Focus: A Multifaceted Battle Against Cancer: Ashley W. Oughterson,MD: Surgeon,Soldier, Leader

Ashley W. Oughterson, MD, (1895-1956) was a longtime faculty surgeon at Yale University. He performed some of the earliest pancreatic resections in the United States. During World War II, Colonel Oughterson was the primary “Surgical Consultant” in the South Pacific and present at nearly every major battle. His meticulously kept diary is regarded as the foremost source detailing wartime surgical care. Colonel Oughterson led the initial Army team to survey Hiroshima and Nagasaki following the nuclear attacks. Thoughout his academic career at Yale, Oughterson was a key leader in several medical and surgical societies. As scientific director of the American Cancer Society, Oughterson lectured widely and guided research priorities in oncology following World War II. Oughterson also authored numerous benchmark papers in surgical oncology that continue to be cited today. These extensive contributions are examined here and demonstrate the wide-ranging impact Oughterson exerted during a formative period of American surgery.     

Exercise Tolerance Can Be Enhanced through a Change in Work Rate within the Severe Intensity Domain: Work above Critical Power Is Not Constant

Introduction

The characterization of the hyperbolic power-time (P-t _lim) relationship using a two-parameter model implies that exercise tolerance above the asymptote (Critical Power; CP), i.e. within the severe intensity domain, is determined by the curvature (W’) of the relationship.

Purposes

The purposes of this study were (1) to test whether the amount of work above CP (W>CP) remains constant for varied work rate experiments of high volatility change and (2) to ascertain whether W’ determines exercise tolerance within the severe intensity domain.

Methods

Following estimation of CP (208 ± 19 W) and W’ (21.4 ± 4.2 kJ), 14 male participants (age: 26 ± 3; peak V˙O2: 3708 ± 389 ml.min^-1) performed two experimental trials where the work rate was initially set to exhaust 70% of W’ in 3 (‘THREE’) or 10 minutes (‘TEN’) before being subsequently dropped to CP plus 10 W.

Results

W>CP for TEN (104 ± 22% W’) and W’ were not significantly different (P>0.05) but lower than W>CP for THREE (119 ± 17% W’, P<0.05). For both THREE (r = 0.71, P<0.01) and TEN (r = 0.64, P<0.01), a significant bivariate correlation was found between W’ and t _lim.

Conclusion

W>CP and t _lim can be greater than predicted by the P-t _lim relationship when a decrement in the work rate of high-volatility is applied. Exercise tolerance can be enhanced through a change in work rate within the severe intensity domain. W>CP is not constant.     

Parity of Indigenous and Non-Indigenous Women in Brazil: Does the Reported Number of Children Born Depend upon Who Answers National Census Questions?

Taking parity as the main analytic variable, the objective of this study is to investigate whether the patterns of response to national census questions in Brazil differ when Indigenous and non-Indigenous women are compared, taking into consideration whether the information was provided by the women directly or by a proxy respondent (another household member or a non-resident). We use data on children ever born to Indigenous and non-Indigenous women from two Brazilian regions, the Northeast and the North. Data on the number of household members, total household rooms, interviewee’s color/race, educational attainment, age, parity, and type of respondent were obtained from the 2010 Brazilian census. The relation between color/race and reported parity, as well as the impact of the type of respondent on this association were assessed with the Zero-inflated Negative Binomial regression, stratified by region (North and Northeast) and urban/rural status. Just over half of census interviewees answered directly the census questions (51.2% in the North and 54.4% in the Northeast). Indigenous women in the North region had the highest percentage of interviews carried out with a non-resident (12.7% total; 15.0% and 3.0% in rural and urban areas, respectively). Regardless of color/race, parity means were considerably higher when the question was answered by the woman directly (93.5%-101.4% and 15.6%-21.7% higher, compared co-resident and non-resident based answers, respectively). Parity underreporting was particularly strong in Indigenous women living in the rural North (16.0% less in comparison to White women). Proxy respondents tend to underestimate the count of children, particularly among Indigenous women from the North. The implementation of certain methodological alternatives in the Brazilian national censuses, such as the selection and training of census takers to work specifically in Indigenous territories, might be a productive means to improve data collection.     

NPY‐Y1 coexpressed with NPY‐Y5 receptors modulate anxiety but not mild social stress response in mice

The Y1 and Y5 receptors for neuropeptide Y have overlapping functions in regulating anxiety. We previously demonstrated that conditional removal of the Y1 receptor in the Y5 receptor expressing neurons in juvenile Npy1r^Y5R?/? mice leads to higher anxiety but no changes in hypothalamus‐pituitary‐adrenocortical axis activity, under basal conditions or after acute restraint stress. In the present study, we used the same conditional system to analyze the specific contribution of limbic neurons coexpressing Y1 and Y5 receptors on the emotional and neuroendocrine responses to social chronic stress, using different housing conditions (isolation vs. group‐housing) as a model. We demonstrated that control Npy1r^2lox male mice housed in groups show increased anxiety and hypothalamus‐pituitary‐adrenocortical axis activity compared with Npy1r^2lox mice isolated for six weeks immediately after weaning. Conversely, Npy1r^Y5R?/? conditional mutants display an anxious‐like behavior but no changes in hypothalamus‐pituitary‐adrenocortical axis activity as compared with their control littermates, independently of housing conditions. These results suggest that group housing constitutes a mild social stress for our B6129S mouse strain and they confirm that the conditional inactivation of Y1 receptors specifically in Y5 receptor containing neurons increases stress‐related anxiety without affecting endocrine stress responses.     

Ferric chloride flocculation plus carbon adsorption allows to reuse spent culture medium of Arthrospira platensis

Arthrospira platensis cultivation produces a saline spent medium that must be treated to allow its reuse, thus saving water and avoiding environmental pollution. This study evaluates the association of flocculation followed by adsorption to treat the spent medium by applying different concentrations of granular activated carbon (GAC) and ferric chloride (F), and using different residence times (T). The simultaneous optimization of the independent variables GAC, F, and T was performed using both a 2³ central composite design and a response surface methodology. The cells cultivated in the medium obtained after the optimal conditions of treatment (GAC = 54.2 g L^?1, F = 10.0 mg L^?1, and T = 30.8 min) provided the highest maximum cell concentration, X_m = 3140 ± 77 mg L^?1 in 0.5 L Erlenmeyer flasks with the highest protein biomass content (44.9%). The treated medium in such conditions was also used in a 3.5 L tubular photobioreactor (PBR), reaching X_m = 4033 ± 110 mg L^?1 and biomass with high contents of both protein (47.3 ± 2.6%) and chlorophyll (9.7 ± 0.3 mg g dry cell^?1). Therefore, this study can contribute to diminishing costs of A. platensis production by reusing its culture medium and improving its biomass quality in PBRs.     

Use of Cystatin C and Serum Creatinine for the Diagnosis of Contrast-Induced Nephropathy in Patients Undergoing Contrast-Enhanced Computed Tomography at an Oncology Centre

ObjectiveOur aim was to assess renal function using as laboratory measurements serum creatinine and cystatin C concentrations before and after administration of low-osmolarity (nonionic) iodinated contrast medium in patients with cancer undergoing computed tomography (CT).MethodsThis prospective study included 400 oncologic outpatients. Serum creatinine and cystatin C concentrations were measured before and 72 h after contrast administration. Glomerular filtration rates (GFRs) were estimated using serum creatinine–based [Modification of Diet in Renal Disease (MDRD) and Cockroft-Gault and cystatin C based (Larsson) equations. Exploratory data analysis was performed. The nonparametric Wilcoxon test was used to compare pre and post contrast of test results and estimated clearance. The confidence interval used in the analysis was 95%.ResultsCompared with the pre-contrast values, the mean serum creatinine concentration was significantly higher and average GFRs estimated using MDRD and Cockcroft-Gault equations were significantly lower after the administration of contrast (p <0.001). It was also observed a significant increase after contrast in the concentration of Cystatin C (p = 0.015). In addition, a decrease in GFR estimated using the average Larsson (p = 0.021) was observed between time points. However, none of the patients presented clinically significant nephropathy.ConclusionsAssessment using serum creatinine and cystatin C concentrations showed changes in renal function among patients with cancer undergoing contrast-enhanced CT examination in this study. No significant renal damage related to the use of low-osmolarity iodinated contrast medium of the type and dosage employed in this study was observed. This contrast medium is thus safe for use in patients with cancer.     

Repetitive DNA Sequences and Evolution of ZZ/ZW Sex Chromosomes in Characidium (Teleostei: Characiformes)

Characidium constitutes an interesting model for cytogenetic studies, since a large degree of karyotype variation has been detected in this group, like the presence/absence of sex and supernumerary chromosomes and variable distribution of repetitive sequences in different species/populations. In this study, we performed a comparative cytogenetic analysis in 13 Characidium species collected at different South American river basins in order to investigate the karyotype diversification in this group. Chromosome analyses involved the karyotype characterization, cytogenetic mapping of repetitive DNA sequences and cross-species chromosome painting using a W-specific probe obtained in a previous study from Characidium gomesi. Our results evidenced a conserved diploid chromosome number of 2n = 50, and almost all the species exhibited homeologous ZZ/ZW sex chromosomes in different stages of differentiation, except C. cf. zebra, C. tenue, C. xavante and C. stigmosum. Notably, some ZZ/ZW sex chromosomes showed 5S and/or 18S rDNA clusters, while no U2 snDNA sites could be detected in the sex chromosomes, being restricted to a single chromosome pair in almost all the analyzed species. In addition, the species Characidium sp. aff. C. vidali showed B chromosomes with an inter-individual variation of 1 to 4 supernumerary chromosomes per cell. Notably, these B chromosomes share sequences with the W-specific probe, providing insights about their origin. Results presented here further confirm the extensive karyotype diversity within Characidium in contrast with a conserved diploid chromosome number. Such chromosome differences seem to constitute a significant reproductive barrier, since several sympatric Characidium species had been described during the last few years and no interespecific hybrids were found.     

Role of platelet-activating factor in pulmonary vascular remodeling associated with chronic high altitude hypoxia in ovine fetal lambs

Platelet-activating factor (PAF) is implicated in pathogenesis of chronic hypoxia-induced pulmonary hypertension in some animal models and in neonates. Effects of chronic hypoxia on PAF receptor (PAF-R) system in fetal pulmonary vasculature are unknown. We investigated the effect of chronic high altitude hypoxia (HAH) in fetal lambs [pregnant ewes were kept at 3,801 m (12,470 ft) altitude from approximately 35 to 145 days gestation] on PAF-R-mediated effects in the pulmonary vasculature. Age-matched controls were kept at sea level. Intrapulmonary arteries were isolated, and smooth muscle cells (SMC-PA) were cultured from HAH and control fetuses. To determine presence of pulmonary vascular remodeling, lung tissue sections were subjected to morphometric analysis. Percentage medial wall thickness was significantly increased (P < 0.05) in arteries at all levels in the HAH lambs. PAF-R protein expression studied by immunocytochemistry and Western blot analysis on lung tissue SMC-PA demonstrated greater PAF-R expression in HAH lambs. PAF-R binding (femtomoles per 10(6) cells) in HAH SMC-PA was 90.3 +/- 4.08 and 66% greater than 54.3 +/- 4.9 in control SMC-PA. Pulmonary arteries from HAH fetuses synthesized >3-fold PAF than vessels from controls. Compared with controls SMC-PA of HAH lambs demonstrated 139% and 40% greater proliferation in 10% FBS alone and with 10 nM PAF, respectively. Our data demonstrate that exposure of ovine fetuses to HAH will result in significant upregulation of PAF synthesis, PAF-R expression, and PAF-R-mediated effects in pulmonary arteries. These findings suggest that increased PAF-R protein expression and increased PAF binding contribute to pulmonary vascular remodeling in these animals and may predispose them to persistent pulmonary hypertension after birth.     

Role of Rho kinases in PKG-mediated relaxation of pulmonary arteries of fetal lambs exposed to chronic high altitude hypoxia

An increase in Rho kinase (ROCK) activity is implicated in chronic hypoxia-induced pulmonary hypertension. In the present study, we determined the role of ROCKs in cGMP-dependent protein kinase (PKG)-mediated pulmonary vasodilation of fetal lambs exposed to chronic hypoxia. Fourth generation pulmonary arteries were isolated from near-term fetuses ( approximately 140 days of gestation) delivered from ewes exposed to chronic high altitude hypoxia for approximately 110 days and from control ewes. In vessels constricted to endothelin-1, 8-bromoguanosine-cGMP (8-Br-cGMP) caused a smaller relaxation in chronically hypoxic (CH) vessels compared with controls. Rp-8-Br-PET-cGMPS, a PKG inhibitor, attenuated relaxation to 8-Br-cGMP in control vessels to a greater extent than in CH vessels. Y-27632, a ROCK inhibitor, significantly potentiated 8-Br-cGMP-induced relaxation of CH vessels and had only a minor effect in control vessels. The expression of PKG was increased but was not accompanied with an increase in the activity of the enzyme in CH vessels. The expression of type II ROCK and activity of ROCKs were increased in CH vessels. The phosphorylation of threonine (Thr)696 and Thr850 of the regulatory subunit MYPT1 of myosin light chain phosphatase was inhibited by 8-Br-cGMP to a lesser extent in CH vessels than in controls. The difference was eliminated by Y-27632. These results suggest that chronic hypoxia in utero attenuates PKG-mediated relaxation in pulmonary arteries, partly due to inhibition of PKG activity and partly due to enhanced ROCK activity. Increased ROCK activity may inhibit PKG action through increased phosphorylation of MYPT1 at Thr696 and Thr850.