Direct 3D imaging through spatial coherence of light

Wide-field imaging is widely adopted due to its fast acquisition, cost-effectiveness and ease of use. Its extension to direct volumetric applications, however, is burdened by the trade-off between resolution and depth of field (DOF), dictated by the numerical aperture of the system. We demonstrate that such trade-off is not intrinsic to wide-field imaging, but stems from the spatial incoherence of light: images obtained through spatially coherent illumination are shown to have resolution and DOF independent of the numerical aperture. This fundamental discovery enabled us to demonstrate an optimal combination of coherent resolution-DOF enhancement and incoherent tomographic sectioning for scanning-free, wide-field 3D microscopy on a multicolor histological section.Comment: 17 pages, 6 figures. Supplemental document available upon request to the authors. Submitted to Lasers and Photonics Review

The unusual association of Graves' disease, chronic spontaneous urticaria, and premature ovarian failure: report of a case and HLA haplotype characterization

Chronic spontaneous urticaria (CSU), defined as the occurrence of spontaneous wheals for more than six weeks, has been associated with autoimmune diseases. Herein, we report the unusual association of CSU, Graves' disease, and premature ovarian failure. Human leukocyte antigen (HLA) studies were performed. A 36-year-old woman presented symptoms and signs of hyperthyroidism for three months. In the same period, the patient complained of widespread urticarial wheals, intensely itchy, and poorly responsive to therapy with antihistaminic agents. Hyperthyroidism was confirmed biochemically, and treatment with methimazole was started. As hyperthyroidism improved, a marked improvement in her urticaria was also observed. However, the patient continued to complain of amenorrhea. Endocrine evaluation, at the age 38, was consistent with premature ovarian failure. This is the first report of coexistence of GD, CSU, and POF. The genetic background of such unusual association is a specific combination of HLA

Alternative sources of neurons and glia from somatic stem cells.

Stem cell populations have been shown to be extremely versatile: they can generate differentiated cells specific to the tissue in which they reside and descendents that are of different germ layer origin. This raises the possibility of obtaining neuronal cells from new biological source of the same adult human subjects. In this study, we found that epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) cooperated to induce the proliferation, self-renewal, and expansion of neural stem cell-like population isolated from several newborn and adult mouse tissues: muscle and hematopoietic tissues. This population, in both primary culture and secondary expanded clones, formed spheres of undifferentiated cells that were induced to differentiate into neurons, astrocytes, and oligodendrocytes. Brain engraftment of the somatic-derived neural stem cells generated neuronal phenotypes, demonstrating the great plasticity of these cells with potential clinical application

A multi-layer mean-field model of the cerebellum embedding microstructure and population-specific dynamics

Mean-field (MF) models are computational formalism used to summarize in a few statistical parameters the salient biophysical properties of an inter-wired neuronal network. Their formalism normally incorporates different types of neurons and synapses along with their topological organization. MFs are crucial to efficiently implement the computational modules of large-scale models of brain function, maintaining the specificity of local cortical microcircuits. While MFs have been generated for the isocortex, they are still missing for other parts of the brain. Here we have designed and simulated a multi-layer MF of the cerebellar microcircuit (including Granule Cells, Golgi Cells, Molecular Layer Interneurons, and Purkinje Cells) and validated it against experimental data and the corresponding spiking neural network (SNN) microcircuit model. The cerebellar MF was built using a system of equations, where properties of neuronal populations and topological parameters are embedded in inter-dependent transfer functions. The model time constant was optimised using local field potentials recorded experimentally from acute mouse cerebellar slices as a template. The MF reproduced the average dynamics of different neuronal populations in response to various input patterns and predicted the modulation of the Purkinje Cells firing depending on cortical plasticity, which drives learning in associative tasks, and the level of feedforward inhibition. The cerebellar MF provides a computationally efficient tool for future investigations of the causal relationship between microscopic neuronal properties and ensemble brain activity in virtual brain models addressing both physiological and pathological conditions

La Prevalenza del Dolore Cronico Non Oncologico nell'Adulto e Patologie Associate: una revisione narrativa della letteratura

Il dolore cronico non oncologico rappresenta un problema sanitario sottostimato dal punto di vista epidemiologico ed in termini di salute pubblica. Esso è una malattia in senso stretto, e rappresenta una delle maggiori motivazioni per cui i soggetti si rivolgono ai servizi sanitari. La grandezza del fenomeno si esprime in termini di sofferenza umana e di costi sociali. L'obiettivo di questa revisione è quello di identificare le cause e la prevalenza del dolore cronico non oncologico nei soggetti adulti. E' stata realizzata una revisione della letteratura dal 1998 al 2012 utilizzando le emeroteche virtuali partendo dalle banche dati (Pub-Med, CINHAL, Cochrane). È stata effettuata una revisione narrativa degli articoli ottenuti. Sono stati esclusi articoli riguardanti cefalee, fasce di etí  pediatriche e geriatriche, oncologici e articoli specifici per patologia. Gli studi ottenuti sono stati classificati per anno, autore campione, metodi, fasce di etí  e definizione di dolore. Sono stati selezionati 7 articoli. Questi studi epidemiologici, realizzati in diverse parti del mondo, riportano un tasso di prevalenza relativo al dolore cronico tra il 16-53%. Emerge una elevata eterogeneití  di risultati relativi alle diagnosi e metodi. Seppure limitato il numero degli articoli, emerge una elevata complessití  del fenomeno.Parole chiave: Dolore Cronico, Prevalenza, EpidemiologiaABSTRACTThe chronic nonmalignant pain is an underestimated epidemiologic health problem. It is a disease in its own right. It is one of the major reasons because patients use health service. The magnitude of chronic pain is in terms of human suffering and costs to society. The aim of this review is to identify the diagnosis and the prevalence of nonmalignant chronic pain in the adults. We have done a review of the literature from 1998 to 2012 using the virtual newspaper libraries starting from data bases (Pub-Med, CINAHL, Cochrane). We have made a narrative review of the articles obtained. Excluding topics of headache, pain for pediatric and geriatric groups, cancer pain and disease-specific items. Studies were classified for year, author sample, methods, age groups and definition of pain. We have obtained 7 articles. These epidemiological studies conducted in different part of the world, reported prevalence rates of chronic pain ranging from 16-53%. They shows a high heterogeneity of results concerning diagnosis and methods. Although limited the number of articles, show the high complexity of the phenomenon.Key Words: Chronic Pain, Prevalence, Epidemiology.

A case of fetal hydrops: prenatal diagnosis and neonatal management

Hydrops fetalis (HF) is a serious fetal condition defined as an abnormal fluid accumulation in fetal extravascular compartments and body cavities caused by either immune or non immune conditions. Immune hydrops is caused by fetal hemolysis medi¬ated by circulating maternal antibodies to fetal red blood cell antigens. Its most common determinant is rhesus incompatibility. Systemic Lupus Eritematosus (SLE) is another rare cause of immune fetal hydrops, when the pregnancy is complicated by the presence of a third degree congenital heart block (CHB). The Neonatal Lupus Syndrome occurs with a prevalence of 2%. We reported the case of severe fetal hydrops in a 31 weeks pregnant woman affected by mild maternal D alloimmunization and SLE. Despite fetal hydrops and a mild positive indirect Coombs’ test, the flow-rate study with the Systolic Peak Velocity (PSV) of the MCA excluded a fetal anemia. At birth, blood gas showed a condition of severe metabolic and respiratory acidosis (pH 6.43, pO2 9.9 mmHg, pCO2 206 mmHg, Base Excess (BE) -35 mmol/l, HCO3- 2.7 mmol/l) and a mild anemia (Hemoglobin 10.3 g/dl). ECG revealed a normal sinus rhythm and a CHB was excluded. Despite the critical clinical condition, no cardiorespiratory or neurological adverse outcomes occurred in the newbor

In vitro and in vivo tetracycline-controlled myogenic conversion of NIH-3T3 cells: evidence of programmed cell death after muscle cell transplantation.

Ex vivo gene therapy of Duchenne muscular dystrophy based on autologous transplantation of genetically modified myoblasts is limited by their premature senescence. MyoD-converted fibroblasts represent an alternative source of myogenic cells. In this study the forced MyoD-dependent conversion of murine NIH-3T3 fibroblasts into myoblasts under the control of an inducible promoter silent in the presence of tetracycline was evaluated. After tetracycline withdrawal this promoter drives the transcription of MyoD in the engineered fibroblasts, inducing their myogenesis and giving rise to β-galactosidase-positive cells. MyoD-expressing fibroblasts withdrew from the cell cycle, but were unable to fuse in vitro into multinucleated myotubes. Five days following implantation of engineered fibroblasts in muscles of C57BL/10J mice we observed a sevenfold increase of β-galactosidase-positive regenerating myofibers in animals not treated with antibiotic compared with treated animals. After 1 week the number of positive fibers decreased and several apoptotic myonuclei were detected. Three weeks following implantation of MyoD-converted fibroblasts in recipient mice, no positive "blue" fiber was observed. Our results suggest that transactivation by tetracycline of MyoD may drive an in vivo myogenic conversion of NIH-3T3 fibroblasts and that, in this experimental setting, apoptosis plays a relevant role in limiting the efficacy of engineered fibroblast transplantation. This work opens the question whether apoptotic phenomena also play a general role as limiting factors of cellmediated gene therapy of inherited muscle disorders

Clinical expression of facioscapulohumeral muscular dystrophy in carriers of 1-3 D4Z4 reduced alleles: Experience of the FSHD Italian National Registry

OBJECTIVES: Facioscapulohumeral muscular dystrophy type 1 (FSHD1) has been genetically linked to reduced numbers ( 64 8) of D4Z4 repeats at 4q35. Particularly severe FSHD cases, characterised by an infantile onset and presence of additional extra-muscular features, have been associated with the shortest D4Z4 reduced alleles with 1-3 repeats (1-3 DRA). We searched for signs of perinatal onset and evaluated disease outcome through the systematic collection of clinical and anamnestic records of de novo and familial index cases and their relatives, carrying 1-3 DRA. SETTING: Italy. PARTICIPANTS: 66 index cases and 33 relatives carrying 1-3 DRA. OUTCOMES: The clinical examination was performed using the standardised FSHD evaluation form with validated inter-rater reliability. To investigate the earliest signs of disease, we designed the Infantile Anamnestic Questionnaire (IAQ). Comparison of age at onset was performed using the non-parametric Wilcoxon rank-sum or Kruskal-Wallis test. Comparison of the FSHD score was performed using a general linear model and Wald test. Kaplan-Meier survival analysis was used to estimate the age-specific cumulative motor impairment risk. RESULTS: No patients had perinatal onset. Among index cases, 36 (54.5%) showed the first signs by 10 years of age. The large majority of patients with early disease onset (26 out of 36, 72.2%) were de novo; whereas the majority of patients with disease onset after 10 years of age were familial (16, 53.3%). Comparison of the disease severity outcome between index cases with age at onset before and over 10 years of age, failed to detect statistical significance (Wald test p value=0.064). Of 61 index cases, only 17 (27.9%) presented extra-muscular conditions. Relatives carrying 1-3 DRA showed a large clinical variability ranging from healthy subjects, to patients with severe motor impairment. CONCLUSIONS: The size of the D4Z4 allele is not always predictive of severe clinical outcome. The high degree of clinical variability suggests that additional factors contribute to the phenotype complexity

Intraarterial Injection of Muscle-Derived Cd34+Sca-1+ Stem Cells Restores Dystrophin in mdx Mice

Duchenne muscular dystrophy is a lethal recessive disease characterized by widespread muscle damage throughout the body. This increases the difficulty of cell or gene therapy based on direct injections into muscles. One way to circumvent this obstacle would be to use circulating cells capable of homing to the sites of lesions. Here, we showed that stem cell antigen 1 (Sca-1), CD34 double-positive cells purified from the muscle tissues of newborn mice are multipotent in vitro and can undergo both myogenic and multimyeloid differentiation. These muscle-derived stem cells were isolated from newborn mice expressing the LacZ gene under the control of the muscle-specific desmin or troponin I promoter and injected into arterial circulation of the hindlimb of mdx mice. The ability of these cells to interact and firmly adhere to endothelium in mdx muscles microcirculation was demonstrated by intravital microscopy after an intraarterial injection. Donor Sca-1, CD34 muscle-derived stem cells were able to migrate from the circulation into host muscle tissues. Histochemical analysis showed colocalization of LacZ and dystrophin expression in all muscles of the injected hindlimb in all of five out of five 8-wk-old treated mdx mice. Their participation in the formation of muscle fibers was significantly increased by muscle damage done 48 h after their intraarterial injection, as indicated by the presence of 12% β-galactosidase–positive fibers in muscle cross sections. Normal dystrophin transcripts detected enzymes in the muscles of the hind limb injected intraarterially by the mdx reverse transcription polymerase chain reaction method, which differentiates between normal and mdx message. Our results showed that the muscle-derived stem cells first attach to the capillaries of the muscles and then participate in regeneration after muscle damage

B-Type Natriuretic Peptide in the Critically Ill with Acute Kidney Injury

Introduction. Acute kidney injury (AKI) is common in the intensive care unit (ICU) and associated with poor outcome. Plasma B-type natriuretic peptide (BNP) is a biomarker related to myocardial overload, and is elevated in some ICU patients. There is a high prevalence of both cardiac and renal dysfunction in ICU patients. Aims. To investigate whether plasma BNP levels in the first 48 hours were associated with AKI in ICU patients. Methods. We studied a cohort of 34 consecutive ICU patients. Primary outcome was presence of AKI on presentation, or during ICU stay. Results. For patients with AKI on presentation, BNP was statistically higher at 24 and 48 hours than No-AKI patients (865 versus 148 pg/mL; 1380 versus 131 pg/mL). For patients developing AKI during 48 hours, BNP was statistically higher at 0, 24 and 48 hours than No-AKI patients (510 versus 197 pg/mL; 552 versus 124 pg/mL; 949 versus 104 pg/mL). Conclusion. Critically ill patients with AKI on presentation or during ICU stay have higher levels of the cardiac biomarker BNP relative to No-AKI patients. Elevated levels of plasma BNP may help identify patients with elevated risk of AKI in the ICU setting. The mechanism for this cardiorenal connection requires further investigation