Postural Balance, Muscle Strength and History of Falls in Kidney Transplant Recipients. Equilibrio posturale, forza muscolare e storia di cadute nei pazienti nefrotrapiantati

Background. Although post-transplantation improvement in quality of life can lead to increased levels of physical activity, the amount achieved still remain lower than those measured in general health population. Moreover, the prevalence of sarcopenia and frailty is also higher among kidney transplant recipients (KTRs) and seems to occur at a younger age compared to the general population. In particular, postural instability has been identified as one of the main factors that can lead to adverse outcomes such as falls in the elderly; so, it is plausible to speculate that people living with a renal transplant may thus also be at increased risk for falling. Additionally, muscle atrophy, commonly reported in KTRs, has consistently been associated with impaired postural control and increased risk for falling. Finally, the side effects of immunosuppressive therapy, that include central neurologic disorders (tremors) and peripheral neuropathy may also hinder the postural control of KTRs. Starting from these assumptions, the overall aim of this project is to characterized KTRs from the functional point of view. Specifically, the project was set up in three steps: compare the static balance control in KTRs with healthy adults, explore the falls’ risk profile of KTRs population, and finally involve patients in an adapted and personalized training program. At the best of our knowledge, this is the first protocol investigating static balance control in KTRs and the effects of an exercise program on this skill. Material and Methods. For the three aims were recruited three different samples. The first was composed by 19 KTRs and 19 healthy adults (HA), with same mean height, weight and age, which are the three determinants of static balance. In this protocol were assessed static balance in three different conditions: open eyes (EO), closed eyes (EC) and dual-task (DT). The second sample for the second project aim was composed by 59 KTRs divided in two groups, the first with 20 KTRs with history of falls in the previous year, and the second with 39 non-fallers. For this study were assessed fall efficacy scale (FES), static balance in the same three conditions of the first protocol, upper and lower limb strength respectively with handgrip strength test and isometric and isokinetic tests for knee and ankle muscles. For the third aim project were recruited 31 KTRs. They were involved in an adapted and personalized training program (10 sessions, 1 hour per session, 2 per week) to improve quality of life, strength and balance. Before and after training period patients’ physical function was evaluated using field tests included in the Senior Fitness Test. Results. The first experiment confirmed that KTRs are generally sedentary, and the differences between KTRs and HA in postural sway in all conditions (EO, EC and DT) reveal that KTRs had higher postural sway scores than HA. Regarding the second study, 20 out of the 59 investigation participants (33.9%) reported at least one fall in the previous year. Our findings, on falling behavior, suggest that the prevalence of falls in KTRs patients is 1.6 to 4.3 times greater than in age-matched healthy people, which is indicative of an increased risk of falling. Moreover, the muscle strength analysis highlighted an overall trend of poorer upper and lower limb strength in fallers compared to non-fallers. Regarding the last part of the project, despite the little number of training sessions and the training period, improvements in all field tests were statistically significant. Conclusions. Results corroborated the hypothesis that adapted physical activity should be prescribed as preventive therapy in KTRs, because despite the improvements in quality of life derived from the transplantation the risk of falls still remain high and strength level still remain low, increasing the risk of fracture, and accidental falls which may worsen quality of life and the health burden of these patients

CLEAR CELL-PAPILLARY RENAL CELL CARCINOMA

Il carcinoma renale papillare a cellule chiare e il carcinoma renale con stroma leiomuscolare sono due entit\ue0 recentemente descritte in letteratura, a comportamento biologico non aggressivo e composte da elementi a citoplasma chiaro e basso grado nucleare, la cui distinzione dai principali istotipi renali e in particolare dal carcinoma renale a cellule chiare di tipo convenzionale risulta spesso complessa. In questa tesi sono stati studiati 14 carcinomi renali papillari a cellule chiare e 7 carcinomi renali con stroma leiomuscolare, utilizzando un ampio pannello immunoistochimico e diverse metodiche di biologia molecolare, allo scopo di definirne maggiormente i caratteri comuni e permettere una loro distinzione pi\uf9 efficace dai pi\uf9 comuni istotipi tumorali renali. Entrambe le entit\ue0 descritte hanno presentato diffusa espressione di CK7, CAIX e costante negativit\ue0 per AMACR. E\u2019 stata inoltre evidenziata la frequente positivit\ue0 per i marcatori 34\u3b2E12 e GATA3. I tumori hanno evidenziato inoltre un profilo genetico stabile, l\u2019assenza di alterazioni del gene VHL e di perdita del cromosoma 3p. Un solo caso, con caratteristiche morfologiche e in parte immunofenotipiche e genetiche del gruppo dei carcinomi renali papillari a cellule chiare, ha presentato negativit\ue0 per 34\u3b2E12, GATA3 e presenza di alterazioni a carico del gene VHL ed \ue8 pertanto stato riclassificato come carcinoma renale a cellule chiare. L\u2019insieme dei caratteri descritti, comuni ai carcinomi renali papillari a cellule chiare e a quelli con stroma leiomuscolare, permettono di distinguerli dagli istotipi renali \u201cconvenzionali\u201d e di ipotizzare una loro origine comune. Tuttavia, la presenza di casi con caratteri in parte sovrapponibili al carcinoma renale a cellule chiare sottolinea la necessit\ue0 dell\u2019utilizzo di pi\uf9 metodiche diagnostiche per loro il riconoscimento nella pratica clinica.Clear cell papillary renal cell carcinoma (CCPRCC) is renal neoplasm that has been recently proposed to be added to the current WHO classification of renal tumors. We collected and described a series of these neoplasms, in order to get insights to their clinico-pathological and molecular profiles. We identified 14 CCPRCC. A first level of Immunohistochemical analysis was performed using CK7, CD10, AE1/AE3, alpha-methylacyl-CoA racemase, PV, S100A1, \u3b1-SMA, caldesmon and desmin. We also performed FISH analysis using probes for chromosome 3 and 3p25, array CGH, VHL sequencing and methylation analysis on a part of the cases. Than with a second level of immunoistochemical analysis, we investigated the immunoexpression of 34\u3b2E12, CK1, CK5, CK10, CK14 and GATA3, looking for specific markers. The mean age of the patients was 61, including 9 males and 5 females. The average tumor diameter was 2,62 cm. CCPRCC presented a thick encapsulation and a tubule-papillary or tubule-cystic morphology composed of clear cells with low-grade nuclei. With the first level of immunoistochemical analyses all cases were positive for CK7 and AE1-AE3 and negative for P504S, Parvalbumin, HMB45 and cathepsin K; 75% and 62% of cases were positive respectively for CD10 and S100A1. No deletion of chromosome 3p, significant VHL methylation or changes in copy number was detected in any case, whereas only one CCPRCC showed VHL mutation and presented deletions in chromosome 3 and 6 at CGH analysis. The second level immunoistochemical analysis showed that 13 of 14 cases of CCPRCC express 34\u3b2E12. The immunoexpression of CK14 had the same result of 34\u3b2E12. All cases were negative for Ck1 and CK10; only 4 cases of CCPRCC were positive for CK5. GATA3 was expressed in 7 of 13 (54%) cases of CCPRCC. Comparing as control the immunoexpression of 292 cases of conventional clear cell RCC 34\u3b2E12 (or CK14) was expressed in 0,3% and GATA3 was expressed in 1% of the cases giving to them a strong specific meaning. We concluded that CCPRCC show strong and diffuse positivity for CK7 and do not show 3p deletion, VHL mutation or methylation abnormalities. These tumors show a genomic stability after wide whole genomic analysis. We propose the immunoistochemical markers 34\u3b2E12 (or CK14) and GATA3 as specific markers useful for the identification of these distinct renal neoplasms

Hepatic pseudocystic metastasis of well-differentiated ileal neuroendocrine tumor: a case report with review of the literature

ABSTRACT: Imaging appearance of cyst-like changes is most frequently described in primary neuroendocrine lesions, especially pancreatic NETs. The imaging finding of a pseudocystic lesion of the liver puts in differential diagnosis many pathologies such as infectious diseases, simple biliary cysts up to biliary cystadenomas and eventually to primary or metastatic malignancies. Primary or metastatic hepatic malignancies with pseudocystic aspects are rare, and a pseudocystic aspect is reported only after neo-adjuvant treatment. Liver metastasis of untreated neuroendocrine tumors are usually solid and, to our knowledge, only two cases of neuroendocrine cystic hepatic metastases of ileal atypical carcinoids have been reported so far. We present a case of a 67 years old man with synchronous finding of an untreated hepatic pseudocystic lesion and an ileal mass histologically diagnosed as a well differentiated (G1) neuroendocrine tumor. VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1443883503102967

Postural control data from prevalent kidney transplant patients with and without history of falls

From Elsevier via Jisc Publications RouterItem not available in this repository.This article presents data from a research paper entitled “Postural balance, muscle strength, and history of falls in end-stage renal disease patients living with a kidney transplant: a cross-sectional study” available in Journal Gait and Posture [1]. In this article, we reported the minimal detectable changes at the 95% level of confidence (MDC95) of postural balance variables measured in eyes open (EO) and eyes closed (EC) conditions, with a stabilometric platform, in 59 kidney transplant (KT) recipients (mean age= 53.2 ± 11 years). In addition, we also performed receiver operating characteristics (ROC) curve analysis to explore the ability of postural balance measures to discriminate fallers and non-fallers (history of falls: yes or no). Sensitivity, specificity and area under the curve (AUC) of mean center of pressure velocity (CoPv), sway area (SA), center of pressure range of displacement in the anterior-posterior (AP) and medio-lateral (ML) directions were calculated. These data can be used by researchers aiming to design psychometric studies of postural balance in KT patients and they also provide clinicians with information on possible prioritization of outcome assessment for future fall-risk research in this clinical population.31pubpu

Absolute Transition Rates for Rare Events from Dynamical Decoupling of Reaction Variables

We introduce a new approach to evaluate transition rates for rare events in complex many-particle systems. Building on a path-integral representation of transition probabilities for Markov processes, the rate is first expressed in terms of a free energy in the transition-path ensemble. We then define an auxiliary process where a suitably defined reaction variable is dynamically decoupled from all the others, whose dynamics is left unchanged. For this system the transition rates coincide with those of a unidimensional process whose only coordinate is the reaction variable. The free-energy difference between the auxiliary and the physical transition-path ensembles is finally evaluated using standard techniques. The efficiency of this method is deemed to be optimal because the physical and auxiliary dynamics differ by one degree of freedom only at any system size. Our method is demonstrated numerically on a simple model of Lennard-Jones particles ruled by the overdamped Langevin equation

Hand Passive Mobilization Performed with Robotic Assistance: Acute Effects on Upper Limb Perfusion and Spasticity in Stroke Survivors

This single arm pre-post study aimed at evaluating the acute effects induced by a single session of robot-assisted passive hand mobilization on local perfusion and upper limb (UL) function in poststroke hemiparetic participants. Twenty-three patients with subacute or chronic stroke received 20 min passive mobilization of the paretic hand with robotic assistance. Near-infrared spectroscopy (NIRS) was used to detect changes in forearm tissue perfusion. Muscle tone of the paretic UL was assessed by the Modified Ashworth Scale (MAS). Symptoms concerning UL heaviness, joint stiffness, and pain were evaluated as secondary outcomes by self-reporting. Significant (p=0.014) improvements were found in forearm perfusion when all fingers were mobilized simultaneously. After the intervention, MAS scores decreased globally, being the changes statistically significant for the wrist (from 1.6±1.0 to 1.1±1.0; p=0.001) and fingers (from 1.2±1.1 to 0.7±0.9; p=0.004). Subjects reported decreased UL heaviness and stiffness after treatment, especially for the hand, as well as diminished pain when present. This study supports novel evidence that hand robotic assistance promotes local UL circulation changes, may help in the management of spasticity, and acutely alleviates reported symptoms of heaviness, stiffness, and pain in subjects with poststroke hemiparesis. This opens new scenarios for the implications in everyday clinical practice. Clinical Trial Registration Number is NCT03243123

Ruthenium(II)-Tris-pyrazolylmethane Complexes Inhibit Cancer Cell Growth by Disrupting Mitochondrial Calcium Homeostasis

While ruthenium arene complexes have been widely investigated for their medicinal potential, studies on homologous compounds containing a tridentate tris(1-pyrazolyl)methane ligand are almost absent in the literature. Ruthenium(II) complex 1 was obtained by a modified reported procedure; then, the reactions with a series of organic molecules (L) in boiling alcohol afforded novel complexes 2-9 in 77-99% yields. Products 2-9 were fully structurally characterized. They are appreciably soluble in water, where they undergo partial chloride/water exchange. The antiproliferative activity was determined using a panel of human cancer cell lines and a noncancerous one, evidencing promising potency of 1, 7, and 8 and significant selectivity toward cancer cells. The tested compounds effectively accumulate in cancer cells, and mitochondria represent a significant target of biological action. Most notably, data provide convincing evidence that the mechanism of biological action is mediated by the inhibiting of mitochondrial calcium intake

Anticancer ruthenium(II) tris(pyrazolyl)methane complexes with bioactive co-ligands

In comparison with Ru-II-arene compounds, the medicinal potential of homologous Ru-II-tpm compounds [tpm = tris(pyrazolyl)methane] is underexplored. Pyridine, 4-pyridinemethanol and four functionalized pyridines, synthesized from the esterification of 4-pyridinemethanol with bioactive carboxylic acids (i.e., ethacrynic acid, ibuprofen, flurbiprofen and naproxen), react with the precursor [RuCl(kappa(3)-tpm)(PPh3)(2)]Cl (1) to afford [RuCl(kappa(3)-tpm)(PPh3)(L)]Cl (2-7, L = pyridine ligand), in 78-91% yields. All products were fully characterized by HR-ESI mass spectrometry, IR and multinuclear NMR spectroscopy and the solid-state structures of two of the complexes, i.e. where L = pyridine and 4-pyridinemethanol, were ascertained by single crystal X-ray diffraction. The {Ru-tpm-PPh3} assembly is stable in D2O and in biological medium (DMEM) at 37 degrees C, with a tendency to slowly dissociate the pyridine ligand. The antiproliferative activity of the complexes was assessed on the cancerous A2780 and A2780cisR cell lines, and the nontumoral HEK 293T cell line; moreover inhibition assays were carried out on the complexes towards COX-2 and GSTP1 enzymes

Nordic Walking can be incorporated in the exercise prescription to increase aerobic capacity, strength and quality of life for elderly: a systematic review and meta-analysis.

Abstract The aim of this systematic review and meta-analysis was to summarize and analyze the effects of Nordic Walking on physical fitness, body composition and quality of life in the elderly. METHODS: keyword "Nordic Walking" associated with "elderly" AND/OR "aging" AND/OR "old subjects" AND/OR "aged" AND/OR "older adults" were used in the onlines database Medline, Embase, PubMed, Scopus, PsycINFO and SPORTDiscus. Only studies written in English language and published in peer-reviewed journals were considered. A meta-analysis was performed and effect sizes calculated. RESULTS: 15 studies were identified; age of participants ranged from 60 to 92 years old. Comparing with a sedentary group, effect sizes showed that Nordic Walking was able to improve dynamic balance (0.30), functional balance (0.62), muscle strength of upper (0.66) and lower limbs (0.43), aerobic capacity (0.92), cardiovascular outcomes (0.23), body composition (0.30) and lipid profile (0.67). It seemed that Nordic Walking had a negative effect on static balance (-0.72). Comparing with a walking (alone) training, effect sizes showed that Nordic Walking improved the dynamic balance (0.30), flexibility of the lower body (0.47) and quality of life (0.53). Walking training was more effective in improving aerobic capacity (-0.21). Comparing Nordic Walking with resistance training, effect sizes showed that Nordic Walking improved dynamic balance (0.33), muscle strength of the lower body (0.39), aerobic capacity (0.75), flexibility of the upper body (0.41), and the quality of life (0.93). CONCLUSIONS: Nordic Walking can be considered as a safe and accessible form of aerobic exercise for the elderly population, able to improve cardiovascular outcomes, muscle strength, balance ability and quality of life

Fast diffusing p75NTR monomers support apoptosis and growth cone collapse by neurotrophin ligands

The p75 neurotrophin (NT) receptor (p75NTR) plays a crucial role in balancing survival-versus-death decisions in the nervous system. Yet, despite 2 decades of structural and biochemical studies, a comprehensive, accepted model for p75NTR activation by NT ligands is still missing. Here, we present a single-molecule study of membrane p75NTR in living cells, demonstrating that the vast majority of receptors are monomers before and after NT activation. Interestingly, the stoichiometry and diffusion properties of the wild-type (wt) p75NTR are almost identical to those of a receptor mutant lacking residues previously believed to induce oligomerization. The wt p75NTR and mutated (mut) p75NTR differ in their partitioning in cholesterol-rich membrane regions upon nerve growth factor (NGF) stimulation: We argue that this is the origin of the ability of wt p75NTR , but not of mut p75NTR, to mediate immature NT (proNT)-induced apoptosis. Both p75NTR forms support proNT-induced growth cone retraction: We show that receptor surface accumulation is the driving force for cone collapse. Overall, our data unveil the multifaceted activity of the p75NTR monomer and let us provide a coherent interpretative frame of existing conflicting data in the literature