Linking emotional valence and anxiety in a mouse insula-amygdala circuit.

Responses of the insular cortex (IC) and amygdala to stimuli of positive and negative valence are altered in patients with anxiety disorders. However, neural coding of both anxiety and valence by IC neurons remains unknown. Using fiber photometry recordings in mice, we uncover a selective increase of activity in IC projection neurons of the anterior (aIC), but not posterior (pIC) section, when animals are exploring anxiogenic spaces, and this activity is proportional to the level of anxiety of mice. Neurons in aIC also respond to stimuli of positive and negative valence, and the strength of response to strong negative stimuli is proportional to mice levels of anxiety. Using ex vivo electrophysiology, we characterized the IC connection to the basolateral amygdala (BLA), and employed projection-specific optogenetics to reveal anxiogenic properties of aIC-BLA neurons. Finally, we identified that aIC-BLA neurons are activated in anxiogenic spaces, as well as in response to aversive stimuli, and that both activities are positively correlated. Altogether, we identified a common neurobiological substrate linking negative valence with anxiety-related information and behaviors, which provides a starting point to understand how alterations of these neural populations contribute to psychiatric disorders.

Orbital Complexity in Intrinsic Magnetic Topological Insulators MnBi_{4}Te_{7} and MnBi_{6}Te_{10}.

Using angle-resolved photoelectron spectroscopy (ARPES), we investigate the surface electronic structure of the magnetic van der Waals compounds MnBi_{4}Te_{7} and MnBi_{6}Te_{10}, the n=1 and 2 members of a modular (Bi_{2}Te_{3})_{n}(MnBi_{2}Te_{4}) series, which have attracted recent interest as intrinsic magnetic topological insulators. Combining circular dichroic, spin-resolved and photon-energy-dependent ARPES measurements with calculations based on density functional theory, we unveil complex momentum-dependent orbital and spin textures in the surface electronic structure and disentangle topological from trivial surface bands. We find that the Dirac-cone dispersion of the topologial surface state is strongly perturbed by hybridization with valence-band states for Bi_{2}Te_{3}-terminated surfaces but remains preserved for MnBi_{2}Te_{4}-terminated surfaces. Our results firmly establish the topologically nontrivial nature of these magnetic van der Waals materials and indicate that the possibility of realizing a quantized anomalous Hall conductivity depends on surface termination.

[Hepatitis B vaccination coverage and booster dose: results from a survey on healthcare students]. / Copertura vaccinale anti-epatite B e dose di rinforzo: risultati di uno studio su una popolazione universitaria.

This study assessed the immunisation status against hepatitis B in healthcare students and residents, before their hospital internship, as suggested by the "National Immunization Prevention Plan 2012-2014". The concentration of antibodies against hepatitis B was measured in 2,491 subjects (70.90% women), born between 1980 and 1993 and visited between January 1st 2000 and July 15th 2012. Personal and serologic data were collected for each subjects. Individuals with antibody less than 10 mIU/mL (327, 13.3%) were given a booster dose and re-tested 2 months later. The multivariate logistic regression evidenced that immunization is influenced by the gender, the age at first vaccination, the time elapsed between first vaccination and antibody measurement. This study confirms the importance of measuring the concentration of antibodies against hepatitis B among healthcare students, even if they have previously been vaccinated, according to the "National Immunization Prevention Plan 2012-2014".

[Results of Regional Project 'Work related Stress' 2004-2006]. / Risultati del Progetto Regionale "Stress ed Attività Lavorativa" 2004-2006.

The present epidemiological study aimed to investigate prevalence and trends of stress-job-related uneasiness and symptoms on a representative sample of Lombardia's working population. Data on occupational events (absenteeism and accidents at work), psychosomatic symptoms and smoke habit have been collected. Prevalence and trends of stress-job-related uneasiness are similar to those reported by the European Foundation in the Report for Sectorial Profiles (2002). The study confirms higher levels of absenteeism in corporations with high prevalence of women and in low socioeconomic level works.

Time trends of myocardial infarction 28-day case-fatality in the 1990s: is there a contribution from different changes among socioeconomic classes?

BACKGROUND/OBJECTIVE: Almost two-thirds of the coronary death rate decrease in the northern Italian Brianza MONICA male population, between 1993-4 and 1997-8, are attributable to a reduction in 28-day myocardial infarction (MI) case-fatality. The present paper investigates the factors associated with MI case-fatality decrease and in particular the role of socio-occupational classes (SOCs). METHODS: Standardised information on acute coronary care and intervention before and during the hospitalisation was collected for all coronary events (n = 1817) registered in 1993-4 and in 1997-8 among 35-64-year-old male residents in Brianza. Deaths within 28 days after MI were carefully investigated. Five SOCs were defined adopting the Erikson-Goldthorpe-Portocarero method. Differences in 28-day MI case-fatality and in acute phase intervention and treatment over time and among SOCs in each period were assessed. RESULTS: 28-day MI case-fatality reduction (27.2%) can be mainly attributed to a decreased proportion of MI events that were fatal before reaching the hospital. In the lower SOCs significant changes in MI case-fatality were detected between 1993-4 and 1997-8. Differences in acute phase intervention and treatment between the periods were observed. SOC differences both in prevalence of out-of-hospital cardiac arrest and in the pre-hospital qualified intervention score were detected in the first period only. CONCLUSIONS: In the study population MI case-fatality reduction can be mainly attributed to a more effective and prompt management before hospitalisation and to an improvement in acute treatment during hospitalisation. This enhancement is made available to the whole population overtaking social differences.

Menopause hormone replacement therapy and cancer risk: an Italian record linkage investigation.

BACKGROUND: The effects of persistence with hormone replacement therapy (HRT) on the risk of hospitalization for cancer and of the route of HRT administration on the risk of breast and colorectal cancer were explored in a large cohort study. PATIENTS AND METHODS: The 73 505 women residing in Lombardia (Italy), aged 45-75 years, who received at least one HRT prescription during 1998-2000 were followed until 2005. Among these, 3687 experienced cancer hospitalization. Proportional hazards model was fitted to estimate the association between cumulative HRT persistence and cancer risk. RESULTS: Compared with women who took HRT for <6 months, those exposed for >2 years showed hazard ratios (HR) of 0.78 (95% confidence interval 0.68-0.92) for colorectal cancer and 1.34 (1.13-1.58) for breast cancer. HR for breast cancer associated with long-term use of transdermal and oral HRT were, respectively, 1.27 (1.07-1.51) and 2.14 (1.43-3.21). CONCLUSIONS: Evidence that long-term use of HRT is associated with increased risk of breast cancer and decreased risk of colorectal cancer is supplied from this study from a southern European population. Our findings indicate that transdermal therapy might have lower effect than oral therapy in increasing breast cancer risk.

Biological consequences of stress: conflicting findings on the association between job strain and blood pressure.

The primary objective is to verify the relation between job strain and clinic blood pressure in a working population from the Milan municipality (1,909 men, 3,786 women) enrolled from 1992 to 1996. Job strain was investigated through the Karasek model. Clinic blood pressure was evaluated using standard procedures from the MONICA project. The association between the two was calculated controlling for age, education, smoking, body mass index, total and high-density lipoprotein (HDL) cholesterol. Significantly, associations were found for systolic blood pressure in men and for both systolic and diastolic blood pressure in women. However, these results do not reflect biological plausibility. The relationship between job strain and blood pressure is an unfinished business: sample characteristics and measurement methods should be carefully considered.

[Nutritional status disorders prevalence rates in a sample of pediatric oncology Day Hospital patients]. / Prevalenza delle alterazioni dello stato nutrizionale in un campione di pazienti afferenti a un day hospital oncologico pediatrico.

BACKGROUND: Nutritional status is more important in children than in adults because it is necessary to support normal growth and development. In industrialized countries the prevalence of nutritional status disorders in the pediatric population are as follows: 35-40% of children are overweight/obese, while the underweight status disappeared in some reports or, when it is present, it is associated with other diseases. The aim of this study was to investigate the prevalence rates of nutritional status disorders among an unselected sample of Pediatric Oncology Day Hospital patients. METHODS: Anthropometric parameters of weight and height have been measured in patients affected with solid tumor either on-therapy or off-therapy (0-24 mo). Then Real Body Weight (% RBW) was estimated referring to National Center for Health Statistic percentiles. The sample was then divided into 4 weight classes (under-weight, normal-weight, over-weight and obese) according to % RBW. RESULTS: Overweight patients (overweight + obese) were 44.4%, and 13.9% underweight. Dividing the patients according to whether they are on-therapy or off-therapy, the prevalence of overweight was 36.9% in the former group and 52.9% in the latter, and the underweight prevalence was 26.3 vs 0%. CONCLUSIONS: Our preliminary data show that in this sample of patients on treatment obesity and overweight are present in a similar percentage of the healthy population, but underweight status prevalence is 26.3%. In the sample of patients off-therapy the underweight status disappeared while the overweight status increased. These data suggest that nutritional assessment in oncologic patients is required in order to provide nutritional strategies.

Myc down-regulation induces apoptosis in M14 melanoma cells by increasing p27(kip1) levels.

In recent years, increasing evidence indicated the importance of a deregulated c-myc gene in the melanoma pathogenesis. We have previously demonstrated that treatment of melanoma cells with c-myc antisense oligodeoxynucleotides can inhibit cell proliferation and activate apoptosis. To gain insight into the mechanisms activated by Myc down-regulation, we have now developed an experimental model that allows modulating Myc protein expression in melanoma cells. This was achieved by originating stable melanoma cell clones expressing ecdysone-inducible c-myc antisense RNA. We show that the induction of c-myc antisense RNA in M14 melanoma cells leads to an inhibition of cell proliferation characterized by accumulation of cells in the G(1) phase of the cell cycle (up to 80%) and activation of apoptosis (50%). These data are associated with an increase of p27(kip1) levels and a significant reduction of the cdk2-associated kinase activity. In addition, we show that an ectopic overexpression of p27(kip1) in this experimental model can enhance the apoptotic rate. Our results indicate that down-regulation of Myc protein induces a G(1) arrest and activates apoptosis by increasing p27(kip1) content in melanoma cells, that are known to be defective for the p16-cyclinD/cdk4-pRb G(1) checkpoint. This is particularly relevant for identifying new therapeutic strategies based on the re-establishment of the apoptotic pathways in cancer cells.

[An exceptional case of hypersensitivity to actinomycin D. Case report and review of the literature]. / Un caso di ipersensibilità alla actinomicina D, un'evenienza eccezionale. Case report e revisione della letteratura.

We report the first case, to our knowledge, of an allergic attack following the administration of Act-D in a 9 year old boy, affected by orbit embrional rabdomyosarcoma. The boy was given most operative therapy according to RMS 96 protocol, IRS group IIb, with Actinomicin D (Act-D), Vincristine and Ifosfamide and RT. Immediately after the beginning of chemotherapy the boy presented with an asthma-like attack (dyspnoea and asthenia), supposed to be a side effect of Ifosfamide administration regressed by intravenous bolus of hydrocortisone and chlorphenamine. In the second chemotherapy cycle concurrent with RT, the Act-D preceded the administration of ifosfamide. Subsequently to the administration of Act-D and RT, without premedication, the boy presented with a face erythema and asthma like attach. Post operative chemotherapy was achieved with no further allergic side effect using premedication with hydrocortisone and chlorphenamine. The boy is now 13 years old, alive and disease free at a three years follow-up.

Increase of cisplatin sensitivity by c-myc antisense oligodeoxynucleotides in a human metastatic melanoma inherently resistant to cisplatin.

In this study, we evaluated the role of the c-myc oncogene in response to cisplatin (DDP) treatment using two melanoma lines derived from the primary tumor (LP) and metastatic lymph node (LM) of the same patient. These cell lines, which retain the phenotypic profile of the original tumors, were studied for growth behavior, expression of c-Myc oncoprotein, and HLA-I antigen. The LM line shows a higher tumorigenic ability, an increased expression of c-Myc protein, and a lack of HLA-I antigen, compared with the LP line. In addition, LP tumor was relatively sensitive to DDP administration, whereas LM tumor was resistant to DDP treatment. To verify whether the increased c-Myc expression observed in the LM line might be responsible for DDP resistance, a c-myc antisense phosphorothioate oligodeoxynucleotide ([S]ODN) was used to down-regulate c-Myc expression. The administration of DDP plus c-myc antisense [S]ODNs produced a decrease in c-Myc protein levels of approximately 50%, accompanied by a tumor weight inhibition of 65%, similar to that obtained when the sensitive line was treated with DDP alone (tumor weight inhibition = 70%). Analysis of apoptosis demonstrated that the sensitivity to DDP of the LP line was related to the ability of tumor cells to undergo apoptosis. Conversely, DDP treatment was not able to induce apoptosis in the LM line, whereas apoptosis was evident both after treatment with c-myc antisense [S]ODNs alone and, more extensively, in combination with DDP. Taken together, these results clearly indicate an important role of c-myc oncogene in the resistance of melanoma to DDP and demonstrate that treatment with c-myc antisense [S]ODN sensitizes a human melanoma line to DDP treatment.

[The false image of a left atrial mass due to a hiatal hernia: a case report]. / Falsa immagine di massa atriale sinistra da ernia iatale: descrizione di un caso.

We report the case of a 69-year-old woman with a history of hypertension and transient ischemic attack who was admitted because of a diagnosis of left atrial mass on transthoracic echocardiography. Monoplane transesophageal echocardiography showed an extracardiac mass compressing the left atrium posteriorly and an apparent intraatrial mass. As the procedure did not clarify the nature of the masses, a thoracic magnetic resonance imaging was performed. This technique revealed a large hiatal hernia impinging on the left atrium without evidence of an upper gastrointestinal tract. Our experience confirm that hiatal hernia may mimic an echocardiographic left atrial mass and should be considered in the differential diagnosis of this finding.

A Comparison of the Effect of Salt on Polypeptides and Translatable mRNAs in Roots of a Salt-Tolerant and a Salt-Sensitive Cultivar of Barley.

The effect of salt stress on polypeptide and mRNA levels in roots of two barley (Hordeum vulgare L.) cultivars differing in salt tolerance (cv CM 72, tolerant; cv Prato, sensitive) was analyzed using two-dimensional polyacrylamide gel electrophoresis. Preliminary experiments indicated that germination of Prato was inhibited significantly in the presence of NaCl, but growth of the surviving Prato seedlings was not substantially different from that of CM 72. Fluorographs of two-dimensional gels containing in vivo labeled polypeptides or in vitro translation products were computer analyzed to identify and quantitate changes that resulted when plants were grown in the presence of 200 millimolar NaCl for 6 days. The patterns of in vivo labeled polypeptides and in vitro products of CM 72 and Prato were qualitatively the same. Salt caused quantitative changes in numerous polypeptides and translatable mRNAs, but, overall, the changes were relatively small. Salt did not induce the synthesis of unique polypeptides or translatable mRNAs and did not cause any to disappear. Because of the similarities of the two cultivars with respect to growth and polypeptide patterns and the slight changes in polypeptide and translation product levels caused by salt, specific polypeptides or translatable mRNAs that are related to salt tolerance in barley could not be identified.

Plasmid distribution and analyses in Rhodopseudomonas sphaeroides.

Ten strains of Rhodopseudomonas sphaeroides were analyzed by agarose gel electrophoresis for plasmid DNA content and, by filter-hybridizations, for their molecular relationships. All strains examined contained at least one plasmid. Several strains carried as many as six different plasmid species with sizes ranging from 42 to 140 kilobases (kb). Those larger than 89 kb showed extensive homology with each other; the 42-kb plasmid of R. sphaeroides strain 2.4.1 was homologous to the smaller plasmid DNA of three other strains. A partial map of the 42-kb plasmid derived from R. sphaeroides 2.4.1 was prepared by analysis of restriction endonuclease digests. Cross-hybridization among the large plasmids indicated that those present in any one strain of R. sphaeroides showed homology to one or more of the large plasmids detected in strains L and 2.4.1.

Identification of nitrogenase and carboxylase genes in the photosynthetic bacteria and cloning of a carboxylase gene from Rhodopseudomonas sphaeroides.

The presumptive genes for the ribulose 1,5-bisphosphate carboxylase large subunit and for nitrogenase-specific components from Rhodopseudomonas sphaeroides and several other photosynthetic bacteria were identified and located by interspecific probing. Restriction digests of R. sphaeroides genomic DNA were hybridized under stringent conditions to cloned DNA from Rhodospirillum rubrum (plasmid pRR2119 carrying the carboxylase gene) and Klebsiella pneumoniae (pSA30 carrying the nitrogenase genes). The nitrogenase probe hybridized with different signal intensities to several distinct HindIII, BglII, EcoRI, BamHI and PvuII fragments of R. sphaeroides 2.4.1.DNA. The carboxylase probe hybridized to only single R. sphaeroides 2.4.1.DNA fragments produced with all five restriction enzymes. A 3000-bp EcoRI-BamHI R. sphaeroides 2.4.1.DNA fragment carrying the presumptive gene for the large subunit of ribulose 1,5-bisphosphate carboxylase was cloned into pBR322 and positively identified by probing with a 32P-labeled internal PstI fragment of the Rhodospirillum carboxylase gene.