Stimulatory effects of CpG oligodeoxynucleotide on dendritic cell‐based immunotherapy of colon cancer in CEA/HLA‐A2 transgenic mice

Immunostimulatory DNA containing unmethylated cytosine‐guanine (CpG) motifs have been successfully used as adjuvants to enhance the immunity of vaccines designed to trigger antitumor T‐cell responses. We examined the effect of a CpG oligodeoxynucleotide (CpG ODN) for its ability to potentiate the activity of tumor antigen‐pulsed dendritic cells (DC) in a clinically relevant mouse model, which is transgenic for both carcinoembryonic antigen (CEA) and HLA‐A2 for the treatment of colon carcinoma in a therapeutic setting. The systemic administration of CpG ODN 1826 alone had modest effect on tumor growth when tumors were palpable and had no effect with larger tumor burden. However, coadministration of CpG ODN 1826 with the vaccine provided significant increase in tumor‐free survival compared with mice immunized with DC‐based vaccines alone. The DC/CpG combined vaccination strategy resulted in increased secretion of Th1 cytokines and HLA‐A2‐restricted CEA‐specific CTL responses were also enhanced. Both tumor regression and extended tumor‐free survival resulting from DC/CpG combination therapy required the participation of T cells. Tumor‐free mice were resistant to tumor rechallenge and immunity conferred by the vaccine was transferable in athymic nude mice. These results provide evidence that vaccination with antigen‐pulsed DC with CpG ODN as adjuvant can lead to effective tumor regression and long‐term survival in a murine model of colon carcinoma. © 2008 Wiley‐Liss, Inc.     

Treatment of acrodermatitis continua of Hallopeau: A case series of 39 patients

Acrodermatitis continua of Hallopeau (ACH) is a rare chronic inflammatory skin disease. Treatment is extremely challenging and mostly based on empirics as there is only scarce evidence from case reports and few small case series. In this retrospective study, patients with ACH treated at five university medical centers were analyzed according to patient and disease characteristics and treatment experience. We identified 39 patients with ACH with a mean age of 54.4 years at onset, of whom 22 (56.4%) were female. A total of 115 systemic treatment courses were analyzed with methotrexate as the most common therapy (27.0%). Overall, effectiveness of systemic treatments was low (excellent response rate: 14.8%). Among non-biologics, excellent response was noted in 21.1% (4/19) of treatment courses with methotrexate, followed by acitretin (13.3%; 2/15). Among biologics, guselkumab (excellent response: 100%; 2/2), secukinumab (excellent response: 42.9%; 3/7) and adalimumab (excellent response: 20.0%; 2/10) were most efficacious. The median drug survival was 7.0 months and did not differ significantly between the subgroup of non-biologic and biologic therapies. To our knowledge, this is the largest case series in ACH investigating patient characteristics and treatment outcomes. Based on our treatment experience, we suggest a treatment algorithm starting with acitretin or methotrexate as first-line therapy, followed by biologics. Cyclosporin may be used for short-term control. However, none of the applied systemic therapies yielded satisfying efficacy in our cohort. In patients with primary non-response, switch of treatment should be evaluated timely on an individual basis, considering possible irreversible disease complications such as nail loss. More research with prospective design is needed to further evaluate traditional and also particularly newer antipsoriatic drugs in ACH.     

Traumatism and poisoning in Jalisco. An autopsy-based study on mortality

The objective of this study was to obtain better information about deaths labeled as "injuries" in the Mexican state of Jalisco than that reported by official agencies. We reviewed 1989 reports of medical-legal autopsies from the whole state. Deaths were classified in relation to external cause, age, sex and alcohol. It was found that the first five most frequent causes of death by injury were: traffic accidents (14.3 x 100,000), homicides (10.0 x 100,000), other accidents (6.1 x 100,000), accidental asphyxia (3.2 x 100,000) and, suicide (2.3 x 100,000). Four fifths of the deaths were in men. The most affected age group was older than 64 (86.6 x 100,000). The rate of alcohol-related deaths was divided in homicides (51.1%), accidents (26.5%) and, suicides (28.7%), with a statistically significant difference (p less than 0.001). It is concluded that the results of this study are more accurate in their external cause than those obtained through death certificates, and the importance that the registrar's office has for the timely recording and study of injuries is emphasized.     

Adverse metabolic and mental health outcomes associated with shiftwork in a population-based study of 277,168 workers in UK biobank*

Background: Reported associations between shiftwork and health have largely been based on occupation-specific, or single sex studies that might not be generalizable to the entire working population. The objective of this study was to investigate whether shiftwork was independently associated with obesity, diabetes, poor sleep, and well-being in a large, UK general population cohort.

Methods: Participants of the UK Biobank study who were employed at the time of assessment were included. Exposure variables were self-reported shiftwork (any shiftwork and night shiftwork); and outcomes were objectively measured obesity, inflammation and physical activity and self-reported lifestyle, sleep and well-being variables, including mental health.

Results: Shiftwork was reported by 17% of the 277,168 employed participants. Shiftworkers were more likely to be male, socioeconomically deprived and smokers, and to have higher levels of physical activity. Univariately, and following adjustment for lifestyle and work-related confounders, shiftworkers were more likely to be obese, depressed, to report disturbed sleep, and to have neurotic traits.

Conclusions: Shiftwork was independently associated with multiple indicators of poor health and wellbeing, despite higher physical activity, and even in shiftworkers that did not work nights. Shiftwork is an emerging social factor that contributes to disease in the urban environment across the working population.

• Key messages

• Studies have linked shiftwork to obesity and diabetes in nurses and industry workers, but little is known about the implications of shiftwork for the general workforce

• In this large cross sectional study of UK workers, shiftwork was associated with obesity, depression and sleep disturbance, despite higher levels of physical activity.

• Shiftwork was associated with multiple indicators of compromised health and wellbeing and were more likely to report neurotic traits and evening preference

     

Parathion, a cholinesterase-inhibiting plaguicide induces changes in tertiary villi of placenta of women exposed: a scanning electron microscopy study.

The objective of this work was to describe the anatomy of placentas from women who were at risk of exposure to parathion during their pregnancy, when examined with the light and scanning electron microscopes. Twenty term placentas were analyzed; 10 from women living in an agricultural area, who were at risk of exposure to parathion during their pregnancy, and 10 from women living in an urban area, not expressly exposed to pesticides. Each sample was examined with both light and scanning electron microscopes. Cholinesterase activity was significantly reduced in blood from women of the exposed group. In some placentas of women exposed to parathion, recent microinfarctions, microcalcifications and increased deposition of fibrinoid material were seen, along with a larger proportion of atypical characteristics of villi, such as bullous and balloon-like formations with nonhomogeneous surface, and other areas devoid of microvilli. These observations suggest that in chronic exposure to pesticides, the rate of atypical characteristics of placental villi increases, which could be related to changes in the fetus biology. In this study, one newborn from the exposed group showed intrauterine growth retardation and another one, some signs of hypoxia.     

?383 A/C tumor necrosis factor receptor 1 polymorphism and ankylosing spondylitis in Mexicans: a preliminary study

The objective of this study was to evaluate the differences in allele and genotype frequencies of ?383 tumor necrosis factor receptor 1 (TNFR1) polymorphism between ankylosing spondylitis (AS) and controls. Mexican Mestizos with AS were matched by gender, age, and ethnicity with healthy controls and compared in allele and genotype frequencies of the ?383 TNFR1 polymorphism. Polymorphisms were genotyped using PCR–RFLP. The AA genotype occurred at a higher frequency in the AS group (92%) compared with controls (79%, P?=?0.03). A allele was increased in AS (96% vs. 88%, P?=?0.015) and was associated with genetic susceptibility for AS (odds ratio?=?3.48, 95% CI?=?1.23–10.61). This preliminary study is the first assessing the association of the ?383 A/C TNFR1 polymorphism with AS, although it has the limitation of a small sample size. These data are of interest for the genetic epidemiology of AS in the Mexican population, requiring further investigation in other countries.     

Effect of chemotherapy on default mode network connectivity in older women with breast cancer

Brain Imaging and Behavior - Chemotherapy may impair cognition and contribute to accelerated aging. The purpose of this study was to assess the effects of chemotherapy on the connectivity of the...