Prebiotics counteract the morphological and functional changes secondary to chronic cisplatin exposition in the proximal colon of mice.

Cisplatin is an antimitotic drug able to cause acute and chronic gastrointestinal side effects. Acute side effects are attributable to mucositis while chronic ones are due to neuropathy. Cisplatin has also antibiotic properties inducing dysbiosis which enhances the inflammatory response, worsening local damage. Thus, a treatment aimed at protecting the microbiota could prevent or reduce the toxicity of chemotherapy. Furthermore, since a healthy microbiota enhances the effects of some chemotherapeutic drugs, prebiotics could also improve this drug effectiveness. We investigated whether chronic cisplatin administration determined morphological and functional alterations in mouse proximal colon and whether a diet enriched in prebiotics had protective effects. The results showed that cisplatin caused lack of weight gain, increase in kaolin intake, decrease in stool production and mucus secretion. Prebiotics prevented increases in kaolin intake, changes in stool production and mucus secretion, but had no effect on the lack of weight gain. Moreover, cisplatin determined a reduction in amplitude of spontaneous muscular contractions and of Connexin (Cx)43 expression in the interstitial cells of Cajal, changes that were partially prevented by prebiotics. In conclusion, the present study shows that daily administration of prebiotics, likely protecting the microbiota, prevents most of the colonic cisplatin-induced alterations.

Psilocybin fungi microdose treatment in major depressive disorder: a case report / Tratamiento con microdosis de hongos con psilocibina en trastorno depresivo mayor: reporte de un caso.

Major depression disorder is an entity with high prevalence and worldwide impact. Current treatments present a non-response rate of 15-30%, and certain adverse effects are seen like apathy syndrome and lack of emotional response. It is stated that the treatment with psilocybin fungi allows the possibility of dose reduction and suspension of classic psychotropic drugs and entails changes on an emotional and behavioral level that result benefic in patients with major depressive syndrome. We present a case of a 19 years old patient with major depressive syndrome diagnosis. Accompaniment and patient advice was made appealing to the right of autonomy, on the psilocybin microdose self-administration process, aiming to reducing health risks and potentiate probable beneficial effects, with weekly evaluations, for a period of 7 months; using clinical anamnesis, laboratory tests and the Hamilton depression scale. As a result of this intervention, a symptomatic complete remission was proven, alongside with the suspension of conventional pharmacological treatment without discontinuation symptoms and improvements at the communicational level, social interaction and general well-being. These findings support the idea that psilocybin microdose treatments are promising tools in depression treatments. Scientific studies are needed in order to certify these findings.

La depresión mayor es una enfermedad de gran prevalencia e impacto mundial. Los tratamientos actuales presentan una tasa de no respuesta del 15 al 30 %, mientras que en casos de eficacia se suelen observar efectos adversos como el síndrome de apatía y la falta de respuesta emocional. Se postula que el tratamiento con hongos psilocibios genera la posibilidad de reducción de dosis y suspensión de psicofármacos clásicos y ocasiona cambios a nivel emocional y comportamental benéficos en pacientes con trastorno depresivo mayor. Este es un caso de un paciente no binario de 19 años de edad con diagnóstico de trastorno depresivo mayor. Se realizó unacompañamiento y asesoramiento del paciente apelando al derecho de autonomía, en el proceso de autoadministración de microdosis de psilocibina, para disminución de riesgos en salud y potenciar efectos benéficos probables, con evaluación semanal, durante un periodo de 7 meses; utilizando la anamnesis clínica, análisis de laboratorio y la escala validada de depresión de Hamilton. Como resultado de esta intervención se evidenció una remisión completa sintomática, la suspensión del tratamiento farmacológico convencional, sin síntomas de discontinuación y mejorías a nivel comunicacional, de interacción social y bienestar general. Estos hallazgos apoyan la idea de que los tratamientos con microdosis de psilocibina son una herramienta prometedora en los tratamientos de depresión. Se necesitan más estudios que aporten evidencia científica para comprobar dichos hallazgos.

A highly conserved glutamic acid in ALFY inhibits membrane binding to aid in aggregate clearance.

Autophagy-linked FYVE protein (ALFY) is a large, multidomain protein involved in the degradation of protein aggregates by selective autophagy. The C-terminal FYVE domain of ALFY has been shown to bind phosphatidylinositol 3-phosphate (PI(3)P); however, ALFY only partially colocalizes with other FYVE domains in cells. Thus, we asked if the FYVE domain of ALFY has distinct membrane binding properties compared to other FYVE domains and whether these properties might affect its function in vivo. We found that the FYVE domain of ALFY binds weakly to PI(3)P containing membranes in vitro. This weak binding is the result of a highly conserved glutamic acid within the membrane insertion loop in the FYVE domain of ALFY that is not present in any other human FYVE domain. In addition, not only does this glutamic acid reduce binding to membranes in vitro and inhibits its targeting to membranes in vivo, but it is also important for the ability of ALFY to clear protein aggregates.

Morphologic evidence of telocytes in human thyroid stromal tissue.

Despite the evidence accumulated over the past decade that telocytes (TCs) are a distinctive, though long neglected, cell entity of the stromal microenvironment of several organs of the human body, to date their localization in the endocrine glands remains almost unexplored. This study was therefore undertaken to examine the presence and characteristics of TCs in normal human thyroid stromal tissue through an integrated morphologic approach featuring light microscopy and ultrastructural analysis. TCs were first identified by immunohistochemistry that revealed the existence of an intricate network of CD34+ stromal cells spread throughout the thyroid interfollicular connective tissue. Double immunofluorescence allowed to clearly differentiate CD34+ stromal cells lacking CD31 immunoreactivity from neighbour CD31+ microvascular structures, and the evidence that these stromal cells coexpressed CD34 and platelet-derived growth factor receptor α further strengthened their identification as TCs. Transmission electron microscopy confirmed the presence of stromal cells ultrastructurally identifiable as TCs projecting their characteristic cytoplasmic processes (i.e., telopodes) into the narrow interstitium between thyroid follicles and blood microvessels, where telopodes intimately surrounded the basement membrane of thyrocytes. Collectively, these morphologic findings provide the first comprehensive demonstration that TCs are main constituents of the human thyroid stroma and lay the necessary groundwork for further in-depth studies aimed at clarifying their putative implications in glandular homeostasis and pathophysiology.

Agrypnia excitata as the main feature in anti-leucine-rich glioma-inactivated 1 encephalitis: a detailed clinical and polysomnographic semiological analysis.

BACKGROUND AND PURPOSE: The core manifestations of leucine-rich glioma-inactivated 1 (LGI1) autoantibody-mediated encephalitis are limbic encephalitis and faciobrachial dystonic seizures. Agrypnia excitata (AE) is a rare syndrome characterized by sleep-wake cycle disruption, autonomic hyperactivation and episodes of oneiric stupor. Only a few diseases are known to present with AE. An autoimmune etiology must be considered when accompanied by neuromyotonia. A case of anti-LGI1 encephalitis presenting with AE is reported. METHODS: Detailed clinical, video-polysomnographic, laboratory, radiological and long-term follow-up assessments were performed. RESULTS: A previously healthy 58-year-old man was referred for a rapidly progressive change in mental status, characterized by persistent drowsiness and confusion, accompanied by frequent episodes of unconscious gestures ranging from simple stereotyped movements to more complex actions mimicking various daily activities. Other symptoms included tachycardia, hyperhidrosis, mild hyponatremia, rare faciobrachial dystonic seizures, and a single generalized tonic-clonic seizure, but no neuromyotonia. Prolonged video-polysomnography excluded epileptic activity and showed continuous monomorphic slowing of background activity not consistent with a regular wakefulness or sleep state. A brain magnetic resonance imaging scan was unremarkable. Brain fluorodeoxyglucose positron emission tomography revealed hypermetabolism of the hippocampi, amygdala and basal ganglia. Anti-LGI1 antibodies were detected in the cerebrospinal fluid. The sleep disorder resolved progressively after starting immunotherapy. CONCLUSIONS: Agrypnia excitata can be a dominant, treatable manifestation of anti-LGI1 encephalitis. Oneiric stupor episodes are a useful clinical feature for establishing diagnostic suspicion and could provide a window to understanding the mechanisms behind some movement disorders in autoimmune encephalitis.

Otilonium Bromide treatment prevents nitrergic functional and morphological changes caused by chronic stress in the distal colon of a rat IBS model.

Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder characterized by periods of remission and exacerbation. Among the risk factors to develop IBS, psychosocial stress is widely acknowledged. The water avoidance stress repeatedly applied (rWAS) is considered effective to study IBS etio-pathogenesis. Otilonium bromide (OB), a drug with multiple mechanisms of action, is largely used to treat IBS patients. Orally administered, it concentrates in the large bowel and significantly ameliorates the IBS symptomatology. Presently, we tested whether rWAS rats developed neuro-muscular abnormalities in the distal colon and whether OB treatment prevented them. The investigation was focussed on the nitrergic neurotransmission by combining functional and morphological methodologies. The results confirm rWAS as reliable animal model to investigate the cellular mechanisms responsible for IBS: exposure to one-hour psychosocial stress for 10 days depressed muscle contractility and increased iNOS expression in myenteric neurons. OB treatment counteracted these effects. We hypothesize that these effects are due to the corticotropin-releasing factor (CRF) release, the main mediator of the psychosocial stress, followed by a CRF1receptor activation. OB, that was shown to prevent CRF1r activation, reasonably interrupted the cascade events that bring to the mechanical and immunohistochemical changes affecting rWAS rat colon.

Impairment in the telocyte/CD34+ stromal cell network in human rheumatoid arthritis synovium.

Telocytes (TCs)/CD34+ stromal cells have recently emerged as peculiar interstitial cells detectable in a variety of organs throughout the human body. TCs are typically arranged in networks establishing unique spatial relationships with neighbour cells and likely contributing to the maintenance of tissue homeostasis by both cell-to-cell contacts and releasing extracellular vesicles. Hence, TC defects are being increasingly reported in different pathologies, such as chronic inflammatory and fibrotic conditions. In this regard, TCs/CD34+ stromal cells have been shown to constitute an intricate interstitial network in the subintimal area of the normal human synovial membrane, but whether they are altered in chronic synovitis has yet to be explored. We therefore undertook a morphologic study to compare the distribution of TCs/CD34+ stromal cells between normal synovium and chronically inflamed synovium from patients with rheumatoid arthritis (RA) by using CD34 immunohistochemistry and CD31/CD34 double immunofluorescence. CD34 immunostaining revealed that, at variance with normal synovium, the inflamed and hyperplastic RA synovial tissue was nearly or even completely devoid of TCs/CD34+ stromal cells. Double immunofluorescence confirmed that almost all CD34+ tissue components detectable in RA synovium were blood vessels coexpressing CD31, while a widespread network of CD31- /CD34+ TCs was clearly evident in the whole sublining layer of normal synovium. In the context of the emerging diverse roles of TCs/CD34+ stromal cells in the regulation of tissue homeostasis and structure, the remarkable impairment in their networks herein uncovered in RA synovium may suggest important pathophysiologic implications that will be worth investigating further.

The structure of a highly-conserved picocyanobacterial protein reveals a Tudor domain with an RNA-binding function.

Cyanobacteria of the Prochlorococcus and marine Synechococcus genera are the most abundant photosynthetic microbes in the ocean. Intriguingly, the genomes of these bacteria are strongly divergent even within each genus, both in gene content and at the amino acid level of the encoded proteins. One striking exception to this is a 62-amino-acid protein, termed Prochlorococcus/ Synechococcushyper-conserved protein (PSHCP). PSHCP is not only found in all sequenced Prochlorococcus and marine Synechococcus genomes, but it is also nearly 100% identical in its amino acid sequence across all sampled genomes. Such universal distribution and sequence conservation suggest an essential cellular role of PSHCP in these bacteria. However, its function is unknown. Here, we used NMR spectroscopy to determine its structure, finding that 53 of the 62 amino acids in PSHCP form a Tudor domain, whereas the remainder of the protein is disordered. NMR titration experiments revealed that PSHCP has only a weak affinity for DNA, but an 18.5-fold higher affinity for tRNA, hinting at an involvement of PSHCP in translation. Isothermal titration calorimetry experiments further revealed that PSHCP also binds single-stranded, double-stranded, and hairpin RNAs. These results provide the first insight into the structure and function of PSHCP, suggesting that PSHCP appears to be an RNA-binding protein that can recognize a broad array of RNA molecules.

Artificial Intelligence and Big Data in Diabetes Care: A Position Statement of the Italian Association of Medical Diabetologists.

Since the last decade, most of our daily activities have become digital. Digital health takes into account the ever-increasing synergy between advanced medical technologies, innovation, and digital communication. Thanks to machine learning, we are not limited anymore to a descriptive analysis of the data, as we can obtain greater value by identifying and predicting patterns resulting from inductive reasoning. Machine learning software programs that disclose the reasoning behind a prediction allow for "what-if" models by which it is possible to understand if and how, by changing certain factors, one may improve the outcomes, thereby identifying the optimal behavior. Currently, diabetes care is facing several challenges: the decreasing number of diabetologists, the increasing number of patients, the reduced time allowed for medical visits, the growing complexity of the disease both from the standpoints of clinical and patient care, the difficulty of achieving the relevant clinical targets, the growing burden of disease management for both the health care professional and the patient, and the health care accessibility and sustainability. In this context, new digital technologies and the use of artificial intelligence are certainly a great opportunity. Herein, we report the results of a careful analysis of the current literature and represent the vision of the Italian Association of Medical Diabetologists (AMD) on this controversial topic that, if well used, may be the key for a great scientific innovation. AMD believes that the use of artificial intelligence will enable the conversion of data (descriptive) into knowledge of the factors that "affect" the behavior and correlations (predictive), thereby identifying the key aspects that may establish an improvement of the expected results (prescriptive). Artificial intelligence can therefore become a tool of great technical support to help diabetologists become fully responsible of the individual patient, thereby assuring customized and precise medicine. This, in turn, will allow for comprehensive therapies to be built in accordance with the evidence criteria that should always be the ground for any therapeutic choice.

Nerve sprouting and neurogenic inflammation characterize the neurogenic detrusor overactive bladder of patients no longer responsive to drug therapies.

Urothelium and Lamina Propria (LP) are considered an integrate sensory system which is able to control the detrusor activity. Complete supra-sacral spinal cord lesions cause Neurogenic Detrusor Overactivity (NDO) whose main symptoms are urgency and incontinence. NDO therapy at first consists in anti-muscarinic drugs; secondly, in intra-vesical injection of botulinum toxin. However, with time, all the patients become insensitive to the drugs and decide for cystoplastic surgery. With the aim to get deeper in both NDO and drug's efficacy lack pathogenesis, we investigated the innervation, muscular and connective changes in NDO bladders after surgery by using morphological and quantitative methodologies. Bladder innervation showed a significant global loss associated with an increase in the nerve endings located in the upper LP where a neurogenic inflammation was also present. Smooth muscle cells (SMC) anomalies and fibrosis were found in the detrusor. The increased innervation in the ULP is suggestive for a sprouting and could condition NDO evolution and drug efficacy length. Denervation might cause the SMC anomalies responsible for the detrusor altered contractile activity and intra-cellular traffic and favour the appearance of fibrosis. Inflammation might accelerate these damages. From the clinical point of view, an early anti-inflammatory treatment could positively influence the disease fate.

Telocyte's contacts.

Telocytes (TC) are an interstitial cell type located in the connective tissue of many organs of humans and laboratory mammals. By means of homocellular contacts, TC build a scaffold whose meshes integrity and continuity are guaranteed by those contacts having a mechanical function; those contacts acting as sites of intercellular communication allow exchanging information and spreading signals. Heterocellular contacts between TC and a great variety of cell types give origin to mixed networks. TC, by means of all these types of contacts, their interaction with the extracellular matrix and their vicinity to nerve endings, are part of an integrated system playing tissue/organ-specific roles.

Adaptive changes of telocytes in the urinary bladder of patients affected by neurogenic detrusor overactivity.

Urinary bladder activity involves central and autonomic nervous systems and bladder wall. Studies on the pathogenesis of voiding disorders such as the neurogenic detrusor overactivity (NDO) due to suprasacral spinal cord lesions have emphasized the importance of an abnormal handling of the afferent signals from urothelium and lamina propria (LP). In the LP (and detrusor), three types of telocytes (TC) are present and form a 3D-network. TC are stromal cells able to form the scaffold that contains and organizes the connective components, to serve as guide for tissue (re)-modelling, to produce trophic and/or regulatory molecules, to share privileged contacts with the immune cells. Specimens of full thickness bladder wall from NDO patients were collected with the aim to investigate possible changes of the three TC types using histology, immunohistochemistry and transmission electron microscopy. The results show that NDO causes several morphological TC changes without cell loss or network interruption. With the exception of those underlying the urothelium, all the TC display signs of activation (increase in Caveolin1 and caveolae, αSMA and thin filaments, Calreticulin and amount of cisternae of the rough endoplasmic reticulum, CD34, euchromatic nuclei and large nucleoli). In all the specimens, a cell infiltrate, mainly consisting in plasma cells located in the vicinity or taking contacts with the TC, is present. In conclusion, our findings show that NDO causes significant changes of all the TC. Notably, these changes can be interpreted as TC adaptability to the pathological condition likely preserving each of their peculiar functions.

Bile salts and alkaline pH reciprocally modulate the interaction between the periplasmic domains of Vibrio cholerae ToxR and ToxS.

ToxR is a transmembrane transcription factor that is essential for virulence gene expression and human colonization by Vibrio cholerae. ToxR requires its operon partner ToxS, a periplasmic integral membrane protein, for full activity. These two proteins are thought to interact through their respective periplasmic domains, ToxRp and ToxSp. In addition, ToxR is thought to be responsive to various environmental cues, such as bile salts and alkaline pH, but how these factors influence ToxR is not yet understood. Using NMR and reciprocal pull down assays, we present the first direct evidence that ToxR and ToxS physically interact. Furthermore, using NMR and DSF, it was shown that the bile salts cholate and chenodeoxycholate interact with purified ToxRp and destabilize it. Surprisingly, bile salt destabilization of ToxRp enhanced the interaction between ToxRp and ToxSp. In contrast, alkaline pH, which is one of the factors that leads to ToxR proteolysis, decreased the interaction between ToxRp and ToxSp. Taken together, these data suggest a model whereby bile salts or other detergents destabilize ToxR, increasing its interaction with ToxS to promote full ToxR activity. Subsequently, as V. cholerae alkalinizes its environment in late stationary phase, the interaction between the two proteins decreases, allowing ToxR proteolysis to proceed.

Identification of a Small Molecule Activator for AphB, a LysR-Type Virulence Transcriptional Regulator in Vibrio cholerae.

AphB is a LysR-type transcriptional regulator (LTTR) that cooperates with a second transcriptional activator, AphA, at the tcpPH promoter to initiate expression of the virulence cascade in Vibrio cholerae. Because it is not yet known whether AphB responds to a natural ligand in V. cholerae that influences its ability to activate transcription, we used a computational approach to identify small molecules that influence its activity. In silico docking was used to identify potential ligands for AphB, and saturation transfer difference nuclear magnetic resonance was subsequently employed to access the validity of promising targets. We identified a small molecule, BP-15, that specifically binds the C-terminal regulatory domain of AphB and increases its activity. Interestingly, molecular docking predicts that BP-15 does not bind in the putative primary effector-binding pocket located at the interface of RD-I and RD-II as in other LTTRs, but rather at the dimerization interface. The information gained in this study helps us to further understand the mechanism by which transcriptional activation by AphB is regulated by suggesting that AphB has a secondary ligand binding site, as observed in other LTTRs. This study also lays the groundwork for the future design of inhibitory molecules to block the V. cholerae virulence cascade, thereby preventing the devastating symptoms of cholera infection.

Repeated otilonium bromide administration prevents neurotransmitter changes in colon of rats underwent to wrap restraint stress.

Otilonium bromide (OB) is a spasmolytic drug successfully used for the treatment of irritable bowel syndrome (IBS). Its efficacy has been attributed to the block of L- and T-type Ca2+ channels and muscarinic and tachykinin receptors in the smooth muscle. Furthermore, in healthy rats, repeated OB administration modified neurotransmitter expression and function suggesting other mechanisms of action. On this basis, we investigated whether repeated OB treatment prevented the functional and neurochemical changes observed in the colon of rats underwent to wrap restrain stress (WRS) a psychosocial stressor considered suitable to reproduce the main IBS signs and symptoms. In control, WRS and OB/WRS rats functional parameters were measured in vivo and morphological investigations were done ex vivo in the colon. The results showed that OB counteracts most of the neurotransmitters changes caused by WRS. In particular, the drug prevents the decrease in SP-, NK1r-, nNOS-, VIP-, and S100ß-immunoreactivity (IR) and the increase in CGRP-, and CRF1r-IR. On the contrary, OB does not affect the increase in CRF2r-IR neurons observed in WRS rats and does not interfere with the mild mucosal inflammation due to WRS. Finally, OB per se increases the Mr2 expression in the muscle wall and decreases the number of the myenteric ChAT-IR neurons. Functional findings show a significantly reduction in the number of spontaneous abdominal contraction in OB treated rats. The ability of OB to block L-type Ca2+ channels, also expressed by enteric neurons, might represent a possible mechanism through which OB exerts its actions.

Chemical Composition, Antimicrobial Activity, and Mode of Action of Essential Oils against Paenibacillus larvae, Etiological Agent of American Foulbrood on Apis mellifera.

This study aimed to characterize the chemical composition of Aloysia polystachia, Acantholippia seriphioides, Schinus molle, Solidago chilensis, Lippia turbinata, Minthostachys mollis, Buddleja globosa, and Baccharis latifolia essential oils (EOs), and to evaluate their antibacterial activities and their capacity to provoke membrane disruption in Paenibacillus larvae, the bacteria that causes the American Foulbrood (AFB) disease on honey bee larvae. The relationship between the composition of the EOs and these activities on P. larvae was also analyzed. Monoterpenes were the most abundant compounds in all EOs. All EOs showed antimicrobial activity against P. larvae and disrupted the cell wall and cytoplasmic membrane of P. larvae provoking the leakage of cytoplasmic constituents (with the exception of B. latifolia EO). While, the EOs' antimicrobial activity was correlated most strongly to the content of pulegone, carvone, (Z)-ß-ocimene, δ-cadinene, camphene, terpinen-4-ol, elemol, ß-pinene, ß-elemene, γ-cadinene, α-terpineol, and bornyl acetate; the volatiles that better explained the membrane disruption were carvone, limonene, cis-carvone oxide, pentadecane, trans-carvyl acetate, trans-carvone oxide, trans-limonene oxide, artemisia ketone, trans-carveol, thymol, and γ-terpinene (positively correlated) and biciclogermacrene, δ-2-carene, verbenol, α-pinene, and α-thujene (negatively correlated). The studied EOs are proposed as natural alternative means of control for the AFB disease.

Phosphorylation of ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) by Akt promotes stability and mitogenic function of S-phase kinase-associated protein-2 (Skp2).

The regulation of the cell cycle by the ubiquitin-proteasome system is dependent on the activity of E3 ligases. Skp2 (S-phase kinase associated protein-2) is the substrate recognition subunit of the E3 ligase that ubiquitylates the cell cycle inhibitors p21(cip1) and p27(kip1) thus promoting cell cycle progression. Increased expression of Skp2 is frequently observed in diseases characterized by excessive cell proliferation, such as cancer and neointima hyperplasia. The stability and cellular localization of Skp2 are regulated by Akt, but the molecular mechanisms underlying these effects remain only partly understood. The scaffolding protein Ezrin-Binding Phosphoprotein of 50 kDa (EBP50) contains two PDZ domains and plays a critical role in the development of neointimal hyperplasia. Here we report that EBP50 directly binds Skp2 via its first PDZ domain. Moreover, EBP50 is phosphorylated by Akt on Thr-156 within the second PDZ domain, an event that allosterically promotes binding to Skp2. The interaction with EBP50 causes cytoplasmic localization of Skp2, increases Skp2 stability and promotes proliferation of primary vascular smooth muscle cells. Collectively, these studies define a novel regulatory mechanism contributing to aberrant cell growth and highlight the importance of scaffolding function of EBP50 in Akt-dependent cell proliferation.

Loss of Interstitial Cells of Cajal and Patterns of Gastric Dysrhythmia in Patients With Chronic Unexplained Nausea and Vomiting.

BACKGROUND & AIMS: Chronic unexplained nausea and vomiting (CUNV) is a debilitating disease of unknown cause. Symptoms of CUNV substantially overlap with those of gastroparesis, therefore the diseases may share pathophysiologic features. We investigated this hypothesis by quantifying densities of interstitial cells of Cajal (ICCs) and mapping slow-wave abnormalities in patients with CUNV vs controls. METHODS: Clinical data and gastric biopsy specimens were collected from 9 consecutive patients with at least 6 months of continuous symptoms of CUNV but normal gastric emptying who were treated at the University of Mississippi Medical Center, and from 9 controls (individuals free of gastrointestinal disease or diabetes). ICCs were counted and ultrastructural analyses were performed on tissue samples. Slow-wave propagation profiles were defined by high-resolution electrical mapping (256 electrodes; 36 cm(2)). Results from patients with CUNV were compared with those of controls as well as patients with gastroparesis who were studied previously by identical methods. RESULTS: Patients with CUNV had fewer ICCs than controls (mean, 3.5 vs 5.6 bodies/field, respectively; P < .05), with mild ultrastructural abnormalities in the remaining ICCs. Slow-wave dysrhythmias were identified in all 9 subjects with CUNV vs only 1 of 9 controls. Dysrhythmias included abnormalities of initiation (stable ectopic pacemakers, unstable focal activities) and conduction (retrograde propagation, wavefront collisions, conduction blocks, and re-entry), operating across bradygastric, normal (range, 2.4-3.7 cycles/min), and tachygastric frequencies; dysrhythmias showed velocity anisotropy (mean, 3.3 mm/s longitudinal vs 7.6 mm/s circumferential; P < .01). ICCs were less depleted in patients with CUNV than in those with gastroparesis (mean, 3.5 vs 2.3 bodies/field, respectively; P < .05), but slow-wave dysrhythmias were similar between groups. CONCLUSIONS: This study defined cellular and bioelectrical abnormalities in patients with CUNV, including the identification of slow-wave re-entry. Pathophysiologic features of CUNV were observed to be similar to those of gastroparesis, indicating that they could be spectra of the same disorder. These findings offer new insights into the pathogenesis of CUNV and may help to inform future treatments.

Sibling cord blood donor program for hematopoietic cell transplantation: the 20-year experience in the Rome Cord Blood Bank.

Umbilical cord blood (UCB) represents a source of hematopoietic stem cells for patients lacking a suitably matched and readily available related or unrelated stem cell donor. As UCB transplantation from compatible sibling provides good results in children therefore directed sibling UCB collection and banking is indicated in family who already have a child with a disease potentially treatable with an allogeneic hematopoietic stem cell transplantation. Particularly, related UCB collection is recommended when the patients urgently need a transplantation. To provide access to all patients in need, we developed a "Sibling cord blood donor program for hematopoietic cell transplantation". Here we report results of this project started 20years ago. To date, in this study a total of 194 families were enrolled, a total of 204 UCB samples were successfully collected and 15 pediatric patients have been transplanted. Recently, some authors have suggested novel role for UCB other than in the transplantation setting. Therefore, future studies in the immunotherapy and regenerative medicine areas could expand indication for sibling directed UCB collection.

The Telocyte Subtypes.

Several cells are endowed in the interstitial space of the connective tissue; among them, a peculiar type has been recently described and named telocyte (TC). The increasing interest on this cell type has allowed identifying it in almost all the organs. All TCs have a proper ultrastructural feature that makes them undoubtedly recognizable under the transmission electron microscope (TEM). On the contrary, a complex often confusing picture comes out from the immunohistochemical investigations either due to the technical procedures used or, intriguingly, to the possibility that diverse subtypes of TC might exist.Among the several markers used to label the TC, the most common are the CD34 and the PDGFRalpha, and, in many organs, the TC expresses both these markers. An exception is represented by the human urinary bladder where none of the TC, as recognized under the TEM, was double labelled. All the data indicate that TCs show immunohistochemical differences depending on the organ where they are located and/or the animal species.On the basis of their ubiquitous distribution, TCs are unanimously considered organizers of the connective tissue because of their ability to form 3-D networks. Close to this common role, numerous other roles have been attributed to the TC. Indeed, each of the TC subtype likely plays an own organ-/tissue-specific role contributing to different aspects of physiological regulation in the various anatomical niches they occupy.