Expression of Concern: Direct observation of the THz Kerr effect (TKE) in deionized, distilled and buffered (PBS) water.

Expression of concern for 'Direct observation of the THz Kerr effect (TKE) in deionized, distilled and buffered (PBS) water' by Andrzej Dobek et al., Phys. Chem. Chem. Phys., 2017, 19, 26749-26757, https://doi.org/10.1039/c7cp04061j.

Terahertz endoscopic imaging for colorectal cancer detection: Current status and future perspectives.

Terahertz (THz) imaging is progressing as a robust platform for myriad applications in the field of security, health, and material science. The THz regime, which comprises wavelengths spanning from microns to millimeters, is non-ionizing and has very low photon energy: Making it inherently safe for biological imaging. Colorectal cancer is one of the most common causes of death in the world, while the conventional screening and standard of care yet relies exclusively on the physician's experience. Researchers have been working on the development of a flexible THz endoscope, as a potential tool to aid in colorectal cancer screening. This involves building a single-channel THz endoscope, and profiling the THz response from colorectal tissue, and demonstrating endogenous contrast levels between normal and diseased tissue when imaging in reflection modality. The current level of contrast provided by the prototype THz endoscopic system represents a significant step towards clinical endoscopic application of THz technology for in-vivo colorectal cancer screening. The aim of this paper is to provide a short review of the recent advances in THz endoscopic technology and cancer imaging. In particular, the potential of single-channel THz endoscopic imaging for colonic cancer screening will be highlighted.

Direct observation of the THz Kerr effect (TKE) in deionized, distilled and buffered (PBS) water.

Nonlinear THz pump-optical probe (THz-OKE) measurements in deionized, distilled and buffered (PBS) water are reported. A laser system that produces pulses at 800 nm, 30 fs FWHM, at a repetition rate of 1 kHz and an energy of 6 µJ per pulse, was a source of the probe optical beam and of the pump beam of THz 2 ps pulses. The electric field strength inducing birefringence in water samples was ETHz = 1.35 × 106 V m-1. These samples were chosen in order to study the effect of ionic concentration on water behavior in the ultrafast time scale. Differentiation between ultrafast effects resulting from internal H2O properties and those resulting from H2O-ion interactions was analyzed. These two effects may be connected to a difference in the fluctuations of the network of intermolecular hydrogen bonds of water molecules in the presence and absence of ions in solution. The results indicate that such fluctuations significantly alter water birefringence amplitude and its dynamics.

Continuous-wave circular polarization terahertz imaging.

Biomedical applications of terahertz (THz) radiation are appealing because THz radiation is nonionizing and has the demonstrated ability to detect intrinsic contrasts between cancerous and normal tissue. A linear polarization-sensitive detection technique for tumor margin delineation has already been demonstrated; however, utilization of a circular polarization-sensitive detection technique has yet to be explored at THz frequencies. A reflective, continuous-wave THz imaging system capable of illuminating a target sample at 584 GHz with either linearly or circularly polarized radiation, and capable of collecting both cross- and copolarized signals remitted from the target, is implemented. To demonstrate the system's utility, a fresh ex vivo human skin tissue specimen containing nonmelanoma skin cancer was imaged. Both polarization-sensitive detection techniques showed contrast between tumor and normal skin tissue, although some differences in images were observed between the two techniques. Our results indicate that further investigation is required to explain the contrast mechanism, as well as to quantify the specificity and sensitivity of the circular polarization-sensitive detection technique.

Single-channel prototype terahertz endoscopic system.

We demonstrate the design and development of an innovative single-channel terahertz (THz) prototype endoscopic imaging system based on flexible metal-coated THz waveguides and a polarization specific detection technique. The continuous-wave (CW) THz imaging system utilizes a single channel to transmit and collect the reflected intrinsic THz signal from the sample. Since the prototype system relies on a flexible waveguide assembly that is small enough in diameter, it can be readily integrated with a conventional optical endoscope. This study aims to show the feasibility of waveguide enabled THz imaging. We image various objects in transmission and reflection modes. We also image normal and cancerous colonic tissues in reflectance mode using a polarization specific imaging technique. The resulting cross-polarized THz reflectance images showed contrast between normal and cancerous colonic tissues at 584 GHz. The level of contrast observed using endoscopic imaging correlates well with contrast levels observed in ex vivo THz reflectance studies of colon cancer. This indicates that the single-channel flexible waveguide-based THz endoscope presented here represents a significant step forward in clinical endoscopic application of THz technology to aid in in vivo cancer screening.

Imaging of ex vivo nonmelanoma skin cancers in the optical and terahertz spectral regions optical and terahertz skin cancers imaging.

We tested the hypothesis that polarization sensitive optical and terahertz imaging may be combined for accurate nonmelanoma skin cancer (NMSC) delineation. Nine NMSC specimens were imaged. 513 µm and 440 nm wavelengths were used for terahertz and optical imaging, respectively. Histopathology was processed for evaluation. Terahertz reflectance of NMSC was quantified. Our results demonstrate that cross-polarized terahertz images correctly identified location of the tumours, whereas cross-polarized and polarization difference optical images accurately presented morphological features. Cross-polarized terahertz images exhibited lower reflectivity values in cancer as compared to normal tissue. Combination of optical and terahertz imaging shows promise for intraoperative delineation of NMSC.

Characterization of bending loss in hollow flexible terahertz waveguides.

Attenuation characteristics of hollow, flexible, metal and metal/dielectric coated polycarbonate waveguides were investigated using an optically pumped far infrared (FIR) laser at 215 µm. The bending loss of silver coated polycarbonate waveguides were measured as a function of various bending angles, bending radii, and bore diameters. Minimal propagation losses of 1.77, 0.96 dB/m were achieved by coupling the lowest loss TE11 mode into the silver or gold coated waveguide, and HE11 mode into the silver/polystyrene coated waveguides respectively. The maximal bending loss was found to be less than 1 dB/m for waveguides of 2 to 4.1 mm bore diameters, with a 6.4 cm bend radius, and up to 150° bending angle. The investigation shows the preservation of single laser mode in smaller bore waveguides even at greater bending angles.

Continuous wave terahertz transmission imaging of nonmelanoma skin cancers.

BACKGROUND AND OBJECTIVE: Continuous wave terahertz imaging has the potential to offer a safe, noninvasive medical imaging modality for delineating human skin cancers. Terahertz pulse imaging (TPI) has already shown that there is contrast between basal cell carcinoma and normal skin. Continuous-wave imaging offers a simpler, lower cost alternative to TPI. The goal of this study was to investigate the feasibility of continuous wave terahertz imaging for delineating skin cancers by demonstrating contrast between cancerous and normal tissue in transmission mode. MATERIALS AND METHODS: Two CO(2) optically pumped far-infrared molecular gas lasers were used for illuminating the tissue at two frequencies, 1.39 and 1.63 THz. The transmitted signals were detected using a liquid Helium cooled Silicon bolometer. Fresh skin cancer specimens were obtained from Mohs surgeries. The samples were processed and imaged within 24 hours after surgery. During the imaging experiment the samples were kept in pH-balanced saline to prevent tissue dehydration. At both THz frequencies two-dimensional THz transmission images of nonmelanoma skin cancers were acquired with spatial resolution of 0.39 mm at 1.4 THz and 0.49 mm at 1.6 THz. For evaluation purposes, hematoxylin and eosin (H&E) histology was processed from the imaged tissue. RESULTS: A total of 10 specimens were imaged and it was determined that for both frequencies, the areas of decreased transmission in the THz image correlated well with cancerous areas in the histopathology. Two negative controls were also imaged. The difference in transmission between normal and cancerous tissue was found to be approximately 60% at both frequencies, which suggests that contrast between normal and cancerous tissue at these frequencies is dominated by differences in water content. CONCLUSIONS: Our results suggest that intraoperative delineation of nonmelanoma skin cancers using continuous-wave terahertz imaging is feasible.

Silymarin modulates doxorubicin-induced oxidative stress, Bcl-xL and p53 expression while preventing apoptotic and necrotic cell death in the liver.

The emergence of silymarin (SMN) as a natural remedy for liver diseases, coupled with its entry into NIH clinical trial, signifies its hepatoprotective potential. SMN is noted for its ability to interfere with apoptotic signaling while acting as an antioxidant. This in vivo study was designed to explore the hepatotoxic potential of Doxorubicin (Dox), the well-known cardiotoxin, and in particular whether pre-exposures to SMN can prevent hepatotoxicity by reducing Dox-induced free radical mediated oxidative stress, by modulating expression of apoptotic signaling proteins like Bcl-xL, and by minimizing liver cell death occurring by apoptosis or necrosis. Groups of male ICR mice included Control, Dox alone, SMN alone, and Dox with SMN pre/co-treatment. Control and Dox groups received saline i.p. for 14 days. SMN was administered p.o. for 14 days at 16 mg/kg/day. An approximate LD(50) dose of Dox, 60 mg/kg, was administered i.p. on day 12 to animals receiving saline or SMN. Animals were euthanized 48 h later. Dox alone induced frank liver injury (>50-fold increase in serum ALT) and oxidative stress (>20-fold increase in malondialdehyde [MDA]), as well as direct damage to DNA (>15-fold increase in DNA fragmentation). Coincident genomic damage and oxidative stress influenced genomic stability, reflected in increased PARP activity and p53 expression. Decreases in Bcl-xL protein coupled with enhanced accumulation of cytochrome c in the cytosol accompanied elevated indexes of apoptotic and necrotic cell death. Significantly, SMN exposure reduced Dox hepatotoxicity and associated apoptotic and necrotic cell death. The effects of SMN on Dox were broad, including the ability to modulate changes in both Bcl-xL and p53 expression. In animals treated with SMN, tissue Bcl-xL expression exceeded control values after Dox treatment. Taken together, these results demonstrated that SMN (i) reduced, delayed onset, or prevented toxic effects of Dox which are typically associated with hydroxyl radical production, (ii) performed as an antioxidant limiting oxidative stress, (iii) protected the integrity of the genome, and (iv) antagonized apoptotic and necrotic cell death while increasing antiapoptotic Bcl-xL protein levels and minimizing the leakage of proapoptotic cytochrome c from liver mitochondria. These observations demonstrate the protective actions of SMN in liver, and raise the possibility that such protection may extend to other organs during Dox treatment including the heart.

Duffy (Fy), DARC, and neutropenia among women from the United States, Europe and the Caribbean.

Neutropenia associated with race/ethnicity has essentially been unexplained and, although thought to be benign, may affect therapy for cancer or other illnesses. A recent study linked a single nucleotide polymorphism (SNP) (rs2814778) in the Duffy antigen/receptor chemokine gene (DARC) with white blood cell count. We therefore analysed the association of the rs2814778 CC, TC and TT genotypes with absolute neutrophil count (ANC) among asymptomatic women from the Caribbean, Europe and the United States. Among 261 study participants, 33/47 women from Barbados/Trinidad-Tobago, 34/49 from Haiti, 26/37 from Jamaica, and 29/38 US-born black women, but only 4/50 from the Dominican Republic and 0/40 US- or European-born whites (P = 0.0001) had the CC genotype. In a linear regression model that included percentage African ancestry, national origin, cytokines, socio-economic factors and the ELA2 rs57834246 SNP, only the DARC rs2814778 genotype and C-reactive protein were associated with ANC (P < 0.0001). Women with the CC genotype had lower ANC than other women. Further research is needed on the associations of rs2814778 genotype with neutropenia and treatment delay in the setting of cancer. A better understanding of these associations may help to improve cancer outcomes among individuals of African ancestry.

Duffy (Fy), DARC, and neutropenia among women from the United States, Europe and the Caribbean.

Neutropenia associated with race/ethnicity has essentially been unexplained and, although thought to be benign, may affect therapy for cancer or other illnesses. A recent study linked a single nucleotide polymorphism (SNP) (rs2814778) in the Duffy antigen/receptor chemokine gene (DARC) with white blood cell count. We therefore analysed the association of the rs2814778 CC, TC and TT genotypes with absolute neutrophil count (ANC) among asymptomatic women from the Caribbean, Europe and the United States. Among 261 study participants, 33/47 women from Barbados/Trinidad-Tobago, 34/49 from Haiti, 26/37 from Jamaica, and 29/38 US-born black women, but only 4/50 from the Dominican Republic and 0/40 US- or European-born whites (P = 0.0001) had the CC genotype. In a linear regression model that included percentage African ancestry, national origin, cytokines, socio-economic factors and the ELA2 rs57834246 SNP, only the DARC rs2814778 genotype and C-reactive protein were associated with ANC (P < 0.0001). Women with the CC genotype had lower ANC than other women. Further research is needed on the associations of rs2814778 genotype with neutropenia and treatment delay in the setting of cancer. A better understanding of these associations may help to improve cancer outcomes among individuals of African ancestry.

Neutropenia in 6 ethnic groups from the Caribbean and the U.S.

BACKGROUND: Low white blood cell counts (WBC) or absolute neutrophil counts (ANC) may delay or prevent the completion of appropriate chemotherapy, especially among women receiving adjuvant therapy for breast and colon cancer, and affect cancer survival. Because race/ethnicity is also associated with survival, the authors compared WBC and ANC in healthy American-born women of African descent and European descent, and women from Barbados/Trinidad-Tobago, the Dominican Republic, Haiti, and Jamaica. METHODS: Blood samples from 261 healthy women ages 20 to 70 years were tested for WBC with differential, cytokine and growth factor levels, and ancestry informative and neutrophil elastase polymorphisms. The authors analyzed the association between neutropenia and serum WBC growth factor levels, cytokine levels, and neutrophil elastase c199a polymorphism. RESULTS: The median WBC and ANC differed among the 6 groups (P < .01 for WBC and P < .0001 for ANC). Dominicans were found to have higher median WBC and ANC than all other groups (P < .03). Neutropenia (ANC < 1500 cu/mm) was observed among 2.7% to 12.5% of the groups of predominantly African descent; no other groups were found to have neutropenia (P < .05). Granulocyte-colony-stimulating factor was found to be lower in white women, but tumor necrosis factor-alpha and C-reactive protein were not found to be correlated with ethnicity. Women of African origin were more likely to have polymorphisms of African ancestry (P < .001) and c199a alleles (P < .0001), which were also associated with low ANC levels. CONCLUSIONS: In the current study, the authors observed a strong association between neutropenia and African descent among asymptomatic women from the U.S. and the Caribbean. Among women of African descent who develop a malignancy, this association may contribute to racial disparities in treatment and outcomes.

Neutropenia in 6 ethnic groups from the Caribbean and the U.S.

BACKGROUND: Low white blood cell counts (WBC) or absolute neutrophil counts (ANC) may delay or prevent the completion of appropriate chemotherapy, especially among women receiving adjuvant therapy for breast and colon cancer, and affect cancer survival. Because race/ethnicity is also associated with survival, the authors compared WBC and ANC in healthy American-born women of African descent and European descent, and women from Barbados/Trinidad-Tobago, the Dominican Republic, Haiti, and Jamaica. METHODS: Blood samples from 261 healthy women ages 20 to 70 years were tested for WBC with differential, cytokine and growth factor levels, and ancestry informative and neutrophil elastase polymorphisms. The authors analyzed the association between neutropenia and serum WBC growth factor levels, cytokine levels, and neutrophil elastase c199a polymorphism. RESULTS: The median WBC and ANC differed among the 6 groups (P < .01 for WBC and P < .0001 for ANC). Dominicans were found to have higher median WBC and ANC than all other groups (P < .03). Neutropenia (ANC < 1500 cu/mm) was observed among 2.7% to 12.5% of the groups of predominantly African descent; no other groups were found to have neutropenia (P < .05). Granulocyte-colony-stimulating factor was found to be lower in white women, but tumor necrosis factor-alpha and C-reactive protein were not found to be correlated with ethnicity. Women of African origin were more likely to have polymorphisms of African ancestry (P < .001) and c199a alleles (P < .0001), which were also associated with low ANC levels. CONCLUSIONS: In the current study, the authors observed a strong association between neutropenia and African descent among asymptomatic women from the U.S. and the Caribbean. Among women of African descent who develop a malignancy, this association may contribute to racial disparities in treatment and outcomes.

Measuring drug concentrations using pulsatile microdialysis: theory and method development in vitro.

A novel method of rapidly sampling drug concentrations, based on pulsatile microdialysis (PMD), was developed. In PMD, a dialysate fluid is pumped into a microdialysis probe, allowed to occupy the probe while at rest for some time, and then flushed at a high rate. A model that is based on a Fick's Laws was solved and tested, using methazolamide (MTZ) as the test drug in a variety of experimental setups, including time-dependent donor concentrations. Calibration plots of the donor versus sample concentrations were linear. There was excellent agreement between the calculated and experimental values of the fraction recovered obtained from the calibration plots. In a system for which the donor concentration declined in a first order manner, the data obtained using PMD and direct sampling of the donor were in nearly exact agreement with the theoretical value of k=0.09 min(-1). PMD was also able to collect data points quickly enough to characterize the rapid binding kinetics of MTZ by activated charcoal. It was concluded that PMD is an accurate method of sampling drug concentrations, and can obtain samples over shorter time intervals and more frequently than previously available methods.