Effect of immunotherapy-infusion time of day on survival of patients with advanced cancers: a study-level meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become the standard of care for numerous malignancies. Emerging evidence suggests that the time of day (ToD) of ICI administration could impact the outcomes of patients with cancer. The consistency of ToD effects on ICI efficacy awaits initial evaluation. MATERIALS AND METHODS: This meta-analysis integrates progression-free survival (PFS) and overall survival (OS) data from studies with a defined 'cut-off' ToD. Hazard ratios (HRs) [95% confidence interval (CI)] of an earlier progression or death according to 'early' or 'late' ToD of ICIs were collected from each report and pooled. RESULTS: Thirteen studies involved 1663 patients (Eastern Cooperative Oncology Group performance status 0-1, 83%; males/females, 67%/33%) with non-small-cell lung cancer (47%), renal cell carcinoma (24%), melanoma (20%), urothelial cancer (5%), or esophageal carcinoma (4%). Most patients received anti-programmed cell death protein 1 or anti-programmed death-ligand 1 (98%), and a small proportion also received anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) (18%). ToD cut-offs were 13:00 or 14:00 (i.e. ICI median infusion time), for six studies, and 16:00 or 16:30 (i.e. reported threshold for weaker vaccination responses) for seven studies. Pooled analyses revealed that the early ToD groups had longer OS (HR 0.50, 95% CI 0.42-0.58; P < 0.00001) and PFS (HR 0.51, 95% CI 0.42-0.61; P < 0.00001) compared with the late ToD groups. CONCLUSIONS: Patients with selected metastatic cancers seemed to largely benefit from early ToD ICI infusions, which is consistent with circadian mechanisms in immune-cell functions and trafficking. Prospective randomized trials are needed to establish recommendations for optimal circadian timing of ICI-based cancer therapies.

Hormones regulating energy homeostasis in breastfeeding versus formula feeding mothers.

To meet energy demands for lactogenesis and to sustain homeostatic conditions post-partum, the organism of breastfeeding mother undergoes combined endocrine and metabolic regulation. The main objective of this study was to determine basal serum concentrations of hormones involved in the maintenance and defense of energy balance in breastfeeding (BF) and formula feeding (FF) mothers. Twenty healthy exclusively breastfeeding mothers at 3rd month of lactation (EBF3), 17 healthy partially breastfeeding at 6th month of lactation (PB6) and 17 healthy FF mothers participated in this study. Fasting serum prolactin (PRL), acylated ghrelin (aGhr), total ghrelin (tGhr), leptin, adiponectin, insulin, and cortisol were determined for all study participants and correlations between studied parameters were calculated for BF women. We found significantly lower basal insulin (p = 0.0048) and cortisol (p = 0.0002) and significantly elevated basal prolactin (p = 0.0020) and leptin (p = 0.0416) in BF when compared with FF women. The differences were not associated with the duration of lactation (3 vs. 6 months), except for PRL, which was highest in EBF3. Levels of Ghr and adiponectin did not differ between study groups. In the BF group, the negative correlations were found between: aGhr and insulin, aGhr and adiponectin, leptin and cortisol, leptin and adiponectin, insulin and adiponectin, cortisol and adiponectin. Positive associations were noted between: insulin and leptin, leptin and aGhr, PRL and leptin, PRL and aGhr. Leptin and insulin correlated positively, whereas adiponectin negatively with BMI. These data may suggest that EBF3 and PB6 as compared with FF mothers, exhibit hormonal regulation which tends to be more advantageous for their metabolic profile and is not related to the duration of breastfeeding within the first 6 months of lactation.

Further characterization of repetitive behavior in C58 mice: developmental trajectory and effects of environmental enrichment.

Aberrant repetitive behaviors are commonly observed in a variety of neurodevelopmental, neurological, and neuropsychiatric disorders. Little is known about the specific neurobiological mechanisms that underlie such behaviors, however, and effective treatments are lacking. Valid animal models can aid substantially in identifying pathophysiological factors mediating aberrant repetitive behavior and aid in treatment development. The C58 inbred mouse strain is a particularly promising model, and we have further characterized its repetitive behavior phenotype. Compared to C57BL/6 mice, C58 mice exhibit high rates of spontaneous hindlimb jumping and backward somersaulting reaching adult frequencies by 5 weeks post-weaning and adult temporal organization by 2 weeks post-weaning. The development of repetitive behavior in C58 mice was markedly attenuated by rearing these mice in larger, more complex environments. In addition to characterizing repetitive motor behavior, we also assessed related forms of inflexible behavior that reflect restricted and perseverative responding. Contrary to our hypothesis, C58 mice did not exhibit increased marble burying nor did they display reduced exploratory behavior in the holeboard task. The C58 strain appears to be a very useful model for the repetitive motor behavior characteristic of a number of clinical disorders. As an inbred mouse strain, studies using the C58 model can take full advantage of the tool kit of modern genetics and molecular neuroscience. This technical advantage makes the model a compelling choice for use in studies designed to elucidate the etiology and pathophysiology of aberrant repetitive behavior. Such findings should, in turn, translate into effective new treatments.

[Health conditions of workers exposed to CS-2 in xanthate plants]. / Badania nad stanem zdrowia zalogi wytwórni ksantogenianów narazonej na dzialanie CS2.

26 men, aged 22-57, with various length of employment in xanthate plant, where they have been exposed to CS2, were subjected to laboratory examinations aiming to find out the effects of this substance on their health state. These studies had been produced by measurements of CS2 concentration in the air of work-posts, lasting for 7 months. This allowed to evaluate the exposure of the subjects and to compare the concentrations with the MAC, actually valid. The obtained results, both in the subjects blood and urine, did not unequivocally indicate any noxious effects of CS2, despite the fact that MAC in the air of working rooms was twice surpassed.