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Objective: This cross-sectional, case-control study aimed to explore the psychodynamic characteristics that influenced adolescents' mental health during the COVID-19 pandemic. Methods: Personality structure impairments, psychodynamic conflicts, defense styles, and mental health issues were examined using the OPD-Structure- and Conflict-Questionnaires, the Defense Style Questionnaire, and the Patient Health Questionnaire in adolescents before (n = 288) and after (n = 451) the COVID-19 pandemic in Germany. Results: Adolescents with mental health issues exhibited greater impairments in personality structure, more immature defense styles, and higher levels of psychodynamic conflicts both before and after the pandemic onset. Comparisons between pre-pandemic and pandemic samples indicated a lower level of the conflict of taking care of oneself versus being cared for in passive mode among adolescents during the pandemic. In-depth analysis of adolescents with mental health issues from the pandemic group revealed significant associations between personality structure impairments and a maladaptive defense style with somatoform, depressive, anxiety, eating, and alcohol use disorders. Conclusion: The findings provide clinically relevant insights into the psychodynamic factors that contributed to the psychological vulnerability of adolescents during the COVID-19 pandemic. These insights can guide the development of targeted psychodynamic interventions to support adolescents' mental health in similar future crises. [ABSTRACT FROM AUTHOR]

Women's empowerment and health literacy are essential for fostering community well-being. Empowering women through education and diverse training plays a crucial role in ensuring their prosperity and overall health. This study investigates the satisfaction and experiences of underprivileged rural mothers participating in a functional literacy education program in the Kailali district, Nepal. We assess participants' perceptions of program effectiveness, examining training content, facilities, and trainers while exploring menstrual hygiene practices and maternal health awareness. Through convenience sampling, 141 underprivileged women from five rural villages near Tikapur were selected from literacy centers run by Mahima Group. Utilizing structured questionnaires and statistical analyses, including descriptive analyses, Spearman's rho correlation, and Pearson's chi-square test, we found that 65.2% of participants expressed high satisfaction levels. Moreover, 96.5% found the program highly effective, with 97.9% reporting improved literacy skills and 96.5% demonstrating increased awareness of menstrual hygiene practices. Additionally, 97.2% agreed that the program enhanced maternal and child health knowledge. Significant correlations were observed among the training course, facilities, trainers, and overall training perception. In line with this, significant associations were found between age groups (p = 0.003) and geographical areas (p = 0.023) with satisfaction levels with the literacy program. These results underscore the satisfaction of participants within the literacy program and its impact on their lives, and advocates for its broader implementation to empower marginalized communities for sustainable development. [ABSTRACT FROM AUTHOR]

(1) Background: The surgical procedure to create an arteriovenous fistula (AVF) can be performed in either an ambulatory or in-patient hospital setting, depending on the case's complexity, the anesthesia type used, and the patient's comorbidities. The main scope of this study is to assess the cost-effectiveness and clinical implications of surgically creating an AVF in both ambulatory and in-hospital settings. (2) Methods: We conducted a retrospective observational study, in which we initially enrolled all patients with end-stage kidney disease (ESKD) admitted to the Vascular Surgery Department, Emergency County Hospital of Targu Mures, Romania, to surgically create an AVF for dialysis, between January 2020 and December 2022. The primary endpoint of this study is to assess the cost-effectiveness of surgically creating an AVF in an ambulatory vs. in-hospital setting by comparing the costs required for the two types of admissions. Further, the 116 patients enrolled in this study were divided into two groups based on their preference for hospitalization: out-patients and in-patients. (3) Results: Regarding in-patient comorbidities, there was a higher prevalence of peripheral artery disease (PAD) (p = 0.006), malignancy (p = 0.020), and previous myocardial infarction (p = 0.012). In addition, active smoking (p = 0.006) and obesity (p = 0.018) were more frequent among these patients. Regarding the laboratory data, the in-patients had lower levels of white blood cells (WBC) (p = 0.004), neutrophils count (p = 0.025), lymphocytes (p = 0.034), and monocytes (p = 0.032), but there were no differences between the two groups regarding the systemic inflammatory biomarkers or the AVF type. Additionally, we did not register any difference regarding the outcomes: local complications (p = 0.588), maturation failure (p = 0.267), and primary patency (p = 0.834). In our subsequent analysis, we discovered no significant difference between the hospitalization type chosen by patients regarding AVF primary patency failure (p = 0.195). We found no significant association between the hospitalization type and the recorded outcomes (all ps > 0.05) in both multivariate linear regression and Cox proportional hazard analysis. (4) Conclusions: In conclusion, there are no significant differences in the clinical implications, short-term and long-term complications of AVF for out-patient and in-patient admissions. Additionally, we found no variation in the costs associated with laboratory tests and surgical supplies for an AVF creation. Therefore, it is safe to perform ambulatory AVFs, which can reduce the risk of hospital-acquired infections and provide greater comfort to the patient. [ABSTRACT FROM AUTHOR]

Background: Healthcare professionals appear to play a key role in shaping pregnant women's views and attitudes towards lifestyle issues, such as exercise. The aim of this study is to investigate the views and beliefs of Greek midwives and obstetricians regarding exercise during pregnancy. Methods: This is a cross-sectional study conducted during the period of January 2022–March 2023. For this study, 237 Greek midwives and obstetricians employed in healthcare settings in Attica, Greece completed an anonymous and self-report questionnaire. Four different/independent models of multivariate analyses of variance were conducted. Results: The vast majority of these healthcare professionals (88.6%) believed that exercise during pregnancy is generally beneficial. According to the multivariate analyses, healthcare professionals with postgraduate/doctoral studies were more likely to believe that (a) exercise is generally beneficial (p = 0.03), (b) pregnant women should be informed about it (p = 0.028), (c) informing pregnant women is necessary/useful (p = 0.023), and (d) pregnant women showed interest in it (p = 0.034). Also, freelance midwives were more likely to believe that pregnant women should be informed about exercise (p = 0.006), and that they showed interest in it (p = 0.034). In addition, (a) freelance midwives (p = 0.050), and those who had experience in antenatal counselling (p = 0.037), as well as (b) obstetricians who were largely experienced in monitoring normal pregnancies (p = 0.001), were less likely to associate exercise during pregnancy with the occurrence of placental abruption. Conclusion: Alongside healthcare professionals' educational level, their professional setting and professional experience emerge as key factors and need to be considered when designing innovative interventions to support exercise during pregnancy. [ABSTRACT FROM AUTHOR]

Background: In the wake of the coronavirus disease 19 (COVID-19) pandemic, affecting healthcare systems globally, urgent research is needed to understand its potential repercussions on the diagnosis and management of cardiovascular disorders. This emphasises the importance of detecting coronary artery anomalies (CAAs), rare conditions that can range from benign to potentially life-threatening manifestations. We aimed to retrospectively assess the impact of the COVID-19 pandemic on the detection of various coronary anomalies using Coronary Computed Tomography Angiography (CCTA) within a regional tertiary cardiology unit in north-eastern Romania, focusing on perceived occurrence in the population under study, types, and related demographic and clinical factors. Methods: We analysed CCTA scans and investigated the trends in CAA detection among cardiology patients over a decade. We compared pre-COVID-19 and pandemic-era data to assess the impact of healthcare utilisation, patient behaviour, and diagnostic approaches on anomaly detection. Results: Our analysis revealed a higher detection rate of CAAs during the pandemic (3.9% versus 2.2%), possibly highlighting differences in patient clinical profile and addressability changes presentation compared to the previous period. Origination and course anomalies, often linked to severe symptoms, were significantly higher pre-COVID-19 (64.1% versus 51.3%). Conversely, intrinsic CAAs, typically asymptomatic or manifesting later in life, notably increased during the pandemic (49.0% versus 61.4%; p = 0.020). Conclusions: Our study underscores a significant rise in CAA detection during the COVID-19 era, potentially linked to changes in cardiovascular and respiratory clinical patterns, with advanced imaging modalities like CCTA offering accuracy in identification. [ABSTRACT FROM AUTHOR]

Background: Pediatric colorectal specialists care for patients with a variety of defecation disorders. Anorectal (AR) manometry testing is a valuable tool in the diagnosis and management of these children. This paper provides a summary of AR manometry techniques and applications as well as a review of AR manometry findings in pediatric patients with severe defecation disorders referred to a pediatric colorectal center. This is the first study describing multi-year experience using a portable AR manometry device in pediatric patients. Methods: An electronic medical record review was performed (1/2018 to 12/2023) of pediatric patients with defecation disorders who had AR manometry testing. Demographics, diagnostic findings, and outcomes are described. Key Results: A total of 297 unique patients (56.9% male, n = 169) had AR manometry testing. Of these, 72% (n = 188) had dyssynergic defecation patterns, of which 67.6% (n = 127) had fecal soiling prior to treatment. Pelvic rehabilitation (PR) was administered to 35.4% (n = 105) of all patients. A total of 79.5% (n = 58) of the 73 patients that had fecal soiling at initial presentation and completed PR with physical therapy and a bowel management program were continent after therapy. AR manometry was well tolerated, with no major complications. Conclusions: AR manometry is a simple test that can help guide the management of pediatric colorectal surgical patients with defecation disorders. As a secondary finding, PR is a useful treatment for patients with dyssynergic stooling. [ABSTRACT FROM AUTHOR]

Background: Parents of children suffering from congenital heart disease experience high levels of stress and negative emotions. Therefore, recognition of parents' emotional states and their ways of coping with it is becoming more and more important. Methods: The study group consisted of 154 parents of newborns and infants with cyanotic congenital heart disease, before and after cardiac surgery (partial or full). To assess parental negative emotions, the level of stress, and strategies of coping with it, standardized questionnaires, such as HADS-M, PSS-10, and COPE, were used. Results: Stress levels in parents were high and associated with negative emotions (anxiety, depression, irritability), as well as the choice of non-constructive coping strategies, which was observed especially in younger parents. Conclusions: Assessing parents' stress levels and ways of coping with stress can improve family functioning and provide better development conditions for the child. [ABSTRACT FROM AUTHOR]

Background: Palliative care (PC) focuses on relieving pain and difficult symptoms rather than treating disease or delaying its progress. Palliative care views death as a natural process and allows patients to live the last phase of their existence in the best possible way, encouraging them to express their opinions and wishes for a good death. Interventions are advocated to control symptoms and distress and promote wellbeing and social functioning. A multidisciplinary approach to support patients receiving palliative care is encouraged. Objective: The aims of this study were to investigate the facilitators and barriers to PC in people with kidney disease from a nursing perspective and to explore predictive factors associated with nurse-perceived facilitators and barriers to PC in people with kidney disease. Design: This study is a survey that adopted a questionnaire created in 2021 with Delphi methology, which included 73 statements divided into 37 facilitators and 36 barriers to PC in patients with kidney disease, to be scored using a Likert scale. Participants and Measurements: Participants were obtained through the membership database of the European Dialysis and Transplant Nurses Association/European Renal Care Association (EDTNA/ERCA) of 2020. Inclusion criteria included being registered as a nurse, an EDTNA/ERCA member and understanding of the English language. The questionnaire was sent via email. Results: Three profiles of respondents were found: the first group was characterized by the highest agreement percentages of facilitators and with an average value of 53.7% in barriers; the second was characterized by a lower endorsement of facilitators and similar agreement to the first group for barriers; the third group had a high probability (>80%) of items endorsing both barriers and facilitators. Predictive variables were significantly associated with "Years in nephrology" and "macro geographic area". Conclusions: This study demonstrates variation in PC practice across Europe. Some professionals identified fewer barriers to PC and appeared more confident when dealing with difficult situations in a patient's care pathway, while others identified more barriers as obstacles to the implementation of adequate treatment. The number of years of nephrology experience and the geographical area of origin predicted how nurses would respond. This study was not registered. [ABSTRACT FROM AUTHOR]

Introduction: Obstructive sleep apnea syndrome (OSAS) is a disorder characterized by partial or total airway obstruction during sleep. Studies have shown variability in the level of knowledge and awareness about OSAS among pediatricians. The management of childhood obstructive sleep apnea syndrome (OSAS) depends on the severity of the disease, the presence of comorbidities, and the child's age. The American Pediatric Academy recommends a multidisciplinary approach involving a pediatrician, a sleep specialist, and an otolaryngologist to provide comprehensive care for children with OSAS. The aim of this cross-sectional study is to evaluate the level of knowledge among pediatricians in Italy regarding the diagnosis of pediatric OSAS. Material and Methods: An anonymized survey was conducted among Italian pediatricians. The survey was administered electronically using Google Forms, and a total of 350 pediatricians were invited to participate. Out of the 350 invitations, 299 pediatricians responded to the survey. The statistical analysis performed consisted of descriptive analysis. The study included 297 pediatricians. Results: Pediatricians demonstrated proficiency in identifying common nocturnal and day symptoms of OSAS. A majority (68.9%) considered the oral and otorhinolaryngologist areas during checkups. Approximately 70.6% took patient weight into account, and 62.8% were aware of the regional diagnostic-therapeutic-assistance pathway. Conclusions: According to the results of this manuscript, there is evidence of a good level of knowledge about OSAS, but disseminating more information about OSAS and all the health issues associated with this syndrome is suggested. This study also has limitations caused by the complexity of the pathology. [ABSTRACT FROM AUTHOR]

As turnover intention is a strong determinant of actual turnover behavior, scholars should identify the determinants of turnover intention. In this context, the aim of this study was to assess the effect of quiet quitting on nurses' turnover intentions. Additionally, this study examined the impact of several demographic and job characteristics on turnover intention. A cross-sectional study with 629 nurses in Greece was conducted. The data were collected in September 2023. Quiet quitting was measured with the "Quiet Quitting" scale. In this study, 60.9% of nurses were considered quiet quitters, while 40.9% experienced high levels of turnover intention. Multivariable regression analysis showed that higher levels of quiet quitting increased turnover intention. Moreover, this study found that turnover intention was higher among females, shift workers, nurses in the private sector, and those who considered their workplace understaffed. Also, clinical experience was associated positively with turnover intention. Since quiet quitting affects turnover intention, organizations, policymakers, and managers should address this issue to improve nurses' intentions to stay at their jobs. [ABSTRACT FROM AUTHOR]

Second-hand smoke (SHS) has adverse effects for pregnant women and foetuses. This controlled and randomized clinical trial evaluated the efficacy of a comic booklet intervention in promoting SHS avoidance among pregnant women and appropriate smoking behaviours among their male partners. We allocated 140 couples to the experimental group (EG), who received the comic booklet and a reminder sticker, and 146 couples to the control group (CG), who received usual care. The primary outcomes were women's self-reported SHS exposure and their male partners' smoking behaviours. Secondary outcomes included knowledge and awareness of SHS. Independent t-tests revealed that three months post-intervention, more male partners in the EG had appropriate self-reported smoking behaviours with a small effect size (Cohen's d = 0.35, 95% CI [0.08, 0.62], p-value = 0.01). Significantly more pregnant women in the EG recognised their partners' appropriate smoking behaviours with a nearly middle effect size (Cohen's d = 0.43, 95% CI [0.16, 0.70], p-value ≤ 0.01). Cues to action showed a significant difference between groups with a small effect size (Cohen's d = 0.36, 95% CI [0.09, 0.63], p-value = 0.01), as evaluated by male partners. These findings suggest that the comic booklet intervention might be effective against SHS exposure by providing several cues to action through knowledge and awareness of SHS. [ABSTRACT FROM AUTHOR]

Existing research concerning the effects of the sitting birth position during the second stage of labour on maternal and neonatal outcomes remains controversial, and there is a lack of studies to explore its effect on the childbirth experience. The objective of this study is to explore whether the sitting birth position would influence maternal and neonatal outcomes, as well as the childbirth experience. The prospective cohort design was conducted in the study from February to June 2023, a total of 222 women (including primiparous women and multiparous women) were enrolled in our study, and they were divided into the sitting position cohort (n = 106) or the lithotomy position cohort (n = 116). The pre-designed questionnaire and Childbirth Experience Questionnaire (CEQ) were used for data collection during hospitalisation. Chi-square, Fisher's exact test, t-tests, or the Mann–Whitney U test were utilised to assess differences between groups. Multivariate linear regression and logistic regression were employed to control possible confounders. The study found that primiparous women in the sitting position cohort had a shorter duration of the second stage of labour, higher spontaneous vaginal birth rates, lower episiotomy rates, and a better childbirth experience (p < 0.01). After adjusting for confounding factors through multiple linear and logistic regression analyses, the results remained consistent with those reported above. No neonate in each cohort had Apgar scores at 1 min and 5 min postpartum less than 7 or a Cord artery pH less than 7.00, regardless of parity. Based on the findings, we recommend that women could take the sitting birth position into account when giving birth for a positive childbirth experience, especially for primiparous women. The study could also serve as a reference for healthcare providers in the management of childbirth positions and the development of high-quality maternal care. [ABSTRACT FROM AUTHOR]

Chronic low back pain (CLBP) is common in primary care, causing disability and economic burden globally. We aimed to compare socio-demographic, health, lifestyle, and psychological factors in people with and without CLBP and correlate them with clinical outcomes in people with CLBP. A total of 253 volunteers with and 116 without CLBP provided sociodemographic information, daily habits, medical history, subjective sleep complaints (Penn State Sleep Questionnaire), low back pain intensity, and disability (Quebec Back Pain Disability Scale), as well as the Zung Self-Rating Scale for self-assessment of depression and Self-Rating Anxiety Scale. CLBP diagnosis was linked with female gender and older age, as well as a higher level of sleep complaints such as sleepiness, OSA and insomnia symptoms, and a higher prevalence of moderate to severe depressive symptoms. The combination of moderate to severe depressive symptoms with obstructive sleep apnea or insomnia symptoms was the most important predictive factor for functional disability in CBLP patients (OR 13.686, 95% CI 4.581–40.885; p < 0.001). In conclusion, depressive symptoms and subjective sleep complaints appear to relate to greater CLBP intensity and/or CLBP-related disability in people with CLBP. A holistic approach is crucial for treating chronic CLBP patients, including psychological and sleep issue assessment and management, to improve their quality of life. [ABSTRACT FROM AUTHOR]

Poor baseline reaction time, as measured via the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT), has been associated with anterior cruciate ligament (ACL) injury risk in adult athletes. Our study sought to determine whether the reaction time and impulse control ImPACT test domains differed between ACL injured and uninjured pediatric athletes. A total of 140 high-school aged athletes comprising 70 athletes who went on to sustain an ACL injury between 2012 and 2018 and 70 age- and sex-matched uninjured controls were included in the study. Mean reaction times were similar for the injured (0.67 s) and uninjured (0.66 s) athletes (p = 0.432), and the impulse control scores were also similar for those with (5.67) and without (6.07) an ACL injury (p = 0.611). Therefore, neurocognitive risk factors for sustaining an ACL injury in adults cannot necessarily be extrapolated to adolescent athletes. Further research is needed to understand why differences exist between injury risk in youth and adult athletes. [ABSTRACT FROM AUTHOR]

Shear wave elastography (SWE) is a non-invasive imaging technique used to quantify the elasticity/stiffness of any tissue. There are normative SWE studies on tonsils in healthy children in the literature. The purpose of this study is to analyze the palatine tonsils in children with acute tonsillitis using ultrasound and SWE. In this prospective study, pediatric patients aged 4–18 years diagnosed with acute tonsillitis and healthy children were included. Those with antibiotic use, chronic tonsillitis, adenoid hypertrophy, and having chronic disease, immunodeficiency, and autoimmune disease, or any rheumatological disease were excluded. The volume and elasticity of palatine tonsil were measured via ultrasound and SWE. The study included 81 (46 female, 35 male) acute tonsillitis patients, and 63 (38 female, 25 male) healthy children between the ages of 4 and 18. Elasticity (kPa) values of tonsils were found significantly higher in the tonsillitis group (SWE-R: 25.39 ± 4.64, SWE-L: 25.01 ± 4.17) compared to the normal group (SWE-R: 9.71 ± 2.37, SWE-L: 9.39 ± 2.19) (p < 0.001). In the tonsillitis group, a significant positive correlation was found between tonsil volume and elasticity (r: 0.774, p: 0.002). In conclusion, in pediatric patients with acute tonsillitis, higher kPa values were obtained with SWE in the palatine tonsils. [ABSTRACT FROM AUTHOR]

There has been no research on the trends in early sexual initiation associated with socio-environmental factors in Korea. This study aimed to examine the trends of early sexual initiation with various socio-environmental factors among adolescents. The Korea Youth Risk Behavior Web-based Survey data were used, and two pooled datasets extracted from the 2006–2008 and 2014–2016 waves were conducted and compared. In this study, early sexual initiation was defined as sexual intercourse at the age of 13 years or younger. The weighted percentage and 95% confidence interval reporting early sexual initiation were estimated, and multiple logistic regression was performed for each subgroup of socio-environmental variables with the 2006–2008 pooled data as a reference. Regardless of sex, the weighted percentage of adolescents with sexual experience who reported early sexual initiation increased in 2014–2016 with statistical significance in most cases. Moreover, the possibility of experiencing early sexual intercourse overtime was more prominent among girls than boys. While indifference to adolescent sexual behavior continues, more adolescents become involved in early sexual initiation. Socio-environmental considerations, such as the establishment of safe environments for adolescents' sexual activity, along with systematized monitoring mechanisms, should be administered. [ABSTRACT FROM AUTHOR]

Simple Summary: The number of pigmented moles is the most important risk factor for melanoma. This "real world" study conducted in 25 Australian childcare centers is the first to show it is possible to prevent a significant proportion of pigmented moles in young Caucasian children by dressing them in UPF 30-50+ clothing that covers at least half their body on a daily basis. Regularly wearing this clothing for 3.5 years was sufficient to prevent almost one-quarter of the pigmented moles that young children developed on their skin. This should, by implication, reduce their risk of developing melanoma in the future. Primary health care providers should stress the importance of garment coverage when recommending sun protection for children and should lobby for all sun-protective clothing standards to assess and report garment coverage, in addition to the transmission of ultraviolet radiation through the fabric (reported as UPF), on clothing labels and packaging for children's clothing, including school uniforms. Numerous pigmented moles are associated with sun exposure and melanomarisk. This cluster randomized controlled trial aimed to determine if sun-protective clothing could prevent a significant proportion of the moles developing in young children (ACTRN12617000621314; Australian New Zealand Clinical Trials Registry. Twenty-five childcare centers in Townsville (19.25° S), Australia, were matched on shade provision and socioeconomic status. One center from each pair was randomized to the intervention arm and the other to the control arm. Children at 13 intervention centers wore study garments and legionnaire hats at childcare and received sun-protective swimwear and hats for home use, while children at the 12 control centers did not. The 1–35-month-old children (334 intervention; 210 control) were examined for moles at baseline (1999–2002) and were re-examined annually for up to 4 years. Both groups were similar at baseline. Children at intervention centers acquired fewer new moles overall (median 12.5 versus 16, p = 0.02; 0.46 versus 0.68 moles/month, p = 0.001) and fewer new moles on clothing-protected skin (6 vs. 8; p = 0.021 adjusted for confounding and cluster sampling) than controls. Intervention children had 24.3% fewer new moles overall (26.5 versus 35) and 31.6% (13 versus 19) fewer moles on clothing-protected skin than controls after 3.5 years. Sunlight's influence on nevogenesis is mitigated when children regularly wear UPF 30-50+ clothing covering half their body, implying that increased clothing cover reduces melanoma risk. Sun-protective clothing standards should mandate reporting of the percentage of garment coverage for childrenswear. [ABSTRACT FROM AUTHOR]

Simple Summary: There is a wide range of choices for combining PD-1/PD-L1 checkpoint inhibitors with other measures in treating tumors, but certain choices of regimens are still controversial. We aimed to investigate the therapeutic efficacy and potential side effects of combination therapy with anti-PD-1/PD-L1 compared to anti-PD-1/PD-L1 monotherapy. Meanwhile, we also explored whether different combination strategies would yield consistent efficacy across different types of tumors. Our study can provide important and useful information for clinicians and encourage the enrollment of more clinical trials for anti-PD-1/PD-L1 combination therapy. Objective: In recent years, the anti-programmed cell death protein-1 and its ligand (PD-1/PD-L1) or combination therapies have been recommended as an alternative emerging choice of treatment for oncology patients. However, the efficacy and adverse events of different combination strategies for the treatment of tumors remain controversial. Methods: PubMed, Embase, Cochrane Library, the American Society of Clinical Oncology (ASCO), and the European Society of Medicine Oncology (ESMO) were searched from database inception until 16 February 2022. The endpoints of objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were analyzed from different treatment schemes and tumor types. The protocol was registered in PROSPERO (CRD42022328927). Results: This meta-analysis included forty-eight eligible studies. Combination therapy has improved ORR (RR = 1.40, p < 0.001), DCR (RR = 1.22, p < 0.001), and PFS (the median survival ratio (MSR) was estimated to be 1.475 p < 0.001) compared to anti-PD-1/PD-L1 but had no significant benefit on OS (MSR was estimated to be 1.086 p = 0.117). Besides, combination treatment strategies are more toxic in any grade AEs (RR = 1.13, p < 0.001) and grade 3–5 AEs (RR = 1.81, p < 0.001). Conclusions: Treatment with PD-1/PD-L1 inhibitors in combination with other antitumor therapies improve patients' ORR, DCR, and PFS compared to anti-PD-1/PD-L1. However, it is regrettable that there is no benefit to OS and an increased risk of AEs in combinatorial therapies. [ABSTRACT FROM AUTHOR]

The present study was designed to examine the direct and indirect contributions of parenting daily hassles and approaches to children's externalizing and internalizing behavior problems during the COVID-19 pandemic. The sample for this study was 338 preschool children (53.6% girls, Mage = 56.33 months, SD = 15.14) and their parents in Turkey. Parents reported their daily hassles, parenting approaches, and children's behavior problems. Findings from the structural equation model showed that higher levels of parenting daily hassles predicted higher levels of externalizing and internalizing behavior problems. In addition, we found an indirect effect of daily hassles on children's internalizing behaviors via positive parenting. Further, there was an indirect path from parenting daily hassles to children's externalizing behaviors through the negative parenting approach. Results are discussed in the context of the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Simple Summary: We have recently reported that the cytosolic C-terminal domain (CTD) of the tumour suppressor PTCH1, the Hedgehog proteins receptor, interacts with the autophagy-related protein ATG101 and impairs autophagic flux. In this study, we identified the interaction region and found that it is absent in a subset of colorectal, stomach and endometrial cancers. We demonstrated that truncation mutants lack the ability to constraint autophagy, resulting in a proliferative advantage and reduced sensitivity to autophagy inducers or glycolysis inhibitors in cell lines harbouring endogenous PTCH1 CTD mutations compared to isogenic cells expressing wild-type PTCH1. In summary, this study highlights the importance of the PTCH1-ATG101 interaction in the regulation of basal and stimulated autophagy and the metabolic flexibility in cancer cells. The Hedgehog receptor, Patched1 (PTCH1), is a well-known tumour suppressor. While the tumour suppressor's activity is mostly ascribed to its function as a repressor of the canonical Smoothened/Gli pathway, its C-terminal domain (CTD) was reported to have additional non-canonical functions. One of them is the reduction of autophagic flux through direct interaction with the Unc-51, like the autophagy activating kinase (ULK) complex subunit autophagy-related protein-101 (ATG101). With the aim of investigating whether this function of PTCH1 is important in cancer cell fitness, we first identified frameshift mutations in the CTD of PTCH1 in cancer databases. We demonstrated that those mutations disrupt PTCH1 interaction with ATG101 and increase autophagic flux. Using deletion mutants of the PTCH1 CTD in co-immunoprecipitation studies, we established that the 1309–1447 region is necessary and sufficient for interaction with ATG101. We next showed that the three most common PTCH1 CTD mutations in endometrial, stomach and colon adenocarcinomas that cause frameshifts at S1203, R1308 and Y1316 lack the ability to interact with ATG101 and limit autophagic flux, determined by bafilomycin A1-sensitive accumulation of the autophagy markers LC3BII and p62. We next engineered PTCH1 indel mutations at S1223 by CRISPR/Cas9 in SW620 colon cancer cells. Comparison of two independent clones harbouring PTCH1 S1223fs mutations to their isogenic parental cell lines expressing wild-type PTCH1 showed a significant increase in basal and rapamycin-stimulated autophagic flux, as predicted by loss of ATG101 interaction. Furthermore, the PTCH1 CTD mutant cells displayed increased proliferation in the presence of rapamycin and reduced sensitivity to glycolysis inhibitors. Our findings suggest that loss of the PTCH1-ATG101 interaction by mutations in the CTD of PTCH1 in cancer might confer a selective advantage by stimulating autophagy and facilitating adaptation to nutrient deprivation conditions. [ABSTRACT FROM AUTHOR]

Background: A prompt and accurate diagnosis of developmental defects of enamel (DDE) is mandatory for proper treatment management. This cross-sectional survey, designed and carried out using anonymous self-administered questionnaires, aimed to assess dental and dental hygiene students' knowledge and their capability to identify different enamel development defects. Methods: The questionnaire consisted of twenty-eight closed-ended questions. Two different samples of undergraduate students were selected and enrolled: a group of dental hygiene (GDH) students and a group of dental (GD) students. A multivariate logistic regression was performed by adopting the correct answers as explanatory variables to assess the difference between the two groups. Results: Overall, 301 completed questionnaires were analyzed: 157 from the GDH and 144 from the GD. The dental student group showed better knowledge than the GDH of enamel hypomineralization and hypoplasia (p = 0.03 for both). A quarter (25.25%) of the total sample correctly identified the period of development of dental fluorosis with a statistically significant difference between the groups (p < 0.01). Amelogenesis imperfecta (AI) was identified as a genetic disease by 64.45% of the sample, with a better performance from the GD (p = 0.01), while no statistical differences were found between the groups regarding molar incisor hypomineralization. Multivariate analysis showed that AI (OR = 0.40, [0.23;0.69], p < 0.01) and caries lesion (OR = 0.58, [0.34;0.94], p = 0.03) were better recognized by the GD. Conclusions: Disparities exist in the knowledge and management of DDE among dental and dental hygiene students in Italy; however, significant knowledge gaps were found in both groups. Education on the diagnosis and treatment of DDE during the training for dental and dental hygiene students needs to be strongly implemented. [ABSTRACT FROM AUTHOR]

Simple Summary: Resistance to standard therapies impose a huge challenge on the treatment for glioblastoma multiforme (GBM), which is often considered as a cell intrinsic property of either GBM or, more significantly, of GBM stem-like cells. Tumor-associated macrophages and microglia (TAMs) take up the majority of the immune population in the tumor microenvironment of GBM and potentially participating in modulating therapy responses. However, little is known about the mechanisms underlying the effect of TAMs on temozolomide (TMZ) induced chemoresistance. Members of the metzincin superfamily such as Matrix Metalloproteases (MMPs) and A Disintegrin and Metalloprotease (ADAM) proteases are important participants in the process of intercellular communications in the tumor microenvironment. Herein, we revealed a novel concept of an intra-tumoral ADAM8 mediated malignant positive feedback loop constituted by the intimate interaction of tumor associated macrophages (TAMs) and GBM cells under TMZ treatment. These findings provide a convincing example and further support the notion that the tumor microenvironment, in addition to GBM cells and GBM stem-like cells, should be considered as an essential modulator of therapy in GBM. In conclusion, our study provides a rational basis for TAM sparing ADAM8-targeting in GBM to optimize standard chemotherapy. Standard chemotherapy of Glioblastoma multiforme (GBM) using temozolomide (TMZ) frequently fails due to acquired chemoresistance. Tumor-associated macrophages and microglia (TAMs) as major immune cell population in the tumor microenvironment are potential modulators of TMZ response. However; little is known about how TAMs participate in TMZ induced chemoresistance. Members of the metzincin superfamily such as Matrix Metalloproteases (MMPs) and A Disintegrin and Metalloprotease (ADAM) proteases are important mediators of cellular communication in the tumor microenvironment. A qPCR screening was performed to identify potential targets within the ADAM and MMP family members in GBM cells. In co-culture with macrophages ADAM8 was the only signature gene up-regulated in GBM cells induced by macrophages under TMZ treatment. The relationship between ADAM8 expression and TAM infiltration in GBM was determined in a patient cohort by qPCR; IF; and IHC staining and TCGA data analysis. Moreover; RNA-seq was carried out to identify the potential targets regulated by ADAM8. CCL2 expression levels were determined by qPCR; Western blot; IF; and ELISA. Utilizing qPCR; IF; and IHC staining; we observed a positive relationship between ADAM8 expression and TAMs infiltration level in GBM patient tissues. Furthermore; ADAM8 induced TAMs recruitment in vitro and in vivo. Mechanistically; we revealed that ADAM8 activated HB-EGF/EGFR signaling and subsequently up-regulated production of CCL2 in GBM cells in the presence of TMZ treatment; promoting TAMs recruitment; which further induced ADAM8 expression in GBM cells to mediate TMZ chemoresistance. Thus; we revealed an ADAM8 dependent positive feedback loop between TAMs and GBM cells under TMZ treatment which involves CCL2 and EGFR signaling to cause TMZ resistance in GBM. [ABSTRACT FROM AUTHOR]

Simple Summary: Multiple myeloma (MM) is characterized by the presence of systemic clinical manifestations. Among them, pneumonia accounts for a significant cause of morbidity and mortality, highlighting an urgent need to explore possible susceptibility and potential mechanisms of pneumonia in MM. Recently, the gut–lung axis has emphasized the relevance of gut microbiota and pneumonia, indicating that the compromised function of gut microbiota may be susceptible to pneumonia. It has been previously shown that intestinal Klebsiella pneumonia enriches in MM patients and promotes MM progression in our previous work. In addition, host metabolism has been identified as a key regulator of MM. However, what role the altered gut microbiota plays in MM with pneumonia remains unknown. In this study, we explored the association between gut microbiota and MM with pneumonia. This is the first study to identify and elucidate the function of gut microbiota involved in MM with pneumonia. Pneumonia accounts for a significant cause of morbidity and mortality in multiple myeloma (MM) patients. It has been previously shown that intestinal Klebsiella pneumonia (K. pneumonia) enriches in MM and promotes MM progression. However, what role the altered gut microbiota plays in MM with pneumonia remains unknown. Here, we show that intestinal K. pneumonia is significantly enriched in MM with pneumonia. This enriched intestinal K. pneumonia links to the incidence of pneumonia in MM, and intestinal colonization of K. pneumonia contributes to pneumonia in a 5TGM1 MM mice model. Further targeted metabolomic assays reveal the elevated level of glutamine, which is consistently increased with the enrichment of K. pneumonia in MM mice and patients, is synthesized by K. pneumonia, and leads to the elevated secretion of TNF-α in the lung normal fibroblast cells for the higher incidence of pneumonia. Inhibiting glutamine synthesis by establishing glnA-mutated K. pneumonia alleviates the incidence of pneumonia in the 5TGM1 MM mice model. Overall, our work proposes that intestinal K. pneumonia indirectly contributes to pneumonia in MM by synthesizing glutamine. Altogether, we unveil a gut–lung axis in MM with pneumonia and establish a novel mechanism and a possible intervention strategy for MM with pneumonia. [ABSTRACT FROM AUTHOR]

Simple Summary: Urothelial carcinoma (UC) of the bladder is the most common malignancy in dialysis patients in Taiwan compared with renal cell carcinoma in Western countries. Radical cystectomy is the standard of care for localized muscle-invasive bladder cancer (MIBC), as well as for selected patients with high-risk non-MIBC. Despite improvements in anesthetic competency, surgical techniques, and postoperative care, dialysis patients undergoing radical cystectomy are at a higher risk of perioperative morbidity and mortality than non-dialysis patients. Due to the relative rarity of the condition, published data on predictors of outcome in ESRD patients undergoing radical cystectomy are scant. Our study revealed that accurate reporting of complications is necessary for preoperative counseling, identifying modifiable risk factors, and planning risk mitigation strategies. High comorbidity and low-volume surgeons were interrelated as notable risk factors for major complications. In addition to tumor-related factors, male sex, older age, and major complications significantly influence survival. Background: We investigated the use of a standardized reporting system to study perioperative complications and oncologic outcomes after radical cystectomy in end-stage renal disease (ESRD) patients with bladder cancer. Methods: We reviewed retrospective outcomes in 141 ESRD patients with bladder cancer who underwent radical cystectomy between 2004 and 2015. Complications were graded using the Clavien–Dindo classification system with 0–2 classified as "No Major Complications" and Clavien 3–5 as "Major Complications". Low-volume surgeons were classified as those performing fewer than nine cases during the study. Fisher's exact test along with the chi-squared test, two-tailed t tests, logistic regression, and the Cox proportional hazard model were used to evaluate all clinically meaningful covariates. Results: Ninety-nine (99, 70.2%) patients had no major complications, and forty-two (29.8%) patients had major complications. Patients in the major complications group were older, had a higher Charlson comorbidity index (CCI), and had a longer hospitalization duration than those in the no major complications group (all, p < 0.05). Major complications were also more common when the procedure was performed by low-volume surgeons (p = 0.003). In multivariate logistic regression models, CCI ≥ 5 (p = 0.006) and low-volume surgeon (p = 0.004) were independent predictors of major complications. According to multivariate analysis with the Cox hazards regression, male sex, age > 70 years, CCI ≥ 5, bladder cancer stage ≥ 3, lymphovascular invasion, and experiencing major complications were significant poor prognostic factors for overall survival (all, p < 0.05). Conclusions: Accurate reporting of complications is necessary for preoperative counseling, identifying modifiable risk factors, and planning risk mitigation strategies. High comorbidity and low-volume surgeons were interrelated as notable risk factors for major complications. In addition to tumor-related factors, male sex, older age, and major complications significantly influence overall survival. [ABSTRACT FROM AUTHOR]

Background and Objectives: surgery for substernal goitre is still debated in the literature, due to the wide range of surgical options. This article outlines the findings of our extensive experiences, which include 264 cases of patients with "goitre plongeant", and compares postoperative complications, despite surgical approaches. Material and Methods: preoperative planning and anatomical landmarks are described to determine the potential need of a combined approach. The surgical procedure is described, along with some stratagems, to ensure that the operation is completed safely. A statistical analysis of complications and the length of stay, with a comparison of cervicotomy and combined access, was performed using the Pearson chi-square significance test. Results: 264 patients underwent thyroid surgery for substernal goitre. The Kocher incision was the surgical approach chosen in 256 patients (96.6%), while an accessory incision was performed in 8 patients (3.4%). The necessity to use a two-fold surgical access was linked to a higher rate of postoperative complications (p-value < 0.01). The average length of stay (LOS) for cervicotomy was 2 days (1–3 days), while the average LOS was 5 days (4–7 days) (p-value = n.s.) for combined access. Conclusions: cervicotomy should be the gold standard technique for exploring intrathoracic goitre with a digital dissection, which, in almost all cases, enables the externalization of the mediastinal portion associated. Sternotomy is related to a higher rate of complications, so it should be performed only in selected cases. Management in large-volume centres may be more appropriate. [ABSTRACT FROM AUTHOR]

Early detection of caries lesions is key to a successful restorative dental treatment plan. The aim of this study was to investigate the preferences and attitude of graduate restorative dentistry residents (RDRs) regarding novel caries diagnostic technologies (NCDT) and to provide a brief overview of available technologies for both specialized and general dental practice. This cross-sectional study used an online questionnaire (17 questions) concerning RDRs' attitude, preferences, and insights regarding five available NCDTs. It was distributed among twenty RDRs at a local government dental school following a review session about NCDTs. Collected responses were analyzed statistically using one-way analysis of variance (ANOVA), chi-squared with Bonferroni correction, and Kruskal-Wallis tests at a 0.05 significance level. Sixty-five percent of RDRs reported an interest in NCDTs as a discussion topic and almost half of them were positive towards their use, however, sixty percent of respondents were hesitant to diagnose caries solely using NCDTs. Fiber-optic-transillumination (FOTI) systems were ranked the best overall and with regard to all the investigated criteria (p < 0.05). Chosen reasons for FOTI included price followed by ease of use. In general, high price rated as the most perceived reason for not choosing a given NCDT followed by low practical applicability. Meanwhile, ease of use followed by relevant application ranked as the main reported reasons to choose an NCDTs. [ABSTRACT FROM AUTHOR]