Environmental enrichment augments the efficacy of idiotype vaccination for B-cell lymphoma

Environmental enrichment is known to positively influence the organism's psychologic and physiologic well-being. However, the effects of environmental enrichment on immune responses and cancer prognosis have not been clearly established and its impact on cancer therapy is unknown. Here, we report that environmental enrichment mediated a statistically significant improvement of the outcome of immunotherapy in an experimental model of B-cell lymphoma. When mice were immunized with an idiotype-vaccine, those maintained under enriched environmental conditions produced statistically significant higher levels of anti-idiotype antibodies and revealed more attenuated tumor growth than those housed in standard environments. Most strikingly, enriched tumor-bearing mice had statistically significant prolonged survival, with 44% of them disease-free compared with 0% in the standard rearing tumor-bearing mice. The possible mechanisms for the enhancement of immunotherapy by environmental enrichment are cognitive, physical activity, and psychologic. The demonstration of synergistic effect of cancer therapy and environmental enrichment on tumor rejection has important implication for cancer treatment.     

Cyclic adenosine 3'',5''-monophosphate inhibits the availability of arachidonate to prostaglandin synthetase in human platelet suspensions.

When thrombin is added to washed human platelets, one of its actions results in activation of a phospholipase that hydrolyzes arachidonic acid from phospholipids. The arachidonate is converted to the cyclic endoperoxides (prostaglandin G2 and prostaglandin H2) by fatty acid cyclo-oxygenase. These compounds are then converted to thromboxane A2, also called rabbit aorta-contracting substance, by thromboxane synthetase. These labile, pharmacologically active compounds then break down to inactive products including thromboxane B2 and malonaldehyde. Incubation of platelets with either dibutyryl cyclic adenosine 3',5'-monophosphate (dBcAMP) or prostaglandin E1 (PGE1) before thrombin addition blocks the subsequent formation of oxygenated products of arachidonic acid including thromboxane A2, thromboxane B2, and malonaldehyde. In contrast, when arachidonic acid is added directly to platelets, prior incubation with dBcAMP or PGE1 does not inhibit production of the prostaglandins or their metabolites. Thrombin treatment of platelets also blocks the acetylation of cyclo-oxygenase by aspirin since the hydrolyzed arachidonic acid competes with aspirin for the active site on cyclo-oxygenase. Prior treatment of platelets with dBcAMP or PGE1 reverses the thrombin inhibition of the acetylation of cyclo-oxygenase. We conclude that agents which elevate platelet cAMP levels inhibit the hydrolysis of arachidonic acid from platelet phospholipids. We also find that prostaglandin synthesis can be dissociated, in part, from platelet aggregation and release, and that cAMP has separate actions on these processes. Higher thrombin concentrations are required to stimulate prostaglandin synthesis (0.05-2 U/ml) than are required to induce [14C]serotonin release (0.02-0.1 U/ml). Furthermore, dBcAMP and PGE1 both inhibit platelet aggregation induced by either arachidonic acid or prostaglandin H2 without affecting the production of prostaglandin metabolites from these compounds.     

Vascular health and longitudinal changes in brain and cognition in middle-aged and older adults

The impact of vascular health on the relations between structural brain changes and cognition was assessed in a longitudinal study of 46 adults, 23 of whom remained healthy for 5 years and 23 of whom had hypertension at baseline or acquired vascular problems during follow-up. At both measurement occasions, the volume of white matter hyperintensities (WMH) and regional brain volumes correlated with age. In 5 years, WMH volume more than doubled in the vascular risk group but did not increase in healthy participants. The frontal lobes had the highest WMH load at baseline and follow-up; the parietal WMH showed the greatest rate of expansion. In the vascular risk group, systolic blood pressure at follow-up correlated with posterior WMH volume. The fastest cortical shrinkage was observed in the prefrontal cortex and the hippocampus. Fluid intelligence correlated with WMH burden and declined along with faster WMH progression. In the vascular risk group, WMH progression and shrinkage of the fusiform cortex correlated with decline in working memory. Thus, poor vascular health contributes to age-related declines in brain and cognition, and some of the age-related declines may be limited to persons with elevated vascular risk.     

Clinical predictors and risk factors for vaginal mesh extrusion

Purposes

Our study aims to enhance the accuracy of the clinical diagnosis in patients with vaginal mesh extrusion following transvaginal mesh placement for pelvic organ prolapse using significant clinical parameters and risk factors.

Methods

All patients who underwent vaginal mesh removal were retrospectively reviewed from January 2000 to May 2014. Eligible patients were divided into two groups according to the presence of vaginal mesh extrusion.

Results

A total of 862 patients, 798 were included. 357 (44.7%) had evidence of vaginal mesh extrusion, and 441 (55.3%) had no evidence of vaginal mesh extrusion. The mean age of the vaginal mesh extrusion group was slightly higher than in the group without vaginal mesh extrusion (58.7 ± 11.2 vs. 56.4 ± 11.5, respectively; p = 0.002). From multivariate analysis, the significant clinical correlations for vaginal mesh extrusion were vaginal bleeding [60 (16.9) vs. 14 (3.2%), p < 0.001], hispareunia [48 (13.5) vs. 15 (3.4%), OR = 4.163, p < 0.001], and vaginal discharge [45 (12.6) vs. 18 (4.1%), p = 0.001]. The risk factors were multiple mesh implantations [218 (67.06) vs. 175 (39.68%), p < 0.001] and menopause [314 (88) vs. 364 (82.7%), p = 0.145]. Demographic data, including BMI, sexual activity, vaginal atrophy, both local and systemic hormonal use, smoking status, and hysterectomy status, were not significantly different, as well as the clinical symptoms including dyspareunia, vaginal infection, and symptomatic vaginal bulge.

Conclusions

Vaginal bleeding, hispareunia, and vaginal discharge were the most significant clinical predictors for raising suspicion of vaginal mesh extrusion. Multiple mesh implantations were a significant risk factor for extrusion.

     

Interleukin-1 antagonizes morphine analgesia and underlies morphine tolerance

Pain sensitivity reflects a balance between pain facilitatory and inhibitory systems. To characterize the relationships between these systems we examined the interactions between the analgesic effects of morphine and the anti-analgesic effects of the pro-inflammatory cytokine interleukin-1 (IL-1). We report that administration of a neutral dose of IL-1beta abolished morphine analgesia in mice, whereas acute or chronic blockade of IL-1 signaling by various IL-1 blockers (IL-1 receptor antagonist (IL-1ra), alpha-melanocyte-stimulating hormone, or IL-1 tri-peptide antagonist) significantly prolonged and potentiated morphine analgesia. Morphine-induced analgesia was also extended in strains of mice genetically impaired in IL-1 signaling (mice with transgenic over-expression of IL-1 receptor antagonist, deletion of the IL-1 receptor type I, or deletion of the IL-1 receptor accessory protein). The finding that IL-1 produces a marked anti-analgesic effect, suggests that it may also be involved in the development of opiate tolerance. Indeed, genetic or pharmacological blockade of IL-1 signaling prevented the development of tolerance following repeated morphine administration. Moreover, acute administration of IL-1ra in wild type mice, either immediately following the cessation of acute morphine analgesia, or following the development of chronic morphine tolerance, re-instated the analgesia, suggesting that blockade of the IL-1 system unmasks the analgesic effect of morphine. These findings suggest that morphine produces an IL-1-mediated homeostatic response, which serves to limit the duration and extent of morphine analgesia and which underlies the development of tolerance.     

Trained Memory of Human Uterine NK Cells Enhances Their Function in Subsequent Pregnancies

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Single-dose fosfomycin trometamol versus 5-day cephalexin regimen for treatment of uncomplicated lower urinary tract infections in women.

A randomized study was conducted to assess the clinical and microbiological efficacies of a single 3-g dose of fosfomycin trometamol for the treatment of uncomplicated lower urinary tract infections in women compared with a 5-day regimen of cephalexin at 0.5 g four times daily. One hundred twelve women, all of whom had documented infections with bacteria sensitive to both antibiotics, were included. Fifty-eight women received fosfomycin trometamol, and 54 women received cephalexin. The two groups did not differ in age, severity, or duration of current urinary tract infection, menstrual status, sexual activity, or use of contraceptives. Ninety percent of pathogens in the fosfomycin trometamol group and 81% in the cephalexin group were Escherichia coli (the difference is not significant [NS]). A clinical evaluation at the 5-day follow-up showed that 91% of the women in each group were free of symptoms, while five women in each group were considered therapy failures and were treated by another antibiotic course. A microbiological evaluation at the 5-day follow-up showed a 91% eradication rate in the fosfomycin trometamol group and an 83% eradication rate in the cephalexin group (NS). At the 1-month follow-up, a clinical evaluation demonstrated prolonged resolution in 86 and 78%, respectively, of the participating women (NS). A microbiological evaluation at 1 month demonstrated prolonged eradication in 47 (81%) women treated with fosfomycin trometamol and in 37 (68%) women treated with cephalexin (NS). Three and six women, respectively, had relapsed. No adverse reactions were reported by the fosfomycin trometamol-treated women, while three women treated with cephalexin reported mild adverse reactions but completed the study period. Fosfomycin trometamol in a single 3-g dose is as effective as a 5-day regimen of cephalexin for the treatment of uncomplicated lower urinary tract infection in women.     

Amiodarone pulmonary toxicity presenting as a solitary lung mass

Following treatment with amiodarone, a patient developed weight loss, fatigue and severe myopathy, without respiratory symptoms. A solitary lung infiltrate, impaired thyroid and liver function tests, and leukocytosis were evident. Biopsies from the lung lesion, liver, and bone marrow revealed foam cells. All these signs and symptoms subsided following cessation of amiodarone therapy. It is demonstrated that amiodarone may induce a localized lung lesion rather than diffuse pulmonary disease.     

Dietary Changes and Anxiety during the Coronavirus Pandemic: Differences between the Sexes

The SARS-CoV-2 (COVID-19) pandemic has been associated with both increased anxiety, deterioration in diet and weight gain. These associations may differ by sex. The present report examines differences by sex in diet quality in order to determine whether associations between diet and psychological stress during the initial phase of the COVID-19 pandemic differed by sex. This online study is available internationally in seven languages. The Mediterranean Diet Score was used to measure diet quality, while the General Anxiety Disorder 7-point scale (GAD-7) was used to measure anxiety. Findings were compared by self-reported sex (male vs. female). A total of 3797 respondents provided informed consent and met eligibility criteria, of whom 526 women were omitted due to being pregnant or six months or less post-partum, or due to reproductive status not being reported. Thus, 3271 individuals are included in the present report, of whom 71.2% were women. The median age of women was 30 (interquartile range (IQR) = 16) years vs. 31 (IQR = 19) years, p = 0.079. The median diet quality score was 9 (IQ = 3) in both women and men (p = 0.75). Despite the overall similarity in diet score, several components of the score differed significantly by sex. Women reported consuming significantly more olive oil, daily servings of vegetables, and weekly servings of sweet baked goods. Men reported consuming significantly more sweetened/carbonated drinks, red meat, alcohol, legumes, and hummus/tahini. Women reported a GAD-7 score of 6 (IQR = 8), while men reported 3 (6), p < 0.001. An inverse association was detected between the Mediterranean diet score and the GAD-7 score in both women (rho = −0.166, p < 0.001) and men (rho = −0.154, p < 0.001), and the correlation coefficients did not differ by sex (p = 0.76). Mediterranean diet score and age both reduced the odds of elevated anxiety (GAD-7 ≥ 10), while female sex, deterioration of diet quality during the outbreak, unemployment, and completing the survey in English increased the odds of this outcome. During the COVID-19 lockdowns, overall diet quality did not differ by sex; however, some differences by sex in components of the total score were detected. Moderate to severe anxiety was positively associated with female sex and poorer diet quality even after controlling for age, employment status, and the language in which the survey was performed.