Cannabis use is associated with an earlier age of onset of psychosis (AOP). However, the reasons for this remain debated.
We applied a Cox proportional hazards model to 410 first-episode psychosis ...patients to investigate the association between gender, patterns of cannabis use, and AOP.
Patients with a history of cannabis use presented with their first episode of psychosis at a younger age (mean years = 28.2, SD = 8.0; median years = 27.1) than those who never used cannabis (mean years = 31.4, SD = 9.9; median years = 30.0; hazard ratio HR = 1.42; 95% CI: 1.16-1.74; P < .001). This association remained significant after controlling for gender (HR = 1.39; 95% CI: 1.11-1.68; P < .001). Those who had started cannabis at age 15 or younger had an earlier onset of psychosis (mean years = 27.0, SD = 6.2; median years = 26.9) than those who had started after 15 years (mean years = 29.1, SD = 8.5; median years = 27.8; HR = 1.40; 95% CI: 1.06-1.84; P = .050). Importantly, subjects who had been using high-potency cannabis (skunk-type) every day had the earliest onset (mean years = 25.2, SD = 6.3; median years = 24.6) compared to never users among all the groups tested (HR = 1.99; 95% CI: 1.50- 2.65; P < .0001); these daily users of high-potency cannabis had an onset an average of 6 years earlier than that of non-cannabis users.
Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users.
To investigate the clinical impact of three available antivirals for early COVID-19 treatment in a large real-life cohort. Between January and October 2022 all outpatients tested positive for ...SARS-CoV-2 referring to IRCCS S. Orsola hospital treated with an early antiviral therapy were enrolled. A comparison between patients treated with nirmatrelvir/ritonavir (NTV/r), molnupiravir (MPV) and remdesivir (RDV) was conducted in term of indications and outcome. To account for differences between treatment groups a propensity score analysis was performed. After estimating the weights, we fitted a survey-weighted Cox regression model with inverse-probability weighting with hospital admission/death versus clinical recovery as the primary outcome. Overall 1342 patients were enrolled, 775 (57.8%), 360 (26.8%) and 207 (15.4%) in MPV, NTV/r and RDV group, respectively. Median age was 73 (59-82) years, male sex was 53.4%. Primary indication was immunosuppression (438, 32.6%), the median time from symptom onset to drug administration was 3 2-4 days. Overall, clinical recovery was reached in 96.9% of patients, with hospital admission rate of 2.6%. No significant differences were found in clinical recovery nor hospitalization. Cox regression showed a decreased probability of hospital admission/ death among prior vaccinated patients compared with unvaccinated (HR 0.31 95%CI 0.14-0.70, p = 0.005). No difference in hospitalization rates in early treatment compared to late treatment were found. No differences among MPV, NTV/r and RDV in terms of clinical recovery or hospitalization were found. Patients not vaccinated had a significant increased risk of hospitalization.
•Paroxysmal painful spasms might be associated with central pontine myelinolisis.•Central pontine myelinolisis may be due to hyperglycemic states.•Central pontine myelinolisis may cause acute-onset ...movement disorders.•Prompt recognition and treatment of acute-onset movement disorders are mandatory.
Liver cancer is the second leading worldwide cause of cancer‑associated mortalities. Hepatocellular carcinoma, which accounts for the majority of liver tumors, ranks fifth among types of human ...cancer. Well‑established risk factors for liver cancer include the hepatitis B and C viruses, aflatoxins, alcohol consumption, and oral contraceptives. Tobacco smoking, androgenic steroids, and diabetes mellitus are suspected risk factors. Current knowledge regarding non‑infective occupational risk factors for liver cancer is inconclusive. The relevance of liver disorders to occupational medicine lies in the fact that the majority of chemicals are metabolized in the liver, and toxic metabolites generated via metabolism are the predominant cause of liver damage. However, their non‑specific clinical manifestations that are similar in a number of liver diseases make diagnosis difficult. Furthermore, concomitant conditions, such as viral hepatitis and alcohol or drug abuse, may mask liver disorders that result from occupational hepatotoxic agents and block the demonstration of an occupational cause. The identification of environmental agents that result in human cancer is a long and often difficult process. The purpose of the present review is to summarize current knowledge regarding the association of non‑infective occupational risk exposure and HCC, to encourage further research and draw attention to this global occupational public health problem.
Abstract Apart from the intestinal environment, inulin induces physiological effects, which includes a reduction in glucose and lipid concentrations and modulation of gastrointestinal motility ...through the release of different peptides. We hypothesized that inulin-enriched pasta may also improve small intestine permeability in relation to zonulin and glucagon-like peptide 2 (GLP-2) levels in healthy young subjects. Twenty healthy, young male volunteers completed a randomized, double-blind crossover study consisting of a 2-week run-in period and two 5-week study periods (11% inulin-enriched or control pasta), with an 8-week washout period in between. The intestinal barrier function was assessed by lactulose-mannitol excretion in urine. Zonulin values and GLP-2 release were evaluated by enzyme-linked immunosorbent assay. In the inulin group, the urinary lactulose recovery was significantly lower than the other 2 groups. There were no significant differences in urinary mannitol levels between groups. Accordingly, the lactulose-mannitol excretion ratio was significantly decreased in the inulin-enriched pasta group compared with the other 2 groups. The inulin-enriched pasta group had significantly lower zonulin serum values and significantly higher GLP-2 basal values when compared with the baseline and control pasta groups. The dietary use of inulin-enriched pasta preserves intestinal mucosal barrier functioning and modulates circulating levels of zonulin and GLP-2, suggesting that prebiotics could be used in the prevention of gastrointestinal diseases and metabolic disorders.
Growing evidences demonstrate that chemokines and chemokine receptors are up-regulated in resident central nervous system cells during Alzheimer's disease contributing to neuroinflammation and ...neurodegeneration. Prokineticin 2 belongs to a new family of chemokines which recently emerged as a critical player in immune system and inflammatory diseases.
Since pharmacological blockade in vitro of the prokineticin system is able to antagonize Amyloid β-induced neurotoxicity, the aim of the present study was to investigate in vivo effects of prokineticin receptor antagonist PC1 on memory impairment in a rodent model of Alzheimer's disease. Rats were intracerebroventricular infused with Aβ1-42 and behavioral responses as well as the expression profile in hippocampus of prokineticin 2 and its receptors were investigated.
Results demonstrated that Aβ1–42-infused rats developed significant memory impairments together with a marked up-regulation of both prokineticin 2 and its receptors in hippocampal neurons and astrocytes. Treatment with PC1 significantly improved learning capability of Aβ1–42-infused rats restoring the balance of prokineticin system.
This study pointed to a neuroprotective role of PC1 on Aβ1-42-induced memory deficits that could be ascribed to the ability of PC1 to modulate rat hippocampal prokineticin system and to recover the impaired Aβ1-42-induced neurogenesis. This suggests that prokineticin system antagonism could be considered as a new approach for the study of AD etiopathology.
•Intracerebroventricolar infusion of Aβ1-42 modulates prokineticin system in rats.•PC1 improves learning capability of Aβ1–42-infused rats decreasing PROK2 levels.•PC1 restores the impaired Aβ1-42-induced neurogenesis in hippocampus.•PC1 decreases iNOS and NF-κB overexpression reducing Aβ1-42-induced gliosis.
In this study, the evolution of the safety, nutritional, and volatile profile of a traditional Italian anchovy sauce with protected designation of origin (PDO), called "colatura di alici di Cetara", ...is investigated after 12, 24, and 48 months of aging in wooden barrels. Some physicochemical parameters, free amino acids, volatile compounds, and histamine contents were evaluated during the aging of the samples. Glutamate, which together with aspartate is responsible for the umami taste, was the predominant free amino acid in the tested fish sauce, with a significant increase during the 48 months of maturation. The total amino acid content of the anchovy sauce increased from 24 to 48 months of aging. The histamine content decreased significantly from 12 to 48 months of ripening. This point is particularly interesting for the sauce safety and confirms the importance of the maturation time of at least 9 months reported in the disciplinary of production. A total of 44 volatile compounds were found in the anchovy sauce samples, of which the largest class was acids, mainly isovaleric acid. The results show that prolonged maturation improves the safety, nutritional, and volatile components of the seasoning "colatura di alici".
Cervical artery dissections may present with mild and misleading symptoms such as a headache or cervical pain. In the absence of early diagnosis and therapy, such patients may have a high risk of ...cerebrovascular events. In order to refine evaluation of cervical artery dissections, we report the experience of a single center, focusing on clinical findings (e.g., headache and pain-related features at onset). From 2012 to 2017, 49 patients with cervical arteries dissections were admitted to our institution; 28 out of 49 patients (57%) presented with a headache or cervical pain, which were evaluated according to the International Classification of Headache Disorders (ICHD-III beta). Item C3a of ICHD-III beta (“pain is severe and continuous for days or longer”) was present in all patients symptomatic for a headache. Another common characteristic was the recent onset, with an average (± SD) timing from the onset of a headache to the first neurologic evaluation of 3 (± 2) days (range 1–5). A refined clinical evaluation of patients presenting with a headache at the Emergency Department could improve the early detection and management of patients with cervical artery dissections, in particular when presenting without other associated neurological symptoms.
Abstract
Elagolix, an orally active non-peptidic GnRH antagonist, has been approved by the Food and Drug Administration for the management of moderate to severe pain associated with endometriosis. As ...the degree of ovarian suppression obtained with elagolix is dose-dependent, pain relief may be achieved by modulating the level of hypo-oestrogenism while limiting side effects. Elagolix may thus be considered a novelty in terms of its endocrine and pharmacological properties but not for its impact on the pathogenic mechanisms of endometriosis, as the target of this new drug is, yet again, alteration of the hormonal milieu. Given the oestrogen-dependent nature of endometriosis, a reduction of side effects may imply a proportionate decrease in pain relief. Furthermore, if low elagolix doses are used, ovulation is not consistently inhibited, and patients should use non-hormonal contraceptive systems and perform serial urine pregnancy tests to rule out unplanned conception during periods of treatment-induced amenorrhoea. If high elagolix doses are used to control severe pain for long periods of time, add-back therapies should be added, similar to that prescribed when using GnRH agonists. To date, the efficacy of elagolix has only been demonstrated in placebo-controlled explanatory trials. Pragmatic trials comparing elagolix with low-dose hormonal contraceptives and progestogens should be planned to verify the magnitude of the incremental benefit, if any, of this GnRH antagonist over currently used standard treatments. The price of elagolix may impact on patient adherence and, hence, on clinical effectiveness. In the USA, the manufacturer AbbVie Inc. priced elagolix (OrilissaTM) at around $10 000 a year, i.e. $845 per month. When faced with unaffordable treatments, some patients may choose to forego care. If national healthcare systems are funded by the tax payer, the approval and the use of a new costly drug to treat a chronic condition, such as endometriosis, means that some finite financial resources will be diverted from other areas, or that similar patients will not receive the same level of care. Thus, defining the overall 'value' of a new drug for endometriosis also has ethical implications, and trade-offs between health outcomes and costs should be carefully weighed up.
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