Offline ventral subiculum-ventral striatum serial communication is required for spatial memory consolidation.

The hippocampal formation is considered essential for spatial navigation. In particular, subicular projections have been suggested to carry spatial information from the hippocampus to the ventral striatum. However, possible cross-structural communication between these two brain regions in memory formation has thus far been unknown. By selectively silencing the subiculum-ventral striatum pathway we found that its activity after learning is crucial for spatial memory consolidation and learning-induced plasticity. These results provide new insight into the neural circuits underlying memory consolidation and establish a critical role for off-line cross-regional communication between hippocampus and ventral striatum to promote the storage of complex information.

Evolution of transmitted HIV-1 drug resistance and viral subtypes circulation in Italy from 2006 to 2016.

OBJECTIVES: The aim was to evaluate the evolution of transmitted HIV-1 drug resistance (TDR) prevalence in antiretroviral therapy (ART)-naïve patients from 2006 to 2016. METHODS: HIV-1 sequences were retrieved from the Antiviral Response Cohort Analysis (ARCA) database and TDR was defined as detection of at least one mutation from the World Health Organization (WHO) surveillance list. RESULTS: We included protease/reverse transcriptase sequences from 3573 patients; 455 had also integrase sequences. Overall, 68.1% of the patients were Italian, the median CD4 count was 348 cells/µL [interquartile range (IQR) 169-521 cells/µL], and the median viral load was 4.7 log10 HIV-1 RNA copies/mL (IQR 4.1-5.3 log10 copies/mL). TDR was detected in 10.3% of patients: 6% carried mutations to nucleos(t)ide reverse transcriptase inhibitors (NRTIs), 4.4% to nonnucleos(t)ide reverse transcriptase inhibitors (NNRTIs), 2.3% to protease inhibitors (PIs), 0.2% to integrase strand transfer inhibitors (INSTIs) and 2.1% to at least two drug classes. TDR declined from 14.5% in 2006 to 7.3% in 2016 (P = 0.003): TDR to NRTIs from 9.9 to 2.9% (P = 0.003) and TDR to NNRTIs from 5.1 to 3.7% (P = 0.028); PI TDR remained stable. The proportion carrying subtype B virus declined from 76.5 to 50% (P < 0.001). The prevalence of TDR was higher in subtype B vs. non-B (12.6 vs. 4.9%, respectively; P < 0.001) and declined significantly in subtype B (from 17.1 to 8.8%; P = 0.04) but not in non-B subtypes (from 6.1 to 5.8%; P = 0.44). Adjusting for country of origin, predictors of TDR were subtype B [adjusted odds ratio (AOR) for subtype B vs. non-B 2.91; 95% confidence interval (CI) 1.93-4.39; P < 0.001], lower viral load (per log10 higher: AOR 0.86; 95% CI 0.75-0.99; P = 0.03), site in northern Italy (AOR for southern Italy/island vs. northern Italy, 0.61; 95% CI 0.40-0.91; P = 0.01), and earlier calendar year (per 1 year more recent: AOR 0.95; 95% CI 0.91-0.99; P = 0.02). CONCLUSIONS: The prevalence of HIV-1 TDR has declined during the last 10 years in Italy.

Altered Functionality, Morphology, and Vesicular Glutamate Transporter Expression of Cortical Motor Neurons from a Presymptomatic Mouse Model of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a lethal disorder characterized by the gradual degeneration of motor neurons in the cerebrospinal axis. Whether upper motor neuron hyperexcitability, which is a feature of ALS, provokes dysfunction of glutamate metabolism and degeneration of lower motor neurons via an anterograde process is undetermined. To examine whether early changes in upper motor neuron activity occur in association with glutamatergic alterations, we performed whole-cell patch-clamp recordings to analyze excitatory properties of Layer V cortical motor neurons and excitatory postsynaptic currents (EPSCs) in presymptomatic G93A mice modeling familial ALS (fALS). We found that G93A Layer V pyramidal neurons exhibited altered EPSC frequency and rheobase values indicative of their hyperexcitability status. Biocytin loading of these hyperexcitable neurons revealed an expansion of their basal dendrite arborization. Moreover, we detected increased expression levels of the vesicular glutamate transporter 2 in cortical Layer V of G93A mice. Altogether our data show that functional and structural neuronal alterations associate with abnormal glutamatergic activity in motor cortex of presymptomatic G93A mice. These abnormalities, expected to enhance glutamate release and to favor its accumulation in the motor cortex, provide strong support for the view that upper motor neurons are involved early on in the pathogenesis of ALS.

Human immunodeficiency virus-1 B and non-B subtypes with the same drug resistance pattern respond similarly to antiretroviral therapy.

We analysed the 12-week virological response to protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) therapy in 1108 patients carrying B or non-B human immunodeficiency virus (HIV)-1 subtypes with matched resistance mutation patterns. Response rates were not significantly different for non-B and B subtypes stratified for treatment status (51.5% vs. 41.5% in naïve patients; 46.7% vs. 38.7% in experienced patients) or regimens (46.9% vs. 39.7% with PI; 56.7% vs. 40% with NNRTI). No difference in response was detected in patients harbouring B and non-B subtypes with any resistance profile. Further studies are advisable to fully test this approach on larger datasets.

Copper distribution and hydrolase activities in a contaminated soil amended with dolomitic limestone and compost.

Chemical fractionation of copper in bulk soil and its distribution in the particle-size fractions were analyzed in a Cu-contaminated soil (674 ± 122 µg Cu g(-1), up to 1900 µg Cu g(-1) in the clay fraction) sampled from a wood preservation site left untreated and subsequently treated with dolomitic limestone (DL, 0.2% w/w) and compost (CM, 5% w/w), singly and in combination (DL+CM). Soil enzymatic activities of leucine aminopeptidase, cellulase, N-acetyl-ß-glucosaminidase, arylsulfatase, ß-glucosidase, acetate esterase, butyric esterase, and acid phosphatase were determined. Chemical speciation showed that Cu was mostly present in the acid-soluble and reducible fractions in both untreated and treated soils, whereas treatments with DL and CM reduced the soluble and exchangeable Cu fractions, due to Cu precipitation and complexation, and increased Cu bound to soil organic matter. Analysis of the particle-size fractions showed that more than 80% of Cu was in the silt and clay fractions and that treatment with CM increased the concentration of Cu in the sand size fractions. Soil treatment with DL and CM, singly or in combination, increased hydrolase activities, mainly in the clay fraction, with the largest positive effects on N-acetyl-ß-glucosaminidase, leucine aminopeptidase, and ß-glucosidase activities. Overall, results confirm that (1) Cu in contaminated soils is mainly bound to the silt-clay fraction, (2) CM additions change its allocation in the particle-size fractions, and (3) treatments with DL and CM singly and in combination reduce Cu solubility and its inhibitory effects on soil enzyme activities.

Conversion of spinal anesthesia into general anesthesia: an evaluation of more than 35,000 spinal anesthetics.

BACKGROUND: The aim of this study was to evaluate the number of conversions from spinal anesthesia (SA) into general anesthesia (GA) in a large number of patients who underwent surgery over a period of twenty-one years. METHODS: From the hospital's database, all surgical procedures performed under SA between January 1, 1988 and December 31, 2008 were retrieved. From this file, all SA cases converted into GA cases requiring endotracheal intubation were selected. Patients were divided in four groups, according to the reason for GA: IMPOSS (SA impossible to perform), FAIL (SA non profound enough for allowing surgery, even with light sedation), INSUFF (SA inadequate for unexpected prolonged duration of surgery), and COMPL (occurrence of complications associated with SA and requiring rapid control of ventilation). Anesthesiologists who performed SA were divided according their experience. The outcomes of patients converted to GA were compared with a matched sample of patients who received planned GA. RESULTS: A total of 35,960 SA cases were performed from 1988 to 2008; 29,220 and 6,740 SA cases were for elective and emergency surgery, respectively. Two hundred seventeen (0.6%) SA cases were converted into GA cases; 80.2% and 19.8% of the conversions were recorded in elective and emergency operations, respectively, with obstetric operations being the most prevalent (82/217). The primary reasons for the conversions, in a rank order, were INSUFF 107 (49.3%), FAIL 84 (38.7%), IMPOSS 13 (5.9%), and COMPL 13 (5.9%). Complications more frequently occurred in the aged population (P<0.05). Anesthesiologists with less experience had higher percentages of FAIL, IMPOSS, INSUFF, and COMPL SA cases in comparison with experienced anesthesiologists (odd ratios being 4.7, 3.0, 2.4, and 4.4, respectively). There was no difference in the frequency of complications compared to a matched sample of 1,000 patients who underwent GA (P=0.65). CONCLUSION: SA has been found to be a safe and highly effective technique. Failure of SA was infrequent in a large number of patients surveyed and most often occurred with less experienced anesthesiologists. Conversion to GA did not produced different outcomes in comparison with planned GA. Prospective studies with a definite protocol for recording data performed on a large number of patients may help in determining the factors associated with conversion from SA into GA and how to avoid these unexpected situations.

Epidural analgesia in children: planning, organization and development of a new program.

BACKGROUND: The goal of the present work is to describe the development and results of the pediatric epidural analgesia program at the ''Hospital Nacional de Pediatria Prof. Dr. J. P. Garrahan'' in Argentina. METHODS: Patients with thoracotomy, abdominal surgery, osteotomy, amputations or severe trauma were included in the program. The program provided training to the entire staff, control and record of pain treatment and its consequences, 24 h a day availability of anesthesia staff and standard polices and procedures. RESULTS: One hundred fifty children under 16 years of age (median age 11 years, median weight 35 kg) were included in the program during the first 18 months. The median of maximum pain reported during activity was 1 (interquartile range 1 to 4 points) using the Visual Analogue Scale (VAS) or Objective Pain Scale (OPS). Eighty seven children (CI 95% 50% to 67%) presented with postoperative nausea and vomiting, urinary retention, itching, motor blockade or sedation. No patient presented with respiratory depression, hypotension, local anaesthetic toxicity, epidural catheter related infection or death during the program evaluation. The postoperative care program enabled a 98-day reduction in treatment in the intensive care unit. CONCLUSION: The safe use of pediatric epidural analgesia in general wards may require the careful selection of patients, systematic assessment by trained personnel, training of medical and nursing personnel, clear distribution of responsibilities, use of printed indications, systematic record of pain, sedation and complications, information and education of patients and parents, supply of systems for airway resuscitation and management and continuous quality control and revision of the methods.

Refeeding syndrome in early pregnancy. Case report.

Refeeding syndrome is a very serious disorder that is not often observed today, as it is more common during times of mass starvation or war. Nowadays, it is sometimes found in patients suffering from anorexia nervosa or neoplastic diseases. A case recently treated in our Intensive Care Unit is described. The patient was pregnant and suffering from Crohn's disease. It is emphasized that although refeeding syndrome is often fatal if not treated early, it is easily prevented or treated with adequate nutritional support.

Sympathetic nervous system and chronic renal failure.

The aim of this work was to review evidence on the role of the sympathetic nervous system (SNS) in chronic renal failure (CRF). Three main points are discussed: 1) SNS and pathogenesis of arterial hypertension; 2) SNS and cardiovascular risk; 3) implication of SNS in arterial hypotension during hemodialysis. Several lines of evidence indicate the presence of a sympathetic hyperactivity in CRF, and its relationship with arterial hypertension. It is suggested that diseased kidneys send afferent nervous signals to central integrative sympathetic nuclei, thus contributing to the development and maintenance of arterial hypertension. The elimination of these impulses with nephrectomy could explain the concomitant reduction of blood pressure. Several experiments confirmed this hypothesis. Regarding SNS and cardiovascular risk, some data suggest that reduced heart rate variability identifies an increased risk for both all causes and sudden death, independently from other recognized risk factors. Symptomatic hypotension is a common problem during hemodialysis treatment, occurring in approximately 20-30% of all hemodialysis sessions and is accompanied by acute withdrawal of sympathetic activity, vasodilation and relative bradicardia. This reflex is thought to be evoked by vigorous contraction of a progressively empty left ventricle, activating cardiac mechanoceptors. This inhibits cardiovascular centers through vagal afferents, and overrides the stimulation by baroreceptor deactivation. Alternative explanations include cerebral ischemia and increased production of nitric oxide, which inhibit central sympathetic activity. It is hoped that therapies aimed at modulating sympathetic nerve activity in patients with CRF will ameliorate their prognosis and quality of life.

Outcome of dialysis patients submitted to coronary revascularization.

Cardiovascular disease accounts for almost half of the total mortality in patients with end stage renal disease (ESRD). It has recently been debated whether coronary revascularization has the same rate of risks and successes in this cohort of patients compared to patients without renal disease. Since 1991, 17 dialysis patients were submitted to coronary revascularization in our center. Seven patients were following peritoneal, 10 hemodialytic treatment. Four patients were submitted to percutaneous transluminal coronary angioplasty (PTCA) and 13 to surgical revascularization (CABG). In 2 patients the coronary lesion was unique, in the others stenosis of multiple vessels were found. Six patients were diabetic. The mean age at the onset of the coronary artery disease (CAD) was 57.17 +/- 11.6 years. The mean time elapsed from the onset of the CAD and the performance of the PTCA or CABG was 30.1 +/- 35.4 months. The mean time from beginning of dialysis treatment to revascularization was 48.2 +/- 39.6 months. Mean hemoglobin values were 9.7 +/- 1 g/dL, mean phosphorus values were 5.2 +/- 8.7 mg/dL, mean cholesterol values were 211 +/- 49.5 mg/dL. The procedure was technically successful in all patients. Mean survival was 25.09 +/- 28.12 months. Twelve patients died, 5 of whom within one month. Survival at one month was 70.5%, at 6 months 58.8%, at one year 52.9%, at 2 years 47%. There was neither significant difference patients submitted to PTCA and those submitted to CABG, nor between diabetic and non-diabetic patients. In conclusion, coronary revascularization in our experience is a high risk procedure in dialysis patients. The reasons for this could be the severe general conditions of these patients affected with diffuse vasculopathy and the long time elapsed since the onset of the ischemic cardiopathy. Thus, our results could suggest the opportunity of performing earlier screening of coronary situation and revascularization treatment in CAD dialysis patients.

Is vecuronium toxicity abolished by hemodialysis? A case report.

Vecuronium is a curaric agent, largely used in anesthesia. Indications as to its employ in uremic patients appear to be debated because of partial renal elimination of the drug. A 52-year-old hemodialyzed woman required transplantectomy for rejection. At awakeness after general anesthesia (induced with fentanyl, propofol, and 6 mg of vecuronium, repeated with a single 2 mg dose 30 min later), she presented diafragmatic and muscular limb weakeness that lasted 180 min in spite of prostigmine administration. A 2 h 30 min predilutional hemofiltration was then performed, which induced rapid disappearance of neuromuscular blockade. Even if vecuronium can be used in dialysis patients, one should remember its possible side effects, especially with repeated doses, in determining prolonged neuromuscular blockade. Cautious use of this drug in renal failure is mandatory. Low dosage must be employed and repeated administration avoided. Neuromuscular blockade seems to be rapidly reversible with dialytic treatment.

[Acute kidney failure caused by cholesterol atheroembolism]. / L'insufficienza renale acuta da ateroembolismo colesterinico.

BACKGROUND: To describe the clinical aspects of renal failure due to cholesterol atheroembolism. METHODS: An hospital based observational study on renal failure due to cholesterol atheroembolism was carried out. Twenty-two cases (19 males, mean age 68 yrs, range 53-83 yrs) were identified from January 1992 to September 1998. RESULTS: Clinical symptoms were acute or rapidly progressive renal failure with blue toe and/or skin livedo reticularis in 13/22 cases (59%) and indolent progressive renal failure in 7/22 cases (32%). In 6/22 cases (27%) an abdominal organ involvement was evident; two (9%) had retinal cholesterol emboli, two (9%) peripheral and two (9%) central nervous system impairment. In 7 patients (32%) the cholesterol atheroembolism occurred spontaneously, while in 15 (68%) it followed invasive or interventional radiology (8 cases, 36%); cardiac or vascular surgery (4 cases, 18%); thrombolytic or anticoagulant therapy (3 cases, 14%). The time interval between the procedure at risk and the onset of symptoms or signs of cholesterol atheroembolism ranged between few hours to 60 days. Eleven patients (50%) required dialysis, which was then withheld in 4 cases (36%), owing to partial functional recovery after a median time of 30 days, ranging from 10 to 690 days. Median follow-up was 2.5 months (ranging from 2 days to 68 months), and eleven patients (50%) deceased. CONCLUSIONS: Cholesterol atheroembolism is a cause of renal failure associated with high mortality rates; its prevention needs the skill of all physicians involved in the care of patients with severe atherosclerosis.

[Metabolic effects of changes in dietary sodium intake in patients with essential hypertension]. / Effetti metabolici delle variazioni dell'apporto alimentare di sodio in pazienti con ipertensione essenziale.

BACKGROUND: To evaluate the metabolic effects of modification of sodium intake in patients with essential hypertension. METHODS: Thirteen patients with essential hypertension (10 M, median age 51 yrs, range 21-64) followed in random order a low-sodium and a high-sodium diet (50 mmol Na/day vs 250 mmol/day for two weeks each). At the end of each diet an evaluation was made of 24 hour blood pressure (ABPM, Spacelabs 90207) and serum concentration of: glucose, total and HDL cholesterol, uric acid, lipoproteins A, B, Lp(a), total proteins, albumin. RESULTS: Twenty-four hours systolic and diastolic BP were significantly higher at the end of high sodium diet than of low sodium diet [respectively 132 mmHg (120-161) vs 128 mmHg (109-150); p = 0.008 and 84 mmHg (71-99) vs 81 mmHg (70-95); p = 0.008)]. No significant variations were found as regards serum glucose and lipidic parameters between low and high sodium diets. Serum uric acid was significantly higher following low sodium diet [5.9 mg/dl (4.5-8) vs 4.6 mg/dl (3.4-6.5); p = 0.003)], as well as serum total proteins [7.2 g/dl (6.9-8.2) vs 7 g/dl (6.5-7.8); p = 0.027)]. A significant direct correlation was found between changes of uric acid and total proteins from low to high sodium diet (Spearman's rho = 0.57; p = 0.04). CONCLUSIONS: In patients with essential hypertension a moderate dietary sodium restriction, able to reduce significantly 24 hours arterial pressure, does not worsen serum glucose nor lipids concentration.

Effect of clonidine on postpartum shivering after epidural analgesia: a randomized, controlled, double-blind study.

In obstetric patients treated with epidural analgesia during labor and delivery, shivering is quite frequent due to stress, vasodilatation, infusion of fluids, low ambient temperature, and the direct effect of solution injected into the epidural space. Sixty obstetric patients who developed shivering after receiving epidural analgesia for delivery were randomly assigned to treatment with clonidine 0.150 mg i.v. (N = 20), meperidine 50 mg i.v. (N = 20), or saline solution (N = 20). Drug administration was double blind. The effect on shivering (graded as all or none), drowsiness, heart rate, and systolic arterial pressure was evaluated 5 min after the study drug was administered. Clonidine was as effective as meperidine in controlling shivering and caused a greater reduction in heart rate. Drowsiness occurred after clonidine as well as meperidine. Thus, clonidine proved to be effective in controlling shivering and adrenergic response after delivery using epidural analgesia and produced an acceptable level of drowsiness.

[In vitro and in vivo effects of propofol on the hemoglobin dissociation curve]. / Effets du propofol sur la courbe de dissociation de l'oxyhémoglobine in vivo et in vitro.

This study assessed in vivo and in vitro the effects of propofol on the affinity of hemoglobin for oxygen in seven ASA 1 adults. For the in vivo study, venous blood samples were withdrawn before and after premedication, after the injection of 2.5 mg.kg-1 of propofol and after 15 minutes of maintenance at an infusion rate of 0.2 mg.kg-1.min-1. For the in vitro study, propofol was added to the blood withdrawn before premedication in order to obtain two samples at a concentration of 1 microgram.mL-1 and 2 micrograms.mL-1 respectively. Propofol changed neither in vivo, nor in vitro, the P50 and the number of Hill indicating the angle of the slope of the dissociation curve, nor in vivo the concentration of 2,3-DPG.

[Oncocytic carcinoma in a horseshoe kidney]. / Carcinoma oncocitario in rene a ferro di cavallo.

The Authors report a rare case of oncocytoma in a horseshoe kidney. The diagnostic path needed to assess the precise anatomy of the malformation and tumoral staging is out lined. Oncological problems dealing with oncocytoma are further discussed, together with the technical and surgical issues pertinent to the clinical case.

[Importance of an outpatient record in obstetric anesthesia]. / Importanza dell'ambulatorio di anestesia ostetrica.

A computerised record was used to collect data following an anesthesiological check-up of pregnant women at approximately 30 weeks of pregnancy. The record was input onto a portable PC in the anesthesia outpatient clinic, memorized on disk (3.5") and then transferred onto a PC network (one PC for each operating theatre) for "real time" consultation of each patient's data. All pregnant women attending the antenatal clinico were also given a folder illustrating epidural anesthetic techniques. Seven hundred and nine outpatient visits have been performed over the past two years with a 62% utilisation ratio. The collection of data using a computerised system allows a rapid and efficacious system of communication to be set up among the membranes of the anesthesiological team, thus encouraging the use of epidural techniques during labour. The distribution of the folder also facilitated the task of the anesthetist who found that pregnant women visiting the anesthesia clinic were already familiar with the epidural technique.