Comparison of detrending methods for optimal fMRI preprocessing

Because of the inherently low signal to noise ratio (SNR) of fMRI data, removal of low frequency signal intensity drift is an important preprocessing step, particularly in those brain regions that weakly activate. Two known sources of drift are noise from the MR scanner and aliasing of physiological pulsations. However, the amount and direction of drift is difficult to predict, even between neighboring voxels. Further, there is no concensus on an optimal baseline drift removal algorithm. In this paper, five voxel-based detrending techniques were compared to each other and an auto-detrending algorithm, which automatically selected the optimal method for a given voxel time-series. For a significance level of P < 10(-6), linear and quadratic detrending moderately increased the percentage of activated voxels. Cubic detrending decreased activation, while a wavelet approach increased or decreased activation, depending on the dataset. Spline detrending was the best single algorithm. However, auto-detrending (selecting the best algorithm or none, if detrending is not useful) appears to be the most judicious choice, particularly for analyzing fMRI data with weak activations in the presence of baseline drift.     

Adrenal gland injury due to gunshot

Adrenal gland trauma is a rare phenomenon, due to the small size and retroperitoneal location of the organ. The majority of adrenal gland trauma is due to blunt force injury and is only rarely encountered due to the penetrating mechanisms. A 20-year-old male sustained a gunshot wound to the left abdomen. Upon exploration, he was found to have a through and through injury to the left adrenal gland, among other injuries. Injury to the adrenal gland due to penetrating trauma is exceptionally rare. The principles of management are to control bleeding from the gland with debridement and hemostasis rather than attempt to resect the entire organ. The management of a penetrating injury to the adrenal gland is straightforward and should not be a contributor to a patient''s morbidity or mortality.     

Insect-Specific Flavivirus Replication in Mammalian Cells Is Inhibited by Physiological Temperature and the Zinc-Finger Antiviral Protein

The genus Flavivirus contains pathogenic vertebrate-infecting flaviviruses (VIFs) and insect-specific flaviviruses (ISF). ISF transmission to vertebrates is inhibited at multiple stages of the cellular infection cycle, via yet to be elucidated specific antiviral responses. The zinc-finger antiviral protein (ZAP) in vertebrate cells can bind CpG dinucleotides in viral RNA, limiting virus replication. Interestingly, the genomes of ISFs contain more CpG dinucleotides compared to VIFs. In this study, we investigated whether ZAP prevents two recently discovered lineage II ISFs, Binjari (BinJV) and Hidden Valley viruses (HVV) from replicating in vertebrate cells. BinJV protein and dsRNA replication intermediates were readily observed in human ZAP knockout cells when cultured at 34 °C. In ZAP-expressing cells, inhibition of the interferon response via interferon response factors 3/7 did not improve BinJV protein expression, whereas treatment with kinase inhibitor C16, known to reduce ZAP’s antiviral function, did. Importantly, at 34 °C, both BinJV and HVV successfully completed the infection cycle in human ZAP knockout cells evident from infectious progeny virus in the cell culture supernatant. Therefore, we identify vertebrate ZAP as an important barrier that protects vertebrate cells from ISF infection. This provides new insights into flavivirus evolution and the mechanisms associated with host switching.     

What Do Medical Students Do and Want When Caring for “Difficult Patients”?

Phenomenon: Medical students, like physicians, experience negative emotions such as frustration when interacting with some patients, and many of these interactions occur for the first time during clinical clerkships. Students receive preclinical training in the social and behavioral sciences, often including learning about “difficult patient” interactions, yet little is known about their desire for training during clinical education. We explored students’ strategies in these difficult clinical interactions, whether they felt prepared by the curriculum, and what support they would have liked. These data inform proposed strategies for supporting clinical learning. Approach: We interviewed 4th-year students about interactions with patients toward whom they felt negative emotions and sought to identify strategies and supports needed in these interactions. Interviews ended when theoretical sufficiency was achieved. We used qualitative content analysis to organize strategies into themes about areas benefiting from curricular supports. We mapped students’ desired curricular support examples to cognitive apprenticeship teaching methods—modeling, coaching, reflection, scaffolding, exploration, and articulation—and aligned them with traditional pedagogical techniques. Findings: We interviewed 26 medical students (44 volunteered/180 invited). Their strategies formed five themes: finding empathy (with a subtheme of focusing on social determinants of health), using learned communication approaches, anticipating challenging interactions, seeking support, and considering it an opportunity for more responsibility. Students described ideal clinical teaching, including postinteraction debriefs with an emphasis on validating their emotional reactions and challenges. Students mentioned all cognitive apprenticeship teaching methods, most prominently modeling (observing supervisors in such interactions) and supported oral reflection. They also identified a need for faculty and resident development to enact these teaching methods. Insights: Although students use some learned strategies in interactions in which they feel negative emotions toward patients, they desire more preparation and support during their clinical rotations. Their desires map to traditional pedagogical techniques and to methods of cognitive apprenticeship. Our findings point to the need to use these techniques to enhance clinical learning for students who experience emotionally challenging patient interactions.     

Adenoviral gene transfer of mutant phospholamban rescues contractile dysfunction in failing rabbit myocytes with relatively preserved SERCA function

In heart failure (HF) a main factor in reduced contractility is reduced SR Ca2+ content and reversed force-frequency response (FFR), ie, from positive to negative. Our arrhythmogenic rabbit HF model exhibits decreased contractility mainly due to an increase in Na/Ca exchange (NCX) activity (with only modest decrease in SR Ca2+-ATPase (SERCA) function), similar to many end-stage HF patients. Here we test whether phospholamban (PLB) inhibition using a dominant-negative mutant PLB adenovirus (K3E/R14E, AdPLB-dn, with beta-galactosidase adenovirus as control) could enhance SERCA function and restore Ca2+ transients and positive FFR in ventricular myocytes from these HF rabbits. HF myocytes infected with AdPLB-dn (versus control) had enhanced Ca2+ transient amplitude (2.0+/-0.1 versus 1.6+/-0.05 F/Fo at 0.5 Hz, P<0.05) and had a positive FFR, whereas acutely isolated HF myocytes or those infected with Adbetagal had negative FFR. Ca2+ transients declined faster in AdPLB-dn versus Adbetagal myocytes (RT50%: 317+/-29 versus 551+/-90 ms at 0.5 Hz, P<0.05) and had an increased SR Ca2+ load (3.5+/-0.3 versus 2.6+/-0.2 F/Fo at 0.5 Hz, P<0.05), indicative of increased SERCA function. Furthermore, this restoration of function was not due to changes in NCX or SERCA expression. Thus, increasing SERCA activity in failing myocytes by AdPLB-dn gene transfer reversed the contractile dysfunction (and restored positive FFR) by increasing SR Ca2+ load. This approach could enhance contractile function in failing hearts of various etiologies, even here where reduced SERCA activity is not the main dysfunction.     

Associations Between Macrolevel Economic Factors and Weight Distributions in Low- and Middle-Income Countries: A Multilevel Analysis of 200?000 Adults in 40 Countries

Objectives. We examined associations between macrolevel economic factors hypothesized to drive changes in distributions of weight and body mass index (BMI) in a representative sample of 200 796 men and women from 40 low- and middle-income countries.Methods. We used meta-regressions to describe ecological associations between macrolevel factors and mean BMIs across countries. Multilevel regression was used to assess the relation between macrolevel economic characteristics and individual odds of underweight and overweight relative to normal weight.Results. In multilevel analyses adjusting for individual-level characteristics, a 1–standard-deviation increase in trade liberalization was associated with 13% (95% confidence interval [CI] = 0.76, 0.99), 17% (95% CI = 0.71, 0.96), 13% (95% CI = 0.76, 1.00), and 14% (95% CI = 0.75, 0.99) lower odds of underweight relative to normal weight among rural men, rural women, urban men, and urban women, respectively. Economic development was consistently associated with higher odds of overweight relative to normal weight. Among rural men, a 1–standard-deviation increase in foreign direct investment was associated with 17% (95% CI = 1.02, 1.35) higher odds of overweight relative to normal weight.Conclusions. Macrolevel economic factors may be implicated in global shifts in epidemiological patterns of weight.Cardiovascular diseases are among the leading causes of death in low- and middle-income countries (LMICs),1 where mortality from such diseases has been increasing and is expected to continue doing so until 2030.2 In parallel to this trend, there has been an increase in average body mass index (BMI; defined as weight in kilograms divided by the square of height in meters) in most regions of the world.3 With population-based studies indicating a U- or J-shaped relation between BMI and cardiovascular disease mortality,4,5 these shifts in BMI may increase the proportion of the population at greatest risk for cardiovascular diseases. As such, increases in BMI may contribute to escalating cardiovascular disease mortality in LMICs,6 highlighting the need for understanding BMI patterns and predictors.Comparative longitudinal data that can be used to monitor BMI changes (often expressed according to prevalence of underweight, overweight, and obesity) across LMICs are scant; however, existing data suggest that the prevalence of underweight has decreased, the prevalence of overweight and obesity has increased, and, in general, there is a greater burden of overweight than underweight in most LMICs, particularly in urban areas.7–9 Shifts in the key determinants of weight, including diet and physical activity, are hypothesized to influence these patterns.3 Major changes in global dietary consumption have increased per capita food intake in LMICs, as well as the proportion of people’s daily diet derived from energy-dense and fatty foods.3,10–12 Although cross-national and longitudinal data on physical activity are limited, available evidence suggests that forms of transportation, employment, and leisure activities have become more sedentary and may contribute to changing patterns of weight at the population level.13,14Macrolevel economic factors, including economic development, urbanization, foreign investment, and trade liberalization, are hypothesized to drive shifting patterns of dietary composition, physical activity, and other determinants of nutritional outcomes.3,15 Economic growth and attendant increases in per capita income, for example, are associated with increased consumption of energy-dense foods,16 and recent cross-national analyses suggest that economic development is associated with a faster rate of growth in the prevalence of overweight among lower-income groups in LMICs.17,18 Urbanization is hypothesized to increase access to processed diets, reduce opportunities for physical activity, and expose residents to food marketing, thereby promoting a more sedentary lifestyle associated with less energy expenditure and greater caloric intake.15The influx of foreign direct investment (FDI), defined as investments by an enterprise in one country intended to acquire a lasting management interest in an enterprise operating in a foreign economy, represents one mechanism through which transnational corporations enter into new markets. FDI inflows are, along with greater openness to trade,19 hypothesized to be a key element in reshaping the global market for food, particularly in LMICs, by threatening traditional modes of agricultural production and facilitating the processing, distribution, and marketing of lower-cost, energy-dense food.20,21Despite the potential role that these macrolevel economic factors may play in shaping the epidemiological pattern of diet, behavior, and weight in LMICs, few empirical studies have investigated the relation between contextual factors and individual weight. A limited number of ecological studies have been conducted,9,22 but their results cannot be used to draw inferences about health at the individual level. Furthermore, the social patterning of diet and physical activity according to area of residence (urban or rural) and gender suggests that the macrolevel factors posited to drive changes in weight may have distinct implications for particular groups of individuals,23,24 and ecological studies cannot assess whether associations between macrolevel economic characteristics and weight vary according to such individual-level characteristics.We used data from a sample of approximately 200 000 adults from 40 LMICs to describe the ecological associations between macrolevel economic factors hypothesized to drive changes in determinants of weight (i.e., economic development, urbanization, FDI, trade liberalization) and average BMIs across countries and examine the association between macrolevel characteristics and the probability at the individual level of underweight and overweight or obesity relative to normal weight. We also assessed cross-level interactions of macrolevel factors with gender and area of residence.     

Cytokeratin deposits in lymph nodes show distinct clinical significance from lymph node micrometastasis in human esophageal cancers

BACKGROUND: Cytokeratin immunostaining is the most common method used to identify micrometastatic cancer cells from the lymph nodes. However, contamination with hyalinized cytokeratin particles, frequently observed in the lymph nodes of esophageal cancer patients, can lead to misinterpretation of cytokeratin immunostaining. MATERIALS AND METHODS: Cytokeratin immunostaining (AE1/AE3) of surgically removed lymph nodes was performed for 41 cases of node-negative, but locally advanced (T3, T4), esophageal cancer patients. Cytokeratin immunoreactivity (CK) was classified as micrometastasis (MM) or cytokeratin deposit (CD) by the presence or absence of tumor nuclei in serial sections given hematoxylin-eosin staining. RESULTS: CK (+) was observed in 18 patients (44%), including 11 with MM (+) (27%) and 10 with CD (+) (24%). There was no correlation between MM and CD, and neither was associated with clinicopathological factors, except for a high incidence of preoperative chemotherapy in CD (+) patients. The presence of CK did not affect postoperative survival of esophageal cancer patients at this limited stage, showing a 5-year survival rate of 57% for CK (+) and 64% for CK (-) (P = 0.6064). Interestingly, patients with MM (+) showed poorer prognosis than MM (-) (5-year survival: 28% vs 79%, P = 0.0188), while CD (+) patients tended to display better prognosis than CD (-) ones (5-year survival: 78% vs 56%, P = 0.1860). CONCLUSIONS: Evaluation by cytokeratin immunostaining of lymph nodes requires careful discrimination of CD from MM, in order to allow MM to be used as a prognostic factor for esophageal cancer patients.