Probiotics for managing patients after bowel preparation for colonoscopy: an interventional, double-arm, open, randomized, multi-center, and national study (COLONSTUDY).

BACKGROUND: Bowel preparation (BP) for colonoscopy induces significant changes in gut microbiota, causing dysbiosis that, in turn, elicits intestinal symptoms. Consequently, probiotics may counterbalance the disturbed microbiota after BP. So, probiotics may restore microbiota homeostasis. METHODS: The current study evaluated the efficacy and safety of Abincol®, an oral nutraceutical containing a probiotic mixture with Lactobacillus plantarum LP01 (1 billion living cells), Lactobacillus lactis subspecies cremoris LLC02 (800 millions living cells), and Lactobacillus delbrueckii LDD01 (200 millions living cells), Patients were randomized in two groups (2:1). Group A took one stick/daily for four weeks after colonoscopy. Group B was considered as control. Patients were evaluated at baseline (T0) and after one (T1), two (T2), and four (T3) weeks. The severity of symptoms was measured by patients using a Visual Analog Scale. RESULTS: Abincol® significantly diminished the presence and the severity of intestinal symptoms at T2 and even more at T3. All patients well tolerated the probiotic mixture. CONCLUSIONS: The present study suggests that Abincol® may be considered an effective and safe therapeutic option in managing patients undergoing BP. The course should last one month.

Probiotic mixture in patients after Helicobacter pylori eradication: a real-life experience.

BACKGROUND: Eradication for Helicobacter pylori usually induces digestive dysbiosis that, in turn, elicits symptoms. Consequently, probiotic supplementation may counterbalance the disturbed microbiota after this procedure. So, probiotics may restore microbiota homeostasis quickly relieve complaints. METHODS: The current study evaluated the efficacy and safety of Abivisor®, a food supplement containing Lacticaseibacillus rhamnosus LR06 (3 billion living cells), Lactiplantibacillus pentosus LPS01(100 million living cells), Lactiplantibacillus plantarum LP01 (1 billion living cells), and N-acetyl cysteine (60 mg). Patients were randomized into two groups (2:1). Group A took one stick/daily for 60 days after eradication. Group B was considered as control. Patients were evaluated at baseline (T0) and after 15 (T1), 30 (T2), and 60 (T3) days. The severity of digestive symptoms was measured by patients using a Visual Analog Scale. The percentage of patients with each symptom was also evaluated. RESULTS: Abivisor® has significantly and progressively diminished intestinal symptoms' presence and severity at T1, T2, and even more at T3. Accordingly, the percentage of symptomatic patients diminished more rapidly and significantly in group A than in B. All patients well tolerated the food supplement. CONCLUSIONS: The present study suggests that Abivisor® may be an effective and safe therapeutic option for managing patients undergoing H. pylori eradication.

Gastric protection in cardiological practice: an Italian survey on the prescriptive attitude.

BACKGROUND: Gastric protection is commonly considered in patients who use medications able to damage gastric mucosa, mainly NSAIDs, antiplatelets, and anticoagulants. Therefore, cardiologists may frequently prescribe drugs to protect the stomach from damaging medications. The present survey investigated the attitude toward using gastric protection by a panel of Italian cardiologists. METHODS: A self-administered questionnaire included three sections concerning practical problems on this issue in clinical practice facing patients with cardiological disorders. The questionnaire was administered in three successive months. RESULTS: Ninety Italian cardiologists completed the questionnaire. They all consider gastric protection, mainly when prescribing potentially noxious medications. Usually, cardiologists prescribe proton pump inhibitors (PPIs) in 60% of their patients. Alginates and mucosal protectors are less considered. As a rule, cardiologists request investigations if the initial treatment fails. Moreover, the safety issue is carefully assessed. Furthermore, this survey experience significantly affected the approach to managing patients who require gastric protection. The participants carefully considered the prescriptive appropriateness of gastric protectors, mainly concerning the PPIs use. Consequently, PPIs were discontinued when inappropriate. A new medical device with triple action (antacid, mucosal protectors, and anti-reflux) contributed to this new attitude. CONCLUSIONS: The present survey underscored that the appropriateness in prescribing gastric protectors is clinically relevant. In addition, a longitudinal survey experience contributed to change the practical approach by highlighting the prescriptive appropriateness of PPIs, and using a new medical device with multiple gastroprotective activities.

Monoclonal Immunoglobulin Crystalline Membranous Nephropathy.

Monoclonal immunoglobulin (MIg) crystalline nephropathies are rare lesions resulting from precipitation of MIgs in the kidney as intracellular or extracellular crystals. We describe a patient with multiple myeloma (IgGλ) and diabetes who presented with nephrotic range proteinuria. Kidney biopsy revealed membranous nephropathy superimposed on diabetic glomerulosclerosis. Glomeruli were negative for PLA2R, THSD7A, and NELL-1. Ultrastructurally, the subepithelial deposits were composed of crystals (ranging from rhomboid to rod to needle shaped), which failed to stain for immunoglobulins by routine immunofluorescence but stained for IgG+λ by paraffin immunofluorescence after pronase digestion. RNA-based immunoglobulin repertoire sequencing performed on bone marrow aspirate identified an IgGλ (γ1) clone, which was highly atypical, combining an extensively mutated (23.6%) Ig heavy chain derived from the IGHV1-24 with low pI and unusual mutations and a light chain derived from an extremely rare germline gene (IGLV10-54). This report expands the pathologic spectrum of MIg crystalline nephropathies by describing a unique case of crystalline nephropathy with IgGλ deposits manifesting as membranous nephropathy.

Recurrent atypical antiglomerular basement membrane nephritis in the kidney transplant.

Atypical antiglomerular basement membrane (anti-GBM) nephritis can be defined as linear GBM staining for monotypic or polytypic immunoglobulin (Ig) by immunofluorescence (IF) without a diffuse crescentic pattern. We describe the clinicopathologic features of 6 patients (18 biopsies) in this first series of recurrent atypical anti-GBM nephritis after kidney transplantation. Recurrent glomerulonephritis occurred at a mean of 3.8 months posttransplant (range 1-7 months). Three index biopsies were for clinical indication, and 3 were protocol biopsies. Glomerular histologic changes were mild, with 2 showing segmental endocapillary hypercellularity, 1 focal glomerular microangiopathy, and the others no significant glomerular histologic changes. All 6 allografts showed monotypic linear glomerular Ig staining by IF: IgG kappa (n = 2), IgG lambda, IgA kappa, IgA lambda, and IgM lambda. Follow-up biopsies were available for 5 patients and showed similar histologic and IF findings without evidence of significant progression. No patients had detectable serum anti-GBM antibody or monoclonal proteins. The mean serum creatinine level on follow-up (24-62 months posttransplant) was 1.8 (range 0.93-2.77) mg/dL; no grafts were lost to recurrent disease. This series demonstrates that monotypic atypical anti-GBM recurs in the allograft and supports the idea that this disease is due to a circulating monoclonal protein.

Coronary microvascular dysfunction and findings of heart failure with preserved ejection fraction in patients with microvascular angina.

BACKGROUND: Coronary microvascular dysfunction (CMD) may cause symptoms of myocardial ischemia (microvascular angina [MVA]), but recent studies suggested that it might also contribute to the syndrome of heart failure with preserved ejection fraction (HFpEF). In this study we assessed the relation of CMD with findings of HFpEF in MVA patients. METHODS: We enrolled 36 consecutive patients with MVA, in whom we assessed: 1) coronary blood flow (CBF) response to adenosine and cold pressor test (CPT) by color-Doppler echocardiography of the left anterior descending coronary artery; 2) complete echocardiographic examination; 3) N-terminal-pro-B-natriuretic peptide (NT-proBNP); 4) grade of dyspnea by the modified Medical Research Scale. RESULTS: Among patients, 15 had definite HFpEF findings (group 1), 12 had equivocal HFpEF findings (group 2) and 9 had no evidence of HFpEF findings (group 3). Group 1 patients were older, had more cardiovascular risk factors and higher NT-proBNP levels (P=0.018), and showed a higher prevalence of diastolic dysfunction. Left ventricle dimensions and systolic function, however, did not differ among groups. Dyspnea was also not significantly different among groups (P=0.19). CBF to adenosine was 1.85±0.47, 1.78±0.40 1.49±0.32 in group 1, 2 and 3, respectively (P=0.13). Similarly, CBF response to CPT was 1.57±0.4, 1.49±0.2 and 1.45±0.3 in the 3 groups, respectively (P=0.74). Both CBF response to adenosine and CPT showed no relation with the severity of dyspnea symptoms. CONCLUSIONS: Our data suggest that in patients with MVA there is no relation between the grade of impairment of coronary microvascular dilatation and findings of HFpEF.

Multiscale Investigation of the Structural, Electrical and Photoluminescence Properties of MoS2 Obtained by MoO3 Sulfurization.

In this paper, we report a multiscale investigation of the compositional, morphological, structural, electrical, and optical emission properties of 2H-MoS2 obtained by sulfurization at 800 °C of very thin MoO3 films (with thickness ranging from ~2.8 nm to ~4.2 nm) on a SiO2/Si substrate. XPS analyses confirmed that the sulfurization was very effective in the reduction of the oxide to MoS2, with only a small percentage of residual MoO3 present in the final film. High-resolution TEM/STEM analyses revealed the formation of few (i.e., 2-3 layers) of MoS2 nearly aligned with the SiO2 surface in the case of the thinnest (~2.8 nm) MoO3 film, whereas multilayers of MoS2 partially standing up with respect to the substrate were observed for the ~4.2 nm one. Such different configurations indicate the prevalence of different mechanisms (i.e., vapour-solid surface reaction or S diffusion within the film) as a function of the thickness. The uniform thickness distribution of the few-layer and multilayer MoS2 was confirmed by Raman mapping. Furthermore, the correlative plot of the characteristic A1g-E2g Raman modes revealed a compressive strain (ε ≈ -0.78 ± 0.18%) and the coexistence of n- and p-type doped areas in the few-layer MoS2 on SiO2, where the p-type doping is probably due to the presence of residual MoO3. Nanoscale resolution current mapping by C-AFM showed local inhomogeneities in the conductivity of the few-layer MoS2, which are well correlated to the lateral changes in the strain detected by Raman. Finally, characteristic spectroscopic signatures of the defects/disorder in MoS2 films produced by sulfurization were identified by a comparative analysis of Raman and photoluminescence (PL) spectra with CVD grown MoS2 flakes.

Development of polymer-based nanoparticles for zileuton delivery to the lung: PMeOx and PMeOzi surface chemistry reduces interactions with mucins.

In this paper, two amphiphilic graft copolymers were synthesized by grafting polylactic acid (PLA) as hydrophobic chain and poly(2-methyl-2-oxazoline) (PMeOx) or poly(2-methyl-2-oxazine) (PMeOzi) as hydrophilic chain, respectively, to a backbone of α,ß-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA). These original graft copolymers were used to prepare nanoparticles delivering Zileuton in inhalation therapy. Among various tested methods, direct nanoprecipitation proved to be the best technique to prepare nanoparticles with the smallest dimensions, the narrowest dimensional distribution and a spherical shape. To overcome the size limitations for administration by inhalation, the nano-into-micro strategy was applied, encapsulating the nanoparticles in water-soluble mannitol-based microparticles by spray-drying. This process has allowed to produce spherical microparticles with the proper size for optimal lung deposition, and, once in contact with fluids mimicking the lung district, able to dissolve and release non-aggregated nanoparticles, potentially able to spread through the mucus, releasing about 70% of the drug payload in 24 h.

Nodular Vascular Transformation of the Lymph Node Sinuses Mimicking Sarcomatoid Change in Renal Cell Carcinoma: A Potential Diagnostic Pitfall.

Vascular transformation of the lymph node sinuses (VTS) is an uncommon phenomenon that is believed to occur secondary to obstruction of efferent lymphatics, frequently occuring in retroperitoneal lymph nodes draining cancer. The nodular subtype of VTS, in particular, can mimic metastatic cancer, such as metastatic renal cell carcinoma with sarcomatoid differentiation, potentially resulting in inaccurate tumor grading and/or staging. We present a case of nodular VTS mimicking metastatic renal cell carcinoma with sarcomatoid differentiation in a patient with high-grade clear cell renal cell carcinoma, and explore the relevant differential diagnosis. Awareness of VTS is essential to avoid misdiagnosis of this benign and curative condition.

The complex phenotype of spinocerebellar ataxia type 48 in eight unrelated Italian families.

BACKGROUND AND PURPOSE: Heterozygous mutations in the STUB1 gene have recently been associated with an autosomal dominant form of spinocerebellar ataxia (SCA) associated with cerebellar cognitive-affective syndrome (CCAS), named SCA48. METHODS: Molecular screening was performed in a cohort of 235 unrelated patients with adult-onset, autosomal dominant (17) or sporadic (218) cerebellar ataxia, negative for pathological trinucleotide expansions in the common SCAs, FRDA and FXTAS loci, by using targeted multigene panels or whole-exome sequencing. Bioinformatics analyses, detailed neurological phenotyping and family segregation studies corroborated the pathogenicity of the novel STUB1 mutations. Clinico-diagnostic findings were reviewed to define the phenotypic spectrum. RESULTS: Eight heterozygous STUB1 mutations were identified, six of which were novel in 11 patients from eight index families, giving an estimated overall frequency of 3.4% (8/235) for SCA48 in our study cohort, rising to 23.5% (4/17) when considering only familial cases. All our SCA48 patients had cerebellar ataxia and dysarthria associated with cerebellar atrophy on brain magnetic resonance imaging; of note, many cases were also associated with parkinsonism, chorea and dystonia. CCAS also occurred frequently, whereas definite signs of pyramidal tract dysfunction and peripheral nervous system involvement were absent. One SCA48 patient presented with hypogonadism, associated with other autoimmune endocrine dysfunctions. CONCLUSIONS: Our results support SCA48 as a significant cause of adult-onset SCA. Besides CCAS, our SCA48 patients often showed movement disorders and other clinical manifestations previously described in SCAR16, linked to biallelic variants in the same gene, thus suggesting a continuous clinical spectrum and significant overlap amongst recessive and dominantly inherited mutations in STUB1.

Estimation of potential soil erosion in the Prosecco DOCG area (NE Italy), toward a soil footprint of bottled sparkling wine production in different land-management scenarios.

Agricultural lands are the widest Human-modified ecosystems, making crop production the most extensive form of land use on Earth. However, in conventional agricultural land management, soil erosion may be boosted up to 1-2 orders of magnitude higher than the natural rates of soil production, making unproductive about the 30% of the world's arable. Nowadays in Europe, vineyards represent the most erosion-prone agricultural lands, especially in Mediterranean countries, showing the highest erosion rates in comparison to other type of land uses. Prosecco wine is produced in NE Italy by a rate of 400 M bottles per year, with the fastest growing demand in the global market at present. A production of 90 M bottles year-1 is currently running in the historical Prosecco DOCG (215 km2), in a steep hilly landscape of Veneto Region (Conegliano-Valdobbiadene). To sustain wine production, agricultural intensification is at present increasing, by re-setting of hillslopes and land use changes towards new vineyard plantations. The aim of this study is to estimate and to map potential soil erosion rate, calculating a sort of "soil footprint" for wine production in different agricultural land-management scenarios. RUSLE model was adopted to estimate potential soil erosion in Mg ha-1 year-1, by using high resolution topographic data (LiDAR), 10 years rainfall data analysis, detailed land use and local soil characteristics. For a conventional land-management scenario the estimated that total potential soil erosion in the Prosecco DOCG area is 411,266 Mg year-1, with an erosion rate of 19.5 Mg ha year-1. Modelled soil erosion is mainly clustered on steep slopes, with rates higher than 40 Mg ha-1 year-1. In Prosecco vineyards potential soil erosion could reach 300,180 Mg year-1, by a mean rate of 43.7 Mg ha-1 year-1, which is 31 times higher than the upper limit of tolerable soil erosion threshold defined for Europe. In contrast, simulation of different nature-based scenarios (hedgerows, buffer strips, and grass cover) showed soil erosion could be effectively reduced: a 100% inter-row grass cover showed a reduction of almost 3 times in vineyards (from 43.7 to 14.6 Mg ha-1 year-1), saving about 50% of soil in the whole Prosecco DOCG. The soil footprint modelled for a conventional land-management scenario is about 3.3 kg every bottle produced; in contrast it would be reduced to 1.1 kg/bottle in the completely green land-management scenario. This study, as the first estimation of potential soil erosion at Prosecco DOCG scale, suggests that an integrated and public soil erosion monitoring system is strongly needed in viticultural area, by implementing direct/indirect field measures with spatial analyses at agricultural landscape scale.

Vegetated Ditches for the Mitigation of Pesticides Runoff in the Po Valley.

In intensive agricultural systems runoff is one of the major potential diffuse pollution pathways for pesticides and poses a risk to surface water. Ditches are common in the Po Valley and can potentially provide runoff mitigation for the protection of watercourses. The effectiveness depends on ditch characteristics, so there is an urgent need for site-specific field trials. The use of a fugacity model (multimedia model) can allows recognition of the mitigation main processes. A field experiment was conducted in order to evaluate the mitigation capacity of a typical vegetated ditch, and results were compared with predictions by a fugacity model. To evaluate herbicide mitigation after an extreme runoff, the ditch was flooded with water containing mesotrione, S-metolachlor and terbuthylazine. Two other subsequent floods with uncontaminated water were applied 27 and 82 days later to evaluate herbicides release. Results show that the ditch can immediately reduce runoff concentration of herbicides by at least 50% even in extreme flooding conditions. The half-distances were about 250 m. As a general rule, a runoff of 1 mm from 5 ha is mitigated by 99% in 100 m of vegetated ditch. Herbicides retention in the vegetated ditch was reversible, and the second flood mobilized 0.03-0.2% of the previous one, with a concentration below the drinking water limit of 0.1 µg L(-1). No herbicide was detected in the third flood, because the residual amount in the ditch was too low. Fugacity model results show that specific physical-chemical parameters may be used and a specific soil-sediment-plant compartment included for modelling herbicides behaviour in a vegetated ditch, and confirm that accumulation is low or negligible for herbicides with a half-life of 40 days or less. Shallow vegetated ditches can thus be included in a general agri-environment scheme for the mitigation of pesticides runoff together with wetlands and linear buffer strips. These structures are present in the landscape, and their environmental role can be exploited by proper management.

Progression of microstructural damage in spinocerebellar ataxia type 2: a longitudinal DTI study.

BACKGROUND AND PURPOSE: The ability of DTI to track the progression of microstructural damage in patients with inherited ataxias has not been explored so far. We performed a longitudinal DTI study in patients with spinocerebellar ataxia type 2. MATERIALS AND METHODS: Ten patients with spinocerebellar ataxia type 2 and 16 healthy age-matched controls were examined twice with DTI (mean time between scans, 3.6 years [patients] and 3.3 years [controls]) on the same 1.5T MR scanner. Using tract-based spatial statistics, we analyzed changes in DTI-derived indices: mean diffusivity, axial diffusivity, radial diffusivity, fractional anisotropy, and mode of anisotropy. RESULTS: At baseline, the patients with spinocerebellar ataxia type 2, as compared with controls, showed numerous WM tracts with significantly increased mean diffusivity, axial diffusivity, and radial diffusivity and decreased fractional anisotropy and mode of anisotropy in the brain stem, cerebellar peduncles, cerebellum, cerebral hemisphere WM, corpus callosum, and thalami. Longitudinal analysis revealed changes in axial diffusivity and mode of anisotropy in patients with spinocerebellar ataxia type 2 that were significantly different than those in the controls. In patients with spinocerebellar ataxia type 2, axial diffusivity was increased in WM tracts of the right cerebral hemisphere and the corpus callosum, and the mode of anisotropy was extensively decreased in hemispheric cerebral WM, corpus callosum, internal capsules, cerebral peduncles, pons and left cerebellar peduncles, and WM of the left paramedian vermis. There was no correlation between the progression of changes in DTI-derived indices and clinical deterioration. CONCLUSIONS: DTI can reveal the progression of microstructural damage of WM fibers in the brains of patients with spinocerebellar ataxia type 2, and mode of anisotropy seems particularly sensitive to such changes. These results support the potential of DTI-derived indices as biomarkers of disease progression.

Effect of whey concentration on protein recovery in fresh ovine ricotta cheese.

Ricotta cheese, particularly the ovine type, is a typical Italian dairy product obtained by heat-coagulation of the proteins in whey. The aim of this work was to investigate the influence of whey protein concentration, obtained by ultrafiltration, on yield of fresh ovine ricotta cheese. Ricotta cheeses were obtained by thermocoagulation of mixtures with protein content of 1.56, 3.10, 4.16, and 7.09g/100g from the mixing of skim whey and ultrafiltered skim whey. A fat-to-protein ratio of 1.1 (wt/wt) was obtained for all mixtures by adding fresh cream. The initial mixtures, as well as the final ricotta cheeses, were analyzed for their composition and by SDS-PAGE. Protein bands were quantified by QuantityOne software (Bio-Rad, Hercules, CA) and identified by liquid chromatography-tandem mass spectrometry. Significant differences in the composition of the ricotta cheese were observed depending on protein concentration. Particularly, ricotta cheese resulting from the mixture containing 7.09g/100g of protein presented higher moisture (72.88±1.50g/100g) and protein (10.18±0.45g/100g) contents than that prepared from the mixture with 1.56g/100g of protein (69.52±1.75 and 6.70±0.85g/100g, respectively), and fat content was lower in this sample (12.20±1.60g/100g) compared with the other treatments, with mean values between 15.72 and 20.50g/100g. Each protein fraction presented a different behavior during thermocoagulation. In particular, the recovery of ß-lactoglobulin and α-lactalbumin in the cheese increased as their content increased in the mixtures. It was concluded that concentrating ovine rennet whey improved the extent of heat-induced protein aggregation during the thermal coagulation process. This resulted in a better recovery of each protein fraction in the product, and in a consequent increase of ricotta cheese yield.

Long-term re-evaluation of primary aldosteronism after medical treatment reveals high proportion of normal mineralocorticoid secretion.

OBJECTIVE: In most cases of primary aldosteronism (PA), An adrenal aldosterone-secreting tumor cannot be reasonably proven, so these patients undergo medical treatment. Controversial data exist about the evolution of PA after medical therapy: long-term treatment with mineralocorticoid antagonists has been reported to normalize aldosterone levels but other authors failed to find remission of mineralocorticoid hypersecretion. Thus, we planned to retest aldosterone secretion in patients with medically treated PA diagnosed at least 3 years before. DESIGN: Retrospective, cross-sectional study. METHODS: The same workup for PA as at diagnosis (basal aldosterone to renin activity ratio (ARR) and aldosterone suppression test) was performed after stopping interfering drugs and low-salt diet, in 34 subjects with PA diagnosed between 3 and 15 years earlier, by case finding from subgroups of hypertensive patients at high risk for PA. Criteria for persistence of PA were the same as at diagnosis (ARR (pg/ml per ng per ml per h) >400, aldosterone >150 pg/ml basally, and >100 pg/ml after saline infusion) or less restrictive. RESULTS: PA was not confirmed in 26 (76%) of the patients and also not in 20 (59%) using the least restrictive criteria suggested by international guidelines. Unconfirmed PA was positively associated with female sex, higher potassium levels, longer duration of hypertension, and follow-up, but not with adrenal mass, aldosterone levels at diagnosis, and treatment with mineralocorticoid antagonists. CONCLUSIONS: This study suggests that mineralocorticoid hyperfunction in patients with PA after medical treatment may decline spontaneously. Higher potassium concentration and duration of treatment seem to increase the probability of this event.

Whole body cholesterol metabolism is impaired in Huntington's disease.

We previously reported impaired cholesterol biosynthesis in rodent Huntington Disease (HD) models and HD patients' fibroblasts and post mortem brains. We also found that plasma levels of 24S-hydroxycholesterol (24OHC), the brain specific elimination product of cholesterol considered a marker of brain cholesterol turnover, were significantly reduced in HD patients at any disease stage. In the present study we analysed by mass spectrometry the fasting plasma levels of cholesterol, its biosynthetic precursors lanosterol and lathosterol, of the whole-body elimination products 27-hydroxycholesterol and of brain 24OHC in a cohort of premanifest and HD patients at different disease stages. We found that the cholesterol precursors lanosterol and lathosterol (both index of whole body cholesterol synthesis), the levels of the bile acid precursor 27-hydroxycholesterol, and of the brain specific 24OHC, were all significantly reduced in manifest HD patients, suggesting that whole-body and brain cholesterol homeostasis are both impaired in HD.

Evaluation of the effects of circular Descemet's membrane incision on the biomechanical, topographic and optical properties of rabbit corneas.

BACKGROUND: Prospective interventional animal case series to investigate quantitatively changes in corneal light-scattering, corneal hysteresis, keratometry and pachymetry induced by circular Descemet's membrane incision. METHODS: Thirty mature New Zealand White rabbits were divided into three study groups: (i) surgical intervention with circular Descemet's incision; (ii) surgical control; and (iii) medical control. Group 1 eyes had two paracenteses placed 120 degrees apart and an 8.5-mm-diameter Descemetorhexis was created with a reverse Sinskey hook. Group 2 eyes had two paracenteses placed 120 degrees apart. The main outcome measures were scatterometry, corneal hysteresis, pachymetry and keratometry measurements, which were performed prior to and 2 weeks following the interventions. Histology and transmission electron microscopy were performed post-mortem in representative eyes. RESULTS: Eyes that had undergone circular Descemet's incision had significantly decreased mean keratometry (43.9 ± 0.7 dioptres [mean ± standard deviation] preoperatively vs. 43.5 ± 0.9 dioptres postoperatively, P = 0.007). Circular Descemet's membrane incision did not significantly change corneal hysteresis (4.4 ± 1.1 mmHg preoperatively vs. 4.6 ± 0.9 mmHg postoperatively, P = 0.664). Corneal light scattering decreased after Descemet's scoring (0.00254 ± 0.00059 preoperatively vs. 0.00206 ± 0.00031 postoperatively, P = 0.0025). Pachymetry measurements remained relatively stable (341.3 ± 18.6 µm preoperatively vs. 330.6 ± 20.0 µm postoperatively) without postoperative oedema. CONCLUSIONS: Circular Descemet's scoring flattened the corneal curvature by a mean of 0.4 dioptres without affecting corneal hysteresis in rabbit corneas. These findings may have important implications for ongoing developments in endothelial keratoplasty.

Responsiveness of different rating instruments in spinocerebellar ataxia patients.

OBJECTIVE: To determine the longitudinal metric properties of recently developed clinical assessment tools in spinocerebellar ataxia (SCA). METHODS: A subset of 171 patients from the EUROSCA natural history study cohort (43 SCA1, 61 SCA2, 37 SCA3, and 30 SCA6) were examined after 1 year of follow-up. Score changes and effect size indices were calculated for clinical scales (Scale for the Assessment and Rating of Ataxia [SARA], Inventory of Non-Ataxia Symptoms [INAS]), functional tests (SCA Functional Index [SCAFI] and components), and a patient-based scale for subjective health status (EQ-5D visual analogue scale [EQVAS]). Responsiveness was determined in relation to the patient's global impression (PGI) of change and reproducibility described as retest reliability for the stable groups and smallest detectable change. RESULTS: Within the 1-year follow-up period, SARA, INAS, and SCAFI but not EQVAS indicated worsening in the whole group and in the groups with subjective (PGI) worsening. SCAFI and its 9-hole pegboard (9HPT) component also deteriorated in the stable groups. Standardized response means were highest for 9HPT (-0.67), SARA (0.50), and SCAFI (-0.48) with accordingly lower sample size estimates of 143, 250, or 275 per group for a 2-arm interventional trial that aims to reduce disease progression by 50%. SARA and EQVAS performed best to distinguish groups classified as worse by PGI. All scales except EQVAS reached the criterion for retest reliability. CONCLUSION: While both the Scale for the Assessment and Rating of Ataxia and the SCA Functional Index (SCAFI) (and its 9-hole pegboard component) had favorable measurement precision, the clinical relevance of SCAFI and 9-hole pegboard score changes warrants further exploration. The EQ-5D visual analogue scale proved insufficient for longitudinal assessment, but validly reflected patients' impression of change.

Autonomic nervous system abnormalities in spinocerebellar ataxia type 2: a cardiovascular neurophysiologic study.

Autonomic nervous system dysfunction is part of the spinocerebellar ataxia (SCA) clinical picture, but few data are available on this topic. The present study is aimed to report a detailed investigation of autonomic nervous system in patients with molecular diagnosis of SCA type 2, one of the most frequent forms and the commonest in Italy. Nine patients with a mild to moderate form of SCA2 underwent a questionnaire about dysautonomic symptoms and a complete cardiovascular neurophysiologic evaluation of both sympathetic and parasympathetic system, comprising head-up tilt, standing, isometric hand grip, cold pressure, mental arithmetic, Valsalva manoeuvre, deep breathing, and hyperventilation tests. An echocardiographic study and Holter-ECG recording were also performed. All patients complained dysautonomic problems regarding urinary tract, cardiovascular system, or gastrointestinal dysfunction. The neurophysiologic study showed both sympathetic and parasympathetic involvement, with highly variable degree and pattern of dysautonomia. The present study results show that the autonomic dysfunction is common in SCA2 representing a significant component of the complex picture of the disease. We found a wide spectrum of cardiovascular autonomic abnormalities, without a typical pattern of dysfunction and without correlation with clinical variables.