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Endolysins have been studied intensively as an alternative to antibiotics. In this study, endolysin derived from a phage which infects methicillin-resistant Staphylococcus aureus (MRSA) was cloned and expressed in Escherichia coli pET28a. Initially, the endolysin was cloned using BamHI/XhoI, resulting in expression of a recombinant endolysin which was expressed in inclusion bodies. While solubilization was successful, the protein remained nonfunctional. Recloning the endolysin using NcoI/XhoI resulted in expression of soluble and functional proteins at 18°C. The endolysin was able to form halo zones on MRSA plates and showed a reduction in turbidity of MRSA growth. Therefore, cloning strategies should be chosen carefully even in an established expression system as they could greatly affect the functionality of the expressed protein.
Advanced care planning (ACP) provides an opportunity for individuals to explore and document their values concerning medical care decisions prior to an acute event. This manuscript explores the value of ACP and compares and contrasts 2 ACP models currently in practice.
This hypothetical case describes an elderly, frail patient with end-stage chronic obstructive pulmonary disease who is also a high user of health care resources. A new palliative care-led outpatient ACP clinic model is described using this example.
Using the ACP clinic model in this case reveals how different a patient's end of life experience may be when proper, proactive planning measures are in place. With proper education and discussion around this patient and family's wishes pertaining to the end of his life, this man was able to change his plan of care from aggressive resuscitation treatment in hospital to a peaceful palliative experience at home.
In this case description, the valuable role of ACP in preserving quality of life for patients, increasing satisfaction with care, and decreasing distress among family members during a medical event is demonstrated.
In this case description, the valuable role of ACP in preserving quality of life for patients, increasing satisfaction with care, and decreasing distress among family members during a medical event is demonstrated.
Cervical cancer is a leading cause of cancer-related mortality in women in China. This analysis is a quantitative evidence synthesis pooling information about each cervical cancer risk factor.
A meta-model was developed to estimate the risk of cervical cancer for a woman aged 18-85 years in Mainland China based on her risk profile at the time of assessment. The meta-model was built using findings of a systematic literature review that identified 21 case-control studies reporting data on 105 groups of cervical cancer risk factors in Chinese women. Extracted risk factors were ranked, and 17 were selected by Chinese clinical experts for inclusion in the meta-model. Risk equations were developed for each selected study. Predicted risks for each study were dependent on the risk profile under consideration and study-specific risks were pooled to an overall risk estimate using a random-effects meta-analysis. Sensitivity analysis was conducted using 100 artificial patient profiles (in the absence of patient data).
Predicted risks for the 100 profiles suggested that the model had good face validity and could differentiate between high and non-high cervical cancer risk profiles.
This innovative meta-model approach assesses cervical cancer risk in Chinese women from a holistic perspective and could be adapted for other diseases and settings.
This innovative meta-model approach assesses cervical cancer risk in Chinese women from a holistic perspective and could be adapted for other diseases and settings.Chronic pain is a debilitating condition that affects roughly a third to a half of the world's population. Despite its substantial effect on society, treatment for chronic pain is modest, at best, notwithstanding its side effects. Hence, novel therapeutics are direly needed. Emerging evidence suggests that calcium plays an integral role in mediating neuronal plasticity that underlies sensitization observed in chronic pain states. The endoplasmic reticulum and the mitochondria are the largest calcium repositories in a cell. Here, we review how stressors, like accumulation of misfolded proteins and oxidative stress, influence endoplasmic reticulum and mitochondria function and contribute to chronic pain. Isoxazole 9 We further examine the shuttling of calcium across the mitochondrial-associated membrane as a mechanism of cross-talk between the endoplasmic reticulum and the mitochondria. In addition, we discuss how endoplasmic reticulum stress, mitochondrial impairment, and calcium dyshomeostasis are implicated in various models of neuropathic pain. We propose a novel framework of endoplasmic reticulum-mitochondria signaling in mediating pain hypersensitivity. These observations require further investigation in order to develop novel therapies for chronic pain.
In clinical practice, waiting 14 days between the administration of pegfilgrastim and subsequent chemotherapy cycle (as recommended by the prescribing information) is sometimes not feasible with multi-cycle dose-dense regimens. This study evaluated the practice related to the use of pegfilgrastim in oncology patients at a multi-hospital health system.
Patients who received pegfilgrastim as primary prophylaxis following dose-dense chemotherapy scheduled every 14 days were included. The primary endpoint was the impact of <14 elapsed days between pegfilgrastim administration and next chemotherapy cycle on the change in mean absolute neutrophil counts (ANC). A generalized linear mixed-effects model with fixed effects for pegfilgrastim delivery method, elapsed days between pegfilgrastim and chemotherapy (fixed categorical effect for 12, 13, 14 days), and ANC at subsequent cycle was fitted to the change in ANC between chemotherapy cycles.
One hundred and sixty four patients with breast cancer who received pegfilgrastim support for dose dense doxorubicin and cyclophosphamide (ddAC) qualified for the model. The mean age was 52 ± 12 years. Eighty-eight percent received pegfilgrastim on-body injector while 13% received pegfilgrastim injection. The mean number of elapsed days between pegfilgrastim and subsequent chemotherapy was 13 ± 0.5 days. The method of pegfilgrastim delivery and elapsed days between pegfilgrastim and chemotherapy administration had no significant effect on the change in ANC (p = 0.8663 and p = 0.8434 respectively); however, patient's age (p = 0.0125) had a significant effect on the change in ANC.
The study findings suggest safety and efficacy when chemotherapy is administered 12-14 days from pegfilgrastim.
The study findings suggest safety and efficacy when chemotherapy is administered 12-14 days from pegfilgrastim.
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