Gene expression profiles of serous, endometrioid, and clear cell subtypes of ovarian and endometrial cancer.

PURPOSE: The presence of similar histologic subtypes of epithelial ovarian and endometrial cancers has long been noted, although the relevance of this finding to pathogenesis and clinical management is unclear. Despite similar clinical characteristics, histologic subtypes of cancers of the ovary and endometrium are treated according to organ of origin. This study compares the gene expression profiles of analogous histologic subtypes of cancers of the ovary and endometrium using the same genomic platform to determine the similarities and differences between these tumors. EXPERIMENTAL DESIGN: Gene expression profiles of 75 cancers (endometrioid, serous, and clear cell) of the ovary and endometrium, five renal clear cell cancers, and seven normal epithelial brushings were determined using a 11,000-element cDNA array. All images were analyzed using BRB ArrayTools. Validation was done using real-time PCR on select genes and immunohistochemical staining. RESULTS: Comparison across endometrial and ovarian cancers and serous and endometrioid tumors showed expression patterns reflecting their organ of origin. Clear cell tumors, however, showed remarkably similar expression patterns regardless of their origin, even when compared with renal clear cell samples. A set of 43 genes was common to comparisons of each of the three histologic subtypes of ovarian cancer with normal ovarian surface epithelium. CONCLUSIONS: The comparison of the gene expression profiles of endometrioid and serous subtypes of ovarian and endometrial cancer are largely unique to the combination of a particular subtype in a specific organ. In contrast, clear cell cancers show a remarkable similarity in gene expression profiles across organs (including kidney) and could not be statistically distinguished.     

Quantitative contributions of gluconeogenesis to glucose production during fasting in type 2 diabetes mellitus

Contributions of gluconeogenesis to glucose production were determined between 14 to 22 hours into a fast in type 2 diabetics (n = 9) and age-weight-matched controls (n = 7); ages, 60.4 +/- 2.3 versus 55.6 +/- 1.2 years and body mass indices (BMI) 28.6 +/- 2.3 versus 26.6 +/- 0.8 kg/m2. Production was measured using a primed-continuous [6,6-2H2]glucose infusion and gluconeogenesis from 2H enrichment at carbons 2 and 5 of blood glucose on 2H2O ingestion. Plasma glucose concentration declined from 9.6 +/- 0.6 at 14 hours to 7.3 +/- 0.6 at 22 hours in the diabetics (P = .001) and from 5.4 +/- 0.1 to 5.0 +/- 0.1 in the controls (P < .05). Production from the 17th to 22nd hour declined 27.1% +/- 0.6% in the diabetics versus 18.5% +/- 0.8% in the controls (P = .001); from 10.4 +/- 0.3 to 7.6 +/- 0.2 versus 10.0 +/- 0.4 to 8.2 +/- 0.4 micromol/kg/min. Percent contributions of gluconeogenesis to production measured at 1 1/2 to 2-hour intervals beginning the 15th hour were 6.8% +/- 1.0% more in the diabetics than controls. The quantity of glucose contributed by gluconeogenesis declined 19.8% +/- 3.8% (P < .001) in the diabetics and 6.9% +/- 2.3% in the controls (P = .05); 7.21 +/- 0.32 to 5.74 +/- 0.26 versus 6.20 +/- 0.28 to 5.75 +/- 0.24 micromol/kg/min. The contribution of glycogenolysis to production, estimated from the difference between production and gluconeogenesis, declined to the same extent in diabetic and control subjects, 40.7% +/- 6.6% and 37.7% +/- 4.1%; from 3.23 +/- 0.35 to 1.86 +/- 0.26 versus 3.81 +/- 0.22 to 2.42 +/- 0.28 micromol/kg/min. Thus, gluconeogenesis contributed more to glucose production in the diabetic than control subjects. Production and the contribution of gluconeogenesis declined more in the diabetic subjects during the fast. The factors regulating these changes remain uncertain.     

Investigating ultrafast carrier dynamics in perovskite solar cells with an extended π-conjugated polymeric diketopyrrolopyrrole layer for hole transportation

Here, we show a new diketopyrrole based polymeric hole-transport material (PBDTP-DTDPP, (poly[[2,5-bis(2-hexyldecyl)-2,3,5,6-tetrahydro-3,6-dioxopyrrolo[3,4-c]pyrrole-1,4-diyl]-alt-[[2,2′-(4,8-bis(4-ethylhexyl-1-phenyl)-benzo[1,2-b:4,5-b′]dithiophene)bis-thieno[3,2-b]thiophen]-5,5′-diyl]])) for application in perovskite solar cells. The material performance was tested in a solar cell with an optimized configuration, FTO/SnO₂/perovskite/PBDTP-DTDPP/Au, and the device showed a power conversion efficiency of 14.78%. The device charge carrier dynamics were investigated using transient absorption spectroscopy. The charge separation and recombination kinetics were determined in a device with PBDTP-DTDPP and the obtained results were compared to a reference device. We find that PBDTP-DTDPP enables similar charge separation time (<∼4.8 ps) to the spiro-OMeTAD but the amount of nongeminate recombination is different. Specifically, we find that the polymeric PBDTP-DTDPP hole-transport layer (HTL) slows-down the second-order recombination much less than spiro-OMeTAD. This effect is of particular importance in studying the charge transportation in optimized solar cell devices with diketopyrrole based HTL materials.

Diketopyrrole based hole-transport organic semiconductor was employed in perovskite solar cells and charge carrier dynamics was explained.     

Reduced contribution of executive functions in impaired working memory performance in mild traumatic brain injury patients

Aim

Mild traumatic brain injury (MTBI) is associated with often selective impairment of both working memory (WM) and the executive functions (EFs). Research indicates that one of the commonest deficits present in MTBI patients falls in the domain of WM. We aimed to investigate the role of EFs in WM impairment following MTBI.

Methods

Performance on the tests of EFs and the verbal and visuo-spatial WM of 30 consecutive MTBI patients were compared with age/education/IQ matched 30 normal healthy control participants. Correlation between EFs and WM was studied separately for the MTBI and the control group.

Results

The MTBI and control group were tested on a range of EF tests and WM. The MTBI group was demonstrated impairment on verbal and visuo-spatial WM and category fluency tests only. Furthermore, the MTBI group had fewer significant correlations between the WM and EFs (5 out of 54 possible correlations) than in the control group (13 out of 54 possible correlations).

Conclusions

We suggest that MTBI may lead to WM deficits as the contribution of executive processes to support the WM is diminished following MTBI. Such an understanding of the poor WM performance in MTBI patients will be helpful when planning appropriate strategies for cognitive rehabilitation.     

Neural correlates of disparity-defined shape discrimination in the human brain

Binocular disparity, the slight differences between the images registered by our two eyes, provides an important cue when estimating the three-dimensional (3D) structure of the complex environment we inhabit. Sensitivity to binocular disparity is evident at multiple levels of the visual hierarchy in the primate brain, from early visual cortex to parietal and temporal areas. However, the relationship between activity in these areas and key perceptual functions that exploit disparity information for 3D shape perception remains an important open question. Here we investigate the link between human cortical activity and the perception of disparity-defined shape, measuring fMRI responses concurrently with psychophysical shape judgments. We parametrically degraded the coherence of shapes by shuffling the spatial position of dots whose disparity defined the 3D structure and investigated the effect of this stimulus manipulation on both cortical activity and shape discrimination. We report significant relationships between shape coherence and fMRI response in both dorsal (V3, hMT+/V5) and ventral (LOC) visual areas that correspond to the observers' discrimination performance. In contrast to previous suggestions of a dichotomy of disparity-related processes in the ventral and dorsal streams, these findings are consistent with proposed interactions between these pathways that may mediate a continuum of processes important in perceiving 3D shape from coarse contour segmentation to fine curvature estimation.     

Gait asymmetries are exacerbated at faster walking speeds in individuals with acute anterior cruciate ligament reconstruction

Previous research suggests more biomechanically demanding tasks (e.g., stair descent, hopping) magnify biomechanical asymmetries compared with walking after anterior cruciate ligament (ACL) reconstruction. However, it is unclear if modifying task-specific constraints, like walking speed also elicits greater biomechanical asymmetries in this population. We examined the effects of manipulating walking speed on ground reaction force (GRF) asymmetries in individuals with ACL reconstruction and uninjured controls. Thirty individuals with ACL reconstruction (age = 20.6 ± 5.4 years, body mass index [BMI] = 23.9 ± 3.3 kg/m²) and 15 controls (age = 23.1 ± 4.5 years, BMI = 23.6 ± 2.7 kg/m²) were tested on an instrumented treadmill at three speeds (100%, 120%, and 80% self-selected speed). Bilateral vertical and posterior-anterior GRFs were recorded at each speed. GRF asymmetries were calculated by subtracting the uninjured from the injured limb at each percent of stance. Statistical parametric mapping was used to evaluate the effects of speed on GRF asymmetries across stance. We found vertical and posterior GRF asymmetries were exacerbated at faster speeds and reduced at slower speeds in ACL individuals but not controls (p < .05). No differences in anterior GRF asymmetries were observed between speeds in either group (p > .05). Our results suggest increasing walking speed magnifies GRF asymmetries in individuals with ACL reconstruction. Statement of Clinical Significance: Evaluating both preferred and fast walking speeds may aid in characterizing biomechanical asymmetries in individuals with ACL reconstruction which may be valuable in earlier rehabilitative time points when more difficult tasks like hopping and running are not feasible.     

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Error associated with antagonist muscle activity in isometric knee strength testing

The purpose of this study was to determine the measurement error associated with antagonist muscle activity in isometric knee strength testing at 60° of knee flexion in both sexes. Muscle specific EMG–contraction intensity relationships were obtained from 22 young people by having them match moment targets ranging from 10% to 100% peak moment. The moments attributed to each of the quadriceps and hamstrings muscles were partitioned using a practical mathematical model. Subject specific EMG–moment relationships were defined for each muscle using second-order polynomial equations. These equations were subsequently used to predict the countermoment associated with antagonist muscle activity. Error during strength testing was calculated by expressing net antagonist moments as a percentage of net agonist moments. The net antagonist moments associated with quadriceps and hamstrings muscle activity were 11.0% and 8.7% of the peak moment values recorded when the same muscle groups were acting as agonists. The error associated with antagonist activity was significantly higher in knee flexion (20.1%) than in knee extension (4.5%). Females displayed significantly higher error in knee flexor testing (P < 0.001). Limb symmetry indices did not change significantly when the countermoments generated by the antagonist muscles were accounted for (P > 0.05). The results of this study indicate that the error associated with antagonist activity in knee extensor testing is relatively small, whereas the error in knee flexor testing is larger. This is due to the quadriceps being much stronger than the hamstrings muscles while displaying similar levels of antagonist activity.