- Chlamydia trachomatis-infected human cells convert ceramide to sphingomyelin without sphingomyelin synthases 1 and 2. [Journal Article]FEBS Lett 2019FL
- The obligate intracellular bacterium Chlamydia trachomatis proliferates in the membranous compartment inclusion formed in host cells. The host ceramide transport protein CERT delivers ceramide from the endoplasmic reticulum to the Golgi complex for the synthesis of sphingomyelin (SM). C. trachomatis has been suggested to employ CERT to produce SM in the inclusion by host SM synthases (SMSs). Here…
The obligate intracellular bacterium Chlamydia trachomatis proliferates in the membranous compartment inclusion formed in host cells. The host ceramide transport protein CERT delivers ceramide from the endoplasmic reticulum to the Golgi complex for the synthesis of sphingomyelin (SM). C. trachomatis has been suggested to employ CERT to produce SM in the inclusion by host SM synthases (SMSs). Here, we found that C. trachomatis proliferates and produces infective progeny even in SMS1 and SMS2 double knockout HeLa cells, but not in the SMS1/SMS2/CERT triple knockout cells. Interestingly, infected cells convert ceramide to SM without host SMSs. These results suggest that C. trachomatis-infected cells can convert ceramide to SM without host SMSs after CERT-mediated transfer of ceramide to the inclusions.
- The use of wearable devices in preventing hospital readmission and in improving the quality of life of chronic patients in the homecare Setting: A Narrative Literature Review. [Journal Article]Prof Inferm 2019 Apr-Jun; 72(2):143-151PI
- Present criteria for prophylactic ICD implantation: Insights from the EU-CERT-ICD (Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators in EUrope) project. [Review]J Electrocardiol 2019JE
- CONCLUSIONS: The EU-CERT-ICD is a prospective investigator-initiated non-randomized, controlled, multicenter observational cohort study done in 44 centers across 15 European countries. A total of 2327 patients with heart failure due to ischemic heart disease or dilated cardiomyopathy indicated for primary prophylactic ICD implantation were recruited between 2014 and 2018 (>1500 patients at first ICD implantation, >750 patients non-randomized non-ICD control group). The primary endpoint was all-cause mortality, and first appropriate shock was co-primary endpoint. At baseline, all patients underwent 12‑lead ECG and Holter-ECG analysis using multiple advanced methods for risk stratification as well as documentation of clinical characteristics and laboratory values. The EU-CERT-ICD data will provide much needed information on the survival benefit of preventive ICD therapy and expand on previous prospective risk stratification studies which showed very good applicability of clinical parameters and advanced risk stratifiers in order to define patient subgroups with above or below average ICD benefit.The EU-CERT-ICD study will provide new and current data about effectiveness of primary prophylactic ICD implantation. The study also aims for improved risk stratification and patient selection using clinical risk markers in general, and advanced ECG risk markers in particular.
- Exploring Incontinence-Associated Dermatitis in a Single Center Intensive Care Unit: A Longitudinal Point Prevalence Survey. [Journal Article]J Wound Ostomy Continence Nurs 2019 Sep/Oct; 46(5):401-407JW
- CONCLUSIONS: These data show the high variability of IAD prevalence over a 1-year period. Characteristics associated with the development of IAD in patients in the ICU included older age, longer lengths of ICU stay, incontinent of liquid feces, and having respiratory or sepsis diagnoses.
- Pre-treatment with the CDK4/6 inhibitor palbociclib improves the efficacy of paclitaxel in TNBC cells. [Journal Article]Sci Rep 2019; 9(1):13014SR
- Triple Negative Breast Cancer (TNBC) is a challenging disease due to the lack of druggable targets; therefore, chemotherapy remains the standard of care and the identification of new targets is a high clinical priority. Alterations in the components of the cell cycle machinery have been frequently reported in cancer; given the success obtained with the CDK4/6 inhibitor palbocicib in ER-positive B…
Triple Negative Breast Cancer (TNBC) is a challenging disease due to the lack of druggable targets; therefore, chemotherapy remains the standard of care and the identification of new targets is a high clinical priority. Alterations in the components of the cell cycle machinery have been frequently reported in cancer; given the success obtained with the CDK4/6 inhibitor palbocicib in ER-positive BC, we explored the potential of combining this drug with chemotherapy in Rb-positive TNBC cell models. The simultaneous combination of palbociclib with paclitaxel exerted an antagonistic effect; by contrast, the sequential treatment inhibited cell proliferation and increased cell death more efficaciously than single treatments. By down-regulating the E2F target c-myc, palbociclib reduced HIF-1α and GLUT-1 expression, and hence glucose uptake and consumption both under normoxic and hypoxic conditions. Importantly, these inhibitory effects on glucose metabolism were enhanced by palbociclib/paclitaxel sequential combination; the superior efficacy of such combination was ascribed to the ability of paclitaxel to inhibit palbociclib-mediated induction of AKT and to further down-regulate the Rb/E2F/c-myc signaling. Our results suggest that the efficacy of standard chemotherapy can be significantly improved by a pre-treatment with palbociclib, thus offering a better therapeutic option for Rb-proficient TNBC.
- Acquired BRAF G469A Mutation as a Resistance Mechanism to First-Line Osimertinib Treatment in NSCLC Cell Lines Harboring an EGFR Exon 19 Deletion. [Journal Article]Target Oncol 2019; 14(5):619-626TO
- CONCLUSIONS: Our in vitro studies revealed the BRAF G469A-activating mutation as a potential mechanism of acquired resistance to first-line osimertinib treatment, and provide a strategy of intervention to overcome this mechanism of resistance.
- Accumulation of sphingomyelin in Niemann-Pick disease type C cells disrupts Rab9-dependent vesicular trafficking of cholesterol. [Journal Article]J Cell Physiol 2019JC
- Niemann-Pick disease type C (NPC) is a genetic disorder in which patient cells have endosomal/lysosomal accumulation of cholesterol and sphingolipids. However, the relationship between sphingolipids and cholesterol accumulation in NPC cells has not been established. Here, we investigated the role of sphingomyelin (SM) on the accumulation of cholesterol in NPC cells. Reduction of SM by inhibition …
Niemann-Pick disease type C (NPC) is a genetic disorder in which patient cells have endosomal/lysosomal accumulation of cholesterol and sphingolipids. However, the relationship between sphingolipids and cholesterol accumulation in NPC cells has not been established. Here, we investigated the role of sphingomyelin (SM) on the accumulation of cholesterol in NPC cells. Reduction of SM by inhibition of the ceramide transfer protein CERT decreased the cholesterol accumulation in NPC cells. The accumulation of SM in NPC cells inhibited the transport of cholesterol to the endoplasmic reticulum. Overexpression of Rab9 in NPC cells reduced the cholesterol accumulation, which was recovered by treatment with SM. In NPC cells that overexpressed a Rab9 constitutively active mutant, SM treatment did not lead to the cholesterol accumulation. These results indicate that SM negatively regulates the Rab9-dependent vesicular trafficking of cholesterol, and a reduction in SM levels in NPC cells recovers the Rab9-dependent vesicular trafficking defect.
- Prediction of mortality benefit based on periodic repolarisation dynamics in patients undergoing prophylactic implantation of a defibrillator: a prospective, controlled, multicentre cohort study. [Journal Article]Lancet 2019; 394(10206):1344-1351Lct
- CONCLUSIONS: Periodic repolarisation dynamics predict mortality reductions associated with prophylactic implantation of ICDs in contemporarily treated patients with ischaemic or non-ischaemic cardiomyopathy. Periodic repolarisation dynamics could help to guide treatment decisions about prophylactic ICD implantation.
- Supervised exercise following bariatric surgery in morbid obese adults: CERT-based exercise study protocol of the EFIBAR randomised controlled trial. [Journal Article]BMC Surg 2019; 19(1):127BS
- CONCLUSIONS: The present study details the exercise programme of the EFIBAR RCT, which may serve: 1) exercise professionals who would like to implement an evidence-based exercise programme for BS patients, and 2) as an example of the application of the CERT criteria.
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- Getting Addiction Into the Nursing Education "Water Supply": A U.K. Case Study. [Journal Article]J Addict Nurs 2019 Jul/Sep; 30(3):149-158JA
- Evidence remains fundamentally unchanged over the last 30 years that nurses are not sufficiently prepared during their undergraduate education to work with alcohol and other drug (AOD) use. Employing a mixed-methods longitudinal panel design, our study objectives were to (a) explore perceptions among entry level nursing students regarding AOD work and (b) explore whether current alcohol and drug …
Evidence remains fundamentally unchanged over the last 30 years that nurses are not sufficiently prepared during their undergraduate education to work with alcohol and other drug (AOD) use. Employing a mixed-methods longitudinal panel design, our study objectives were to (a) explore perceptions among entry level nursing students regarding AOD work and (b) explore whether current alcohol and drug education efforts impact on the perception of AOD by nursing students over time. Two hundred forty-two students were recruited (94% response rate). Most (86%) of the study participants identified AOD training as relevant/extremely relevant to their future practice. After exposure to AOD sessions in the nursing curriculum, there was no significant change to participants' score on either alcohol or drug role security between T1 and T2/T3. However, there was a statistically significant improvement in alcohol therapeutic commitment between T1 and T2/T3 (F(2, 136) = 5.87, p < .01), but not between T2 and T3; conversely, drug therapeutic commitment was significantly higher at T2 but signficantly lower at T3 (F(2, 149) = 254.19, p < .0001). There was no significant difference in alcohol or drug role security between the three nurse training pathways. However, alcohol and drug therapeutic commitment scores at T1 were significantly higher in students taking the mental health field/track (F(2, 160) = 9.45, p < .001, and F(2, 236) = 15.23, p < .0001). Although the positive message is that students recognize the importance of the topic to their future practice, concerns remain regarding the impact and efforts of readiness for practice. Over a 3-year training period, no significant gains were made in increasing students' knowledge and skills, and their training experiences in clinical practice appear to have a negative effect on "therapeutic commitment" influenced by exposure/contact to patients with drug use disorders specifically and less than positive mentoring experiences with qualified nursing staff. How to address these issues is explored including the need to perhaps shift the focus of attention from "negative attitudes" held by students to exploring the barriers and obstacles in upskilling nursing faculty and clinical mentors so that they feel able and willing to teach and be a role model of good practice in this area.