Extending the concept of moral distress to parents of infants hospitalized in the NICU: a qualitative study in Greece.

BACKGROUND: The hospitalization of infants in the neonatal intensive care unit (NICU) is an ethically challenging situation. A limited number of studies have extended the concept of moral distress to parents of infants hospitalized in the NICU. This topic requires further investigation. METHODS: The present prospective qualitative study was conducted from February 2023 to May 2023. Data were collected through semistructured in-depth interviews, which were conducted in-person with fifteen parents of infants who were hospitalized in the NICU at the time of the interviews. Purposive sampling was used. The data were classified and analyzed using thematic analysis. RESULTS: Three themes emerged from the data analysis performed for this empirical study. One intrapersonal dimension featuring two aspects (one dynamic and one static) and another interpersonal dimension focusing on parental moral distress emerged from the data analysis. Furthermore, seven subthemes emerged across these themes: (1) self-directed negative feelings were experienced by parents due to their inability to fulfill their caregiving/parental roles; (2) intense internal conflict was experienced by parents in response to a moral dilemma that was difficult, which was perceived as irresolvable; (3) objectively unjustified, self-directed negative feelings of guilt or failure were experienced by parents; (4) parents experienced moral distress due to the poor image of the ill infants; (5) inadequate information may predispose parents to experience moral distress (6) neonatologists' caring behaviors were unduly perceived by parents as paternalistic behaviors; (7) reasonable or justified institutional rules were unduly perceived by parents as constraint. CONCLUSIONS: In general, the results of this study support the integrated definition of parental moral distress proposed by Mooney-Doyle and Ulrich. Furthermore, the present study introduces new information. The study distinguishes between the dynamic and static aspects of the intrapersonal dimension of the phenomenon of parental moral distress. Moreover, participants experienced moral distress because they unduly perceived certain situations as causing moral distress. In addition, inadequate information may predispose parents to experience moral distress. The findings of this study may contribute promote family-centered care in the NICU context.

Understanding the Ethical Issues of Brain-Computer Interfaces (BCIs): A Blessing or the Beginning of a Dystopian Future?

In recent years, scientific discoveries in the field of neuroscience combined with developments in the field of artificial intelligence have led to the development of a range of neurotechnologies. Advances in neuroimaging systems, neurostimulators, and brain-computer interfaces (BCIs) are leading to new ways of enhancing, controlling, and "reading" the brain. In addition, although BCIs were developed and used primarily in the medical field, they are now increasingly applied in other fields (entertainment, marketing, education, defense industry). We conducted a literature review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to provide background information about ethical issues related to the use of BCIs. Among the ethical issues that emerged from the thematic data analysis of the reviewed studies included questions revolving around human dignity, personhood and autonomy, user safety, stigma and discrimination, privacy and security, responsibility, research ethics, and social justice (including access to this technology). This paper attempts to address the various aspects of these concerns. A variety of distinct ethical issues were identified, which, for the most part, were in line with the findings of prior research. However, we identified two nuances, which are related to the empirical research on ethical issues related to BCIs and the impact of BCIs on international relationships. The paper also highlights the need for the cooperation of all stakeholders to ensure the ethical development and use of this technology and concludes with several recommendations. The principles of bioethics provide an initial guiding framework, which, however, should be revised in the current artificial intelligence landscape so as to be responsive to challenges posed by the development and use of BCIs.

Next-Generation Sequencing of microRNAs in Small Abdominal Aortic Aneurysms: MiR-24 as a Biomarker.

BACKGROUND: Small abdominal aortic aneurysms (AAAs) are asymptomatic but can potentially lead to rupture if left undetected. To date, there is a lack of simple nonradiologic routine tests available for diagnosing AAAs. MicroRNAs (miRNAs) have been proven to be good-quality biomarkers in several diseases, including AAA. METHODS: An attempt to identify a panel of circulating miRNAs with differential expression in AAAs via next-generation sequencing (NGS) was performed in serum samples: small AAAs (n = 3), large AAAs (n = 3), and controls (n = 3). For miR-24, validation with real-time polymerase chain reaction (PCR) was undertaken in a larger group (n = 80). RESULTS: In the NGS study, 23 miRNAs were identified as differentially expressed (with statistical significance) in small AAAs in comparison with controls. Among them, miR-24 showed the largest upregulation with 23-fold change (log2FC 4.5, P = 0.024). For large AAAs compared with controls, and small AAAs compared with large AAAs, a panel of 33 and 131 miRNAs showed statistically significant differential expression, respectively. Based on the results of the NGS stage, a literature search was performed, and information regarding AAA pathogenesis, coronary artery disease, and peripheral arterial disease was documented where applicable: miR-24, miR-103, miR-193a, miR-486, miR-582, and miR-3663. Of these 6 miRNAs, miR-24 was chosen for further validation with real-time PCR. Additionally, in the NGS study analysis, 17 miRNAs were common between the small-large AAAs, small AAAs-controls, and large AAAs-controls comparisons: miR-7846, miR-3195, miR-486-2, miR-3194, miR-5589, miR-1538, miR-3178, miR-4771-1, miR-5695, miR-6504, miR-1908, miR-6823, miR-3159, miR-23a, miR-7853, miR-496, and miR-193a. Interestingly, in the validation stage with real-time PCR, miR-24 was found downregulated in small and large AAAs compared with controls (fold-changes: 0.27, P = 0.015 and 0.15, P = 0.005, respectively). No correlation was found between average Ct values, aneurysm diameter, and patients' age. CONCLUSIONS: Our findings further highlight the importance of miR-24 as a potential biomarker as well as a therapeutic target for abdominal aneurysmal disease. Future research and validation of a panel of miRNAs for AAA would aid in diagnosis and discrimination between diseases with overlapping pathogeneses.

Shedding Light on Colorectal Cancer: An In Vivo Raman Spectroscopy Approach Combined with Deep Learning Analysis.

Raman spectroscopy has emerged as a powerful tool in medical, biochemical, and biological research with high specificity, sensitivity, and spatial and temporal resolution. Recent advanced Raman systems, such as portable Raman systems and fiber-optic probes, provide the potential for accurate in vivo discrimination between healthy and cancerous tissues. In our study, a portable Raman probe spectrometer was tested in immunosuppressed mice for the in vivo localization of colorectal cancer malignancies from normal tissue margins. The acquired Raman spectra were preprocessed, and principal component analysis (PCA) was performed to facilitate discrimination between malignant and normal tissues and to highlight their biochemical differences using loading plots. A transfer learning model based on a one-dimensional convolutional neural network (1D-CNN) was employed for the Raman spectra data to assess the classification accuracy of Raman spectra in live animals. The 1D-CNN model yielded an 89.9% accuracy and 91.4% precision in tissue classification. Our results contribute to the field of Raman spectroscopy in cancer diagnosis, highlighting its promising role within clinical applications.

Limitation of Non-Beneficial Interventions and their Impact on the Intensive Care Unit Costs.

Introduction: Using a plan to limit non-beneficial life support interventions has significantly reduced harm and loss of dignity for patients at the end of life. The association of these limitations with patients' clinical characteristics and health care costs in the intensive care unit (ICU) needs further scientific evidence. Aim of the study: To explore decisions to limit non-beneficial life support interventions, their correlation with patients' clinical data, and their effect on the cost of care in the ICU. Material and Methods: We included all patients admitted to the general ICU of a hospital in Greece in a two-year (2019-2021) prospective study. Data collection included patient demographic and clinical variables, data related to decisions to limit (withholding, withdrawing) non-beneficial interventions (NBIs), and economic data. Comparisons were made between patients with and without limitation decisions. Results: NBIs were limited in 164 of 454 patients (36.12%). Patients with limitation decisions were associated with older age (70y vs. 62y; p<0,001), greater disease severity score (APACHE IV, 71 vs. 50; p<0,001), longer length of stay (7d vs. 4.5d; p<0,001), and worse prognosis of death (APACHE IV PDR, 48.9 vs. 17.35; p<0,001). All cost categories and total cost per patient were also higher than the patient without limitation of NBIs (9247,79€ vs. 8029,46€, p<0,004). The mean daily cost has not differed between the groups (831,24€ vs. 832,59€; p<0,716). However, in the group of patients with limitations, all cost categories, including the average daily cost (767.31€ vs. 649.12€) after the limitation of NBIs, were reduced to a statistically significant degree (p<0.001). Conclusions: Limiting NBIs in the ICU reduces healthcare costs and may lead to better management of ICU resource use.

Parental Home Safety Practices for Domestic Accident Prevention: How Prepared Were Parents for COVID-19 Confinement? A Cross-Sectional Study.

(1) Background: Children are susceptible to home injuries. How prepared parents were to protect their children from accidents before and during the COVID-19 quarantine is uncertain. (2) Methods: We conducted a community-based, cross-sectional study in Greece between November and December 2021. We asked parents to complete an anonymous questionnaire voluntarily. Questions focused on accident-preventive measures taken at home during the COVID-19 quarantine. (3) Results: A greater proportion of parents took protective measures for a safer home before the lockdown than during the quarantine, while an interesting percentage of parents never utilized preventive measures for their children. Slightly more than half (58.6%) of parents did not seem to worry about a possible increase in domestic accidents during the quarantine. It was observed that those who had one or two children took more protective measures than those with more than two children. Older parents seemed to explain to their children how to access emergency services more often. Mothers stayed at home with the children more often, and their education affected the presence of some of the assessed measures. In our logistic regression modeling, parental concern about accidents was more related to the incidence of an accident during the pandemic and attendance at seminars. (4) Conclusions: Although the COVID-19 lockdowns disorganized family life, parents were aware of the importance of their parenting role in creating a safe environment for children, but according to the study, there is room for improvement.

Pedunculated Focal Nodular Hyperplasia: When in Doubt, Should We Cut It Out?

Focal nodular hyperplasia (FNH) is the second most common benign hepatic tumor and can rarely present as an exophytic solitary mass attached to the liver by a stalk. Most FNH cases are usually detected as incidental findings during surgery, imaging or physical examination and have a high female predominance. However, the pedunculated forms of FNH are particularly rare and commonly associated with severe complications and diagnostic challenges. Hence, our study aims to provide a comprehensive summary of the available data on the pedunculated FNH cases among adults and children. Furthermore, we will highlight the role of different therapeutic options in treating this clinical entity. The use of imaging techniques is considered a significant addition to the diagnostic toolbox. Regarding the optimal treatment strategy, the main indications for surgery were the presence of symptoms, diagnostic uncertainty and increased risk of complications, based on the current literature. Herein, we also propose a management algorithm for patients with suspected FNH lesions. Therefore, a high index of suspicion and awareness of this pathology and its life-threatening complications, as an uncommon etiology of acute abdomen, is of utmost importance in order to achieve better clinical outcomes.

Predictive Factors for Anastomotic Leakage Following Colorectal Cancer Surgery: Where Are We and Where Are We Going?

Anastomotic leakage (AL) remains one of the most severe complications following colorectal cancer (CRC) surgery. Indeed, leaks that may occur after any type of intestinal anastomosis are commonly associated with a higher reoperation rate and an increased risk of postoperative morbidity and mortality. At first, our review aims to identify specific preoperative, intraoperative and perioperative factors that eventually lead to the development of anastomotic dehiscence based on the current literature. We will also investigate the role of several biomarkers in predicting the presence of ALs following colorectal surgery. Despite significant improvements in perioperative care, advances in surgical techniques, and a high index of suspicion of this complication, the incidence of AL remained stable during the last decades. Thus, gaining a better knowledge of the risk factors that influence the AL rates may help identify high-risk surgical patients requiring more intensive perioperative surveillance. Furthermore, prompt diagnosis of this severe complication may help improve patient survival. To date, several studies have identified predictive biomarkers of ALs, which are most commonly associated with the inflammatory response to colorectal surgery. Interestingly, early diagnosis and evaluation of the severity of this complication may offer a significant opportunity to guide clinical judgement and decision-making.

Circulating miRNAs as Biomarkers for Diagnosis, Surveillance, and Postoperative Follow-Up of Abdominal Aortic Aneurysms.

BACKGROUND: To provide a summary of the current state of research in English medical literature on circulating miRNAs as biomarkers for abdominal aortic aneurysm (AAA). Additionally, for the most commonly mentioned circulating miRNAs in the literature, to attempt a documentation of the biological mechanisms underlying their role in AAA development. METHODS: A literature search was undertaken in the MEDLINE database. Only reports that involved peripheral blood samples (whole blood, plasma, and serum) were included. The following terms were used in combination: microrna, mirna, AAA, human, circulating, plasma, serum, endovascular, and endovascular aneurysm repair (EVAR). RESULTS: A total of 25 reports, published from 2012 to 2022 were included with a total of 1,259 patients with AAA, predominantly men (N = 1,040, 90%). Six of these reports recruited healthy donors who underwent ultrasound screening for AAA as control samples. The majority of studies were undertaken in plasma samples and the most preferred microRNA profiling method was real - time quantitative polymerase chain reaction (qRT-PCR). The following 9 miRNAs (out of a total of 76) were studied in more than 2 references: miR-145, miR-24, miR-33, miR-125, let-7, miR-15, miR-191, miR-29, and miR-133. CONCLUSIONS: The 9 miRNAs described in this study, are implicated in known pathogenetic mechanisms of AAA, such as atherosclerosis, vascular smooth muscle cell (VSMCs) phenotype switch and apoptosis, vascular inflammation, extracellular matrix (ECM) degradation, and lipid metabolism. Identifying disease-specific miRNAs, in combination with other clinical parameters, as indicators of AAA, is crucial for early diagnosis as well as follow-up of AAAs. For future research on miRNAs as AAA biomarkers, strict case and control group definitions, sample acquisition protocols, and miRNA expression profiling techniques are warranted.

Tumor-infiltrating lymphocytes, PD-L1, and MMR-deficiency combined characterization may identify subgroups of rectal cancer patients who would benefit from immunotherapy.

INTRODUCTION: Mismatch repair deficiency, immunological fertility, and PD-L1 expression status are key histopathological and molecular features defining tumor responsiveness to immunotherapy and, eventually, prognosis. These were investigated in a series of locally advanced rectal cancer patients treated with postoperative chemotherapy and radiotherapy. MATERIALS AND METHODS: Tumor-infiltrating lymphocyte (TIL) density was assessed in hematoxylin-eosin tissue sections. PD-L1 expression and the expression of MMR proteins (MLH1, PSM2, MSH2, and MSH6) were assessed with immunohistochemistry. Their association with histopathological variables (node involvement and tumor budding) and prognosis was assessed. RESULTS: The TIL-density was significantly higher in the invading tumor front and was inversely related to tumor budding and directly with better overall survival (OS) and distant metastasis-free survival (DMFS) (p = 0.02 and 0.02, respectively). Cancer cell PD-L1 expression was related to high TIL-density (p < 0.01) but not to prognosis, although its overexpression defined a trend for poorer OS in patients with high TIL-density. High PD-L1 expression by stroma infiltrating immune cells was linked with better OS and DMFS (p = 0.007 and 0.001, respectively. MMR deficiency was recorded in 26.2 % of cases, and this was linked with higher TIL-density, but not with prognosis. CONCLUSIONS: Dense intratumoral lymphocytic infiltration relates to a better prognosis in rectal cancer, although it is also linked with PD-L1 expression that may adversely modulate the anti-tumor effects of TILs. This latter subgroup of patients (high TIL-density/high cancer cell PD-L1 expression) could be an additional target for anti-PD-1/PD-L1 immunotherapy, along with the established subgroup of MMR deficient patients.

Eugenol Reduced ΜPO, CD45 and HMGB1 Expression and Attenuated the Expression of Leukocyte Infiltration Markers in the Intestinal Tissue in Biliopancreatic Duct Ligation-Induced Pancreatitis in Rats.

Background and Objectives: Inflammation and dysregulation in the intestinal barrier function in acute pancreatitis (AP) trigger pancreatic lesions, systemic inflammatory response, and multiple organ dysfunction. Eugenol, as the main component of clove (Syzygium aromaticum), is known for its antioxidant and anti-inflammatory properties. We studied the potentially beneficial effect of eugenol in a rodent model of biliopancreatic duct ligation-induced AP. Materials and Methods: Rats were randomly divided into three groups: Sham, AP, and AP + eugenol (15 mg/kg/day). Serum TNFα, IL-6, IL-18, and resistin levels, as well as IL-6, TNFα, MPO, HMGB1, and CD45 tissue expression, were determined at various timepoints after the induction of AP. Results: Eugenol attenuated hyperemia and inflammatory cell infiltration in the intestinal mucosal, submucosal, and muscular layers. IL-6 and resistin serum levels were significantly reduced in the AP + eugenol group, while serum TNFα and IL-18 levels remained unaffected overall. TNFα pancreatic and intestinal expression was attenuated by eugenol at 72 h, while IL-6 expression was affected only in the pancreas. MPO, CD45, and HMGB1 intestinal expression was significantly reduced in eugenol-treated rats. Conclusions: Eugenol managed to attenuate the inflammatory response in the intestine in duct ligation-induced AP in rats.

A qualitative study of nursing practitioners' experiences with COVID-19 patients dying alone in Greece.

Background: In Greece, there is still limited research on death in isolation due to COVID-19. This deserves attention because of the recent financial crisis, which profoundly impacted public health, and the high relevance of the Hippocratic tradition to the moral values of clinical practice. Methods: A prospective qualitative study using in-depth interviews with 15 frontline nursing practitioners working in a COVID-19 ward or intensive care unit (ICU) was conducted from July 2021 to December 2021. Results: The inability of family members to say a final goodbye before, during, or after death by performing proper mourning rituals is extremely inhuman and profoundly impacts the mental health status of patients, family members, and nursing practitioners. Patients and their family members strongly desire to see each other. Epidemiology, liability, and proper nursing performance emerged as reasons for the enforced strict visitation restrictions. Participants emphasized that visitations should be allowed on an individual basis and highlighted the need for the effective use of remote communication technology, which, however, does not substitute for in-person contact. Importantly, physicians allowed "clandestine" visits on an individual basis. Nursing practitioners had a strong empathic attitude toward both patients and their families, and a strong willingness to provide holistic care and pay respect to dead bodies. However, they also experienced moral distress. Witnessing heartbreaking scenes with patients and/or their families causes nursing practitioners to experience intense psychological distress, which affects their family life rather than nursing performance. Ultimately, there was a shift from a patient-centered care model to a population-centered care model. Furthermore, we identified a range of policy- and culture-related factors that exaggerate the negative consequences of dying alone of COVID-19. Conclusion: These results reinforce the existing literature on several fronts. However, we identified some nuances related to political decisions and, most importantly, convictions that are deeply rooted in Greek culture. These findings are of great importance in planning tailored interventions to mitigate the problem of interest and have implications for other similar national contexts.

Is It Safe to Stay at Home? Parents' Perceptions of Child Home Injuries during the COVID-19 Lockdown.

The COVID-19 pandemic and stay-at-home regulations have increased child home injuries. This study illustrates the type and frequency of child home injuries in Greece during the COVID-19 lockdown. Moreover, the survey reports the results on parents' proposals regarding child injuries at home during the COVID-19 quarantine. A community-based, cross-sectional, descriptive study was conducted from November to December 2021 in Greece. Parents were asked to voluntarily complete an anonymous questionnaire, designed for the needs of the research. A statistical analysis of the data was performed using the Kolmogorov-Smirnov and Shapiro-Wilk tests for a normal distribution, a chi-squared (χ2) test to compare percentages among different groups and a non-parametric Mann-Whitney U test to determine the differences in Likert scale variables between two groups. A total of 130 parents with at least one child were questioned through an online questionnaire survey. Of the parents, 39.3%, stated that the number of accidents in their home increased. The most frequent accidents were injuries (49.3%). Most of the accidents occurred inside the house (75.8%) and were observed among children aged 0-4 years. A high percentage of children's accidents was observed in rural/island areas or in the suburbs. Children who were with either their father or mother had one accident, and a higher number of accidents occurred when the children were with their grandparents, with the nanny or alone. For those parents who had difficulty supervising their child, child accidents increased compared to parents who had the ability to supervise. It was noticed that parents who knew how to provide a safe home stated that the number of accidents remained the same. Parents must organize a safer home. Authorities should educate parents on child injury prevention and provide them with financial facilities to provide a safer house.

Stem Cell Therapies for Gastrointestinal Anastomotic Healing: A Systematic Review and Meta-Analysis on Results from Animal Studies.

BACKGROUND: Despite considerable progress in surgical techniques, anastomotic leak (AL) is a common complication after gastrointestinal surgery. Stem cells are a promising therapy to improve healing and have been used in gastrointestinal anastomoses. In this study, we perform a systematic review and meta-analysis to evaluate the efficacy of stem cell therapies in preventing ALs among animal studies. METHODS: A systematic review of the literature was performed by searching PubMed, Web of Science, and the Cochrane Library. We considered all anastomoses of the gastrointestinal tract (excl. biliary) from the esophagus to the rectum. Outcomes included AL rates on postoperative day (POD) 7 and the latest time point reported. RESULTS: Fourteen studies were identified, evaluating stem cells in gastrointestinal anastomoses, of which 1 was on esophageal, 2 on gastric, 2 on small intestinal, and 9 on colorectal anastomoses. Meta-analysis did not show significant differences in AL rates on POD 7 (odds ratio [OR] 0.34, 95% confidence interval [CI]: 0.04-3.15, p = 0.248, I2 = 34.1%, 95% CI: 0-75.2%, Q = 6.07, df = 4, p = 0.194), but there was a nonsignificant trend for lower AL rates at the latest time point reported (OR 0.28, 95% CI: 0.08-1.01, p = 0.052, I2 = 34%, 95% CI: 0-70.8%, Q = 10.6, df = 7, p = 0.157). CONCLUSION: Stem cell therapy may be associated with lower AL rates in gastrointestinal anastomoses, though meta-analysis is severely inhibited by heterogeneous study design. More studies are needed to determine the therapeutic potential of stem cells.

A Comprehensive Review of the Cardiovascular Protective Properties of Silibinin/Silymarin: A New Kid on the Block.

Silibinin/silymarin has been used in herbal medicine for thousands of years and it is well-known for its hepato-protective properties. The present comprehensive literature review aimed to critically summarize the pharmacological properties of silymarin extract and its main ingredient silibinin in relation to classical cardiovascular risk factors (e.g., diabetes mellitus, etc.). We also assessed their potential protective and/or therapeutic application in cardiovascular diseases (CVDs), based on experimental and clinical studies. Pre-clinical studies including in vitro tests or animal models have predominantly implicated the following effects of silymarin and its constituents: (1) antioxidant, (2) hypolipidemic, (3) hypoglycemic, (4) anti-hypertensive and (5) cardioprotective. On the other hand, a direct amelioration of atherosclerosis and endothelial dysfunction after silymarin administration seems weak based on scarce data. In clinical trials, the most important findings are improved (1) glycemic and (2) lipid profiles in patients with type 2 diabetes mellitus and/or hyperlipidemia, while (3) the anti-hypertensive effects of silibinin/silymarin seem very modest. Finally, the changes in clinical endpoints are not robust enough to draw a firm conclusion. There are significant limitations in clinical trial design, including the great variety in doses and cohorts, the underlying conditions, the small sample sizes, the short duration and the absence of pharmacokinetic/pharmacodynamic tests prior to study commitment. More data from well-designed and high-quality pre-clinical and clinical studies are required to firmly establish the clinical efficacy of silibinin/silymarin and its possible therapeutic application in cardiovascular diseases.

Lipophagy-Related Protein Perilipin-3 and Resistance of Prostate Cancer to Radiation Therapy.

PURPOSE: Radiation therapy is a principal treatment modality for localized and locally advanced prostate cancer (PCa). Metabolic alterations, including lipid metabolism, may reduce treatment efficacy, resulting in tumor relapse and poor therapeutic outcome. In the current study, we investigated the role of the lipophagy-related protein perilipin-3 (PLIN3) and the lysosomal acid lipase (LAL) in PCa response to radiation therapy. METHODS AND MATERIALS: We explored the in vitro and xenograft (in NOD SCID and R2G2 mice) response to radiation of either PLIN3-depleted or LAL-depleted hormone-refractory (DU145, PC3) and hormone-responsive (22Rv1) PCa cell lines. Moreover, we evaluated the clinical role of PLIN3 and LAL protein expression in a series of PCa tissue specimens from patients treated with radical radiation therapy. RESULTS: In vitro and in vivo experiments showed reduced proliferation and strong radiosensitization of all studied PCa cell lines upon PLIN3 depletion. In vivo experiments demonstrated the significantly augmented radiation therapy efficacy upon PLIN3 depletion, resulting in extensive tissue necrosis. Overexpression of PLIN3 in tissue specimens was correlated with an increased MIB1 proliferation index, increased autophagy flux, reduced response to radiation therapy, and poor prognosis. The effect of LAL depletion on radiation therapy was of lesser importance. CONCLUSIONS: Assessment of PLIN3 expression may identify subgroups of patients with PCa who are less responsive to radiation therapy and at high risk of relapse after irradiation. Whether radiation therapy efficacy may be enhanced by concurrent autophagy or PLIN3 inhibition in this subgroup of patients demands clinical evaluation.

Postoperative hypofractionated-accelerated radiotherapy (HypoAR) for locally advanced rectal cancer.

BACKGROUND: despite the advances in preoperative hypofractionated-accelerated radiotherapy for patients with locally advanced rectal cancer, postoperative radiotherapy delivered with standard fractionation (46-50 Gy in 5 weeks) remains a standard adjuvant schedule. The role of hypofractionated-accelerated radiotherapy in a postoperative setting remains largely unexplored. METHODS: eighty-eight patients with rectal cancer infiltrating the rectal wall and/or having metastasis to the perirectal lymph nodes were treated with surgery followed by adjuvant chemotherapy and, subsequently, with hypofractionated-accelerated radiotherapy. Ten fractions of 3.4 Gy were delivered to the pelvis for 10 consecutive fractions, within 12 days. The follow-up of patients alive at the time of analysis ranges from 12-120 months (median 48). RESULTS: mild abdominal discomfort and diarrhoea were frequent, but medical medication was demanded in 14/88 (15.9%) of patients. The incidence of late toxicities was low; 4/88 (3.5%) patients complained for intermittent intestinal urgency. Locoregional recurrence occurred in 8/88 patients (9%). The 5-year locoregional relapse-free survival was achieved in 89.7% of patients, and this dropped to 84% in node-positive patients (P = 0.45). The 5-year disease-specific overall survival was 72.4%. Nodal involvement showed a trend to negatively affect prognosis (5-year overall survival 68.2 vs. 79.6%; P = 0.23). CONCLUSION: postoperative hypofractionated-accelerated radiotherapy has minimal early and late toxicity. The locoregional control and disease-specific survival rates are similar to the expected from conventional postoperative chemoradiotherapy. The 2.5-fold decrease of radiotherapy treatment time, reduction of waiting lists and the lower overall cost of radiotherapy are additional benefits associated with hypofractionated-accelerated radiotherapy.

Pro-inflammatory cytokines/chemokines, TNF-α, IL-6 and MCP-1, as biomarkers for the nephro- and pneumoprotective effect of silibinin after hepatic ischemia/reperfusion: Confirmation by immunohistochemistry and qRT-PCR.

The present study investigated the potential nephro- and pneumoprotective effect of silibinin (Si) after hepatic ischemia-reperfusion (I/R) injury, by measuring pro-inflammatory factors. Sixty-three rats were randomly assigned into three groups, as follows: (a) the sham group (n = 7 rats), subjected to opening and closing the abdomen; (b) the control group (n = 28 rats), subjected to 45-min hepatic ischemia followed by reperfusion; and (c) the silibinin group (n = 28), subjected to 45-min hepatic ischemia followed by intravenous administration of lyophilised SLB-HP-ß-CD before reperfusion. Control and silibinin groups were further subdivided into time-point groups, according to the duration of reperfusion. TNF-α, IL-6 and MCP-1 expressions were determined immunohistochemically and by qrT-PCR at each time-point. Kidney TNF-α expression was significantly lower at 180 and 240 min, while lung TNF-α expression was significantly lower at 240 min. Comparison between the control and Si group at the same time-points showed very strong evidence of difference at 240 min, with the levels of IL-6 shifting towards lower values in the Si group. Finally, we found a high MCP-1 expression after 120 min. We conclude that hepatic I/R injury remotely increases pro-inflammatory mediators in the kidney and lung, whereas silibinin shows a time-dependent nephro- and pneumoprotective effect.

Career barriers for women in surgery.

BACKGROUND: Despite the increasing numbers of female medical students, surgery remains male-dominated. PURPOSE: To highlight the principal career obstacles experienced by aspiring female surgeons. METHODS: A narrative review of literature on the position and career barriers of female surgeons has been conducted, using the MEDLINE and EMBASE databases. MAIN FINDINGS: Implicit and even explicit biases against female surgeons remain prevalent, negatively impacting their training performance and overall professional trajectory. Female surgeons are globally underrepresented in leadership positions and senior academic rankings, especially that of a full professor. They feel hampered by lack of effective mentorship, whose value for a successful career has been acknowledged by all medical students, surgeons and surgical leaders. Their work-life imbalance is sometimes expressed as lower likelihood than their male contemporaries of getting married or having children and may be attributed to their conventional association with the role of caretaker, their personal desire to accommodate occupational and family duties and the inadequate implementation of parental leave and childcare policies. Female surgeons' "infertility" may be further explained by direct and indirect pregnancy-related difficulties. Female surgeons are also financially undercompensated compared to their male contemporaries. Finally, specialty-specific challenges should not be overlooked. CONCLUSIONS: While encouraging steps have been made, women in surgery feel still hindered by various obstacles. The qualitative, interview-based nature of current literature requires more meticulous studies on these barriers with a more quantitative and objective approach. Attenuation of gender imbalance in surgical specialties requires further changes in mentality and more targeted modifications in relevant policies.

Effects of the Antioxidant Quercetin in an Experimental Model of Ulcerative Colitis in Mice.

Background and Objectives: Quercetin, a member of the flavanol family found in many fruits, vegetables, leaves and grains has been found to have a wide range of biological effects on human physiology. The aim of this study was to investigate the effects of quercetin, when administered orally in the form of the water-soluble inclusion complex with hydroxypropyl-b-cyclodextrin (Que-HP-ß-CD), in an experimental model of ulcerative colitis in mice. Materials and Methods: Animals received either Dextran Sodium Sulphate (DSS), to induce colitis, + Que-HP-ß-CD (Group A), DSS alone (Group B) or no intervention (control, Group C) for 7 days. All animals were weighed daily, and evaluation of colitis was performed using the Disease Activity Index (DAI). On day 7 a blood sample was taken from all animals, they were then euthanised, the large intestine was measured, and histological and immunochemical analyses were performed. Results: The DAI demonstrated an increase over time for the groups receiving DSS (Groups A and B) compared with the control group (Group C), with a significant degree of protection being observed in the group that also received quercetin (Group A): The DAI over time slope for Group B was higher than that for Group A by 0.26 points/day (95% Cl 0.20−0.33, p < 0.01). Weight calculations and immunohistochemistry results validated the DAI findings. Conclusions: In conclusion, the administration of quercetin in an ulcerative colitis model in mice presents a therapeutic/prophylactic potential that warrants further investigation.