Patient-reported outcome measures in patients undergoing radiotherapy for head and neck cancer.

OBJECTIVES: Head and neck (H&N) cancer patients experience significant acute side effects from treatment. This study evaluates prospectively collected patient-reported outcomes (PROs) in H&N patients undergoing radiotherapy (RT) to assess feasibility of electronically collecting PROs and to objectively document symptom acuity and trajectory during RT. MATERIALS AND METHODS: H&N patients undergoing radical RT at our multicentre institution completed a 12-item partial survey of the Vanderbilt Head & Neck Symptom Survey 2.0 prior to RT and weekly on RT. Between October 2016 and October 2018, 318 of 333 patients completed a baseline survey and at least one weekly survey. RESULTS: The average number of weekly questionnaires completed was 5 (range 1-8). The mean maximum symptom scores were highest for dysgeusia (5.8/10), pain (5.4/10), mucositis (4.8/10), weight loss due to swallowing (4.5/10) and mucus causing choking/gagging (4.3/10). On multivariate analysis, female gender, sinonasal, nasopharynx and oropharynx primaries were associated with a greater risk of moderate-severe pain (p < 0.05). Sinonasal, nasopharynx, oral cavity, oropharynx and thyroid primaries were associated with a greater risk of moderate-severe mucositis during radiation (p < 0.0001). Salivary gland, sinonasal, nasopharynx and oropharynx primaries and higher radiation dose were associated with a greater risk of moderate-severe dysgeusia (all p < 0.05). CONCLUSIONS: Electronic PRO collection during H&N cancer RT is feasible. H&N cancer patients experience significant symptoms during RT, and the most severe symptoms reported were dysgeusia, pain and mucositis. Oropharynx cancer patients reported the highest symptom scores during RT.

In Vitro Biomechanical Testing of the Tube Knot.

OBJECTIVE: To compare in vitro biomechanical properties of the tube knot (TB) to a crimp clamp (CC) system, and square knot (SQ) using 3 monofilament materials. STUDY DESIGN: In vitro biomechanical study. SAMPLE POPULATION: Suture loops (n=20 per material/knot construct). METHODS: Monotonic tensile loading (300 mm/min single pull to failure) was performed on knots tied using 3 knots (TB, 5-throw SQ, and CC system) with each of 3 materials (40# Securos® nylon, #2 polypropylene, and #2 nylon). Ultimate tensile strength, elongation, and stiffness were measured and compared by sequential 1- and 2-way ANOVA. RESULTS: Ultimate tensile strength was greatest with 40# nylon CC (mean ± SD, 293.6 ± 26.2 N), followed by TB (289.8 ± 9.2 N) and SQ (252.2 ± 8.5 N) with no significant difference between CC and TB. TB with #2 polypropylene (158.1 ± 7.4 N) and #2 nylon (126.3 ± 5.5 N) had significantly greater tensile strength than SQ with #2 polypropylene (143.6 ± 5.3 N) and #2 nylon (110.7 ± 6.2 N). Elongation at failure was significantly greater in 40# nylon TB (25.3 ± 3.2 mm) and SQ (10.8 ± 1.6 mm) compared to CC (5.3 ± 1.0 mm). Both material and knotting method had an effect on ultimate tensile strength, elongation at failure, and stiffness, based on 2-way ANOVA. CONCLUSION: Ultimate tensile strength of TB was equivalent to that of CC; however, elongation at failure was greatest for TB, which may be of concern for clinical applications.

Training Veterinary Students to Perform Ovariectomy Using theMOOSE Spay Model with Traditional Method versus the Dowling Spay Retractor.

Educators understand the importance of developing safe and effective methods to teach veterinary students basic surgical skills. Ovariectomy (OVE) is a procedure that employs many of the skills agreed to be vital for a newly graduated veterinarian. This study endeavored to compare two methods of teaching OVE on a model based on assessment of procedure time and skill performance scores. Students' opinions regarding their experience are also reported. Students performed the Dowling Spay Retractor (DSR) method more quickly (p<.001) but with performance scores similar to the traditional (T) method depicted in textbooks. Students responded positively when surveyed regarding their experience with the training and the DSR method.

Comparison between Training Models to Teach Veterinary Medical Students Basic Laparoscopic Surgery Skills.

The objective of this study was to compare the effectiveness of two different laparoscopic training models in preparing veterinary students to perform basic laparoscopic skills. Sixteen first- and second-year veterinary students were randomly assigned to a box trainer (Group B) or tablet trainer (Group T). Training and assessment for both groups included two tasks, "peg transfer" and "pattern cutting," derived from the well-validated McGill University Inanimate System for Training and Evaluation of Laparoscopic Skills. Confidence levels were compared by evaluating pre- and post-training questionnaires. Performance of laparoscopic tasks was scored pre- and post-training using a rubric for precision and speed. Results revealed a significant improvement in student confidence for basic laparoscopic skills (p<.05) and significantly higher scores for both groups in both laparoscopic tasks (p<.05). No significant differences were found between the groups regarding their assessment of the video quality, lighting, and simplicity of setup (p=.34, p=.15, and p=.43, respectively). In conclusion, the low-cost tablet trainer and the more expensive box trainer were similarly effective in preparing pre-clinical veterinary students to perform basic laparoscopic skills on a model.

An elucidation of neutrophil functions against Mycobacterium tuberculosis infection.

We characterized the functions of neutrophils in response to Mycobacterium tuberculosis (M. tb) infection, with particular reference to glutathione (GSH). We examined the effects of GSH in improving the ability of neutrophils to control intracellular M. tb infection. Our findings indicate that increasing the intracellular levels of GSH with a liposomal formulation of GSH (L-GSH) resulted in reduction in the levels of free radicals and increased acidification of M. tb containing phagosomes leading to the inhibition in the growth of M. tb. This inhibitory mechanism is dependent on the presence of TNF-α and IL-6. Our studies demonstrate a novel regulatory mechanism adapted by the neutrophils to control M. tb infection.

Bilateral Diffuse Leukoencephalopathy in an Electrocuted Patient Where the Brain Was Not in the Pathway of Conduction.

Electrocution, damage caused by electric current passing through the body, is usually a serious event causing significant morbidity or even mortality. Graded damage is seldom encountered. According to Ohm's law, the current is directly proportional to the applied voltage and inversely proportional to the resistance of a circuit. Electric current is expected to travel through cells that have the least resistance. Therefore, cells that allow action potential to travel down their cell membrane are presumably the ones with the least resistance. Among these are neurons and cells within the cardiac conduction system. Within a neuron, the axon will conduct electricity better than the cell body. While there have been a few cerebral white matter lesions caused by electrocution described in the literature, the mechanism is not fully understood. We report a patient with bilateral symmetrical subcortical abnormality where the electric current entered one hand and exited through her legs without affecting the head directly. We reviewed the literature and we hope it will further our understanding of how electrocution affects the central nervous system and which groups and parts of neurons are more susceptible than others.

Analysis of glutathione levels in the brain tissue samples from HIV-1-positive individuals and subject with Alzheimer's disease and its implication in the pathophysiology of the disease process.

HIV-1 positive individuals are at high risk for susceptibility to both pulmonary tuberculosis (TB) and extra-pulmonary TB, including TB meningitis (TBM) which is an extreme form of TB. The goals of this study are to determine the mechanisms responsible for compromised levels of glutathione (GSH) in the brain tissue samples derived from HIV-1-infected individuals and individuals with Alzheimer's disease (AD), investigate the possible underlying mechanisms responsible for GSH deficiency in these pathological conditions, and establish a link between GSH levels and pathophysiology of the disease processes. We demonstrated in the autopsied human brain tissues that the levels of total and reduced forms of GSH were significantly compromised in HIV-1 infected individuals compared to in healthy subjects and individuals with AD. Brain tissue samples derived from HIV-1-positive individuals had substantially higher levels of free radicals than that derived from healthy and AD individuals. Enzymes that are responsible for the de novo synthesis of GSH such as γ-glutamate cysteine-ligase catalytic subunit (GCLC-rate limiting step enzyme) and glutathione synthetase (GSS-enzyme involved in the second step reaction) were significantly decreased in the brain tissue samples derived from HIV-1-positive individuals with low CD4 + T-cells (< 200 cells/mm(3)) compared to healthy and AD individuals. Levels of glutathione reductase (GSR) were also decreased in the brain tissue samples derived from HIV-1 infected individuals. Overall, our findings demonstrate causes for GSH deficiency in the brain tissue from HIV-1 infected individuals explaining the possible reasons for increased susceptibility to the most severe form of extra-pulmonary TB, TBM.

Complement 3 Receptor Expression in Individuals with Type 2 Diabetes.

BACKGROUND: According to the World Health Organization, as of 2014 9% of the world's adult population is affected by diabetes. Uncontrolled diabetes is a pro-inflammatory process that increases generation of reactive oxygen species (ROS). METHODS: The production of ROS leads to a chronic increase in oxidative stress which results in an increased susceptibility to infections. Individuals with type 2 diabetes mellitus (T2DM) are highly susceptible to Mycobacterium tuberculosis (M. tb) infection. Previous research has demonstrated that glutathione (GSH) plays an important role in the control of M. tb infection. Recent studies have demonstrated that phagocytosis of M.tb is diminished in patients with T2DM. Phagocytosis in macrophages is thought to be mediated in part by complement protein 3b (C3b)-complement protein receptor 3b (C3R) interactions. Since C3b production is not diminished in patients with T2DM we propose that C3R production is reduced and is the cause for impaired macrophage phagocytosis as well as IL-12 and IFN-γ signaling. CONCLUSION: This study utilizes a quantitative PCR (qPCR), demonstrating decreased transcription of C3R mRNA in patients with T2DM as compared to non-diabetics.

Liposomal Glutathione Supplementation Restores TH1 Cytokine Response to Mycobacterium tuberculosis Infection in HIV-Infected Individuals.

Cytokines are signaling biomolecules that serve as key regulators of our immune system. CD4(+) T-cells can be grouped into 2 major categories based on their cytokine profile: T-helper 1 (TH1) subset and T-helper 2 (TH2) subset. Protective immunity against HIV infection requires TH1-directed CD4 T-cell responses, mediated by cytokines, such as interleukin-1ß (IL-1ß), IL-12, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α). Cytokines released by the TH1 subset of CD4 T-cells are considered important for mediating effective immune responses against intracellular pathogens such as Mycobacterium tuberculosis (M. tb). Oxidative stress and redox imbalance that occur during HIV infection often lead to inappropriate immune responses. Glutathione (GSH) is an antioxidant present in nearly all cells and is recognized for its function in maintaining redox homeostasis. Our laboratory previously reported that individuals with HIV infection have lower levels of GSH. In this study, we report a link between lower levels of GSH and dysregulation of TH1- and TH2-associated cytokines in the plasma samples of HIV-positive subjects. Furthermore, we demonstrate that supplementing individuals with HIV infection for 13 weeks with liposomal GSH (lGSH) resulted in a significant increase in the levels of TH1 cytokines, IL-1ß, IL-12, IFN-γ, and TNF-α. lGSH supplementation in individuals with HIV infection also resulted in a substantial decrease in the levels of free radicals and immunosuppressive cytokines, IL-10 and TGF-ß, relative to those in a placebo-controlled cohort. Finally, we determined the effects of lGSH supplementation in improving the functions of immune cells to control M. tb infection by conducting in vitro assays using peripheral blood mononuclear cells collected from HIV-positive individuals at post-GSH supplementation. Our studies establish a correlation between low levels of GSH and increased susceptibility to M. tb infection through TH2-directed response, which may be relieved with lGSH supplementation enhancing the TH1 response.

Investigating the causes for decreased levels of glutathione in individuals with type II diabetes.

Tuberculosis (TB) remains an eminent global burden with one third of the world's population latently infected with Mycobacterium tuberculosis (M. tb). Individuals with compromised immune systems are especially vulnerable to M. tb infection. In fact, individuals with Type 2 Diabetes Mellitus (T2DM) are two to three times more susceptible to TB than those without T2DM. In this study, we report that individuals with T2DM have lower levels of glutathione (GSH) due to compromised levels of GSH synthesis and metabolism enzymes. Transforming growth factor beta (TGF-ß), a cytokine that is known to decrease the expression of the catalytic subunit of glutamine-cysteine ligase (GCLC) was found in increased levels in the plasma samples from individuals with T2DM, explaining the possible underlying mechanism that is responsible for decreased levels of GSH in individuals with T2DM. Moreover, increased levels of pro-inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-17 (IL-17) were observed in plasma samples isolated from individuals with T2DM. Increased levels of IL-6 and IL-17 was accompanied by enhanced production of free radicals further indicating an alternative mechanism for the decreased levels of GSH in individuals with T2DM. Augmenting the levels of GSH in macrophages isolated from individuals with T2DM resulted in improved control of M. tb infection. Furthermore, cytokines that are responsible for controlling M. tb infection at the cellular and granuloma level such as tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), interleukin-2 (IL-2), interferon-gamma (IFN-γ), and interleukin-12 (IL-12), were found to be compromised in plasma samples isolated from individuals with T2DM. On the other hand, interleukin-10 (IL-10), an immunosuppressive cytokine was increased in plasma samples isolated from individuals with T2DM. Overall, these findings suggest that lower levels of GSH in individuals with T2DM lead to their increased susceptibility to M. tb infection.

Glutathione synthesis is compromised in erythrocytes from individuals with HIV.

We demonstrated that the levels of enzymes responsible for the synthesis of glutathione (GSH) such as glutathione synthase (GSS), glutamate-cysteine ligase-catalytic subunit (GCLC), and glutathione reductase (GSR) were significantly reduced in the red blood cells (RBCs) isolated from individuals with human immunodeficiency virus (HIV) infection and this reduction correlated with decreased levels of intracellular GSH. GSH content in RBCs can be used as a marker for increased overall oxidative stress and immune dysfunctions caused by HIV infection. Our data supports our hypothesis that compromised levels of GSH in HIV infected individuals' is due to decreased levels of GSH-synthetic enzymes. The role of GSH in combating oxidative stress and improving the functions of immune cells in HIV patients' indicates the benefit of an antioxidant supplement which can reduce the cellular damage and promote the functions of immune cells.