NQO1 expression in pancreatic cancer and its potential use as a biomarker.

Pancreatic ductal adenocarcinoma (PDA) is rarely curable due to regional/metastatic spread at diagnosis. Identification of molecular markers may enhance diagnosis and early detection of PDA. The 2-electron reductase, NAD(P)H:quinone oxidoreductase (NQO1) has been found to be overexpressed in many solid tumors including PDA, and may be a useful clinically relevant diagnostic marker of malignancy. For this study, we used 37 surgical resection cases: 24 PDAs and 13 benign pancreatic tissue specimens. An additional 16 specimens from pancreatic endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) were included as a pilot series. NQO1 was detected by avidin-biotin based immunohistochemical and immunocytochemical methods. Both staining intensity and proportion of NQO1 positive tumor cells were scored. Moderate to strong (2 to 3+) staining for NQO1 was detected in 22/24 (92%) surgically resected PDAs, 9/9 (100%) EUS-FNAs with malignant diagnoses, one cytologically atypical but not diagnostic for malignancy EUS-FNA, and 1/6 (17%) EUS-FNAs initially diagnosed as negative for malignancy. Subsequent histologic assessment confirmed malignancy in all 9 cytologically positive EUS-FNAs and in the atypical case. The NQO1 positive case initially diagnosed as negative for malignancy showed no evidence of carcinoma on subsequent tissue biopsy. NQO1 staining was also observed in some benign ducts/cells; however, correlation of NQO1 expression with cellular morphology assessment minimizes the risk of false positive diagnosis. NQO1 is consistently overexpressed in PDA. Although NQO1 is observed in some benign tissue components, this marker may be a clinically useful diagnostic adjunct for detection of PDA, independent of tumor grade/stage.     

Humanized anti-interleukin-2 (IL-2) receptor alpha therapy: long-term results in uveitis patients and preliminary safety and activity data for establishing parameters for subcutaneous administration

Therapy for severe uveitis is frequently long-term immunosuppression using systemic corticosteroids and cytotoxic agents, but side effects make long-term therapy difficult. A long-term (>4 year) Phase I/II single armed interventional study using intravenous anti-IL-2 receptor alpha treatments (daclizumab) and a short-term Phase II study evaluating the use of a subcutaneous daclizumab formulation were conducted. Patients were tapered off their systemic immunosuppressive therapy and received daclizumab infusions or subcutaneous injections at intervals varying from 2 to 6 weeks. In the long-term study, seven of ten enrolled patients were tapered from their original immunosuppressive medications and maintained exclusively on repeated daclizumab infusions for control of their uveitis for over 4 years. No patient was permanently removed from therapy for an adverse event ascribed to the medication. The use of 6-week infusion intervals led to recurrence of uveitis, while 2- to 4-week intervals did not. Only one patient developed measurable anti-daclizumab antibodies but this disappeared when subcutaneous therapy was begun. In the short-term study, four of the five patients receiving the subcutaneous formulation met the study endpoints for success within the first 12 weeks. All five were successful by 26 weeks. These studies provide preliminary evidence that regularly administered long-term daclizumab therapy can be given in lieu of standard immunosuppression for years to treat severe uveitis and that subcutaneously administered daclizumab appeared to be a clinically viable treatment strategy. These studies suggest that anti-IL-2 receptor blockade could be useful in the treatment of Th1-mediated autoimmune conditions.     

Guava Fruit and Acacia pennata Vegetable Intake Association with Frailty of Older Adults in Northern Thailand

As Thailand moves toward an aging society, frailty has become a concern amongst northern Thai elderly. The causes of frailty are multifactorial and include genetic, environmental, and socio-economic factors; diet is of particular interest. A cross-sectional study was conducted from September to October 2017 to investigate what kind of diets normally consumed by 350 Thai elders were associated with frailty using a questionnaire and frailty determination by Fried’s phenotype followed by phytochemical analyses of the diets. The multivariable logistic regression analysis demonstrated a significant positive association between certain foods and lower frailty. Guava fruit and Acacia pennata vegetable consumption had lower odds of frailty, which were 0.52 times (95% CI 0.28–0.96, p = 0.037) and 0.42 times (95% CI 0.21–0.83, p = 0.012) when adjusted for the potential confounders. The phytochemical analyses of guava fruit showed a significantly higher amount of total flavonoids (p < 0.001), total phenolic compounds (p = 0.002), and antioxidant capacity, including DPPH (p < 0.001), ABTS (p < 0.001), and FRAP (p = 0.002) when compared to those of banana. Acacia pennata vegetable contained a significantly higher amount of total phenolic compounds (p = 0.012) when compared to those of lettuce. These findings may assist in health promotion programs of frailty prevention by encouraging an increase in consumption of either guava fruit or Acacia pennata vegetable among Thai elderly.     

Association between leptin,obesity, hormonal interplay and male infertility

Male infertility is a major health problem worldwide. We investigated a possible association between leptin, obesity, hormonal interplay and male infertility. This cross‐sectional study of 313 males (178 infertile and 135 fertile) was carried out in 2017. The subjects were categorised by body mass index (BMI) and body fat percentage (BF%) into normal weight, overweight and obese. Significantly higher levels of BMI and BF% (p‐value < 0.001) and lower levels of FSH, LH, testosterone, and SHBG (p‐value < 0.001) were found in infertile males. However, no significant difference was observed in leptin levels (p‐value = 0.35). Leptin levels were significantly higher, and all the sex hormones were significantly lower (p‐value < 0.001) in obese subjects, whereas according to BF% only leptin, FSH and SHBG were significantly different. Leptin showed a significant positive correlation with BMI and BF% (p < 0.001). A strong positive link to serum testosterone was found with age, FSH, and LH (p < 0.001) and a negative one with BMI and BF% (p < 0.001). In mutivariable anlaysis, after adjusting for the other covariates, a significant association between FSH and testosterone (p‐value <0.001) was found. Serum leptin levels did not differ significantly in fertile and infertile groups, and no association was found with infertility. Furthermore, male obesity was found to be associated with infertility with the decrease in levels of sex hormones.     

Sclerosing Sertoli cell tumor of the testis

Sclerosing Sertoli-cell tumor is a rare, sex-cord-stromal tumor of the testis with distinct clinical and pathological features with only 14 such cases reported in contemporary literature. We report such a tumor in a young diabetic and hypertensive male. Serum beta-HCG, alpha-protein and LDH levels were normal. Pathological examination of right radical orchidectomy specimen was consistent with sclerosing sub-type of Sertoli-cell testicular tumor with no invasion. He remains free of disease recurrence at 6 years following surgery.     

In vivo imaging and tracking of individual nanodiamonds in drosophila melanogaster embryos

In this work, we incorporate and image individual fluorescent nanodiamonds in the powerful genetic model system Drosophila melanogaster. Fluorescence correlation spectroscopy and wide-field imaging techniques are applied to individual fluorescent nanodiamonds in blastoderm cells during stage 5 of development, up to a depth of 40 µm. The majority of nanodiamonds in the blastoderm cells during cellularization exhibit free diffusion with an average diffusion coefficient of (6 ± 3) × 10⁻³ µm²/s, (mean ± SD). Driven motion in the blastoderm cells was also observed with an average velocity of 0.13 ± 0.10 µm/s (mean ± SD) µm/s and an average applied force of 0.07 ± 0.05 pN (mean ± SD). Nanodiamonds in the periplasm between the nuclei and yolk were also found to undergo free diffusion with a significantly larger diffusion coefficient of (63 ± 35) × 10⁻³ µm²/s (mean ± SD). Driven motion in this region exhibited similar average velocities and applied forces compared to the blastoderm cells indicating the transport dynamics in the two cytoplasmic regions are analogous.OCIS codes: (160.4236) Nanomaterials, (160.2540) Fluorescent and luminescent materials, (180.2520) Fluorescence microscopy