Calcium signaling: breast cancer’s approach to manipulation of cellular circuitry

xlomafota.13 shared this article with you from Inoreader Calcium signaling: breast cancer's approach to manipulation of cellular circuitry Via Latest Results for Biophysical Reviews Abstract Calcium is a versatile element that participates in cell signaling for a wide range of cell processes such as death, cell cycle, division, migration, invasion, metabolism, differentiation, autophagy, transcription, and others. Specificity of calcium in each of these processes is achieved through modulation of intracellular calcium concentrations by changing the characteristics (amplitude/frequency modulation) or location (spatial modulation) of the signal. Breast cancer utilizes calcium signaling as an advantage for survival and progression. This review integrates evidence showing that increases in expression of calcium channels, GPCRs, pumps, effectors, and enzymes, as well as resulting intracellular calcium signals, lead to high calcium and/or an elevated calcium- mobilizing capacity necessary for malignant functions such as migratory, invasive, proliferative, tumorigenic, or metastatic capacities. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

What Are the Preferences of Patients With Rheumatoid Arthritis for Treatment Modification? A Scoping Review

xlomafota.13 shared this article with you from Inoreader What Are the Preferences of Patients With Rheumatoid Arthritis for Treatment Modification? A Scoping Review Via Latest Results for The Patient - Patient-Centered Outcomes Research Abstract Objectives Optimal care of rheumatoid arthritis (RA) patients entails regular assessment of disease activity and appropriate adjustment of disease-modifying antirheumatic drugs (DMARDs) until a predefined treatment goal is achieved. This raises questions about the approach to treatment decision making among RA patients and their preference for associated treatment changes. We aimed to systematically identify and synthesize the available evidence of RA patients' preferences regarding DMARD modification with an emphasis on escalating, tapering, stopping, or switching of DMARDs. Methods A scoping review was undertaken to gauge the breadth of evidence from the range of studies relating to RA patients' preferences for DMARD modification. Pertinent databases were searched for relevant studies published between 1988 and 2019. Conventional content analysis was applied to generate themes about how patients perceive changes to their RA treatment. Results Of the 1730 distinct articles identified, 32 were included for review. Eight studies investigated RA patients' perceptions of switching to other DMARDs, 18 studies reported RA patients' preferences for escalating treatment, and six studies explored the possibility of tapering or stopping of biologic DMARDs. Four overarching themes relating to RA patients' preferences for treatment modification were identified: (i) patient satisfaction, (ii) patients' beliefs, (iii) information needs, and (iv) patient–clinician relationships. Conclusion Uptake of treatment changes in clinical practice can be improved by understanding how RA patients approach the decision to modify their treatment and how this relates to their satisfaction, beliefs, information needs, and relationships with clinicians. Future work is needed to systematically determine the significance of these factors in RA patients' decision-making processes. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Development of a Patient-Reported Outcome Measure for Non-Alcoholic Steatohepatitis (NASH-CHECK): Results of a Qualitative Study

xlomafota.13 shared this article with you from Inoreader Development of a Patient-Reported Outcome Measure for Non-Alcoholic Steatohepatitis (NASH-CHECK): Results of a Qualitative Study Via Latest Results for The Patient - Patient-Centered Outcomes Research Abstract Background Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease characterized by excessive liver fat accumulation, inflammation, cell injury, and fibrosis. It is viewed as largely asymptomatic in its earlier (non-cirrhotic) stages, and information on the patient-perceived impact of NASH is scarce. Objective This study aimed to develop a NASH-specific patient-reported outcome (PRO) measure (NASH-CHECK) for use as a trial endpoint, using methods compliant with regulatory expectations. Methods A NASH conceptual model was developed based on the literature and clinical/patient expert review. The model guided concept elicitation (CE) interviews in patients with non-cirrhotic NASH recruited via a US tertiary care center. NASH-CHECK content was generated via thematic analysis of CE data and review by clinical/patient experts. Cognitive debriefing (CD) interviews with US patients evaluated content validity. Results The literature review confirmed that NASH impacts on functioning and health-related quality of life (HRQoL). Overall, 23 CE and 20 CD interviews were conducted. Key symptoms reported in CE interviews included pain in the upper-right abdomen (n = 14), fatigue (n = 18), poor sleep quality (n = 12), impaired memory (n = 13), and reduced focus (n = 11); key HRQoL impacts included impaired physical functioning, reduced ability to conduct daily living tasks, reduced quality of relationships, low mood, anxiety, and self-consciousness. The 52-item first-draft NASH-CHECK was reduced to 31 items based on patient feedback on item relevance, acceptability, and comprehension. Conclusions The interviews revealed key symptoms and broad HRQoL impacts of NASH. As a disease-specific PRO measure assessing symptoms and HRQoL, the NASH-CHECK is relevant, comprehensive, and acceptable to patients and clinicians. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clinical and Economic Burden of Pediatric Mild-to-Moderate Atopic Dermatitis: A Population-Based Nested Case–Control Study in Sweden

xlomafota.13 shared this article with you from Inoreader Clinical and Economic Burden of Pediatric Mild-to-Moderate Atopic Dermatitis: A Population-Based Nested Case–Control Study in Sweden Via Latest Results for Dermatology and Therapy Abstract Introduction Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition characterized by pruritic, eczematous lesions. Recent evidence suggests that AD may be a systemic disorder, implying that management of this disease extends beyond merely controlling symptoms associated with AD. Even though this disease is highly prevalent in children and patients typically present with mild-to-moderate symptoms, the disease burden is not well established. Methods A large, retrospective cohort study of Swedish population data was conducted to compare the clinical burden in terms of healthcare resource use and direct medical costs for pediatric mild-to-moderate (pM2M) AD patients (≤ 14 years of age, N = 87,721) with matched controls. The burden of a severe AD cohort was also evaluated. Severity of AD was defined by treatment usage and systemic treatment was used as a proxy for severe AD. A robust approach was used by including any type of secondary care visits known to be more common in AD patients than in the general population; however, data for primary care visits were not available. Results For healthcare resource use, the incidence rate ratio (pM2M AD versus reference cohort) of secondary care visits ranged from 1.56 to 2.35 during each of 5 years after AD onset (all p < 0.001), with largest differences seen in years 1–2. The average direct medical cost (SD) was €1111 (3416) and €524 (2446) in the pM2M AD and reference cohorts, respectively. The corresponding estimate in the severe AD cohort was €1906 (7067). Including all secondary care visits and pharmacy-dispensed medications, the pM2M AD cohort was shown to have an additional €118.9 million in direct medical costs over 5 years compared with the reference cohort. Conclusions This study shows significant clinical and economic burden of pM2M AD with important secondary care resource utilization, suggesting a need for further research to increase treatment options and improve the management of these patients. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Two-Year US Pharmacovigilance Report on Brodalumab

xlomafota.13 shared this article with you from Inoreader Two-Year US Pharmacovigilance Report on Brodalumab Via Latest Results for Dermatology and Therapy Abstract Introduction Brodalumab is a human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. In the United States, brodalumab carries a boxed warning about suicidal ideation and behavior; however, no causal association was established between brodalumab and suicides reported during pivotal trials. We have previously reported results from an analysis of 1-year pharmacovigilance data in patients in the United States who took brodalumab, in which the most commonly reported adverse event was psoriasis flare. There were no completed suicides, suicide attempts, or serious fungal infections. Here, we provide a 2-year US pharmacovigilance report. Methods This analysis summarizes pharmacovigilance data reported to Ortho Dermatologics by US patients and healthcare providers from August 15, 2017, through August 14, 2019. The most common adverse events listed in the brodalumab package insert (incidence ≥ 1%; arthralgia, headache, fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, injection-site reactions, influenza, neutropenia, and tinea infections) and adverse events of special interest are reported. Results Data were collected from 2677 patients in the United States who took brodalumab, with an estimated exposure of 1656 patient-years. Arthralgia was the most commonly reported adverse event (73 events; 0.04 events per patient-year). No suicide attempts or completed suicides were reported; there were 25 reports of depression. There were 46 serious infections and no serious fungal infections. One event of Crohn's disease was reported, which led to discontinuation. There were 13 malignancies, with none deemed related to brodalumab. Conclusions This pharmacovigilance report supports the safety profile of brodalumab previously reported from long-term analyses of clinical trials and 1-year pharmacovigilance data. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Identification of characteristics, risk factors, and predictors of recurrent LVAD thrombosis: conditions in HeartWare devices

xlomafota.13 shared this article with you from Inoreader Identification of characteristics, risk factors, and predictors of recurrent LVAD thrombosis: conditions in HeartWare devices Via Latest Results for Journal of Artificial Organs Abstract Background Redictors of repetitive left-ventricular assist device (LVAD)-thrombosis have not been studied yet. Methods We identified predictors of recurrent LVAD thrombosis in HeartWare (HVAD) patients in a long-term study from 2010 until 2020. We included all patients with two or more thrombolysis treatments for repetitive HVAD thrombosis and effectiveness of thrombolytic therapy was defined as freedom from stroke, death, another HVAD thrombosis, or surgical device exchange within 30 days after the event. Study endpoints also include all-cause mortality and heart transplantation. Results A total of 534 HVAD implantations have been screened, and 73 patients (13.7%) developed first HVAD thrombosis after a median of 10 months (IQR; 6–21 months). 46 of these patients had effective thrombolysis in 71.7% (n = 33/46). After a median of 14 months (IQR 4–32 months) follow-up, 17 patients (51.5%) had developed a second HVAD thrombosis and all were treated with t-PA therapy again, resulting in effectiveness in 76.5% (n = 13/17). The four patients with ineffective t-PA therapy underwent subsequent surgical HVAD exchange. Multiple Cox regression model analysis revealed time interval between HVAD implantation and first thrombosis as an independent risk factor of recurrent thrombosis (HR, 0.93, 95% CI 0.87–0.99, p = 0.031). Kaplan–Meier analysis at 3 year follow-up showed no significant difference in overall survival for recurrent vs non-recurrent thrombosis groups (log-rank test, p� �= 0.959). Conclusion Recurrent HVAD thrombosis mostly appears within 12 months after first thrombosis. Systemic t-PA therapy for recurrent pump thrombosis seems safe, achieving comparable effectiveness rates to initial t-PA therapy. Survival does not differ between patients with or without recurrent HVAD thrombosis. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effects of Heat and Chemical Pretreatments of Banana Peels for Metal Removal in Single and Multimetal Systems

xlomafota.13 shared this article with you from Inoreader Effects of Heat and Chemical Pretreatments of Banana Peels for Metal Removal in Single and Multimetal Systems Via Latest Results for Water, Air, & Soil Pollution Abstract This study investigated and compared the influence of pretreatments (heat and chemical) on banana peels and their subsequent efficacy in removing toxic metals (Cu, Pb, Zn, Cd) from single and multimetal systems. Banana peels were pretreated using heat (autoclaving, microwaving, boiling) and chemical (acetic acid, nitric acid, NaOH, detergent, methanol, and DMSO) treatments, prior to biosorption tests. Results revealed that pretreatment using detergent enabled banana peels to biosorb metals at relatively higher amounts in both single (Cu-96.26%, Pb-96.72%, Zn-95.75%, Cd-96.92%) and multimetal (Cu-92.43%, Pb-95.91%, Zn-91.88%, Cd-94.42%) systems. Biosorption by detergent-treated peels were profoundly effective when 0.10 g was used, with initial metal concentration of 10 mg/l, agitation speed of 120 rpm and a solution with pH 5. Characterization of detergent pretreated banana peels via FTIR analysis showed that different pretreatments applied d id not significantly modify the presence of functional groups. As such, the preexisting functional groups such as hydroxyl, amino, carboxyl, and carbonyl groups were deemed responsible for metal removal. SEM-EDX analysis on detergent pretreated peels suggested that improvement to metal removal may be attributed to enlarged pore size. This suggested that pretreatment with detergent, and as with most chemicals, presented a more feasible and economical approach than heat treatments to successfully enhance metal biosorption by banana peels for wastewater treatment. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clinical and radiological outcome after anterior cruciate ligament reconstruction using the T-lock Osteotrans resorbable tendon anchor: early experience and midterm follow-up

xlomafota.13 shared this article with you from Inoreader Clinical and radiological outcome after anterior cruciate ligament reconstruction using the T-lock Osteotrans resorbable tendon anchor: early experience and midterm follow-up Via Latest Results for BMC Musculoskeletal Disorders Abstract Purpose Reconstruction of the Anterior cruciate ligament (ACL) using tendon grafting is an established method for restoring knee function and stability. Multiple methods are established for graft fixation. Several involve anchoring the autograft distant to the joint with hardware that remains implanted. This study reports the first early to midterm results in patients who received ACL reconstruction (ACLR) using the T-Lock Osteotrans femoral near joint fixation method with a tibial fixation using the BioactIF Osteotrans interference screw. Methods This consecutive prospective series included 20 Patients (14 Male, 6 Female) with a primary ACL rupture. All patients were treated with an ACLR using a semitendinosus autograft fixated with the T-Lock Osteotrans and were followed-up postoperatively. The following parameters were assessed: Side-to-side difference of the posterior-anterior translation measured using the KT-1000 arthrometer, Tegner activity score, Lysholm score, IKDC subjective knee evaluation form. Magnetic resonance imaging (MRI) was done to assess tunnel enlargement and integrity of the anchoring device. Results The average follow-up duration was 2 years (range 1–4.2 years). One patient was lost to follow-up. Two Patients suffered a traumatic ACL re-rupture 2 years postoperatively and received a 2-stage revision ACLR. Difference in the posterior-anterior translation was 1.8 mm (range 0–5). The median Tegner score was 6 (range 4–10) and 9 patients (45%) returned to their preinjury level of activity. The mean IKDC subjective knee evaluation form scored 91 points (range 77–100). The mean Lysholm score was 86 points (74–96). All mentioned scores were significantly better compared to preoperative values. No relevant tunnel enlargement was seen on MRI. The anchoring device was evaluated to be intact in all patients. Conclusion ACLR with the aforementioned procedure leads to good clinical and radiological outcome. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Surgical site infections after distal radius fracture surgery:

xlomafota.13 shared this article with you from Inoreader Surgical site infections after distal radius fracture surgery: a nation-wide cohort study of 31,807 adult patients Via Latest Results for BMC Musculoskeletal Disorders Abstract Background Surgical site infections (SSI) after distal radius fracture (DRF) surgery have not previously been studied as the primary outcome in a large population with comparative data for different surgical methods. The aims of this study were 1) to compare SSI rates between plate fixation, percutaneous pinning and external fixation, and 2) to study factors associated with SSI. Methods We performed a nation-wide cohort study linking data from the Swedish national patient register (NPR) with the Swedish prescribed drug register (SPDR). We included all patients ≥18 years with a registration of a surgically treated DRF in the NPR between 2006 and 2013. The primary outcome was a registration in the SPDR of a dispensed prescription of peroral Flucloxacillin and/or Clindamycin within the first 8 weeks following surgery, which was used as a proxy for an SSI. The SSI rates for the three main surgical methods were calculated. Logistic regression was used to study the association between surgical method and the primary outcome, adjusted for potential confounders including age, sex, fracture type (closed/open), and a dispensed prescription of Flucloxacillin and/or Clindamycin 0–8 weeks prior to DRF surgery. A classification tree analysis was performed to study which factors were associated with SSI. Results A total of 31,807 patients with a surgically treated DRF were included. The proportion of patients with an SSI was 5% (n = 1110/21,348) among patients treated with plate fixation, 12% (n = 754/6198) among patients treated with percutaneous pinning, and 28% (n = 1180/4261) among patients treated with external fixation. After adjustment for potential confounders, the surgical method most strongly associated with SSI was external fixation (aOR 6.9 (95% CI 6.2–7.5, p < 0.001)), followed by percutaneous pinning (aOR 2.7 (95% CI 2.4–3.0, p < 0.001)) (reference: plate fixation). The classification tree analysis showed that surgical method, fracture type (closed/open), age and sex were factors associated with SSI. Conclusions The SSI rate was highest after external fixation and lowest after plate fixation. The results may be useful for estimation of SSI burdens after DRF surgery on a population basis. For the physician, they may be useful for  estimating the likelihood of SSI in individual patients. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The faster the better? Time to first CT scan after admission in moderate-to-severe traumatic brain injury and its association with mortality

xlomafota.13 shared this article with you from Inoreader The faster the better? Time to first CT scan after admission in moderate-to-severe traumatic brain injury and its association with mortality Via Latest Results for Neurosurgical Review Abstract Fast acquisition of a first computed tomography (CT) scan after traumatic brain injury (TBI) is recommended. This study is aimed at investigating whether the length of the period preceding initial CT scan influences mortality in patients with leading TBI. A retrospective cohort analysis of patients registered in the TraumaRegister DGU® was conducted including adult patients with TBI, defined as Abbreviated Injury ScaleHead ≥ 3 and GCS ≤ 13 who had been treated in level 1 or 2 trauma centers from 2007–2016. Patients were grouped according to time intervals either from trauma or from admission to CT. A total of 6904 patients met the inclusion criteria. Mean time period from trauma to hospital admission was 68.8 min. From admission to first CT, a mean of 19.0 min elapsed. Trauma severity was higher in groups with a longer duration from trauma to CT as represented by a mean (± standard deviation) Injury Severity Score (ISS) of 19.8 ± 9.0, 20.7 ± 9.3, and 21.4 ± 7.5 and similar distribution of mortality of 24.9%, 29.9%, and 36.3% in the ≤ 60-min, 61–120-min, and ≥ 121-min groups, respectively. An adjusted multivariable logistic regression model showed a significant influence of the level of the trauma center (p = 0.037) but not for interval from admission to CT (p = 0.528). TBI patients with a longer time span from trauma to first CT were more severely injured and demonstrated a worse prognosis, but received a CT scan faster when duration from admission is observed. The duration until the CT scan was obtained showed no significant impact on the mortality. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Influence of Biochar Particle Size and Concentration on Pb and As Availability in Contaminated Mining Soil and Phytoremediation Potential of Poplar Assessed in a Mesocosm Experiment

xlomafota.13 shared this article with you from Inoreader Influence of Biochar Particle Size and Concentration on Pb and As Availability in Contaminated Mining Soil and Phytoremediation Potential of Poplar Assessed in a Mesocosm Experiment Via Latest Results for Water, Air, & Soil Pollution Abstract Metal(loid)s found at many sites as a result of human activities induce contamination of ecosystems, which threatens the environment and public health. Several approaches can be used in order to reduce such negative impacts of pollutants, and among them, phytoremediation has gained attractive attention. The objective of the present study was to assess the capacity of Populus euramericana, Dorskamp cultivar, for the phytoremediation of metal(loid)s on a technosol (former mining site) highly contaminated mainly with Pb and As, and amended with biochars having different particle sizes. In a 46-day mesocosm glasshouse pot experiment, technosol was mixed at three ratios (0, 2, or 5% w/w) with four different hardwood-derived biochars (with various particle sizes) in order to study the biochar application rate and particle size effects on soil pore water (SPW) characteristics, on poplar growth, and on metal(loid) distribution and concentrati ons in the plant organs. The results showed that all biochars tested had a significant impact on several SPW physico-chemical parameters. Especially, biochar additions reduced available Pb concentrations but with no effect on As. In such conditions, Populus growth in amended technosol increased whatever rate and particle size of biochar used. Metal(loid) concentrations and repartition in plant organs showed the following: (1) for Pb, a higher root concentration with low aerial part translocation, which depended on biochar used, and (2) for As, mainly a root sequestration. We identified biochar with the finest particle size and combined with P. euramericana, Dorskamp, was the most suitable as remediation tools for Pb stabilization in post-mining contaminated soils. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.