Effectiveness of a web-enabled psychoeducational resource for postpartum depression and anxiety among women in British Columbia.

PURPOSE: Postpartum depression (PPD) and anxiety (PPA) affect nearly one-quarter (23%) of women in Canada. eHealth is a promising solution for increasing access to postpartum mental healthcare. However, a user-centered approach is not routinely taken in the development of web-enabled resources, leaving postpartum women out of critical decision-making processes. This study aimed to evaluate the effectiveness, usability, and user satisfaction of PostpartumCare.ca, a web-enabled psychoeducational resource for PPD and PPA, created in partnership with postpartum women in British Columbia. METHODS: Participants were randomized to either an intervention group (n = 52) receiving access to PostpartumCare.ca for four weeks, or to a waitlist control group (n = 51). Measures evaluating PPD (Edinburgh Postnatal Depression Scale) and PPA symptoms (Perinatal Anxiety Screening Scale) were completed at baseline, after four weeks, and after a two-week follow-up. User ratings of website usability and satisfaction and website metrics were also collected. RESULTS: PPD and PPA symptoms were significantly reduced for the intervention group only after four weeks, with improvements maintained after a two-week follow-up, corresponding with small-to-medium effect sizes (PPD: partial η2 = 0.03; PPA: partial η2 = 0.04). Intervention participants were also more likely than waitlist controls to recover from clinical levels of PPD symptoms (χ 2 (1, n = 63) = 4.58, p = .032) and PostpartumCare.ca's usability and satisfaction were rated favourably overall. CONCLUSION: Findings suggest that a web-enabled psychoeducational resource, created in collaboration with patient partners, can effectively reduce PPD and PPA symptoms, supporting its potential use as a low-barrier option for postpartum women. TRIAL REGISTRATION: Protocol for this trial was preregistered on NIH U.S. National Library of Medicine, ClinicalTrials.gov as of May 2022 (ID No. NCT05382884).

Endovascular coiling versus neurosurgical clipping in the management of aneurysmal subarachnoid haemorrhage in the elderly: a multicenter cohort study.

The comparability of endovascular coiling over neurosurgical clipping has not been firmly established in elderly patients with aneurysmal subarachnoid haemorrhage (aSAH). Data were obtained from all patients with aSAH aged ≥60 across three tertiary hospitals in Singapore from 2014 to 2019. Outcome measures included modified Rankin Scale (mRS) score at 3 and at 6 months, and in-hospital mortality. Of the 134 patients analyzed, 84 (62.7%) underwent coiling and 50 (37.3%) underwent clipping. The endovascular group showed a higher incidence of good mRS score 0-2 at 3 months (OR = 2.45 [95%CI:1.16-5.20];p = 0.018), and a lower incidence of in-hospital mortality (OR = 0.31 [95%CI:0.10-0.91];p = 0.026). There were no significant difference between the two treatment groups in terms of good mRS score at 6 months (OR = 1.98 [95%CI:0.97-4.04];p = 0.060). There were no significant differences in the incidence of complications, such as aneurysm rebleed, delayed hydrocephalus, delayed ischemic neurological deficit and venous thromboembolism between the two treatment groups. However, fewer patients in the coiling group developed large infarcts requiring decompressive craniectomy (OR = 0.32 [95%CI:0.12-0.90];p = 0.025). Age, admission WFNS score I-III, and coiling were independent predictors of good functional outcomes at 3 months. Only age and admission WFNS score I-III remained significant predictors of good functional outcomes at 6 months. Endovascular coiling, compared with neurosurgical clipping, is associated with significantly better short term outcomes in carefully selected elderly patients with aSAH. Maximal intervention is recommended for aSAH in the young elderly age group and those with favorable WFNS scores.

The magic of small-molecule drugs during ex vivo expansion in adoptive cell therapy.

In the past decades, advances in the use of adoptive cellular therapy to treat cancer have led to unprecedented responses in patients with relapsed/refractory or late-stage malignancies. However, cellular exhaustion and senescence limit the efficacy of FDA-approved T-cell therapies in patients with hematologic malignancies and the widespread application of this approach in treating patients with solid tumors. Investigators are addressing the current obstacles by focusing on the manufacturing process of effector T cells, including engineering approaches and ex vivo expansion strategies to regulate T-cell differentiation. Here we reviewed the current small-molecule strategies to enhance T-cell expansion, persistence, and functionality during ex vivo manufacturing. We further discussed the synergistic benefits of the dual-targeting approaches and proposed novel vasoactive intestinal peptide receptor antagonists (VIPR-ANT) peptides as emerging candidates to enhance cell-based immunotherapy.

Development and testing of a multi-lingual Natural Language Processing-based deep learning system in 10 languages for COVID-19 pandemic crisis: A multi-center study.

Purpose: The COVID-19 pandemic has drastically disrupted global healthcare systems. With the higher demand for healthcare and misinformation related to COVID-19, there is a need to explore alternative models to improve communication. Artificial Intelligence (AI) and Natural Language Processing (NLP) have emerged as promising solutions to improve healthcare delivery. Chatbots could fill a pivotal role in the dissemination and easy accessibility of accurate information in a pandemic. In this study, we developed a multi-lingual NLP-based AI chatbot, DR-COVID, which responds accurately to open-ended, COVID-19 related questions. This was used to facilitate pandemic education and healthcare delivery. Methods: First, we developed DR-COVID with an ensemble NLP model on the Telegram platform (https://t.me/drcovid_nlp_chatbot). Second, we evaluated various performance metrics. Third, we evaluated multi-lingual text-to-text translation to Chinese, Malay, Tamil, Filipino, Thai, Japanese, French, Spanish, and Portuguese. We utilized 2,728 training questions and 821 test questions in English. Primary outcome measurements were (A) overall and top 3 accuracies; (B) Area Under the Curve (AUC), precision, recall, and F1 score. Overall accuracy referred to a correct response for the top answer, whereas top 3 accuracy referred to an appropriate response for any one answer amongst the top 3 answers. AUC and its relevant matrices were obtained from the Receiver Operation Characteristics (ROC) curve. Secondary outcomes were (A) multi-lingual accuracy; (B) comparison to enterprise-grade chatbot systems. The sharing of training and testing datasets on an open-source platform will also contribute to existing data. Results: Our NLP model, utilizing the ensemble architecture, achieved overall and top 3 accuracies of 0.838 [95% confidence interval (CI): 0.826-0.851] and 0.922 [95% CI: 0.913-0.932] respectively. For overall and top 3 results, AUC scores of 0.917 [95% CI: 0.911-0.925] and 0.960 [95% CI: 0.955-0.964] were achieved respectively. We achieved multi-linguicism with nine non-English languages, with Portuguese performing the best overall at 0.900. Lastly, DR-COVID generated answers more accurately and quickly than other chatbots, within 1.12-2.15 s across three devices tested. Conclusion: DR-COVID is a clinically effective NLP-based conversational AI chatbot, and a promising solution for healthcare delivery in the pandemic era.

Regional and country-level trends in cervical cancer screening coverage in sub-Saharan Africa: A systematic analysis of population-based surveys (2000-2020).

BACKGROUND: Sub-Saharan Africa (SSA) has the highest cervical cancer (CC) burden globally-worsened by its HIV epidemics. In 2020, the World Health Organization (WHO) introduced a CC elimination strategy with goals for vaccination, screening, and treatment. To benchmark progress, we examined temporal trends in screening coverage, percent screened at least twice by the age of 45, screening coverage among women living with HIV (WLHIV), and pre-cancer treatment coverage in SSA. METHODS AND FINDINGS: We conducted a systematic analysis of cross-sectional population-based surveys. It included 52 surveys from 28 countries (2000 to 2020) with information on CC screening among women aged 25 to 49 years (N = 151,338 women). We estimated lifetime and past 3-year screening coverage by age, year, country, and HIV serostatus using a Bayesian multilevel model. Post-stratification and imputations were done to obtain aggregate national, regional, and SSA-level estimates. To measure re-screening by age 45, a life table model was developed. Finally, self-reported pre-cancer treatment coverage was pooled across surveys using a Bayesian meta-analysis. Overall, an estimated 14% (95% credible intervals [95% CrI]: 11% to 21%) of women aged 30 to 49 years had ever been screened for CC in 2020, with important regional and country-level differences. In Eastern and Western/Central Africa, regional screening coverages remained constant from 2000 to 2020 and WLHIV had greater odds of being screened compared to women without HIV. In Southern Africa, however, screening coverages increased and WLHIV had equal odds of screening. Notably this region was found to have higher screening coverage in comparison to other African regions. Rescreening rates were high among women who have already been screened; however, it was estimated that only 12% (95% CrI: 10% to 18%) of women had been screened twice or more by age 45 in 2020. Finally, treatment coverage among 4 countries with data was 84% (95% CrI: 70% to 95%). Limitations of our analyses include the paucity of data on screening modality and the few countries that had multiple surveys. CONCLUSION: Overall, CC screening coverage remains sub-optimal and did not improve much over the last 2 decades, outside of Southern Africa. Action is needed to increase screening coverage if CC elimination is to be achieved.

Enculturating, embedding and investing in fundamental care in an academic health science centre.

AIM: This manuscript aims to provide a discursive description of how one academic health care centre is enculturating, embedding and investing in the fundamental care framework and lessons learned that can serve as a blueprint for other organizations. BACKGROUND: A call to action to focus on fundamental care is not new as the initial Fundamentals of Care (FoC) Framework has been evolving over the last decade through efforts lead by the International Learning Collaborative (ILC). Now more than ever, there is a pressing need for leaders to influence a humane, compassionate evidence-informed approach to the COVID-19 pandemic and beyond by embedding an FoC framework and focusing on fundamental care as part of their academic mandate and daily care practices. DESIGN: This discursive paper delineates an evolving and ongoing enculturation, embeddedness and investment in advancing fundamental care as part of a larger academic practice strategy and quality improvement plan that is evidence-informed and collaborative in nature. METHOD: The action framework (value, talk, do, own and research fundamental care) developed by ILC guides efforts to how the FoC framework was embedded into one academic health science centre's strategic directions, academic practice strategy, professional practice model, quality plan and research and innovation platform. CONCLUSION: An overview of how we leveraged the FoC and ILC Leadership frameworks in our efforts to enculturate, embed and invest in advancing fundamental care and lessons learned that may inform other healthcare organizations in their efforts. IMPACT ON NURSING SCIENCE, PRACTICE OR DISCIPLINARY KNOWLEDGE: Underpinning all of our efforts is the integral value we place on fundamental care to guide how we practice, educate and learn, discover and innovate and lead at x. We shared how we value, talk, do, own and research fundamental care by having it embedded into our strategic directions, academic practice strategy, professional practice model, quality aims and research and innovation platform. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Can fundamental care be advanced using the science of care framework?

AIMS: This manuscript aims to provide a description of an evidence-informed Science of Care practice-based research and innovation framework that may serve as a guiding framework to generate new discoveries and knowledge around fundamental care in a more integrated manner. BACKGROUND: New ways of thinking about models of care and implementation strategies in transdisciplinary teams are required to accelerate inquiry and embed new knowledge and innovation into practice settings. A new way of thinking starts with an explicit articulation and commitment to the core business of the healthcare industry which is to provide quality fundamental care. DESIGN: This discursive paper delineates an iteratively derived Science of Care research and innovation framework (Science of Care Framework) that draws from a targeted literature review. METHOD: The Science of Care Framework integrates caring science with safety and symptom sciences with implementation, improvement, innovation and team sciences. Each science dimension is described in terms of seminal and evolving evidence and theoretical explanations, focusing on how these disciplines can support fundamental care. CONCLUSIONS: The Science of Care Framework can serve as a catalyst to guide future efforts to propel new knowledge and discoveries around fundamental care and how best to implement it into clinical practice through a transdisciplinary lens. IMPACT ON NURSING SCIENCE, PRACTICE, OR DISCIPLINARY KNOWLEDGE: The Science of Care Framework can accelerate nursing discipline-specific knowledge generation alongside inter and transdisciplinary insights. The novel articulation of the Science of Care Framework can be used to guide further inquiries that are co-designed, and led, by nurses into integrated models of care and innovations in clinical practice.

Inhibition of NADPH Oxidase-ROS Signal using Hyaluronic Acid Nanoparticles for Overcoming Radioresistance in Cancer Therapy.

Upregulation of NADPH oxidases (NOXs) in cancer cells leads to chronic increase in intracellular reactive oxygen species (ROS) and adaptation to a high ROS level for cell survival and, thereby, low sensitivity to radiotherapy. To overcome resistance to radiotherapy, we have developed a bioactive and CD44 targeted hyaluronic acid nanoparticle encapsulated with an NOX inhibitor, GKT831 (HANP/GKT831). We found that HANP/GKT831 had stronger inhibitory effects on ROS generation and cell proliferation than that of GKT831 alone in cancer cells. Systemic delivery of HANP/GKT831 led to the targeted accumulation in breast cancer patient derived xenograft (PDX) tumors in nude mice. Importantly, the combination of systemic delivery of HANP/GKT831 with a low dose of local radiotherapy significantly enhanced tumor growth inhibition in breast cancer PDX models. Our results showed that HANP/GKT831 primed tumor cells to radiation-induced DNA damage and cell death by downregulation of DNA repair function and oncogenic signal pathways.

Identifying and adapting interventions to reduce documentation burden and improve nurses' efficiency in using electronic health record systems (The IDEA Study): protocol for a mixed methods study.

BACKGROUND: Although EHR systems have become a critical part of clinical care, nurses are experiencing a growing burden due to documentation requirements, taking time away from other important clinical activities. There is a need to address the inefficiencies and challenges that nurses face when documenting in and using EHRs. The objective of this study is to engage nurses in generating ideas on how organizations can support and optimize nurses' experiences with their EHR systems, thereby improving efficiency and reducing EHR-related burden. This work will ensure the identified solutions are grounded in nurses' perspectives and experiences and will address their specific EHR-related needs. METHODS: This mixed methods study will consist of three phases. Phase 1 will evaluate the accuracy of the EHR system's analytics platform in capturing how nurses utilize the system in real-time for tasks such as documentation, chart review, and medication reconciliation. Phase 2 consists of a retrospective analysis of the nursing-specific analytics platform and focus groups with nurses to understand and contextualize their usage patterns. These focus groups will also be used to identify areas for improvement in the utilization of the EHR. Phase 3 will include focus groups with nurses to generate and adapt potential interventions to address the areas for improvement and assess the perceived relevance, feasibility, and impact of the potential interventions. DISCUSSION: This work will generate insights on addressing nurses' EHR-related burden and burnout. By understanding and contextualizing inefficiencies and current practices, opportunities to improve EHR systems for nursing professional practice will be identified. The study findings will inform the co-design and implementation of interventions that will support adoption and impact. Future work will include the evaluation of the developed interventions, and research on scaling and disseminating the interventions for use in different organizations, EHR systems, and jurisdictions in Canada.

Isolated Tricuspid Valve Replacement for Infective Endocarditis.

Background: Existing data regarding isolated tricuspid valve replacement for primary tricuspid valve disease such as infective endocarditis (IE) are limited. The aim of this study was to review our experience of isolated tricuspid valve replacement for IE. Methods: A retrospective review was performed to evaluate the perioperative and long-term outcomes of patients undergoing isolated tricuspid valve replacement for IE at our tertiary referral center between January 2000 and December 2014. Surgical outcomes were reviewed to include survival and postoperative complications. Results: Seven patients underwent isolated tricuspid valve replacement for IE during the study period. Mean age was 41 ± 14 years with six (86%) males. Six patients (86%) were intravenous drug users. Five patients (71%) presented with septic emboli to the lungs. Five patients (71%) had active endocarditis at the time of surgery. The indications for surgery were heart failure in three patients (43%), persistent sepsis in three patients (43%) and both in one patient (14%). Methicillin-sensitive Staphylococcus aureus was the most common infective organism, isolated in five patients (71%). There were no in-hospital mortalities or permanent pacemaker implantations. Follow-up was completed in 86% of the cases. The median follow-up period was 13 months (range 2 to 129 months). Three patients (43%) died during the follow-up period, at 7 months, 8 months and 13 months, respectively. All deaths were associated with prosthetic valve IE and recurrent intravenous drug use. Conclusions: This study supplements the paucity of data pertaining to tricuspid valve replacement for IE in the local population. Survival outcomes can be improved with prompt surgical intervention, optimal medical optimization, and a holistic, psychosocial approach targeting intravenous drug abuse.

Advanced iron oxide nanotheranostics for multimodal and precision treatment of pancreatic ductal adenocarcinoma.

Despite current advances in new approaches for cancer detection and treatment, pancreatic cancer remains one of the most lethal cancer types. Difficult to detect early, aggressive tumor biology, and resistance to chemotherapy, radiotherapy, and immunotherapy result in a poor prognosis of pancreatic cancer patients with a 5-year survival of 10%. With advances in cancer nanotechnology, new imaging and drug delivery approaches that allow the development of multifunctional nanotheranostic agents offer opportunities for improving pancreatic cancer treatment using precision oncology. In this review, we will introduce potential applications of innovative theranostic strategies to address major challenges in the treatment of pancreatic cancer at different disease stages. Several important issues concerning targeted delivery of theranostic nanoparticles and tumor stromal barriers are discussed. We then focus on the development of a magnetic iron oxide nanoparticle platform for multimodal therapy of pancreatic cancer, including MRI monitoring targeted nanoparticle/drug delivery, therapeutic response, and tumor re-staging, activation of tumor immune response by immunoactivating nanoparticle and magnetic hyperthermia therapy, and intraoperative interventions for improving the outcome of targeted therapy. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Centration and Stability of Small-Aperture Intraocular Lens in Aberrated Eyes.

PURPOSE: To investigate the visual outcomes and postoperative stability of IC-8 intraocular lens (AcuFocus, Inc) implantation following femtosecond laser-assisted cataract surgery. METHODS: In this prospective study, the IC-8 IOL was implanted in the non-dominant eye of 12 patients. Centration and uncorrected and corrected distance, intermediate, and near visual acuities (UDVA, UIVA, UNVA, CDVA, CIVA, CNVA) were evaluated up to postoperative month 3 (POM3). Means ± standard deviations are reported in logMAR units. RESULTS: There were no significant differences in absolute, vertical, and horizontal centration postoperatively versus intraoperatively. From intraoperative to POM3, mean displacement was 0.17 ± 0.09 and 0.14 ± 0.07 mm (P = .52) relative to the capsulorhexis and 0.28 ± 0.22 and 0.25 ± 0.14 mm relative to the limbus (P = .62), respectively. Centration remained within the 1.36-mm IC-8 aperture. Excluding patients with ocular comorbidities, from preoperatively to POM3, UDVA improved significantly from 0.52 ± 0.39 to 0.20 ± 0.11 logMAR (P = .024), with an efficacy index of 0.80 ± 0.31. The safety index was 1.30 ± 0.40, with no adverse events experienced. At POM3, CDVA, UIVA, and UNVA of 0.04 ± 0.05, 0.27 ± 0.11, and 0.22 ± 0.10 logMAR were achieved, respectively. Binocularly, all achieved UDVA of 20/25 or better and UIVA and UNVA of N6 and better. CONCLUSIONS: The IC-8 IOL can attain good centration and positional stability up to POM3. It enables both extended depth of focus and tolerance to aberration, making it capable of achieving spectacle independence after surgery. [J Refract Surg. 2022;38(2):98-105.].

Non-invasive detection and complementary diagnosis of liver metastases via chemokine receptor 4 imaging.

Noninvasive detection of early-stage liver metastases from different primary cancers is a pressing unmet medical need. The lack of both molecular biomarkers and the sensitive imaging methodology makes the detection challenging. In this study, we observed the elevated expression of chemokine receptor 4 (CXCR4) in uveal melanoma (UM) patient liver tissues, and high CXCR4 expression in liver metastases of UM murine models, regardless of the expression levels in the primary tumors. Based on these findings, we identified CXCR4 as an imaging biomarker and exploited a CXCR4-targeted MRI contrast agent ProCA32.CXCR4 for molecular MRI imaging. ProCA32.CXCR4 has strong CXCR4 binding affinity, high metal selectivity, and r1 and r2 relaxivities, which enables the sensitive detection of liver micrometastases. The MRI imaging capacity for detecting liver metastases was demonstrated in three UM models and one ovarian cancer model. The imaging results were validated by histological and immunohistochemical analysis. ProCA32.CXCR4 has strong potential clinical application for non-invasive diagnosis of liver metastases.

Virtual care to increase military medical centre capacity in the primary health care setting: A prospective self-controlled pilot study of symptoms collection and telemedicine.

INTRODUCTION: The Singapore Armed Forces (SAF) recognises the potential benefits and looks to harnessing telemedicine for primary health care services. In this prospective self-controlled pilot study, we aimed to evaluate the safety, efficiency and user satisfaction outcomes of virtual care (VC) at a military medical centre. METHODS: Out of 320 patients seen during the study period, 28 were enrolled in this study and underwent on-premises VC, comprising digital symptoms collection and telemedicine in addition to the usual in-person physician consultation. Safety outcomes were measured based on the diagnostic concordance between physicians. Efficiency was measured based on consultation times, and user satisfaction was evaluated using a standard questionnaire. RESULTS: There was a higher caseload of both upper respiratory infections and dermatological conditions in our population, in which telemedicine performed well. In terms of safety, telemedicine achieved a mean diagnostic concordance of 92.8% compared to in-person consultations. In terms of efficiency, consultation times were 26.2% - or 2 minutes and 15 seconds - shorter on average with telemedicine (p = 0.0488). User satisfaction was favourable, with 85.5% of patients satisfied with the VC experience. DISCUSSION: This study has been invaluable in showing that on-premises telemedicine is a safe, efficient and effective means to extend and increase our surge capacity for primary health care. Our results have given us reasonable confidence to explore a larger-scale implementation in our network of military medical centres in the future.

Deep learning-based natural language processing in ophthalmology: applications, challenges and future directions.

PURPOSE OF REVIEW: Artificial intelligence (AI) is the fourth industrial revolution in mankind's history. Natural language processing (NLP) is a type of AI that transforms human language, to one that computers can interpret and process. NLP is still in the formative stages of development in healthcare, with promising applications and potential challenges in its applications. This review provides an overview of AI-based NLP, its applications in healthcare and ophthalmology, next-generation use case, as well as potential challenges in deployment. RECENT FINDINGS: The integration of AI-based NLP systems into existing clinical care shows considerable promise in disease screening, risk stratification, and treatment monitoring, amongst others. Stakeholder collaboration, greater public acceptance, and advancing technologies will continue to shape the NLP landscape in healthcare and ophthalmology. SUMMARY: Healthcare has always endeavored to be patient centric and personalized. For AI-based NLP systems to become an eventual reality in larger-scale applications, it is pertinent for key stakeholders to collaborate and address potential challenges in application. Ultimately, these would enable more equitable and generalizable use of NLP systems for the betterment of healthcare and society.

Claisened Hexafluoro Inhibits Metastatic Spreading of Amoeboid Melanoma Cells.

Metastatic melanoma is characterized by poor prognosis and a low free-survival rate. Thanks to their high plasticity, melanoma cells are able to migrate exploiting different cell motility strategies, such as the rounded/amoeboid-type motility and the elongated/mesenchymal-type motility. In particular, the amoeboid motility strongly contributes to the dissemination of highly invasive melanoma cells and no treatment targeting this process is currently available for clinical application. Here, we tested Claisened Hexafluoro as a novel inhibitor of the amoeboid motility. Reported data demonstrate that Claisened Hexafluoro specifically inhibits melanoma cells moving through amoeboid motility by deregulating mitochondrial activity and activating the AMPK signaling. Moreover, Claisened Hexafluoro is able to interfere with the adhesion abilities and the stemness features of melanoma cells, thus decreasing the in vivo metastatic process. This evidence may contribute to pave the way for future possible therapeutic applications of Claisened Hexafluoro to counteract metastatic melanoma dissemination.

Corneal neuromediator profiles following laser refractive surgery.

Laser refractive surgery is one of the most commonly performed procedures worldwide. In laser refractive surgery, Femtosecond Laser in Situ Keratomileusis and Refractive Lenticule Extraction have emerged as promising alternatives to microkeratome Laser in Situ Keratomileusis and Photorefractive Keratectomy. Following laser refractive surgery, the corneal nerves, epithelial and stromal cells release neuromediators, including neurotrophins, neuropeptides and neurotransmitters. Notably, nerve growth factor, substance P, calcitonin gene-related peptide and various cytokines are important mediators of neurogenic inflammation and corneal nerve regeneration. Alterations in neuromediator profiles and ocular surface parameters following laser refractive surgery are attributed to the surgical techniques and the severity of tissue insult induced. In this review, we will discuss the (1) Functions of neuromediators and their physiological and clinical significance; (2) Changes in the neuromediators following various laser refractive surgeries; (3) Correlation between neuromediators, ocular surface health and corneal nerve status; and (4) Future directions, including the use of neuromediators as potential biomarkers for ocular surface health following laser refractive surgery, and as adjuncts to aid in corneal regeneration after laser refractive surgery.

Acetylation of KLF5 maintains EMT and tumorigenicity to cause chemoresistant bone metastasis in prostate cancer.

Advanced prostate cancer (PCa) often develops bone metastasis, for which therapies are very limited and the underlying mechanisms are poorly understood. We report that bone-borne TGF-ß induces the acetylation of transcription factor KLF5 in PCa bone metastases, and acetylated KLF5 (Ac-KLF5) causes osteoclastogenesis and bone metastatic lesions by activating CXCR4, which leads to IL-11 secretion, and stimulating SHH/IL-6 paracrine signaling. While essential for maintaining the mesenchymal phenotype and tumorigenicity, Ac-KLF5 also causes resistance to docetaxel in tumors and bone metastases, which is overcome by targeting CXCR4 with FDA-approved plerixafor. Establishing a mechanism for bone metastasis and chemoresistance in PCa, these findings provide a rationale for treating chemoresistant bone metastasis of PCa with inhibitors of Ac-KLF5/CXCR4 signaling.