Acute rejection features in dual kidney transplant recipients from elderly donors: comparison of calcineurin inhibitor-based and calcineurin inhibitor-free immunosuppressive protocols.

Features of acute rejection in dual kidney transplant have not been studied. The aim of this study is to compare acute rejections in dual kidney transplant recipients from elderly donors on different immunosuppressive protocols. Sixty-nine patients were evaluated: 28 received calcineurin inhibitor-based (group 1) and 41 received calcineurin inhibitor-free immunosuppression (group 2). Histology of all donor kidneys was evaluated before implantation. All rejections showed tubulitis in both groups, and were classified as T cell-mediated acute rejections. Incidence and Banff grade of rejections in the two groups were not significantly different. Late rejections however, were observed in group 1 ( P < 0.01) whereas steroid-resistant rejections occurred in group 2 ( P < 0.03). C4d deposition was only observed in group 2. Occurrence of acute rejection was significantly associated with graft loss due to interstitial fibrosis/tubular atrophy in both groups. In group 1 mean serum creatinine levels of patients with rejections at six months and one year were higher than those of patients without rejections ( P < 0.03 and P < 0.009, respectively). In group 2 they were higher at six months ( P < 0.01) but not at one year. In addition, graft loss due to interstitial fibrosis/tubular atrophy occurred in 3/28 patients in group 1 (10.7%, OR= 1.95, 95%CI 1.02–3.71), and in 1/41 patients in group 2 (2.4%, OR= 0.41, 95%CI 0.07–2.24). Taken together these results suggest better renal function in patients on calcineurin inhibitor-free immunosuppression. In conclusion, acute rejections were detrimental irrespective of the type of immunosuppression, but different features were observed with each therapy. A tailored approach should be advantageous for prevention and treatment of acute rejections

Left atrial conduit flow rate at baseline and during exercise: an index of impaired relaxation in HFpEF patients

Aims In healthy subjects, adrenergic stimulation augments left ventricular (LV) long-axis shortening and lengthening, and increases left atrial (LA) to LV intracavitary pressure gradients in early diastole. Lower increments are observed in patients with heart failure with preserved ejection fraction (HFpEF). We hypothesized that exercise in HFpEF would further impair passive LV filling in early-mid diastole, during conduit flow from pulmonary veins. Methods and results Twenty HFpEF patients (67.8 ± 9.8 years; 11 women), diagnosed using 2007 ESC recommendations, underwent ramped semi-supine bicycle exercise to submaximal target heart rate (∼100 bpm) or symptoms. Seventeen asymptomatic subjects (64.3 ± 8.9 years; 7 women) were controls. Simultaneous LA and LV volumes were measured from pyramidal 3D-echocardiographic full-volume datasets acquired from an apical window at baseline and during stress, together with brachial arterial pressure. LA conduit flow was computed from the increase in LV volume from its minimum at end-systole to the last frame before atrial contraction (onset of the P wave), minus the reduction in LA volume during the same time interval; the difference was integrated and expressed as average flow rate, according to a published formula. The slope of single-beat preload recruitable stroke work (PRSW) quantified LV inotropic state. 3D LV torsion (rotation of the apex minus rotation of the base divided by LV length) was also measurable, both at rest and during stress, in 10 HFpEF patients and 4 controls. There were divergent responses in conduit flow rate, which increased by 40% during exercise in controls (+17.8 ± 37.3 mL/s) but decreased by 18% in patients with HFpEF (−9.6 ± 42.3 mL/s) (P = 0.046), along with congruent changes (+1.77 ± 1.13°/cm vs. −1.94 ± 2.73°/cm) in apical torsion (P = 0.032). Increments of conduit flow rate and apical torsion during stress correlated with changes in PRSW slope (P = 0.003 and P = 0.006, respectively). Conclusions In HFpEF, conduit flow rate decreases when diastolic dysfunction develops during exercise, in parallel with changes in LV inotropic state and torsion, contributing to impaired stroke volume reserve. Conduit flow is measurable using 3D-echocardiographic full-volume atrio-ventricular datasets, and as a marker of LV relaxation can contribute to the diagnosis of HFpEF

Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography

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Erratum: A microscopic view on the Mott transition in chromium-doped V 2 O 3

Nature Communications 1, Article number: 105 (2010); published: 02 November 2010; updated: 17 January 2012. In Figure 2 of this Article, panel labels c and d were inadvertently switched. A typographical error was also introduced in the last sentence of the legend, which should have read 'The scale bar in panel c represents 10 μm'

Astrocyte inactivation of the pRb pathway predisposes mice to malignant astrocytoma development that is accelerated by PTEN mutation

We have inactivated pRb, p107, and p130 in astrocytes by transgenic expression of T (a truncated SV40 T antigen) under the GFAP promoter. Founder mice died perinatally with extensive expansion of neural precursor and anaplastic astrocyte populations. In astrocytes, aberrant proliferation and extensive apoptosis were induced. Using a conditional allele of T, early lethality was circumvented, and adult mice developed high-grade astrocytoma, in which regions of decreased apoptosis expressed activated Akt. Indeed, astrocytoma development was accelerated in a , but not , background. These studies establish a highly penetrant preclinical model for astrocytoma based on events observed in the human disease and further provide insight into the role of PTEN mutation in astrocytoma progression

Observation of Exclusive Gamma Gamma Production in p pbar Collisions at sqrt{s}=1.96 TeV

We have observed exclusive \gamma\gamma production in proton-antiproton collisions at \sqrt{s}=1.96 TeV, using data from 1.11 \pm 0.07 fb^{-1} integrated luminosity taken by the Run II Collider Detector at Fermilab. We selected events with two electromagnetic showers, each with transverse energy E_T > 2.5 GeV and pseudorapidity |\eta| < 1.0, with no other particles detected in -7.4 < \eta < +7.4. The two showers have similar E_T and azimuthal angle separation \Delta\phi \sim \pi; 34 events have two charged particle tracks, consistent with the QED process p \bar{p} to p + e^+e^- + \bar{p} by two-photon exchange, while 43 events have no charged tracks. The number of these events that are exclusive \pi^0\pi^0 is consistent with zero and is < 15 at 95% C.L. The cross section for p\bar{p} to p+\gamma\gamma+\bar{p} with |\eta(\gamma)| < 1.0 and E_T(\gamma) > 2.5$ GeV is 2.48^{+0.40}_{-0.35}(stat)^{+0.40}_{-0.51}(syst) pb.Comment: 7 pages, 4 figure

Assessment of the olfactory function in Italian patients with type 3 von Willebrand disease caused by a homozygous 253 Kb deletion involving VWF and TMEM16B/ANO2.

Type 3 Von Willebrand disease is an autosomal recessive disease caused by the virtual absence of the von Willebrand factor (VWF). A rare 253 kb gene deletion on chromosome 12, identified only in Italian and German families, involves both the VWF gene and the N-terminus of the neighbouring TMEM16B/ANO2 gene, a member of the family named transmembrane 16 (TMEM16) or anoctamin (ANO). TMEM16B is a calcium-activated chloride channel expressed in the olfactory epithelium. As a patient homozygous for the 253 kb deletion has been reported to have an olfactory impairment possibly related to the partial deletion of TMEM16B, we assessed the olfactory function in other patients using the University of Pennsylvania Smell Identification Test (UPSIT). The average UPSIT score of 4 homozygous patients was significantly lower than that of 5 healthy subjects with similar sex, age and education. However, 4 other members of the same family, 3 heterozygous for the deletion and 1 wild type, had a slightly reduced olfactory function indicating that socio-cultural or other factors were likely to be responsible for the observed difference. These results show that the ability to identify odorants of the homozygous patients for the deletion was not significantly different from that of the other members of the family, showing that the 253 kb deletion does not affect the olfactory performance. As other genes may compensate for the lack of TMEM16B, we identified some predicted functional partners from in silico studies of the protein-protein network of TMEM16B. Calculation of diversity for the corresponding genes for individuals of the 1000 Genomes Project showed that TMEM16B has the highest level of diversity among all genes of the network, indicating that TMEM16B may not be under purifying selection and suggesting that other genes in the network could compensate for its function for olfactory ability

Microgenomic Analysis in Skeletal Muscle: Expression Signatures of Individual Fast and Slow Myofibers

BACKGROUND: Skeletal muscle is a complex, versatile tissue composed of a variety of functionally diverse fiber types. Although the biochemical, structural and functional properties of myofibers have been the subject of intense investigation for the last decades, understanding molecular processes regulating fiber type diversity is still complicated by the heterogeneity of cell types present in the whole muscle organ. METHODOLOGY/PRINCIPAL FINDINGS: We have produced a first catalogue of genes expressed in mouse slow-oxidative (type 1) and fast-glycolytic (type 2B) fibers through transcriptome analysis at the single fiber level (microgenomics). Individual fibers were obtained from murine soleus and EDL muscles and initially classified by myosin heavy chain isoform content. Gene expression profiling on high density DNA oligonucleotide microarrays showed that both qualitative and quantitative improvements were achieved, compared to results with standard muscle homogenate. First, myofiber profiles were virtually free from non-muscle transcriptional activity. Second, thousands of muscle-specific genes were identified, leading to a better definition of gene signatures in the two fiber types as well as the detection of metabolic and signaling pathways that are differentially activated in specific fiber types. Several regulatory proteins showed preferential expression in slow myofibers. Discriminant analysis revealed novel genes that could be useful for fiber type functional classification. CONCLUSIONS/SIGNIFICANCE: As gene expression analyses at the single fiber level significantly increased the resolution power, this innovative approach would allow a better understanding of the adaptive transcriptomic transitions occurring in myofibers under physiological and pathological condition

Broncalt®, class ii medical device, in patients with chronic relapsed upper airways disease: A survey in clinical practice

Chronic respiratory otorhinolaryngological (ORL) diseases may exacerbate. Broncalt® is a class II Medical Device containing: thermal water (Medesano, PR, Italy), hyaluronic acid, and grapefruit seed extract. It could exert a safe and effective anti-inflammatory, washing, and antimicrobial activity. The current survey, conducted in clinical practice of 84 Italian ORL centers, evaluated its safety and efficacy in the treatment of patients with exacerbated chronic upper airways disease. The 459 (254 males, mean age 44.7 years) patients were evaluated at baseline (T0) and after a 2-week treatment (T1), treated or not-treated with Broncalt®. Signs and symptoms severity were measured by visual analogue scale. Broncalt® significantly, quickly, and safely diminished the clinical features in all sub-groups (p&lt;0.001 for all). In conclusion, Broncalt® is a class II Medical Device able to exert a safe, quick, and effective activity in patients with relapsed chronic ORL disorders. (www.actabiomedica.it)

Broncalt®, class II medical device, in patients with acute upper airways disease: A survey in clinical practice

Inflammation is a common pathogenic mechanism involved in many otorhinolaryngological (ORL) disorders. Broncalt® is a class II Medical Device containing: Thermal water (Medesano, PR, Italy), hyaluronic acid, and grapefruit seed extract. It has been reported that it exerted a safe and effective anti-inflammatory, washing, and antimicrobial activity by virtue of these components. Therefore, the aim of the current survey, conducted in clinical practice of 84 Italian ORL centers, was to evaluate its safety and efficacy in the treatment of patients with acute upper airways disease. The 3,533 (1,797 males, mean age 43.5 years) patients were evaluated at baseline (T0) and after a 2-week treatment (T1) with or without Broncalt®. Signs and symptoms severity were measured by visual analogue scale. Broncalt® significantly and safely diminished the clinical features in all sub-groups (p&lt;0.001 for all). Interestingly, Broncalt® significantly induced a faster symptom relief already within 3 days after the start of the treatment. In conclusion, Broncalt® is a class II Medical Device able to exert a safe and effective activity in patients with acute ORL disorders. (www.actabiomedica.it)