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.

Outcome of lumbar intervertebral foraminal stenosis surgery and depression.

A total of 58 patients consecutively underwent surgical treatment for lumbar intervertebral foraminal stenosis. We performed a microsurgical combined transarticular lateral and medial procedure with partial facetectomy in all patients to decompress the affected nerve root. All patients underwent assessment of depressive symptoms by means of the Zung Self Depression Scale (SDS). Subjective pain was self-evaluated by the Visual Analogue Scale (VAS). Both the tools were administered preoperatively, at 3 and 12 months' follow-up 0. The difference between the three SDS scores was significant (Friedman ANOVA, χ(2) = 53.171, p < 0.00001). The Wilcoxon rank test showed significant difference between preoperative SDS scores as compared with three months follow-up (Z = -6.393, p < 0.0001) and the last, in turn, as compared with twelve months follow- up (Z = -3.720, p = 0.0002). The comparison between preoperative and 12 months' follow-up also reached significance (Z = -3.285, p = 0.001). About VAS, the difference between the three VAS scores was significant (Friedman ANOVA, χ(2) = 69.932, p < 0.00001). The Wilcoxon rank test showed significant difference between preoperative VAS scores as compared with 3 months' follow-up (Z = -6.567, p < 0.0001) and the last, in turn, as compared with 12 months' follow-up (Z = -3.153, p < 0.002). The comparison between preoperative and 12 months' follow-up was also significance (Z = -5.520, p < 0.0001). Our results would alert clinicians to accurately consider the real need to treat and to include a careful psychiatric and psychological evaluation of these patients in the diagnosis and follow-up 0.

Physiologically based pharmacokinetic models for the transport of trichloroethylene in adipose tissue.

In this paper we present three physiologically based pharmacokinetic (PBPK) models for the systemic transport of trichloroethylene (TCE), with a focus on the adipose, or fat tissue. TCE is a widespread environmental contaminant, and has been shown to produce toxic effects in both animals and humans. A key characteristic of TCE is its tendency to accumulate in fat tissue, which has a major impact on the overall systemic disposition of TCE. Here we use PBPK models to predict the dynamics of TCE in the various tissues and organs, including the adipose tissue. The first model utilizes the standard 'perfusion-limited' compartmental model for the fat tissue, while the second model uses a 'diffusion-limited' model to describe the transport through the adipose tissue. Both of these ODE models are based on 'well-mixed' and rapid equilibrium assumptions, and do not take into account the specific and largely heterogeneous physiology of adipose tissue. The third model we discuss is a PBPK hybrid model with an axial-dispersion type model for the adipose tissue. This PDE-based model is designed to capture key physiological heterogeneities of fat tissue, including widely varying fat cell sizes, lipid distribution, and blood flow properties. Model simulations demonstrate that this model may be well-suited to predict the experimental behavior of TCE in adipose tissue using parameter estimation techniques.

[Retroperitoneal mixoid liposarcoma: a difficult diagnosis with often unfavorable prognosis. Case report]. / Liposarcoma mixoide retroperitoneale: patologia di difficile interpretazione e spesso di prognosi sfavorevole. Un caso clinico.

Liposarcoma is the most common adult soft tissue sarcoma. The hallmark is the immature fat cell or lipoblast. It occurs in late adult life, frequently in the lower extremities, in the retroperitoneal, perineal and mesenteric region. Retroperitoneal liposarcoma doesn't produce symptoms until it is very large. A review of the literature is made and the case of a 65-years old man, submitted to surgical treatment for a bulky retroperitoneal mixoid liposarcoma is reported.

Metaphit amplifies long-term potentiation (LTP) in the mouse hippocampus.

The influence of metaphit, a phencyclidine derivative, on the amplitude of Long-Term Potentiation (LTP) in the mouse hippocampus was investigated. Mice (C57BL/6) of both sexes were injected with metaphit (80 mg/kg) and hippocampal slices were prepared at 3, 24, 48 hrs and 6 days following injection. The extracellular evoked potentials were recorded from the pyramidal cell layer following Schaffer collateral stimulation. The threshold value, defined as the minimum strength of the stimuli to evoke a 0.1 mV potential, was about 5 fold greater in metaphit slices than in control slices 3 hr following injection, and then declined to the control value within 6 days. The magnitude of LTP was also amplified by metaphit in a time-dependent fashion. The effect was visible three hours after injection, reached its maximum at 48 hr and then declined to a level slightly higher than control at 6 days following injection. These results demonstrate that metaphit, a compound known to induce audiogenic seizures, is able to modify synaptic plasticity in the hippocampus. Presented results are also in agreement with our previous data which demonstrated an interaction between the mechanisms of LTP and audiogenic seizure.

Ultrashort electromagnetic signals: biophysical questions, safety issues, and medical opportunities.

Ultrashort electromagnetic pulses are being increasingly produced by modern high power microwave and laser devices. These ultrashort pulses can produce electromagnetic transients in tissue that prompt safety questions concerning the possible exposure of living beings to ultrashort electromagnetic pulses. The existence of electromagnetic transients may permit meaningful advances in medical therapy and imaging. Electromagnetic transients, potential medical applications, and anticipated research avenues relevant to occupational health and safety issues are discussed.

Transurethral microwave thermotherapy in the treatment of symptomatic benign prostatic hyperplasia.

One hundred and forty-four patients with symptomatic benign prostatic hyperplasia were treated by transurethral microwave thermotherapy between January and December 1991. Before entering the study, all patients had a Boyarsky symptom score > or = 8, peak flow rate < or = 15 ml/s and postvoiding residual urine < or = 200 ml. Transurethral thermotherapy with the Prostatron (Technomed) was carried out as a single session (60 min) without any analgesia or sedation. Acute urinary retention occurred in 19.4% of the patients after treatment requiring catheterization for 2-3 weeks; morbidity rate was 5.5%. Six months after treatment, Boyarsky symptom score decreased from 11.73 +/- 4.97 to 4.40 +/- 3.21 (mean values +/- SD); peak flow rate increased on average from 8.97 +/- 4.18 to 13.07 +/- 4.87 ml/s and postvoiding residual urine decreased from 135 +/- 17.9 to 63 +/- 34.7 ml. Slight further improvement was shown, in a few patients, at the 1-year follow-up visit.

Animal-to-human extrapolation using compartmental models.

We have been studying how to use compartmental models to reliably extrapolate toxicological experimental results from one animal species to another with the ultimate goal of useful extrapolation to man. We have taken, as the fundamental core of our analysis, the physically necessary equations describing mass balance. These equations are the classical Fickian equations of the form VdC/dt = Q(a - v). These equations are not a complete set since they are insufficient to provide estimation of venous, arterial, or tissue concentrations with time. Therefore, the mass balance equations must be augmented with additional phenomenological relations to permit the desired calculations. Many investigators use the venous exist condition. While it is clear how to extrapolate the mass balance equations from one sized animal to another or from one species to another, it is not clear how to extrapolate the venous exit condition. In this research we have evaluated the venous exit condition by comparing it with approximate analyses of perfusion and substance diffusion in the tissue.

[Surgical treatment of unrepairable vesicovaginal fistulas]. / La terapia chirurgica delle fistole vescico-vaginali non riparabili.

The authors discuss different types of urinary diversion as the therapy of unrepairable vesico-vaginal fistulas. They also describe the therapy performed in their experience and underline that, at the moment, rectal bladder is to be considered the best solution.

Chemically induced aneuploidy in female germ cells.

Female mice were dosed with the spindle poisons colcemid (5 mg/kg) or colchicine (2 mg/kg) or with a dihydropyridazinone (ICI 109,081; 5 mg/kg; which inhibits oocyte maturation) or with saline, the vehicle control. The dosed females (whose ovulation was synchronized using exogenous gonadotrophins) were mated with undosed males, 12 or 3 h prior to ovulation, coresponding to MI or MII stages in preovulatory oocytes. First-cleavage embryos derived from these matings were then analysed for numerical chromosome aberrations. There were no numerical aberrations in the embryos derived from control matings. Polyploid embryos were isolated from females dosed with colchicine. When females were dosed 3 h prior to ovulation (PO) 26% of the first-cleavage embryos were polyploid; in those dosed 12 h PO it was 100%. Colcemid and ICI 109,081 induced both polyploid and aneuploid embryos; with colcemid these aberrations were only observed in the embryos derived from oocytes of females dosed 3 h PO. At this sample time 4% of the embryos were polyploid and 24% were aneuploid. In contrast, the majority of aberrations induced by ICI 109,081 were observed in females dosed 12 h PO where 10% of the embryos were polyploid and 3% were aneuploid.

Species-specific response to the rodent carcinogens 1,2-dimethylhydrazine and 1,2-dibromo-3-chloropropane in rodent bone-marrow micronucleus assays.

1,2-Dimethylhydrazine is confirmed as active in the mouse bone-marrow micronucleus assay when administered as an aqueous solution via oral gavage to three different strains of mice. It is also shown to be inactive in a corresponding rat assay under similar conditions of test. The observations were independently repeated in two laboratories. In contrast, 1,2-dibromo-3-chloropropane showed the reverse profile, being active in the rat bone-marrow assay but inactive in the mouse; the latter observations were also made in two laboratories. The carcinogen procarbazine was active in both species. These findings are discussed within the context of the present GeneTox revision of the standard test protocol of the rodent bone-marrow micronucleus assay.

Mutagenicity to bacteria, cultured cells, and rodents of the human carcinogen chlornaphazine.

The human carcinogen and nitrogen mustard chlornaphazine (CN) has been confirmed to be mutagenic to Salmonella and, unexpectedly, the more so when evaluated in the presence of liver S9 mix. It also has been established as clastogenic to Chinese hamster lung cells exposed in vitro to dose levels greater than 2.5 micrograms/ml. Chlornaphazine subdued mice at doses of 5 g/kg, but only the occasional death occurred during the 4 days following oral administration of this dose in corn oil. Consequently, a median lethal dose level was not established. Nonetheless, dose levels of 500 mg/kg or greater gave a clear positive response in both the mouse and the rat bone marrow micronucleus assay. Although depression of erythropoeisis was observed in mice, a clastogenic response still was observed in the bone marrow 24 hr after dosing. The positive response in the rat was greater than that observed in the mouse. The present data provide a further instance of an established human carcinogen being readily detected by standard in vitro and in vivo mutagenicity assays.

The assessment of micronucleated polychromatic erythrocytes in rat bone marrow. Technical and statistical considerations.

Traditionally, the mouse is the species of choice for the rodent bone marrow micronucleus assay (MN). However, the rat is used for most other toxicological studies. The suitability of the rat as a test species for the MN was therefore investigated. In this paper, the methodological aspects of the assay have been considered. The distribution and incidence of micronucleated polychromatic erythrocytes (MPEs) on bone marrow slides prepared by two techniques, the conventional smear and the paint-brush technique, were assessed in control and cyclophosphamide-dosed male and females rats. MPEs were shown to be homogeneously distributed when assessed over a large number of PEs on slides prepared by both techniques, but when viewed over a few hundred PEs (less than 500 PEs), the incidence of MPEs on the same slides was seen to vary considerably (0-10 MPEs/500 PEs). Variability was within acceptable limits when at least 1000 PEs/animal were analysed. The spontaneous incidence of MPEs in the AP rat is low (0-2 MPEs/1000 PEs). Cyclophosphamide increased the incidence markedly and there was a wide inter-animal variability in the response (10-40 MPEs/1000 PEs). The paint-brush technique is considered technically simpler and recommended over the smear technique. This study shows that MPEs can be accurately scored in the bone-marrow of the rate provided due consideration is given to staining and sample size of PEs analysed per animal.

The cytonucleus test in the rat: a combined metaphase and micronucleus assay.

The suitability of the rat as a species choice for the micronucleus assay and the possibility of combining both metaphase and micronucleus analysis using one set of animals were investigated. Cyclophosphamide, trenimon, vinblastine sulphate and dimethyl benzanthracene were used to optimise the study design and experimental procedures. The sample times ranged from 12 to 72 h after a single dose of the compound. A maximal response in both micronucleus and chromosome aberration induction was observed 24 h after dosing. This sample time is recommended as the single sample time for the screening of all classes of compound. Using the optimal conditions, a number of different mutagens/carcinogens were then analysed for the induction of both micronuclei and chromosome aberrations in the same animal. The compounds selected were mitomycin C, methotrexate, 5-fluorouracil, hexamethyl phosphoramide, benzo[a]pyrene, benzidine and diaminoterphenyl. The results show that the rat is a responsive test species and that it is possible to combine both metaphase and micronucleus analysis in the same animal.

Sodium fluoride and chromosome damage (in vitro human lymphocyte and in vivo micronucleus assays).

The clastogenic potential of sodium fluoride was determined both in vitro (using cultured human lymphocytes) and in vivo (using the rat bone-marrow micronucleus test). The incidence of chromosome aberrations in human lymphocyte cultures exposed to 20 or 40 micrograms/ml sodium fluoride (3 and 9% respectively) was significantly increased compared with control cultures (0.5%). However, the incidence of micronucleated polychromatic erythrocytes in male AP rats dosed 1000 mg/kg NaF (the maximum tolerated dose over 24 h) or 500 mg/kg NaF was similar to that in the animals dosed distilled water (vehicle control). Thus, sodium fluoride is clastogenic in vitro but not in vivo.