Cribriform-Morular Variant of Papillary Thyroid Carcinoma: Ultrastructural Study and Somatic/Germline Mutation Analysis of the APC Gene

Cribriform-morular variant of papillary carcinoma is a distinctive histological variant of thyroid cancer, characterized by intermingled cribriform, follicular, papillary, trabecular, and morular architecture. These tumors are known to be associated with familial adenomatous polyposis (FAP), but are also encountered in non-FAP patients. The authors report on ultrastructural and genetic studies of 3 patients with this type of carcinoma-associated FAP. There were numerous microfilaments approximately 100?nm long at the nuclear clearing area of the morular regions. Two of the 3 patients showed germline APC mutations, and 1 had so somatic APC mutation. Both mutations were in previously unreported regions. The study provides new information for understanding the development of this rare tumor.     

A tomato-rich diet is related to depressive symptoms among an elderly population aged 70 years and over: A population-based,cross-sectional analysis

BackgroundEnhanced oxidative stress or defective anti-oxidant defenses are related to the pathogenesis of depressive symptoms. Lycopene is the most powerful antioxidant amongst the carotenoids. The aim of this study was to investigate the relationship between different vegetables, including tomatoes/tomato products (a major source of lycopene), and depressive symptoms in a community-based elderly population.MethodsWe analyzed a cross-sectional survey including 986 community-dwelling elderly Japanese individuals aged 70 years and older. Dietary intake was assessed using a valid self-administered diet-history questionnaire, and depressive symptoms were evaluated using the 30-item Geriatric Depression Scale with 2 cut-off points: 11 (mild and severe) and 14 (severe) or use of anti-depressive agents.ResultsThe prevalence of mild and severe and severe depressive symptoms was 34.9% and 20.2%, respectively. After adjustments for potentially confounding factors, the odds ratios of having mild and severe depressive symptoms by increasing levels of tomatoes/tomato products were 1.00, 0.54, and 0.48 (p for trend <0.01). Similar relationships were also observed in the case of severe depressive symptoms. In contrast, no relationship was observed between intake of other kinds of vegetables and depressive symptoms.LimitationsThis is a cross-sectional study, and not for making a clinical diagnosis of depressive episodes.ConclusionsThis study demonstrated that a tomato-rich diet is independently related to lower prevalence of depressive symptoms. These results suggest that a tomato-rich diet may have a beneficial effect on the prevention of depressive symptoms. Further studies are needed to confirm these findings.     

Using a High-Speed Movie Camera to Evaluate Slice Dropping in Clinical Image Interpretation with Stack Mode Viewers

The purpose of this study is to verify objectively the rate of slice omission during paging on picture archiving and communication system (PACS) viewers by recording the images shown on the computer displays of these viewers with a high-speed movie camera. This study was approved by the institutional review board. A sequential number from 1 to 250 was superimposed on each slice of a series of clinical Digital Imaging and Communication in Medicine (DICOM) data. The slices were displayed using several DICOM viewers, including in-house developed freeware and clinical PACS viewers. The freeware viewer and one of the clinical PACS viewers included functions to prevent slice dropping. The series was displayed in stack mode and paged in both automatic and manual paging modes. The display was recorded with a high-speed movie camera and played back at a slow speed to check whether slices were dropped. The paging speeds were also measured. With a paging speed faster than half the refresh rate of the display, some viewers dropped up to 52.4 % of the slices, while other well-designed viewers did not, if used with the correct settings. Slice dropping during paging was objectively confirmed using a high-speed movie camera. To prevent slice dropping, the viewer must be specially designed for the purpose and must be used with the correct settings, or the paging speed must be slower than half of the display refresh rate.     

Evaluation of Malignant Breast Lesions Using High-resolution Readout-segmented Diffusion-weighted Echo-planar Imaging: Comparison with Pathology

Purpose:We aimed to investigate the performance of high resolution-diffusion-weighted imaging (HR-DWI) using readout-segmented echo-planar imaging in visualizing malignant breast lesions and evaluating their extent, using pathology as a reference.Methods:This retrospective study included patients who underwent HR-DWI with surgically confirmed malignant breast lesions. Two radiologists blinded to the final diagnosis evaluated HR-DWI independently and identified the lesions, measuring their maximum diameters. Another radiologist confirmed if those lesions were identical to the pathology. The maximum diameters of the lesions between HR-DWI and pathology were compared, and their correlations were calculated using Spearman’s correlation coefficient. Apparent diffusion coefficient (ADC) values of the lesions were measured.Results:Ninety-five mass/64 non-mass lesions were pathologically confirmed in 104 females. Both radiologists detected the same 93 mass lesions (97.9%). Spearman’s correlation coefficient for mass lesions were 0.89 and 0.90 (P < 0.0001 and 0001) for the two radiologists, respectively. The size differences within 10 mm were 90.3% (84/93) and 94.6% (88/93) respectively. One radiologist detected 35 non-mass lesions (54.7%) and another radiologist detected 32 non-mass lesions (50.0%), of which 28 lesions were confirmed as identical. Spearman’s correlation coefficient for non-mass lesions were 0.59 and 0.22 (P = 0.0002 and 0.22), respectively. The mean ADC value of mass lesions and non-mass lesions were 0.80 and 0.89 × 10⁻³ mm²/s, respectively.Conclusion:Using HR-DWI, malignant mass lesions were depicted with excellent agreement with the pathological evaluation. Approximately half of the non-mass lesions could not be identified, suggesting a current limitation of HR-DWI.     

Single serum cortisol values at 09:00 h can be indices of adrenocortical function in children with Kawasaki disease treated with intravenous immunoglobulin plus prednisolone

Combination treatment with intravenous immunoglobulin (IVIG) plus prednisolone is effective for prevention of cardiovascular complications in children with Kawasaki disease (KD). However, administration of prednisolone for approximately 20 d in this regimen causes adrenocortical suppression in a high proportion of treated children. To establish a simple method to screen for this suppression, we performed a prospective study on 72 children with KD treated with this regimen in our institution from February 2012 to March 2014. By performing ROC analysis of 21 initial patients treated between February and June 2012, a serum cortisol value at 09:00 h of 5 mcg/dL was established as a threshold for intact adrenocortical function, which is equivalent to a peak serum cortisol value of higher than 15 mcg/dL in the CRH stimulation test. Then, we applied this screening test to 51 subsequent patients treated between July 2012 and March 2014. Approximately 90% of the patients with morning serum cortisol values above 5 mcg/dL 2 to 6 mo after the cessation of initial prednisolone treatment had peak serum cortisol values exceeding 15 mcg/dL, suggesting the efficacy of this approach.     

Natural resistance to worms exacerbates bovine tuberculosis severity independently of worm coinfection

Pathogen interactions arising during coinfection can exacerbate disease severity, for example when the immune response mounted against one pathogen negatively affects defense of another. It is also possible that host immune responses to a pathogen, shaped by historical evolutionary interactions between host and pathogen, may modify host immune defenses in ways that have repercussions for other pathogens. In this case, negative interactions between two pathogens could emerge even in the absence of concurrent infection. Parasitic worms and tuberculosis (TB) are involved in one of the most geographically extensive of pathogen interactions, and during coinfection worms can exacerbate TB disease outcomes. Here, we show that in a wild mammal natural resistance to worms affects bovine tuberculosis (BTB) severity independently of active worm infection. We found that worm-resistant individuals were more likely to die of BTB than were nonresistant individuals, and their disease progressed more quickly. Anthelmintic treatment moderated, but did not eliminate, the resistance effect, and the effects of resistance and treatment were opposite and additive, with untreated, resistant individuals experiencing the highest mortality. Furthermore, resistance and anthelmintic treatment had nonoverlapping effects on BTB pathology. The effects of resistance manifested in the lungs (the primary site of BTB infection), while the effects of treatment manifested almost entirely in the lymph nodes (the site of disseminated disease), suggesting that resistance and active worm infection affect BTB progression via distinct mechanisms. Our findings reveal that interactions between pathogens can occur as a consequence of processes arising on very different timescales.

Interactions between pathogens cooccurring within a single host can have profound effects on infection outcomes, ranging from the severity of clinical disease in individual hosts to the rate of disease spread across populations (1–3). Because most hosts are commonly infected by more than one type of pathogen at a time (4), understanding the consequences of pathogen interactions during concurrent infection (or coinfection) is essential for effective disease management and control. While many studies focus on pathogen interactions that are the result of one pathogen responding to the simultaneous presence of another (5), two pathogens need not overlap in time to interact with one another. For example, heterologous immunity, where prior exposure or infection with one pathogen modifies the immune response to another, can drive both positive and negative interactions between pathogens (6). This phenomenon highlights how modifications of the host immune system by one pathogen that occur during the lifetime of a host (i.e., in ecological time) can shape future responses to secondary pathogens. Likewise, strong selection pressure imposed by pathogens on hosts, particularly on immune function (7), can result in modifications of the host immune system that occur over generations (i.e., in evolutionary time), a process which should also affect responses to secondary infections. In this case, a historical population-level response to selection by one pathogen may generate heritable differences among individuals in contemporary responses to another. Crucially, ecological- vs. evolutionary-scale interactions between pathogens may operate for different reasons, so distinguishing between the two is integral to understanding both the mechanistic basis and consequences of these interactions.Helminths, or parasitic worms, and tuberculosis (TB) are involved in one of the most geographically extensive of pathogen interactions (2, 8). Both pathogens affect approximately one-third of the world’s human population and are widespread in domestic and wild animals (9–11). Caused by bacteria in the Mycobacterium tuberculosis complex, including M. tuberculosis (Mtb), the causative agent of human TB, and Mycobacterium bovis (Mb), the causative agent of bovine TB, TB is responsible for 2 million human deaths (12) and 25% of all disease-related cattle deaths (13) annually. In humans, about 10% of individuals infected with Mtb progress to active pulmonary disease, but the mechanisms underlying progression to active TB are poorly defined (14). Accumulating evidence suggests that coinfection with worms may be a factor in TB disease progression (2, 15), although some studies do not support this link, highlighting the complex nature of worm–TB interactions (16). Interestingly, research in laboratory animals suggests that enhanced immunity (i.e., resistance) to worms can compromise a host’s ability to control TB even in the absence of active worm infection (17–20), implying that evolved defenses against worms may independently affect the response to TB. Considered in light of widespread worm resistance in human and animal populations (21, 22) and the broad geographic coincidence of worms and TB, worm–TB interactions may represent an illustrative case where variation in evolved resistance to one pathogen (worms) contributes to variable responses to another (TB).In this study, we tested the hypothesis that resistance to worms modifies the host response to TB. To do this, we monitored gastrointestinal (GI) worm (specifically strongyle nematode) and Mb infections in a cohort of wild African buffalo (Syncerus caffer) to assess the effects of natural variation in worm resistance on the incidence, severity, and progression of bovine TB (BTB). In previous work, we demonstrated the presence of an ecological interaction between worms and BTB in buffalo by showing that clearance of active worm infection via anthelmintic treatment reduces BTB-associated mortality (23). Thus, we took advantage of the fact that half of our study animals were subject to long-term deworming to compare the relative effects of worm coinfection vs. natural worm resistance on BTB outcomes. We found evidence of a genetic basis to worm resistance in buffalo and that buffalo with resistance to worms were more severely affected by BTB in terms of both mortality risk and disease progression. However, the mechanisms by which natural variation in the host response to worms was associated with BTB progression appeared to be distinct from the effects of anthelmintic treatment. Our results suggest that negative effects of worms on BTB outcomes occur as a result of both concurrent worm infection and genetically based differences in host responsiveness to worms. This discovery fundamentally alters our understanding of the timescales over which worms and TB interact in real-world populations.