Pathologic Considerations and Standardization in Mesothelioma Clinical Trials

The accurate diagnosis of mesothelioma is critical for the appropriate clinical management of this cancer. Many issues complicate making the diagnosis of mesothelioma including the presence of reactive mesothelial cells in benign pleural effusions, the heterogeneity of mesothelioma histopathology, the relatively high incidence of other epithelial malignancies that metastasize to the pleura, and primary sarcomas that arise within the pleura. Given the rapidly evolving field of molecular profiling and the need for translational correlates in mesothelioma clinical trials, the National Cancer Institute (NCI)–International Association for the Study of Lung Cancer–Mesothelioma Applied Research Foundation Clinical Trials Planning Meeting was convened in March 2017 to develop a consensus on standard pathology guidelines for future NCI-sponsored clinical trials in mesothelioma. This consensus statement covers recommendations for specimen handling, pathologic classification and diagnosis, biobanking, and tissue correlative studies.     

Age-dependent alterations in the number,volume, and localization of islands of Calleja within the olfactory tubercle

The incidence of olfactory perceptual dysfunction increases substantially with aging. Putative mechanisms for olfactory sensory loss are surfacing, including neuroanatomical modifications within brain regions responsible for odor information processing. The islands of Calleja (IC) are dense cell clusters localized within the olfactory tubercle, a cortical structure receiving monosynaptic input from the olfactory bulb. The IC are hypothesized to be important for intra- and extra-olfactory tubercle information processing, and thus olfaction. However, whether the anatomy of the IC are affected throughout normal aging remains unclear. By examining the IC of C57bl/6 mice throughout adulthood and early aging (4–18 months of age), we found that the number of IC decreases significantly with aging. Stereological analysis revealed that the remaining IC in 18-month-old mice were significantly reduced in estimated volume compared with those in 4- month-old mice. We additionally found that whereas young adults (4 months of age) possess greater numbers of IC within the posterior parts of the olfactory tubercle, by 18 months of age, a greater percentage of IC are found within the anterior-most part of the olfactory tubercle, perhaps providing a substrate for the differential access of the IC to odor information throughout aging. These results show that the IC are highly plastic components of the olfactory cortex, changing in volume, localization, and even number throughout normal aging. We predict that modifications among the IC throughout aging and age-related neurodegenerative disorders might be a novel contributor to pathological changes in olfactory cortex function and olfactory perception.     

Evidence of Thymus-Independent Local and Systemic Antibody Responses to Cryptosporidium parvum Infection in Nude Mice

Differences in susceptibility to persistent cryptosporidial infection between two strains of adult athymic nude mice prompted us to investigate the immune mechanism(s) that may control resistance to infection in these T-cell-deficient mice. We studied fecal oocyst shedding, serum and fecal parasite-specific antibody responses, and fecal immunoglobulin levels in athymic C57BL/6J nude and athymic BALB/cJ nude mice following oral inoculation with Cryptosporidium parvum oocysts at 8 to 9 weeks of age. C57BL/6J nude mice had significantly higher fecal parasite-specific immunoglobulin A (IgA) (days 27, 31, 35, and 42 postinoculation) and IgM (days 10, 17, 24, 28, 31, 38, 42, and 48 postinoculation) levels than BALB/cJ nude mice (P < 0.05) and significantly higher serum parasite-specific IgA levels at 63 days postinoculation (P < 0.03). Moreover, C57BL/6J nude mice shed significantly fewer C. parvum oocysts than BALB/cJ nude mice from days 52 to 63 postinoculation (P < 0.05). In contrast, BALB/cJ nude mice had higher levels of non-parasite-specific IgA (days 38 to 63 postinoculation) and IgM (days 24, 35, 38, and 52 postinoculation) than C57BL/6J nude mice in feces (P < 0.05). These data suggest that parasite-specific fecal antibodies may be associated with resistance to C. parvum in C57BL/6J nude mice.     

Dermatology in Media: More than Meets the Eye

Dermatologic conditions frequently portrayed in visual art forms are of considerable significance due its influence on public perception of the field. Skin conditions are utilized in television and film to quickly portray character traits to the audience. Most often, these conditions carry negative connotations when attached to characters, being used as visual cues to symbolize immorality, evilness, and unattractiveness. The misrepresentation of dermatologic conditions in film can cause trivialization of skin disease in society. Affected patients, as well as the general public, can suffer as a result of this misinformation. Key words: Dermatology; media; movie; television; film; society

Dermatologic depictions are prevalent in visual broadcast media, including television, movies, and social media, pervading virtually all genres.¹ In turn, film plays an influential role on community sentiment and the perception of dermatology.In film, skin conditions are often depicted realistically (i.e., occurs on an actor without a role in the film) or symbolically. Cinematic plots involving skin may be attractive to film makers due to the perceived ease of conveying symbolic messages and creating memorable impressions in the eyes of the audience.² Many films develop character traits through speech, behavior, and interactions with other characters. However, through symbolic depiction, directors can employ a variety of cutaneous conditions to easily influence viewers and illustrate characters with psychological and psychiatric conditions limited by production constraints.²Most often, symbolic depictions are used to induce sympathy or convey immorality or evilness. In a review performed by Croley et al¹, the dichotomous dermatologic depictions between heroes and villains in film visually illustrate the contrasting morality between these character types. A variety of dermatological conditions are used for this purpose. Classic dermatologic features of villains include facial scars, alopecia, deep rhytides, periorbital hyperpigmentation, rhinophyma, verruca vulgaris, extensive tattoos, large facial nevi, poliosis, and albinism or gray-hued complexions.¹ These foretelling marks are commonly used to represent the villainous character’s inward corruption and troubled past, which in turn serves the purpose of easily instilling fear and apprehension in the audience.Croley et al¹ went on to evaluate the hero-villain skin dichotomy in film by comparing dermatologic findings of the all-time top 10 American film heroes to the all-time top 10 American film villains. The results showed that 0 percent of the heroes and 60 percent of the villainous characters display dermatologic conditions. Most commonly, villains had alopecia (30%), periorbital hyperpigmentation (30%), deep rhytides on the face (20%), multiple scars on the face (20%), verruca vulgaris on the face (20%), and rhinophyma (10%). Darth Vader from "Star Wars" is noted as the ultimate example. When unmasked, he displays gray pallor, periorbital hyperpigmentation, alopecia, and facial scars to externally signify his internal evilness.¹Comedies also employ dermatologic findings as a means to enhance character development. However, instead of symbolizing immorality, comedies more often encourage viewers to laugh about social problems and psychological distress stemming from skin disease.² "Austin Powers in Goldmember" is a striking example, in which the protagonist Austin Powers repeatedly jokes about a minor character with a nevus before having an outburst alluding to his repulsion towards the character’s nevus.Another popular platform which often employs skin disease to represent unattractiveness are television series. Throughout its 10 seasons, the series "Friends" had 199 references to dermatology.⁴ The three dermatologic categories with highest frequencies were hair (91/199, 45.7%), skin growths/pigmented lesions (19/199, 9.6%), and cosmetic products (15/199, 7.5%).⁴ Hair is related to attractiveness numerous times throughout the series. For example, one episode portrays a neighbor who is feared and called a yeti for having long hair and then becomes attractive once he cuts it short. Skin growths and pigmented lesions are the mentioned second most frequently. This group includes references to supernumerary nipples, freckles, moles, and an unknown skin growth. Unattractiveness of this category is displayed by a main character who loses a date due to his supernumerary nipple. Another important dermatologic topic touched on is sunburn and tanning. Ten references made were about tanning throughout the series and each reference portrayed tanning as positive and attractive.⁴     

The effect of recall on estimation of incidence rates for injury in Ghana.

BACKGROUND: Injury is a major public health problem in many developing countries. Due to limitations of vital registry and health service data, surveys are an important tool to obtain information about injury in these countries. The value of such surveys can be limited by incomplete recall. The most appropriate recall period to use in surveys on injury in developing countries has not been well addressed. METHODS: A household survey of injury in Ghana was conducted. Estimated annual non-fatal injury incidence rates were calculated for 12 recall periods (1-12 months prior to the interview, with each successively longer period including the preceding shorter periods). RESULTS: There was a notable decline in the estimated rate from 27.6 per 100 per year for a one-month recall period to 7.6 per 100 per year for a 12-month recall period (72% decline). The extent of this decline was not influenced by age, gender, rural versus urban location, nor by type of respondent (in-person versus proxy). Rate of decline was influenced by severity of injury. Injuries resulting in <7 days of disability showed an 86% decline in estimated rates from a one-month to a 12-month recall period, whereas injuries resulting in > or =30 days of disability showed minimal decline. CONCLUSIONS: In this setting, longer recall periods significantly underestimate the injury rate compared to shorter recall periods. Shorter recall periods (1-3 months) should be used when calculating the overall non-fatal injury incidence rate. However, longer recall periods (12 months) may be safely used to obtain information on the more severe, but less frequent, injuries.     

Response surface methodology for studying the effect of processing conditions on some nutritional and textural properties of bambara groundnuts (Voandzei subterranea) during canning

The response surface methodology and central composite rotatable design for K=3 was used to study the combined effect of blanching, soaking and sodium hexametaphosphate salt concentration on moisture, ash, leached solids, phytates, tannins and hardness of bambara groundnut during canning. Regression models were developed to predict the effects of the processing parameters on the studied indices. Significant interactions were observed between all the factors with high regression coefficients (64.4-82.6%). Blanching and soaking of the seeds prior to canning led to increases in moisture content and leached solids, while significant decreases were observed for phytates, tannins and hardness of the canned bambara groundnuts. Increasing the concentration of sodium salt added during soaking caused significant (P相似文献   

Sulfatase 2 up-regulates glypican 3, promotes fibroblast growth factor signaling, and decreases survival in hepatocellular carcinoma

It has been shown that the heparin-degrading endosulfatase, sulfatase 1 (SULF1), functions as a liver tumor suppressor, but the role of the related sulfatase, sulfatase 2 (SULF2), in liver carcinogenesis remains to be elucidated. We investigated the effect of SULF2 on liver tumorigenesis. Expression of SULF2 was increased in 79 (57%) of 139 hepatocellular carcinomas (HCCs) and 8 (73%) of 11 HCC cell lines. Forced expression of SULF2 increased HCC cell growth and migration, whereas knockdown of SULF2 using short hairpin RNA targeting SULF2 abrogated HCC cell proliferation and migration in vitro. Because SULF1 and SULF2 desulfate heparan sulfate proteoglycans (HSPGs) and the HSPG glypican 3 (GPC3) is up-regulated in HCC, we investigated the effects of SULF2 on GPC3 expression and the association of SULF2 with GPC3. SULF2-mediated cell growth was associated with increased binding of fibroblast growth factor 2 (FGF2), phosphorylation of extracellular signal-regulated kinase and AKT, and expression of GPC3. Knockdown of GPC3 attenuated FGF2 binding in SULF2-expressing HCC cells. The effects of SULF2 on up-regulation of GPC3 and tumor growth were confirmed in nude mouse xenografts. Moreover, HCC patients with increased SULF2 expression in resected HCC tissues had a worse prognosis and a higher rate of recurrence after surgery. Conclusion: In contrast to the tumor suppressor effect of SULF1, SULF2 has an oncogenic effect in HCC mediated in part through up-regulation of FGF signaling and GPC3 expression.