German nation-wide in-patient treatment of abdominal aortic aneurysm — trends between 2005 and 2019 and impact of the SARS-CoV-2 pandemic

Purpose Aim of this study was to analyze hospitalizations due to ruptured and non-ruptured abdominal aortic aneurysms (rAAA, nrAAA) in Germany between 2005 and 2021 to determine long-term trends in treatment and the impact of the SARS-CoV-2 pandemic. Materials and Methods Fully anonymized data were available from the research data center (RDC) of the German Federal Statistical Office (Destatis). All German hospitalizations with the ICD-10 code “I71.3, rAAA” and “I71.4, nrAAA” in 2005 and 2010–2021 were analyzed. Results We report data of a total of 202,951 hospitalizations. The number of hospitalizations increased from 2005 to 2019 (14,075 to 16,051, + 14.0%). The rate of open repair (OR) constantly decreased, whereas the rate of endovascular aortic repair (EVAR) increased until 2019. During the pandemic, the number of hospitalizations due to nrAAA dropped from 13,887 (86.5%) in 2019 to 11,278 (85.0%) in 2021. The strongest decrease of hospitalizations for AAA was observed during the first wave of the SARS-CoV-2-pandemic in spring 2020 (-25.5%). Conclusion Over the past decades, we observed an increasing number of hospitalizations due to AAA accompanied by a shift from OR to EVAR especially for nrAAA. During the lockdown measures due to the SARS-CoV-2-pandemic, a decrease in hospitalizations for nrAAA (but not for rAAA) was shown in 2020 and furthermore in 2021 with no rebound of treatment of nrAAA suggesting an accumulation of untreated AAA with a potentially increased risk of rupture

A methoxy derivative of resveratrol analogue selectively induced activation of the mitochondrial apoptotic pathway in transformed fibroblasts

Resveratrol (R-3), a trihydroxy trans-stilbene from grape, inhibits multistage carcinogenesis in animal models. A resveratrol derivative 3,4,5,4′-tetrahydroxystilbene (R-4) exhibits potent growth inhibitory effect against transformed human cells. Here we report that 3,4,5,4′-tetramethoxystilbene (MR-4), converted from R-4, was more potent against cancer cell lines (WI38VA, IMR-90SV, HeLa, LNCaP, HT-29, and HepG2), but had almost no inhibitory effect on the growth of normal cells (WI38, IMR-90, BJ-T) at the concentrations tested. The IC50 value of MR-4 on the growth inhibition of transformed WI38VA human cells was 0.5 μM, as compared to the value of greater than 50 μM for the normal WI38 cells. Resveratrol, however, did not exhibit such clear differential effect and the IC50 value of R-3 for WI38VA cells was about 50 μM. The growth inhibitory effect of MR-4 correlated with the induction of apoptosis in the transformed cells. When normal WI38 cells and transformed WI38VA cells were compared, MR-4 induced increases of the Bax/Bcl-2 mRNA ratio, p53 and Bax protein level, activation of caspases, and DNA fragmentation in transformed, but not in normal cells. Further analysis revealed that MR-4 caused a rapid appearance of perinuclear aggregation of mitochondria in WI38VA but not in WI38 cells, suggesting that the mitochondria could serve as an early target of MR-4. R-3 also induced apoptosis and mitochondrial clustering but only at a much higher concentration, close to 500 μM. Taken together, the specific activation of the mitochondria-mediated apoptotic pathway could be a major reason for the striking differential growth inhibitory effect of MR-4

Black tea extract prevents lipopolysaccharide-induced NF-κB signaling and attenuates dextran sulfate sodium-induced experimental colitis

<p>Abstract</p> <p>Background</p> <p>Black tea has been shown to elicit anti-oxidant, anti-carcinogenic, anti-inflammatory and anti-mutagenic properties. In this study, we investigated the impact of black tea extract (BTE) on lipopolysaccharide (LPS)-induced NF-κB signaling in bone marrow derived-macrophages (BMM) and determined the therapeutic efficacy of this extract on colon inflammation.</p> <p>Methods</p> <p>The effect of BTE on LPS-induced NF-κB signaling and pro-inflammatory gene expression was evaluated by RT-PCR, Western blotting, immunofluorescence and electrophoretic mobility shift assay (EMSA). The <it>in vivo </it>efficacy of BTE was assessed in mice with 3% dextran sulfate sodium (DSS)-induced colitis. The severity of colitis was measured by weight loss, colon length and histologic scores.</p> <p>Results</p> <p>LPS-induced IL-12p40, IL-23p19, IL-6 and IL-1β mRNA expressions were inhibited by BTE. LPS-induced IκBα phosphorylation/degradation and nuclear translocation of NF-κB/p65 were blocked by BTE. BTE treatment blocked LPS-induced DNA-binding activity of NF-κB. BTE-fed, DSS-exposed mice showed the less weight loss, longer colon length and lower histologic score compared to control diet-fed, DSS-exposed mice. DSS-induced IκBα phosphorylation/degradation and phosphorylation of NF-κB/p65 were blocked by BTE. An increase of cleaved caspase-3 and poly (ADP-ribose) polymerase (PARP) in DSS-exposed mice was blocked by BTE.</p> <p>Conclusions</p> <p>These results indicate that BTE attenuates colon inflammation through the blockage of NF-κB signaling and apoptosis in DSS-induced experimental colitis model.</p

Polyphenols Sensitization Potentiates Susceptibility of MCF-7 and MDA MB-231 Cells to Centchroman

Polyphenols as “sensitizers” together with cytotoxic drugs as “inducers” cooperate to trigger apoptosis in various cancer cells. Hence, their combination having similar mode of mechanism may be a novel approach to enhance the efficacy of inducers. Additionally, this will also enable to achieve the physiological concentrations facilitating significant increase in the activity at concentrations which the compound can individually provide. Here we propose that polyphenols (Resveratrol (RES) and Curcumin (CUR)) pre-treatment may sensitize MCF-7/MDA MB-231 (Human Breast Cancer Cells, HBCCs) to Centchroman (CC, antineoplastic agent). 6 h pre-treated cells with 10 µM RES/CUR and 100 µM RES/30 µM CUR doses, followed by 10 µM CC for 18 h were investigated for Ser-167 ER-phosphorylation, cell cycle arrest, redox homeostasis, stress activated protein kinase (SAPKs: JNK and p38 MAPK) pathways and downstream apoptosis effectors. Low dose RES/CUR enhances the CC action through ROS mediated JNK/p38 as well as mitochondrial pathway in MCF-7 cells. However, RES/CUR sensitization enhanced apoptosis in p53 mutant MDA MB-231 cells without/with involvement of ROS mediated JNK/p38 adjunct to Caspase-9. Contrarily, through high dose sensitization in CC treated cells, the parameters remained unaltered as in polyphenols alone. We conclude that differential sensitization of HBCCs with low dose polyphenol augments apoptotic efficacy of CC. This may offer a novel approach to achieve enhanced action of CC with concomitant reduction of side effects enabling improved management of hormone-dependent breast cancer

Growth Inhibition of Human Gynecologic and Colon Cancer Cells by Phyllanthus watsonii through Apoptosis Induction

Phyllanthus watsonii Airy Shaw is an endemic plant found in Peninsular Malaysia. Although there are numerous reports on the anti cancer properties of other Phyllanthus species, published information on the cytotoxicity of P. watsonii are very limited. The present study was carried out with bioassay-guided fractionation approach to evaluate the cytotoxicity and apoptosis induction capability of the P. watsonii extracts and fractions on human gynecologic (SKOV-3 and Ca Ski) and colon (HT-29) cancer cells. P. watsonii extracts exhibited strong cytotoxicity on all the cancer cells studied with IC50 values of ≤ 20.0 µg/mL. Hexane extract of P. watsonii was further subjected to bioassay-guided fractionation and yielded 10 fractions (PW-1→PW-10). PW-4→PW-8 portrayed stronger cytotoxic activity and was further subjected to bioassay-guided fractionation and resulted with 8 sub-fractions (PPWH-1→PPWH-8). PPWH-7 possessed greatest cytotoxicity (IC50 values ranged from 0.66 – 0.83 µg/mL) and was selective on the cancer cells studied. LC-MS/MS analysis of PPWH-7 revealed the presence of ellagic acid, geranic acid, glochidone, betulin, phyllanthin and sterol glucoside. Marked morphological changes, ladder-like appearance of DNA and increment in caspase-3 activity indicating apoptosis were clearly observed in both human gynecologic and colon cancer cells treated with P. watsonii especially with PPWH-7. The study also indicated that P. watsonii extracts arrested cell cycle at different growth phases in SKOV-3, Ca Ski and HT-29 cells. Cytotoxic and apoptotic potential of the endemic P. watsonii was investigated for the first time by bioassay-guided approach. These results demonstrated that P. watsonii selectively inhibits the growth of SKOV-3, Ca Ski and HT-29 cells through apoptosis induction and cell cycle modulation. Hence, P. watsonii has the potential to be further exploited for the discovery and development of new anti cancer drugs

"I want more time with my doctor": a quantitative study of time and the consultation

Background. Although consultations have increased in length, patients still express dissatisfaction with how much time they spend with their doctor. Objectives. This study aimed to explore aspects of consultation time and to examine the correlates of patients' desire for more time. Methods. A quantitative cross-sectional design was used. General practice patients from eight UK practices (n = 294) completed a questionnaire following a consultation regarding their satisfaction with the consultation, their beliefs about how long the consultation lasted (perceived time) and how long they would have preferred it to last (preferred time). The actual consultation length (real time) was recorded by the doctor. Results. The majority of patients underestimated how long the consultation took, and a large minority stated that they would have preferred more time. When controlling for both real time and perceived time, a preference for more time was correlated with a dissatisfaction with the emotional aspects of the consultation and a lower intention to comply with the doctors recommendations. It was unrelated to satisfaction with the information giving and examination components of the consultation. Conclusion. Patients' dissatisfaction with consultation length could be managed by making consultations longer. Alternatively, it could also be managed by changing how a given time is spent. In particular, a doctor who listens and tries to understand their patient may make the patient feel more satisfied with the consultation length and subsequently more motivated to follow any recommendations for change

"I want more time with my doctor": a quantitative study of time and the consultation

Background. Although consultations have increased in length, patients still express dissatisfaction with how much time they spend with their doctor. Objectives. This study aimed to explore aspects of consultation time and to examine the correlates of patients' desire for more time. Methods. A quantitative cross-sectional design was used. General practice patients from eight UK practices (n = 294) completed a questionnaire following a consultation regarding their satisfaction with the consultation, their beliefs about how long the consultation lasted (perceived time) and how long they would have preferred it to last (preferred time). The actual consultation length (real time) was recorded by the doctor. Results. The majority of patients underestimated how long the consultation took, and a large minority stated that they would have preferred more time. When controlling for both real time and perceived time, a preference for more time was correlated with a dissatisfaction with the emotional aspects of the consultation and a lower intention to comply with the doctors recommendations. It was unrelated to satisfaction with the information giving and examination components of the consultation. Conclusion. Patients' dissatisfaction with consultation length could be managed by making consultations longer. Alternatively, it could also be managed by changing how a given time is spent. In particular, a doctor who listens and tries to understand their patient may make the patient feel more satisfied with the consultation length and subsequently more motivated to follow any recommendations for change