Reducing local tension to repair nasal septal deviation and spur.

OBJECTIVES: To introduce our method managing nasal septal spurs during endoscopic septoplasty. METHODS: We conducted a prospective study of cases treated with endoscopic septoplasty between March 2022 and June 2023. We innovated a surgical method to reduce the local mucosal tension at the spur by cutting the spur above and below the bony connection, and reducing the chance of mucosal tear and loss during dissection. The authors performed these cases at the First Affiliated Hospital of Fujian Medical University, where 40 surgeries were performed with regular postoperative follow-ups for 6-12 months. RESULTS: All patients' clinical symptoms improved significantly after surgery. After 2-4 weeks of follow-up, the mucosa could recover to the preoperative state on both sides of the nasal septum. CONCLUSION: This surgical method is suitable for most patients with nasal septal deviation, especially those with a spur, which can effectively reduce the chance of nasal septal mucosa tear and accelerate postoperative recovery. LEVEL OF EVIDENCE: Ⅳ.

Pre-cooling for Reducing Pain from Local Anesthetic Injections for Hemorrhoidectomy: An Open-label, Randomized, Crossover Trial.

Objectives: Excisional hemorrhoidectomy (EH) is sometimes same-day surgery under local anesthesia (LA); however, the LA injection can be painful. We conducted an open-label, crossover, randomised controlled trial to evaluate the efficacy and safety of pre-cooling in reducing pain associated with LA injection. Methods: Patients aged ≥ 20 years undergoing bilateral EH were randomly assigned to 1 of 2 pre-cooling sequences: a cooling-first sequence and a cooling-second sequence. In the first intervention phase, 2 minutes of pre-cooling was applied before LA injection in patients randomized to the cooling-first sequence; patients in the cooling-second sequence were asked to wait for 2 minutes (without pre-cooling) before LA injection. The pre-cooling sequences and the perianal sides targeted for injection were reversed in the second intervention phase. The primary outcome was the visual analogue scale (VAS) rating for pain from LA injection, which was obtained twice for each patient. Adverse events due to pre-cooling (e.g., skin disorders) were documented. Results: Of 114 screened patients, 51 were randomized to the cooling-first (n = 26; analyzed: n = 26) or cooling-second sequence (n = 25; analyzed: n = 25). The 2-minute pre-cooling was completed by 48 patients (94%). VAS scores for LA injection pain decreased significantly with pre-cooling compared to without (difference estimate, -1.71; 95% confidence interval, -2.12 to -1.31; p< 0.001). No adverse events were reported. Conclusions: Two minutes of skin pre-cooling effectively and safely reduces LA injection pain in patients undergoing EH.

Deep Angiomyxoma of the Knee: a Rare Case Report.

Background: Deep angiomyxoma (DAM) is a slow-growing benign tumor with high risk of local recurrence after surgical resection. Although DAM in a lower extremity is extremely rare, clinicians must be aware of its possible occurrence. Suspicion can be made based on clinical examination and radiological imaging but final diagnosis is confirmed on histopathological examination and immunohistochemistry. We intend to present an extremely rare case of DAM in the knee, managed successfully with marginal excision. Case Presentation: A 4-year-old male child presented with the complains of a painless, progressively increasing, soft, non-tender, and fluctuant swelling in his right knee. The plain radiograph showed a non-calcified soft-tissue swelling and MRI revealed a multi-loculated cystic lesion with multiple septations. A pre-operative diagnosis of a benign cystic lesion was made. It was managed by marginal excision of the tumor and a histological diagnosis of DAM was made. IHC staining showed positivity for SMA, CD34 and vimentin were focally positive, while desmin and calponin were negative. At 12 months of follow-up, the patient had a normal painless gait and full knee ROM, without any local recurrence. Conclusion: DAM is a rare tumor which is often misdiagnosed. In this report, we present a rare case of benign cystic lesion which turned out to be DAM on HPE of resected specimen. Marginal excision of this lesion revealed good outcomes with no recurrence until 12 months of final follow-up. With this, we conclude that surgical excision should be the gold standard in cases of DAM.

Effectiveness of Regional Nerve Blocks Versus Local Anesthetic Infiltration for Elective Hand and Wrist Surgery.

BACKGROUND: Pain relief by different methods in elective hand and wrist surgery is pivotal for patients undergoing elective wrist and hand surgery. AIM: To evaluate the effectiveness and duration of peripheral nerve block versus local surgical site anesthetic infiltration among patients undergoing elective wrist and hand surgery. SUBJECTS AND METHODS: This study was carried out in the Orthopaedic Department of Duhok Emergency Teaching Hospital, Duhok, Kurdistan region, Iraq. All patients who attended the Orthopaedic Department (total number=496) for elective hand and wrist surgery between November 2021 and November 2022 were included in the study, but only 300 patients completed the study protocol after the exclusion of 196 patients. Three methods of nerve block were used for postoperative pain relief. The degree and duration of pain relief were assessed. RESULTS: Patients who underwent ultrasound-guided nerve block had more duration of pain relief when compared to those patients who underwent local surgical site anesthetic infiltration and anatomical landmark nerve block (p<0.01), while patients who underwent local surgical site anesthetic infiltration had better pain relief when compared to those patients who underwent ultrasound-guided nerve block and anatomical landmark nerve block (p<0.01 for the group experiencing mild pain and p=0.12 for the group experiencing moderate pain and p<0.01 for the group experiencing severe pain). CONCLUSION: Ultrasound-guided nerve block is better for a longer duration of pain relief postoperatively than local surgical site anesthetic infiltration, while local surgical site anesthetic infiltration more effectively controls the severity of pain following elective hand and wrist surgery.

Addressing Worker Safety and Health Through the Lens of Strategic Enforcement-Part One.

Ensuring the safety and health of workers in this country, who are employed at millions of workplaces that present a dizzying array of hazards, is daunting. Every day, workers are maimed or die from workplace injuries or occupational illnesses. Hence, government agencies must use all available means to ensure the laws intended to keep workers safe and healthy in their workplaces are maximally effective in accomplishing that purpose. This paper addresses this challenge through the lens of strategic enforcement. It examines how federal and state authority are designed to interact to ensure worker protection in this space, and focuses on what tools for deterring violations - many unrecognized or underutilized by worker safety agencies - are available to leverage the limited resources that inevitably constrain the agencies' reach. The forthcoming Part II will, among other things, showcase a number of noteworthy state and local initiatives that exceed the federal standard.

Formulation of Neem and Echinacea Gel for Oral Health Along With the Evaluation of Antimicrobial, Cytotoxic, Anti-inflammatory, and Free Radical Scavenging Activity: An In Vitro Study.

Background Herbs have been used in medical practice for centuries and continue to play a significant role in modern complementary and alternative medicine. Phytochemicals in these herbs possess strong antioxidant and anti-inflammatory properties, which are beneficial in targeting oral health issues, such as dental plaque, gingivitis, and oral microbial infections. As research progresses, the challenge remains to translate these natural compounds into safe, effective, and accessible treatments for a wide range of diseases. Aim The aim of this research was to formulate the neem and echinacea gel along with the evaluation of antimicrobial, anti-inflammatory, free-radical scavenging activity, and cytotoxic potential. Materials and methods The neem and echinacea gel was prepared using a concentrated powdered mixture of neem and echinacea (5 grams each) to which 100 ml of distilled water was added, and the mixture was boiled for 30 minutes at 60°C. The 10 ml concentrate was mixed with 20 ml of a carbopol and carboxymethyl cellulose (CMC) mixture and mixed thoroughly, which resulted in neem and echinacea gel. Then, the antimicrobial, anti-inflammatory, cytotoxic potential, and free-radical scavenging activity of the gel were evaluated. The data obtained were statistically analyzed with the help of a paired t-test, where a p-value of less than 0.05 was considered statistically significant. Results The antimicrobial assay showed that neem and echinacea gel at the concentration of 100 micrograms showed a greater zone of inhibition against Staphylococcus aureus (3.15 ± 0.26), Streptococcus mutans (2.48 ± 0.45), Enterococcus faecalis (2.89 ± 0.15), and Candida albicans (4.28 ± 0.87). The cytotoxic test revealed that even at an 80 µg concentration of the extract, more than 70% of the nauplii were vital, which indicated that the gel was not cytotoxic. The highest anti-inflammatory activity (78.39 ± 1.82) of the gel was seen at 50 micrograms when compared with diclofenac sodium (73.16 ± 1.80). The free radical scavenging activity showed that the 2,2-diphenyl-1-picrylhydrazyl (DPPH) absorbance of the neem and echinacea extract was highest at 50 micrograms.  Conclusion The combination of neem and echinacea extract-based gel possessed high antimicrobial and anti-inflammatory activity when compared with standard drugs, such as amoxicillin and diclofenac sodium. The antioxidant activity of the gel was equal to butylated hydroxytoluene (BHT), and also the gel has a low cytotoxic potential even at its higher concentrations. Hence, the gel can be used as a natural remedy with minimal side effects, making it a valuable alternative to chemical agents.

Evidence and emerging trends in local therapy for metastatic hormone-sensitive prostate cancer: a narrative review.

Introduction: Metastatic hormone-sensitive prostate cancer (mHSPC) displays both simultaneous and sequential patterns of metastasis, emphasizing a comprehensive treatment approach that integrates both local therapy and systemic treatment strategies. The increasing use of molecular imaging has led to a rise in mHSPC diagnoses, underscoring the importance of identifying the right patient population and effective treatment concepts for this disease state. Results: Two prospective trials, HORRAD and STAMP EDE, investigated prostate radiotherapy (RT) for mHSPC; however, they did not show an overall survival (OS) benefit in the unselected cohort. Nonetheless, RT showed favorable outcomes in patients with fewer than five bone metastases, resulting in a 7% 3-year survival improvement and supporting the integration of RT in multimodal treatment for men with oligometastatic mHSPC. Regarding cytoreductive prostatectomy (cRP), the TRoMbone Trial confirmed its feasibility and safety. In addition, findings from the FUSCC-OMPCa Trial demonstrated improved 3-year radiographic progression-free survival and OS rates with acceptable rates of complications and incontinence. Recent data from the LoMP registry have further supported superior OS and cancer-specific survival (CSS) in patients undergoing cRP compared to systemic therapy alone. Notably, no significant differences in OS and CSS were observed between the cRP and RT groups. However, cRP-treated patients exhibited superior 2-year local event-free survival when compared to those treated with RT. Conclusion: RT in combination with systemic therapy remains the established first-line treatment for low-burden mHSPC, though the exact definition of low metastatic burden remains contentious. Precise assessment of metastatic burden is vital to identify patients who would derive the greatest benefit from RT. As treatment paradigms evolve, embracing multimodal approaches holds potential for optimizing outcomes in patients with mHSPC. Further research is needed to solidify the role of cRP as a standard therapeutic approach and to refine treatment strategies for improved patient outcomes.

CHNet: A multi-task global-local Collaborative Hybrid Network for KRAS mutation status prediction in colorectal cancer.

Accurate prediction of Kirsten rat sarcoma (KRAS) mutation status is crucial for personalized treatment of advanced colorectal cancer patients. However, despite the excellent performance of deep learning models in certain aspects, they often overlook the synergistic promotion among multiple tasks and the consideration of both global and local information, which can significantly reduce prediction accuracy. To address these issues, this paper proposes an innovative method called the Multi-task Global-Local Collaborative Hybrid Network (CHNet) aimed at more accurately predicting patients' KRAS mutation status. CHNet consists of two branches that can extract global and local features from segmentation and classification tasks, respectively, and exchange complementary information to collaborate in executing these tasks. Within the two branches, we have designed a Channel-wise Hybrid Transformer (CHT) and a Spatial-wise Hybrid Transformer (SHT). These transformers integrate the advantages of both Transformer and CNN, employing cascaded hybrid attention and convolution to capture global and local information from the two tasks. Additionally, we have created an Adaptive Collaborative Attention (ACA) module to facilitate the collaborative fusion of segmentation and classification features through guidance. Furthermore, we introduce a novel Class Activation Map (CAM) loss to encourage CHNet to learn complementary information between the two tasks. We evaluate CHNet on the T2-weighted MRI dataset, and achieve an accuracy of 88.93% in KRAS mutation status prediction, which outperforms the performance of representative KRAS mutation status prediction methods. The results suggest that our CHNet can more accurately predict KRAS mutation status in patients via a multi-task collaborative facilitation and considering global-local information way, which can assist doctors in formulating more personalized treatment strategies for patients.

Integrated approaches for comprehensive cetacean research and conservation in the East China Sea.

This study thoroughly examines three cetacean monitoring methods and assessing their advantages and limitations, establishing a foundational basis for comprehensive information on composition, distribution, and behavior. While real-time and non-invasive, visual surveys favor surface-active cetaceans and are weather-dependent. Local ecological knowledge supplements insights into group behavior. Environmental DNA (eDNA) analysis efficiently detects species like the narrow-ridged finless porpoise (Neophocaena asiaeorientalis) and common bottlenose dolphin (Tursiops truncatus), offering non-invasive, and spatially adept monitoring. Furthermore, eDNA provides prey species information, revealing the narrow-ridged finless porpoise's winter migration to deeper waters due to prey distribution. The study identifies prevalent prey species, like the Japanese Anchovy (Engraulis japonicus) and Osbeck's grenadier anchovy (Coilia mystus), offering insights into the porpoise's feeding ecology and adaptation to changing prey availability in winter. This study systematically compares diverse methodologies employed in cetacean surveys, thereby yielding a comprehensive understanding of cetacean distribution, behavior, and feeding ecology.

Diversity of ecotypes of five species of ryegrass from Northwestern Spain by phenotypic traits and microsatellites.

BACKGROUND: The Agricultural Research Centre of Mabegondo (Xunta de Galicia, A Coruña, Spain) conserves one of the most important collections of phytogenetic resources of ecotypes and natural populations of grassland species from northwestern Spain, among them populations of ryegrass (Lolium spp.), one of the most cultivated forage grasses in the world. The objective of the present study was to evaluate the diversity among commercial cultivars and natural ryegrass populations with phenotypic traits and molecular markers. RESULTS: Eleven polymorphic microsatellites loci were used to analyze 58 ecotypes and 10 cultivars (680 DNA samples in total) differentiating 673 genotypes. Two main groups were detected by the Structure analysis, one related to Lolium perenne and a second to Lolium multiflorum. The first group showed two subgroups and the second three. The cluster of L. multiflorum showed two subgroups not related with the third cluster including commercial varieties, one from the Canary Islands (with Lolium rigidum included) and a second one from northwestern Spain, which presented specific agromorphological characteristics, such as lower FES (number of days from 1 January, when three heads per plant were flowering per plot), CRE (growth in flowering, in g of dry matter), and AIN (number of inflorescences per plant). CONCLUSIONS: This is the first time that a large amount of data on ryegrass from the Iberian Peninsula has been analyzed, obtaining a clear genetic differentiation of the autochthonous varieties from the commercial varieties analyzed. In addition, the genetic structure found in the ecotypes was related to the phenotypic variation analyzed. Being of interest in the conservation of biodiversity and in obtaining better adapted varieties of ryegrasses, due to their specific phenotypic traits, such as a lower FES, CRE and AIN.

Regulating Local Electron Density of Cyano Sites in Graphitic Nitride Carbon by Giant Internal Electric Field for Efficient CO2 Photoreduction to Hydrocarbons.

Selective photocatalytic CO2 reduction to high-value hydrocarbons using graphitic carbon nitride (g-C3N4) polymer holds great practical significance. Herein, the cyano-functionalized g-C3N4 (CN-g-C3N4) with a high local electron density site is successfully constructed for selective CO2 photoreduction to CH4 and C2H4. Wherein the potent electron-withdrawing cyano group induces a giant internal electric field in CN-g-C3N4, significantly boosting the directional migration of photogenerated electrons and concentrating them nearby. Thereby, a high local electron density site around its cyano group is created. Moreover, this structure can also effectively promote the adsorption and activation of CO2 while firmly anchoring *CO intermediates, facilitating their subsequent hydrogenation and coupling reactions. Consequently, using H2O as a reducing agent, CN-g-C3N4 achieves efficient and selective photocatalytic CO2 reduction to CH4 and C2H4 activity, with maximum rates of 6.64 and 1.35 µmol g-1 h-1, respectively, 69.3 and 53.8 times higher than bulk g-C3N4 and g-C3N4 nanosheets. In short, this work illustrates the importance of constructing a reduction site with high local electron density for efficient and selective CO2 photoreduction to hydrocarbons.

Racial, ethnic, and neighborhood socioeconomic disparities in local cannabis retail policy in California.

BACKGROUND: Policies governing legal cannabis commerce can vary widely within a U.S. state when local control exists. Disproportionate distribution of policies allowing retail sale, protecting public health, or promoting equity in licensing may contribute to differences in health and economic outcomes between sociodemographic subgroups. This cross-sectional study jointly examined racial, ethnic, and neighborhood socioeconomic characteristics of Californians subject to specific local cannabis policies to identify such disparities. METHODS: Local laws in effect January 1, 2020, governing retail cannabis sales (bans, expanding buffers from youth-serving sites, restricting advertising, promoting equity in licensing, and capping outlets) were determined for California's 539 jurisdictions. The number of Asian, Black, Latinx, and white residents in socioeconomic advantaged versus disadvantaged neighborhoods (Census block groups) was determined using 2015-2019 American Community Survey data. We estimated proportions of the sociodemographic subpopulations covered by specific policies based on the block group's jurisdiction. To ascertain disparities in coverage proportions were compared across subgroups using Z-tests with the Bonferroni correction. RESULTS: Residents of socioeconomically advantaged neighborhoods were more likely to live in jurisdictions allowing retail cannabis commerce than those in disadvantaged neighborhoods (61.7 % versus 54.8 %). Black residents in advantaged neighborhoods were most likely to live where retailing was allowed (69 %), and white residents in disadvantaged neighborhoods least likely (49 %). Latinx and Black populations from disadvantaged neighborhoods were most likely to live in jurisdictions with stronger advertising restrictions (66 %). Equity in licensing policy was more prevalent for Black residents living in advantaged neighborhoods (57 %) than disadvantaged neighborhoods (49 %). CONCLUSIONS: Local cannabis policies potentially protecting public health and social equity are unequally distributed across race, ethnicity, and socioeconomic characteristics in California. Research examining whether differential policy exposure reduces, creates, or perpetuates cannabis-related health and socioeconomic disparities is needed.

Population diversity control based differential evolution algorithm using fuzzy system for noisy multi-objective optimization problems.

The objective measurements of the real-world optimization problems are mostly subject to noise which occurs due to several reasons like human measurement or environmental factors. The performance of the optimization algorithm gets affected if the effect of noise is higher than the negligible limit. The previous noise handling optimization algorithms use a large population size or multiple sampling at same region which increases the total count of function evaluations, and few methods work for a particular problem type. To address the above challenges, a Differential Evolution based Noise handling Optimization algorithm (NDE) to solve and optimize noisy bi-objective optimization problems is proposed. NDE is a Differential Evolution (DE) based optimization algorithm where the strategies for trial vector generation and the control parameters of DE algorithm are self-adapted using fuzzy inference system to improve the population diversity along the evolution process. In NDE, explicit averaging based method for denoising is used when the noise level is higher than negligible limit. Extending noise handling method enhances the performance of the optimization algorithm in solving real world optimization problems. To improve the convergence characteristics of the proposed algorithm, a restricted local search procedure is proposed. The performance of NDE algorithm is experimented using DTLZ and WFG problems, which are benchmark bi-objective optimization problems. The obtained results are compared with other SOTA algorithm using modified Inverted Generational Distance and Hypervolume performance metrics, from which it is confirmed that the proposed NDE algorithm is better in solving noisy bi-objective problems when compared to the other methods. To further strengthen the claim, statistical tests are conducted using the Wilcoxon and Friedman rank tests, and the proposed NDE algorithm shows significance over the other algorithms rejecting the null hypothesis.

Enhancing pancreatic cancer immunotherapy: Leveraging localized delivery strategies through the use of implantable devices and scaffolds.

Pancreatic cancer (PC) remains the predominant type of upper gastrointestinal tract cancer, associated with heightened morbidity and a survival rate below 12%. While immunotherapy has brought about transformative changes in the standards of care for most solid tumors, its application in PC is hindered by the ''cold tumor'' microenvironment, marked by the presence of immunosuppressive cells. Modest response rates in PC are attributed, in part to, the fibrotic stroma that obstructs the delivery of systemic immunotherapy. Furthermore, the occurrence of immune-related adverse events (iRAEs) often necessitates the use of sub-therapeutic doses or treatment discontinuation. In the pursuit of innovative approaches to enhance the effectiveness of immunotherapy for PC, implantable drug delivery devices and scaffolds emerge as promising strategies. These technologies offer the potential for sustained drug delivery directly to the tumor site, overcoming stromal barriers, immunosuppression, T cell exclusion, immunotherapy resistance, optimizing drug dosage, and mitigating systemic toxicity. This review offers a comprehensive exploration of pancreatic ductal adenocarcinoma (PDAC), the most common and aggressive form of PC, accompanied by a critical analysis of the challenges the microenvironment presents to the development of successful combinational immunotherapy approaches. Despite efforts, these approaches have thus far fallen short in enhancing treatment outcomes for PDAC. The review will subsequently delve into the imperative need for refining delivery strategies, providing an examination of past and ongoing studies in the field of localized immunotherapy for PDAC. Addressing these issues will lay the groundwork for the development of effective new therapies, thereby enhancing treatment response, patient survival, and overall quality of life for individuals diagnosed with PDAC.

Endoscopic Evacuation of Acute Subdural Hematomas: A New Selection Criterion.

Introduction Acute subdural hematomas (ASDHs) have a high mortality rate and unfavorable outcomes especially in the elderly population even after surgery is performed. The conventional recommended surgeries by the Brain Trauma Foundation in 2006 were craniotomies or craniectomies for ASDH. As the world population ages, and endoscopic techniques improve, endoscopic surgery should be utilized to improve the outcomes in elderly patients with ASDH. Materials and Methods This was a single-center retrospective report on our series of six patients that underwent endoscopic ASDH evacuation (EASE). Demographic data, the contralateral global cortical atrophy (GCA) score, evacuation rates, and outcomes were analyzed. Results All patients' symptoms and Glasgow Coma Scale improved or were similar after EASE with no complications. Good outcome was seen in 4 (66.7%) patients. Patients with poor outcome had initial low Glasgow Coma Scale scores on admission. The higher the contralateral GCA score, the higher the evacuation rate ( r = 0.825, p ≤ 0.043). All the patients had a GCA score of ≥7. Conclusion EASE is at least not inferior to craniotomy for the elderly population in terms of functional outcome for now. Using the contralateral GCA score may help identify suitable patients for this technique instead of just using a cut-off age as a criteria.

Combined impact of local anaesthetic infiltration through wound catheter and epidural analgesia following surgical hepatectomy: a meta-analysis.

Introduction: A meta-analysis was performed to examine the effects of wound catheter (WC) local anaesthetic infiltration (LAI) and epidural analgesia (EA) in open hepatectomy (OH). Material and methods: A systematic literature review was performed, which found 350 subjects with OH at the baseline of the studies; 159 of them were treated with WC local anaesthetic infiltration, and 191 used EA. Results: WC LAI substantially reduced the functional recovery time (MD = -0.64; 95% CI, -1.02 to -0.26, p < 0.001) and increased the pain score on the second postoperative day (MD = 0.25; 95% CI: 0.10-0.40, p < 0.001) compared to EA in OH patients. WC LAI did not vary from EA in OH patients in second postoperative opiate use (MD = -14.86; 95% CI: -32.88 to 3.16, p = 0.11) or overall complication rate (OR = 0.66; 95% CI: 0.41-1.04, p = 0.07). Conclusions: WC LAI showed a non-significant difference in opiate consumption on the second postoperative day and in the overall complication rate, compared with EA, but it showed a lower functional recovery time and higher pain score.

Contrast-Enhanced Mammography in Local Staging of Screen-Detected Breast Cancer.

BACKGROUND: BreastScreen Australia, the population mammographic screening program for breast cancer, uses two-view digital screening mammography ± ultrasound followed by percutaneous biopsy to detect breast cancer. Secondary breast imaging for further local staging, not performed at BreastScreen, may identify additional clinically significant breast lesions. Staging options include further mammography, bilateral ultrasound, and/or contrast-based imaging (CBI) [magnetic resonance imaging (MRI) or contrast-enhanced mammography (CEM)]. CBI for local staging of screen-detected cancer was introduced at an academic hospital breast service in Melbourne, VIC, Australia. We report findings for otherwise occult disease and resulting treatment changes. MATERIAL AND METHODS: Patients staged using CEM between November 2018 and April 2022 were identified from hospital records. Data were extracted from radiology, pathology, and breast unit databases. CEM-detected abnormalities were documented as true positive (TP) for invasive cancer or ductal carcinoma in situ (DCIS), or otherwise false positive (FP). The impact on surgical decisions was assessed. RESULTS: Of 202 patients aged 44-84 years, 60 (30%) had 74 additional findings [34 (46%) TP, 40 (54%) FP]. These were malignant in 29/202 (14%) patients (79% invasive cancers, 21% DCIS). CEM resulted in surgical changes in 43/202 (21%) patients: wider resection (24/43), conversion to mastectomy (6/43), contralateral breast surgery (6/43), additional ipsilateral excision (5/43), and bracketing (2/43). Additional findings were more common for patients with larger index lesions and for invasive cancer, but there was no significant variation by age, breast density, or index lesion grade. CONCLUSIONS: CEM for local staging of screen-detected breast cancers identified occult malignancy in 14% of patients. CEM improves local staging and may facilitate appropriate management of screen-detected breast cancers.

Regional invasion history and land use shape the prevalence of non-native species in local assemblages.

The ecological impact of non-native species arises from their establishment in local assemblages. However, the rates of non-native spread in new regions and their determinants have not been comprehensively studied. Here, we combined global databases documenting the occurrence of non-native species and residence of non-native birds, mammals, and vascular plants at regional and local scales to describe how the likelihood of non-native occurrence and their proportion in local assemblages relate with their residence time and levels of human usage in different ecosystems. Our findings reveal that local non-native occurrence generally increases with residence time. Colonization is most rapid in croplands and urban areas, while it is slower and variable in natural or semi-natural ecosystems. Notably, non-native occurrence continues to rise even 200 years after introduction, especially for birds and vascular plants, and in other land-use types rather than croplands and urban areas. The impact of residence time on non-native proportions is significant only for mammals. We conclude that the continental exchange of biotas requires considerable time for effects to manifest at the local scale across taxa and land-use types. The unpredictability of future impacts, implied by the slow spread of non-native species, strengthens the call for stronger regulations on the exchange of non-native species to reduce the long-lasting invasion debt looming on ecosystems' future.

Bioactivation of cinnamic alcohol in a reconstructed human epidermis model and evaluation of sensitizing potency of the identified metabolites.

Background: Cinnamic alcohol is a natural compound, widely used in fragrances, which can cause allergic contact dermatitis. Cinnamic alcohol lacks intrinsic reactivity and autoxidation or metabolic activation is necessary for it to act as a sensitizer. Methods: Bioactivation of cinnamic alcohol was explored using human liver microsomes, human liver S9 and SkinEthic™ Reconstructed Human Epidermis. A targeted multiple reaction monitoring mass spectrometry method was employed to study and quantify cinnamic alcohol along with eight potential phase I or phase II metabolites. The reconstructed human epidermis model, treated with cinnamic alcohol, was also analyzed with a non-targeted high-resolution mass spectrometry method to identify metabolites not included in the targeted method. Results: Two metabolites identified with the targeted method, namely, pOH-cinnamic alcohol and pOH-cinnamic aldehyde, have not previously been identified in a metabolic in vitro system. Their reactivity toward biologically relevant nucleophiles was investigated and compared to their sensitizing potency in vivo in the murine local lymph node assay (LLNA). According to the LLNA, the pOH-cinnamic alcohol is non-sensitizing and pOH-cinnamic aldehyde is a moderate sensitizer. This makes pOH-cinnamic aldehyde less sensitizing than cinnamic aldehyde, which has been found to be a strong sensitizer in the LLNA. This difference in sensitizing potency was supported by the reactivity experiments. Cinnamic sulfate, previously proposed as a potential reactive metabolite of cinnamic alcohol, was not detected in any of the incubations. In addition, experiments examining the reactivity of cinnamic sulfate toward a model peptide revealed no evidence of adduct formation. The only additional metabolite that could be identified with the non-targeted method was a dioxolan derivative. Whether or not this metabolite, or one of its precursors, could contribute to the sensitizing potency of cinnamic alcohol would need further investigation. Discussion: Cinnamic alcohol is one of the most common fragrance allergens and as it is more effective to patch test with the actual sensitizer than with the prohapten itself, it is important to identify metabolites with sensitizing potency. Further, improved knowledge of metabolic transformations occurring in the skin can improve prediction models for safety assessment of skin products.

Evidence for an adult summer diapause in mountain pine beetle (Coleoptera: Curculionidae) that varies geographically and among haplogroups.

Identifying dormancy traits is important for predicting insect population success, particularly in a changing climate that could disrupt evolved traits. The mountain pine beetle (Dendroctonus ponderosae Hopkins) is native to North America, is responsible for millions of acres of tree mortality, and is expanding northward in Canada. Research has identified thermal traits important to epidemic-phase ecology that vary among populations. Genomic research identified 3 mountain pine beetle haplogroups representing Pleistocene glacial refugia. Significant variation in generation timing aligning with the haplogroups has been observed. The adult stage was previously identified as the likely cause of differences among populations, although the mechanism(s) remain unclear. We tested for an adult summer diapause that varies among populations from 2 haplogroups, southern Colorado (CO) (central haplogroup) and southern Idaho (ID) (eastern haplogroup) using respirometry and reproduction experiments. Warm temperatures (25 °C) resulted in reduced respiration rates of central haplogroup mountain pine beetle compared to a cool temperature treatment (15 °C), whereas respiration of the eastern haplogroup did not differ between the treatments. Mated pairs of central haplogroup mountain pine beetle reared/held at 15 °C were more likely to be classified with a higher reproductive success rating compared to pairs reared/held at 25 °C. These results support a facultative summer adult diapause in southern CO central haplogroup mountain pine beetle. Manifestation of this diapause was low/absent among adults from the northerly ID location. This diapause likely serves to maintain univoltinism shown to be important for mountain pine beetle epidemic-phase ecology. The variation occurring among haplogroups highlights the long-term, evolved processes driving local adaptations in mountain pine beetle.