Potential Consequences Research Articles

Impact of a national audit on child and adolescent psychiatrists' prescribing practices.

A look back review of South Kerry Child and Adolescent Mental Health Services (CAMHS) in Ireland, known as the 'Maskey report' (MR), highlighted substandard prescribing practices. The aim of this 'Maskey Impact Study' (MIS) was to explore changes to child and adolescent psychiatrists' prescribing practices following the MR. The study was cross-sectional and mixed method. A study specific questionnaire was distributed electronically to psychiatrists working in CAMHS (n = 160). 102 psychiatrists participated in the study (response rate 63.8%). Perceived improvement in prescribing practices included improved medical record keeping (63.7%), consent documentation (53.9%), medication information provision (41.2%) and physical health monitoring (60.8%). However, 43.1% of psychiatrists reported a reluctance to prescribe medication even when clinically indicated and 50% were more likely to avoid off-label use. Most respondents reported increased stress levels (80.4%) with higher stress being significantly associated with reticence in prescribing (χ2 = 11.746, p < .001) and avoiding off-label use (χ2 = 15.392, p < 0.001). Thematic analysis highlighted increased medication hesitancy, enforced 'meaningless' bureaucracy and medication mistrust among families. Although improvements reported are welcomed, the increased hesitancy of medication use, avoidance of prescribing more than one medication, and avoidance of off-label use, is of concern with potential unintended adverse consequences. Reluctance in prescribing may deprive youth of access to evidence-based treatments and limit exposure of NCHDs to the safe practice of consultant-initiated psychopharmacology. Further research will be important to determine if this impacts clinical care. Continued education in psychopharmacology is essential along with increased public awareness of the evidence for medication, to help restore public confidence and trust in psychopharmacology.

Ethical Problems of Observational Studies and Big Data Compared to Randomized Trials.

The temptation to use prospective observational studies (POS) instead of conducting difficult trials (RCTs) has always existed, but with the advent of powerful computers and large databases, it can become almost irresistible. We examine the potential consequences, were this to occur, by comparing two hypothetical studies of a new treatment: one RCT, and one POS. The POS inevitably submits more patients to inferior research methodology. In RCTs, patients are clearly informed of the research context, and 1:1 randomized allocation between experimental and validated treatment balances risks for each patient. In POS, for each patient, the risks of receiving inferior treatment are impossible to estimate. The research context and the uncertainty are down-played, and patients and clinicians are at risk of becoming passive research subjects in studies performed from an outsider's view, which potentially has extraneous objectives, and is conducted without their explicit, autonomous, and voluntary involvement and consent.

Griefbots, Deadbots, Postmortem Avatars: on Responsible Applications of Generative AI in the Digital Afterlife Industry

To analyze potential negative consequences of adopting generative AI solutions in the digital afterlife industry (DAI), in this paper we present three speculative design scenarios for AI-enabled simulation of the deceased. We highlight the perspectives of the data donor, data recipient, and service interactant – terms we employ to denote those whose data is used to create ‘deadbots,’ those in possession of the donor’s data after their death, and those who are meant to interact with the end product. We draw on the scenarios to map out several key ethical concerns posed by ‘re-creation services’ and to put forward recommendations on the ethical development of AI systems in this specific area of application. The recommendations, targeted at providers of AI-enabled re-creation services, include suggestions for developing sensitive procedures for retiring deadbots, ensuring meaningful transparency, restricting access to such services to adult users only, and adhering to the principle of mutual consent of both data donors and service interactants. While we suggest practical solutions to the socio-ethical challenges posed by the emergence of re-creation services, we also emphasize the importance of ongoing interdisciplinary research at the intersection of the ethics of AI and the ethics of the DAI.

Terrorist attacks in Turkey: An analysis of counter-terrorism medicine

Aim: The objective of this research was to perform an medicine analysis of terrorist attacks in Türkiye. Methods: This study is a retrospective cross-sectional research. Study population consisted of terrorist incidents that occurred in Türkiye, as provided by the START Global Terrorism Database for the period from 1970 to 2020. Various characteristics of terror attacks in Türkiye were analyzed and presented in tabular form. Results: Over the past 51 years in Türkiye, there have been a total of 4,485 terrorist incidents, with 91.2% reaching their intended targets as orchestrated by terrorist organizations. Of these incidents, 2,767 had detrimental economic impacts. Additionally, 17,570 individuals experienced adverse medical effects. Among the 81 provinces in Turkey, Istanbul witnessed the highest number of terrorist incidents and suffered the most significant medical consequences. Conclusion: Türkiye has been significantly impacted by terrorist incidents over the past decade, particularly in metropolitan provinces like Istanbul. These events have negatively affected both the health and economic well-being of many individuals. In response, while the country has implemented various security measures and preparedness strategies to mitigate such incidents, there is also a critical need to improve the readiness of healthcare services to effectively handle the potential consequences of terrorist attacks. This includes advancing anti-terror medicine and tactical medicine capabilities, as well as strengthening mass casualty management systems. Such improvements will ensure a more effective and coordinated response to large-scale emergencies, ultimately saving lives and reducing the long-term impacts on society.

Dine in or Takeout? Trends on Restaurant Service Demand amid the COVID-19 Pandemic

The COVID-19 pandemic has caused unprecedented damage to restaurant businesses, especially indoor dining services, because of the widespread fear of coronavirus exposure. In contrast, the online food ordering and delivery services, led by DoorDash, Grubhub, and Uber Eats, filled in the vacancy and achieved explosive growth. As a result, the restaurant industry is experiencing dramatic transformations under the crossfire of these two driving forces. However, these changes are not fully exposed because of the lack of firsthand data, let alone their potential consequences and implications. This study, thus, leverages foot traffic data to reveal and understand the trends of restaurant service demand through the pandemic. We devise a mixture model to decompose the aggregate foot traffic by dwelling time patterns into dine-in and takeout volumes. The transitions of demand structures are then identified for various restaurant sectors by service types, price levels, and locations. We observe that limited-service and budget restaurants saw a significantly faster recovery than full-service counterparts given their comparative advantages in adapting toward takeout channels. But, in the long run, our results suggest more robust demands for dine-in services at full-service restaurants, particularly those that provide more premium dining experiences. Comparatively, the off-line channels at limited-service restaurants appeared vulnerable to the cannibalization from online ordering and delivery channels, which strengthened even after society moved out of lockdown. Regionally, exurban restaurants seem to trend toward the takeout mode, whereas urban areas did not see a notable modal migration between dine-in and takeout from restaurants.

Modelling lung infection with Klebsiella pneumoniae after murine traumatic brain injury

Pneumonia is a common comorbidity in patients with severe traumatic brain injury (TBI), and is associated with increased morbidity and mortality. In this study, we established a model of intratracheal Klebsiella pneumoniae administration in young adult male and female mice, at 4 days following an experimental TBI, to investigate how K. pneumoniae infection influences acute post-TBI outcomes. A dose-response curve determined the optimal dose of K. pneumoniae for inoculation (1 x 10^6 colony forming units), and administration at 4 days post-TBI resulted in transient body weight loss and sickness behaviors (hypoactivity and acute dyspnea). K. pneumoniae infection led to an increase in pro-inflammatory cytokines in serum and bronchoalveolar lavage fluid at 24 h post-infection, in both TBI and sham (uninjured) mice. By 7 days, when myeloperoxidase + neutrophil numbers had returned to baseline in all groups, lung histopathology was observed with an increase in airspace size in TBI + K. pneumoniae mice compared to TBI + vehicle mice. In the brain, increased neuroinflammatory gene expression was observed acutely in response to TBI, with an exacerbated increase in Ccl2 and Hmox1 in TBI + K. pneumoniae mice compared to either TBI or K. pneumoniae alone. However, the presence of neuroinflammatory immune cells in the injured brain, and the extent of damage to cortical and hippocampal brain tissue, was comparable between K. pneumoniae and vehicle-treated mice by 7 days. Examination of the fecal microbiome across a time course did not reveal any pronounced effects of either injury or K. pneumoniae on bacterial diversity or abundance. Together, these findings demonstrate that K. pneumoniae lung infection after TBI induces an acute and transient inflammatory response, primarily localized to the lungs with some systemic effects. However, this infection had minimal impact on secondary injury processes in the brain following TBI. Future studies are needed to evaluate the potential longer-term consequences of this dual-hit insult.

Incidence of resistance to ALS and ACCase inhibitors in Echinochloa species and soil microbial composition in Northern Italy

The increasing amount of weeds surviving herbicide represents a very serious problem for crop management. The interaction between microbial community of soil and herbicide resistance, along with the potential evolutive consequences, are still poorly known and need to be investigated to better understand the impact on agricultural management. In our study, we analyzed the microbial composition of soils in 32 farms, located in the Northern Italy rice-growing area (Lombardy) with the aim to evaluate the relationship between the microbial composition and the incidence of resistance to acetolactate synthase (ALS) and acetyl-CoA carboxylase (ACCase) inhibiting herbicides in Echinochloa species. We observed that the coverage of weeds survived herbicide treatment was higher than 60% in paddy fields with a low microbial biodiversity and less than 5% in those with a high microbial biodiversity. Fungal communities showed a greater reduction in richness than Bacteria. In soils with a reduced microbial diversity, a significant increase of some bacterial and fungal orders (i.e. Lactobacillales, Malasseziales and Diaporthales) was observed. Interestingly, we identified two different microbial profiles linked to the two conditions: high incidence of herbicide resistance (H-HeR) and low incidence of herbicide resistance (L-HeR). Overall, the results we obtained allow us to make hypotheses on the greater or lesser probability of herbicide resistance occurrence based on the composition of the soil microbiome and especially on the degree of biodiversity of the microbial communities.

Prevalence of Vitamin D Deficiency among Patients Attending Tertiary Level Hospitals in Bangladesh: Hospital-Based Cross-Sectional Study

Introduction: Vitamin D (Vit D) is essential for calcium and phosphate homeostasis, critical for bone growth and remodeling. Its deficiency leads to conditions like osteomalacia and rickets, with adverse effects on osteoporosis, growth, and skeletal health. This study aimed to assess Vitamin D Deficiency prevalence among patients in Bangladeshi tertiary-level hospitals. Materials and Methods: A prospective cross-sectional study was conducted from January to December 2019 at Cumilla Medical College Hospital and Central Medical College Hospital. We enrolled 1250 patients meeting inclusion criteria and collected data via a pre-designed questionnaire. Results: Most participants (31.8%) were aged 31-40, with a mean age of 37.31±13.37. Male patients constituted 53.3%, and 46.7% were female. Rural residents accounted for 52.6%, while 25.8% lived in urban areas, and the rest abroad, mainly the Middle East. The majority (88.5%) belonged to middle-class families, and only 1.5% reported sufficient sun exposure. Strikingly, 54.2% were Vitamin D deficient, 40% had insufficient levels, and only 6.4% had adequate Vit D. Conclusion: This study highlights a significant prevalence of Vitamin D deficiency among patients in Bangladeshi tertiary hospitals. The data underscore the urgent need for healthcare authorities to address this public health concern. Policymakers and healthcare providers should be aware of the potential long-term health consequences of Vitamin D deficiency, emphasizing the importance of strategies to promote adequate Vit D levels in the population. Medicine Today 2023 Vol.36 (1): 17-22

Adverse childhood experiences and risk of late-life dementia: a systematic review and meta-analysis.

Adverse childhood experiences (ACEs) refer to distressing events before age 18 that can lead to potential mental and physical health consequences. This systematic review and meta-analysis aimed to examine the association between ACEs and the risk of dementia in elderly adults who experienced ACEs during childhood, addressing the existing inconsistencies and methodological variations. A comprehensive search strategy was employed across key databases (PubMed, Web of Science, Scopus, and Embase) to identify relevant articles. Our primary outcome was ACEs-dementia risk, and our secondary outcome was mild cognitive impairment risk. A quality assessment was conducted using the Newcastle-Ottawa Quality Assessment Scale and GRADE. A random-effects model was utilized to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were performed to explore potential sources of heterogeneity and assess the reliability of the results. Out of 1,376 screened papers, nine studies were included. The studies consisted of two case-control, one prospective cohort, and six retrospective cohort studies conducted in the UK, France, USA, China, and Spain. Five studies were of good methodological quality according to the NOS. according to the GRADE, all outcomes were classified as very low or low quality of evidence. A significant association was observed between ACEs and dementia risk (OR = 1.35; 95% CI 1.20, 1.52; P = 0.00001) and mild cognitive impairment risk (OR = 1.28; 95% CI 0.63, 2.62; P = 0.49). A meta-analysis by type of adversity revealed significant results for the maltreatment subgroup(OR = 1.30; 95% CI 0.07-1.58; P = 0.007; I² = 0%). Subgroup analysis based on the dementia definition revealed no between-subgroup difference (P = 0.71) between tool-based and register/criteria-based subgroups. No possibility of Publication bias was observed upon inspection of the funnel plot. Adverse childhood experiences may be associated with an increased risk of dementia. However, caution is warranted in interpreting these results due to the limited number of studies. Larger high-quality studies investigating the association between ACEs and dementia risk are needed to confirm the reliability of our results.

Activation of innate immunity selectively compromises mitochondrial complex I, proline oxidation, and flight activity in the major arbovirus vector Aedes aegypti.

Aedes aegypti females are natural vectors of important arboviruses such as dengue, zika, and yellow fever. Mosquitoes activate innate immune response signaling pathways upon infection, as a resistance mechanism to fight pathogens and limit their propagation. Despite the beneficial effects of immune activation for insect vectors, phenotypic costs ultimately affect their fitness. However, the underlying mechanisms that mediate these fitness costs remain poorly understood. Given the high energy required to mount a proper immune response, we hypothesized that systemic activation of innate immunity would impair flight muscle mitochondrial function, compromising tissue energy demand and flight activity. Here, we investigated the dynamic effects of activation of innate immunity by intra-thoracic zymosan injection on A. aegypti flight muscle mitochondrial metabolism. Zymosan injection significantly increased defensin A expression in fat bodies in a time-dependent manner that compromised flight activity. Although oxidant levels in flight muscle were hardly altered, ATP-linked respiratory rates driven by mitochondrial pyruvate+proline oxidation were significantly reduced at 24 h upon zymosan injection. Oxidative phosphorylation coupling was preserved regardless of innate immune response activation along 24 h. Importantly, rotenone-sensitive respiration and complex I-III activity were specifically reduced 24 h upon zymosan injection. Also, loss of complex I activity compromised ATP-linked and maximal respiratory rates mediated by mitochondrial proline oxidation. Finally, the magnitude of innate immune response activation negatively correlated with respiratory rates, regardless of the metabolic states. Collectively, we demonstrate that activation of innate immunity is strongly associated with reduced flight muscle complex I activity with direct consequences to mitochondrial proline oxidation and flight activity. Remarkably, our results indicate a trade-off between dispersal and immunity exists in an insect vector, underscoring the potential consequences of disrupted flight muscle mitochondrial energy metabolism to arbovirus transmission.

Phyto-synthesized silver nanoparticles from Sargassum subrepandum: anticancer, antimicrobial, and molluscicidal activities

In the realm of nanotechnology, the use of algae to produce nanoparticles is an environmentally friendly, sustainable, and economically viable strategy. In the present study, the brown macroalgae Sargassum subrepandum was utilized to effectively produce silver nanoparticles (AgNPs). Through various characterization techniques, the AgNPs’ structural integrity was confirmed. AgNPs exhibited significant antimicrobial activity against Pseudomonas aeruginosa and Fusarium equiseti. AgNPs showed cytotoxic effects on the MCF-7 breast adenocarcinoma cell line with an IC50 of 12.5 µg/ml. Treatment with AgNPs resulted in a marked reduction in cell viability, alongside evident apoptotic and necrotic morphological changes in the cancer cells. Through molecular docking studies, a deeper understanding of the interaction between AgNPs and crucial proteins related to cancer has been achieved, AgNPs showed a promising molluscicidal action on Biomphalaria alexandrina snails, a Schistosoma mansoni intermediate host. The half-lethal dose (LC50) of AgNPs was determined to be 0.84 mg/L. The potential consequences of its administration include potential disruptions to the glycolysis profile, as well as potential impacts on the steroidal hormone’s estrogen and testosterone and certain kidney function tests. This study highlights the diverse uses of algae-synthesized AgNPs, ranging from healthcare to environmental management, demonstrating their importance in advancing nano-biotechnological solutions.

THE USE OF ANTIBIOTICS IN FOOD ANIMALS – A THREAT TO HUMAN HEALTH

Background: Antibiotics are widely used in food animals to prevent disease, promote growth and maintain productivity. Modern animal production practices involve regular use of antimicrobials, but abusive use can lead to harmful consequences. The aim of this review was to provide comprehensive information regarding the risk of regular application of antibiotics in food animals, the potential consequences and impact on human health, and options for the prevention of antibiotic resistance in the food chain. Review Results: Although organizations such as WHO, UN, and EU have taken steps to reduce and limit the use of antibiotics in animals, these are proving insufficient in developing countries. In many countries, the antibiotics used in animals appear to exceed that in humans. The abuse in food animals promotes the development of antibiotic-resistant bacteria and resistance genes that can be transmitted to humans through food consumption and direct contact with animal food or environment mechanisms. This can lead to human infections with antibiotic-resistant bacteria, causing treatment failure and, therefore, more severe and longer-lasting illnesses, increased hospitalization rates, more deaths and higher costs to society. Furthermore, as food animals and animal-derived foods are traded globally, they contribute to antibiotic resistance in countries far from where the problem originates. Conclusion: Overcoming the problem of antibiotic resistance requires a multidisciplinary approach with effective action coordination and information exchange between the agricultural, food, veterinary and health sectors. Through international cooperation, efforts should focus on reducing unnecessary antibiotics use and reducing the spread of antibiotic-resistant bacteria, but national-level action on antibiotic resistance and food safety is also essential.

Deciphering novel TCF4-driven mechanisms underlying a common triplet repeat expansion-mediated disease.

Fuchs endothelial corneal dystrophy (FECD) is an age-related cause of vision loss, and the most common repeat expansion-mediated disease in humans characterised to date. Up to 80% of European FECD cases have been attributed to expansion of a non-coding CTG repeat element (termed CTG18.1) located within the ubiquitously expressed transcription factor encoding gene, TCF4. The non-coding nature of the repeat and the transcriptomic complexity of TCF4 have made it extremely challenging to experimentally decipher the molecular mechanisms underlying this disease. Here we comprehensively describe CTG18.1 expansion-driven molecular components of disease within primary patient-derived corneal endothelial cells (CECs), generated from a large cohort of individuals with CTG18.1-expanded (Exp+) and CTG 18.1-independent (Exp-) FECD. We employ long-read, short-read, and spatial transcriptomic techniques to interrogate expansion-specific transcriptomic biomarkers. Interrogation of long-read sequencing and alternative splicing analysis of short-read transcriptomic data together reveals the global extent of altered splicing occurring within Exp+ FECD, and unique transcripts associated with CTG18.1-expansions. Similarly, differential gene expression analysis highlights the total transcriptomic consequences of Exp+ FECD within CECs. Furthermore, differential exon usage, pathway enrichment and spatial transcriptomics reveal TCF4 isoform ratio skewing solely in Exp+ FECD with potential downstream functional consequences. Lastly, exome data from 134 Exp- FECD cases identified rare (minor allele frequency <0.005) and potentially deleterious (CADD>15) TCF4 variants in 7/134 FECD Exp- cases, suggesting that TCF4 variants independent of CTG18.1 may increase FECD risk. In summary, our study supports the hypothesis that at least two distinct pathogenic mechanisms, RNA toxicity and TCF4 isoform-specific dysregulation, both underpin the pathophysiology of FECD. We anticipate these data will inform and guide the development of translational interventions for this common triplet-repeat mediated disease.

Impact of Intermittent Hypoxia Related to Obstructive Sleep Apnoea Syndrome on Low-Grade Inflammation in Hypertensive Patients: Potential Implications for Cardiovascular Risk

There is evidence for a particular relationship between low-grade inflammation (LGI) and intermittent hypoxia (IH) related to obstructive sleep apnoea syndrome (OSAS). However, despite the potential deleterious cardiovascular consequences associated with this LGI in hypertensive patients, few studies have investigated the impact of IH related to OSAS on CRP levels in this subpopulation. In total, 1404 hypertensive patients were selected retrospectively from the Sleep Laboratory database. CRP levels ≥3 mg/L but &lt;10 mg/L were used as cut-offs to identify hypertensive patients with LGI. Logistic regressions were conducted to examine the risk of LGI associated with IH related to OSAS in hypertensive patients. LGI was frequent (33.8%) in hypertensive patients. After adjustment for confounders, multivariate logistic regressions revealed that only moderate to severe OSAS (apnoea–hypopnoea index ≥ 15/h) with high IH (oxygen desaturation index ≥ 15/h) [OR 1.51 (95% CI 1.06–2.14)] was significantly associated with LGI in hypertensive patients (p-value = 0.045). Consistent with our hypothesis, our results demonstrated the existence of a particular subtype of hypertensive patients at high cardiovascular risk characterised by the presence of LGI induced by IH hypoxia related to moderate to severe OSAS, which justifies the establishment of adequate management of this pathology to allow better cardiovascular prevention in this subpopulation.

A novel approach detection for IIoT attacks via artificial intelligence

A novel approach detection for IIoT attacks via artificial intelligence

The effects of the predictability of acclimatory temperature on the growth and thermal tolerance of juvenile Spinibarbus sinensis

Heated effluent injection, cold hypolimnetic water inputs from dams, and extreme weather events can lead to unpredictable temperature fluctuations in natural waters, impacting fish performance and fitness. We hypothesized that fish exposed to such unpredictable fluctuations would exhibit weaker growth and enhanced thermal tolerance compared to predictable conditions. Qingbo (Spinibarbus sinensis) was selected as the experimental subject in this study. The qingbo were divided into a constant temperature group (C, 22 ± 0.5 °C), a predictable temperature fluctuation group (PF, 22 ± 4 °C, first warming, then cooling within a day) and an unpredictable temperature fluctuation group (UF, 22 ± 4 °C, the order of warming or cooling is random). After 40 days of temperature acclimation, the growth, metabolic rate, spontaneous activity, thermal tolerance, plasma cortisol concentration and liver hsp70 level of the fish were measured. Unexpectedly, neither the PF nor the UF group showed decreased growth compared to the C group. This could be attributed to the fact that temperature variation did not lead to a substantial increase in basic energy expenditure. Furthermore, feeding rates increased due to temperature fluctuations, although the difference was not significant. Both the PF and UF groups exhibited increased upper thermal tolerance, but only the UF group exhibited improved lower thermal tolerance and higher liver hsp70 levels compared to the C group. The qingbo that experienced unpredictable temperature fluctuations had the best thermal tolerance among the 3 groups, which might have occurred because they had the highest level of hsp70 expression. This may safeguard fish against the potential lethal consequences of extreme temperatures in the future. These findings suggested that qingbo exhibited excellent adaptability to both predictable and unpredictable temperature fluctuations, which may be associated with frequent temperature fluctuations in its natural habitat.

Circulating Biomarkers in Pulmonary Arterial Hypertension: An Update

Pulmonary arterial hypertension (PAH) is a rare subtype of group 1 pulmonary hypertension (PH) diseases, characterized by high pulmonary artery pressure leading to right ventricular dysfunction and potential life-threatening consequences. PAH involves complex mechanisms: vasoconstriction, vascular remodeling, endothelial dysfunction, inflammation, oxidative stress, fibrosis, RV remodeling, cellular hypoxia, metabolic imbalance, and thrombosis. These mechanisms are mediated by several pathways, involving molecules like nitric oxide and prostacyclin. PAH diagnosis requires clinical evaluation and right heart catheterization, confirming a value of mPAP ≥ 20 mmHg at rest and often elevated pulmonary vascular resistance (PVR). Even if an early and accurate diagnosis is crucial, PAH still lacks effective biomarkers to assist in its diagnosis and prognosis. Biomarkers could contribute to arousing clinical suspicion and serve for prognosis prediction, risk stratification, and dynamic monitoring in patients with PAH. The aim of the present review is to report the main novelties on new possible biomarkers for the diagnosis, prognosis, and treatment monitoring of PAH.

Non-invasive surveillance of shared pathogens in the Eurasian brown bear (Ursus arctos) human interface

Multi-host communities are perfect scenarios for the emergence and spread of pathogens, threatening the recovery of endangered, isolated, or inbred populations, such as the brown bear (Ursus arctos) in northwestern Spain. The population recovery in recent years has forced bears to occupy highly anthropized areas, increasing their interaction with human and domestic animals, with potential consequences for global health. During 2022–2023 a survey of parasites, bacteria and viruses shared between wildlife, domestic animals and humans was performed in this population using non-invasive surveillance, i.e., bear fecal samples (n = 73) and sponge-based sampling of trees (n = 42; 14 rubbed trees and 28 control trees). Pathogen detection rates were defined as the percentage of qPCR or culture-positive samples. Generalized linear models were fitted to assess their relationship with environmental variables including dispersion of the human population, and percentage of agricultural and periurban habitats in a 6 km-buffer around each sample. Canine Adenovirus type 1 (45.2%), Giardia spp. (15.1%), Salmonella spp. (12.3%), and extended-spectrum-beta-lactamases (ESBL) Escherichia coli (1.4%) were identified in fecal samples. In contrast, only five sponges from three rubbed and two control trees resulted positive to E. coli (14.3%). The results suggest that several pathogens are common in the Cantabrian brown bear population and that anthropization of the territory modulates their prevalence and richness.The effective design of management programs for bear conservation will require a one-health approach, in which genetic analysis of non-invasive samples can be key tools for the sanitary surveillance at the wildlife-livestock-human interface.

Abstract LBO1-05: Impact of age and ovarian function suppression (OFS) on endocrine response to short preoperative endocrine therapy (ET): Results from the multicenter ADAPTcycle trial (n=4,334)

Abstract Background: In HR+/HER2- early breast cancer (EBC), short preoperative endocrine therapy (ET) is a promising tool for ET-efficacy assessment based on Ki67-decrease after 2-4 weeks of ET. Low post-endocrine Ki67 (Ki67post) is associated with good prognosis in large prospective trials. WSG-ADAPT demonstrated that ET-response is a valid criterion for decisions in uncertain adjuvant chemotherapy indications, e.g., in premenopausal patients (pts) with N0 and Recurrence Score (RS, Oncotype DX®) RS 16-25 or with N1 and RS ≤25. Preliminary results from the phase III ADAPTcycle trial indicated higher efficacy of preoperative ET in premenopausal pts. if ovarian function suppression (OFS) was used together with tamoxifen (TAM) or aromatase inhibitors (AI). In the final screening population, we are now able to confirm these results and investigate the influence of age subgroups, RS, individual biological markers, and OFS on ET-response. Methods: In ADAPTcycle (n=5,290 screened, 1,670 randomized by 06/23; 84 sites in Germany), N0-1 pts with RS &amp;gt;25 or N2-3 pts with RS ≤25 and ET-response were randomized to (neo)adjuvant chemotherapy (CT) followed by ET vs. ribociclib + AI (premenopausal: +GnRH). In premenopausal pts, participation with N1-disease and RS ≤25 or N0 and RS 16-25 was allowed irrespective of ET-response, but randomization recommended only for ET-responders; in the preoperative phase, OFS+TAM or AI for ET-response assessment was protocol-recommended. Results: This analysis includes all pts with complete baseline characteristics (including RS) and ET-response data (n=4,334); ET-response was defined as Ki67post ≤10% (central pathology) after 2-4 weeks (if OFS: 4 weeks) of therapy. ER, PR, and HER2-levels were analyzed by IHC and mRNA. Median age was 56 years (22-87y). 55% had cT2-4 tumors; 28% had cN+ disease; 42% were G3 (central lab). Median RS was 20, median baseline Ki67 25%. n=1,368 were ≤50y and premenopausal (“≤50y”): n=314 (23.0%) and 255 (18.6%) were treated by AI+OFS and TAM+OFS, respectively. 2,966 were &amp;gt;50y or postmenopausal (“ &amp;gt;50y”), of whom 2,565 received AI (86.5%). ET-response occurred in 48.2% of “≤50y” vs. 72.7% in “ &amp;gt;50y” pts (p&amp;lt; 0.001). We observed significant differences in ET-response rates between “≤50y” vs. “ &amp;gt;50y” with TAM alone (34.7% vs. 46.4%); In “≤50y” pts, 55.7% ET-response occurred with TAM+OFS vs. 76.4% with AI+OFS, comparable to 76.8% in “ &amp;gt;50y” patients with AI. Moreover, OFS led to higher ET-response rates (by uni- and multivariable analysis) even in the small (n=78) group of premenopausal pts &amp;gt;50y. Remarkably, even in pts with RS &amp;gt;25, substantial ET-response rates were observed with AI: 66.7% (“≤50y”, AI+OFS), 55.6% (“ &amp;gt;50y”, AI) vs. lower rates with TAM alone (&amp;gt;50y: 18.2%; &amp;lt; 50y: 15.8%). ET-response rate in “≤50y” pts was associated with ET type, RS, and baseline Ki67 in both uni- and multivariable analysis, but not age subgroup (≤40 vs. 41-50y). ER, PR, and HER2 expression by IHC or RT-PCR were associated with ET-response by univariable (but not multivariable) analysis. In “ &amp;gt;50y” pts, by uni- and multivariable analysis, again ET-type, RS, and baseline Ki67, as well as ER-expression (by IHC) and ESR1, PR, and HER2-expression (by RT-PCR) were associated with higher ET-response rates. Conclusions: With about 10,000 pre- and postmenopausal pts, ADAPT and ADAPTcycle provide the largest international database regarding ET-response. ADAPTcycle confirms ADAPT ET-response rates in pts receiving TAM or AI; adding OFS to either improves ET-response, irrespective of RS. ET-response measurement adds value in therapy decisions, particularly in ≤50y N0-1 pts. ET-response might provide key information even in pts with high RS; outcome data of ADAPTcycle will reveal potential clinical consequences. Optimal preoperative ET, especially in premenopausal pts, might even enable sparing chemotherapy in additional pts. Citation Format: Oleg Gluz, Matthias Christgen, Ulrike Nitz, Sherko Küemmel, Michael Braun, Marc Thill, Rachel Wuerstlein, Pauline Wimberger, Andreas Hartkopf, Christian Schem, Matthias Zaiss, Vesna Bjelic-Radisic, Marianne Just, Kristina Veselinovic, Myriam Vincent, Monika Graeser, Katja Krauss, Oliver Hoffmann, Kerstin Lüdtke-Heckenkamp, Ronald Kates, Christine zu Eulenburg, Katarzyna Jozwiak, Sandy Burmeister, Rick Baehner, Peter Schmid, Hans-Heinrich Kreipe, Nadia Harbeck. Impact of age and ovarian function suppression (OFS) on endocrine response to short preoperative endocrine therapy (ET): Results from the multicenter ADAPTcycle trial (n=4,334) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr LBO1-05.

Making a Bad Situation Worse: Current and Potential Unintended Consequences of Juvenile Registration for Sexual Offences.

Within the US, children and adolescents who engage in sexually abusive behavior are often subjected to sex offender registration and notification requirements, which contribute to stigmatization and forfeiture of their civil rights without empirical basis (Lancaster, 2011; Pickett et al., 2023; Zilney & Zilney, 2009). To date, 39 states subject children with adjudicated sexual offenses to sex offender registration requirements, with most recent estimates revealing that approximately 200,000 youth have been placed on sex offender registries within the US and many are now on the registry as adults (Pickett et al., 2020). This severe response-by both members of the public and policymakers-toward children who engage in inappropriate sexual behavior is imposed upon children and adolescents with adjudicated sexual offenses in an effort to meet goals of reducing sexual violence and increasing community safety. Within the current discourse, we review the history of registration and notification practices for adolescents with sexual offenses, describe what registration and notification policies entail, and then present empirical and theoretical evidence of the harmful outcomes associated with implementation of registration and notification requirements for sexual offenses. Thus, the predominant aim of this discourse is to encourage thoughtful and critical examination of registration and notification policies and their iatrogenic impacts.