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Introduction: Admission of metastatic cancer patients to the intensive care unit (ICU) poses medical and ethical challenges in the absence of reliable prognostic tools to guide decision-making. Material and Methods: We retrospectively analyzed the medical charts of 129 consecutive patients with metastatic solid tumors admitted to the ICU between January and September 2014 and identified prognostic factors (PFs) using Cox models. Results: The mean patient age at ICU admission was 58.9 years (range, 25–81 years; males, 51%). Performance status (PS) was 0–1 and 2–3 in 61% and 39% of the patients, respectively. The most prevalent cancers were lung cancer (20%), sarcoma (17%), and breast cancer (16%). ICU admission was attributable to the cancer itself (53%), cancer treatment toxicity (43%), and comorbidities (37%). The median overall survival (OS) after ICU admission was 2.6 months; 15% of the patients died during the ICU stay. Poor PFs for OS were PS >1 before ICU admission (p = 0.007) and ICU admission for the cancer itself (p < 10−3). After ICU discharge, 58% and 42% of the patients received systemic treatment within 12 months and showed good PS recovery, respectively. Multiple organ failure and a multidisciplinary decision to limit therapeutic efforts were poor PFs for reinitiation of systemic treatment (p = 0.2 and 0.006, respectively), and the latter was also a poor PF for PS recovery (p = 0.004). Discussion: In the ICU, the OS of adult patients with solid tumors was similar to that of the noncancer population. For ICU admissions related to the cancer itself, the prognosis is poor.

Saponins exhibit several biological and pharmacological activities, such as antibacterial, anti-inflammatory and anticancer effects. Many studies attribute their activities to their interactions with cholesterol. In this study, we focus on the steroid saponin ginsenoside Rh2, one of the active principles of Panax ginseng root. Some evidence suggests that lipid rafts, defined as nanodomains enriched in cholesterol and sphingolipids, could be involved in the Rh2-induced apoptosis. However, the role of membrane lipids, especially cholesterol, in this process is still poorly understood. Here, we demonstrate that (i) A549, THP-1 and U937 cells are all susceptible to the Rh2-induced apoptosis but to a differential extent and (ii) the cytotoxic effect inversely correlates with the cell membrane cholesterol content. Upon cholesterol depletion via methyl-β-cyclodextrin, those three cells lines become more sensitive to Rh2-induced apoptosis. Then, focusing on the cholesterol-auxotroph U937 cell line, we showed that Rh2 alters plasma membrane fluidity by compacting the hydrophobic core of lipid bilayer (DPH anisotropy) and relaxing the interfacial packaging of the polar head of phospholipids (TMA-DPH anisotropy). The treatment with Rh2 conducts to the dephosphorylation of Akt and the activation of the intrinsic pathway of apoptosis (loss of mitochondrial membrane potential, caspase-9 and -3 activation). All these features are induced faster in cholesterol-depleted cells, which could be explained by faster cell accumulation of Rh2 in these conditions. This work is the first reporting that membrane cholesterol could delay the activity of ginsenoside Rh2, renewing the idea that saponin cytotoxicity is ascribed to an interaction with membrane cholesterol.

Tremor is a common side effect of tacrolimus correlated with peak‐dose drug concentration. LCPT, a novel, once‐daily, extended‐release formulation of tacrolimus, has a reduced C max with comparable AUC exposure, requiring a ~30% dose reduction vs. immediate‐release tacrolimus. In this phase 3b study, kidney transplant recipients (KTR) on a stable dose of tacrolimus and with a reported clinically significant tremor were offered a switch to LCPT. Tremor pre‐ and seven d post‐conversion was evaluated by independent, blinded movement disorder neurologists using the Fahn–Tolosa–Marin (FTM) scale and by an accelerometry device; patients completed the QUEST (quality of life in essential tremor) and the Patient Global Impression of Change. There were 38 patients in the mITT population. A statistically and clinically significant improvement in tremor (FTM score, amplitude as measured by the accelerometry device and QOL [p‐values

Krabbe disease is a fatal rare inherited lipid storage disorder affecting 1:100,000 births. This illness is caused by mutations in the galc gene encoding for the enzyme galactosylceramidase (GALC). Dysfunction of GALC has been linked to the toxic build-up of the galactolipid, galactosylsphingosine (psychosine), which induces cell death of oligodendrocytes. Previous studies show that phospholipase A2 (PLA2) may play a role in psychosine induce cell death. Here, we demonstrate that non-selective inhibition of cPLA2/sPLA2 and selective inhibition of cPLA2, but not sPLA2, also attenuates psychosine-induced cell death of human astrocytes. This study shows that extracellular calcium is required for psychosine induced cell death, but intracellular calcium release, reactive oxygen species or release of soluble factors are not involved. These findings suggest a cell autonomous effect, at least in human astrocytes. Supporting a role for PLA2 in psychosine-induced cell death of oligodendrocytes and astrocytes, the results show inhibition of PLA2 attenuates psychosine-induced decrease in the expression of astrocyte marker vimentin as well as myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG) and the neuronal marker SMI-32 in organotypic slice cultures. These findings provide further mechanistic details of psychosine-induced death of glia and suggest a role for PLA2 in the process. This work also supports the proposal that novel drugs for Krabbe disease may require testing on astrocytes as well as oligodendrocytes for more holistic prediction of pre-clinical and clinical efficacy.

We examined the association between intimate partner violence and unmet need for modern contraception in post-conflict Liberia. This is a secondary analysis of data collected using the Priorities for Local AIDS Control Efforts (PLACE) method. Data from 499 sexually experienced young women (aged 14-25) in Montserrado County, Liberia were examined. Intimate partner violence (55.7%), unintended pregnancy (83.2%), and abortion (45.3%) were pervasive in the study population. An estimated 35.9% of respondents had an unmet need for modern contraception. However, multivariate logistic regression results did not reveal an association between intimate partner violence and unmet need (OR 1.11; 95% CI 0.70-1.75). Among covariates examined, only contraceptive use at sexual debut (26.1%) was significantly associated with unmet need (OR 0.27; 95% CI 0.14-0.52). Liberian youth need information about and access to modern contraceptive methods besides condoms. Interventions to identify and treat victims of violence are also needed.

The maze test is a complex cognitive task involving visuoperceptual, planning and foresight abilities. EEGs were recorded from 20 healthy subjects according to the 10/20 system. Coherence is analogous to a correlation coefficient between the signals recorded by two electrodes and is computed between each electrode paired to all other electrodes. The maze test provoked changes of coherence mainly within the prefrontal regions, between parietal and central electrodes paired with frontal electrodes, especially the right frontopolar and the left prefrontal electrodes, and in the posterior temporal, parietal and occipital regions. EEG coherence analysis detects changes in regions known to be involved in visual processing and executive functions.

1. 1. Steady-state plasma level samples of sixty-five schizophrenic patients from two psychiatric hospitals assigned to three treatment groups (amitriptyline 150 mg/day, perphenazine 20 mg/day and a combination of amitriptyline and perphenmazine at 150 mg and 20 mg/day) were assayed for amitriptyline (AT), endogenous nortriptyline (NT) and perphenazine (PPZ) using gas-liquid chromatography. 2. 2. Results reveal that AT and NT levels are independent of sex and hospital environment. 3. 3. PPZ significantly increased the steady-state NT plasma levels, probably through inhibition of the hydroxylation biotransformation pathway, but had no effect on AT levels, thus indicating that PPZ has no influence on the desmethylation pathway, or alternatively, the hydroxylation of AT.

Twenty-two hospitalized schizophrenic patients, participating in a large-scale phase II double-blind dose-effect study (30, 60, and 120 mg weekly) of penfluridol, a new diphenylbutylpiperidine neuroleptic, were maintained on a regular dosage regimen for 13 wk. Several blood samples were taken during the last dosage interval. Results show that the peak concentration develops within 12 hr after the last dose. A rapid decline, probably due to tissue re-equilibration, then occurs and is followed by a much slower falloff. Detectable concentrations 168 hr after administration are consistent with the long duration of action of penfluridol. Statistically significant differences between doses were found in the analysis of variance of plasma concentrations at all sampling times and in mean steady-state plasm concentrations. Wide differences in plasma concentrations were noted in patients receiving the same absolute dose, but a good relationship was defined between mean steady-state concentration and the dose expressed as mg per either kg of body weight or square meter of body surface area.