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The decisions about the built environment and the building codes in urban conservation plans have a critical role for a true conservation practice. Besides the necessity of planning decisions that are formed according to a holistic conservation policy, the building regulations and codes have direct effects in sustaining the characteristic and authentic features of the built environment. In urban conservation areas, buildings can be categorized in three groups: cultural assets that are already registered as heritage sites, existing buildings that do not present heritage value and proposed buildings that do not exist currently. The conservation law in Turkey provides a specific mechanism for monitoring and controlling registered heritage sites; however, this mechanism is quite limited for unregistered or new buildings in urban conservation areas. Therefore, within urban conservation plans, the decisions about the unregistered or new buildings become a primary challenge for the protection of authentic physical features in urban areas. Urbanization over the traditional urban area of Giresun dating to the late 19th and early 20th centuries has created obvious integration problems between new and old sites. The limited registration for traditional buildings, the insufficiency in codes and limitations for new buildings, the lack of a holistic planning policy, and the existence of unharmonious new buildings within and around the urban conservation area are the current problems in Giresun. These problems have been mainly caused by the building decisions of former urban conservation plans. This paper aims to share and argue the principles and decisions of the Revision Plan of Giresun Urban Conservation Area.

The Masquelet technique for the treatment of large bone defects is a two-stage procedure based on an induced membrane. We eliminate the first surgical step by using a decellularized dermal skin graft (Epiflex®) populated with bone marrow mononuclear cells (BMC), as a replacement for the induced membrane. The aim of this study was to demonstrate the feasibility of this technology and provide evidence of equivalent bone healing in comparison to the induced membrane-technique. Therefore, 112 male Sprague–Dawley rats were allocated in six groups and received a 10 mm femoral defect. Defects were treated with either the induced membrane or decellularized dermis, with or without the addition of BMC. Defects were then filled with a scaffold (β-TCP), with or without BMC. After a healing time of eight weeks, femurs were taken for histological, radiological and biomechanical analysis. Defects treated with Epiflex® showed increased mineralization and bone formation predominantly in the transplanted dermis surrounding the defect. No significant decrease of biomechanical properties was found. Vascularization of the defect could be enhanced by addition of BMC. Considering the dramatic reduction of a patient’s burden by the reduced surgical stress and shortened time of treatment, this technique could have a great impact on clinical practice.

Reflective learning is considered an advanced form of learning; however, it has not been routinely incorporated into postgraduate and subspecialty educational surgical portfolios. The concept of training portfolios is not clearly understood by both trainees and teachers. Subspecialty surgical programmes rely heavily on logbooks and other forms of formative assessment to certify candidates. Case-based self-reflection in postgraduate training may be used as an additional educational tool and incorporated into the curricula vitae of trainees. We describe the method used to assess a vascular case, based on a self-reflective training method (vascular case portfolio).

Purpose: To compare staining and artificial accelerating aging-dependent changes in color, translucency, and gloss of cloud-shade and one-shade resin composite., Methods: The "cloud-shade" composites were Filtek Easy Match Universal Restorative (FU) and SimpliShade (SS): three shades each (light, medium and dark), while the "one shade" composites were Admira Fusion x-tra (AD) and Venus Diamond One (VE). Polymerized composite specimens (10 mm in diameter, 2 mm-thick) were polished using PoGo disks for 40 seconds. Color, translucency, and gloss measurements were performed before and after exposure to 3.8-day staining in coffee or wine (equivalent to a year of service with a 15-minute exposure per day), or exposure to 150 kJ/m² of accelerated aging (n= 5 per condition x three conditions, for a total of 15 specimens per shade). Color and translucency were measured using a benchtop spectrophotometer, and CIEDE2000 color differences (ΔE₀₀) and translucency parameter (TP₀₀) were calculated. Gloss (gloss units, GU) was measured using a small-area gloss meter. Gloss retention percentages after staining and aging were calculated. A two-way ANOVA was used to compare the effect of material and procedure, while a Tukey's post hoc multiple comparison test was used to assess differences among levels within each variable (α= 0.05)., Results: The AD exhibited the best color stability upon staining, while VE was the most stable when exposed to artificial aging. Statistically significant differences were recorded among materials and procedures (P< 0.001), and their interactions (P< 0.01). AD also exhibited the highest TP stability upon staining, while the TP of FU was the most stable when exposed to artificial aging. Statistically significant differences were recorded among materials and procedures (P< 0.001), and their interactions (P< 0.01). Gloss retention upon staining and aging was greater than 90% for all tested materials. Statistically significant differences were recorded among materials (P< 0.001), procedures (P< 0.05), and their interactions (P< 0.01)., Clinical Significance: Staining and artificial accelerated aging changes in color, translucency parameter, and gloss retention of cloud-shade and one-shade resin composites were material- and procedure-dependent., Competing Interests: The authors declared no conflict of interest., (Copyright©American Journal of Dentistry.)

Aims: It is extremely important to determine the relationship between COPD and self-management (SM) in the disease process. However, the impact of symptom management (SpM) on this relationship is still unclear. The study aimed to examine the mediating role of SpM in the effect of the COPD stage on SM., Design: A predictive correlational study was reported following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines., Methods: This study was conducted between 15 February 2023 and 15 June 15 2023, with 306 patients. Data were collected using the Symptom Management Scale for Self-Efficacy and the Chronic Disease Self-Management Scale. Descriptive statistics and Process Macro Model 4 in the SPSS program were used for data analysis., Results: Most of the patients were in the moderate stage of COPD; their SM scores were at low levels; SpM scores were at moderate levels. The model was significant, and the variables explained 65% of the model. The COPD stage was significantly positively correlated with SpM and negatively correlated with SM. There was a significant positive impact between SpM and SM. The positive and significant standardised indirect effect of SpM on SM evidenced a full mediating effect., Conclusions: Symptom management has a full mediating role in the effect of the COPD stage on SM. It was revealed that the level of SM can be increased by achieving SpM., Implications for the Profession And/or Patient Care: Symptoms are vital in COPD. Progression of COPD increases symptom severity. Being successful in SpM greatly contributes to the achievement of self-management. Therefore, nurses should definitely consider symptom control in strengthening self-management in the care of patients with COPD., Patient or Public Contribution: Patients' COPD stage was determined by a pulmonologist involved in the study. Voluntary patients with COPD hospitalised in the pulmonology clinic were included in the study., (© 2024 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.)

The study aimed to examine the moderator effect of organ transplant waiting time on hopelessness and death anxiety. The study was conducted in a descriptive and correlational design with 378 patients on the transplant waiting list (Agust 2021- March 2022). Multiple linear regression and PROCESS macro-Model 1 were used in the analyses. In this study, the STROBE checklist was followed. According to the results of the regression analysis, waiting for a transplant for 6-10 years reduced death anxiety by 9.38 times and waiting for a transplant for 16-20 years increased death anxiety by 31.3 times. The predictors in the regression analysis explained 33% of the model. The moderator effect constituted 6.4% of the explained part of the model, which was 25.4%; the R 2 change was 3.4% and significant. We found that the longer the waiting period for organ transplant recipients, the higher the hopelessness and death anxiety., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The phosphatases INPP4B and PTEN are tumor suppressors that are lost in nearly half of advanced metastatic cancers. The loss of PTEN in prostate epithelium initially leads to an upregulation of several tumor suppressors that slow the progression of prostate cancer in mouse models. We tested whether the loss of INPP4B elicits a similar compensatory response in prostate tissue and whether this response is distinct from the one caused by the loss of PTEN. Knockdown of INPP4B but not PTEN in human prostate cancer cell lines caused a decrease in EZH2 expression. In Inpp4b -/- mouse prostate epithelium, EZH2 levels were decreased, as were methylation levels of histone H3. In contrast, Ezh2 levels were increased in the prostates of Pten -/- male mice. Contrary to PTEN, there was a positive correlation between INPP4B and EZH2 expression in normal human prostates and early-stage prostate tumors. Analysis of single-cell transcriptomic data demonstrated that a subset of EZH2-positive cells expresses INPP4B or PTEN, but rarely both, consistent with their opposing correlation with EZH2 expression. Unlike PTEN, INPP4B did not affect the levels of SMAD4 protein expression or Pml mRNA expression. Like PTEN, p53 protein expression and phosphorylation of Akt in Inpp4b -/- murine prostates were elevated. Taken together, the loss of INPP4B in the prostate leads to overlapping and distinct changes in tumor suppressor and oncogenic downstream signaling.

SARS-CoV-2, the virus that causes COVID-19, is prone to mutations and the generation of genetic variants. Since its first outbreak in 2019, SARS-CoV-2 has continually evolved, resulting in the emergence of several lineages and variants of concern (VOC) that have gained more efficient transmission, severity, and immune evasion properties. The World Health Organization has given these variants names according to the letters of the Greek Alphabet, starting with the Alpha (B.1.1.7) variant, which emerged in 2020, followed by the Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529) variants. This review explores the genetic variation among different VOCs of SARS-CoV-2 and how the emergence of variants made a global impact on the pandemic.

Background: The most important problem of chronic obstructive pulmonary disease (COPD) patients is acute exacerbation. Researching this experience and examining its relationship with death is extremely important in patient care., Methods: This study was conducted to reveal the experiences of individuals with a history of acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) and their thoughts on death by qualitative empirical research. The study was conducted in a pulmonology clinic between July and September 2022. In-depth face-to-face interviews were conducted with patients in their rooms using a semi-structured form created specifically for the study and used as a data collection tool. With patient consent, interviews were recorded and documented. During the data analysis phase, the Colaizzi method was used. The study was presented in accordance with the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist for qualitative research., Results: The study was completed with 15 patients. A total of 13 of the patients were male and the mean age was 65 years. Patient statements were coded after the interviews and collected under 11 sub-themes. These sub-themes were categorized under the following main themes: recognizing AECOPDs, AECOPD instant experiences, post-AECOPD, and thoughts on death., Conclusion: Patients were able to recognize the symptoms of an AECOPD, that the severity of the symptoms increased during the exacerbation, that they felt regret or anxiety about re-exacerbation, and that all of these factors contributed to their fear of death., (JCOPDF © 2023.)

Tumor recurrence following potentially curative therapy constitutes a major obstacle to achieving cures in patients with cancer. Recurrent tumors frequently arise from a population of residual cancer cells - also referred to as minimal residual disease (RD) or persister cells - that survive therapy and persist for prolonged periods prior to tumor relapse. While there has been significant recent progress in deciphering tumor-cell-intrinsic pathways that regulate residual cancer cell survival and recurrence, much less is known about how the tumor microenvironment (TME) of residual tumors impacts persister cancer cells or tumor recurrence. In this review, we highlight recent studies exploring the regulation and function of immune cells in RD and discuss therapeutic opportunities to target immune cells in residual tumors., Competing Interests: Declaration of interests No interests are declared by the authors., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Patients with chronic obstructive pulmonary disease are among the most risky groups for Coronavirus Disease 2019. The study was conducted with a case-control group design in order to determine the coronavirus disease 2019 infection-related characteris- tics of chronic obstructive pulmonary disease patients with and without inhaler training., Material and Methods: A total of 106 patients, being case group (n = 53) and control group (n = 53), were included in the study sample through purposive and simple random sampling methods. While the control group did not receive training, the case group received inhaler training in 2017-2018. Inhaler training was conducted face-to-face using the demonstration method. Patients were evaluated according to their coronavirus disease 2019 (approved by a physician positive polymerase chain reaction) status from the beginning of the pandemic to the time they were included in the study (June 2021)., Results: The rate of incorrect inhaler use was determined to be 39.6% of the patients in the control group, which is statistically differ- ent from the case group (P < .001). It was also determined that 17.9% of the patients in the study sample had contracted coronavirus disease 2019. It was found that the presence of symptoms for at least 1 month following the negative polymerase chain reaction result was significantly higher in the control group (P = .018). It was determined that the case group patients were more careful compared to the control group in terms of coronavirus disease 2019 measures (P < .031). The patients in the case group reported that inhaler medicines were also effective in protecting against other respiratory system diseases (P = .006)., Conclusion: Few patients with chronic obstructive pulmonary disease have been infected. It was concluded that the coronavirus disease 2019 symptoms lasted longer in the control group than in the case group.

Phosphoinositides (PIs) are relatively rare lipid components of the cellular membranes. Their homeostasis is tightly controlled by specific PI kinases and PI phosphatases. PIs play essential roles in cellular signaling, cytoskeletal organization, and secretory processes in various diseases and normal physiology. Gene targeting experiments strongly suggest that in mice with deficiency of several PI phosphatases, such as Pten, Mtmrs, Inpp4b, and Inpp5b, spermatogenesis is affected, resulting in partial or complete infertility. Similarly, in men, loss of several of the PI phosphatases is observed in infertility characterized by the lack of mature sperm. Using available gene expression databases, we compare the expression of known PI phosphatases in various testicular cell types, infertility patients, and mouse age-dependent testicular gene expression, and discuss their potential roles in testis physiology and spermatogenesis., (© The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Severe dyspnea and poor quality of life are common in chronic obstructive pulmonary disease (COPD). The most important reason for this is wrong applications in inhaler treatment. In addition, inhaler treatments that support non-pharmacological methods increase the effectiveness of the drug. The aim of this study was to determine the effects of breathing exercises and inhaler training for chronic obstructive pulmonary disease patients on the severity of dyspnea and life quality., Methods: The research was a randomized controlled trial. A total of 67 patients with COPD were included. The patients were randomized into two groups. Intervention group 1 were given pursed lip breathing exercise and inhaler training and Intervention group 2 were given only inhaler training. A follow-up after 4 weeks was carried out in both groups. Patient outcomes in both groups were assessed by a COPD assessment test (CAT), the Modified Medical Research Council (mMRC) scale, and the St. George's Respiratory Questionnaire scale (SGRQ). This study followed the CONSORT checklist for randomized controlled trials. In the data analysis, independent t, Mann-Whitney U, ANOVA, Wilcoxon analysis, and Pearson chi-square tests were used., Results: The pursed lips exercise and inhaler drug use skills of patients in both groups increased (p<0.001). The median value of the CAT and mMRC scores were statistically significant for both groups (p<0.005). The mean of life quality scores of patients in both groups decreased, and this result was found to be statistically significant in all sub-dimensions and in the total scale score for both groups (p<0.001). Although the increase in the quality of life and the decrease in the severity of dyspnea of the patients in both groups were significant, neither group was superior to the other (p>0.05)., Conclusions: As a result of the study, it was found that the skill of using the inhaler and the life quality of the patients increased, and the severity of dyspnea decreased. Supporting inhaler treatments with non-pharmacological methods can increase drug efficacy and quality of life., Trial Registration: ClinicalTrials.gov NCT04739488. Registered on 21 Feb 2021., (© 2022. The Author(s).)

In recent years, new nicotine delivery methods have emerged, and many users are choosing electronic cigarettes (e-cigarettes) over traditional tobacco cigarettes. E-cigarette use is very popular among adolescents, with more than 3.5 million currently using these products in the US. Despite the increased prevalence of e-cigarette use, there is limited knowledge regarding the health impact of e-cigarettes on the general population. Based on published findings by others, E-cigarette is associated with lung injury outbreak, which increased health and safety concerns related to consuming this product. Different components of e-cigarettes, including food-safe liquid solvents and flavorings, can cause health issues related to pneumonia, pulmonary injury, and bronchiolitis. In addition, e-cigarettes contain alarmingly high levels of carcinogens and toxicants that may have long-lasting effects on other organ systems, including the development of neurological manifestations, lung cancer, cardiovascular disorders, and tooth decay. Despite the well- documented potential for harm, e-cigarettes do not appear to increase susceptibility to SARS-CoV- 2 infection. Furthermore, some studies have found that e-cigarette users experience improvements in lung health and minimal adverse effects. Therefore, more studies are needed to provide a definitive conclusion on the long-term safety of e-cigarettes. The purpose of this review is to inform the readers about the possible health-risks associated with the use of e-cigarettes, especially among the group of young and young-adults, from a molecular biology point of view., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier B.V.)

A high fat diet and obesity have been linked to the development of metabolic dysfunction and the promotion of multiple cancers. The causative cellular signals are multifactorial and not yet completely understood. In this report, we show that Inositol Polyphosphate-4-Phosphatase Type II B (INPP4B) signaling protects mice from diet-induced metabolic dysfunction. INPP4B suppresses AKT and PKC signaling in the liver thereby improving insulin sensitivity. INPP4B loss results in the proteolytic cleavage and activation of a key regulator in de novo lipogenesis and lipid storage, SREBP1. In mice fed with the high fat diet, SREBP1 increases expression and activity of PPARG and other lipogenic pathways, leading to obesity and non-alcoholic fatty liver disease (NAFLD). Inpp4b -/- male mice have reduced energy expenditure and respiratory exchange ratio leading to increased adiposity and insulin resistance. When treated with high fat diet, Inpp4b -/- males develop type II diabetes and inflammation of adipose tissue and prostate. In turn, inflammation drives the development of high-grade prostatic intraepithelial neoplasia (PIN). Thus, INPP4B plays a crucial role in maintenance of overall metabolic health and protects from prostate neoplasms associated with metabolic dysfunction.

With advances in medical technology, the number of people over the age of 60 is on the rise, and thus, increasing the prevalence of age-related pathologies within the aging population. Neurodegenerative disorders, cancers, metabolic and inflammatory diseases are some of the most prevalent age-related pathologies affecting the growing population. It is imperative that a new treatment to combat these pathologies be developed. Although, still in its infancy, the CRISPR-Cas9 system has become a potent gene-editing tool capable of correcting gene-mediated age-related pathology, and therefore ameliorating or eliminating disease symptoms. Deleting target genes using the CRISPR-Cas9 system or correcting for gene mutations may ameliorate many different neurodegenerative disorders detected in the aging population. Cancer cells targeted by the CRISPR-Cas9 system may result in an increased sensitivity to chemotherapeutics, lower proliferation, and higher cancer cell death. Finally, reducing gene targeting inflammatory molecules production through microRNA knockout holds promise as a therapeutic strategy for both arthritis and inflammation. Here we present a review based on how the expanding world of genome editing can be applied to disorders and diseases affecting the aging population., (Copyright: © 2020 Caobi et al.)

Inositol polyphosphate-4-phosphatase type II (INPP4B) is a dual-specificity phosphatase that acts as a tumor suppressor in multiple cancers. INPP4B dephosphorylates phospholipids at the 4th position of the inositol ring and inhibits AKT and PKC signaling by hydrolyzing of PI(3,4)P2 and PI(4,5)P2, respectively. INPP4B protein phosphatase targets include phospho-tyrosines on Akt and phospho-serine and phospho-threonine on PTEN. INPP4B is highly expressed in testes, suggesting its role in testes development and physiology. The objective of this study was to determine whether Inpp4b deletion impacts testicular function in mice. In testis, Inpp4b expression was the highest in postmeiotic germ cells in both mice and men. The testes of Inpp4b knockout male mice were significantly smaller compared to the testes of wild-type (WT) males. Inpp4b-/- males produced fewer mature sperm cells compared to WT, and this difference increased with age and high fat diet (HFD). Reduction in early steroidogenic enzymes and luteinizing hormone (LH) receptor gene expression was detected, although androgen receptor (AR) protein level was similar in WT and Inpp4b-/- testes. Germ cell apoptosis was significantly increased in the knockout mice, while expression of meiotic marker γH2A.X was decreased. Our data demonstrate that INPP4B plays a role in maintenance of male germ cell differentiation and protects testis functions against deleterious effects of aging and high fat diet., Competing Interests: The authors have declared that no competing interests exist.

Multiple sclerosis (MS) is an immune-mediated demyelinating disorder of unknown etiology. Both genetic-susceptibility and environment exposures, including vitamin D deficiency, Epstein-Barr viral and Herpesvirus (HHV-6) infections are strongly implicated in the activation of T cells and MS-pathogenesis. Despite precise knowledge of how these factors could be operating alone or in combination to facilitate and aggravate the disease progression, it is clear that prolonged induction of inflammatory molecules and recruitment of other immune cells by the activated T cells results in demyelination and axonal damage. It is imperative to understand the risk factors associated with MS progression and how these factors contribute to disease pathology. Understanding of the underlying mechanisms of what factors triggers activation of T cells to attack myelin antigen are important to strategize therapeutics and therapies against MS. Current review provides a detailed literature to understand the role of both pathogenic and non-pathogenic factors on the impact of MS., (© 2018 Wiley Periodicals, Inc.)

Purpose: The aim of this study was to evaluate the effects of 4 mouth rinses on the color stability of two different resin composites., Materials and Methods: A2 shade sonic-activated bulk fill material SonicFill (Kerr) and conventional nanohybrid composite Filtek Z550 (3M ESPE) were used. Forty disc-shaped specimens (10 mm x 2 mm) were fabricated for both composites and finished using 400-grit SiC paper and polished. After polishing and immersing in distilled water for 24h all specimens were subjected to color measurements. The baseline color values (L*, a*, b*) of each specimen were measured with a colorimeter. Following baseline measurement each composite group was divided into 5 groups: Oral-B Pro Expert Clinic Line Alcoholfree (Oral-B) group, Listerine Tooth Defense Rinse (Listerine) group, Pharmol Zn Mouth rinse (Çözümilaç) group, Nilera Mouth rinse (Nilera) group and Distilled water (control) group. The specimens were incubated in mouth rinses (20 ml) at 37°C for 12 hours and subjected to color measurement. Two-way ANO VA was used for statistical analysis (p<0.05)., Results: SonicFill showed significantly higher discoloration when exposed to Oral-B Pro Expert Clinic Line Alcohol-free, Listerine Tooth Defense Rinse and Pharmol Zn Mouth rinse. The color differences of two resin composites were not statistically significant for distilled water and Nilera Mouth rinse., Conclusion: Within the limits of this study it can be concluded that the SonicFill showed higher discoloration than nanohybrid resin composite Filtek Z550., Competing Interests: Conflict of interest: None declared.