Principal factors that determine the extension of detection range in molecular beacon aptamer/conjugated polyelectrolyte bioassays.

A strategy to extend the detection range of weakly-binding targets is reported that takes advantage of fluorescence resonance energy transfer (FRET)-based bioassays based on molecular beacon aptamers (MBAs) and cationic conjugated polyelectrolytes (CPEs). In comparison to other aptamer-target pairs, the aptamer-based adenosine triphosphate (ATP) detection assays are limited by the relatively weak binding between the two partners. In response, a series of MBAs were designed that have different stem stabilities while keeping the constant ATP-specific aptamer sequence in the loop part. The MBAs are labeled with a fluorophore and a quencher at both termini. In the absence of ATP, the hairpin MBAs can be opened by CPEs via a combination of electrostatic and hydrophobic interactions, showing a FRET-sensitized fluorophore signal. In the presence of ATP, the aptamer forms a G-quadruplex and the FRET signal decreases due to tighter contact between the fluorophore and quencher in the ATP/MBA/CPE triplex structure. The FRET-sensitized signal is inversely proportional to [ATP]. The extension of the detection range is determined by the competition between opening of the ATP/MBA G-quadruplex by CPEs and the composite influence by ATP/aptamer binding and the stem interactions. With increasing stem stability, the weak binding of ATP and its aptamer is successfully compensated to show the resistance to disruption by CPEs, resulting in a substantially broadened detection range (from millimolar up to nanomolar concentrations) and a remarkably improved limit of detection. From a general perspective, this strategy has the potential to be extended to other chemical- and biological-assays with low target binding affinity

A Retrospective Analysis of the Impact of Metastasectomy on Prognostic Survival According to Metastatic Organs in Patients With Metastatic Renal Cell Carcinoma

This study evaluated the effects of metastasectomy on overall survival (OS) and progression-free survival (PFS) in metastatic renal cell carcinoma (mRCC) according to metastatic organs. The medical records (2005–2017) of 273 patients with mRCC were analyzed retrospectively to evaluate OS and PFS according to metastatic organs and their metastasectomy states. The Cox proportional hazard model was used to determine the prognostic significance of metastasectomy. The Kaplan-Meier curve and log-rank test were used to compare groups with different modalities and metastatic organs at a statistical significance of p < 0.05. The overall median age was 57 years; 175 (64.3%) and 83 (30.4%) patients received cytoreductive nephrectomy and metastasectomy, respectively. The metastasectomy group was significantly younger and had a lower clinical T stage with significantly better PFS/OS (20.2/32.0 vs. 9.7/12.8 months) than that in the non-metastasectomy group (N = 190, p < 0.05). Liver with lung metastases were the worst metastatic combination for survivals in which liver metastasis was the only significant unfavorable risk factor for both PFS (HR 1.67) and OS (HR 1.74) (p < 0.05). Multivariable analysis confirmed that metastasectomy was a significant favorable risk factor for PFS (HR 0.70) and OS (HR 0.56) (p < 0.05) along with non-clear cell type (HR 0.61 for PFS), whereas the nuclear grade and poor Heng risk group were unfavorable risk factors (HR > 2.0) for both PFS and OS (p < 0.05). Metastasectomy and the affected metastatic organs significantly influenced prognostic survival in mRCC

Predictors of Hospitalization Among Newly Admitted Skilled Nursing Facility Residents: Rethinking the Role of Functional Decline

Purpose: Hospital transfer from a skilled nursing facility (SNF) is costly, and many are potentially preventable. This study examines: 1) whether functional decline is a predictor of hospital transfer, and 2) the magnitude of relationships between predictors (functional impairment and chronic medical illness) and hospital transfer from SNFs. Methods: We used Minimum Data Set (MDS) Version 2.0 in the state of Michigan between 2007 and 2009. In total, 196,662 new SNF admissions were observed. Multilevel generalized estimating equations and regression models were performed for each functional and clinical domain while adjusting for demographic variables and change in activities of daily living (ADL). Results: 65% of recently admitted SNF residents experienced functional decline after SNF admission, and 58% were readmitted to a hospital. Residents who needed extensive assistance or were completely dependent in their functional domains had pressure ulcers, deteriorated mood or lower cognitive performance scale scores. These residents experienced higher chances of hospital transfer. However, a deteriorated ADL played a significant role in all multivariate models, indicating that a decline in ADL is a stronger predictor of hospital transfer than other functional or clinical predictors. Conclusion: Although all functional impairments and chronic medical illness can be associated with hospital transfer, functional decline may be the most important predictor of hospital transfer in patients newly admitted to an SNF

Second-Line Irinotecan, Leucovorin, and 5-Fluorouracil for Gastric Cancer Patients after Failed Docetaxel and S-1

Background. This retrospective study aimed to assess the efficacy and toxicities of second-line chemotherapy with irinotecan, leucovorin, and 5-fluorouracil (5-FU) in metastatic gastric cancer (MGC) patients previously treated with docetaxel and S-1 with or without oxaliplatin (DS/DOS). Patients and Methods. We reviewed the data of patients who had previously been treated with first-line DS/DOS and received biweekly irinotecan-based chemotherapy (FOLFIRI/IFL) between October 2004 and November 2011. Results. A total of 209 cycles were administered to 35 patients, with a median of 4 (range, 1–22) cycles each. The overall response rate in 29 response-assessable patients was 17.2%, including 2 complete and 3 partial responses. The median progression-free and overall survivals were 3.81 (95% confidence interval [CI], 1.82–5.80) months and 6.24 (95% CI, 1.44–11.04) months, respectively. The major grade 3/4 toxicity was neutropenia (8.6%). Conclusion. FOLFIRI/IFL chemotherapy showed modest antitumour activity and tolerable toxicities in DS/DOS-treated MGC patients

Second-Line Irinotecan, Leucovorin, and 5-Fluorouracil for Gastric Cancer Patients after Failed Docetaxel and S-1

Background. This retrospective study aimed to assess the efficacy and toxicities of second-line chemotherapy with irinotecan, leucovorin, and 5-fluorouracil (5-FU) in metastatic gastric cancer (MGC) patients previously treated with docetaxel and S-1 with or without oxaliplatin (DS/DOS). Patients and Methods. We reviewed the data of patients who had previously been treated with firstline DS/DOS and received biweekly irinotecan-based chemotherapy (FOLFIRI/IFL) between October 2004 and November 2011. Results. A total of 209 cycles were administered to 35 patients, with a median of 4 (range, 1-22) cycles each. The overall response rate in 29 response-assessable patients was 17.2%, including 2 complete and 3 partial responses. The median progression-free and overall survivals were 3.81 (95% confidence interval [CI], 1.82-5.80) months and 6.24 (95% CI, 1.44-11.04) months, respectively. The major grade 3/4 toxicity was neutropenia (8.6%). Conclusion. FOLFIRI/IFL chemotherapy showed modest antitumour activity and tolerable toxicities in DS/DOS-treated MGC patients

W poszukiwaniu kobiecej tożsamości w neokonfucjańskim Joseon: analiza przestępstw dotyczących kobiet w „Sabeobpumbo”

This research analyzes female-related cases in Sabeobpumbo (사법품보, 司法稟報) to examine Joseon women’s identity and perceptions of their role in the patriarchal society. Since women’s chastity was directly related to their social value, it was sometimes traded for their lives. Women were often unfairly reprehended when involved in domestic conflicts because of their lower status and they have been understood as individuals who faithfully followed the agnatic principle. However, there were exceptions, and Sabeobpumbo contained extraordinary accounts of various Joseon women in which they were described as independent and displayed active defiance in response to their highly conservative society while hoping to break free from the rigid social structure. In some cases, Joseon women decisively left their husbands for various reasons, mostly involving financial instability or neglecting duties. Furthermore, some women went to incredible lengths to preserve their husband’s and his family’s dignity. Interestingly enough, these women were not only absolved from their actions but even met with silent approval from the public. These examples provide an intriguing perspective that directly clashes with the accepted norms during the Joseon Dynasty and calls for further research on the complexities of female identity as a Joseon woman.  Niniejsze badanie opisanych w Sabeobpumbo (사법품보; 司法稟報) przypadków przestępstw dotyczących kobiet ma na celu analizę przykładów mówiących o kobiecej tożsamości z czasów Joseon, jak i percepcji roli kobiet w patriarchalnym społeczeństwie. Cnotliwość kobiet odgrywała olbrzymią rolę w ich życiu gdyż korelowała z ich społeczną ‘wartością’. Kobiety z racji swego niskiego statusu często były niesprawiedliwie piętnowane za udział w konfliktach domowych. Przyjmowano także, że mają się one wiernie stosować do zasad starszeństwa i podległości. Zdarzały się jednakże wyjątki. Sabeobpumbo zawiera szczególnego rodzaju świadectwa dotyczące koreańskich kobiet, w których opisane są one jako jednostki niezależne i buntujące się przeciwko konserwatywnemu społeczeństwu, działające z nadzieją na przełamanie ograniczeń sztywnych ram społecznych. W pewnych przypadkach kobiety z Joseon świadomie i z różnych przyczyn opuszczały swoich mężów, choć w znacznej mierze było to spowodowane brakiem stabilności finansowej lub zaniedbywaniem przez nich męskich obowiązków. Zaskakująco niektóre z nich dołożyły jednocześnie wszelkich starań, by nie tylko zachować, ale i by zadbać o honor męża i jego rodziny. Co ciekawe, kobiety te nie tylko zostały uniewinnione z zarzucanych im czynów, ale nawet spotkały się z cichą aprobatą opinii publicznej. Te przykłady prezentują zaskakującą perspektywę, która bezpośrednio kłóci się z przyjętymi w czasach dynastii Joseon normami i daje podstawę do dalszych badań nad złożonością koreańskiej tożsamości kobiecej