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Covid-19 infection has more relevant consequences in frail and comorbid patients, but little is known about its course in patients with hematologic malignancies. In this report, we would like to present the case of a patient with multiple myeloma treated with recent autologous bone marrow stem cell transplantation and affected by Covid-19 pneumonia, presenting with a possible reinfection or an extremely long viral shedding., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2023 Tehran University of Medical Sciences.)

Purpose: To assess the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) and computed tomography (CT) within Bosniak IIF/III categories., Methods: After cystic renal mass diagnosis by contrast-enhanced CT, all patients with Bosniak score ≥ II also underwent CEUS between March 2017 and March 2019. Their exams were retrospectively analyzed. One experienced uro-radiologist performed every CEUS and reviewed the exams according to the EFSUMB 2020 Position Statement, while blinded to clinical data. CT Bosniak scores were retrospectively given blindly by two uro-radiologists (CT 1 and CT 2). We compared CEUS, CT 1 and CT 2 scores to clinical findings and histological tests. Clinical performance characteristics and area under the receiver operating characteristic (ROC) curves (AUCs) were determined separately for CEUS and CT, and then compared., Results: 101 cystic masses were analyzed. In Bosniak categories IIF and III, the AUCs were 0.854 for CT 1, 0.779 for CT 2, and 0.746 for CEUS., Conclusion: Despite some statistical limitations, this study confirms that among cystic renal masses, those classified as Bosniak IIF and III are the most difficult to assess. The diagnostic performances of CEUS and CT are similar within this group. However, in experienced hands, CEUS could be valuable in further evaluation of ambiguous cystic masses, and in more ductile, safer, and cost-effective surveillance of those classified as Bosniak IIF and III. When challenging cystic renal masses occur, CEUS is a useful tool for clinical management and for the follow-up of non-surgical lesions., (© 2022. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

The whole-genome sequencing (WGS) of eighteen S. marcescens clinical strains isolated from 18 newborns hospitalized in the Neonatal Intensive Care Unit (NICU) at Pescara Public Hospital, Italy, was compared with that of S. marcescens isolated from cradles surfaces in the same ward. The identical antibiotic resistance genes (ARGs) and virulence factors were found in both clinical and environmental S. marcescens strains. The aac(6')-Ic , tetA(41) , bla SRT-3 , adeFGH , rsmA , and PBP3 (D350N) genes were identified in all strains. The SRT-3 enzyme, which exhibited 10 amino acid substitutions with respect to SST-1, the constitutive AmpC β-lactamase in S. marcescens , was partially purified and tested against some β-lactams. It showed a good activity against cefazolin. Both clinical and environmental S. marcescens strains exhibited susceptibility to all antibiotics tested, with the exception of amoxicillin/clavulanate.

Bronchiolitis is a clinical syndrome involving the lower respiratory tract of infants and young children. The majority of patients recover using adequate hydration and oxygen (O 2 ) therapy, while a small number of patients require ventilatory assistance. Beyond these therapeutical approaches, there are no available strategies for patients that do not improve. Hypothermia is a measure used to prevent neonatal hypoxic-ischemic encephalopathy by preventing carbon dioxide (CO 2 ) production and subsequent tissue damage. Other medical applications of hypothermia have been proposed, such as in acute respiratory failure and necrotizing colitis. Case report: We report the case of a 50-day-old girl hospitalized with severe bronchiolitis caused by respiratory syncytial virus. On admission, the girl presented severe hypercapnic respiratory failure, requiring intubation and ventilatory support with conventional and non-conventional systems. However, the patient's general conditions worsened with elevated O 2 demand, thus whole-body hypothermia was attempted and performed for 48 h, with a gradual improvement in the respiratory function. No adverse effects were detected. Conclusions: Whole-body hypothermia could have a critical role as a rescue treatment in infants affected by severe hypercapnic respiratory failure, at the expense of few and rare side effects (bradycardia, coagulopathy, hyperglycemia). Notably, beyond reducing CO 2 production, whole-body hypothermia might have an impact in restoring lung function in newborns using bronchiolitis refractory to maximal medical therapy and invasive ventilation.

Descending control from the brain to the spinal cord shapes our pain experience, ranging from powerful analgesia to extreme sensitivity. Increasing evidence from both preclinical and clinical studies points to an imbalance toward descending facilitation as a substrate of pathological pain, but the underlying mechanisms remain unknown. We used an optogenetic approach to manipulate serotonin (5-HT) neurons of the nucleus raphe magnus that project to the dorsal horn of the spinal cord. We found that 5-HT neurons exert an analgesic action in naïve mice that becomes proalgesic in an experimental model of neuropathic pain. We show that spinal KCC2 hypofunction turns this descending inhibitory control into paradoxical facilitation; KCC2 enhancers restored 5-HT-mediated descending inhibition and analgesia. Last, combining selective serotonin reuptake inhibitors (SSRIs) with a KCC2 enhancer yields effective analgesia against nerve injury-induced pain hypersensitivity. This uncovers a previously unidentified therapeutic path for SSRIs against neuropathic pain.

Infant-directed speech (IDS), the particular form of spontaneous language observed in interactions between parents and their infants, is a crucial aspect of the mother-infant interaction and an index of the attunement of maternal linguistic input to her infant communicative abilities and needs during dyadic interactions. The present study aimed to explore linguistic and pragmatic features of IDS during mother-infant interactions at 3-month of infant age. The effects of infant (birth status: preterm vs. full-term birth), maternal (perceived parenting stress) and dyadic (dyadic co-regulation) factors on IDS were explored. Results evidenced few differences between the groups on IDS linguistic characteristics. Moreover, observing the interaction of birth status and dyadic co-regulation, full-term mothers varied their IDS pragmatic features according to the quality of co-regulation while preterm mothers did not. Parenting stress was associated to specific linguistic IDS features independently from the birth status. Findings are discussed underling implications for the study of preterm dyads interactions and the importance to consider the interplay of several factors in affecting the quality of IDS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Spinelli, Lionetti, Garito, Shah, Logrieco, Ponzetti, Cicioni, Di Valerio and Fasolo.)

Abstract: In allogeneic hematopoietic stem cell transplantation (AHSCT), falls can lead to immediate and late consequences and in some cases to death. We analyzed risks and causes of falls with root cause analysis (RCA) based on which improvement interventions were implemented.A retrospective observational study was conducted to analyze with RCA data of incidence reports and medical records of patients admitted; an expert panel identified actions to prevent falls, which were collected in a checklist.Between December 2017 and November 2019, 214 patients were admitted to ordinary hospital stays for AHSCT or AHSCTrelated complications. In this period, 15 falls, involving 11 patients, occurred resulting in a 2.32 d/patient incidence. In 66.67% of cases minor head trauma occurred. Diuretic drugs (93.33%), induced hyper-diuresis in nonbladder catheter patients (93.33%) and antihypertensive drugs (93.33%) were reported as most common cause in our incident reports. The most frequent fall time slot was between 10 PM and 7 AM (60%). We determined with RCA diuretics and consequent induced hyper-diuresis (80%), self-insufficiency (40%), antihypertensive (33.3%) and noncompliance (33.3%) as the most common cause of falls. Finally, 16 actions, collected in a "safe comfort" checklist, were identified to prevent falls.Diuretic drugs inducing hyper-diuresis, self-insufficiency, poor patient compliance, orthostatic hypotension, fever, night-time and obstacles within inpatient units are the most common contributing factors. Therefore, administration of diuretic and antihypertensive drugs should be rescheduled and a multidimensional risk assessment scale integrated with a preventive action plan, such as the safe comfort checklist, should be implemented to reduce falls., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Phospholipases A 2 (PLA 2 s) and PLA 2 -like proteins are significant components of snake venoms. Some of these proteins act as potent toxins causing muscle necrosis, which may lead to amputation in severe envenomings. Fundamental aspects of the mechanism of action of these toxins are still not completely known. Myotoxin-I is a catalytically active Asp49 PLA 2 from the venom of Bothrops asper, a medically relevant pit viper from Central America. Myotoxin-II is a catalytically inactive Lys49 PLA 2 -homolog also present in the venom of this snake. For the first time, the in vivo cellular localization of these myotoxins was studied in mouse skeletal muscle using immunofluorescence. Results showed that after 5 min of injection in the gastrocnemius muscle, both toxins initially interacted with the sarcolemma, and some colocalization with nuclei was already evident, especially for Mt-II. After 3 h of injection, a significant colocalization with the nuclei was observed for both toxins. These in vivo results confirm the importance of the initial interaction of these toxins with the sarcolemma and furthermore highlight the internalization and interaction of the toxins with nuclei during their pathophysiological activities, as observed in recent studies using cell culture., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Coping with threatening situations requires both identifying stimuli that predict danger and selecting adaptive behavioural responses to survive 1 . The dorsomedial prefrontal cortex (dmPFC) is a critical structure that is involved in the regulation of threat-related behaviour 2-4 . However, it is unclear how threat-predicting stimuli and defensive behaviours are associated within prefrontal networks to successfully drive adaptive responses. Here we used a combination of extracellular recordings, neuronal decoding approaches, pharmacological and optogenetic manipulations to show that, in mice, threat representations and the initiation of avoidance behaviour are dynamically encoded in the overall population activity of dmPFC neurons. Our data indicate that although dmPFC population activity at stimulus onset encodes sustained threat representations driven by the amygdala, it does not predict action outcome. By contrast, transient dmPFC population activity before the initiation of action reliably predicts avoided from non-avoided trials. Accordingly, optogenetic inhibition of prefrontal activity constrained the selection of adaptive defensive responses in a time-dependent manner. These results reveal that the adaptive selection of defensive responses relies on a dynamic process of information linking threats with defensive actions, unfolding within prefrontal networks., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Biopesticide-based crop protection is constantly challenged by insect resistance. Thus, expansion of available biopesticides is crucial for sustainable agriculture. Although Bacillus thuringiensis is the major agent for pesticide bioprotection, the number of bacteria species synthesizing proteins with biopesticidal potential is much higher. The Bacterial Pesticidal Protein Resource Center (BPPRC) offers a database of sequences for the control of insect pests, grouped in structural classes. Here we present IDOPS, a tool that detects novel biopesticidal sequences and analyzes them within their genetic environment. The backbone of the IDOPS detection unit is a curated collection of high-quality hidden Markov models that is in accordance with the BPPRC nomenclature. IDOPS was positively benchmarked with BtToxin_Digger and Cry_Processor. In addition, a scan of the UniProtKB database using the IDOPS models returned an abundance of new pesticidal protein candidates distributed across all of the structural groups. Gene expression depends on the genomic environment, therefore, IDOPS provides a comparative genomics module to investigate the genetic regions surrounding pesticidal genes. This feature enables the investigation of accessory elements and evolutionary traits relevant for optimal toxin expression and functional diversification. IDOPS contributes and expands our current arsenal of pesticidal proteins used for crop protection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Díaz-Valerio, Lev Hacohen, Schöppe and Liesegang.)

This report highlights the importance for neonatologists/pediatricians of considering Marcus Gunn jaw-winking syndrome among differential diagnoses of ptosis. A detailed clinical assessment is crucial to promptly recognize and appropriately manage it., Competing Interests: None declared., (© 2020 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

The clinical approach plays a pivotal role in neonates with evidence of a skull mass, together with the need of monitoring unclear cases. Indeed, apparently transient alterations of the skull may be neural tube defects, which need prompt treatment., Competing Interests: None declared., (© 2020 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Background: The aim of this study was to investigate the influence of the aortic arch type on technical and clinical success of carotid artery stenting (CAS) procedure., Methods: Clinical and anatomical data of consecutive patients who underwent CAS from 2010 to 2018 were prospectively collected and retrospectively analyzed. Primary outcome was technical success, define as successful stent delivery and deployment and <30% residual carotid stenosis. Secondary outcomes were death, stroke, myocardial infarction (MI) and transient ischemic attack (TIA) rates at 30 days after CAS. Subgroups analysis with asymptomatic and symptomatic patients were also performed., Results: During the study period, 523 patients were enrolled and analyzed. Among these, 176 (33.6%) had Type I, 227 (43.4%) had Type II and 120 (23.0%) had Type III or bovine aortic arch (BAA) type. Technical success rate was achieved in 96.0% of cases. At 30 days, if compared with Type I or II, patient with Type III or BAA experienced a higher death rate (0 vs. 0 vs. 1.8%, respectively; P=0.056) and combined postoperative stroke/TIA rate (3% vs. 2.8% vs. 9.9%, respectively; P=0.012). No differences for same outcomes between asymptomatic and symptomatic patients were described, although the latter group experienced more postoperative MI. A multivariate analysis revealed Type III or BAA as an independent risk factor for postoperative stroke/TIA (HR 3.23, IC95% 1.40-7.45; P=0.006)., Conclusions: In this cohort of patients, death and postoperative neurological complications rates were associated with Type III or BAA, irrespective of symptomatic patients' status. Extremely attention is required during perioperative period in patients who were candidate to CAS and with challenging aortic arch anatomy.

Congenital diaphragmatic hernia is a rare condition associated with pulmonary complications as the abdominal viscera herniated into the chest may affect lungs development. We present the case of a male newborn baby with a prenatal diagnosis of a posterolateral defect (Bochdalek hernia) involving the right side. The infant underwent surgical repair at 3 days of life, and the post-surgery chest X-ray did not reveal morpho-structural alterations of the lungs and diaphragmatic profile. Our clinical case shows that patients may have a better lung outcome despite an initial unfavorable picture. Prenatal diagnosis is essential in identifying infants with congenital diaphragmatic hernia, especially those cases at higher risk for the worse outcomes, to optimize their clinical and surgical management., (© 2020 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

The aim of this study was to assess the impact of osteopathic manipulative treatment (OMT) on newborn babies admitted at a neonatal intensive care unit (NICU). This was an observational, longitudinal, retrospective study. All consecutive admitted babies were analyzed by treatment (OMT vs. usual care). Treatment group was randomly assigned. Between-group differences in weekly weight change and length of stay (LOS) were evaluated in the overall and preterm populations. Among 1249 babies (48.9% preterm) recorded, 652 received usual care and 597 received OMT. Weight increase was more marked in the OMT group than in the control group (weekly change: +83 g vs. +35 g; p < 0.001). Similar trends were found in the subgroup of preterm babies. A shorter LOS was found in the OMT group vs. the usual care group both in overall population (average mean difference: -7.9 days, p = 0.15) and in preterm babies (-12.3 days; p = 0.04). In severe preterm babies, mean LOS was more than halved as compared to the control group. OMT was associated with a more marked weekly weight increase and, especially in preterm babies, to a relevant LOS reduction: OMT may represent an efficient support to usual care in newborn babies admitted at a NICU.

The nuclear ribosomal DNA internal transcribed spacer (ITS) is accepted as the genetic marker or barcode of choice for the identification of fungal samples. Here, we present a protocol to analyze fungal ITS data, from quality preprocessing of raw sequences to identification of operational taxonomic units (OTUs), taxonomic classification, and assignment of functional traits. The pipeline relies on well-established and manually curated data collections, namely the UNITE database and the FUNGuild script. As an example, real ITS data from culturable endophytic fungi were analyzed, providing detailed descriptions for every step, parameter, and downstream analysis, and finishing with a phylogenetic analysis of the sequences and assigned ecological roles. This article constitutes a comprehensive guide for researchers that have little familiarity with bioinformatic analysis of essential steps required in further ecological studies of fungal communities. © 2020 by John Wiley & Sons, Inc. Basic Protocol 1: Raw sequencing data processing Support Protocol: Building a BLAST database Basic Protocol 2: Obtaining information from databases Basic Protocol 3: Phylogenetic analysis., (© 2020 John Wiley & Sons, Inc.)

Nearly all species rely on visual and nonvisual cues to guide navigation, and which ones they use depend on the environment and task demands. The postsubiculum (PoS) is a crucial brain region for the use of visual cues, but its role in the use of self-movement cues is less clear. We therefore evaluated rats' navigational performance on a food-carrying task in light and in darkness in rats that had bilateral neurotoxic lesions of the PoS. Animals were trained postoperatively to exit a refuge and search for a food pellet, and carry it back to the refuge for consumption. In both light and darkness, control and PoS-lesioned rats made circuitous outward journeys as they searched for food. However, only control rats were able to accurately use visual or self-movement cues to make relatively direct returns to the home refuge. These results suggest the PoS's role in navigation is not limited to the use of visual cues, but also includes the use of self-movement cues. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Head direction (HD) cells fire as a function of the animal's directional heading and provide the animal with a sense of direction. In rodents, these neurons are located primarily within the limbic system, but small populations of HD cells are found in two extralimbic areas: the medial precentral cortex (PrCM) and dorsal striatum (DS). HD cell activity in these structures could be driven by output from the limbic HD circuit or generated intrinsically. We examined these possibilities by recording the activity of PrCM and DS neurons in control rats and in rats with anterodorsal thalamic nucleus (ADN) lesions, a manipulation that disrupts the limbic HD signal. HD cells in the PrCM and DS of control animals displayed characteristics similar to those of limbic HD cells, and these extralimbic HD signals were eliminated in animals with complete ADN lesions, suggesting that the PrCM and DS HD signals are conveyed from the limbic HD circuit. Angular head velocity cells recorded in the PrCM and DS were unaffected by ADN lesions. Next, we determined if the PrCM and DS convey necessary self-motion signals to the limbic HD circuit. Limbic HD cell activity recorded in the ADN remained intact following combined lesions of the PrCM and DS. Collectively, these experiments reveal a unidirectional functional relationship between the limbic HD circuit and the PrCM and DS; the limbic system generates the HD signal and transmits it to the PrCM and DS, but these extralimbic areas do not provide critical input or feedback to limbic HD cells. NEW & NOTEWORTHY Head direction (HD) cells have been extensively studied within the limbic system. The lesion and recording experiments reported here examined two relatively understudied populations of HD cells located outside of the canonical limbic HD circuit in the medial precentral cortex and dorsal striatum. We found that HD cell activity in these two extralimbic areas is driven by output from the limbic HD circuit, revealing that HD cell circuitry functionally extends beyond the limbic system.

[Purpose] The aim of this study was to estimate the prevalence of abnormal shoulder ultrasonographic findings in a sample of asymptomatic women. [Subjects and Methods] A secondary analysis of a cross-sectional study was performed. We recruited 305 women (aged 18-56 years). All the subjects had a structured interview screening for self-reported symptoms and underwent a shoulder ultrasonographic examination, in which both shoulders were examined. The radiologist was blinded to the clinical history of the participants. All detectable shoulder abnormalities were collected. [Results] Of the subjects, 228 (74.75%) were asymptomatic at both shoulders, and 456 asymptomatic shoulders were analyzed. Lack of uniformity (supraspinatus, infraspinatus, subscapularis, and biceps brachii long head) was found in 28 shoulders (6.14%), 19 (4.17%) on the dominant side and 9 (1.97%) on the non-dominant side. Tendinosis (supraspinatus, infraspinatus, subscapularis, and biceps brachii long head) was found in 19 shoulders (5.32%), 12 (2.63%) on the dominant side and 7 (1.53%) on the non-dominant side. Calcification and other abnormal findings were reported. [Conclusion] The most common abnormalities were calcifications within the rotator-cuff tendons and humeral head geodes; other degenerative findings were less common.

Introduction: The work provides the analysis of the nursing reports written by the nursing staff on duty at the asylum "Paolo Pini" from 1944 to 1947., Objective: description of the nursing report evolution, analyses of the quantitative and qualitative matters. Study of the evolution of the records: enhancement of the description of the patient, integration between medical and nursing assistance, assumption of responsi- bility (for instance through the signature)., Methods: A sampling of 355 medical records has been analysed. The nursing records have been identified according to the theoretical model of Marisa Cantarelli. They have been compared with the current standard reported in literature. If recognizable signatures were present, they have been checked in the archives of the Province of Milan., Results: 219 records concerning nursing assistance have been selected. The record changed during the years assuming a definite structure, and became a pre printed form; its use spread in all the wards of the hospital. The record deals with nursing assistance needs, and improves during the years becoming more and more detailed and regular., Conclusions: During the analysed time frame, the nursing reports at "Paolo Pini" improve and become more exhaustive and regular; they prove to be part of the medical record, showing a good integration between doctors and nurses activities. The evolution of this tool confirms the need of highlighting and improving the assistance practice.

Head direction (HD) cells fire when an animal faces a particular direction in its environment, and they are thought to represent the neural correlate of the animal's perceived spatial orientation. Previous studies have shown that vestibular information is critical for generating the HD signal but have not delineated whether information from all three semicircular canals or just the horizontal canals, which are primarily sensitive to angular head rotation in the horizontal (yaw) plane, are critical for the signal. Here, we monitored cell activity in the anterodorsal thalamus (ADN), an area known to contain HD cells, in epstatic circler (Ecl) mice, which have a bilateral malformation of the horizontal (lateral) semicircular canals. Ecl mice and their littermates that did not express the mutation (controls) were implanted with recording electrodes in the ADN. Results confirm the important role the horizontal canals play in forming the HD signal. Although normal HD cell activity (Raleigh's r > 0.4) was recorded in control mice, no such activity was found in Ecl mice, although some cells had activity that was mildly modulated by HD (0.4 > r > 0.2). Importantly, we also observed activity in Ecl mice that was best characterized as bursty--a pattern of activity similar to an HD signal but without any preferred firing direction. These results suggest that the neural structure for the HD network remains intact in Ecl mice, but the absence of normal horizontal canals results in an inability to control the network properly and brings about an unstable HD signal. Significance statement: Cells in the anterior dorsal thalamic nucleus normally fire in relation to the animal's directional heading with respect to the environment--so-called head direction cells. To understand how these head direction cells generate their activity, we recorded single-unit activity from the anterior dorsal thalamus in transgenic mice that lack functional horizontal semicircular canals. We show that the neural network for the head direction signal remains intact in these mice, but that the absence of normal horizontal canals results in an inability to control the network properly and brings about an unstable head direction signal., (Copyright © 2016 the authors 0270-6474/16/360741-14$15.00/0.)

Pemetrexed and Carboplatin are two well-known chemioterapic agents used for the treatment of many tumors, especially for lung cancer and mesothelioma. Peripheral ischemic events related to Pemetrexed and Carboplatin are rarely reported. We herein report a case of lower limb acute ischemia related to combined treatment of Pemetrexed and Carboplatin. A 68-year-old woman was given the chemiotherapic treatment with combination of Pemetrexed and Carboplatin after pleural resection for a malignant pleural mesothelioma. Immediately after the second cycle of treatment, the patient experienced sudden acute left lower limb ischemia. Symptoms resolved after an intra-operative thrombolytic and spasmolytic therapy.

Identifying the neural mechanisms underlying spatial orientation and navigation has long posed a challenge for researchers. Multiple approaches incorporating a variety of techniques and animal models have been used to address this issue. More recently, virtual navigation has become a popular tool for understanding navigational processes. Although combining this technique with functional imaging can provide important information on many aspects of spatial navigation, it is important to recognize some of the limitations these techniques have for gaining a complete understanding of the neural mechanisms of navigation. Foremost among these is that, when participants perform a virtual navigation task in a scanner, they are lying motionless in a supine position while viewing a video monitor. Here, we provide evidence that spatial orientation and navigation rely to a large extent on locomotion and its accompanying activation of motor, vestibular, and proprioceptive systems. Researchers should therefore consider the impact on the absence of these motion-based systems when interpreting virtual navigation/functional imaging experiments to achieve a more accurate understanding of the mechanisms underlying navigation.

Head-direction cells have frequently been regarded as an internal 'compass' that can be used for navigation, although there is little evidence showing a link between their activity and spatial behavior. In a navigational task requiring the use of internal cues to return to a home location without vision (path integration), we found a robust correlation between head-direction cell activity and the rat's heading error in the rat's homing behavior. We observed two different correction processes that rats used to improve performance after an error. The more frequent one consists of 'resetting' the cell whenever the rat returns to the home location. However, we found that when large errors occur, the head-direction system has the ability to 'remap' and set a new reference frame, which is then used in subsequent trials. We also offer some insight into how these two correction processes operate when rats make an error.

Successful navigation requires a constantly updated neural representation of directional heading, which is conveyed by head direction (HD) cells. The HD signal is predominantly controlled by visual landmarks, but when familiar landmarks are unavailable, self-motion cues are able to control the HD signal via path integration. Previous studies of the relationship between HD cell activity and path integration have been limited to two or more arenas located in the same room, a drawback for interpretation because the same visual cues may have been perceptible across arenas. To address this issue, we tested the relationship between HD cell activity and path integration by recording HD cells while rats navigated within a 14-unit T-maze and in a multiroom maze that consisted of unique arenas that were located in different rooms but connected by a passageway. In the 14-unit T-maze, the HD signal remained relatively stable between the start and goal boxes, with the preferred firing directions usually shifting <45° during maze traversal. In the multiroom maze in light, the preferred firing directions also remained relatively constant between rooms, but with greater variability than in the 14-unit maze. In darkness, HD cell preferred firing directions showed marginally more variability between rooms than in the lighted condition. Overall, the results indicate that self-motion cues are capable of maintaining the HD cell signal in the absence of familiar visual cues, although there are limits to its accuracy. In addition, visual information, even when unfamiliar, can increase the precision of directional perception.

The use of cheap and easy to handle reagents, such as I(2) and Et(3) SiH, at low temperature allows the regioselective removal of benzyl protecting groups from highly O-benzylated carbohydrates. The observed regioselectivity is dependent on the nature of the precursor, the least accessible carbinol often being liberated. A mechanistic investigation reveals that in situ generated HI is the promoter of the process, whereas the regioselectivity appears to be mainly controlled by steric effects. However, the presence of an electron withdrawing acyl protecting group can switch the regioselectivity to favour deprotection of the carbinol position farthest from the ester group. The protocol is experimentally simple and provides straightforward access in useful yields to a wide range of partially protected mono- and disaccharide building blocks that are valuable for the synthesis of either biologically useful oligosaccharides or highly functionalised chiral compounds. Partially protected sugars thus obtained can also be coupled in situ with a glycosyl donor, as illustrated by the one-pot synthesis of a Lewis X mimic from fully protected precursors., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Mannosyl trihaloacetimidate donors equipped with a 2-O-Fmoc group can be effectively activated by catalytic Bi(OTf)(3) in glycosidations. Despite the expected participating effect of the Fmoc group, the reaction solvent was found to be decisive for obtaining highly selective alpha-mannosylations. The Fmoc 2-O-protecting group can be then simply removed from the obtained di-oligosaccharide in the same vessel where the glycosidation is conducted. The resulting oligosaccharide can thus be directly employed as a glycosyl acceptor for further elongation. The preparation of biologically important linear and branched oligomannoses incorporated into HIV gp120 demonstrates that iteration of this one-pot sequence leads to very straightforward oligosaccharide assembly. As an additional result, a rapid approach has been disclosed for accessing a 3,6-OH mannose building-block to be incorporated in branched structures. This relies on a double reductive opening of a di-O-benzylidene mannose intermediate whose regioselectivity appears to be independent of the configuration of the five-membered benzylidene., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Previous studies have identified neurons throughout the rat limbic system that fire as a function of the animal's head direction (HD). This HD signal is particularly robust when rats locomote in the horizontal and vertical planes, but is severely attenuated when locomoting upside-down (Calton & Taube, 2005). Given the hypothesis that the HD signal represents an animal's sense of directional heading, we evaluated whether rats could accurately navigate in an inverted (upside-down) orientation. The task required the animals to find an escape hole while locomoting inverted on a circular platform suspended from the ceiling. In Experiment 1, Long-Evans rats were trained to navigate to the escape hole by locomoting from either one or four start points. Interestingly, no animals from the 4-start point group reached criterion, even after 29 days of training. Animals in the 1-start point group reached criterion after about six training sessions. In Experiment 2, probe tests revealed that animals navigating from either 1- or 2-start points utilized distal visual landmarks for accurate orientation. However, subsequent probe tests revealed that their performance was markedly attenuated when navigating to the escape hole from a novel start point. This absence of flexibility while navigating upside-down was confirmed in Experiment 3 where we show that the rats do not learn to reach a place, but instead learn separate trajectories to the target hole(s). Based on these results we argue that inverted navigation primarily involves a simple directional strategy based on visual landmarks., (Copyright 2010 Elsevier Inc. All rights reserved.)

The pentasaccharide sequence of the most active components of the antitumor drug PI-88, currently in phase II clinical trial, has been rapidly assembled in high overall yield and in only three steps starting from three monosaccharide building blocks. The procedure takes advantage of the first reported strategy of sequential one-pot glycosidations conducted exclusively under catalytic activation. In addition, the procedure relies only on shelf-stable and mild promoters such as Yb(OTf)(3) and Bi(OTf)(3).

The aim of this study was to further characterize the memory-enhancing profile of S 18986 a positive allosteric modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors. S 18986 was studied in two mouse models of age-related memory deficits, using radial maze paradigms involving long-term/declarative memory and short-term/working memory. Aged mice exhibited severe deficits when compared with their younger counterparts in the two behavioural tests. S 18986 at the dose of 0.1 mg/kg selectively improved aged mouse performance in the test of long-term/declarative memory flexibility and exerted a beneficial effect on short-term retention of successive arm-visits in the short-term/working memory test. This study confirms the memory-enhancing properties of S 18986 and, in line with emerging data on multiple AMPA modulators, highlights the relevance of targeting AMPA receptors in the development of new memory enhancers.

Alkyl thio-, phenyl seleno-, and phenyl thioglycosides can be prepared through short synthetic sequences based on the generation of glycosyl iodides as versatile intermediates. In addition, a novel cheap combined system (stoichiometric NBS and catalytic Bi(OTf)3) has been developed for rapid and efficient activation of a wide variety of thio- and selenoglycoside donors.

Background: The cost associated with education of residents is of interest from an educational as well as a political perspective. Most studies report a single institution's actual incurred costs, based on traditional cost accounting methods. We quantified the minimum instructional and program-specific administrative costs for residency training in internal medicine., Methods: Using the Accreditation Council for Graduate Medical Education program requirements for internal medicine as minimum standards for teaching and administrative effort, we quantified the minimum instructional and administrative costs for sponsorship of an accredited residency program in internal medicine. We also analyzed the impact of resident complement and program curricular emphasis (outpatient, inpatient, or traditional) on the per-resident cost. The main outcome measure was the minimum annual per-resident cost of instruction and program-specific administration., Results: Using the assumptions in this model, we estimated the annual cost per resident of implementing the program requirements to be $50,648, $35,477, $28,517, and $26,197 for inpatient intensive residency programs with resident complements of 21, 42, 84, and 126, respectively. For outpatient intensive residency programs of identical resident complements, we estimated the annual per-resident cost to be $58,025, $42,853, $35,894, and $33,574 for similar resident complements. Fixed costs mandated by the program requirements, which did not vary across program size or configuration, were estimated to be $640,737., Conclusions: There are fixed and variable costs associated with sponsorship of accredited internal medicine residency programs. The minimum cost per resident of education and departmental administration varies inversely with program size within the sizes examined.

The restoration of coronally fractured anterior teeth without surgical invasion is contingent upon several factors. Specifically, the biologic width of the tooth should not be violated by the apical extent of the fracture, and the residual root structure must possess an adequate ferrule. In patients with these conditions, it is possible to prosthetically restore the tooth following orthodontic extrusion. This article describes a technique in which orthodontic extrusion is utilized to provide adequate tooth structure for the prosthetic restoration of patients who presented with fractured anterior teeth.

Objectives: The aim of the present study is to analyze the results achieved with the ileal bladder according to the VIP (vescica ileale Padovana) procedure., Methods/results: We compared the results obtained in 31 patients with invasive bladder cancer who underwent radical surgery (22 underwent the ileal conduit procedure and 9 were treated by orthotopic bladder substitution) and analyzed the early complications, long-term results and physiological data of the group submitted to the VIP procedure. In the patient group submitted to the VIP procedure, there was only one case who required removal of the new bladder due to an enteroneovesical fistula. Another case developed medium serrate anular stricture of the bulbar urethra about 8 months postoperatively and was treated by endoscopic urethrotomy. The uroradiologic and urodynamic evaluations confirmed urinary tract stability integrity of renal function and good adaptation of the new reservoir. The andrological studies showed complete sexual potency in 2 of 9 patients., Conclusions: The VIP procedure appears to be a good technique, with complications no greater than those of traditional urinary diversion, and improves the quality of life of patients undergoing radical surgery for invasive bladder cancer.

The authors report a case of ureterocolic fistula secondary to diverticulitis of left colon. The pathological findings of this uncommon case is described.

The paper reports the study of 35 patients affected by pancreatic and periampullary carcinoma. The authors analyse the results of six patients treated using pancreaticoduodenectomy with pyloric preservation and compare the results to those achieved using Whipple's operation.