No paradox, no progress: inverse cancer comorbidity in people with other complex diseases

In the past 5 years, several leading groups have attempted to explain why individuals with Down's syndrome have a reduced risk of many solid tumours and an increased risk of leukaemia and testicular cancer. Niels Bohr, the Danish physicist, noted that a paradox could initiate progress. We think that the paradox of a medical disorder protecting against cancer could be formalised in a new model of inverse cancer morbidity in people with other serious diseases. In this Personal View, we review evidence from epidemiological and clinical studies that supports a consistently lower than expected occurrence of cancer in patients with Down's syndrome, Parkinson's disease, schizophrenia, diabetes, Alzheimer's disease, multiple sclerosis, and anorexia nervosa. Intriguingly, most comorbidities are neuropsychiatric or CNS disorders. We provide a brief overview of evidence indicating genetic and molecular connections between cancer and these complex diseases. Inverse comorbidity could be a valuable model to investigate common or related pathways or processes and test new therapies, but, most importantly, to understand why certain people are protected from the malignancy.     

High prevalence of chronic pelvic pain in women in Ribeirão Preto, Brazil and direct association with abdominal surgery

INTRODUCTION:

Chronic pelvic pain is a disease that directly affects the social and professional lives of women.

OBJECTIVE:

To estimate the prevalence of this clinical condition and to identify independent factors associated with it in women living in Ribeirão Preto, Brazil.

METHODS:

A one-year cross-sectional study was conducted in a population sample of 1,278 women over the age of 14 years. The target population was predominantly composed of women who are treated by the public health system. The questionnaire was administered by interviewers who were not linked to the city health care programs. The prevalence of the morbidity was estimated. First, we identified the significant variables associated with pelvic pain (p<0.10) and then we attributed values of 0 or 1 to the absence or presence of these variables. Logistic regression analysis was used to identify and estimate the simultaneous impact of the independent variables. The results were expressed by odds ratio and their 95% confidence interval with p<0.05.

RESULTS:

The disease was found in 11.5% (147/1,278) of the sample. The independent predictors were dyspareunia, previous abdominal surgery, depression, dysmenorrhea, anxiety, current sexual activity, low back pain, constipation, urinary symptoms, and low educational level.

CONCLUSION:

The prevalence of chronic pelvic pain in Ribeirão Preto is high and is associated with conditions that can usually be prevented, controlled, or resolved by improvement of public health policies and public education.     

Hybrid layer thickness and morphology: Influence of cavity preparation with air abrasion

Dentinal surfaces prepared with air abrasion have considerably different characteristics from those prepared with conventional instruments. Different hybrid layer morphology and thickness occur, which can result in differences in the quality of restorations placed on dentinal surfaces prepared with a diamond bur compared to surfaces prepared using air abrasion. The objective of this study was to compare the hybrid layer thickness and morphology formed utilizing Scotchbond Multi-Purpose Plus (SBMP) on dentin prepared with a diamond bur in a high-speed handpiece and on dentin prepared using air abrasion. Flat dentin surfaces obtained from five human teeth were prepared using each method, then treated with the dentin adhesive system according to manufacturer's instructions. After a layer of composite was applied, specimens were sectioned, flattened, polished, and prepared for scanning electron microscopy. Ten different measurements of hybrid layer thickness were obtained along the bonded surface in each specimen. SBMP produced a 3.43 ± 0.75 μm hybrid layer in dentin prepared with diamond bur. This hybrid layer was regular and found consistently. In the air abrasion group, SBMP produced a 4.94 ± 1.28 μm hybrid layer, which was regular and found consistently. Statistical ANOVA (P = 0.05) indicated that there was a statistically significant difference between the groups. These data indicate that the air abrasion, within the parameters used in this study, provides a thick hybrid layer formation.     

The role of obesity as a modifying factor in patients undergoing non-surgical periodontal therapy

Background: Earlier studies have shown an association between obesity and periodontitis, which is mediated by cytokine production. The aim of this study is to assess the role of obesity as a modifying factor on periodontal clinical parameters and on circulating proinflammatory cytokine levels in subjects undergoing non‐surgical periodontal treatment. Methods: Twenty‐seven obese subjects and 25 normal‐weight subjects were enrolled in this study. Subjects in both groups had generalized chronic periodontitis. The periodontal parameters measured before and 3 months after non‐surgical periodontal therapy were: visible plaque index, bleeding gingival index, bleeding on probing, probing depth, and clinical attachment level. In addition, subjects underwent anthropometric measurements and serum analyses of fasting glucose, glycated hemoglobin, interleukin‐1β, interleukin‐6, tumor necrosis factor‐α, and interferon‐γ. Results: Periodontal therapy significantly decreased visible plaque index, bleeding gingival index, bleeding on probing, probing depth of 4 to 6 mm, probing depth ≥7 mm, clinical attachment level of 4 to 6 mm, and clinical attachment level ≥7 mm in both groups (P ≤0.05). Circulating proinflammatory cytokines significantly decreased in obese and normal‐weight subjects after periodontal treatment (P ≤0.05). However, interleukin‐6 and tumor necrosis factor‐α levels remained higher in obese subjects 3 months after treatment (P ≤0.05). Conclusion: Obesity does not seem to play a negative role by interfering in the improvement of the periodontal clinical response or decreasing circulating proinflammatory cytokine levels after periodontal treatment.     

Immunogenic characterization and epitope mapping of transmissible gastroenteritis virus RNA dependent RNA polymerase

Coronavirus RNA synthesis is a sophisticated process performed by a viral multienzymatic replicase complex, together with cellular factors. A key enzyme of this replication complex is the RNA dependent RNA polymerase (RdRp). To study the replication of coronavirus genome, six monoclonal antibodies (mAbs) specific for transmissible gastroenteritis virus (TGEV) RdRp were generated and characterized. His-tagged RdRp was expressed in baculovirus, purified and used as immunogen to produce mAbs. The TGEV RdRp was recognized by these mAbs in the context of virus infection by immunofluorescence analysis and Western blot. Epitope mapping by Pepscan indicated that RdRp mAbs recognized four non-overlapping linear epitopes located in a 62-amino acid region of the N-terminal domain, suggesting that this region may constitute an immunodominant domain. The availability of TGEV RdRp mAbs will be instrumental to study coronavirus replication and to analyze the function of RdRp in pathogenesis.     

The African swine fever virus lectin EP153R modulates the surface membrane expression of MHC class I antigens

We have modeled a 3D structure for the C-type lectin domain of the African swine fever virus protein EP153R, based on the structure of CD69, CD94 and Ly49A cell receptors, and this model predicts that a dimer of EP153R may establish an asymmetric interaction with one MHC-I molecule. A functional consequence of this interaction could be the modulation of MHC-I expression. By using both transfection and virus infection experiments, we demonstrate here that EP153R inhibits MHC-I membrane expression, most probably by impairing the exocytosis process, without affecting the synthesis or glycosylation of MHC antigens. Interestingly, the EP153-mediated control of MHC requires the intact configuration of the lectin domain of the viral protein, and specifically the R133 residue. Interference of EP153R gene expression during virus infection and studies using virus recombinants with the EP153R gene deleted further support the inhibitory role of the viral lectin on the expression of MHC-I antigens.     

Interplay among cellular polarization, lipoprotein metabolism and hepatitis C virus entry

Hepatitis C virus (HCV) infects more than three million new individuals worldwide each year. In a high percent age of patients, acute infections become chronic, eventually progressing to fibrosis, cirrhosis, and hepatocellular carcinoma. Given the lack of effective prophylactic or therapeutic vaccines, and the limited sustained virological response rates to current therapies, new approaches are needed to prevent, control, and clear HCV infection.Entry into the host cell, being the first step of the viral cy...