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One of the top challenges in education and neuroscience consists in translating laboratory results into strategies to improve learning and memory in teaching environments. In that sense, during the last two decades, researchers have discovered specific temporal windows around learning, during which the intervention with some experiences induces modulatory effects on the formation and/or persistence of memory. Based on these results, the aim of the present study was to design a specific strategy to improve the memory of students in a high-school scenario, by assessing the effect of a novel situation experienced close to learning. We found that the long-term memory about a geometrical figure was more precise in the group of students that faced a novel situation 1 h before or after learning the figure than the control group of students who did not face the novelty. This enhancement was probably triggered by processes acting on memory formation mechanisms that remained evident 45 days after learning, indicating that the improvement was sustained over time. In addition, our results showed that novelty no longer improved the memory if it was experienced 4 h before or after learning. However, far beyond this window of efficacy, when it was faced around 10 h after learning, the novel experience improved the memory persistence tested 7 days later. In summary, our findings characterized different temporal windows of the effectiveness of novelty acting on memory processing, providing a simple and inexpensive strategy that could be used to improve memory formation and persistence in high-school students.

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Essentials Platelet packing density in a hemostatic plug limits molecular movement to diffusion. A diffusion-dependent steep thrombin gradient forms radiating outwards from the injury site. Clot retraction affects the steepness of the gradient by increasing platelet packing density. Together, these effects promote hemostatic plug core formation and inhibit unnecessary growth. SUMMARY: Background Hemostasis studies performed in vivo have shown that hemostatic plugs formed after penetrating injuries are characterized by a core of highly activated, densely packed platelets near the injury site, covered by a shell of less activated and loosely packed platelets. Thrombin production occurs near the injury site, further activating platelets and starting the process of platelet mass retraction. Tightening of interplatelet gaps may then prevent the escape and exchange of solutes. Objectives To reconstruct the hemostatic plug macro- and micro-architecture and examine how platelet mass contraction regulates solute transport and solute concentration in the gaps between platelets. Methods Our approach consisted of three parts. First, platelet aggregates formed in vitro under flow were analyzed using scanning electron microscopy to extract data on porosity and gap size distribution. Second, a three-dimensional (3-D) model was constructed with features matching the platelet aggregates formed in vitro. Finally, the 3-D model was integrated with volume and morphology measurements of hemostatic plugs formed in vivo to determine how solutes move within the platelet plug microenvironment. Results The results show that the hemostatic mass is characterized by extremely narrow gaps, porosity values even smaller than previously estimated and stagnant plasma velocity. Importantly, the concentration of a chemical species released within the platelet mass increases as the gaps between platelets shrink. Conclusions Platelet mass retraction provides a physical mechanism to establish steep chemical concentration gradients that determine the extent of platelet activation and account for the core-and-shell architecture observed in vivo.

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Gonadotrophin-releasing hormone (GnRH) neurones fire spontaneous bursts of action potentials, although little is understood about the underlying mechanisms. In the present study, we report evidence for two types of bursting/oscillation driven by different mechanisms. Properties of these different types are clarified using mathematical modelling and a recently developed active-phase/silent-phase correlation technique. The first type of GnRH neurone (1-2%) exhibits slow (∼0.05 Hz) spontaneous oscillations in membrane potential. Action potential bursts are often observed during oscillation depolarisation, although some oscillations were entirely subthreshold. Oscillations persist after blockade of fast sodium channels with tetrodotoxin (TTX) and blocking receptors for ionotropic fast synaptic transmission, indicating that they are intrinsically generated. In the second type of GnRH neurone, bursts were irregular and TTX caused a stable membrane potential. The two types of bursting cells exhibited distinct active-phase/silent-phase correlation patterns, which is suggestive of distinct mechanisms underlying the rhythms. Further studies of type 1 oscillating cells revealed that the oscillation period was not affected by current or voltage steps, although amplitude was sometimes damped. Oestradiol, an important feedback regulator of GnRH neuronal activity, acutely and markedly altered oscillations, specifically depolarising the oscillation nadir and initiating or increasing firing. Blocking calcium-activated potassium channels, which are rapidly reduced by oestradiol, had a similar effect on oscillations. Kisspeptin, a potent activator of GnRH neurones, translated the oscillation to more depolarised potentials, without altering period or amplitude. These data show that there are at least two distinct types of GnRH neurone bursting patterns with different underlying mechanisms.

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Cell responses are commonly heterogeneous, even within a subpopulation. In the present study, we investigate the source of heterogeneity in the Ca(2+) response of anterior pituitary lactotrophs to a Ca(2+) mobilisation agonist, thyrotrophin-releasing hormone. This response is characterised by a sharp increase of cytosolic Ca(2+) concentration as a result of mobilisation of Ca(2+) from intracellular stores, followed by a decrease to an elevated plateau level that results from Ca(2+) influx. We focus on heterogeneity of the evoked Ca(2+) spike under extracellular Ca(2+) free conditions. We introduce a method that uses the information provided by a mathematical model to characterise the source of heterogeneity. This method compares scatter plots of features of the Ca(2+) response obtained experimentally with those made from the mathematical model. The model scatter plots reflect random variation of parameters over different ranges, and matching the experimental and model scatter plots allows us to predict which parameters are most variable. We find that a large degree of variation in Ca(2+) efflux is a likely key contributor to the heterogeneity of Ca(2+) responses to thyrotrophin-releasing hormone in lactotrophs. This technique is applicable to any situation in which the heterogeneous biological response is described by a mathematical model.

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SUMMARY: Factor XI (FXI) deficiency is a rare bleeding disorder, resulting in a wide range of bleeding manifestations, from asymptomatic bleeding to injury-related bleeding. To identify mutations in FXI-deficient patients and to establish a possible relationship between clinical phenotype and genotype, we studied two patients from Southern Italy with FXI deficiency. They were identified by presurgical or routine laboratory screening. None of them showed bleeding. Three different mutations were detected (Glu117Stop, Cys118Arg and Trp497Gly); two of them were novel (Cys118Arg and Trp497Gly). One patient (with severe FXI levels) showed a compound heterozygosity (Glu117Stop with Cys118Arg). Two novel missense mutations were highly conserved among different species. In our patients, bleeding tendency did not appear to be correlated with FXI levels or with a single mutation in heterozygosis. On the other hand, the compound heterozygosis might explain low FXI levels, but it is not associated with bleeding. Our data confirm that a severe FXI deficiency is not necessarily associated with bleeding.

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Pregnancy is a condition of excessive clotting due to a decrease of some coagulation factors and a reduction of anticoagulant proteins, such as protein S. It is known that the causes of congenital or acquired thrombophilia may be associated with an increased risk of venous thromboembolism during pregnancy and/or obstetric complications, such early or late fetal loss, intrauterine fetal deaths, pre-eclampsia, fetal growth restriction. During pregnancy the use of a prophylaxis with antithrombotic drugs is considered at present a promising opportunity to significantly reduce the prevalence of thromboembolic complications, improving maternal and fetal outcomes. This article is a review to most recent evidence of pregnant anticoagulant prophylaxis in women with previous thromboembolic events.

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The authors report a case report of rare disease interesting the digestive tract and often associated to the other gastrointestinal pathologies and/or pulmonary diseases and can be also associated to not gastrointestinal conditions such as collagen-vascular disease, transplantation, AIDS, use of corticosteroid and chemotherapy; other causes can be iatrogenic such as traumatic gastrointestinal endoscopy (a mucoses biopsy, a polipectomy) or the assumption of lattulosio; in 15-20% of cases the pneumatosis cystoides intestinalis is considered primitive. In the our case the Pneumatosis coli was associated to administration of acarbose; in international literature only four papers in the English language were reported. Our patient showed a strongly aspecific symptomatology and easily attributable in first line or to the pathology of base (diabetic patient) or to the assumption of the acarbose; from about 7-8 months she showed unexplained episodes of crampy abdominal pain, diarrhea with 3-4 defecations/die with semiliquid and normochromic stools, tenesmus and a not better specified loss of weight. The diagnosis was been performed by colonoscopy and confirmed by abdominal CT scan with water enema and histologically; we have used the traditional radiology only to exclude the involvement of other gastroenteric districts. The patient was been treated with O2-therapy associated to antibiotics treatment; the suspension of the causal factor, the acarbose, has been of not secondary importance; the complete resolution of disease was obtained after 15 days of therapy.

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The organizational appropriateness of hospital stays is an expression of a hospital's efficiency and aim of the management control. The AEP (American Version)/PRUO (Italian Version) protocol is specific for measuring the organizational appropriateness of hospital stays. The aim of this study is the comparative analysis of the organizational appropriateness of hospital stays in Careggi Hospital of Florence and in all hospital Departments in 1995 and 1998. In 1998 the AEP/PRUO protocol was applied to 2148 samples of hospital stays out of 38,968 eligible hospitalizations, and in 1995 a sample of 1989 hospital stays out of 35,108. In 1998 2,148 admissions and 15,338 days of hospitalization were tested. In 1995, 1989 admission days and 12,264 days of hospitalization were tested, 63 departments were studied. In 1995 the first edition of the protocol was applied, in 1998 the second. A sample of 218 of the 1998 hospital stays was tested with both editions to evaluate the impact of differences. In 1998, with the second edition of the protocol, the inappropriateness rate of admission days and hospitalization days and the rate of in-patients inappropriate hospital stays was respectively 38.0%, 43.8% and 18.5%. Compared with 1995 results, the rates increased +6.2%, 6% and +7.5% respectively. Instead, with the first edition of the protocol, the rates were 29.7%, 37.6% and 10.7% and, compared with 1995, they were reduced -2.1%, -0.6% and -0.3%. The longitudinal multilevel analysis has allowed the evaluation of the performance of each department.

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This retrospective, observational study was performed to evaluate the structure and the content of the nursing documentation in the Azienda ospedaliera Careggi, Firenze in 1998. To this aim we review 1964 nursing records including both notes by turns and care plans. One-thousand-one-hundred-and-twenty-five records came from surgical and 839 from medical wards. From the selected records, every day of the hospital stay, including both the admission and the discharge, were evaluated, so that the studied days were a total of 18,683. Only 32% of the nursing records had a global assessment of patient situation on admission. A medical diagnosis was observed in 84% of the cases, but a nursing diagnosis was absent in over 99.5% of the charts. During stay most notes were related to medical treatment and visits. Nursing notes were lacking in 32% of turns, while "nothing to report" was recorded in another 15.5% of cases. A nursing care plan was present in a minority of records. A final evaluation of planned nursing interventions was reported in approximately 5% of the charts. Nursing care plans were updated during stay in less than one tenth of cases. Discharges notes were absent in slightly more than 80% of the cases. This survey confirms the importance of continuing education and supervision in nursing documentations, if a reliable source of nursing information has to be developed. Future nursing records should include only essential information, avoiding any overlap with medical charts.

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BACKGROUND AND AIMS: The clinical significance of dolichoarteriopathies (kinking, coiling, tortuosity) and their prognosis have not yet been clearly defined. A study was performed in outpatients in order to evaluate the cardiovascular risk factors of dolichoarteriopathies. METHODS: A total of 1220 subjects (620 males and 600 females, aged between 25 and 89 years old) were examined using color Doppler ultrasonography of the extracranial carotid arteries with an Acuson 128 XP-5 scan and 7 MHz linear probe. The reason for the test was the presence of clinical symptoms or cardiovascular risk factors. The risk factors studied included: arterial hypertension [systolic (> 140 mmHg) and/or diastolic arterial pressure (> 90 mmHg)], hypercholesterolemia (total cholesterol > 200 mg/dl), diabetes mellitus, cigarette smoking. Patients were divided as follows: patients with arterial hypertension alone, patients with arterial hypertension associated with other cardiovascular risk factors (hypercholesterolemia, diabetes mellitus, smoking), patients with other cardiovascular risk factors (hypercholesterolemia, diabetes mellitus, smoking), patients without risk factors. RESULTS: In 316 (25.9%) patients with dolichoarteriopathies, arterial hypertension alone was present in 98 (31%), arterial hypertension associated with other cardiovascular risk factors in 85 (26.3%) and other cardiovascular risk factors in 54 (17%), whereas 75 (25%) did not present cardiovascular risk factors. In the 904 subjects without dolichoarteriopathies, arterial hypertension alone was present in 254 (28%), arterial hypertension associated with other cardiovascular risk factors in 213 (23.6%) and other cardiovascular risk factors in 191 (21.1%), whereas 241 (27.2%) did not present cardiovascular risk factors. In 316 subjects with dolichoarteriopathies, cardiovascular risk factors were equally present in the two sexes without statistically significant differences. In cases with kinking and tortuosity, cardiovascular risk factors were equally present in the two sexes, whereas colling was more frequently associated with arterial hypertension alone in males and with arterial hypertension associated with other risk factors in females, showing a statistically significant difference. CONCLUSIONS: The findings of this study reveal that the presence of risk factors in patients with dolichoarteriopathies is comparable to that in subjects without dolichoarteriopathies. Also in the three types of dolichoarteriopathies (kinking, coiling and tortuosity), cardiovascular risk factors were equally present. Therefore, these results appear to lay the role of arterial hypertension or other cardiovascular risk factors in the genesis of diolichoarteriopathies open to question.

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