Physical functioning and risk for sleep disorders in US adults: results from the National Health and Nutrition Examination Survey 2005-2014.

OBJECTIVES: Sleep disorders (SDs), particularly problems with falling asleep or daytime sleepiness, have negative impact on health and longevity. Sleep deprivation is also associated with a decline in physical functioning (PF) that mediates the ability to perform activities of daily living. But it remains unknown if deterioration in PF can predict the risk of having a SD. Therefore, the purpose of the present study is to assess the risk of SD associated with PF status in the US adult population. STUDY DESIGN: Cross-sectional study design with data from the National Health and Nutrition Examination Survey from year 2005 to year 2014. METHODS: PF limitation is assessed by reported difficulty in performing 10 tasks selected from PF questionnaire. SD is identified by subjective description of presence of doctor diagnosed SD. Also, five categories of comorbidities that caused difficulty in carrying out these tasks were created. RESULTS: The adults with self-reported PF limitation have 41% higher odds of having a SD (odds ratio [OR] = 1.41, 95% confidence interval [CI] = 1.22-1.59). Moreover, participants having cognitive problems and cardiovascular and pulmonary disorders as secondary conditions that cause difficulty in PF have 145% and 28% higher odds (OR = 2.45 and 1.28; 95% CI = 2.01-3.01 and 1.08-1.53, respectively) of having a SD. Also, females have a 27% lower odds of having a SD than males (OR = 0.73, 95% CI = 0.63-0.83). CONCLUSION: Risk for SD is associated with increasing level of functional disability. We advocate the importance of engagement in physical activities to prevent or delay the onset of SD.

Patterns and risk factors for locoregional failures after mastectomy for breast cancer: an International Breast Cancer Study Group report.

BACKGROUND: Rates and risk factors of local, axillary and supraclavicular recurrences can guide patient selection and target for postmastectomy radiotherapy (PMRT). PATIENTS AND METHODS: Local, axillary and supraclavicular recurrences were evaluated in 8106 patients enrolled in 13 randomized trials. Patients received chemotherapy and/or endocrine therapy and mastectomy without radiotherapy. Median follow-up was 15.2 years. RESULTS: Ten-year cumulative incidence for chest wall recurrence of >15% was seen in patients aged <40 years (16.1%), with ≥4 positive nodes (16.5%) or 0-7 uninvolved nodes (15.1%); for supraclavicular failures >10%: ≥4 positive nodes (10.2%); for axillary failures of >5%: aged <40 years (5.1%), unknown primary tumor size (5.2%), 0-7 uninvolved nodes (5.2%). In patients with 1-3 positive nodes, 10-year cumulative incidence for chest wall recurrence of >15% were age <40, peritumoral vessel invasion or 0-7 uninvolved nodes. Age, number of positive nodes and number of uninvolved nodes were significant parameters for each locoregional relapse site. CONCLUSION: PMRT to the chest wall and supraclavicular fossa is supported in patients with ≥4 positive nodes. With 1-3 positive nodes, chest wall PMRT may be considered in patients aged <40 years, with 0-7 uninvolved nodes or with vascular invasion. The findings do not support PMRT to the dissected axilla.

Transmission dynamics of the amphibian ranavirus Ambystoma tigrinum virus.

Transmission is central to pathogen fitness and strongly influences the impact of pathogens on host populations. Particularly important to transmission dynamics is the distinction between direct transmission requiring close physical contact (e.g. bumping, fighting, or coughing) and indirect transmission from environmental sources such as contaminated substrates. We present data from 4 experiments addressing the form, routes, and timing of transmission of Ambystoma tigrinum virus (ATV) among tiger salamanders Ambystoma tigrinum nebulosum. Our data suggest that ATV is efficiently transmitted by direct interactions between live animals (bumping, biting and cannibalism) as well as by necrophagy and indirectly via water and fomites. Determining which form of transmission is most important in nature is essential for understanding transmission at the population level. Our experiments also revealed an important temporal aspect of infectiousness: larval salamanders become infectious soon after exposure to ATV and their propensity to infect others increases with time. These results begin to clarify the mechanisms and dynamics of ATV transmission and lead to key questions that need to be addressed in future research.

Evidence for emergence of an amphibian iridoviral disease because of human-enhanced spread.

Our understanding of origins and spread of emerging infectious diseases has increased dramatically because of recent applications of phylogenetic theory. Iridoviruses are emerging pathogens that cause global amphibian epizootics, including tiger salamander (Ambystoma tigrinum) die-offs throughout western North America. To explain phylogeographical relationships and potential causes for emergence of western North American salamander iridovirus strains, we sequenced major capsid protein and DNA methyltransferase genes, as well as two noncoding regions from 18 geographically widespread isolates. Phylogenetic analyses of sequence data from the capsid protein gene showed shallow genetic divergence (< 1%) among salamander iridovirus strains and monophyly relative to available fish, reptile, and other amphibian iridovirus strains from the genus Ranavirus, suggesting a single introduction and radiation. Analysis of capsid protein sequences also provided support for a closer relationship of tiger salamander virus strains to those isolated from sport fish (e.g. rainbow trout) than other amphibian isolates. Despite monophyly based on capsid protein sequences, there was low genetic divergence among all strains (< 1.1%) based on a supergene analysis of the capsid protein and the two noncoding regions. These analyses also showed polyphyly of strains from Arizona and Colorado, suggesting recent spread. Nested clade analyses indicated both range expansion and long-distance colonization in clades containing virus strains isolated from bait salamanders and the Indiana University axolotl (Ambystoma mexicanum) colony. Human enhancement of viral movement is a mechanism consistent with these results. These findings suggest North American salamander ranaviruses cause emerging disease, as evidenced by apparent recent spread over a broad geographical area.

Who is not reassured following benign diagnosis of breast symptoms?

UNLABELLED: Many women fail to be reassured about their breast symptom following benign diagnosis. Identification of the factors contributing to this continued anxiety is important in order that appropriate intervention can be incorporated into the care of women undergoing diagnosis. In this study, we measured levels of anxiety, depression, stress, perceived personal risk of breast cancer, fear of breast cancer treatment and general health anxiety along with clinical and demographic variables in women undergoing investigation of breast symptoms. We then assessed if these factors were associated with reassurance about the breast symptom immediately following benign diagnosis. METHODS: Women attending a specialist 'one-stop' breast clinic completed a questionnaire in the clinic prior to diagnosis and a reassurance measure post-benign breast symptom diagnosis. RESULTS: Post-diagnosis, 67% of women were reassured however, 33% were not reassured about their breast symptom despite a benign diagnosis. Women who were not reassured were more likely to be educated only to high school level and have presenting symptoms of a change in breast shape/dimpling of the breast. There was a trend for women who were not reassured to have breast pain and be diagnosed with a benign breast cyst. Examination of the psychological variables showed that women who were not reassured compared to reassured women had higher levels of health anxiety, perceived stress, fear of breast cancer treatment and general anxiety. Logistic regression analysis entering all the predictors suggests that level of education was the strongest predictor of lack of reassurance following benign diagnosis. CONCLUSION: This study found that a significant proportion of women who undergo investigation and receive a benign diagnosis of their breast symptom experience uncertainty. Our finding that women who were not reassured were more likely to be educated only to high school level suggests that this group may benefit from additional information about breast symptoms and benign diagnosis. Additionally, our results indicate that women with high levels of anxiety, perceived stress and general worry about their health may need further reassurance in the immediate diagnosis phase. Further research focussing on how reassurance is interpreted in the context of women's perceptions about breast symptoms and breast disease is important so that appropriate support can be offered for women undergoing diagnosis of breast symptoms.

Carbon localisation of impalpable breast lesions.

BACKGROUND: Hookwire localisation (HL) is the most widely used technique for excision of impalpable breast lesions. This method has several drawbacks, particularly with logistics. Carbon localisation (CL) is an alternative procedure which is logistically superior to HL, but comparisons of accuracy and costs have not been reported. METHODS: A consecutive case series of all patients from Northwestern BreastScreen undergoing either CL or HL between January 1999 and March 2001. FINDINGS: Of 511 procedures, 219 CLs and 292 HLs were performed. The accuracy of excision did not vary significantly. Where a preoperative diagnosis of malignancy had been made by percutaneous needle biopsy (PNB), the margins were <1mm in 27 of the CL group (18.9%) and 21 of the HL group (29.2%) (P=0.087). Cost analysis was very favourable for CL performed concurrently with PNB since the costs were incremental. INTERPRETATION: At service delivery level, CL is an accurate alternative to HL with better logistics and favourable costs. Nationally, it has the potential to improve the cost effectiveness of breast screening programmes.

Transmission of the Ambystoma tigrinum virus to alternative hosts.

Ambystoma tigrinum virus (ATV) is a lethal virus originally isolated from Sonora tiger salamanders Ambystoma tigrinum stebbinsi in the San Rafael Valley in southern Arizona. USA. ATV is implicated in several salamander epizootics. We attempted to transmit ATV experimentally to fish and amphibians by injection, water bath exposure, or feeding to test whether ATV can cause clinical signs of infection or be recovered from exposed individuals that do not show clinical signs. Cell culture and polymerase chain reaction of the viral major capsid protein gene were used for viral detection. Salamanders and newts became infected with ATV and the virus was recovered from these animals, but virus could not be recovered from any of the frogs or fish tested. These results suggest that ATV may only infect urodeles and that fish and frogs may not be susceptible to ATV infection.

Transitional zone and anterior peripheral zone of the prostate. A correlation of small-volume cancer in the biopsy cores and high psa with positive anterior margins in radical prostatectomy specimens.

INTRODUCTION: Prognostically significant prostatic adenocarcinomas (PAC) may pose diagnostic problems if they were localized in the anterior peripheral zone (APZ) or transitional zone (TZ). MATERIALS AND METHODS: 108 cases of PAC were reviewed along with serum PSA and TRUS biopsies. The PACs were divided into 22 TZ, 17 APZ and 69 posterior peripheral zone (PPZ) PACs according to the location of the main tumor mass in the TZ and anterior or posterior half of the peripheral zone in the radical prostatectomy (RP) specimens. RESULTS: In comparison with PPZ PAC, TZ PAC had a higher cancer volume in RP specimens (4 +/- 2.1 vs. 2.5 +/- 1.7 cm3, p < 0.01), a higher serum PSA (16.5 +/- 9.8 vs. 8.4 +/- 4.5 microg/l, p < 0.001), a biopsy with a small cancer volume (3.8 +/- 2.1 vs. 11.8 +/- 9.4 mm, p < 0.005), and a lower Gleason's score (4.8 +/- 2.1 vs. 6.5 +/- 1.7). APZ PAC was characterized by the cancer volume in RP and biopsy and PSA intermediate between those of TZ and PPZ PAC. Among 24 PACs with a total cancer core length of <3 mm, 19 cases were from the TZ and APZ groups and also had a higher cancer volume and PSA than those from the PPZ group (2.9 +/- 1.8 vs. 1.5 +/- 1.3 and 13.7 +/- 8.3 vs. 9.6 +/- 4 microg/l, respectively). Furthermore, there was a better correlation coefficient (r(2)) of tumor volume in the biopsy and RP for PPZ than for all zones PAC (r2 = 0.75 vs. 0.29). TZ and APZ carcinomas were associated with extension or satellite nodules of PAC in the PPZ that may be diagnosed with biopsies. These PACs were associated with positive anterior resection margin due to extracapsular extension of the carcinoma or intracapsular dissection in 6 and 5 cases respectively. CONCLUSIONS: TZ and APZ PACs accounted for the poor correlation between the tumor volume in the biopsy and the RP, and were associated with positive anterior resection margins. One core biopsy with a total cancer core length of <3 mm and PSA >10 microg/l are suspicious for TZ and APZ PCA in patients with undetectable tumors with DRE or TRUS. Clinically insignificant PACs tend to be associated with cancer core <3 mm and PSA <10 microg/l.

Lactation affects expression of intermediate filaments in human breast epithelium.

The human breast contains two epithelial lineages, luminal epithelial and myoepithelial. Specific patterns of expression of intermediate filaments have previously been demonstrated in the resting breast. To determine how terminal differentiation and lactation influenced expression of intermediate filaments in breast epithelial cells, we used Western blot analysis to measure the levels of vimentin, alpha-smooth muscle actin, keratin 14, and keratin 18 in the resting and lactating breast. Confocal immunofluorescence was used to determine the subcellular site of localization of the intermediate filaments. Vimentin was localised to myoepithelial cells in both the resting and lactating gland. There was a four-fold increase in vimentin protein levels in lactating tissue relative to resting tissue, and this may be related to increased cellular activity of the myoepithelial cells which surround secretory alveoli. Alpha-smooth muscle actin and keratin 14 were detected in myoepithelial cells, and similar levels of expression were found in lactating and resting tissue. In the resting breast, keratin 18 and keratin 8 were detected in luminal epithelial cells in a filamentous form, whereas in lactating tissue it was present in a punctate form in luminal cells and also seen as granules in the lumen of alveoli. Our results indicate that intermediate filament expression patterns are altered in the lactating human breast, and this may reflect their role in the fully functional gland.

Tubular carcinoma of the breast: prognosis and response to adjuvant systemic therapy.

BACKGROUND: Tubular carcinoma of the breast is an uncommon and usually small tumour, and is thought to have a favourable prognosis. The present study examined the long-term prognosis of patients with tubular breast carcinoma and the roles of axillary dissection and adjuvant therapy. METHODS: Eighty-six tubular cases were identified from a large worldwide database of 9520 breast carcinoma patients entered into randomized adjuvant therapy trials run by the International Breast Cancer Study Group from 1978 to 1999. These patients were followed for a median of 12 years. RESULTS: Forty-two (49%) cases were node-positive, of which 33 (79%) had 1-3 nodes involved. Ten (32%) of the 31 smaller tumours (< or = 1 cm in size) were node-positive. Patients with node-positive tubular carcinoma had a significantly better 10-year relapse-free survival (P = 0.006) and survival (P < 0.0001) compared with non-tubular node-positive cases. Overall survival was similar for node-positive and node-negative tubular carcinoma. Overall, 71 patients (83%) received some form of adjuvant systemic therapy. Of the 86 cases, 43 (50%) received more than one course of chemotherapy. There was an 85% decrease in the risk of death for patients who received more than one course of chemotherapy compared to those who did not (hazard ratio 0.15, 95% confidence interval (CI): 0.03-0.82; P = 0.03). CONCLUSIONS: Compared to other histological types of breast cancer, tubular carcinoma has a better long-term prognosis. Adjuvant chemotherapy may further improve prognosis and involvement of axillary nodes may not be an indicator for early death due to breast carcinoma.

Incidental prostatic adenocarcinomas and putative premalignant lesions in TURP specimens collected before and after the introduction of prostrate-specific antigen screening.

BACKGROUND: Since the introduction of prostate-specific antigen (PSA) screening for the detection of prostatic adenocarcinoma (PCA), there has been an increase in the incidence of stage T1c PCA. The purpose of this study was to compare the frequency of incidental PCA found in transurethral resection of prostate (TURP) specimens for a 14-month period during 1989-1990 (before PSA screening was available) with the incidence of PCA for a 32-month period during 1997-1999 (after PSA screening became available). DESIGN: Consecutive TURP specimens from the 2 time periods were reviewed to identify incidental PCA, prostatic intraepithelial neoplasia (PIN), and atypical adenomatous hyperplasia (AAH). Cases of TURP for palliative treatment of known advanced PCA were excluded from the study. All TURP specimens were fixed in 10% buffered formalin and were processed according to the same protocol. RESULTS: We reviewed 533 and 449 TURP specimens for the time periods 1989-1990 and 1997-1999, respectively. Comparison of the results for these 2 time periods revealed that the combined prevalence of T1a and T1b PCA decreased over time from 12.9% to 8.0% (P =.06) with the introduction of PSA screening. A new group of T1c PCA was established in the post-PSA screening period of 1997-1999. There were no statistically significant differences in the incidences of T1a PCA, PIN, and AAH in TURP specimens for the 2 time periods. CONCLUSION: The decreased incidence of T1b PCA in TURP specimens for the 1997-1999 period represents a shift in PCA staging. Some PCAs previously staged as T1b are now staged as T2 carcinomas, as a result of PSA screening and earlier clinical detection. The introduction of PSA screening has had no influence on the incidence of T1a PCA, PIN, or AAH in TURP specimens.

Foraging under the risk of cannibalism leads to divergence in body size among tiger salamander larvae.

Populations of plants and animals are almost always made up of individuals of different sizes. In populations where cannibalism is common, this size variation can influence rates of mortality and growth and affect population regulation. Size variation can be caused by a variety of mechanisms. One of these is due to size-specific responses to the threat of predation by potentially cannibalistic conspecifics. We investigated the role of anti-predator behavior in size structure development within single-aged cohorts of Arizona tiger salamander larvae. In a laboratory experiment, we show that size variation increases over time within groups of salamanders, even if they are fed in isolation. We also show that increasing the size of neighbors decreases the feeding rate of small salamander larvae. However, increasing density of neighbors did not have a significant effect on feeding rate. These results are consistent with the hypothesis that size variation among tiger salamander larvae is, in part, a result of size-specific responses to predation risk. We discuss the potential for feedback between size structure development, predation risk, and rates of cannibalism.

Photographic memory, money, and liposuction: survey of medical students' wish lists.

OBJECTIVES: To examine whether medical students made fewer altruistic wishes and more money oriented wishes in later years of the medical course than students in earlier years. DESIGN: Anonymous questionnaire survey. SETTING: Auckland University School of Medicine. PARTICIPANTS: 520 medical students from 6 years of the course responded to the questionnaire item "If you had three wishes what would you wish for?" MAIN OUTCOME MEASURES: Proportion of wishes in various categories. RESULTS: The three most popular categories of wishes were happiness (34% of students), money (32%), and altruistic wishes (31%). Rates of altruistic wishes (odds ratio=1.05, 95% confidence interval 0.94 to 1.18; P=0.36) and wishes for money (odds ratio=0.96, 0.86 to 1.08; P=0.52) did not vary over the years of the course. Female medical students were more likely than males to make altruistic wishes (36% v 26%; chi(2)=5.68, P=0. 02), intimacy wishes (25% v 18%; chi(2)=3.74, P=0.05), and happiness wishes (42% v 26%; chi(2)=18.82, P=0.0001). Men were more likely than women to make sexual wishes (5% v 0.8%; chi(2)=7.34, P=0.01). CONCLUSIONS: We found no evidence that students were less altruistic and more money oriented in the later years of the medical course.

Spindle cell lipoma of the breast.

Spindle cell lesions, which commonly arise in the soft tissues, may present in the breast and be difficult to distinguish from primary mammary spindle cell tumors. We present the case of a 28 year old woman with a 1.5 cm circumscribed spindle cell lipoma lying deep within the tissue of the right breast. Thin, uniform spindle cells were associated with collagen bundles, mature adipocytes and entrapped normal mammary ducts, lobules, vessels and nerves, appearances which simulated an aggressively infiltrating tumor. The spindle cells proved immunoreactive to CD34 and vimentin but non-reactive for cytokeratin, S100, desmin, smooth muscle actin and Factor VIII. Although surgical resection was incomplete, the patient is alive and without evidence of tumor recurrence 12 months postoperatively. In our case, a conservative approach to management was justified and supported by the patient's subsequent clinical course. This case exemplifies the diagnostic challenge of spindle cell lesions arising in breast tissue and the value of immunoperoxidase stains.

Multicycle high-dose chemotherapy and filgrastim-mobilized peripheral-blood progenitor cells in women with high-risk stage II or III breast cancer: five-year follow-up.

PURPOSE: To determine the safety and efficacy of multiple cycles of dose-intensive, nonablative chemotherapy in women with poor-prognosis breast cancer. PATIENTS AND METHODS: Women with stage II breast cancer and 10 or more involved nodes or four or more involved nodes and estrogen receptor-negative tumors and women with stage III disease received three cycles of epirubicin 200 mg/m2 and cyclophosphamide 4 g/m2, with progenitor cell and filgrastim support every 28 days (n = 79) or 21 days (n = 20). Patients were reviewed at least twice yearly thereafter. Twenty-six patients had bone marrow and apheresis collections assessed for the presence of micrometastatic tumor cells. RESULTS: Ninety-nine women (median age, 43 years; range, 24 to 60 years) were treated. Ninety-two completed all three cycles of chemotherapy. The major toxicity was severe, reversible myelosuppression that was more prolonged with successive cycles, and this did not differ between patients given treatment every 28 days and those treated every 21 days. Febrile neutropenia occurred in 176 (61%) of 287 cycles. Severe mucositis (grade 3 or 4) occurred in 23% of cycles but tended to be short-lived and was reversible. The cardiac ejection fraction fell by a median of 4% during treatment, and three patients developed evidence of cardiac failure after chemotherapy. Two patients (2%) died of acute toxicity. Three of 26 patients had evidence of circulating micrometastatic tumor cells. The actuarial distant disease-free and overall survival rates at 60-month follow-up were 64% (95% confidence interval [CI], 53% to 75%) and 67% (95% CI, 56% to 78%), respectively. CONCLUSION: Multiple cycles of dose-intensive, nonablative chemotherapy is a feasible and safe approach. Disease control and survival are similar to those in other studies of myeloablative chemotherapy in poor-prognosis breast cancer. The regimen is being evaluated in a randomized trial of the International Breast Cancer Study Group.

Composite renal cell carcinoma and angiomyolipoma: a study of the histogenetic relationship of the two lesions.

The purpose of the present study was to investigate the possible histogenetic relationship of renal cell carcinoma (RCC) and angiomyolipoma (AMYL) occurring in the same renal nodule by examining two cases of composite RCC and AMYL in patients without stigmata of tuberous sclerosis and by reviewing the medical literature of similar cases. Case 1 represents an epithelioid variant of AMYL with multiple additional nodules of typical AMYL in a surgically removed kidney. The patient subsequently developed a lesion consisting of a mixture of epithelioid variant of AMYL and RCC 24 months later in the retroperitoneum and, an additional 4 months later, in the liver. The RCC cells resembled mononucleated epithelioid cells of the epithelioid AMYL except that they were focally reactive with epithelial membrane antigen (EMA) in the retroperitoneum and focally reactive with both EMA and cytokeratin (CK) in the liver. Case 2 consisted of a typical AMYL admixed with a chromophil cell RCC. A review of the medical literature revealed seven additional cases with histopathological findings similar to this case. All cases had multiple foci of typical AMYL. Immunostaining results are available in five tumors. Chromophil RCC showed variable reactivity with CK and EMA. In addition, RCC in the two cases in the present study also displayed a positive reaction with mucin staining and a positive reactivity with carcinoembryonic antigen. There appears to be a spectrum of histopathological and immunohistochemical changes from the epithelioid variant of AMYL through a mixed epithelioid AMYL/RCC to chromophil RCC in three successive specimens in case 1. Moreover, the intimate admixture of AMYL and RCC and the similar expression of epithelial markers of RCC in the two cases in the present study, as well as other cases in the literature, suggest that some RCC develop from the same precursor cell as AMYL or from a component of AMYL.

Implementation of image-guided large-core needle biopsy of the breast on a limited budget.

Image-guided large-core needle biopsy (LCNB) of the breast is becoming widely accepted as an accurate, minimally invasive and economical way to obtain a tissue diagnosis of breast lesions. However, much of this work has been done with expensive dedicated equipment, often favouring stereotaxic guidance. Image-guided LCNB was introduced to Middlemore Hospital based around existing inexpensive equipment, and stereotaxic or ultrasound guidance was chosen depending on which showed the lesion best. Multidisciplinary clinical, radiological and pathological assessment of each case was performed. The results of 213 biopsies (112 stereotaxic and 101 ultrasound guidance) are reported here. Malignancy was shown or suspected in 85 biopsies (40%). The absolute sensitivity for malignancy was 97% with complete sensitivity of 100%. The absolute specificity was 100% and the complete specificity 98.5%. Large-core needle biopsy can be successfully implemented in a large institution without investment in expensive equipment while maintaining high ratios of malignant/benign biopsies. Attention to technique and careful multidisciplinary review are important to the success of such a programme.