the relationship between minor cognitive dysfunction or delirium detected in the early post-surgical phase and the 1-year mortality after index hip fracture. SUBJECTS AND METHODS: We enrolled 514 patients with hip fracture (77.4 % women), aged 65 years or older (mean age 83.1 ± 7.3 years), who underwent surgical hip fracture repair. Patients were assessed daily from the second to the fourth post-operative day and at 3, 6, and 12 months thereafter. All participants underwent comprehensive assessment, including detection of delirium by using the confusion assessment method and evaluation of cognitive function by using mini-mental state examination (MMSE; score range 0 to 30, with lower scores indicating poorer performance). In the absence of delirium, post-surgical cognitive dysfunction was defined as having low performance on MMSE. Vital status of 1 year after the index fracture and date of death were gathered from local registries. RESULTS: The observed 1-year mortality rate was 14.8 %. Men were more likely to die than women within 1 year of the index fracture (p < 0.01). Compared to participants with better cognitive performance, those with MMSE < 24, as well as those with delirium in the post-operative phase, showed a significantly higher 1-year mortality rate (23.3 versus 17.9 and 8.1 %, respectively). Independent of age and sex, post-operative cognitive dysfunction as well as delirium was both associated with a 2-fold increased mortality risk. CONCLUSIONS: The presence of minor cognitive dysfunction in the early post-surgical phase is a negative prognostic factor for mortality among elderly hip fracture patients. The burden of minor cognitive dysfunction is likely superimposed on that of delirium in subgroups of frail patients.

Epidemiology of hip and knee pain in a community based sample of Italian persons aged 65 and older.

OBJECTIVE: To describe prevalence, characteristics and correlates of hip pain (HP) and knee pain (KP) in an Italian community based cohort aged 65 and older (65+). METHOD: Baseline survey (1998-2000), population-based study in the Chianti area (Tuscany, Italy); 1299 persons aged 65+ were selected from the city registry of Greve in Chianti and Bagno a Ripoli (multistage sampling method); 1006 participants (564 women and 442 men, age 75.2+/-7.1) provided information for this analysis. Persons reporting HP/KP in the past 4 weeks were recorded and their Western Ontario and McMaster University Osteoarthritis Index pain score (WPS-range 0-20) calculated. Potential correlates of HP/KP, including clinical, lifestyle and psycho-social features and physical measures, were tested in age- and gender-adjusted regression analyses and then entered a multivariate regression model. RESULTS: HP was reported by 11.9% participants, while 22.4% reported KP and 7.2% both conditions. Climbing/descending stairs and walking were the activities eliciting more severe pain in either condition. Average WPSs were 5.6+/-3.5 for HP and 5.4+/-10.4 for KP. Both HP and KP were related to back pain, reduced hip abduction, reduced muscle power and increased trunk flexibility. HP was also related to KP and poor self-rated health (SRH), while KP to HP, foot pain, high body mass index, reduced knee passive flexion and knee extension torque, low education. CONCLUSION: In a community sample of an Italian persons aged 65+, the prevalence of KP almost doubled that of HP. While both conditions were related to pain in other joints and specific joint impairment, only HP was related to poor SRH, and only KP to mechanical overload.

Extradural motor cortex stimulation as a method to treat advanced Parkinson's disease: new perspectives in geriatric medicine.

Motor fluctuations not controlled by pharmacological therapy are often encountered in long-term Parkinson's disease (PD). Neurosurgery treatment represented by deep brain stimulation (DBS) was considered a valid alternative to pharmacological treatment. Unfortunately this method is most effective in patients under age of 70. Recently it has been suggested that extradural motor cortex stimulation (EMCS) could be a valid cost-effective alternative to DBS to control motor symptoms in patients affected by Parkinson's disease. The relevant non-invasive surgical technique makes this treatment particularly indicated in geriatric patients. Brain atrophy, cognitive impairment, psychiatric symptoms are not an absolute contraindication to the treatment. We submitted to EMCS an outpatient afferent to our geriatric department, a woman 68 yrs old. The patient showed an improvement of 35% as measured by the Unified Parkinson Disease Rating Scale (UPDRS) scale after the surgery. If our findings will be confirmed in larger series, a new dimension will be added to the treatment of PD.

New aspects of the insulin resistance syndrome: impact on haematological parameters.

AIM/HYPOTHESIS: Previous studies have shown that insulin has an important in vitro role in the regulation of human erythropoiesis. We investigated whether in vivo hyperinsulinaemia/insulin resistance affects haematological parameters. METHODS: A total of 608 subjects between 22 and 99 years of age were enrolled in the Chianti study, an epidemiological study of factors affecting mobility in old age. The degree of insulin resistance was assessed using the homeostasis model. RESULTS: We found a correlation between insulin resistance and red blood cell count, (r = 0.14 p < 0.001), plasma haemoglobin (r = 0.16 p < 0.001), haematocrit (r = 0.15 p < 0.001) and plasma iron (r = 0.1 p < 0.05) concentrations. Red blood cell count was also associated with the other biological markers of insulin resistance syndrome. Subjects with higher insulin resistance (4 degrees quartile) had higher red blood cell count, plasma triglycerides and low density lipoproteins (LDL) cholesterol concentrations and lower high density lipoproteins (HDL) cholesterol concentrations then subjects at the lowest quartiles of insulin resistance. Insulin resistance and BMI were significant and independent predictors of red blood cell count even when the analysis was adjusted for age, sex, waist-to-hip ratio, plasma iron and drug intake. CONCLUSION/HYPOTHESIS: Our findings provide in vivo evidence of a relation between hyperinsulinaemia/insulin resistance, the main variables of insulin resistance syndrome and erythropoiesis. Increased red blood cell count could be considered as a new aspect of the insulin resistance syndrome that could contribute to the increased risk of developing cardiovascular problems.

Subsystems contributing to the decline in ability to walk: bridging the gap between epidemiology and geriatric practice in the InCHIANTI study.

BACKGROUND: Older patients are often referred to geriatricians because of complaints of progressive difficulties in walking. The diagnostic and therapeutic approach to these patients is complex. Multiple physiologic subsystems may influence the ability to walk, and no standard criteria are currently available to establish whether these subsystems are functioning within the normal range. To address this lack of knowledge we conducted the InCHIANTI study. OBJECTIVE: To identify measures that clinicians can use to understand the causes of walking difficulties in older persons. DESIGN: A population-based study of persons living in the Chianti geographic area (Tuscany, Italy). PARTICIPANTS: 1,453 persons (age-range 20-102 years; 91.6% of the eligible) selected from city registry of Greve in Chianti and Bagno a Ripoli (Tuscany, Italy), using a multistage sampling method. MEASUREMENTS: Factors that influence walking ability were classified into six main physiologic subsystems: central nervous system, perceptual system, peripheral nervous system, muscles, bone/joints, and energy production/delivery. Measures of the integrity and functioning of each of these proposed subsystems were identified and administered to all participants. CONCLUSIONS: Data collected in InCHIANTI will be used to identify the main risk factors that influence loss of the ability to walk in older persons, to define physiologic subsystems that are critical for walking, to select the best measures of their integrity, and to establish critical ranges in these measures that are compatible with "normal" walking ability. The final goal is to translate epidemiological research into a geriatric clinical tool that makes possible more precise diagnosis and more effective treatment in patients with walking dysfunction.

Preventive health care for older women: life-style recommendations and new directions.

One of the key paradoxes in gerontology is that, despite a higher longevity, aging women experience worse health and longer disability than men. However, there is growing evidence that changes in life-style, medical interventions and systematic screening for certain diseases may substantially reduce the excess risk of major chronic conditions and disability in aging women, and therefore improve the quality of their late life. The potentials and public health implications of prevention in older women have been recently emphasized, not only by the scientific literature, but also by the media. More and more women are turning to their primary care physicians or other health professionals to seek counselling and help on how to reduce the burden of chronic disease and disability in old age by quitting smoking, eating a healthy diet, increasing physical activity, and coping with stress. Hormone replacement therapy also has a central role in this action of prevention. To maximize compliance, women should be provided a few guidelines that are easy to understand, and can be followed without interfering too much with their daily life activities. This article reviews the current literature on prevention in older women to select preventive strategies that are based on robust scientific evidence. This list of guidelines should be considered as a starting point for all those who are in charge of caring for middle-aged and older women.

Factors related to the length of in-hospital stay of geriatric patients.

The aim of this study was to evaluate factors predicting length of stay in hospital of geriatric patients. Study participants were 402 patients (183 males and 219 females) consecutively admitted to four geriatric wards located in Chieti, Perugia, Pescara and Prato, Italy. Information on potential predictors of length of stay was collected; in particular, we assessed the presence and severity of specific chronic medical conditions, level of physical function, cognitive status, and depressive symptoms. Moreover, information on family and social support was obtained. In general, participants were old, often cognitively impaired and physically disabled. Average length of stay ranged from 9.4 +/- 3.3 days (Perugia) to 14.1 +/- 7.2 days (Chieti), and was statistically different across centers (p < 0.001). None of the specific medical diagnoses was associated with different length of stay. However, higher comorbidity score (p < 0.001), living alone (p < 0.01), lower MMSE score (p = 0.03), and poor functional status (p = 0.05) were all associated with longer length of stay. When these variables were included in a multivariate model predicting length of stay, differences between centers were no longer statistically significant. Findings of this study show that specific medical diagnoses are not adequate instruments to estimate length of stay in geriatric units. Other assessment systems based on extension of the social network, comorbidity, and the cognitive as well as the functional level need to be developed.

Kinematic characteristics of standing disequilibrium: reliability and validity of a posturographic protocol.

OBJECTIVE: To investigate retest reliability and concurrent validity of the fundamental measurements made of a posturographic protocol that employs quiet standing to quantify the severity and the nature of patients' postural disturbances. STUDY DESIGN: Retrospective complete block design. SETTING: Geriatric rehabilitation department. PARTICIPANTS: Thirty-six participants (age range, 67 to 86 yrs) having normal, moderate, or severe levels of disequilibrium. METHODS: Quiet standing was evaluated on three occasions using a three-dimensional motion analysis system and a force platform. Eight testing conditions, designed to vary task difficulty by controlling the contributions of vision, foot proprioception, and base-of-support width, were administered. MAIN OUTCOME MEASURES: Retest reliability of body sway, joint alignment, body position, and motor coordination indicators were evaluated by intraclass correlation coefficients (ICCs). Concurrent validity of protocol measures was evaluated by the prediction of disequilibrium from a stepwise linear discriminant analysis. RESULTS: ICCs indicated high level of retest reliability for all variables but those of motor coordination, which was not influenced by testing conditions. Discriminant analysis resulted in a four-factor discriminator that included measures of body sway, position, alignment, and motor coordination. The derived linear discriminate function correctly classified 96% of the patients' level of disequilibrium. CONCLUSIONS: The posturographic protocol has the potential to be a useful tool for evaluating severity and nature of postural instability and the effects of pharmacologic and rehabilitative treatment. Results also indicate that combining direct body measurements with force-plate data has the potential to expose the underlying impairments that cause disequilibrium, determine their pathogenesis, and evaluate compensatory strategies.

Measuring muscular strength of the lower limbs by hand-held dynamometer: a standard protocol.

The aim of this study is to describe the reliability of measuring maximal strength of eight muscle groups of the lower limb by a hand-held dynamometer, according to a standard assessment protocol. The study population consisted of 26 patients (14 males and 12 females; age range 60-90 years) admitted to a geriatric hospital. Multiple assessments of muscle strength by two different examiners were compared to estimate test-retest and inter-rater reliability. The range of strength evaluated across the eight muscle groups was 2.1-29.8 Kg/force. Overall, short-term (same day) and long-term (one week apart) test-retest and inter-rater reliability were very high, with 60% of the intraclass correlation coefficient values above 0.8, and the majority above 0.7. No significant differences in strength were found comparing the left and the right side of each muscle group. Differences between values collected in the same subject by two different examiners, and by the same examiner at different points in time were similar, not influenced by the average strength of the muscle group, and significantly larger for long-term than for short-term comparisons. By using a standardized measurement protocol, reliable measurements of muscle strength can be obtained by a hand-held dynamometer in frail older persons.

Is the telephone interview for cognitive status a valid alternative in persons who cannot be evaluated by the Mini Mental State Examination?

The Mini Mental State Examination (MMSE), a widely used tool for first-line assessment of cognitive function, cannot be fully administered to persons with severe visual or upper extremity impairments. This cross-sectional study, which was performed in a sample of patients admitted to the outpatient clinic of the INRCA Geriatric Department "I Fraticini" (Firenze, Italy) and their relatives, evaluated whether the Telephone Interview for Cognitive Status (TICS), a test originally created for telephone screening of cognitive impairment, is a valid alternative for assessment of cognition in persons who cannot provide valid responses to all the MMSE items. Fifteen subjects in each of seven MMSE strata (9-11, 12-14, 15-17, 18-20, 21-23, 24-26, 27-30) were consecutively selected. Inclusion criteria were: age > or = 60 years; Italian as the main language; education > or = 3 years; medical stability; and ability to complete the MMSE. At admission, participants were examined for dementia by an expert clinician according to the DSM IV criteria. Italian versions of the TICS and the MMSE were administered face-to-face by two trained interviewers. The TICS was readministered face-to-face one week later by the same interviewer that had previously administered the test. The TICS showed good test-retest reproducibility. Assessments taken one week apart differed on average by 0.52 +/- 1.9 points (p < 0.01), indicating a systematic improvement. The TICS explained 96% of the variance in the MMSE, and this association was independent of age, gender and education. More than 90% of the cases "screening positive" (i.e., scoring below a certain cut-off) by the TICS, were also identified as "screening positive" when comparable MMSE cut-off scores were used. Using comparable cut-off scores, the sensitivity and specificity of TICS and MMSE in detecting a standard clinical diagnosis of dementia largely overlapped. In persons who cannot be evaluated with the MMSE in its full form, the face-to-face administration of the TICS is a reliable and valid alternative.

Maternal and fetal catecholamines and uterine incision-to-delivery interval during elective cesarean.

The fetal sympathoadrenal system is activated during periods of intrauterine stress such as inadequate uterine perfusion. During cesarean, the period of interruption of utero-placental blood flow is extended as the time interval from uterine incision to delivery increases. An increasing uterine incision-to-delivery interval with spinal or general anesthesia has been associated with a poorer neonatal outcome. This association has not been demonstrated previously in patients undergoing cesarean delivery under epidural anesthesia. We investigated the correlation between prolonged uterine incision-to-delivery intervals, fetal catecholamine concentrations, and fetal blood gas values at delivery in 25 parturients undergoing cesarean under epidural anesthesia and in 28 under spinal anesthesia. Infants delivered after prolonged uterine incision-to-delivery intervals had significantly lower pH values in both the epidural and spinal groups. With longer uterine incision-to-delivery intervals, umbilical arterial norepinephrine concentrations were increased significantly. Umbilical arterial pH values were significantly lower in infants with higher umbilical arterial catecholamine concentrations. The importance of minimizing the uterine incision-to-delivery interval, regardless of the type of anesthetic selected, is demonstrated.

[Dyslipidemia and hyperbaric osteonecrosis in the rat]. / Dyslipidémie et ostéonécrose hyperbare chez le rat.

The authors subjected 149 adult Sprague-Dawley rats to repeated experimental dives, simulated to 160 m. Histopathological examination (femurs and tibias) revealed no evidence of osteonecrosis in either normal or dyslipidaemic animals. Study of the calcium metabolism using 45Ca revealed a significant drop in the levels of free and bound calcium and in the rate of exchange between the two compartments, in the dyslipidaemic animal placed in hyperbaric conditions.