Observation of Collider Muon Neutrinos with the SND@LHC Experiment.

We report the direct observation of muon neutrino interactions with the SND@LHC detector at the Large Hadron Collider. A dataset of proton-proton collisions at sqrt[s]=13.6 TeV collected by SND@LHC in 2022 is used, corresponding to an integrated luminosity of 36.8 fb^{-1}. The search is based on information from the active electronic components of the SND@LHC detector, which covers the pseudorapidity region of 7.2<η<8.4, inaccessible to the other experiments at the collider. Muon neutrino candidates are identified through their charged-current interaction topology, with a track propagating through the entire length of the muon detector. After selection cuts, 8 ν_{µ} interaction candidate events remain with an estimated background of 0.086 events, yielding a significance of about 7 standard deviations for the observed ν_{µ} signal.

Notch pathway promotes ovarian cancer growth and migration via CXCR4/SDF1α chemokine system.

Ovarian cancer is the most deadly gynecological malignancy. Understanding the molecular pathogenesis of ovarian cancer is critical to provide new targeted therapeutic strategies. Recent evidence supports a role for Notch in ovarian cancer progression and associates its dysregulation to poor overall survival. Similarly, CXCR4/SDF1α signalling correlates with ovarian cancer progression and metastasis. Recent findings indicate that Notch promotes CXCR4/SDF1α signalling and its effect on cell growth and migration; nonetheless, up to now, the association between Notch and CXCR4/SDFα in ovarian cancer has not been reported. Thereby, the aim of this study was to investigate if Notch and CXCR4/SDF1α cooperate in determining ovarian cancer growth, survival and migration. To address this issue, Notch signalling was inhibited by using γ-secretase inhibitors, or upregulated by forcing of Notch1 expression in ovarian cancer cell lines. Our results indicated that Notch activity influenced tumour cell growth and survival and positively regulated CXCR4 and SDF1α expression. CXCR4/SDF1α signalling mediated the effect of Notch pathway on ovarian cancer cell growth and SDF1α-driven migration. Additionally, for the first time, we demonstrated that Notch signalling activation can be detected in ovarian cancer specimens by immunohistochemistry analysis of the Notch transcriptional target, HES6 and is positively correlated with high expression levels of CXCR4 and SDF1α. Our results demonstrate that Notch affects ovarian cancer cell biology through the modulation of CXCR4/SDF1α signalling and suggest that Notch inhibition may be a rationale therapeutic approach to hamper ovarian cancer progression mediated by the CXCR4/SDF1α axis.

Pharmacokinetic behavior of gadoteridol injection.

RATIONALE AND OBJECTIVES: To assess the safety and pharmacokinetics of gadoteridol injection (0.5 M) in 18 healthy male volunteers in a phase I clinical trial. METHODS: Volunteers were assigned to one of six dosing groups: 0.05, 0.1, 0.15, 0.2, 0.25, and 0.3 mmol/kg gadoteridol (0.5 M), in an ascending dose study. Physical examination, vital signs, electrocardiogram, clinical laboratory tests, and serum and urine samples were obtained at selected time points before and after administration of gadoteridol. RESULTS AND CONCLUSIONS: No significant changes in vital signs, physical examination, clinical laboratory values, or electrocardiogram, that were believed by the principal investigator to be related to the administration of the contrast agent, were observed. A single adverse event (transient hive) believed to be related to contrast agent administration was observed in one volunteer. Pharmacokinetic data show that the elimination half-life and the distribution half-life were independent of the dose used. The mean distribution half-life was 0.20 +/- 0.04 hours, the mean elimination half-life was 1.57 +/- 0.08 hours, and greater than 94% of the drug was excreted in the urine in 24 hours.

Phase II clinical trial of gadoteridol injection, a low-osmolal magnetic resonance imaging contrast agent.

RATIONALE AND OBJECTIVES: The safety and efficacy of a new, low-osmolal magnetic resonance imaging contrast medium, gadoteridol injection, were evaluated in a phase II, open-label study at doses ranging from 0.05 to 0.30 mmol/kg. METHODS: Eighty-six patients with a diagnosis of intracranial tumor received gadoteridol injection followed by magnetic resonance imaging. RESULTS: Two adverse events (headache, taste disturbance) in 2 of 86 (2.3%) patients were reported. Both were of mild intensity and resolved without treatment and without residual effects. In 4 of 86 (4.7%) patients, 5 laboratory changes were reported by the investigators as possibly related to gadoteridol injection. Efficacy evaluation was conducted in 80 of the 86 patients who received gadoteridol injection. In these patients, a total of 119 lesions was identified, and each was evaluated at four time points after contrast administration, yielding a total of 476 lesion studies. Marked enhancement was demonstrated in 402 of 476 (84%) lesions, whereas slight enhancement was demonstrated in 62 of 476 (13%) lesions. The difference in both the incidence and degree of enhancement of pathology between the predose and postdose images was highly significant (P less than .001). CONCLUSIONS: Overall, enhanced images provided more diagnostic information and facilitated detection of more lesions than precontrast images. Gadoteridol injection at doses up to 0.3 mmol/kg is a safe and effective magnetic resonance imaging contrast agent for use in patients with intracranial tumors.

Diapering choices: a critical review of the issues.

Careful consideration is needed to determine which diapering system may be best suited to an institution's or individual's needs. A critical review of five issues--skin care, infection control, other health-related concerns, environmental and safety aspects, and time/cost issues--reveals that: (a) superabsorbent paper diapers reduce the incidence and severity of diaper dermatitis and control the spread of infection in caregiving surroundings; (b) cloth and paper diapers have different effects on the environment and neither type of diaper is clearly superior to the other; and (c) the cost of disposable diapers and reusable commercial-laundered diapers may be comparable, although home-laundered diapers are least expensive if the caregiver's labor is not considered.

Familial congenital brachial palsy.

Eight relatives in a Sicilian family, including a sibship of 5, were affected with severe unilateral congenital brachial palsy (CBP) in a pattern suggesting autosomal dominant inheritance with reduced penetrance (6 cases affected on the right, 2 on the left). X-linked inheritance with expression in heterozygous females cannot be excluded.

Effect of a digital imaging network on physician behavior in an intensive care unit.

This study examined the effect of a medical image management network on the behavior of physicians working in a medial intensive care unit (MICU). For 1 year, 8-week periods during which chest radiographs were digitized and made available to MICU physicians on a digital display console were alternated with 8-week periods during which only film images were available. Clinical efficacy during the periods was compared by measuring the time between completion of imaging examinations and initiation of specific clinical actions such as placement and positioning of tubes. Results indicate that the time required to take some clinical actions decreased with the immediate availability of images on the digital display console. Established procedures for obtaining radiologic information were altered by the digital imaging network. The time at which physicians viewed images changed, and consultations between MICU staff and radiologists decreased. These results indicate that behavior patterns are altered when a new technology replaces an existing one. Optimal use of this technology may require changes in the logistics of clinical practice.

Micromere-specific cell surface proteins of 16-cell stage sea urchin embryos.

Evidence is presented of cell-type specificity of surface proteins from the 16-cell stage sea urchin embryo. The protein composition of the micromere cell surface has been examined by 125I labelling of intact cells followed by SDS-PAGE. In Arbacia punctulata, four high molecular weight (HMW) proteins are detected on the surface of isolated micromeres--but not on mesomere-macromere fractions. In Strongylocentrotus droebachiensis, a micromere-specific protein of 133 K molecular weight (MW) was identified. This 133 K protein binds to wheat germ agglutinin (WGA) but not to concanavalin A (conA). Lectin binding was studied using a new technique. The procedure involves the separation, by SDS-PAGE, of iodinated cell-surface proteins followed by their electrophoretic transfer to lectin-coated nitrocellulose membranes. Using this procedure, cell-type-specific surface proteins which are also lectin-binding-specific, were detected.

[Effects of systemic administration of kainic acid on GABAergic and glutaminergic transmission in various areas of the brain]. / Effetti della somministrazione sistemica di acido kainico sulla transmissione GABAergica e glutamatergica in diverse aree cerebrali.

In the present study that Authors have investigated the effects of systemic injection of kainic acid on aminoacidergic transmission of different rat brain regions. Kainic acid has been used to produce an experimental model of limbic epilepsy characterized by two different phases (KA1 and KA2). Results obtained show a significant decrease of glutamic and aspartic acids (excitatory aminoacids) and glicine and taurine (inhibitory aminoacids) in both phases at hippocampal level. On the contrary GABA concentration seems to be increased.

Altered time course of changes in the hippocampal concentration of excitatory and inhibitory amino acids during kainate-induced epilepsy.

The temporal sequence of electrophysiological and biochemical correlates of epilepsy induced by systemic injection of kainic acid (15 mg/kg i.p.) was investigated in male rats. A significant decrease in the hippocampal concentration of glutamate and aspartate was observed 20 min after the injection. These decreases preceded both electrographic and behavioral manifestations of epilepsy, thus suggesting a causal relationship between acidic amino acid changes and the genesis of kainate-induced hyperactivity. About 30-45 min after kainate injection, a decrease in glutamate, aspartate, glycine and taurine and no change in GABA concentration were observed. Bioelectrical activity, recorded in the regio inferior (CA3) of the hippocampus or in the fascia dentata revealed the presence of high frequency bursts separated by a long-lasting depression of discharge. About 55-75 min after the injection, the number of spikes in each burst increased and the duration and frequency of interictal pauses decreased. This stage was characterized by a decrease in glutamate and aspartate, restoration to normal of glutamine, glycine and taurine and a decrease in GABA.

Effects of calcitonin on the brain of aged rats.

We have recently demonstrated that calcitonin, a putative neuromodulator, may influence extrapyramidal motor system by decreasing nigro-striatal dopaminergic function. Since calcitonin is extensively used in aged patients, we have investigated whether calcitonin might influence extrapyramidal motor behavior (haloperidol-induced catalepsy and apomorphine-induced hyperactivity) in rats of different ages. Intracerebroventricular injection of salmon calcitonin (1 micrograms/kg) prevented apomorphine-induced hyperactivity in 2, 7, 18 or 21 month old rats, but potentiated haloperidol-induced catalepsy only in 2 or 7 month old rats. In addition, in all the animals salmon calcitonin significantly decreased the secretion of prolactin, an anterior pituitary hormone that may act at central level enhancing nigro-striatal dopaminergic activity.

[Effects of dopaminergic drugs on the concentrations of PGE2 and PGF2alpha in various brain regions]. / Effetti di farmaci dopaminergici sulle concentrazioni di PGE2 e PGF2alpha in alcune regioni cerebrali.

It has long been shown by Biggio and Guidotti that multisynaptic nigro-cerebellar pathway of dopaminergic origin can control cerebellar cyclic guanosinmonophosphate (cGMP) content, a good index of the activity of Purkinje cells. In this line, it has been reported that haloperidol and sulpiride, significantly decrease cerebellar cGMP content while opposite changes are observed with apomorphine. In an attempt to establish whether other cerebellar cGMP-related parameters may be influenced by dopamine drugs. Authors have investigated the effects of haloperidol, sulpiride and apomorphine on cerebellar PGE2 and PGF2alpha. Results obtained indicate that haloperidol and sulpiride significantly reduce cerebellar PGE2 and PGF2alpha content while opposite changes are induced by apomorphine. Similar results have been observed in substantia nigra but not in other brain regions, such as corpus striatum and medial basal hypothalamus. The possibility that the observed changes in cerebellar PG-content may result from the modulation of striatal dopamine receptors is discussed.

[Neuroendocrine modulation of haloperidol-induced catalepsy]. / Modulazione neuroendocrina della catalessi indotta da aloperidolo.

Evidence has been accumulated implicating sex hormones as possible modulators of extrapyramidal motor function. In the present study we have investigated the effects of estrogens, progesterone, testosterone, prolactin and calcitonin on behavioral parameters related to nigro-striatal dopaminergic system, such as haloperidol-induced catalepsy in male rats. It was found that 7-days estradiol benzoate treatment (5 micrograms/rat/day) significantly increases haloperidol-induced catalepsy, suggesting a possible antidopaminergic activity of estrogens. On the other hand, prolactin facilitates nigro-striatal dopaminergic transmission. Interestingly, 7 day treatment with medroxy-acetate progesterone (MAP, 5 mg/Kg, i.p.) brings about a trend to a decrease in haloperidol-induced catalepsy, while no significantly effect was observed following acute MAP administration at the same dose. So, it is tempting to speculate that chronic progestinic treatment may result in an increase in dopaminergic tonus. Testosterone, acutely administered (5mg/kg.s.c.) induces changes similar to those observed following progesterone administration. Finally, also calcitonin is able to influence haloperidol-induced catalepsy by markedly increasing it.

[Modification of the nigro-striatal system by estrogens and prolactin. Clinical and experimental data]. / Modulazione del sistema nigrico-striatale da parte di estrogenie prolattina. Dati clinici e sperimentali.

We have investigated the effects of estrogens and prolactin on nigro-striatal dopaminergic function. In this regard, apomorphine-induced hyperactivity has been evaluated in hyperprolactinemic rats. Results obtained suggest the possibility that hyperprolactinemia potentiates nigro-striatal dopaminergic transmission inducing, in chronic, charges in dopamine receptor sensitivity. As a neurochemical parameter of the extrapyramidal motor system, we have investigated the activity of the GABA-synthesizing enzyme glutamate decarboxylase (GAD, EC 4.1.1.15) in corpus striatum and substantia nigra. Hyperprolactinemia induced by anterior pituitary homograft under the kidney capsule or systemic sulpiride injection significantly increases GAD activity. In contrast, estrogen treatment decreases nigral GAD activity even though increases plasma prolactin levels. From a clinical point of view, preliminary data indicating a good therapeutical efficacy of estrogens and progesterone in psychiatric patients are reported.

[Hyperprolactinemia and catalepsy induced by haloperidol]. / Iperprolattinemia e catalessi indotta da aloperidolo.

The effect of endogenous hyperprolactinemia induced by pituitary transplantation under the kidney capsule on haloperidol induced catalepsy was evaluated in male Wistar rats treated with two doses of the drug (500 gamma/kg; 2 mg/kg i.p.). Rats of 220 +/- 30 g received intraperitoneal injection of haloperidol. Every five minutes following drug administration the rats were assessed for catalepsy by placing the forepaw on a horizontal bar, and observed for two minutes. Data obtained show that hyperprolactinemia potentiates the cataleptic score in rats treated with dose of 500 gamma/kg i.p., while no significant difference was observed between hyperprolactinemic rats and control rats, at the dose of 2 mg/kg i.p. of haloperidol.