Value: Changes in the Detection and Recognition Thresholds of Three Basic Tastes in Lung Cancer Patients Receiving Cisplatin and Paclitaxel and Its Association with Nutritional and Quality of Life Parameters

We evaluated the effects of cisplatin and paclitaxel on taste acuity and their associations with nutritional and health-related quality of life (HRQL) in patients with advanced non-small-cell lung cancer (NSCLC). Forty chemotherapy (CT)-naïve patients were assessed at baseline and after two cycles of paclitaxel and cisplatin. The taste evaluation was performed using a rinsing technique to identify detection and recognition thresholds (DT and RT) of bitter, sweet, and umami tastes. At baseline, 37.5% of the patients reported dysgeusia. After CT, the patients showed lower medians DT (p = 0.017) and RT (p = 0.028) for umami taste. These decreases were associated with clinical neuropathy, worse HRQL, and a tendency toward increased appetite loss. Additionally, CT did not significantly reduce the median DT for sweet (p = 0.09), which is associated with lower intake of protein (p = 0.015), animal protein (p = 0.010), fat (p = 0.004), and iron (p = 0.047). CT decreased the median DT for bitter (p = 0.035); however, this decrease was not associated with nutritional parameters or with HRQL. Sensitivity to taste increased with paclitaxel and cisplatin CT, making foods more unpleasant, and it was associated with neuropathy, worse HRQL, and reduced nutrient intake in advanced NSCLC patients. The protocol was registered at clinicaltrials.gov (NCT01540045).     

Knowledge, attitudes, and practices of baccalaureate nursing students regarding oral health assessment

Good oral health is important to overall health. Oral and pharyngeal cancers account for 2% of all cancers, yet no significant improvement in mortality has been demonstrated over the past 30 years. Nurses are in a unique position to integrate and conduct oral health assessments across a wide range of practice settings. Although nursing programs include health assessment and promotion in their curricula, there is poor integration of oral health as a focus. This study aimed to identify the knowledge, attitudes, and practices of baccalaureate nursing students about oral health assessment. A convenience sample of 163 students in two undergraduate courses within a baccalaureate nursing education program was surveyed. Findings indicated that these nursing students felt that oral health was essential to their nursing practice; however, they did not have a full understanding of the key components of an oral health examination or about effective smoking cessation strategies.     

Invasion profiles of Brazilian field isolates of Plasmodium falciparum: phenotypic and genotypic analyses

The invasion of red blood cells (RBCs) by Plasmodium falciparum is dependent on multiple molecular interactions between erythrocyte receptors and parasite ligands. Invasion studies using culture-adapted parasite strains have indicated significant receptor heterogeneity. It is not known whether this heterogeneity reflects the parasite invasion arsenal in the field. We have studied the invasion phenotypes of 14 distinct field isolates from the Legal Amazon areas of Brazil by using erythrocyte invasion assays to investigate invasion into normal, enzyme-treated, and clinical-mutant RBCs. Analysis of these isolates revealed four distinct invasion profiles. Using En(a-) cells to get an unequivocal estimate of the use of glycophorin A (GPA) as a receptor, we found that the 175-kDa erythrocyte-binding antigen (EBA-175)/GPA pathway was used by a minority of the parasite isolates studied. Although polymorphism of region II domains at specific amino acid positions in both EBA-140 and EBA-181 was found in these field isolates, this did not correlate with invasion profiles and thus receptor selectivity. These studies have further confirmed the existence of a significant diversity of invasion pathways in nature and suggest that additional parasite ligands will have to be targeted to devise global vaccines that will work in the field.     

Decreased bone density in men on methadone maintenance therapy

Aims Opioid use may impact adversely upon skeletal health. Participants in methadone maintenance programmes commonly have prolonged exposure to opioids. We sought to determine whether participants in a methadone maintenance programme have evidence of altered bone mineral density (BMD) and bone turnover. Design Cross‐sectional study of people taking methadone maintenance therapy (MMT). Setting Clinical research centre. Participants Eighty‐three people (48 men, 35 women) who had taken MMT for a median (interquartile range) of 11 (6–16) years. Comparison data were from both a normative database and control subjects recruited and assessed at the same location as the participants taking MMT. Measurements BMD at lumbar spine, total hip and total body; biochemical markers of bone turnover. Findings In men taking MMT, BMD was lower than normal at each skeletal site [mean, 95% confidence interval Z‐score ?1.1 (?1.6 to ?0.7) at the lumbar spine, ?1.0 (?1.3 to ?0.7) at the total hip, and ?1.1 (?1.4 to ?0.8) at the total body, P < 0.001 at each site]. BMD in the women taking MMT was not different from control values. Bone turnover was within the normal range in both genders. Serum testosterone was lower in the men taking MMT than in controls. Conclusions BMD is lower than normal throughout the skeleton in men, but not women, taking MMT. Assessment of skeletal health, including estimation of absolute fracture risk, should be undertaken in men participating in methadone maintenance programmes.     

Chromosomal translocations and karyotype complexity in chronic lymphocytic leukemia: A systematic reappraisal of classic cytogenetic data

The significance of chromosomal translocations (CTRAs) and karyotype complexity (KC) in chronic lymphocytic leukemia (CLL) remains uncertain. To gain insight into these issues, we evaluated a series of 1001 CLL cases with reliable classic cytogenetic data obtained within 6 months from diagnosis before any treatment. Overall, 320 cases were found to carry ≥1 CTRAs. The most frequent chromosome breakpoints were 13q, followed by 14q, 18q, 17q, and 17p; notably, CTRAs involving chromosome 13q showed a wide spectrum of translocation partners. KC (≥3 aberrations) was detected in 157 cases and significantly (P < 0.005) associated with unmutated IGHV genes and aberrations of chromosome 17p. Furthermore, it was identified as an independent prognostic factor for shorter time‐to‐first‐treatment. CTRAs were assigned to two categories (i) CTRAs present in the context of KC, often with involvement of chromosome 17p aberrations, occurring mostly in CLL with unmutated IGHV genes; in such cases, we found that KC rather than the presence of CTRAs per se negatively impacts on survival; (ii) CTRAs in cases without KC, having limited if any impact on survival. On this evidence, we propose that all CTRAs in CLL are not equivalent but rather develop by different processes and are associated with distinct clonal behavior. Am. J. Hematol. 89:249–255, 2014. © 2013 Wiley Periodicals, Inc.     

Murine Recombinant Angiotensin-Converting Enzyme 2: Effect on Angiotensin II-Dependent Hypertension and Distinctive Angiotensin-Converting Enzyme 2 Inhibitor Characteristics on Rodent and Human Angiotensin-Converting Enzyme 2

A newly produced murine recombinant angiotensin (Ang)-converting enzyme 2 (ACE2) was characterized in vivo and in vitro. The effects of available ACE2 inhibitors (MLN-4760 and 2 conformational variants of DX600, linear and cyclic) were also examined. When murine ACE2 was given to mice for 4 weeks, a marked increase in serum ACE2 activity was sustainable. In acute studies, mouse ACE2 (1 mg/kg) obliterated hypertension induced by Ang II infusion by rapidly decreasing plasma Ang II. These effects were blocked by MLN-4760 but not by either form of DX600. In vitro, conversion from Ang II to Ang-(1-7) by mouse ACE2 was blocked by MLN-4760 (10(-6) m) but not by either form of DX600 (10(-5) m). Quantitative analysis of multiple Ang peptides in plasma ex vivo revealed formation of Ang-(1-9) from Ang I by human but not by mouse ACE2. Both human and mouse ACE2 led to the dissipation of Ang II with formation of Ang (1-7). By contrast, mouse ACE2-driven Ang-(1-7) formation from Ang II was blocked by MLN-4760 but not by either linear or cyclic DX600. In conclusion, sustained elevations in serum ACE2 activity can be accomplished with murine ACE2 administration, thereby providing a strategy for ACE2 amplification in chronic studies using rodent models of hypertension and cardiovascular disease. Human but not mouse ACE2 degrades Ang I to form Ang-(1-9). There are also species differences regarding rodent and human ACE2 inhibition by known inhibitors such that MLN-4760 inhibits both human and mouse ACE2, whereas DX600 only blocks human ACE2 activity.     

Causal effect of disconnection lesions on interhemispheric functional connectivity in rhesus monkeys

In the absence of external stimuli or task demands, correlations in spontaneous brain activity (functional connectivity) reflect patterns of anatomical connectivity. Hence, resting-state functional connectivity has been used as a proxy measure for structural connectivity and as a biomarker for brain changes in disease. To relate changes in functional connectivity to physiological changes in the brain, it is important to understand how correlations in functional connectivity depend on the physical integrity of brain tissue. The causal nature of this relationship has been called into question by patient data suggesting that decreased structural connectivity does not necessarily lead to decreased functional connectivity. Here we provide evidence for a causal but complex relationship between structural connectivity and functional connectivity: we tested interhemispheric functional connectivity before and after corpus callosum section in rhesus monkeys. We found that forebrain commissurotomy severely reduced interhemispheric functional connectivity, but surprisingly, this effect was greatly mitigated if the anterior commissure was left intact. Furthermore, intact structural connections increased their functional connectivity in line with the hypothesis that the inputs to each node are normalized. We conclude that functional connectivity is likely driven by corticocortical white matter connections but with complex network interactions such that a near-normal pattern of functional connectivity can be maintained by just a few indirect structural connections. These surprising results highlight the importance of network-level interactions in functional connectivity and may cast light on various paradoxical findings concerning changes in functional connectivity in disease states.     

A Real-Time Method to Evaluate the Nasal Deposition and Clearance of Acetone in the Human Volunteer

Nasal dosimetry models have become increasingly quantitative as insights into tissue deposition/clearance and computational fluid dynamics have become available. Validation of these models requires sufficient experimental data. However, investigations into respiratory deposition, particularly in human volunteers, have been historically limited due to methodological limitations. To overcome this, a method for evaluating the nasal wash-in, wash-out phenomena of a highly water-soluble compound in human volunteers was developed and characterized. This methodology was assessed using controlled human inhalation exposures to uniformly labeled [13 C]acetone at approximately 1 ppm concentration for 30 min under different breathing maneuvers (inhale nose/exhale nose; inhale nose/exhale mouth; inhale mouth/exhale nose). A small-diameter air-sampling probe inserted in the nasopharyngeal cavity of the volunteer was connected directly to an ion-trap mass spectrometer capable of sampling every 0.8 s. A second ion-trap mass spectrometer simultaneously sampled from the volunteer's exhaled breath stream via a breath-inlet device interface. Together, the two mass spectrometers provided real-time appraisal of the [13 C]acetone concentrations in the nasopharyngeal region and in the exhaled breath stream before, during, and after the different breathing maneuvers. The breathing cycle (depth and frequency) and heart rate were concurrently monitored throughout the exposure using a heart-rate monitor and a human plethysmograph to differentiate inhalation and exhalation. Graphical overlay of the plethysmography results with the mass spectrometer measurements show clear quantifiable differences in [13 C]acetone levels at the nasal probe as a function of breathing maneuvers. Breath-by-breath analyses of [13 C]acetone concentrations indicate that between 40 and 75% of the compound is absorbed upon inhalation and nearly all of that absorbed is released back into the breath stream during exhalation.