N-Myristoytransferase Inhibition Causes Mitochondrial Iron Overload and Parthanatos in TIM17A-Dependent Aggressive Lung Carcinoma.

Unlabelled: Myristoylation is a type of protein acylation by which the fatty acid myristate is added to the N-terminus of target proteins, a process mediated by N-myristoyltransferases (NMT). Myristoylation is emerging as a promising cancer therapeutic target; however, the molecular determinants of sensitivity to NMT inhibition or the mechanism by which it induces cancer cell death are not completely understood. We report that NMTs are a novel therapeutic target in lung carcinoma cells with LKB1 and/or KEAP1 mutations in a KRAS-mutant background.

Quantitative Aggregation of Microbiome Sequencing Data Provides Insights into the Associations between the Skin Microbiome and Psoriasis.

Although prior studies have reported distinct skin microbiome profiles associated with psoriasis, differences in methods and analyses limit generalizable conclusions. Individual studies have actually reported conflicting findings; for example, and have been significantly associated with both psoriatic lesions and healthy skin. Qualitative reviews have attempted to summarize this body of work, but there is great variability across the studies' findings and methods.

Alcohol and Smoking Cessation as Potential Modulators for Smoking-Associated Psoriasis Risk in Postmenopausal Women: The Women's Health Initiative.

Background: The association of alcohol with psoriasis has been inconsistent among studies.

Objectives: We aimed (1) to determine whether alcohol consumption (by status, frequency, and subtype of alcohol) modulates smoking-related psoriasis risk in postmenopausal women while stratifying for smoking status and pack-years and (2) to evaluate the effect of smoking cessation on psoriasis risk in postmenopausal women.

Methods: This prospective cohort study included 106,844 postmenopausal women enrolled in the Women's Health Initiative between 1993 and 1998.

BCG hydrogel promotes CTSS-mediated antigen processing and presentation, thereby suppressing metastasis and prolonging survival in melanoma.

Background: The use of intralesional BCG (intralesional live BCG) for the treatment of metastatic melanoma resulted in regression of directly injected, and occasionally of distal lesions. However, intralesional-BCG is less effective in patients with visceral metastases and did not significantly improve overall survival.

Methods: We generated a novel BCG lysate and developed it into a thermosensitive PLGA-PEG-PLGA hydrogel (BCG hydrogel), which was injected adjacent to the tumor to assess its antitumor effect in syngeneic tumor models (B16F10, MC38).

The Effect of Systemic Antibiotics for Suppurative Skin and Soft Tissue Infections on the Skin Microbiome.

Background: Skin and soft tissue infections (SSTIs) are very common bacterial infections. There are few data on the microbiome of persons with and without SSTIs and the effects of systemic antibiotic therapy.

Methods: We sampled the skin microbiome from 10 outpatients with acute suppurative SSTI before and after systemic antibiotic therapy and enrolled 10 matched controls.

Tocilizumab overcomes chemotherapy resistance in mesenchymal stem-like breast cancer by negating autocrine IL-1A induction of IL-6.

Triple-negative breast cancer (TNBC) patients with mesenchymal stem-like (MSL) subtype have responded poorly to chemotherapy whereas patients with basal-like 1 (BL1) subtype achieved the best clinical response. In order to gain insight into pathways that may contribute to the divergent sensitivity to chemotherapy, we compared the inflammatory profile of the two TNBC subtypes treated with docetaxel. Cellular signaling analysis determined that docetaxel activated MAPK pathway in MSL TNBCs but not BL1 TNBCs.

Survival of mechanically ventilated ward patients and association with organisational factors: a multicentre prospective study.

Objectives: Determine 90-day mortality of mechanically ventilated ward patients outside the intensive care unit (ICU) and its association with organisational factors.

Design: Multicentre prospective observational study of mechanically ventilated ward patients. Modified Poisson regression was used to assess association between nurse to patient ratio (NPR) and 90-day mortality, adjusted for designated medical team, Society of Critical Care Medicine (SCCM) triage priority and centre effect.

A phase 1/2 clinical trial of the nitric oxide synthase inhibitor L-NMMA and taxane for treating chemoresistant triple-negative breast cancer.

The inducible nitric oxide signaling (iNOS) pathway is associated with poor prognosis in triple-negative breast cancer (TNBC). Prior studies using in vivo models showed that inhibition of the iNOS signaling pathway using the pan-NOS inhibitor NG-monomethyl-l-arginine (L-NMMA) reduced tumor growth and enhanced survival in patients with TNBC. Here, we report a first-in-class phase 1/2 trial of L-NMMA combined with taxane for treating patients with chemorefractory, locally advanced breast cancer (LABC) or metastatic TNBC.

Association between baseline insulin resistance and psoriasis incidence: the Women's Health Initiative.

Small-scale studies offer conflicting evidence regarding the relationship/association between psoriasis and insulin resistance by HOMA-IR (homeostasis model assessment of insulin resistance). The purpose of this study was to assess the association between baseline HOMA-IR and psoriasis incidence in a large-scale longitudinal cohort of postmenopausal women. The analysis included 21,789 postmenopausal women from the Women's Health Initiative.

Characterization of a Myeloid Activation Signature that Correlates with Survival in Melanoma Patients.

Understanding the cellular interactions within the tumor microenvironment (TME) of melanoma paved the way for novel therapeutic modalities, such as T cell-targeted immune checkpoint inhibitors (ICI). However, only a limited fraction of patients benefits from such therapeutic modalities, highlighting the need for novel predictive and prognostic biomarkers. As myeloid cells orchestrate the tumor-specific immune response and influence the efficacy of ICI, assessing their activation state within the TME is of clinical relevance.

Interaction of body mass index or waist-to-hip ratio and sun exposure associated with nonmelanoma skin cancer: A prospective study from the Women's Health Initiative.

Background: The incidence of nonmelanoma skin cancer (NMSC) exceeds the incidence of all other types of cancers combined. Cumulative sun exposure and intermittent sun exposure are known risk factors for the development of NMSC. Because obesity has been shown to decrease the risk of NMSC incidence, this study investigated whether the risk of NMSC with sun exposure was consistent across different levels of body size.

Practical methods for effective vancomycin-resistant enterococci (VRE) surveillance: experience in a liver transplant surgical intensive care unit.

Objective: We evaluated the utility of vancomycin-resistant Enterococcus (VRE) surveillance by varying 2 parameters: admission versus weekly surveillance and perirectal swabbing versus stool sampling.

Design: Prospective, patient-level surveillance program of incident VRE colonization.

Setting: Liver transplant surgical intensive care unit (SICU) of a tertiary-care referral medical center with a high prevalence of VRE.

Both the intratumoral immune and microbial microenvironment are linked to recurrence in human colon cancer: results from a prospective, multicenter nodal ultrastaging trial.

Colon cancer (CC) is the third most common cancer diagnosed in the United States and the incidence has been rising among young adults. We and others have shown a relationship between the immune infiltrate and prognosis, with improved disease-free survival (DFS) being associated with a higher expression of CD8 T cells. We hypothesized that a microbial signature might be associated with intratumoral immune cells as well as DFS.

Bacillus Calmette-Guérin Alters Melanoma Microenvironment Favoring Antitumor T Cell Responses and Improving M2 Macrophage Function.

Intralesional bacillus Calmette-Guérin (BCG) has long been a relatively inexpensive therapy for inoperable cutaneous metastatic melanoma (CMM), although intralesional BCG skin mechanisms remain understudied. We analyzed intralesional BCG-treated CMM lesions combined with studies to further investigate BCG-altered pathways. Since macrophages play a pivotal role against both cancer and mycobacterial infections, we hypothesized BCG regulates macrophages to promote antitumor immunity.

Effects of repetitive transcranial magnetic stimulation on improvement of cognition in elderly patients with cognitive impairment: a systematic review and meta-analysis.

Objective: This systematic review and meta-analysis aimed to examine the effects of repetitive transcranial magnetic stimulation (rTMS) on cognitive function in older patients with cognitive impairment.

Methods: A literature search was performed for articles published in English using the 10 databases (MEDLINE, EMBASE, PsycINFO, INSPEC, the Cumulative Index to Nursing and Allied Health Literature Plus, AMED, Biological Sciences, ClinicalTrials.gov, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews) from their inception to May 2016.

Insights into Local Tumor Microenvironment Immune Factors Associated with Regression of Cutaneous Melanoma Metastases by Bacille Calmette-Guérin.

bacille Calmette-Guérin (BCG) is listed as an intralesional (IL) therapeutic option for inoperable stage III in-transit melanoma in the National Comprehensive Cancer Network Guidelines. Although the mechanism is unknown, others have reported up to 50% regression of injected lesions, and 17% regression of uninjected lesions in immunocompetent patients after direct injection of BCG into metastatic melanoma lesions in the skin. BCG and other mycobacteria express ligands capable of stimulating the γ9δ2 T cells.

Characterization of the microbiome of nipple aspirate fluid of breast cancer survivors.

The microbiome impacts human health and disease. Until recently, human breast tissue and milk were presumed to be sterile. Here, we investigated the presence of microbes in the nipple aspirate fluid (NAF) and their potential association with breast cancer.

Effects of Intra-Operative Total Intravenous Anaesthesia with Propofol versus Inhalational Anaesthesia with Sevoflurane on Post-Operative Pain in Liver Surgery: A Retrospective Case-Control Study.

Background: Patients receiving total intravenous anesthesia (TIVA) with propofol have been shown to experience less postoperative pain. We evaluated the post-operative analgesic effects of propofol compared with sevoflurane maintenance of anesthesia in liver surgery. This study was registered at ClinicalTrials.

Social and psychological barriers to private retirement savings in Hong Kong.

Using a phone survey conducted among Hong Kong workers, we examined the association of institutional, social, and psychological factors with engagement in both private retirement savings and the total amount of savings. Alarmingly, this study demonstrates that approximately 42% of Hong Kong workers do not save privately for their retirement. We found that age, education, number of children, support from spouse and friends, social regulation, perceived financial knowledge, and financial management capacity are associated with engagement in private retirement savings.

Mental and physical activities delay cognitive decline in older persons with dementia.

Objectives: To examine the effects of cognitive stimulation (mahjong) and physical exercise (tai chi [TC]) on cognitive performance in persons with dementia.

Design: Cluster-randomized open-label controlled design.

Setting: Nursing homes.

Vocal fold vibration measurements using laser Doppler vibrometry.

The objective of this study was to measure the velocity of the superior surface of human vocal folds during phonation using laser Doppler vibrometry (LDV). A custom-made endoscopic laser beam deflection unit was designed and fabricated. An in vivo clinical experimental procedure was developed to simultaneously collect LDV velocity and video from videolaryngoscopy.

Leisure activities alleviate depressive symptoms in nursing home residents with very mild or mild dementia.

Objectives: : To examine whether leisure activities can alleviate depressive symptoms among nursing home residents with very mild to mild dementia.

Methods: : A cluster-randomized open-label controlled design. Thirty-six residents with at least moderate depressive symptoms were randomized by home into three conditions-mahjong (a.

Social exchanges and subjective well-being: do sources of positive and negative exchanges matter?

Objectives: To decompose the effects of positive and negative social exchanges on well-being in terms of relationship type (vertically extended family, horizontally extended family, or nonfamily) and subjective closeness (close vs. peripheral).

Methods: One thousand and five Chinese older adults rated each network member on positive and negative exchanges, which were aggregated for each relationship type and closeness category.