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Hepatocellular carcinoma (HCC) incidence is continuously increasing worldwide, due to the rise of metabolic dysfunction-associated steatohepatitis (MASH) cases. Cholesterol is an essential driver of the metabolic dysregulations that promote HCC progression. Liver X Receptor (LXR) is a nuclear receptor best known for the regulation of lipid and cholesterol homeostasis, with a prominent function in the liver and in the intestine. Here, we aimed to explore whether modifications in intestinal lipid metabolism may contribute to the onset of HCC, particularly taking into account cholesterol metabolism and LXRs. To study the progression of MASH to HCC, we induced metabolic HCC in wild-type male mice and mice carrying an intestinal chronic activation of LXRα. Also, we analysed human hepatic transcriptome datasets. The increased consumption of fat and carbohydrates drives the intestinal activation of LXRα and accelerates the onset of the hepatic tumours. Chronic intestinal-specific activation of LXRα enhances HCC progression only in the presence of a high cholesterol intake. In HCC, despite the increased hepatic cholesterol content, LXR is not active, thus driving liver cancer development. Intriguingly, in line with these results in the mouse model, LXR transcriptome is also downregulated in human hepatocarcinoma and its expression level in liver tumours directly correlates with a decreased survival rate in patients. Overall, our findings establish the relevance of the intestine in influencing the susceptibility to MASH-HCC and point to intestinal LXRα activation as a driver of metabolic liver cancer in the presence of dietary cholesterol., (© 2024. The Author(s).)

One hundred and eighteen patients with neurasthenia, as defined by ICD 10 (International Classification of Diseases), participated in a randomised, double-blind, placebo-controlled trial of pivagabine (4-[(2,2-dimethyl-1-oxopropyl)amino]butanoic acid, CAS 69542-93-4, Tonerg). Pivagabine 1800 mg/d was administered orally for four weeks. At the end of the trial, active medication was significantly superior to placebo on the Clinical Global Impression (CGI) improvement of illness scale. In addition, pivagabine treatment reduced the physical and mental fatigability of patients, and increased their sense of well-being.

This paper reports on the effectiveness of oral lamotrigine in 15 patients suffering from "essential" trigeminal neuralgia and in five patients suffering symptomatic trigeminal neuralgia concomitant with multiple sclerosis. We recorded objective and subjective pain ratings and correlated them to daily dosage (400 mg maximum) and plasma levels of the drug. We detected pain relief proportional to daily dosage and to drug plasma levels. Eleven of the cases affected by the "essential" form of neuralgia showed complete pain relief on reaching their maximum daily dosage. All cases affected by the symptomatic form had complete pain relief. We could detect no changes from these results by the end of the follow-up period (3 to 8 months after the study ended).

This study was designed to assess the relevance of normal aging to performance in a variety of neuropsychological tests, in a wide range of age groups. The battery included tests of several cognitive abilities of varying complexity (attention, orientation, memory, self-regulation, categorial ability and so on). The results showed that some tests (Orientation, Attention, Digit Span, Naming, Block Design, Self-regulation, Calculation, Weigl) are not significantly affected by aging while in others performance clearly declines with age. However, the age at onset of the decline is far from uniform. In some tests (Logical Memory, delayed recall section of Supraspan Test, Hooper Test, Finger Tapping Test) it is manifest in early middle age while in others (Faces Recognition, Set Test, Reproduction of Geometric Designs) it does not appear until much later in life.

Prophylaxis continues to be an area for discussion in the therapy of the hemophilic child. In fact, standard parameters are still not used in the evaluation of the efficacy of this treatment. At the Milan University Pediatric Clinic we have begun three different prophylactic programs with 52 children with ages ranging from 12 months to 14 years 7 months. We have evaluated the efficacy of these regimes comparing the data obtained in the 12 months following the start of the program with those obtained in the 12 months prior to it. Our data, even though they pertain to a limited number of children, show that continuous prophylaxis is truly efficacious if it is begun early before the onset of an arthopathy. Therapeutic prophylaxis however for the stabilizing of a target joint is usually better accepted by the children and their parents. The high cost of the prophylactic programs can nevertheless be justified by the better quality of life of the patients.

Haemophilia is a bleeding disorder characterized by decreased activity of the circulating antihemophilic factor, with different degrees of severity. The prognosis of the disease for an useful normal life is good, providing an adeguate follow-up. We think that the auxological determinants of growth and nutritional status must enter as points of a multicentre follow-up sheet of haemophilia in the pediatric age. We have tried such an approach in 13 patients; preliminary results have shown that all patients are growing well with some degrees of discrete malnutrition (arm circumference less than -1.6 SD). From costitutional point of view, haemophilic boys show a discrete "lean" body pattern (W/H2 less than or equal to O SD(with their trunk longer than legs. Data from other studies are wellcome for confirming our first impressions.

Studies of in vivo recovery, longevity and dose response of factor VIII following infusions of a new factor VIII concentrate (Koate, Cutter Laboratories) yielded results similar to those reported using other sources of factor VIII. Koate has been demonstrated to be clinically effective in classic hemophilia. This preparation was produced by refinements of the methods first described by Hershgold, Pool and Pappenhagen in 1966. By these procedures a high purity factor VIII concentrate is obtained being some 65 to 170 fold purified. This factor VIII concentrate was clinically evaluated in 11 hemophilic children (one of them with 7 Bethesda Units inhibitor) who received a total of 13 separate infusions. Biologic half-life values determined in two subjects resulted 12 and 9,5 hours comparing favorably with those previously reported. Initial 50% disappearance averaged 5,4 and 4,8 hours respectively. In vivo recovery of the infused factor VIII activity averaged 98 +/- 12,75%. Dose response measurements showed that 1 unit/Kg gave an in vivo increase in circulating activity of 1,97 +/- 0,93%.