Una proposta di formazione dagli specializzandi per gli specializzandi: i "gruppi incognitivi"

PREMESSA: Dalla curiosit\ue0 e dai dubbi per questioni che quotidianamente incontriamo nella pratica clinica \ue8 nata l'idea di costruire un gruppo che, attraverso il confronto tra noi Specializzandi e la condivisione di approfondimenti su temi specifici, potesse dare delle risposte e stimolare nuovi interrogativi. Si \ue8 dato cos\uec vita a questo gruppo, chiamato, un po' socraticamente, gruppo incognitivo. Questi gli obiettivi originari: 1. soddisfare, in aggiunta all'offerta del regolare piano accademico, il nostro bisogno di "formazione continua", 2. Confrontarsi tra Specializzandi su questioni pragmatiche, 3. "imparare ad insegnare", attraverso la preparazione di una lezione e quindi la sua esposizione, 4. realizzare un compendio che potesse essere utilizzato "al letto del malato" e quindi fruito anche da chi non avesse la possibilit\ue0 di partecipare agli incontri OBIETTIVO: Tutti gli specializzandi della scuola di Specialit\ue0 in Geriatria sono stati invitati, di volta in volta, a partecipare agli incontri e a preparare una lezione da presentare al gruppo su un argomento di loro scelta. La partecipazione agli incontri era su base volontaria. La possibilit\ue0 di partecipare agli incontri era stata estesa anche a strutturati e studenti di medicina. Per ogni incontro si chiedeva di presentare un file in formato Word, di poche pagine, che sintetizzasse in versione schematica quanto espresso nella lezione. Gli specializzandi hanno utilizzato libri di testo, articoli scientifici e contenuti di Uptodate. Il luogo degli incontri \ue8 stato la biblioteca della scuola di Specialit\ue0 di Geriatria ove avevamo a disposizione un supporto multimediale per la proiezione delle presentazioni. La durata degli incontri \ue8 stata variabile, a seconda della complessit\ue0 dell'argomento e della scelta di colui che esponeva, nella media circa 80 minuti. RISULTATI: Da Ottobre 2014 a Maggio 2015 abbiamo svolto 13 incontri con contenuti trasversali. Di seguito l'elenco degli argomenti: malnutrizione nell'anziano, i criteri di Beers e i farmaci inappropriati nell'anziano, gli inibitori dell'acetilcolinesterasi (nota AIFA e scheda tecnica dei farmaci), algoritmo Advance Life Support, infezioni delle vie urinarie, terapia farmacologica dei disturbi del comportamento e psicologici nella demenza, reverse therapy della emorragie maggiori correlate agli anticoagulanti diretti ed indiretti, tachicardie sopraventricolari e ventricolari, dispnea acuta, polmonite, endocarditi, reazioni cutanee da farmaco (quest'ultimo presentato da una specializzanda in Dermatologia). Ogni incontro era monotematico e veniva presentato da uno o due specializzandi. Di solito l'argomento veniva esposto dalla stessa persona che l'aveva proposto. Tra i limiti di questo progetto l'"autoreferenzialit\ue0" in quanto le informazioni veicolate non sono state passate al vaglio di un specialista in materia, pertanto non sempre siamo riusciti a dare una risposta soddisfacente a tutti gli interrogativi emersi. Questo \ue8 stato comunque di stimolo per ulteriori approfondimenti. CONCLUSIONI: Abbiamo realizzato una compendio che raccoglie i contenuti degli incontri esposti sopra. Come gi\ue0 accennato sopra, ci\uf2 che rende questi contenuti particolarmente fruibili \ue8 la loro pragmaticit\ue0 per la pratica clinica. Abbiamo in previsione di proseguire con un secondo ciclo di incontri da settembre 2015. Tra gli argomenti gi\ue0 in programma: iponatremia, questioni di bioetica, reazioni trasfusionali, principi base di neuroimaging. L'obiettivo con il prossimo anno \ue8 quello di coinvolgere specializzandi di altre Scuole. L'ultimo incontro tenuto da una Specializzanda di Dermatologia ha avuto un impatto molto positivo e desideriamo ripetere l'esperienza

Petrology, Mineral and Isotope Geochemistry of the External Liguride Peridotites (Northern Apennines, Italy)

Mantle peridotites of the External Liguride (EL) units (Northern Apennines) represent slices of subcontinental lithospheric mantle emplaced at the surface during early stages of rifting of the Jurassic Ligurian Piemontese basin. Petrological, ion probe and isotopic investigations have been used to unravel the nature of their mantle protolith and to constrain the timing and mechanisms of their evolution. EL peridotites are dominantly fertile spinel Iherzolites partly recrystallizfd in the plagiodase Iherzplite stability field Clinopyroxenes stable in the spinel-facies assemblage have nearly fiat REE patterns (CeN/SmN=0·6-0·8) at (10-16)×C1 and high Na, Sr, Ti and Zr contents. Kaersutitic-Ti-pargasitic amphiboles also occur in the spinel-facies assemblage. Their LREE-depleted REE spectra and very low Sr, Zr and Ba contents indicate that they crystallized from hydrous fluids with low concentrations of incompatible elements. Thermometric estimates on the spinelfacies parageneses yield lithospheric equilibrium temperatures in the range 1000-1100°C, in agreement with the stability of amphibole, which implies T<1100°C. Sr and Nd isotopic compositions, determined on carefully handpicked clinopyroxene separates, plot within the depleted end of the MORB field (87Sr/86Sr=0·70222-0·70263; 143Nd/144Nd=0·513047-0·513205) similar to many subcontinental orogenic spinel Iherzolites from the western Mediterranean area (e.g. Ivrea Zpne and Lanzfl N). The interpretation of the EL Iherzolites as subcontinental lithospheric mantle is reinforced by the occurrence of one extremely depleted isotopic composition (87Sr/86Sr=0·701736; 143Nd/144Nd=0·513543). Sr and Nd model ages, calculated assuming both CHUR and DM mantle sources, range between 2·4 Ga and 780 Ma. In particular, the 1·2-Ga Sr age and the 780-Ma Nd age can be regarded as minimum ages of differentiation. The transition from spinel-to plagioclase-facies assemblage, accompanied by progressive deformation (from granular to tectonite-mylonite textures), indicate that the EL Iherzolites experienced a later, subsolidus decompressional evolution, starting from subcontinental lithospheric levels. Sm/Nd isochrons on plagioclase-clinopyroxene pairs furnish ages of ∽165 Ma. This early Jurassic subsolidus decompressional history is consistent with uplift by means of denudation in response to passive and asymmetric lithospheric extension. This is considered to be the most suitable geodynamic mechanism to account for the exposure of huge bodies of subcontinental lithospheric mantle during early stages of opening of an oceanic basi

RIPK3-Dependent Recruitment of Low-Inflammatory Myeloid Cells Does Not Protect from Systemic Salmonella Infection

ABSTRACT Regulated macrophage death has emerged as an important mechanism to defend against intracellular pathogens. However, the importance and consequences of macrophage death during bacterial infection are poorly resolved. This is especially true for the recently described RIPK3-dependent lytic cell death, termed necroptosis. Salmonella enterica serovar Typhimurium is an intracellular pathogen that precisely regulates virulence expression within macrophages to evade and manipulate immune responses, which is a key factor in its ability to cause severe systemic infections. We combined genetic and pharmacological approaches to examine the importance of RIPK3 for S. Typhimurium-induced macrophage death using conditions that recapitulate bacterial gene expression during systemic infection in vivo. Our findings indicate that noninvasive S. Typhimurium does not naturally induce macrophage necroptosis but does so in the presence of pan-caspase inhibition. Moreover, our data suggest that RIPK3 induction (following caspase inhibition) does not impact host survival following S. Typhimurium infection, which differs from previous findings based on inert lipopolysaccharide (LPS) injections. Finally, although necroptosis is typically characterized as highly inflammatory, our data suggest that RIPK3 skews the peritoneal myeloid population away from an inflammatory profile to that of a classically noninflammatory profile. Collectively, these data improve our understanding of S. Typhimurium-macrophage interactions, highlight the possibility that purified bacterial components may not accurately recapitulate the complexity of host-pathogen interactions, and reveal a potential and unexpected role for RIPK3 in resolving inflammation. IMPORTANCE Macrophages employ multiple strategies to limit pathogen infection. For example, macrophages may undergo regulated cell death, including RIPK3-dependent necroptosis, as a means of combatting intracellular bacterial pathogens. However, bacteria have evolved mechanisms to evade or exploit immune responses. Salmonella is an intracellular pathogen that avoids and manipulates immune detection within macrophages. We examined the contribution of RIPK3 to Salmonella-induced macrophage death. Our findings indicate that noninvasive Salmonella does not naturally induce necroptosis, but it does so when caspases are inhibited. Moreover, RIPK3 induction (following caspase inhibition) does not impact host survival following Salmonella systemic infection. Finally, our data show that RIPK3 induction results in recruitment of low-inflammatory myeloid cells, which was unexpected, as necroptosis is typically described as highly inflammatory. Collectively, these data improve our understanding of pathogen-macrophage interactions, including outcomes of regulated cell death during infection in vivo, and reveal a potential new role for RIPK3 in resolving inflammation

Wound care challenges in children and adults with spina bifida: An open-cohort study

Skin breakdown is a frequent concern for individuals with spina bifida. We explored wound incidence in patients with spina bifida and how it varies across a person\u27s life span and functional neurologic level. We examined the settings in which skin breakdown most commonly occurred, looking for evidence of chronic, non-healing wounds. We also sought to develop criteria to improve wound monitoring. We identified reported wound episodes in an open-cohort study over a 13-year period, examining the hospital and outpatient clinical records of spina bifida patients at Children\u27s National Medical Center (CNMC). Current age, age at wound presentation, sex, weight, functional neurologic level, wound location, setting in which the wound was acquired, the development of a chronic wound, and presence of a shunt were recorded. Of the 376 patients in our clinical population, 123 (average age: 18.8 years, range: infancy–56 years) developed a total of 375 wounds; the majority of patients who developed one wound went on to develop one or more additional wounds, and 20 patients developed chronic wounds. Our data suggest that age bracket (adolescents), wheelchair use, and bare feet, as well as possibly obesity and reduced executive functioning, are key risk factors for wound development. These findings have led to a focused effort to increase wound education and prevention. In addition we report on our early experience using a wound care specialist to champion this initiative

Virtual Reality for Pediatric Sedation: A Randomized Controlled Trial Using Simulation.

INTRODUCTION: Team training for procedural sedation for pediatric residents has traditionally consisted of didactic presentations and simulated scenarios using high-fidelity mannequins. We assessed the effectiveness of a virtual reality module in teaching preparation for and management of sedation for procedures. METHODS: After developing a virtual reality environment in Second Life® (Linden Lab, San Francisco, CA) where providers perform and recover patients from procedural sedation, we conducted a randomized controlled trial to assess the effectiveness of the virtual reality module versus a traditional web-based educational module. A 20 question pre- and post-test was administered to assess knowledge change. All subjects participated in a simulated pediatric procedural sedation scenario that was video recorded for review and assessed using a 32-point checklist. A brief survey elicited feedback on the virtual reality module and the simulation scenario. RESULTS: The median score on the assessment checklist was 75% for the intervention group and 70% for the control group (P = 0.32). For the knowledge tests, there was no statistically significant difference between the groups (P = 0.14). Users had excellent reviews of the virtual reality module and reported that the module added to their education. CONCLUSIONS: Pediatric residents performed similarly in simulation and on a knowledge test after a virtual reality module compared with a traditional web-based module on procedural sedation. Although users enjoyed the virtual reality experience, these results question the value virtual reality adds in improving the performance of trainees. Further inquiry is needed into how virtual reality provides true value in simulation-based education

CACHD1 is an α2δ-like protein that modulates CaV3 voltage-gated calcium channel activity

The putative cache (Ca2+ channel and chemotaxis receptor) domain containing 1 (CACHD1) protein has predicted structural similarities to members of the alpha2delta voltage-gated Ca2+ channel (VGCC) auxiliary subunit family. CACHD1 mRNA and protein were highly expressed in the male mammalian CNS, in particular in the thalamus, hippocampus and cerebellum, with a broadly similar tissue distribution to CaV3 subunits, in particular, CaV3.1. In expression studies, CACHD1 increased cell-surface localization of CaV3.1 and these proteins were in close proximity at the cell surface consistent with the formation of CACHD1-CaV3.1 complexes. In functional electrophysiological studies, co-expression of human CACHD1 with CaV3.1, CaV3.2 and CaV3.3 caused a significant increase in peak current density and corresponding increases in maximal conductance. By contrast, alpha2delta-1 had no effect on peak current density or maximal conductance in either CaV3.1, CaV3.2 or CaV3.3. Comparison of CACHD1-mediated increases in CaV3.1 current density and gating currents revealed an increase in channel open probability. In hippocampal neurons from male and female E19 rats, CACHD1 overexpression increased CaV3-mediated action potential (AP) firing frequency and neuronal excitability. These data suggest that CACHD1 is structurally an alpha2delta-like protein that functionally modulates CaV3 voltage-gated calcium channel activity

Asymptomatic bacteriuria in sickle cell disease: a cross-sectional study

BACKGROUND: It is known that there is significant morbidity associated with urinary tract infection and with renal dysfunction in sickle cell disease (SCD). However, it is not known if there are potential adverse outcomes associated with asymptomatic bacteriuria (ASB) infections in sickle cell disease if left untreated. This study was undertaken to determine the prevalence of ASB, in a cohort of patients with SCD. METHODS: This is a cross-sectional study of patients in the Jamaican Sickle Cell Cohort. Aseptically collected mid-stream urine (MSU) samples were obtained from 266 patients for urinalysis, culture and sensitivity analysis. Proteinuria was measured by urine dipsticks. Individuals with abnormal urine culture results had repeat urine culture. Serum creatinine was measured and steady state haematology and uric acid concentrations were obtained from clinical records. This was completed at a primary care health clinic dedicated to sickle cell diseases in Kingston, Jamaica. There were 133 males and 133 females in the sample studied. The mean age (mean ± sd) of participants was 26.6 ± 2.5 years. The main outcome measures were the culture of ≥ 10(5 )colony forming units of a urinary tract pathogen per milliliter of urine from a MSU specimen on a single occasion (probable ASB) or on consecutive occasions (confirmed ASB). RESULTS: Of the 266 urines collected, 234 were sterile and 29 had significant bacteriuria yielding a prevalence of probable ASB of 10.9% (29/266). Fourteen patients had confirmed ASB (prevalence 5.3%) of which 13 had pyuria. Controlling for genotype, females were 14.7 times more likely to have confirmed ASB compared to males (95%CI 1.8 to 121.0). The number of recorded visits for symptomatic UTI was increased by a factor of 2.5 (95% CI 1.4 to 4.5, p < 0.005) but serum creatinine, uric acid and haematology values were not different in patients with confirmed ASB compared with those with sterile urine. There was no association with history of gram negative sepsis. CONCLUSION: ASB is a significant problem in individuals with SCD and may be the source of pathogens in UTI. However, further research is needed to determine the clinical significance of ASB in SCD

Transmission of Avian Influenza A Viruses among Species in an Artificial Barnyard

Waterfowl and shorebirds harbor and shed all hemagglutinin and neuraminidase subtypes of influenza A viruses and interact in nature with a broad range of other avian and mammalian species to which they might transmit such viruses. Estimating the efficiency and importance of such cross-species transmission using epidemiological approaches is difficult. We therefore addressed this question by studying transmission of low pathogenic H5 and H7 viruses from infected ducks to other common animals in a quasi-natural laboratory environment designed to mimic a common barnyard. Mallards (Anas platyrhynchos) recently infected with H5N2 or H7N3 viruses were introduced into a room housing other mallards plus chickens, blackbirds, rats and pigeons, and transmission was assessed by monitoring virus shedding (ducks) or seroconversion (other species) over the following 4 weeks. Additional animals of each species were directly inoculated with virus to characterize the effect of a known exposure. In both barnyard experiments, virus accumulated to high titers in the shared water pool. The H5N2 virus was transmitted from infected ducks to other ducks and chickens in the room either directly or through environmental contamination, but not to rats or blackbirds. Ducks infected with the H7N2 virus transmitted directly or indirectly to all other species present. Chickens and blackbirds directly inoculated with these viruses shed significant amounts of virus and seroconverted; rats and pigeons developed antiviral antibodies, but, except for one pigeon, failed to shed virus

Managing urinary tract infections

Urinary tract infections (UTI) are common in childhood. Presence of pyuria and bacteriuria in an appropriately collected urine sample are diagnostic of UTI. The risk of UTI is increased with an underlying urological abnormality such as vesicoureteral reflux, constipation, and voiding dysfunction. Patients with acute pyelonephritis are at risk of renal scarring and subsequent complications such as hypertension, proteinuria with and without FSGS, pregnancy-related complications and even end-stage renal failure. The relevance and the sequence of the renal imaging following initial UTI, and the role of antimicrobial prophylaxis and surgical intervention are currently undergoing an intense debate. Prompt treatment of UTI and appropriate follow-up of those at increased risk of recurrence and/or renal scarring are important