The diagnostic value of conventional radiography and musculoskeletal ultrasonography in calcium pyrophosphate deposition disease: a systematic literature review and meta-analysis.

OBJECTIVE: To examine and compare the accuracy of conventional radiography (CR) and musculoskeletal ultrasonography (US) in the diagnosis of calcium pyrophosphate (CPP) crystals deposition disease (CPPD). DESIGN: A systematic search of electronic databases (PubMed, Embase, and Cochrane), conference abstracts and reference lists was undertaken. Studies which evaluated the accuracy of CR and/or US in the diagnosis of CPPD, using synovial fluid analysis (SFA), histology or classification criteria as reference tests were included. Subgroup analyses by anatomic site and by reference test were performed. RESULTS: Twenty-six studies were included. Using SFA/histology as reference test, CR and US showed an excellent (CR AUC = 0.889, 95%CI = 0.811-0.967) and an outstanding (US AUC = 0.954, 95%CI = 0.907-1.0) diagnostic accuracy (p < 0.01), respectively. Furthermore, US showed a higher sensitivity (0.85, 95%CI = 0.79-0.90 vs 0.47, 95%CI = 0.40-0.55) and only a little lower specificity (0.87, 95%CI = 0.83-0.91 vs 0.95, 95%CI = 0.92-0.97) than CR. A considerable heterogeneity between the studies was found, with adopted reference test being the main source of heterogeneity. In fact, subgroup analysis showed a significant change in the diagnostic accuracy of CR, but not of US, using Ryan and McCarty criteria or SFA/histology as reference test (CR: AUC = 0.956, 95%CI = 0.925-1.0 vs AUC = 0.889, 95%CI = 0.828-0.950, respectively, p < 0.01) (US: AUC = 0.922, 95%CI = 0.842-1.0 vs AUC = 0.957, 95%CI = 0.865-1.0, respectively, p = 0.08) CONCLUSIONS: Although US is more sensitive and a little less specific than CR for identifying CPP crystals, both these two techniques showed a great diagnostic accuracy and should be regarded as complementary to each other in the diagnostic work-up of patients with CPPD.

The folding and aggregation properties of a single KH-domain protein: Ribosome binding factor A (RbfA) from Pseudomonas aeruginosa.

BACKGROUND: Ribosome-binding factor A from the pathogenic bacterium Pseudomonas aeruginosa (PaRbfA) is a small ribosome assembly factor, composed by a single KH domain, involved in the maturation of the 30S subunit. These domains are characterized by the ability to bind RNA or ssDNA and are often located in proteins involved in a variety of cellular functions. However, although the ability of proteins to fold properly, to misfold or to aggregate is of paramount importance for their cellular functions, limited information is available on these dynamic properties in the case of KH domains. METHODS: PaRbfA thermodynamic stability and folding mechanism: Far-UV CD and fluorescence spectroscopy, stopped-flow kinetics and chevron plot analysis, site-directed mutagenesis. Fibrils characterization: FT-IR spectroscopy, Thioflavin T fluorescence, Transmission Electron Microscopy (TEM) and X-ray fibrils diffraction. RESULTS: Quantitative analysis of the (un)folding kinetics of PaRbfA show that, in vitro, the protein folds via a 3-states mechanism involving a transiently populated folding intermediate. We also provide experimental evidences that PaRbfA can form ordered fibrils endowed with cross-ß structure even in mild conditions. CONCLUSION: These results lead to the hypothesis that the folding intermediate of PaRbfA may expose (some of) the predicted amyloidogenic regions, which could act as aggregation nuclei in the fibrillogenesis. GENERAL SIGNIFICANCE: The methodological approach presented herein could be readily adapted to verify the ability of other KH domain proteins to form cross-ß structured fibrils and to transiently populate a folding intermediate.

Empowering crop resilience to environmental multiple stress through the modulation of key response components.

Crop plants have developed a multitude of defense and adaptation responses to protect themselves against invading pathogens and challenging environmental stresses, mostly operating jointly. The plant perception of overall stress induces a coordinated response mediated by complex signaling networks. Experimental evidences proved that plant response to combined biotic and abiotic stresses substantially diverge from the responses to individual stresses. Moreover, the cross-talk of signaling pathways involved in responding to biotic and abiotic stresses is pivoted on several converging elements able to simultaneously modulate the timing and amplitude of the overall plant response. Comprehensively, the interaction between biotic and abiotic stresses can dramatically changes the plant response to the individual stress and the phenotypical outcome of each stress factor. System biology and data mining can synergistically help biologists in finding out regulative mechanisms and key genes controlling the response to biotic and abiotic stresses. Deploying new genetic engineering solutions can rely on the modification of genes involved in resistance/tolerance processes and/or in the modulation of regulatory elements. Finally, a model of the engineered crop for enhanced tolerance to pressures resulting from invasive pathogens and abiotic constraints in semiarid and warm environment is discussed.

Deep-sequencing of Solanum commersonii small RNA libraries reveals riboregulators involved in cold stress response.

Among wild species used in potato breeding, Solanum commersonii displays the highest tolerance to low temperatures under both acclimated (ACC) and non-acclimated (NACC) conditions. It is also the first wild potato relative with a known whole genome sequence. Recent studies have shown that abiotic stresses induce changes in the expression of many small non-coding RNA (sncRNA). We determined the small non-coding RNA (sncRNAome) of two clones of S. commersonii contrasting in their cold response phenotypes via smRNAseq. Differential analysis provided evidence that expression of several miRNAs changed in response to cold stress conditions. Conserved miR408a and miR408b changed their expression under NACC conditions, whereas miR156 and miR169 were differentially expressed only under ACC conditions. We also report changes in tasiRNA and secondary siRNA expression under both stress conditions. Our results reveal possible roles of sncRNA in the regulatory networks associated with tolerance to low temperatures and provide useful information for a more strategic use of genomic resources in potato breeding.

Ultrasound in the assessment of musculoskeletal involvement in systemic lupus erythematosus: state of the art and perspectives.

Musculoskeletal manifestations are extremely common in patients with systemic lupus erythematosus. Transient and migratory arthralgia is frequently reported even without clinical signs of joint or tendon inflammation. In less than 15% of patients, joints may be more severely affected by deforming (Jaccoud's arthropathy) and/or erosive arthropathy (Rhupus syndrome). In recent years, ultrasound has emerged as a promising imaging technique for the assessment of musculoskeletal involvement in systemic lupus erythematosus, having demonstrated the ability to detect inflammation and structural damage both at articular and periarticular level. Recent ultrasound studies have also revealed new insights into musculoskeletal involvement in patients with systemic lupus erythematosus, some of them questioning the traditional concepts of systemic lupus erythematosus arthropathy, with potential clinical, prognostic and therapeutic implications. In daily clinical practice, the use of ultrasound in the assessment of joint and tendon involvement in patients with systemic lupus erythematosus is still limited. Several methodological issues encountered in ultrasound studies evaluating musculoskeletal involvement in systemic lupus erythematosus patients need to be addressed in order to improve both the reliability and clinical usefulness of ultrasound findings. This paper reviews ultrasound studies assessing musculoskeletal involvement in patients with systemic lupus erythematosus, highlighting certainty, limits, potential applications and future perspectives of ultrasound use in systemic lupus erythematosus patients.

N6L pseudopeptide interferes with nucleophosmin protein-protein interactions and sensitizes leukemic cells to chemotherapy.

NPM1 is a multifunctional nucleolar protein implicated in several processes such as ribosome maturation and export, DNA damage response and apoptotic response to stress stimuli. The NPM1 gene is involved in human tumorigenesis and is found mutated in one third of acute myeloid leukemia patients, leading to the aberrant cytoplasmic localization of NPM1. Recent studies indicated that the N6L multivalent pseudopeptide, a synthetic ligand of cell-surface nucleolin, is also able to bind NPM1 with high affinity. N6L inhibits cell growth with different mechanisms and represents a good candidate as a novel anticancer drug for a number of malignancies of different histological origin. In this study we investigated whether N6L treatment could drive antitumor effect in acute myeloid leukemia cell lines. We found that N6L binds NPM1 at the N-terminal domain, co-localizes with cytoplasmic, mutated NPM1, and interferes with its protein-protein associations. N6L toxicity appears to be p53 dependent but interestingly, the leukemic cell line harbouring the mutated form of NPM1 is more resistant to treatment, suggesting that NPM1 cytoplasmic delocalization confers protection from p53 activation. Moreover, we show that N6L sensitizes AML cells to doxorubicin and cytarabine treatment. These studies suggest that N6L may be a promising option in combination therapies for acute myeloid leukemia treatment.

Systemic lupus erythematosus arthropathy: the sonographic perspective.

Background Despite being promising, the use of ultrasound (US) in the assessment of musculoskeletal manifestations of systemic lupus erythematosus (SLE) is still limited. Literature on this topic is scarce and the spectrum and clinical relevance of US abnormalities has not yet been outlined. With this paper, we aim to explore the panel of joint and tendon US findings in a group of SLE patients. Methods Twenty-five consecutive SLE patients, with current or medical history of musculoskeletal symptoms, were studied. All patients underwent routine clinical examination and US evaluation. The US examination targeted sites clinically involved in the physical examination and/or indicated as painful in the patient's medical history. Results One or more US changes were found in all the patients. US abnormalities were detected in 85 out of the 243 scanned joints (35%), in 70 out of the 215 scanned tendons (32.6%) and in 10 out of the 41 scanned entheses (24.4%). Synovial effusion, synovial hypertrophy, "mixed" synovitis (coexistence of synovial effusion and synovial hypertrophy), joint dislocation, bone erosion, and cartilage damage were found in 9.5%, 11.5%, 14%, 3.7%, 2.1%, and 4.5% of the scanned joints, respectively. Tenosynovitis, tendon dislocation, tendon tear, tendon thinning, and tendinitis/peritendinitis were detected in 17.7%, 8.4%, 0.9%, 4.2%, and 4.7% of the scanned tendons, respectively. Power Doppler signal, hypoechogenicity, thickening, enthesophytes, calcifications, and bone erosions were detected at the entheseal level in 12.2%, 9.8%, 12.2%, 7.3%, 7.3%, and in 0% of the scanned entheses, respectively. Conclusions This study revealed an unexpectedly wide heterogeneity of US pathologic findings in the joints and tendons of patients with SLE. A broad spectrum of US changes also involving anatomic structures not considered in previous investigations, including entheses and tendons with no synovial sheath, was detected. These preliminary results suggest that US is able to identify several US "patterns" whose clinical, prognostic, and pathogenetic significance is still to be defined.

Structural investigation of nucleophosmin interaction with the tumor suppressor Fbw7γ.

Nucleophosmin (NPM1) is a multifunctional nucleolar protein implicated in ribogenesis, centrosome duplication, cell cycle control, regulation of DNA repair and apoptotic response to stress stimuli. The majority of these functions are played through the interactions with a variety of protein partners. NPM1 is frequently overexpressed in solid tumors of different histological origin. Furthermore NPM1 is the most frequently mutated protein in acute myeloid leukemia (AML) patients. Mutations map to the C-terminal domain and lead to the aberrant and stable localization of the protein in the cytoplasm of leukemic blasts. Among NPM1 protein partners, a pivotal role is played by the tumor suppressor Fbw7γ, an E3-ubiquitin ligase that degrades oncoproteins like c-MYC, cyclin E, Notch and c-jun. In AML with NPM1 mutations, Fbw7γ is degraded following its abnormal cytosolic delocalization by mutated NPM1. This mechanism also applies to other tumor suppressors and it has been suggested that it may play a key role in leukemogenesis. Here we analyse the interaction between NPM1 and Fbw7γ, by identifying the protein surfaces implicated in recognition and key aminoacids involved. Based on the results of computational methods, we propose a structural model for the interaction, which is substantiated by experimental findings on several site-directed mutants. We also extend the analysis to two other NPM1 partners (HIV Tat and CENP-W) and conclude that NPM1 uses the same molecular surface as a platform for recognizing different protein partners. We suggest that this region of NPM1 may be targeted for cancer treatment.

Entheseal involvement in systemic lupus erythematosus: are we missing something?

Background Musculoskeletal involvement is extremely common in patients with systemic lupus erythematosus (SLE). Continuing the research initiated in patients with inflammatory arthritis, recent studies have shown the potential role of musculoskeletal ultrasound (MSUS) in the evaluation of clinical and subclinical lupus synovitis. The inflammatory process in SLE is traditionally considered to be localized at synovial tissue areas while enthesis is not included among the possible targets of the disease. Patients and methods Entheses included in the Glasgow Ultrasound Enthesitis Scoring System were scanned in a cohort of 20 SLE patients serving as disease controls in an MSUS study aimed at assessing enthesitis in patients with psoriatic arthritis. We describe in detail four cases with unexpected and unequivocal expressions of MSUS enthesitis according to the OMERACT definition. Three out of four patients had no predisposing factors for enthesopathy. Case no. 2 was treated with a variable-dose prednisone regimen. Results In the four cases MSUS examination revealed relevant grey-scale and power Doppler abnormalities at the entheseal level, most commonly at the distal insertion of the patellar tendon. Signs of clinical enthesitis were detected in only one patient. Conclusions This case series shows for the first time the presence of clearly evident MSUS findings indicative of enthesitis in four out of 20 SLE patients (20%), raising the hypothesis that enthesis could be a missing target in the clinical evaluation of SLE patients. Our case series justifies further investigations for a better evaluation of the prevalence, characteristics and clinical relevance of entheseal involvement in SLE.

Tubercular liver abscess: an uncommon presentation of disseminated tuberculosis.

We present a case of tubercular liver abscess with disseminated tuberculosis, associated with underlying HIV infection. The patient responded well to percutaneous drainage of the abscess and first-line quadruple antitubercular therapy. We report this case to highlight a rare manifestation of a common disease and to create greater awareness which may ensure timely diagnosis and avoid unnecessary surgical intervention.

The MyD88 rs6853 and TIRAP rs8177374 polymorphic sites are associated with resistance to human pulmonary tuberculosis.

Toll-like receptors recognize several components of Mycobacterium tuberculosis, the main causative agent of tuberculosis. The signaling pathways leading to activation of the immune response require the MyD88 and TIRAP genes. The hypothesis that polymorphic variants of these genes influenced resistance to pulmonary tuberculosis was tested by a case-control study (400 cases and 400 controls). Heterozygosity at the polymorphic sites MyD88 rs6853 (alleles: A, G) or TIRAP rs8177374 (S180L) (alleles: C, T) is associated with resistance to pulmonary tuberculosis (P: 7.8 × 10(-8) and 2 × 10(-6), respectively). Double heterozygosity confers higher protection levels (P: 10(-14) to 2 × 10(-16)). The logistic regression model displayed that the double homozygous genotype GG/TT predisposes to the disease (odds ratio (OR): 5.78) and the AG/TT genotype combination neutralizes the protective activity exerted by AG (OR: 3.05). The same model showed that the risk of developing the disease increases with age from 31-40 years to 71-80 years (OR: 1.32-13.59).

Prevention of acute renal failure post-contrast imaging in cardiology: a randomized study.

BACKGROUND: The contrast-induced nephropathy (CIN) is the third most common cause of acute renal failure (ARF) and the worsening in a pre-existing chronic renal failure (CRF), with a foreseeable increase of morbidity, mortality, length of the stay in hospital and, as a consequence, of the health costs. We studied the effectiveness of N-acetylcysteine (NAC) associated with sodium bicarbonate (Na2HCO3) infusion in order to prevent CIN in patients undergoing coronary angiography with administration of contrast medium. MATERIALS AND METHODS: 296 patients with indication to perform coronary angiography were included in a randomized, observational study. All patients were randomly assigned to receive pre- and post-contrast hydration with 1500 ml of 0.9% saline solution infusion (Group A) or NAC (1200 mg × 2 days) + Na2HCO3 (Group B). The primary end-point was to examine CIN appearance, defined as a raise in serum values of Cr (Creatinine) ≥ 0.5 mg/dl or ≥ 25% within 24-72 hours after the exposure to the contrast medium. RESULTS: It has been observed a frequency of CIN of 9.4% in Gr. A compared to 7.2% in Gr. B. Nevertheless, when we put these results through a more accurate screening according to gender, degree of raise in creatinine levels and the extent of change in GFR (glomerular filtration rate), we observed a very different behaviour. In patients with normal Cr and CrCl (Clearance of Creatinine) the frequency of CIN was similar in both group A and B (approximately 5%). In patients with normal Cr but reduced ClCr the use of NAC was more effective than hydration in preventing CIN (0% vs 18% in prevalence respectively in B and A group). In patients with moderately reduced Cr and CrCl, hydration with saline solution was more effective than NAC + Na2HCO3 (8.6% vs 17.6%) while in patients with severe CRF the combined use of NAC + Na2HCO3 showed off to be very successful in preventing CIN compared to the merely hydration (0% vs 50%). CONCLUSIONS: In patients affected by severe CRF who are undergoing investigations with contrast medium administration, such as coronary angiography, the combined use of NAC + Na2HCO3 infusion significantly reduces the risk of developing CIN. In other circumstances the final result is related to the degree of previous GFR or creatinine values alteration or to gender. In such situations the combined use of both substances is more questionable and sometimes ineffective.

A united event grand canonical Monte Carlo study of partially doped polyaniline.

A Grand Canonical Monte Carlo scheme, based on united events combining protonation/deprotonation and insertion/deletion of HCl molecules is proposed for the generation of polyaniline structures at intermediate doping levels between 0% (PANI EB) and 100% (PANI ES). A procedure based on this scheme and subsequent structure relaxations using molecular dynamics is described and validated. Using the proposed scheme and the corresponding procedure, atomistic models of amorphous PANI-HCl structures were generated and studied at different doping levels. Density, structure factors, and solubility parameters were calculated. Their values agree well with available experimental data. The interactions of HCl with PANI have been studied and distribution of their energies has been analyzed. The procedure has also been extended to the generation of PANI models including adsorbed water and the effect of inclusion of water molecules on PANI properties has also been modeled and discussed. The protocol described here is general and the proposed United Event Grand Canonical Monte Carlo scheme can be easily extended to similar polymeric materials used in gas sensing and to other systems involving adsorption and chemical reactions steps.

Efficacy of calcium channel blockers in the treatment of the myocardial bridging: a pilot study.

BACKGROUND: Myocardial Bridging (MB) is defined as a segment of a major epicardial coronary artery, the "tunnelled artery", that goes intramurally through the myocardium beneath the muscle bridge. MATERIALS AND METHODS: A 69-year-old male patient with a story of arterial hypertension and dyslipidemia in treatment with converting enzyme inhibitors (ACE-I), antiplatelet therapy and HMG-CoA reductase inhibitors and calcium channel blockers, presented with anginal-like chest pain and dyspnea. The coronary angiography showed a myocardial bridging and no hemodynamically significant coronary artery disease. RESULTS: On admission in our Department, the exercise cyclo ergometer test was significant for > 3 mm ST segment depression in the anterior and lateral leads (V3, V4, V5, V6) associated with chest pain. The coronary angiography revealed a 40% stenosis of the distal tract of the right coronary artery (RCA), a 30% stenosis of the proximal tract of the left anterior descending artery (LAD) and 40% of the proximal tract of the first diagonal branch. A 30% stenosis in the middle tract of the left circumflex coronary artery (LCX) was then detected. A marked systolic localized narrowing (90%) on the middle tract of the LAD, after the second diagonal branch (a myocardial bridge) was also detected. After eight months, the exercise cyclo ergometer test using a standard Bruce protocol was normal and, after sixteen months, no significant coronary artery disease (< 50%) and no myocardial bridging were detected by the coronary 64-multislice spiral computed tomography. Two years later, the patient was readmitted to our Department because of angina-like chest pain during light exertion in the last two months. The coronary angiography of the right system revealed a 30% stenosis of the proximal tract and a 50% stenosis of the distal tract of the RCA. The coronary angiography of the left system showed a 30% stenosis of the proximal tract of the LAD and 85% of the middle tract of the first diagonal branch. A 40% stenosis in the middle tract of the left circumflex coronary artery (LCX) was then detected. No MB of the middle tract of the LAD was detected, and a bare metal stent (Presillion 2.5 x 12 mm) was deployed in the middle tract of the first diagonal branch. CONCLUSIONS: After 2 years, the administration of the calcium channel blockers has been effective in the treatment of the MB but no effect on the atherosclerotic plaque growth has been demonstrated.

Catheter ablation of atrial tachycardia after interatrial defect repair with patch apposition.

A 54-year-old woman with history of septal atrial mixoma surgically treated and drug-refractory supraventricular tachyarrhythmia underwent catheter ablation of macro-reentry areas near the pericardial patch placed to repair an interatrial defect. The use of ablative therapy has been successful to cure this arrhythmia.

Hemi- and monoataxia in cerebellar hemispheres and peduncles stroke lesions: topographical correlations.

Limb ataxia of sudden onset is due to a vascular lesion in either the cerebellum or the brainstem (posterior circulation, PC, territory). This sign can involve both the upper and the lower limb (hemiataxia) or only one limb (monoataxia). The topographical correlates of limb ataxia have been studied only in brainstem strokes. Therefore, it is not yet known whether this sign is useful to localize the lesion within the entire cerebellar system, both the cerebellar hemisphere and the cerebellar brainstem pathways. Limb ataxia was semi-quantified according to the International Cooperative Ataxia Rating Scale in 92 consecutive patients with acute PC stroke. Limb ataxia was present in 70 patients. Four topographical patterns based on magnetic resonance imaging findings were identified: picaCH pattern (posterior inferior cerebellar artery infarct); scaCH pattern (superior cerebellar artery infarct); CH/CP pattern (infarct involving both the cerebellum and the brainstem cerebellar pathways); and CP pattern (infarct involving the brainstem cerebellar pathways). Hemiataxia was present in (47/70; 67.1%) and monoataxia in (23/70; 32.9%) of patients. Monoataxia involved the upper limb in (19/70; 27.1%) and the lower limb in (4/70; 5.7%) of patients. Limb ataxia usually localized the lesion ipsilaterally (picaCH, scaCH, CH/CP, and CP patterns involving the medulla and sometimes the pons) (53/70; 75.7%), but it might be due also to contralateral (CP pattern involving the pons or midbrain) (16/70; 22.9%) or bilateral lesions (1/70). Limb ataxia usually localizes the lesion ipsilaterally but the infarct might be sometimes contralateral. The occurrence of monoataxia may suggest that the cerebellar system is somatotopically organized.

Stimulating visual exploration of the neglected space in the early stage of stroke by hemifield eye-patching: a randomized controlled trial in patients with right brain damage.

BACKGROUND: It has been well established that the presence of neglect is a predictor of poor functional outcome after stroke. Most rehabilitation studies on neglect have been performed with at least two months post-stroke. However, a recent series of stroke management indications highlight the importance of early rehabilitation treatment and evidence regarding neglect rehabilitation in the early phase after stroke is needed. AIM: To evaluate the effectiveness of right half-field patches in treating neglect in patients during the early phase of stroke. DESIGN: Randomized controlled trial. SETTING: Acute care setting in an urban general hospital. POPULATION: Eighteen patients with left unilateral neglect recruited among 56 patients consecutively admitted with right hemispheric stroke. METHODS: The patients were evaluated at pre-treatment, post-treatment, and at a 7-day follow-up. The experimental group received right half-field patch treatment (n=10) for approximately 8 hours a day for 15 consecutive days. The control group received visual scanning training (n=8) for 40 minutes every weekday in a 15 day period. RESULTS: Both groups significantly improved their performance in all outcome measures. No difference in the amount of improvement between the two groups was found. CONCLUSION: Right half-field eye patching could be a promising technique for treating visual spatial neglect during the early stages of stroke. CLINICAL REHABILITATION IMPACT: The eye-patching technique may represent an easily applicable and inexpensive method for neglect rehabilitation in the early stage after stroke.

Reversine increases multipotent human mesenchymal cells differentiation potential.

Among different human stem cell sources, adult mesenchymal stem cells from bone marrow (BMSCs), and more recently from adipose tissues (ASCs), have shown their capability to differentiate into a variety of different cell types, including osteoblasts, adipocytes, and muscle cells. However, mesenchymal stem cell differentiation toward certain cell types (including skeletal and cardiac muscle), while shown to be achievable, still suffers of low yields and needs to be greatly improved before any therapeutic application could be foreseen. A possible way of achieving this goal is by using a chemical-pharmacological approach to increase stem cell plasticity. Along this line, we envisioned the possibility of pre-treating BMSCs and ASCs with reversine, a synthetic purine that has been shown to induce adult cells de-differentiation. In the current study we tested reversine effects on both BMSCs and ASCs to increase their differentiation toward osteoblasts, smooth and skeletal muscle cells. Reversine pre-treatment, at very low concentration (50 nM), caused a marked increase in the differentiation yields of both BMSCs and ASCs.

Abnormal tactile temporal discrimination in psychogenic dystonia.

OBJECTIVE: Neurophysiologic studies demonstrated that patients with primary torsion dystonia (PTD) and with psychogenic dystonia (Psy-D) share similar abnormalities in the motor system. In this study, we evaluated somatosensory function in Psy-D by testing temporal discrimination threshold (TDT), and compared the results with those obtained in patients with PTD. METHODS: TDT of tactile stimuli was assessed in 10 patients with Psy-D, 10 patients with PTD, and 16 control subjects. The 2 groups of patients were matched for age, gender, disease duration, and distribution of dystonia. Tactile stimuli consisted of pairs of non-noxious electrical shocks delivered to the right or left hand at interstimulus interval increasing from 0 to 400 msec, in 10-msec steps. TDT was defined as the value at which subjects recognized the 2 stimuli as asynchronous. RESULTS: TDT was higher in Psy-D and PTD compared to control subjects, for both the right and the left hand. In a subgroup of patients with unilateral dystonia (Psy-D = 4, PTD = 5), TDT did not differ between the affected and the unaffected side in both groups of patients. Disease duration was not correlated to the increased TDT value. CONCLUSIONS: Our study suggests an impaired processing of somatosensory inputs in both Psy-D and PTD. These abnormalities might represent a neurophysiological trait predisposing to develop a dystonic posture triggered by psychiatric and psychological factors.

The role of extracellular conditions during CaCo-2 cells growth: a preliminary study for numerical model validation.

OBJECTIVES: One important limitation in cell therapy protocols, and regenerative medicine (an innovative and promising strategy for different pathologies treatment), is the lack of knowledge about cells engraftment, proliferation and differentiation. In order to allow an efficient and successful cell transplant, it is necessary to predict the logistics, economic and timing issues during cellular injection. It has been reported that several parameters, such as cells number, temperature and extracellular pH (pH0) value can influence metabolic pathways and cellular growth. Numerical analysis and model can help to reduce and understand the effects of the above environmental conditions on cell survival. The aim of this paper is to develop the first step of cells transplantation in order to identify "in vitro", which parameters can be useful to develop and validate a numerical model, able to evaluate "in vivo" cells engraftment and proliferation. MATERIAL AND METHODS: We studied the variation of extracellular parameters--such as medium volume, buffer system, nutrient concentrations and temperature on human colon carcinoma cells (CaCo-2) "in vitro culture"--pursuing the goal of understanding in deeper details cellular processes such as growth, metabolic activity, survival and pH0. RESULTS: Results showed that CaCo-2 cells growth and mortality increase after two days in culture when cells were suspended in 3.5 ml volume to respect of 10 ml volume. Different temperature values influenced CaCo-2 cells growth and metabolic activity showing a direct relationship with the volume of the medium. CONCLUSIONS: Our results describe as CaCo-2 cell growth, metabolic activity, mortality and extracellular pH were influenced by extracellular parameters, enabling us to develop and validate a numerical model to be use to predict cells engraftment and proliferation.