cytology based on sonographic criteria as for the general population and American Thyroid Association guidelines.BACKGROUND This study aimed to highlight cultural barriers faced by surgeons pursuing a surgical career faced by surgeons at a tertiary care hospital in Pakistan. As more females opt for a surgical career, barriers faced by female surgeons are becoming increasingly evident, many of which are rooted in cultural norms. In Pakistan, a predominantly Muslim-majority, low middle-income country, certain societal expectations add additionally complexity and challenges to existing cultural barriers. METHODS A cross-sectional survey was administered via e-mail to the full-time faculty and trainees in the Department of Surgery at the Aga Khan University Hospital, Karachi, Pakistan, from July 2019 to November 2019. RESULTS In total, 100 participants were included in this study, with the majority being residents (55.6%) and consultants (33.3%). 71.9% of female surgeons felt that cultural barriers towards a surgical career existed for their gender, as compared to 25.4% of male surgeons (p  less then  0.001). 40.6% of females reported having been discouraged by family/close friends from pursuing surgery, as compared to only 9.0% of males (p  less then  0.001). Moreover, a greater percentage of females surgeons were responsible for household cooking, cleaning and laundry, as compared to male surgeons (all p  less then  0.001). Lastly, 71.4% of female surgeons felt that having children had hindered their surgical career, as compared to 4.8% of males (p  less then  0001). CONCLUSION Our study shows that significant cultural barriers exist for females pursuing a surgical career in our setting. Findings such as these emphasize the need for policy makers to work towards overcoming cultural barriers.INTRODUCTION For energy production, cancer cells maintain a high rate of glycolysis instead of oxidative phosphorylation converting glucose into lactic acid. buy NSC 309132 This metabolic shift is useful to survive in unfavorable microenvironments. We investigated whether a positive glycolytic profile (PGP) in gastric adenocarcinomas may be associated with unfavorable outcomes under an anticancer systemic therapy, including the anti-angiogenic ramucirumab. MATERIALS AND METHODS Normal mucosa (NM) and primary tumor (PT) of 40 metastatic gastric adenocarcinomas patients who received second-line paclitaxel-ramucirumab (PR) were analyzed for mRNA expression of the following genes HK-1, HK-2, PKM-2, LDH-A, and GLUT-1. Patients were categorized with PGP when at least a doubling of mRNA expression (PT vs. NM) in all glycolytic core enzymes (HK-1 or HK-2, PKM-2, LDH-A) was observed. PGP was also related to TP53 mutational status. RESULTS Mean LDH-A, HK-2, PKM-2 mRNA expression levels were significantly higher in PT compared with NM. 18 patients were classified as PGP, which was associated with significantly worse progression-free and overall survival times. No significant association was observed between PGP and clinical-pathologic features, including TP53 positive mutational status, in 28 samples. CONCLUSIONS Glycolytic proficiency may negatively affect survival outcomes of metastatic gastric cancer patients treated with PR systemic therapy. TP53 mutational status alone does not seem to explain such a metabolic shift.Women in reproductive age with rheumatic diseases (RD) are especially vulnerable for depression and anxiety which negatively impacts the pregnancy, birth, and RD. The purpose of this study is to describe the frequency of anxiety and depression symptoms employing the Hospital Anxiety and Depression Scale (HADS) in women in reproductive age. We conducted an observational, single-center, cross-sectional, and descriptive study in reproductive-age, non-pregnant women without a prior psychiatric diagnosis. Differences between disease groups, subscale results, and disease activity were analyzed with the Chi square, Mann-Whitney U test, or Kruskal-Wallis test. A total of 100 women were included. Mean age was 35.3 years (SD = 10.07). The most frequent diagnosis was rheumatoid arthritis (RA) with 48, followed by systemic lupus erythematosus (SLE) with 30. A total of 66 (66%) patients had an abnormal HADS score (probable or possible cases) in either subscale. More than 50% of RA patients had an abnormal HADS score. We found an association between RA disease activity groups and total HADS score (p = 0.003). Furthermore, we found a statically significant association between RA activity groups and HADS anxiety subscales group classification (p = 0.01). No differences between disease activity groups of SLE or other diseases and HADS classification or total score was found (p = 0.277). A high frequency of probable or possible cases of depression and anxiety were recognized in reproductive-age women with RD. A high RA disease activity was associated with a high total HADS score and an increased presence of anxiety symptoms.Increased proteolytic activity of cysteine cathepsins has long been known to facilitate malignant progression, and it has also been associated with tumor-promoting roles of myeloid-derived suppressor cells (MDSCs). Consequently, cysteine cathepsins have gained much attention as potential targets for cancer therapies. However, cross-talk between tumor cells and MDSCs needs to be taken into account when studying the efficacy of cathepsin inhibitors as anti-cancer agents. Here, we demonstrate the potential of the MDA-MB-231 breast cancer cell line to generate functional MDSCs from CD14+ cells of healthy human donors. During this transition to MDSCs, the overall levels of cysteine cathepsins increased, with the largest responses for cathepsins L and X. We used small-molecule inhibitors of cathepsins L and X (i.e., CLIK-148, Z9, respectively) to investigate their functional impact on tumor cells and immune cells in this co-culture system. Interactions with peripheral blood mononuclear cells reduced MDA-MB-231 cell invasion, while inhibition of cathepsin X activity by Z9 restored invasion. Inhibition of cathepsin L activity using CLIK-148 resulted in significantly increased CD8+ cytotoxicity. Of note, inhibition of cathepsins L and X in separate immune or tumor cells did not promote these functional changes. Together, our findings underlie the importance of tumor cell-immune cell interactions in the evaluation of the anti-cancer potential of cysteine cathepsin inhibitors.