Auranofin sensitizes breast cancer cells to paclitaxel mediated cell death via regulating FOXO3/Nrf2/Keap1 signaling pathway.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor which acts as a regulator for cellular oxidative stress, and tightly regulated by Kelch-like ECH-associated protein 1 (Keap1). In this study, we found that auranofin and paclitaxel combination treatment increased TUNEL positive apoptotic cells and enhanced the DNA damage marker γ-H2AX in MCF-7 and MDA-MB-231 breast cancer cells. The immunoblotting analysis revealed the combination of auranofin and paclitaxel significantly increased the FOXO3 expression in a concentration dependent manner. Further we observed that auranofin and paclitaxel treatment prevents the translocation of Nrf2 in a concentration dependent manner. The increased FOXO3 expression might be involved in the cytoplasmic degradation of Nrf1-Keap1 complex. Further, the molecular docking results confirm auranofin act as the agonist for Foxo3. Therefore, the present results suggest that auranofin sensitize the breast cancer cells to paclitaxel via regulating FOXO3/Nrf2/Keap1signaling pathway.

Virtual Versus In-Person Head and Neck Physical Examination Training in Medical Students: A Pilot Assessment.

OBJECTIVE: To compare the effect of virtual and in-person head and neck physical examination training events on medical student confidence in performing examination maneuvers and seeking mentorship from otolaryngology faculty and residents. METHODS: Training events were held with first-year medical student volunteers in 2020 (in-person) and 2021 (virtual). Participants in both cohorts were given didactics on head and neck cancer, trained to perform a head and neck physical examination, and demonstrated their clinical skills to otolaryngology faculty and residents. Pre- and post-training surveys were utilized to assess the following outcomes: participant head and neck cancer knowledge, confidence in performing examination maneuvers, and confidence in seeking mentorship in otolaryngology. Differences in outcomes between training settings were assessed by comparing participant survey responses pre- and post- training. RESULTS: Both in-person and virtual training modalities improved participant confidence in performing the physical examination. There was no significant difference in the degree of improvement between training types. In-person training significantly increased participant confidence in seeking mentorship from otolaryngology faculty and residents (P = .003), while virtual training did not (P = .194). CONCLUSION: Virtual training modalities are feasible methods of teaching the head and neck physical examination. Instruction through a video conferencing platform has the potential to be incorporated into traditional in-person medical education in a permanent fashion. This pilot study can inform future studies directly comparing in-person and virtual physical examination training modalities.

A new pyrimidine alkaloid from the roots of Tadehagi triquetrum (L.) H.Ohashi.

Tadehagi triquetrum (L.) H.Ohashi, also known as Desmodium triquetrum (Fabaceae) is the most important plant in the herbal remedies. The present study focus on the isolation, in-silico and in-vitro studies of the two alkaloids C1 (5-(4-[(methylcarbamoyl) amino]-2-oxopyrimidin-1(2H)-yl) tetrahydrofuran-2-yl) methyl methyl carbamate is novel alkaloid and C2 13-Docosenamide is a known alkaloid. The chemical structures of compounds have been elucidated based on comprehensive techniques like GCMS, IR and NMR. In order to know the molecular mechanisms for the two compounds, in silico molecular docking study has been performed. Both compounds have shown perfect binding affinity to the enzymes TNF α, IL-4, IL-13 and 5 LOX Enzyme. The compounds also exhibited comparable G-scores and Glide energy values in comparison with the standard dexamethasone. In addition both the compounds have been tested for in vitro antioxidant assay by using ABTS and DPPH method and the results were compared with standard ascorbic acid.

An integrated nutrition and health program package on IYCN improves breastfeeding but not complementary feeding and nutritional status in rural northern India: A quasi-experimental randomized longitudinal study.

BACKGROUND: Undernutrition below two years of age remains a major public health problem in India. We conducted an evaluation of an integrated nutrition and health program that aimed to improve nutritional status of young children by improving breast and complementary feeding practices over that offered by the Government of India's standard nutrition and health care program. METHODS: In Uttar Pradesh state, through multi-stage cluster random sampling, 81 villages in an intervention district and 84 villages in a comparison district were selected. A cohort of 957 third trimester pregnant women identified during house-to-house surveys was enrolled and, following childbirth, mother-child dyads were followed every three months from birth to 18 months of age. The primary outcomes were improvements in weight-for-age and length-for-age z scores, with improved breastfeeding and complementary feeding practices as intermediate outcomes. FINDINGS: Optimal breastfeeding practices were higher among women in intervention than comparison areas, including initiating breastfeeding within one hour of delivery (17.4% vs. 2.7%, p<0.001), feeding colostrum (34.7% vs. 8.4%, p<0.001), avoiding pre-lacteals (19.6% vs. 2.1%, p<0.001) and exclusively breastfeeding up to 6 months (24.1% vs. 15.3%, p = 0.001). However, differences were few and mixed between study arms with respect to complementary feeding practices. The mean weight-for-age z-score was higher at 9 months (-2.1 vs. -2.4, p = 0.0026) and the prevalence of underweight status was lower at 12 months (58.5% vs. 69.3%, p = 0.047) among intervention children. The prevalence of stunting was similar between study arms at all ages. Coefficients to show the differences between the intervention and comparison districts (0.13 cm/mo) suggested significant faster linear growth among intervention district infants at earlier ages (0-5 months). INTERPRETATION: Mothers participating in the intervention district were more likely to follow optimal breast, although not complementary feeding practices. The program modestly improved linear growth in earlier age and weight gain in late infancy. Comprehensive nutrition and health interventions are complex; the implementation strategies need careful examination to improve feeding practices and thus impact growth. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov, NCT00198835.

A case of bilateral aberrant pectoralis minor insertion with absent coracohumeral ligament: Clinical relevance and controversies.

Aberrant insertions of the pectoralis minor tendon are quite rare. Most cases are incidental findings during cadaver dissections, on an MRI or during surgical procedures of the shoulder joint. Rarely the aberrant insertion points can be a source of pain or restriction of the shoulder joint. From the literature review, we found that there has been no mention regarding the frequency of occurrence of this variation with respect to unilateral or bilateral occurence, and only three cases have been reported, in which aberrant bilateral insertions have been documented of which two were noted during cadaveric dissection and one radiologically. We report a rare case of aberrant bilateral insertions of the pectoralis minor, which was found during an arthroscopic procedure, and we discuss its clinical and surgical implications.

Studies on Photocleavage, DNA Binding, Cytotoxicity, and Docking Studies of Ruthenium(II) Mixed Ligand Complexes.

This article describes the synthesis and characterization of three new Ru(II) polypyridyl complexes including [Ru(phen)2(dpphz)]2+ (1), [Ru(bpy)2(dpphz)]2+ (2) and [Ru(dmb)2(dpphz)]2+ (3) where dpphz = dipyrido[3,2-a:2',3'-c] phenazine-11-hydrazide, phen =1,10-phenanthroline, bpy = 2,2'-bipyridine and dmb = 4,4'-dimethyl2,2'-bipyridine. The binding behaviors of these complexes to calf thymus DNA (CT-DNA) were explored by spectroscopic titrations, viscosity measurements. Results suggest that these complexes can bind to CT-DNA through intercalation. However, their binding strength differs from each other; this may be attributed to difference in the ancillary ligand. The cytotoxicity of 1-3 was evaluated by MTT assay; results indicated that all complexes have significant dose dependent cytotoxicity with HeLa tumor cell line. All complexes exhibited efficient photocleavage of pBR322 DNA upon irradiation. The DNA binding ability of 1-3 was also studied by docking the complexes into B-DNA using docking program.

PBK/TOPK enhances aggressive phenotype in prostate cancer via ß-catenin-TCF/LEF-mediated matrix metalloproteinases production and invasion.

A current challenge in prostate cancer treatment is how to differentiate aggressive disease from indolent prostate cancer. There is an urgent need to identify markers that would accurately distinguish indolent prostate cancer from aggressive disease. The aim of this study was to evaluate the role of PDZ Domain-binding kinase (PBK) in prostate cancer and to determine if PBK expression enhances aggressiveness in prostate cancer. Using archival tissue samples, gain-of-function and loss-of-function studies, we show that PBK expression is up-regulated in prostate cancer, and its expression level is commensurate with invasiveness. Modulation of PBK expression and function causally regulates the invasive ability of prostate cancer cells. Production of matrix metalloproteinases-2 and -9, which are key players in metastatic invasion, is up-regulated, and the promoters of these genes are transcriptionally activated by PBK via increased ß-catenin-TCF/LEF signaling. Prostate cancer tissue specimens show that PBK's expression correlates with aggressive disease and distant metastasis in bone, lymph node and abdomen. Our in vitro and in situ data are in agreement that PBK could be a prognostic biomarker for prostate cancer that would discriminate aggressive prostate cancer from indolent disease, and is a potential target for the therapeutic intervention of aggressive prostate cancer in men.

Complications of femtosecond-assisted laser in-situ keratomileusis flaps.

Femtosecond-assisted laser in-situ keratomileusis flaps have revolutionized refractive surgery since their introduction. Although these lasers are exceedingly safe, complications still do occur. This review focuses specifically on examining the literature and evidence for flap complications during femtosecond-assisted laser in-situ keratomileusis as well as their management.

Cellular uptake, cytotoxicity, apoptosis and DNA-binding investigations of Ru(II) complexes.

Three new compounds, [Ru(Hdpa)2PyIP](ClO4)2·2H2O (1) [Ru(Hdpa)2FyIP](ClO4)2·2H2O (2) and [Ru(Hdpa)2IIP](ClO4)2·2H2O (3) have been synthesized and characterized by spectroscopic techniques such as elemental analysis, UV/Vis, FT-IR, (1)H NMR, (13)C NMR and mass spectra. The CT-DNA binding properties of 1-3 have been investigated by absorption, emission spectroscopy and viscosity measurements. Experimental results suggested that they can interact with DNA through intercalative mode with different binding strengths. These were found to promote the cleavage of plasmid DNA. Cell viability results indicated that all compounds showed significant dose dependent cytotoxicity in selected cell lines and 1 shown higher cytotoxicity than cisplatin on HeLa cells. Cellular uptake studies were studied by flow cytometry and confocal microscopy.

Synthesis, interaction with DNA, cytotoxicity, cell cycle arrest and apoptotic inducing properties of ruthenium(II) molecular "light switch" complexes.

In an endeavor toward the development of metal-based anticancer drugs, we present here the design, synthesis and characterization of three ruthenium(II) functionalized phenanthroline complexes with extended π-conjugation. These complexes have been shown to act as promising CT-DNA intercalators as evidenced by UV-visible, luminescence, emission quenching by [Fe(CN)6](4-), DNA competitive binding with ethidium bromide and salt dependent studies. All three complexes [Ru(Hdpa)2PPIP](2+) (1), [Ru(Hdpa)2PIP](2+) (2), [Ru(Hdpa)24HEPIP](2+) (3) clearly demonstrated that they can bind to DNA through the intercalation mode. Cell viability experiments indicated that all complexes showed significant dose dependent cytotoxicity in selected cell lines. The apoptosis and cell cycle arrest were also investigated. The complexes were docked into DNA-base-pairs using the 'GOLD' (Genetic Optimization for Ligand Docking), docking program.

Synthesis, DNA-binding, cytotoxicity, photo cleavage, antimicrobial and docking studies of Ru(II) polypyridyl complexes.

Three Ruthenium(II) polypyridine complexes, [Ru(phen)2(mipc)](2+)(1), [Ru(bpy)2(mipc)](2+) (2) and [Ru(dmb)2(mipc)](2+)(3) [mipc = 2-(6-methyl-3-(1H-imidazo[4, 5-f][1,10]-phenanthroline-2-yl)-4H-chromene-4-one, phen = 1,10-phenanthroline,bpy = 2, 2'bipyridine,dmb = 4, 4'-dimethyl-2, 2'-bipyridine] have been synthesized and characterized by elemental analysis, IR, UV-Vis, (1)H& (13)C NMR and mass spectra. The DNA-binding properties of the Ruthenium(II) complexes were investigated by spectrophotometric methods, viscosity measurements and light switch studies. These three complexes have been focused on photo activated cleavage studies with pBR-322 and antimicrobial studies. Experimental results indicate that the three complexes intercalate into DNA base pairs and follows the order of 1 > 2 > 3 respectively. Molecular docking studies also support the DNA interactions with complexes through hydrogen bonding and vander Waal's interactions. Cytotoxicity studies with Hela cell lines has been revealing about anti tumor activity of these complexes.

Trends in female representation in published ophthalmology literature, 2000-2009.

PURPOSE: To examine trends in female first and last authors in clinical ophthalmology literature published from January 2000 to December 2009. METHODS: A total of 3760 articles in American Journal of Ophthalmology (AJO), 2347 articles in Archives of Ophthalmology (Archives), and 3838 articles in Ophthalmology spanning 10 years of published ophthalmology peer-reviewed literature were examined. All original research articles and brief reports indexed online were included. Author gender was determined by an exhaustive Internet search. Articles were excluded if the sex of the author could not be determined or was not applicable (for example, articles by a study group rather than an individual author). RESULTS: Gender information was identified in 86.8% of articles for first authors and 86% for last authors. The number of female first authors (P < 0.0001) and last authors (P = 0.005) increased significantly in the study period in all journals examined, with a significant association between the sex of the first and last authors (OR = 2.19; 95% CI, 1.96-2.46; P < 0.0001), when examining all articles. Female representation increased for last authors significantly only in Ophthalmology. There was a significant correlation between gender of the first author and total number of authors that was not observed with last-author sex. CONCLUSIONS: Female first authorship has increased from 2000 to 2009 and is correlated with the gender of the last author; however, there were fewer female last authors compared to female first authors in the same period.

Comparison of expert graders to computer-assisted image analysis of the retina in retinopathy of prematurity.

AIMS: To determine correlation of width and tortuosity between expert graders and computer-assisted image analysis of the retina in narrow-field images of eyes with retinopathy of prematurity. METHODS: 11 digital images were selected based on severity of retinopathy of prematurity (ROP). Narrow field images were analysed for width and tortuosity of vessels using computer-aided image analysis of the retina (CAIAR), an image analysis software, and by four ROP experts. Spearman correlation coefficients (ρ) assessed the correlation of CAIAR grading with expert grading. Intra-class correlations assessed agreement among graders. Width and tortuosity were compared among severity of ROP and treatment status using analysis of variance and generalised estimating equations. RESULTS: Expert measurements correlated well with measures from CAIAR for venule width (ρ=0.57-0.66) and arteriole tortuosity (ρ=0.71-0.81). Measurements from four graders agreed moderately well (intra-class correlations were 0.49 and 0.69 for venule width and arteriole tortuosity, respectively). Increased severity of ROP (no pre-plus/plus, pre-plus, plus) was associated with larger width (linear trend p=0.02 in two graders) and tortuosity (linear trend p<0.03 in all graders). Tortuosity measurements by CAIAR and graders were statistically different between treated and untreated eyes (p<0.002). CONCLUSIONS: We found moderate correlation between expert graders' assessment of vessel tortuosity and width and CAIAR using narrow-field images.

Gender characteristics among academic ophthalmology leadership, faculty, and residents: results from a cross-sectional survey.

PURPOSE: To determine if there is any association in ophthalmology between the gender of the chairperson and residency program director and the gender of faculty and residents. METHODS: An anonymous electronic survey was sent to 121 ophthalmology residency program directors. Demographic information pertaining to size, location, academic or community affiliation, and gender distribution of the faculty, residents, residency program directors and chairs was obtained. RESULTS: The response rate was 45.45% with 55 residency program directors responding to the survey. Academic programs comprised 53 (96%) of the programs studied. Male department chairs led all 53 (96%) programs. In terms of the residency program director gender, 37 (67%) were male, whereas 18 (34%) were female. Female faculty and residents comprised 313 (28%) and 270 (45%), respectively. Compared to departments with male chairs, departments with a female chair had a higher crude proportion of female faculty (35% vs. 28%; P = 0.300) and female residents (50% vs. 45%; P = 0.660), although there was no statistical difference. Departments with either a male or female residency program director had similar number of female faculty (28% vs. 28%; P = 0.991) and residents (44% vs. 46%; P = 0.689). CONCLUSIONS: We found no significant association between the gender of the residency program director and chairperson with the proportion of female faculty and residents. Given a higher ratio of female residents relative to female faculty, it is probable that graduating female residents are choosing not to pursue academic medicine, shrinking the potential pool of female candidates for positions of departmental leadership.

Outcomes after breast conservation treatment with radiation in women with ductal carcinoma in situ and prior nonbreast malignancy.

Management of ductal carcinoma in situ (DCIS) of the breast is controversial, as not all patients progress to invasive carcinoma. This report analyzes the outcomes after breast conservation treatment (BCT) with radiation in patients with DCIS following prior malignancy at another anatomic site. The study cohort was comprised of 14 women with DCIS who were treated between 1978 and 2003. The median age at diagnosis of DCIS was 54 years (mean 56; range 37-78) and for the prior nonbreast malignancy was 44 years (mean 47; range 27-76). All patients underwent breast conservation surgery followed by whole breast radiation and tumor bed boost. The median and mean follow-up times after treatment of DCIS were 8.0 and 9.1 years, respectively (range 2-18). The median and mean interval period between the prior malignancy and DCIS was 6.0 and 8.2 years, respectively (range 1-30). There was one (7%) local failure, two (14%) contralateral breast cancers, and one (7%) death from breast cancer that occurred 7 years after BCT following contralateral invasive breast cancer. In this cohort of 14 patients treated for DCIS of the breast after a prior nonbreast malignancy, treatment for DCIS resulted in a high rate of local control and should be considered for curative intent.