Portable Diffuse Reflectance Spectroscopy for Non-invasive and Quantitative Assessment of the Parathyroid Glands Viability During Surgery

Portable Diffuse Reflectance Spectroscopy for Non-invasive and Quantitative Assessment of the Parathyroid Glands Viability During Surgery Mark Romine, Linh Luong, Alex Moazzen, Katie Cho and Paul Lee The parathyroid glands (PTGs) are responsible for the regulation of calcium levels in the blood by secreting a parathyroid hormone. This parathyroid hormone then regulates the body’s absorption, storage, and secretion of calcium, which can directly affect the way muscles and nerves operate. PTGs are often at risk of damage, or accidental removal during thyroid surgeries, because it is challenging to identify PTGs and to determine their viability. Current methods of visual inspections are often subjective and blood panels have long processing times. Diffuse Reflectance Spectroscopy (DRS) may provide a solution for the noninvasive, rapid, and quantitative assessment of the viability of PTGs. DRS is a non-invasive technique that uses the reflectance properties of tissue to quantify the hemoglobin (Hb) and concentrations and tissue oxygenation. DRS consists of a white LED (wavelength 400nm – 700nm) for a light source, a compact spectrometer that records tissue reflectance and a fiber optic probe. In this project, we have built a portable DRS system and verified the performance of the prototyped DRS system. We have characterized a signal-to-noise ratio (SNR) on tissue simulating optical phantom and the computed SNR is around 40 dB as expected. Also, we have demonstrated that DRS can measure the change in oxygenation values in our blood phantom testing. These bench-top tests show that our protype is ready for human study during a thyroid surgery

Wireless, Handheld Diffuse Reflectance Spectroscopy to Quantify Tissue Microvascular Hemodynamics

Diffuse Reflectance Spectroscopy (DRS) is a non-invasive optical method to characterize tissue optical properties for disease diagnosis and health monitoring. Two optical fibers are often used in a DRS system: one to deliver light to the tissue and the other to gather diffuse reflectance spectra, which provide quantitative details about the structure and composition of the tissue. The conventional DRS system, however, is expensive, bulky, and composed of fragile optical fibers and multiple electrical connections. Here we propose to build a wireless, handheld, and fiber-less diffuse optical spectroscopy system. Unfortunately, the diffusion approximation utilized for data analysis of the conventional DRS is no longer valid due to the non-contact configuration of the fiber-less DRS system. To analyze the collected diffuse reflectance spectra using the handheld spectrometer, we have built a reflectance lookup table (LUT) using Monte Carlo simulation. Also, we have conducted some tests using a blood liquid phantom that is made of water, intralipid, and bovine blood, simulating human tissues to evaluate our DRS system with our LUT to extract the phantom\u27s oxygen saturation (SO2). The results show that portable spectrometer estimated SO2 values agree with the traditional DRS system. These results demonstrate that our handheld equipment can accurately estimate tissue oxygenation and hemoglobin levels, thus providing a mean of rapid quantitative tools assessing microvascular hemodynamics

DNA base sequence effects on bulky lesion-induced conformational heterogeneity during DNA replication

4-Aminobiphenyl (ABP) and its structure analog 2-aminofluorene (AF) are well-known carcinogens. In the present work, an unusual sequence effect in the 5′-CTTCTG1G2TCCTCATTC-3′ DNA duplex is reported for ABP- and AF-modified G. Specifically, the ABP modification at G1 resulted in a mixture of 67% major groove B-type (B) and 33% stacked (S) conformers, while at the ABP modification at G2 exclusively resulted in the B-conformer. The AF modification at G1 and G2 lead to 25%:75% and 83%:17% B:S population ratios, respectively. These differences in preferred conformation are due to an interplay between stabilizing (hydrogen bonding and stacking that is enhanced by lesion planarity) and destabilizing (solvent exposure) forces at the lesion site. Furthermore, while the B-conformer is a thermodynamic stabilizer and the S-conformer is a destabilizer in duplex settings, the situation is reversed at the single strands/double strands (ss/ds) junction. Specifically, the twisted biphenyl is a better stacker at the ss/ds junction than the coplanar AF. Therefore, the ABP modification leads to a stronger strand binding affinity of the ss/ds junction than the AF modification. Overall, the current work provides conformational insights into the role of sequence and lesion effects in modulating DNA replication

Restoring Wholeness to Psychiatry: Models of Understanding

Psychiatric practice is at a critical juncture in its evolution. Its identified model for understanding the complexity of individuals and their conditions has been the biopsycho-social-spiritual model since it was first proposed nearly half a century ago. In practice, this construct is being challenged by a biomedical model which asserts all psychiatric conditions can be reduced to either neurotransmitter or gene-based causation. We explore how models are used in science to approximate larger reality, with a focus on Systems Theory, which is the philosophical foundation for the bio-psycho-social-spiritual model to describe why this model is necessarily more complete than the biomedical model. Several examples are presented to illustrate the practical limitations of the reductionist biomedical model and illuminate the impact of its narrow lens upon the assessment and treatment of patients. We argue that the biomedical model is inadequate as it prevents empowerment of the individual and it fails to recognize top-down causation, which are two identifiable strengths of the bio-psycho-social-spiritual model

Neurotropic Lineage III Strains of \u3cem\u3eListeria monocytogenes\u3c/em\u3e Disseminate to the Brain without Reaching High Titer in the Blood

Listeria monocytogenes is thought to colonize the brain using one of three mechanisms: direct invasion of the blood-brain barrier, transportation across the barrier by infected monocytes, and axonal migration to the brain stem. The first two pathways seem to occur following unrestricted bacterial growth in the blood and thus have been linked to immunocompromise. In contrast, cell-to-cell spread within nerves is thought to be mediated by a particular subset of neurotropic L. monocytogenes strains. In this study, we used a mouse model of foodborne transmission to evaluate the neurotropism of several L. monocytogenes isolates. Two strains preferentially colonized the brain stems of BALB/cByJ mice 5 days postinfection and were not detectable in blood at that time point. In contrast, infection with other strains resulted in robust systemic infection of the viscera but no dissemination to the brain. Both neurotropic strains (L2010-2198, a human rhombencephalitis isolate, and UKVDL9, a sheep brain isolate) typed as phylogenetic lineage III, the least characterized group of L. monocytogenes. Neither of these strains encodes InlF, an internalin-like protein that was recently shown to promote invasion of the blood-brain barrier. Acute neurologic deficits were observed in mice infected with the neurotropic strains, and milder symptoms persisted for up to 16 days in some animals. These results demonstrate that neurotropic L. monocytogenes strains are not restricted to any one particular lineage and suggest that the foodborne mouse model of listeriosis can be used to investigate the pathogenic mechanisms that allow L. monocytogenes to invade the brain stem. IMPORTANCE Progress in understanding the two naturally occurring central nervous system (CNS) manifestations of listeriosis (meningitis/meningoencephalitis and rhombencephalitis) has been limited by the lack of small animal models that can readily distinguish between these distinct infections. We report here that certain neurotropic strains of Listeria monocytogenes can spread to the brains of young otherwise healthy mice and cause neurological deficits without causing a fatal bacteremia. The novel strains described here fall within phylogenetic lineage III, a small collection of L. monocytogenes isolates that have not been well characterized to date. The animal model reported here mimics many features of human rhombencephalitis and will be useful for studying the mechanisms that allow L. monocytogenes to disseminate to the brain stem following natural foodborne transmission

Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids

Hepatic gluconeogenesis from amino acids contributes significantly to diabetic hyperglycemia, but the molecular mechanisms involved are incompletely understood. Alanine transaminases (ALT1 and ALT2) catalyze the interconversion of alanine and pyruvate, which is required for gluconeogenesis from alanine. We find that ALT2 is overexpressed in the liver of diet-induced obese and db/db mice and that the expression of the gene encoding ALT2 (GPT2) is downregulated following bariatric surgery in people with obesity. The increased hepatic expression of Gpt2 in db/db liver is mediated by activating transcription factor 4, an endoplasmic reticulum stress-activated transcription factor. Hepatocyte-specific knockout of Gpt2 attenuates incorporation o

Effects of the neonicotinoid pesticide thiamethoxam at field-realistic levels on microcolonies of Bombus terrestris worker bumble bees

Copyright © 2013 Elsevier. Notice: this is the author’s version of a work that was accepted for publication in Ecotoxicology and Environmental Safety. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Ecotoxicology and Environmental Safety, 2014, Vol. 100, pp. 153-158 at: http://dx.doi.org/10.1016/j.ecoenv.2013.10.027Neonicotinoid pesticides are currently implicated in the decline of wild bee populations. Bumble bees, Bombus spp., are important wild pollinators that are detrimentally affected by ingestion of neonicotinoid residues. To date, imidacloprid has been the major focus of study into the effects of neonicotinoids on bumble bee health, but wild populations are increasingly exposed to alternative neonicotinoids such as thiamethoxam. To investigate whether environmentally realistic levels of thiamethoxam affect bumble bee performance over a realistic exposure period, we exposed queenless microcolonies of Bombus terrestris L. workers to a wide range of dosages up to 98 μg kg−1 in dietary syrup for 17 days. Results showed that bumble bee workers survived fewer days when presented with syrup dosed at 98 μg thiamethoxam kg−1, while production of brood (eggs and larvae) and consumption of syrup and pollen in microcolonies were significantly reduced by thiamethoxam only at the two highest concentrations (39, 98 μg kg−1). In contrast, we found no detectable effect of thiamethoxam at levels typically found in the nectars of treated crops (between 1 and 11 μg kg−1). By comparison with published data, we demonstrate that during an exposure to field-realistic concentrations lasting approximately two weeks, brood production in worker bumble bees is more sensitive to imidacloprid than thiamethoxam. We speculate that differential sensitivity arises because imidacloprid produces a stronger repression of feeding in bumble bees than thiamethoxam, which imposes a greater nutrient limitation on production of brood.Natural Environment Research Council (NERC

The Marker State Space (MSS) Method for Classifying Clinical Samples

The development of accurate clinical biomarkers has been challenging in part due to the diversity between patients and diseases. One approach to account for the diversity is to use multiple markers to classify patients, based on the concept that each individual marker contributes information from its respective subclass of patients. Here we present a new strategy for developing biomarker panels that accounts for completely distinct patient subclasses. Marker State Space (MSS) defines "marker states" based on all possible patterns of high and low values among a panel of markers. Each marker state is defined as either a case state or a control state, and a sample is classified as case or control based on the state it occupies. MSS was used to define multi-marker panels that were robust in cross validation and training-set/test-set analyses and that yielded similar classification accuracy to several other classification algorithms. A three-marker panel for discriminating pancreatic cancer patients from control subjects revealed subclasses of patients based on distinct marker states. MSS provides a straightforward approach for modeling highly divergent subclasses of patients, which may be adaptable for diverse applications. © 2013 Fallon et al

Food Insecurity Prevalence Across Diverse Sites During COVID-19: A Year of Comprehensive Data

Key Findings NFACT includes 18 study sites in 15 states as well as a national poll, collectively representing a sample size of more than 26,000 people. Some sites have implemented multiple survey rounds, here we report results from 22 separate surveys conducted during the year since the COVID-19 pandemic began in March 2020. 18 out of 19 surveys in 14 sites with data for before and since the pandemic began found an increase in food insecurity since the start of the COVID-19 pandemic as compared to before the pandemic. In nearly all surveys (18/19) that measured food insecurity both before and during the pandemic, more Black, Indigenous, and People of Color (BIPOC) were classified as food insecure during the pandemic as compared to before it began. Prevalence of food insecurity for BIPOC respondents was higher than the overall population in the majority of surveys (19/20) sampling a general population. In almost all surveys (21/22), the prevalence of food insecurity for households with children was higher than the overall prevalence of food insecurity. Food insecurity prevalence was higher for households experiencing a negative job impact during the pandemic (i.e. job loss, furlough, reduction in hours) in nearly all surveys and study sites (21/22). Food insecurity prevalence in most sites was significantly higher before COVID-19 than estimates from that time period. Reporting a percent change between pre and during COVID-19 prevalence may provide additional information about the rate of change in food insecurity since the start of the pandemic, which absolute prevalence of food insecurity may not capture. Results highlight consistent trends in food insecurity outcomes since the start of the COVID-19 pandemic, across diverse study sites, methodological approaches, and time