Activation of homologous recombination in G1 preserves centromeric integrity.

Centromeric integrity is key for proper chromosome segregation during cell division1. Centromeres have unique chromatin features that are essential for centromere maintenance2. Although they are intrinsically fragile and represent hotspots for chromosomal rearrangements3, little is known about how centromere integrity in response to DNA damage is preserved. DNA repair by homologous recombination requires the presence of the sister chromatid and is suppressed in the G1 phase of the cell cycle4. Here we demonstrate that DNA breaks that occur at centromeres in G1 recruit the homologous recombination machinery, despite the absence of a sister chromatid. Mechanistically, we show that the centromere-specific histone H3 variant CENP-A and its chaperone HJURP, together with dimethylation of lysine 4 in histone 3 (H3K4me2), enable a succession of events leading to the licensing of homologous recombination in G1. H3K4me2 promotes DNA-end resection by allowing DNA damage-induced centromeric transcription and increased formation of DNA-RNA hybrids. CENP-A and HJURP interact with the deubiquitinase USP11, enabling formation of the RAD51-BRCA1-BRCA2 complex5 and rendering the centromeres accessible to RAD51 recruitment and homologous recombination in G1. Finally, we show that inhibition of homologous recombination in G1 leads to centromeric instability and chromosomal translocations. Our results support a model in which licensing of homologous recombination at centromeric breaks occurs throughout the cell cycle to prevent the activation of mutagenic DNA repair pathways and preserve centromeric integrity.

Children's expectations about the stability of others' knowledge and preference states.

It is a crucial ability to predict others' psychological states across time and contexts. Focusing on cultural inventions such as songs and stories, we contrasted children's attributions of stability with others' knowledge and preference states across time and space and whether these attributions change as a function of children's familiarity with the known/liked items. Children (91 4-year-olds and 97 6-year-olds) were introduced to characters who knew or liked a song, a story, a game and a dance that were either novel or familiar. Children were asked whether the characters would still know/like these when they move to another city or when they grow up to be an adult. Both age groups expected these attributes to be more durable in the moving scenario compared with the growing-up scenario, but this trend became more robust with age. Whereas overall children did not judge knowledge as more durable than preferences, children found knowledge to be more enduring with age. The 6-year-olds' stability attributions also increased when known/liked items were familiar. These results suggest that, across the preschool years, children become more nuanced in their predictions about the future forms of knowledge and preference states.

MIS-C Treatment: Is glucocorticoid monotherapy enough for mild cases?

BACKGROUND: The effectiveness of using only glucocorticoids (GCs) in mild multisystem inflammatory syndrome (MIS-C) cases was compared with combined treatment [GCs + Intravenous immune globulin (IVIG)]. METHODS: This retrospective cohort study was conducted between June 1, 2020, and June 1, 2022, in a tertiary care center in Istanbul, Turkey. Clinical and investigational data of the MIS-C patients were analyzed. The patients were divided into two groups: those who received only GCs and those who received the GCs + IVIG combination. The primary outcome focused on assessing the deterioration of the patient's clinical condition, the occurrence of shock, admission to the pediatric intensive care unit (PICU), and the need for additional immunosuppressive medication. Secondary outcomes included evaluating the course of cardiovascular and infection-related complications observed at the one-year follow-up. RESULTS: Ninety-seven MIS-C patients with a median age of 41 (3- 214) months were enrolled. Fifty-six (57.7%) patients were male. All the patients had fever at admission with a temperature of 39 °C (37.5 °C-40.1 °C). Thirty-two patients (33%) had cardiac findings on echocardiography [left ventricular dysfunction (n= 13, 13.5%), coronary artery involvement (n= 11, 11.3%), and dilation of cardiac cavities and/or increased cardiac muscle thickness (n= 8, 8.2%)]. Thirteen patients (13.5%) required intensive care. All patients received GCs [only GCs (group I; n= 65, 67%)], and 32 patients (33%) with severe manifestations and/or cardiac involvement received GCs + IVIG (group II). No mortality was observed. None of the patients had any complaints at the one-year follow-up, and all echocardiography findings were normal. CONCLUSION: This study provides preliminary evidence that GC monotherapy is a safe treatment alternative for mild MIS-C cases without cardiac involvement.

XBP1 Activation Reduces Severity of Polycystic Kidney Disease due to a Nontruncating Polycystin-1 Mutation in Mice.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in Pkd1 and Pkd2. They encode the polytopic integral membrane proteins polycystin-1 (PC1) and polycystin-2 (PC2), respectively, which are expressed on primary cilia. Formation of kidney cysts in ADPKD starts when a somatic second hit mechanism inactivates the wild-type Pkd allele. Approximately one quarter of families with ADPDK due to Pkd1 have germline nonsynonymous amino acid substitution (missense) mutations. A subset of these mutations is hypomorphic, retaining some residual PC1 function. Previous studies have shown that the highly conserved Ire1 α -XBP1 pathway of the unfolded protein response can modulate levels of functional PC1 in the presence of mutations in genes required for post-translational maturation of integral membrane proteins. We examine how activity of the endoplasmic reticulum chaperone-inducing transcription factor XBP1 affects ADPKD in a murine model with missense Pkd1 . METHODS: We engineered a Pkd1 REJ domain missense murine model, Pkd1 R2216W , on the basis of the orthologous human hypomorphic allele Pkd1 R2220W , and examined the effects of transgenic activation of XBP1 on ADPKD progression. RESULTS: Expression of active XBP1 in cultured cells bearing PC1 R2216W mutations increased levels and ciliary trafficking of PC1 R2216W . Mice homozygous for Pkd1 R2216W or heterozygous for Pkd1 R2216Win trans with a conditional Pkd1 fl allele exhibit severe ADPKD following inactivation in neonates or adults. Transgenic expression of spliced XBP1 in tubule segments destined to form cysts reduced cell proliferation and improved Pkd progression, according to structural and functional parameters. CONCLUSIONS: Modulating ER chaperone function through XBP1 activity improved Pkd in a murine model of PC1, suggesting therapeutic targeting of hypomorphic mutations.

The effect of yoga practice on pain intensity, menstruation symptoms and quality of life of nursing students with primary dysmenorrhea.

The researchers aimed to determine the effects of yoga on pain severity, menstrual symptoms and quality of life of undergraduate nursing students with primary dysmenorrhea. The 60 female students were divided into intervention (n = 30) and control groups (n = 30) by block randomization. In the study, data were evaluated with the Visual Analog Scale for Pain, the Menstruation Symptom Scale and the Short Form-36 Health Survey Scale. The 12-week intervention program, which included all components of Hatha yoga, was carried out twice a week for a total of 24 sessions of 60 min. The control group did not receive any intervention. The severity of menstrual pain and symptoms decreased in yoga group compared to control group, and there were significant improvements in quality of life (p < 0.001). The researchers shows that regular Hatha yoga may be a possible nonpharmacological treatment for primary dysmenorrhea in young women in this study.

Immunosuppressive calcineurin inhibitor cyclosporine A induces proapoptotic endoplasmic reticulum stress in renal tubular cells.

Current immunosuppressive strategies in organ transplantation rely on calcineurin inhibitors cyclosporine A (CsA) or tacrolimus (Tac). Both drugs are nephrotoxic, but CsA has been associated with greater renal damage than Tac. CsA inhibits calcineurin by forming complexes with cyclophilins, whose chaperone function is essential for proteostasis. We hypothesized that stronger toxicity of CsA may be related to suppression of cyclophilins with ensuing endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in kidney epithelia. Effects of CsA and Tac (10 µM for 6 h each) were compared in cultured human embryonic kidney 293 (HEK 293) cells, primary human renal proximal tubule (PT) cells, freshly isolated rat PTs, and knockout HEK 293 cell lines lacking the critical ER stress sensors, protein kinase RNA-like ER kinase or activating transcription factor 6 (ATF6). UPR was evaluated by detection of its key components. Compared with Tac treatment, CsA induced significantly stronger UPR in native cultured cells and isolated PTs. Evaluation of proapoptotic and antiapoptotic markers suggested an enhanced apoptotic rate in CsA-treated cells compared with Tac-treated cells as well. Similar to CsA treatment, knockdown of cyclophilin A or B by siRNA caused proapoptotic UPR, whereas application of the chemical chaperones tauroursodeoxycholic acid or 4-phenylbutyric acid alleviated CsA-induced UPR. Deletion of protein kinase RNA-like ER kinase or ATF6 blunted CsA-induced UPR as well. In summary, inhibition of cyclophilin chaperone function with ensuing ER stress and proapoptotic UPR aggravates CsA toxicity, whereas pharmacological modulation of UPR bears potential to alleviate renal side effects of CsA.

Examination of individuals' depression, anxiety, and stress levels during the COVID-19 pandemic in Turkey.

PURPOSE: This research was conducted to determine the depression, anxiety, and stress levels of individuals during the COVID-19 epidemic. In addition, the compatibility of the Depression-Anxiety-Stress Scale (DASS-21) scale results with the participants' feeling depressed, anxious, and stressed were examined. DESIGN AND METHODS: The sample of the study consisted of 870 individuals over the age of 18 between May-August 2021. The data of the study were collected online, using the personal information form and DASS-21. RESULTS: In our study, it was observed that 22.3 % of the participants were severely depressed, 19.0 % were highly anxious and 14.3 % were highly stressed. In addition, a relationship was determined between many sociodemographic variables and depression, anxiety, and stress levels. It was found that individuals who were not vaccinated, did not receive health care, and were not satisfied with health care were more depressed, anxious, and stressed. The agreement between all DASS-21 sub-dimensions and participants' feeling is poor in terms of Cohen's kappa. The agreement is poor in the anxiety sub dimension, but moderate in the other sub-dimensions in terms of Gwet's AC1. PRACTICE IMPLICATIONS: It is recommended that nurses develop new care and evaluation strategies for the psychosocial field in order to protect and maintain the health of individuals during the COVID-19 pandemic process, as well as more practices promoting the COVID-19 vaccine in our country.

Connexin43 is differentially distributed within renal vasculature and mediates profibrotic differentiation in medullary fibroblasts.

Connexins (Cxs) form gap junctions for intercellular exchange of inorganic ions and messenger molecules. In the kidney, Cxs play essential roles within its compartments, but data on the precise cellular localization and cell type-related function of their isoforms are scarce. We tested whether Cx43 distribution is restricted to vascular and interstitial cells and whether medullary fibroblasts express Cx43 to coordinate profibrotic signaling. Confocal immunofluorescence techniques, ultrastructural labeling, and functional experiments in cell culture were performed. Cx43 was chiefly expressed in the vasculature but was absent from tubular epithelia. All arterial, arteriolar, and lymphatic endothelia showed continuous Cx43 signal along their borders. In the inner medulla, only the interstitium showed Cx43 signals, which were assigned to fibroblasts and their processes. Cultured Cx43-expressing medullary fibroblasts served to study the role of gap junctions in a profibrotic context. In a dye spreading assay, Cx43-sensitive diffusion of Lucifer yellow was dependent on gap junctional passage. The addition of transforming growth factor-ß1 (5 ng/mL for 48 h) activated Cx43 biosynthesis and caused Cx43-sensitive transformation of the fibroblasts into a myofibroblast phenotype. This suggested that Cx43 gap junctional channels enable the coordination of profibrotic signaling between cells of the medullary interstitium. In summary, we demonstrate the presence of Cx43-expressing gap junctions within the two major renal compartments, the vasculature and interstitium. Endothelial Cx43 likely provides functions of an earlier-defined "electrical syncytium" within the vascular wall. Additionally, Cx43 facilitates profibrotic signaling between medullary interstitial fibroblasts.

The relationship between quality of life and fear of Turkish individuals during the COVID-19 pandemic: A cross-sectional study.

OBJECTIVE: In this study, it was aimed to determine the relationship between quality of life and the fear experienced due to the COVID-19 pandemic. METHOD: This cross-sectional descriptive study was conducted with a total of 1060 participants from Turkey's 65 provinces. The research data were collected through an online questionnaire consisting of three parts: "Personal Information Form", "The Fear of COVID-19 Scale (FCS)" and "World Health Organization Life Quality Scale-Short Form (WHOQOL-BREF)". Independent two-group t-test (Student's t-test), and one-way ANOVA test were used to compare the means of groups. The Pearson Correlation Coefficient was calculated to determine the level of correlation between two independent continuous variables. A value of p < .05 was accepted as the threshold for statistical significance. RESULTS: The fear levels of women, married individuals and primary school graduates were found to be high, while quality of life was low among participants with poor economic status, those with COVID-19 symptoms and subjects who had been in close contact with a COVID-19-positive patient. In addition, there was an inverse relationship between the level of fear related to COVID-19 and quality of life (physical and psychological health). PRACTICE IMPLICATIONS: Nurses are recommended to develop new care and evaluation strategies that will cover psychosocial and economic areas, as well as physical health, in order to protect and maintain the well-being of individuals during the COVID-19 pandemic.

Mapping of carbon monoxide related death risk in Turkey: a ten-year analysis based on news agency records.

BACKGROUND: Carbon-monoxide (CO) poisoning is a substantial cause of preventable mortality. In Turkey, no nationwide data are being collected nowadays. In our study, we aimed to assess the trend in deaths related to CO exposure in all provinces of Turkey in a 10-year period by using the records of a news agency which collects the news from the majority of the national newspapers, local newspapers and television channels. METHODS: In this study, 27,881 news items that were released between January 2008 to December 2017 which included keywords of "poisoning" and "death" or "carbon monoxide" and "death" were evaluated. 2667 non-fire related deaths were used in the final analyses. RESULTS: In a 10-year period, the risk of CO-related death in Turkey was 0.35/100000. 1371 (51.4%) of the victims were male and the median age of the patients was 45 years (range, 15 days-108 years). Most of the deaths occurred ≥50 years of age. Stoves were the predominant source [n = 2096 (78.6%)]. There was a stagnating trend of CO-related deaths. Most of the incidents occurred in winter. The Middle Anatolian region was of the highest risk in CO-related mortality. CONCLUSIONS: In conclusion, CO poisoning is still a considerable public health concern in Turkey. Results of our study showed that stoves are still frequently being used and are the cause of death especially in rural areas with lower socioeconomic status. A better organized, nationwide surveillance and management approaches are needed to demonstrate the true burden CO related morbidity and mortality as well as its prevention in Turkey.

The relationship of postpartum sleep quality and breastfeeding self-efficacy of Turkish mothers.

INTRODUCTION: Breastfeeding self-efficacy reflects the mother's confidence regarding breastfeeding, and it positively affects breastfeeding. Traditionally, people attach importance to breastfeeding in Turkey and the vast majority of mothers breastfeed their babies. It is a known fact that mothers feel sleepless and tired in the postpartum period reduces the amount of secreted milk. However, it is not known whether there is a relationship between the perception of breastfeeding self-efficacy which positively affects breastfeeding and sleep quality of the mothers in this period. AIM: This study was conducted in order to determine the relationship between sleep quality and breastfeeding self-efficacy of the mothers in the postpartum period. MATERIALS AND METHODS: This descriptive study included 128 primiparous women who had vaginal deliveries from 2 January to 27 May 2018 in a public obstetrics and children's hospital in Mersin. The data of the research were gathered with a questionnaire intended for collecting the sociodemographic characteristics of mothers who completed their second week in the postpartum period, Postpartum Sleep Quality Scale intended for determining their sleep quality and Breastfeeding Self-efficacy Scale intended for determining their breastfeeding self-efficacy. The data obtained were assessed with the Pearson correlation coefficient to determine the relationship between the descriptive statistics and two continuous variables. RESULTS: The mean score gotten by the mothers from Postpartum Sleep Quality Scale and Breastfeeding Self-efficacy Scale was determined to be '33.57 ± 11.26' and '46.82 ± 14.89', respectively. A strong relationship in the negative direction was detected between the scores gotten from Postpartum Sleep Quality Scale and Breastfeeding Self-efficacy Scale (p < 0.01). CONCLUSIONS: As a result of the research, it was determined that as the sleep quality of mothers in the postpartum period increases their breastfeeding self-efficacy increases as well. In the light of the results obtained, it is suggested that nurses, being aware that there is a strong relationship between sleep quality and breastfeeding self-efficacy in the postpartum period, should pay more attention to the role of education and counselling in these subjects. In addition, it is recommended that nurses make attempts intended for improving the sleep quality of primiparous individuals in order to increase their self-efficacy of breastfeeding.

Global structural changes of an ion channel during its gating are followed by ion mobility mass spectrometry.

Mechanosensitive ion channels are sensors probing membrane tension in all species; despite their importance and vital role in many cell functions, their gating mechanism remains to be elucidated. Here, we determined the conditions for releasing intact mechanosensitive channel of large conductance (MscL) proteins from their detergents in the gas phase using native ion mobility-mass spectrometry (IM-MS). By using IM-MS, we could detect the native mass of MscL from Escherichia coli, determine various global structural changes during its gating by measuring the rotationally averaged collision cross-sections, and show that it can function in the absence of a lipid bilayer. We could detect global conformational changes during MscL gating as small as 3%. Our findings will allow studying native structure of many other membrane proteins.

Mechanism of inhibition of CYP1A1 and glutathione S-transferase activities in fish liver by quercetin, resveratrol, naringenin, hesperidin, and rutin.

Quercetin, resveratrol, naringenin, hesperidin, and rutin are phenolic compounds/flavonoids that may have roles in the reduction of cancer susceptibility. In this study, in vitro modulatory effects of them were studied on liver CYP1A1 associated 7-ethoxyresorufin-O-deethylase (EROD) activity and glutathione S-transferase (GST) activity of leaping mullet (Liza saliens). All of the phenolic compounds/flavonoids used exerted an inhibitory effect on both EROD and GST activities of fish. Quercetin, resveratrol, hesperidin, and rutin were found to inhibit EROD activity in a competitive manner; on the other hand, naringenin was found to inhibit EROD activity in a noncompetitive manner. Ki values of quercetin, resveratrol, naringenin, hesperidin, and rutin were calculated from Dixon plots as 0.12 µM, 0.67 µM, 2.63 µM, 18 µM and 0.1 mM, respectively. Resveratrol, quercetin, and hesperidin were found to inhibit GST activity in a competitive manner; on the other hand, rutin and naringenin were found to inhibit GST activity in a mixed-type manner. Ki values of resveratrol, quercetin, hesperidin, naringenin, and rutin were calculated from Dixon plots as 3.2 µM, 12.5 µM, 45 µM, 128 µM, and 150 µM, respectively. The results suggest that quercetin and resveratrol containing foods are effective in the prevention and treatment of cancer.

Study of light-induced MscL gating by EPR spectroscopy.

A number of techniques developed to investigate protein structure and function depend on chemically modifying and/or labeling of proteins. However, in the case of homooligomeric proteins, the presence of multiple identical subunits obstructs the introduction of residue-specific labels to only one or several subunits, selectively. Here, in order to study the initial conformational changes of a homopentameric mechanosensitive ion channel during its gating, we developed a method for labeling a defined number of subunits of the channel with two different cysteine-specific compounds simultaneously. The first one is a light-sensitive channel activator that determines the degree of openness of the ion channel upon irradiation. The second one is a spin label, containing an unpaired electron, which allows following the resulting structural changes upon channel gating by electron paramagnetic resonance spectroscopy. With this method, we could open MscL into different sub-open states. As the number of light switches per channel increased, the intersubunit spin-spin interactions became less, indicating changes in intersubunit proximities and opening of the channel. The ability of controlled activation of MscL into different open states with a noninvasive trigger and following the resulting conformational changes by spectroscopy will pave the way for detailed spectroscopic studies in the area of mechanosensation.

Bright ion channels and lipid bilayers.

If we look at a simple organism such as a zebrafish under a microscope, we would see many cells working in harmony. If we zoomed in, we would observe each unit performing its own tasks in a special aqueous environment isolated from the other units by a lipid bilayer approximately 5 nm thick. These confined units are social: they communicate with one another by sensing and responding to the chemical changes in their environment through receptors and ion channels. These channels control the highly specific and selective passage of ions from one side of the cell to the other and are embedded in lipid bilayers. The movement of ions through ion channels supports excitation and electrical signaling in the nervous system. Ion channels have fascinated scientists not only because of their specificity and selectivity, but also for their functions, the serious consequences when they malfunction, and the other potential applications of these molecules. Light is a useful trigger to control and manipulate ion channels externally. With the many state-of-the-art optical technologies available, light offers a high degree of spatial and temporal control, millisecond precision, and noninvasive intervention and does not change the chemical environment of the system of interest. In this Account, we discuss research toward the dynamic control of lipid bilayer assembly and channel function, particularly the transport across the lipid bilayer-ion channel barrier of cells using light. We first summarize the manipulation of ion channel activity with light to modulate the channel's natural activity. Based on the type of photoswitch employed, we can achieve novel functionalities with these channels, and control neural activity. Then we discuss the recent developments in light-induced transport through lipid bilayers. We focus on three different approaches: the incorporation of photoswitchable copolymers into the lipids, the doping of the lipid bilayer with photosensitive amphiphiles and the preparation of the lipid bilayers solely from photoswitchable lipids. These examples reflect the versatility of what we can achieve by manipulating biological systems with light, from triggering the permeability of a specific area of a lipid bilayer to controlling the behavior of a whole organism.

Quality of sexual life and its effect on marital adjustment of Turkish women in pregnancy.

Pregnancy is an important period of a woman's life that can affect marital relationships because of decrease in the sexual function. This study aimed to examine the effect of sexual life on the marital adjustment of 607 healthy, pregnant women using the self-administered Sexual Quality of Life Questionnaire-Female and the Marital Adjustment Scale. Results showed that 30% of the pregnant women experienced problems during sexual intercourse and 50% had painful intercourse. The median total score of the Sexual Quality of Life Questionnaire-Female for pregnant women was 35.5, and the median total score of the Marital Adjustment Scale was 41.0. The authors found a positive moderate level correlation between the sexual quality of life for women and their marital adjustment for being pregnant (r = 0.468, p =.001). The results imply that the variance in the sexual activity during the childbearing period does occur and pregnant women need to be assessed regularly with regards to their sexuality by health care providers in a professional atmosphere.

Unusual neonatal case of superior mesenteric artery syndrome with Meckel's diverticulum and literature review.

Superior mesenteric artery syndrome (SMAS) is a rare cause of duodenal obstruction which is characterized by compression of the duodenum due to narrowing of the space between the superior mesenteric artery and aorta. Incomplete duodenal obstruction due to SMAS in neonates is rarely reported in the literature. In this case, it is a full-term 2-day-old male with the complaint of recurrent vomiting starting soon after birth. The patient was diagnosed with SMAS and duodenoduodenostomy was performed. Accompanying Meckel's diverticulum was excised.

El síndrome de la arteria mesentérica superior (SMAS) es una causa rara de obstrucción duodenal que se caracteriza por la compresión del duodeno debido al estrechamiento del espacio entre la arteria mesentérica superior y la aorta. La obstrucción duodenal incompleta por SMAS en recién nacidos rara vez se informa en la literatura. En este caso se trata de un varón de 2 días nacido a término que presenta vómitos recurrentes desde poco después del nacimiento. El paciente fue diagnosticado de SMAS y se le realizó duodenoduodenostomía. Se extirpó el divertículo de Meckel que lo acompañaba.

Propolis-Loaded Poly(lactic-co-glycolic Acid) Nanofibers: An In Vitro Study.

Nanofibers have high potential through their high porosity, small pore sizes, lightweight materials, and their ability to mimic the extracellular matrix structure for use in the manufacture of wound dressings for wound treatment. In this study, poly(lactic-co-glycolic acid) (PLGA) nanofibers were produced by electrospinning. Propolis was loaded into the PLGA nanofibers by the dropping method. The average diameters and effects of propolis loading on the morphology of 37.5, 50, and 100% propolis-loaded PLGA nanofibers (PLGA-P37.5, PLGA-P50, and PLGA-P100) were evaluated by scanning electron microscopy (SEM). The successful loading of propolis into PLGA nanofibers was confirmed with Fourier transform infrared spectroscopy (FTIR) analysis. In vitro propolis release was examined at physiological pH. The antioxidant activity of propolis-loaded nanofibers was studied with 2,2-diphenyl-1-picrylhydrazyl (DPPH). Antimicrobial activities of the nanofibers against Escherichia coli, Staphylococcus aureus and Candida albicans strains were determined by the disk diffusion method. Consequently, PLGA-P50 and PLGA-P100 showed high antimicrobial activity on S. aureus and C. albicans. Cell viability was tested by 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, and propolis-loaded PLGA nanofibers were found to be biocompatible with human fibroblast cells. In the wound scratch assay, propolis-loaded nanofibers supported wound closure with cell migration and proliferation. Thus, in vitro wound closure properties of propolis-loaded PLGA nanofibers were evaluated for the first time in the literature.

Immunosuppression with cyclosporine versus tacrolimus shows distinctive nephrotoxicity profiles within renal compartments.

AIM: Calcineurin inhibitors (CNIs) are the backbone for immunosuppression after solid organ transplantation. Although successful in preventing kidney transplant rejection, their nephrotoxic side effects contribute to allograft injury. Renal parenchymal lesions occur for cyclosporine A (CsA) as well as for the currently favored tacrolimus (Tac). We aimed to study whether chronic CsA and Tac exposures, before reaching irreversible nephrotoxic damage, affect renal compartments differentially and whether related pathogenic mechanisms can be identified. METHODS: CsA and Tac were administered chronically in wild type Wistar rats using osmotic minipumps over 4 weeks. Functional parameters were controlled. Electron microscopy, confocal, and 3D-structured illumination microscopy were used for histopathology. Clinical translatability was tested in human renal biopsies. Standard biochemical, RNA-seq, and proteomic technologies were applied to identify implicated molecular pathways. RESULTS: Both drugs caused significant albeit differential damage in vasculature and nephron. The glomerular filtration barrier was more affected by Tac than by CsA, showing prominent deteriorations in endothelium and podocytes along with impaired VEGF/VEGFR2 signaling and podocyte-specific gene expression. By contrast, proximal tubule epithelia were more severely affected by CsA than by Tac, revealing lysosomal dysfunction, enhanced apoptosis, impaired proteostasis and oxidative stress. Lesion characteristics were confirmed in human renal biopsies. CONCLUSION: We conclude that pathogenetic alterations in the renal compartments are specific for either treatment. Considering translation to the clinical setting, CNI choice should reflect individual risk factors for renal vasculature and tubular epithelia. As a step in this direction, we share protein signatures identified from multiomics with potential pathognomonic relevance.

Determination of the use of traditional practices to ease labour among Turkish women.

The purpose of this study was to determine the use of traditional practices to ease labour among Turkish women. Face-to-face interviews were conducted with 809 women by using an investigator-designed questionnaire. The mean age of the women was 28.9 ± 8.33 years (min = 15, max = 74), 49.4% were between 20-29 years of age and more than half (56.2%) of the women had had one to two pregnancies. The results showed that traditional practices were known and applied mostly by the women who were at an advanced age, less educated and who lived in rural areas. In addition, the knowledge and application status of traditional practices related to religious beliefs were found to be very high compared with superstitious practices. It was suggested that nurses provide culturally competent care that requires a commitment by the individual nurse to develop, refine and use specific skills in the care of women.