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49, 95% CI[0.23-1.03], P = .06), while AYA were more likely to use social media for cancer-care (aOR = 1.79[1.08-2.99], P = .03). Although confidence at using online information for cancer-care decision making did not differ between age groups, increasing age had a non-significant trend towards reduced confidence (aOR = 0.99 per year [0.97-1.00], P = .09). Most commonly researched and desired online information were causes/risk factors/symptoms, treatment options, and prognosis/outcomes. CONCLUSIONS Age may influence the use of internet and social media for cancer-care, and older cancer survivors may be less confident at evaluating online information for cancer-care decision making. Future research should explore other strategies at meeting the informational needs of older cancer survivors. OBJECTIVES Tremendous progress has been made in the treatment of multiple myeloma; however, the majority of this success has been demonstrated in younger patients. With 36% of patients >80 years-old at diagnosis, it is important to understand if older patients are receiving similar benefits. MATERIALS AND METHODS We identified 2155 patients diagnosed with myeloma at age 80 or older in the Surveillance, Epidemiology, and End Results Program (SEER)-Medicare database from 2007 to 2013. A cohort of 2933 similar patients diagnosed with myeloma at age 70-79 was used for comparison using a difference-in-differences design. RESULTS Only 51% of patients >80 years-old at diagnosis received systemic anti-myeloma treatment. Treatment was associated with a 26% decrease in hazard for death, independent of age, race, gender, poverty, comorbidities, and proxy measures of performance status. In the 70-79 cohort, treatment was associated with a 22% decrease in hazard for death. Based on the difference-in-differences design, there is no statistically significant difference in treatment benefit based on age cohort (p = .610). CONCLUSIONS Anti-myeloma treatment produces a similar survival benefit among the oldest patients. The population over 80, when myeloma incidence peaks, is projected to triple over the next few decades. It is imperative that we continue to advance our understanding of the needs of this vulnerable subgroup of patients with myeloma. Loudness dependence of auditory evoked potentials (LDAEP) has long been considered to reflect central basal serotonin transmission. However, the relationship between LDAEP and individual serotonin receptors and transporters has not been fully explored in humans and may involve other neurotransmitter systems. To examine LDAEP's relationship with the serotonin system, we performed PET using serotonin-1A (5-HT1A) imaging via [11C]CUMI-101 and serotonin transporter (5-HTT) imaging via [11C]DASB on a mixed sample of healthy controls (n = 4 4 females, 0 males), patients with unipolar (MDD, n = 11 4 females, 7 males) and bipolar depression (BD, n = 8 4 females, 4 males). On these same participants, we also performed electroencephalography (EEG) within a week of PET scanning, using 1000 Hz tones of varying intensity to evoke LDAEP. We then evaluated the relationship between LDAEP and 5-HT1A or 5-HTT binding in both the raphe (5-HT1A)/midbrain (5-HTT) areas and in the temporal cortex. We found that LDAEP was significantly correlated with 5-HT1A positively and with 5-HTT negatively in the temporal cortex (p less then 0.05), but not correlated with either in midbrain or raphe. In males only, exploratory analysis showed multiple regions in which LDAEP significantly correlated with 5-HT1A throughout the brain; we did not find this with 5-HTT. This multimodal study partially validates preclinical models of a serotonergic influence on LDAEP. Replication in larger samples is necessary to further clarify our understanding of the role of serotonin in perception of auditory tones. BAY 85-3934 HIF modulator Engineering biotechnological microorganisms to use methanol as a feedstock for bioproduction is a major goal for the synthetic metabolism community. Here, we aim to redesign the natural serine cycle for implementation in E. coli. We propose the homoserine cycle, relying on two promiscuous formaldehyde aldolase reactions, as a superior pathway design. The homoserine cycle is expected to outperform the serine cycle and its variants with respect to biomass yield, thermodynamic favorability, and integration with host endogenous metabolism. Even as compared to the RuMP cycle, the most efficient naturally occurring methanol assimilation route, the homoserine cycle is expected to support higher yields of a wide array of products. We test the in vivo feasibility of the homoserine cycle by constructing several E. coli gene deletion strains whose growth is coupled to the activity of different pathway segments. Using this approach, we demonstrate that all required promiscuous enzymes are active enough to enable growth of the auxotrophic strains. Our findings thus identify a novel metabolic solution that opens the way to an optimized methylotrophic platform. CONTEXT There has been a growing consensus that parenteral nutrition and hydration is to be forgone in terminally ill patients with cancer. However, it remains unclear what the beliefs and perceptions of parenteral nutrition and hydration by the family members are. OBJECTIVES To clarify their beliefs and perceptions and to examine the relationships between the factors of family members, their beliefs and perceptions, and their overall satisfaction with the care the patient received at the place of death. METHODS This study was performed as a part of the cross-sectional anonymous nationwide survey of the bereaved family members of cancer patients in Japan. RESULTS In total, 1001 questionnaires were sent and 610 were returned. Among these, 499 were analyzed. Regarding the prevalence of beliefs and perceptions about parenteral nutrition and hydration, 'When a patient cannot eat enough, parenteral hydration is needed' was the highest (87.7%), followed by 'The opinions of medical staff are important in the issue of parenteral nutrition and hydration', 'Parenteral hydration serves as a substitute for oral hydration', and 'If I were a patient and could not eat enough, parenteral hydration would be needed' (85.1, 81.0, and 80.0%, respectively). We extracted two concepts as follows 'Belief that parenteral nutrition and hydration are beneficial' and 'Perceived need for parenteral nutrition and hydration'. They were not identified as independent determinants of overall care satisfaction. CONCLUSION This study showed that beliefs and perceptions about parenteral nutrition and hydration were important in the family members in palliative care. CONTEXT Symptom management is essential in the end of life care of long-term care facility residents. OBJECTIVES To study discrepancies and possible associated factors in staff and family carers' symptom assessment scores for residents in the last week of life. METHODS A post mortem survey in Belgium, the Netherlands and Finland staff and family carers completed the "End-Of-Life in Dementia - Comfort Assessment in Dying" scale (EOLD-CAD), rating 14 symptoms on a 1 to 3-point scale. Higher scores reflect better comfort. We calculated mean paired differences in symptom, subscale and total scores at a group level and interrater agreement and percentage of perfect agreement at a resident level. RESULTS Mean staff scores significantly reflected better comfort than those of family carers for the total EOLD-CAD (31.61 versus 29.81; P-value less then 0.001) and for the physical distress ( 8.64 vs 7.62; P-value less then 0.001) and dying symptoms (8.95 vs 8.25; P-value less then 0.001) subscales. No significant differences were found for emotional distress and well-being The largest discrepancies were found for "gurgling", "discomfort", "restlessness" and "choking" for which staff answered "not at all" whereas the family carer answered "a lot", in respectively 9.5, 7.3, 6.7 and 6.1% of cases. Interrater agreement κ ranged from 0.106 to 0.204, the extent of perfect agreement from 40.8 for lack of serenity to 68.7 % for crying. CONCLUSION There is a need for improved communication between staff andfamily and discussion about symptom burden in the dying phase in long-term care facilities. PC-FACS (FastArticleCriticalSummaries forClinicians inPalliativeCare) provides hospice and palliative care clinicians with concise summaries of the most important findings from more than 100 medical and scientific journals. If you have colleagues who would benefit from receiving PCFACS, please encourage them to join the AAHPM at aahpm.org. Comments from readers are welcomed at [email protected]. CRISPR (clustered, regularly interspaced, short palindromic repeats)/CRISPR-associated protein 9 (Cas9) system has emerged as a powerful genome-editing tool to correct genetic disorders. However, successful intracellular delivery of CRISPR/Cas9, especially in the form of ribonucleoprotein (RNP), remains elusive for clinical translation. Herein, we describe a supramolecular polymer that can mediate efficient controlled delivery of Cas9 RNP in vitro and in vivo. This supramolecular polymer system is prepared by complexing disulfide-bridged biguanidyl adamantine (Ad-SS-GD) with β-cyclodextrin-conjugated low-molecular-weight polyethyleneimime (CP) through supramolecular assembly to generate CP/Ad-SS-GD. Due to multiple, strong hydrogen bonding and salt bridge effects, CP/Ad-SS-GD well interact with Cas9 RNP to form stable nanocomplex CP/Ad-SS-GD/RNP, which can be readily released in the reductive intracellular milieu as a result of the cleavage of disulfide bonds. The supramolecular polymer ensures the efficient intracellular delivery and the release of Cas9 RNP into 293T cells and colorectal cancer (CRC) cells, thus displaying high genome-editing activity in vitro. Importantly, we also found that hyaluronic acid (HA)-decorated CP/Ad-SS-GD/RNP nanocomplexes targeting mutant KRAS effectively inhibit tumor growth as well as metastasis in the tumor-bearing mouse models. Collectively, our findings provide a promising therapeutic strategy against mutant KRAS for the treatment of CRC-activated RAS pathways, offering a new therapeutic genome-editing modality for the colorectal cancer treatment. Paper is a common material that is promising for constructing microfluidic chips (lab-on-a-paper) for diagnostics and drug delivery for biomedical applications. In the past decade, extensive research on paper-based microfluidics has accumulated a large number of scientific publications in the fields of biomedical diagnosis, food safety, environmental health, drug screening and delivery. This review focuses on the recent progress on paper-based microfluidic technology with an emphasis on the design, optimization and application of the technology platform, in particular for medical diagnostics and drug delivery. Novel advances have concentrated on engineering paper devices for point-of-care (POC) diagnostics, which could be integrated with nucleic acid-based tests and isothermal amplification experiments, enabling rapid sample-to-answer assays for field testing. Among the isothermal amplification experiments, loop-mediated isothermal amplification (LAMP), an extremely sensitive nucleic acid test, specifically identifies ultralow concentrations of DNA/RNA from practical samples for diagnosing diseases.
Website: https://www.selleckchem.com/products/molidustat-(bay85-3934).html
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