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.

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.

The association of elevated plasma cortisol and early atherosclerosis as demonstrated by coronary angiography.

To study the association of plasma cortisol and coronary atherosclerosis, we elected 71 male outpatients who had coronary angiography as part of their evaluation at our facility. Forty-eight percent of the angiograms showed no evidence of coronary artery disease (CAD), 20% showed mild CAD, and 32% showed moderate to severe CAD. We found significant correlations between elevated serial morning plasma cortisols and moderate to severe coronary atherosclerosis. Using the odds ratio, we compared plasma cortisol to the major risk factors for coronary artery disease. Plasma cortisol was second only to serum cholesterol as a discriminator in our patient population between diseased and non-diseased patients. We found a significant correlation between plasma cortisol and cholesterol, blood pressure, and smoking- the three cardinal risk factors for CAD. The highest degree of correlation was found between cortisol and cholesterol. The possible significance of the association of cortisol and the major risk factors for CAD is discussed.

Induction and transmission of chemically induced chromosome aberrations in female germ cells.

Female mice were dosed with a number of chemical clastogens. The dosed females were then mated 28.5, 6.5, and 0.5 days after dosing, corresponding to various developmental stages of oogenesis (ie, early pre-antral to late antral stages). One-cell embryos derived from these mating were then isolated and analysed for structural and/or numerical chromosome aberrations. Chromosome damage, either structural or numerical, was induced only in oocytes at the late antral stages of oogenesis (i.e. when females were dosed 0.5 days prior to mating). There were few chromosome aberrations in embryos obtained from females dosed 6.5 or 28.5 days prior to mating. The results show that the analysis of one-cell embryos derived from the germ cells of dosed females is a potentially useful test system for the identification of chemically induced structural and numerical chromosome aberrations. However, the technically demanding methods involved in the preparation of these one-cell embryos prevent their use for routine screening purposes.

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.

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.

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.

4-Chloromethylbiphenyl (4CMB)--an in vivo cytogenetic study in the Chinese hamster (Cricetulus griseus).

The study was part of the UK EMS Genetic Toxicology trial, to determine the clastogenic potential of 4CMB in the bone-marrow cell chromosomes of the Chinese hamster. At dose levels of 50, 100, 200, 300 and 400 mg/kg of 4CMB statistical analysis of the data failed to show any significant differences in chromosomal damage between negative controls and 4CMB-treated groups. However, numerical increases in chromosomal damage were observed in the 4CMB-treated groups. The aberrations were at a low frequency but included the more severe types of chromosomal damage, such as exchange figures and dicentric chromosomes.

The use of fertilised mouse eggs in detecting potential clastogens.

Male mice were treated with methyl methanesulphonate (MMS) and then serially mated to females in oestrus, over the whole of the spermatogenic cycle. Chromosome preparations were made from fertilised eggs obtained from the matings and cultured overnight in the presence of a mititic inhibitor. No chromosomally abnormal eggs were found in matings using untreated animals but matings involving MMS-treated males produced a variety of abnormalities. The most sensitive stage in the spermatogenic cycle was 8 days after treatment, corresponding to the testicular sperm stage of spermatogenesis. At this sampling time 97% of the eggs analysed were chromosomally abnormal and the aberrations detected were predominantly 'shattered' male chromosomes. The aberration frequency in the post-meiotic stages decreased steadily up to day 20. No further structural chromosome aberrations were detected, until day 48, when chromosome fragments were detected in 2 eggs (4%) indicating that pre-meiotic damage can be induced and transmitted. The low background frequency obtained with the procedures used in this study enhances the sensitivity of the system for experimentally assessing the effects of clastogenic agents on male and female germ cells.

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.

[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.

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.

[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.

Mammalian male germ cell cytogenetics.

The methods used for the detection of chemically induced chromosome damage in male germ cells are discussed. These tests have been divided into direct and indirect cytogenetic methods. The direct methods assess chromosome damage in the dosed animal but analysis is restricted to the dividing spermatogonia and spermatocytes. Using indirect methods, chromosome damage is assessed in the F1 progeny of the dosed male and analysis covers all germ cell stages. Both methods can provide evidence of germ cell exposure but the data obtained from the indirect tests are considered more relevant since a positive result clearly constitutes unequivocal evidence of transmitted damage. The analysis of one-cell embryos from matings involving dosed parents is considered to be the most useful indirect test system since both structural and numerical aberrations in male and female F1 offspring can be assessed. Although relevant to the assessment of mutagenic hazard, the technically demanding methods used in the germ cell techniques prevent their use for preliminary screening programmes.