Multiple Behavioral Risk Factors As Assets for Chronic Disease Prevention: Observations From Urban Primary Care Settings in Crete, Greece.

AIM: This study aimed to assess the health profile of patient-attendees visiting primary healthcare (PHC) practice settings in the midst of the COVID-19 pandemic and to explore the relationships between multiple behavioral risk factors (MBRFs) and consultation-driven health information. Multiple behavioral risk factors involve a variety of unhealthy behaviors that are associated with an increased prevalence of non-communicable diseases (NCDs). SUBJECTS AND METHODS: The study design was based on a dataset analysis, afterward exploring the feasibility and diagnostic capacity of respiratory morbidity aspects from a study previously conducted. The study dataset contained information regarding socio-demographic characteristics, health habits, clinical information, and reported comorbidities from 183 primary care patient-attendees. A categorical regression analysis was performed, using as a numeric variable the multiple MBRFs (clustering of 0 to four factors) in order to examine relationships with the basic and clinical characteristics of the patient-attendees. RESULTS: Based on this secondary analysis, it was found that the prevalence of MBRFs is quite common among patient-attendees visiting urban PHC facilities. The prevalence of current smoking, sleep deprivation, increased body weight, and medium/high perceived stress levels were 33.9%, 52.5%, 83.1%, and 35.0%, respectively. An increased occurrence of MBRFs might be significantly predicted by the lower age of patient-attendees (b = -0.221, p = 0.05), by the absence of gray hair at an early age (b = -0.144, p = 0.042), by the physical discomfort during activities (b = 0.191, p = 0.017), or by the lower oxygen saturation (b = -0.184, p = 0.004). Diabetes mellitus (25.1%) was the most prevalent condition, followed by bronchial asthma (18.6%) and depression (15.8%). CONCLUSIONS: Lower age, absence of premature hair whitening, physical discomfort during activities, and lower oxygen saturation are linked with an increased occurrence of MBRFs, leading to a neglected way of living. Those factors could be used to alert researchers, policymakers, and PHC professionals to act accordingly in order to prevent or early diagnose NCDs.

Assessing feasibility of targeted primary care referrals for patients with clinical suspicion of interstitial lung disease using lung ultrasound: a prospective case finding study. The potential benefits of LUS utilization.

BACKGROUND: In Primary Health Care (PHC) many interstitial lung disease (ILD) cases may remain at diagnostic delay, due to their challenging presentation and the limited experience of general practitioners (GPs) in recognizing their early symptoms. OBJECTIVE: We have designed a feasibility study to investigate early ILD case-finding competency between PHC and tertiary care. METHODS: A cross-sectional prospective case-finding study was launched at two private health care centers of Heraklion, Crete, Greece, during nine months (2021-2022). After clinical assessment by GP, PHC attenders, who agreed to participate in the study, were referred to the Respiratory Medicine Department, University Hospital of Heraklion, Crete, underwent Lung Ultrasound (LUS) and those with an overall suspicion for ILDs underwent high resolution computed tomography (HRCT) scan. Descriptive statistics and chi-square tests were used. Multiple Poisson regression analysis was performed to explain positive LUS and HRCT decision with selected variables. RESULTS: One hundred and nine patients out of 183 were finally included (54.1% females; mean age 61, SD: 8.3 years). Thirty-five (32.1%) were current smokers. Overall, two out of ten cases were assessed to need HRCT due to a moderate or high suspicion (19.3%; 95%CI 12.7, 27.4). However, in those who had dyspnea in relation to counterparts, a significantly higher percentage of patients with LUS findings (57.9% vs. 34.0%, p=0.013) was found, as in those who had crackles (100.0% vs. 44.2%, p= 0.005). Detected possible ILD provisional labelling cases were 6, and most importantly, 5 of those cases were considered highly suspicious for further evaluation based on LUS findings. CONCLUSIONS: This is a feasibility study exploring potentials by combining data of medical history, basic auscultation skills, as crackles detection, and inexpensive and radiation-free imaging technique, such as LUS. Cases of ILD labeling may be hidden within PHC, sometimes, much before any clinical manifestation.

Cellulite: Current Treatments, New Technology, and Clinical Management.

BACKGROUND: Cellulite is a well-known concern for many women; however, treatment can prove challenging because of the complexities of cellulite etiology, the various factors contributing to its appearance, and the multitude of therapies and procedures available. OBJECTIVE: To discuss current cellulite treatment options and effective clinical management. METHODS: A roundtable meeting was convened to discuss and share views on current cellulite treatment options, new technologies, and clinical management. The participants' views helped guide a narrative review on this topic. RESULTS: Advanced interventions for cellulite treatment-such as physical and acoustic subcision, radiofrequency, and injectable biostimulators-are gradually being established, with accumulating evidence showing efficacy, patient satisfaction, and potentially long-lasting outcomes. Cellulite severity rating scales are necessary for assessing treatment outcomes, but these can be complex to use in clinical practice, and the majority do not include patient or clinician perspectives. CONCLUSION: With the advent of new treatments and technologies, cosmetic surgeons and dermatologists will need to tailor their approach to each patient's needs and manage patient expectations because multimodal methods are likely to be required to address the various factors underlying cellulite appearance.

Cellulite: Clinical Challenges and Future Perspectives.

BACKGROUND: Existing cellulite interventions pose various clinical challenges related mostly to ecchymosis and recovery time. OBJECTIVE: To discuss the current treatment options for minimizing recovery time, efficacy of these options, and investigations into possible future approaches. METHODS: A roundtable meeting was convened to discuss and share views on the clinical challenges seen in the present practice of cellulite treatments along with future approaches and mitigation strategies. The participants' views helped guide a narrative review on this topic. RESULTS: Cosmetic clinicians have a range of new interventions to choose from for cellulite improvement, each with different benefits and safety aspects. Bruising is a typical side effect that is seen with treatments targeting the fibrous septa, such as subcision and injectable treatments, and in some cases may produce long-lasting hyperpigmentation from postinflammatory hyperpigmentation or hemosiderin staining. Various strategies that could potentially mitigate bruising and other adverse effects of cellulite treatment are under clinical investigation, including, but not limited to, different injection techniques and dilutions, compression garments, cold packs, arnica gel, pulsed dye laser treatment, intralesional epinephrine, and tranexamic acid. CONCLUSION: Clinical challenges including varying treatment outcomes and certain treatment sequelae remain, and further research is needed to prevent side effects and improve treatment outcomes.

A Spatial and Functional Interaction of a Heterotetramer Survivin-DNA-PKcs Complex in DNA Damage Response.

Substantial evidence has shown that overexpression of the inhibitor of apoptosis protein (IAP) survivin in human tumors correlates significantly with treatment resistance and poor patient prognosis. Survivin serves as a radiation resistance factor that impacts the DNA damage response by interacting with DNA-dependent protein kinase (DNA-PKcs). However, the complexity, molecular determinants, and functional consequences of this interrelationship remain largely unknown. By applying coimmunoprecipitation and flow cytometry-based Förster resonance energy transfer assays, we demonstrated a direct involvement of the survivin baculovirus IAP repeat domain in the regulation of radiation survival and DNA repair. This survivin-mediated activity required an interaction of residues S20 and W67 with the phosphoinositide 3-kinase (PI3K) domain of DNA-PKcs. In silico molecular docking and dynamics simulation analyses, in vitro kinase assays, and large-scale mass spectrometry suggested a heterotetrameric survivin-DNA-PKcs complex that results in a conformational change within the DNA-PKcs PI3K domain. Overexpression of survivin resulted in enhanced PI3K enzymatic activity and detection of differentially abundant phosphopeptides and proteins implicated in the DNA damage response. The survivin-DNA-PKcs interaction altered the S/T-hydrophobic motif substrate specificity of DNA-PKcs with a predominant usage of S/T-P phosphorylation sites and an increase of DNA-PKcs substrates including Foxo3. These data demonstrate that survivin differentially regulates DNA-PKcs-dependent radiation survival and DNA double-strand break repair via formation of a survivin-DNA-PKcs heterotetrameric complex. SIGNIFICANCE: These findings provide insight into survivin-mediated regulation of DNA-PKcs kinase and broaden our knowledge of the impact of survivin in modulating the cellular radiation response.See related commentary by Iliakis, p. 2270 GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/9/2304/F1.large.jpg.

Double targeting of Survivin and XIAP radiosensitizes 3D grown human colorectal tumor cells and decreases migration.

BACKGROUND AND PURPOSE: In the present study, we aimed to investigate the effect of single and double knockdown of the inhibitor of apoptosis proteins (IAP) Survivin and X-linked IAP (XIAP) on three-dimensional (3D) clonogenic survival, migration capacity and underlying signaling pathways. MATERIALS AND METHODS: Colorectal cancer cell lines (HCT-15, SW48, SW480, SW620) were subjected to siRNA-mediated single or Survivin/XIAP double knockdown followed by 3D colony forming assays, cell cycle analysis, Caspase activity assays, migration assays, matrigel transmigration assays and Western blotting (Survivin, XIAP, Focal adhesion kinase (FAK), p-FAK Y397, Akt1, p-Akt1 S473, Extracellular signal-regulated kinase (ERK1/2), p-ERK1/2 T202/Y204, Glycogen synthase kinase (GSK)3ß, p-GSK3ß S9, nuclear factor (NF)-κB p65). RESULTS: While basal cell survival was altered cell line-dependently, Survivin or XIAP single and Survivin/XIAP double knockdown enhanced cellular radiosensitivity of all tested cancer cell lines grown in 3D. Particularly double knockdown conditions revealed accumulation of cells in G2/M, increased subG1 fraction, elevated Caspase 3/7 activity, and reduced migration. Intracellular signaling showed dephosphorylation of FAK and Akt1 upon Survivin and/or Survivin/XIAP silencing. CONCLUSIONS: Our results strengthen the notion of Survivin and XIAP to act as radiation resistance factors and further indicate that these apoptosis-regulating proteins are also functioning in cell cycling and cell migration.