Modulation of the K/BxN arthritis mouse model and the effector functions of human fibroblast-like synoviocytes by liver X receptors.

The role of liver X receptors (LXR) in rheumatoid arthritis (RA) remains controversial. We studied the effect of LXR agonists on fibroblast-like synoviocytes (FLS) from RA patients and the K/BxN arthritis model in LXRα and ß double-deficient (Nr1h2/3-/-) mice. Two synthetic LXR agonists, GW3965 and T0901317, were used to activate LXRs and investigate their effects on cell growth, proliferation and matrix metalloproteinases, and chemokine production in cultured FLS from RA patients. The murine model K/BxN serum transfer of inflammatory arthritis in Nr1h2/3-/- animals was used to investigate the role of LXRs on joint inflammation in vivo. LXR agonists inhibited the FLS proliferative capacity in response to TNF, the chemokine-induced migration, the collagenase activity in FLS supernatant and FLS CXCL12 production. In the K/BxN mouse model, Nr1h2/3-/- animals showed aggravated arthritis, histological inflammation, and joint destruction, as well as an increase in synovial metalloproteases and expression of proinflammatory mediators such as IL-1ß and CCL2 in joints compared with wild type animals. Taken together, these data underscore the importance of LXRs in modulating the joint inflammatory response and highlight them as potential therapeutic targets in RA.

On a path toward a broad-spectrum anti-viral: inhibition of HIV-1 and coronavirus replication by SR kinase inhibitor harmine.

IMPORTANCE: This study highlights the crucial role RNA processing plays in regulating viral gene expression and replication. By targeting SR kinases, we identified harmine as a potent inhibitor of HIV-1 as well as coronavirus (HCoV-229E and multiple SARS-CoV-2 variants) replication. Harmine inhibits HIV-1 protein expression and reduces accumulation of HIV-1 RNAs in both cell lines and primary CD4+ T cells. Harmine also suppresses coronavirus replication post-viral entry by preferentially reducing coronavirus sub-genomic RNA accumulation. By focusing on host factors rather than viral targets, our study offers a novel approach to combating viral infections that is effective against a range of unrelated viruses. Moreover, at doses required to inhibit virus replication, harmine had limited toxicity and minimal effect on the host transcriptome. These findings support the viability of targeting host cellular processes as a means of developing broad-spectrum anti-virals.

Convergent adaptation of true crabs (Decapoda: Brachyura) to a gradient of terrestrial environments.

For much of terrestrial biodiversity, the evolutionary pathways of adaptation from marine ancestors are poorly understood, and have usually been viewed as a binary trait. True crabs, the decapod crustacean infraorder Brachyura, comprise over 7,600 species representing a striking diversity of morphology and ecology, including repeated adaptation to non-marine habitats. Here, we reconstruct the evolutionary history of Brachyura using new and published sequences of 10 genes for 344 tips spanning 88 of 109 brachyuran families. Using 36 newly vetted fossil calibrations, we infer that brachyurans most likely diverged in the Triassic, with family-level splits in the late Cretaceous and early Paleogene. By contrast, the root age is underestimated with automated sampling of 328 fossil occurrences explicitly incorporated into the tree prior, suggesting such models are a poor fit under heterogeneous fossil preservation. We apply recently defined trait-by-environment associations to classify a gradient of transitions from marine to terrestrial lifestyles. We estimate that crabs left the marine environment at least seven and up to 17 times convergently, and returned to the sea from non-marine environments at least twice. Although the most highly terrestrial- and many freshwater-adapted crabs are concentrated in Thoracotremata, Bayesian threshold models of ancestral state reconstruction fail to identify shifts to higher terrestrial grades due to the degree of underlying change required. Lineages throughout our tree inhabit intertidal and marginal marine environments, corroborating the inference that the early stages of terrestrial adaptation have a lower threshold to evolve. Our framework and extensive new fossil and natural history datasets will enable future comparisons of non-marine adaptation at the morphological and molecular level. Crabs provide an important window into the early processes of adaptation to novel environments, and different degrees of evolutionary constraint that might help predict these pathways.

Post-Cambrian survival of the tubicolous scalidophoran Selkirkia.

Scalidophoran worms represent common infaunal components of early and middle Cambrian Burgess Shale-type fossil biotas. Early scalidophorans resemble extant priapulids based on overall morphology, but the genus Selkirkia represents the earliest record of tube dwelling for the group. Despite its ubiquitous presence in exceptional marine deposits, whether the exclusively Cambrian occurrence of Selkirkia reflects its entire evolutionary history or is affected by taphonomic biases remains unresolved. Here, we demonstrate the post-Cambrian survival of Selkirkia based on new material from the Lower Ordovician Fezouata Shale biota of Morocco. The discovery of Selkirkia in the Fezouata Shale extends the biostratigraphic range of the genus by 25 million years and its palaeobiogeographic occurrence to the high latitudes of Gondwana, strengthens the evolutionary links between Cambrian and Ordovician Burgess Shale-type biotas and increases scalidophoran diversity for the Fezouata Shale biota otherwise consisting exclusively of the palaeoscolecid Palaeoscolex? tenensis. The tube of Selkirkia underwent negligible external change for over 40 million years, indicating a high degree of morphological stasis during the Early Palaeozoic. A tubicolous mode of life is rare among extant priapulids and expressed only in Maccabeus, which forms a delicate tube from agglutinated plant debris, unlike the macroscopic secreted cuticular tube of Selkirkia.

Cost-effectiveness of robotic vs laparoscopic distal pancreatectomy. Results from the national prospective trial ROBOCOSTES.

INTRODUCTION: Although several studies report that the robotic approach is more costly than laparoscopy, the cost-effectiveness of robotic distal pancreatectomy (RDP) over laparoscopic distal pancreatectomy (LDP) is still an issue. This study evaluates the cost-effectiveness of the RDP and LDP approaches across several Spanish centres. METHODS: This study is an observational, multicenter, national prospective study (ROBOCOSTES). For one year from 2022, all consecutive patients undergoing minimally invasive distal pancreatectomy were included, and clinical, QALY, and cost data were prospectively collected. The primary aim was to analyze the cost-effectiveness between RDP and LDP. RESULTS: During the study period, 80 procedures from 14 Spanish centres were analyzed. LDP had a shorter operative time than the RDP approach (192.2 min vs 241.3 min, p = 0.004). RDP showed a lower conversion rate (19.5% vs 2.5%, p = 0.006) and a lower splenectomy rate (60% vs 26.5%, p = 0.004). A statistically significant difference was reported for the Comprehensive Complication Index between the two study groups, favouring the robotic approach (12.7 vs 6.1, p = 0.022). RDP was associated with increased operative costs of 1600 euros (p < 0.031), while overall cost expenses resulted in being 1070.92 Euros higher than the LDP but without a statistically significant difference (p = 0.064). The mean QALYs at 90 days after surgery for RDP (0.9534) were higher than those of LDP (0.8882) (p = 0.030). At a willingness-to-pay threshold of 20,000 and 30,000 euros, there was a 62.64% and 71.30% probability that RDP was more cost-effective than LDP, respectively. CONCLUSIONS: The RDP procedure in the Spanish healthcare system appears more cost-effective than the LDP.

Post-traumatic cortical cystic lesions in children: three case reports and a systematic review of the literature.

Post-traumatic cortical cystic lesions are rare radiolucent lesions that appear as a complication of low-severity fractures in children. Their relevance lies in the fact that few cases of these lesions have been described to date, so they are little known among clinicians caring for children. Three case reports of well-circumscribed cortical lytic lesions detected at 2-4 months during the follow-up of non-displaced distal radius fractures in children aged 9, 7, and 2 years are presented. The consistent clinical history and typical radiological features allowed the accurate diagnosis of post-traumatic cortical cystic lesion, without the need for advanced imaging tests or biopsy. At 12-, 8- and 11-month follow-ups, respectively, the lesions either disappeared or decreased in size. This benign and self-limited lesion should be correctly recognized to avoid confusion with other diagnoses, advanced imaging tests or biopsies, and unnecessary parental concerns.

Synthetic suture tape for medial patellofemoral ligament reconstruction is an effective treatment for complex paediatric patellofemoral instability.

PURPOSE: To assess the outcomes of medial patellofemoral ligament (MPFL) reconstruction using synthetic suture tape in paediatric patients with patellofemoral instability (PFI). METHODS: This ambispective comparative study, conducted from 2014 to 2022, included paediatric patients who underwent MPFL reconstruction with synthetic suture tape and had a minimum follow-up of 1 year. Pre- and postoperative clinical and functional outcomes, patient satisfaction and complications were assessed. RESULTS: The study comprised 22 patients (29 knees), with a median age at surgery of 14.4 years (interquartile range [IQR] 10.9-16.7) and a median follow-up of 46.5 months (24.7-66). Notably, 13 knees (44.8%) had open growth plates at the time of surgery. The cohort included patients with Down syndrome (3 patients), Ehlers-Danlos (2), arthrogryposis (1), generalized joint hypermobility (8) and previous unsuccessful PFI surgeries (8). Concomitant procedures were performed on 16 knees. Postoperatively, improvements were observed in all but one patient, who reported residual pain. There were two other complications: one suture-tape rupture and one surgical wound infection. Functional scores significantly improved: Kujala, +14 points (7-29) (p < 0.001); IKDC, +10.5 points (5.2-25.3) (p < 0.001); Tegner, +2 points (0-4) (p < 0.001); Lysholm, +15 points (0-37.5) (p < 0.001). Most patients achieved excellent outcomes by Crosby-Insall criteria (21 patients, 72.4%) and reported high satisfaction (23 patients, 79.3%). CONCLUSIONS: MPFL reconstruction using synthetic suture tape is a viable and effective treatment for paediatric patients with PFI, particularly for those with connective tissue disorders, generalized joint hypermobility or past surgical failures, significantly enhancing clinical and functional outcomes with an acceptable complication rate. LEVEL OF EVIDENCE: Level IV.

Physeal Migration During Knee-guided Growth With Tension Band Plates: Influence of Implant Position.

OBJECTIVE: Physeal migration during guided growth with tension band plates (TBPs) has been poorly described. The positioning factors associated with this phenomenon and its clinical implications are unknown. Our aim is to determine the influence of implant position on the risk of physeal migration during knee-guided growth with TBP. METHODS: Retrospective study of 491 patients who underwent temporary hemi or epiphysiodesis with TBP around the knee between 2007 and 2019. We identified 29 patients who presented physeal migration during follow-up. Demographic and clinical data were collected, and the following measures were obtained from the immediate postoperative radiographs: epiphyseal screw base-physis distance/epiphyseal screw tip-physis distance, interscrew angle, epiphyseal screw-physis angle(ES-PHa)/metaphyseal screw-physis angle, plate-physis angle, epiphyseal screw-plate angle/metaphyseal screw-plate angle, and epiphyseal screw-physis length ratio. Using follow-up radiographs, the type of physeal migration of the epiphyseal screw (touch, occupy, or traverse) and the status of the physis after implant removal (unaltered, physeal bar, and skeletal maturity) were also recorded. A descriptive analysis of the cases and a case-control comparison of imaging studies were performed. RESULTS: The median patient age at intervention was 12.2 years (interquartile range: 11.3 to 14.1), and 76% were males. A statistically significant difference between cases and controls was obtained for epiphyseal screw base-physis distance (3.7 vs 6.3; P = 0.029), epiphyseal screw tip-physis distance (3.6 vs 7.85; P = 0.002), ES-PHa (-0.1 vs 7.45; P = 0.007), and plate-physis angle (85.45 vs 88.60; P = 0.012). In a categorical analysis, a significant difference was found for the ES-PHa categories ( P = 0.002) and for the ES-PHa/metaphyseal screw-physis angle categorical pair ( P = 0.018). In 16, 17, and 12 cases the physis was touched, occupied, or traversed, respectively, although we found no physeal alterations after plate removal. CONCLUSIONS: In our study, physeal migration of TBP is not an uncommon phenomenon, although no physeal abnormalities were detected. Convergent placement of the epiphyseal screw with the base or tip close to the physis should be avoided as this position is associated with a higher risk of physeal migration. LEVEL OF EVIDENCE: Level III-case-control study.

Feeding patterns of Atlantic salmon (Salmo salar) parr are better explained by local drivers than by macroecological drivers.

We modeled feeding of the Atlantic salmon (Salmo salar) parr to understand the role of global (cross-continental) and regional (river) spatial scales for delineating feeding patterns. The diet composition differed between Eurasia and North America populations. Geographic location (latitude and elevation) had an influence for the most common prey (Ephemeroptera, Diptera and Plecoptera). The random factors (sampling location and river) had a strong explanatory power in our models, suggesting that local drivers may override the effects of large-scale drivers.

Transphyseal arthroscopic anterior cruciate ligament reconstruction in children under 12 years.

BACKGROUND: The incidence of anterior cruciate ligament (ACL) injuries in children is on the rise. Despite this trend, the optimal management of these injuries remains a matter of ongoing debate. In this light, our study seeks to assess the clinical, radiological, and functional outcomes of transphyseal ACL reconstruction in preadolescent patients in the medium-term. METHODS: This prospective study included preadolescent patients aged up to 12 years who underwent ACL transphyseal reconstruction between 2010 and 2020 and had a minimum follow-up of 2 years. Clinical assessments encompassed joint stability and range of motion. Furthermore, leg length discrepancy (LLD) and femorotibial alignment were evaluated both clinically and radiologically using full-length lower limb standing radiographs. Pre- and postoperative functional outcomes were assessed using the International Knee Documentation Committee (IKDC) and Lysholm scales, and the return to normal sports activity was evaluated using the ACL-Return to Sport after Injury (ACL-RSI) scale. Complications and relevant follow-up data were also recorded. Statistical analyses were conducted to evaluate these outcomes. RESULTS: A total of 35 preadolescent patients, consisting of 24 males and 11 females, with a mean age at surgery of 11.2 ± 0.7 years (8.7-12), were included in the study. The mean follow-up was 52.3 ± 20.7 months (24.1-95.9). No significant growth disturbances or clinically relevant LLD were evidenced. All patients demonstrated clinically stable knees with full range of motion at the 2-year follow-up. There were statistically significant improvements in pre- and postoperative IKDC (39.3 ± 13.5 vs. 99.7 ± 0.8, p < 0.005) and Lysholm scores (48.2 ± 15.1 vs. 99.6 ± 1.4, p < 0.005). All but two patients were able to return to their pre-injury level of sports activity, with a mean ACL-RSI score of 93.5 ± 1.3. The analysis revealed an 8.6% rerupture rate and an 11.4% rate of contralateral ACL injuries, with 5-year survival rates of 92.3% and 88.8%, respectively. Subgroup analyses based on age, gender, surgical delay, or associated meniscal lesions did not reveal any significant differences in functional outcomes. Additionally, there was no discernible relationship between age or timing of ACL reconstruction and the risk of meniscal injuries. CONCLUSIONS: Our study reinforces the value of ACL reconstruction in skeletally immature preadolescent patients, with transphyseal technique proven to be a safe, effective, and technically simpler option, even for children under the age of 12. The findings indicate excellent functional outcomes, a high rate of successful return to sporting activities, and minimal to no incidence of growth-related complications in the medium-term. LEVEL OF EVIDENCE: Level II, prospective comparative cohort study, before and after intervention.

Outpatient Foot-Sparing Surgery Is Safe in Selected Patients with Diabetic Foot Infections.

OBJECTIVE: To determine if outpatient foot-sparing surgery for patients with diabetic foot infections (DFIs) is associated with a higher rate of treatment failure or longer healing time. METHODS: In this prospective observational study, the authors consecutively recruited a cohort of 200 patients with moderate and severe DFIs from the Diabetic Foot Unit of Hospital San Juan de Dios, Caja Costarricense de Seguro Social, San José de Costa Rica, Costa Rica from October 15, 2020 to December 15, 2021. They compared outpatients with those admitted. Cox univariate analysis was performed, with time to treatment failure and time to healing as dependent variables and outpatient management as the independent variable. RESULTS: Seventy-one patients underwent surgery on an outpatient basis (35.5%), and 129 (64.5%) were admitted. Sixty of 111 patients (54.1%) with moderate infections were treated as outpatients versus 11 of 89 (12.4%) of those with severe infections. Twelve (16.9%) of the outpatients and 26 (20.2%) of those admitted presented failure (P = .57). The Cox univariate analysis with time to failure of treatment associated with outpatient management reported a hazard ratio of 1.26 (95% CI, 0.64-2.50; P = .50), and the analysis regarding healing time reported a hazard ratio of 0.91 (95% CI, 0.66-1.25; P = .56). CONCLUSIONS: Foot-sparing surgery on an outpatient basis was safe in more than half the cases of moderate DFIs, especially in patients with osteomyelitis. This approach is not associated with treatment failure or a longer healing time. Patients with severe infections, penetrating injuries, necrosis, or high inflammatory response and those with peripheral arterial disease who require revascularizations should be admitted to the hospital.

Is reduction necessary in overriding metaphyseal distal radius fractures in children under 11 years: a systematic review and meta-analysis of comparative studies.

OBJECTIVE: To determine the necessity of reduction in the treatment of overriding metaphyseal distal radius fractures (DRF) in children under 11 years. METHODS: In this systematic review and meta-analysis, PubMed, Embase, and Cochrane databases were searched to retrieve studies published from inception to 2023. Two reviewers independently screened for studies with observational or randomized control design comparing two treatments for overriding metaphyseal DRF in patients under 11 years: simple casting without reduction (SC group) versus closed reduction plus casting or pin fixation (CRC/F group); with varying outcomes reported (CRD471761). The risk of bias was assessed using the ROBINS-I tool. RESULTS: Out of 3,024 screened studies, three met the inclusion criteria, 180 children (mean age 7.1 ± 0.9 years) with overriding metaphyseal DRF: SC-group (n = 79) versus CRC/F-group (n = 101). Both treatment groups achieved 100% fracture consolidation without requiring further manipulation. The SC-group showed significantly fewer complications (mean difference [MD] 0.08; 95% CI [0.01, 0.53]; I2 = 22%; P < 0.009) and trends towards better sagittal alignment (MD 5.11; 95% CI [11.92, 1.71]; I2 = 94%; P < 0.14), less reinterventions (MD 0.31; 95% CI [0.01, 8.31]; P < 0.48), and fewer patients with motion limitation at the end of follow-up (MD 0.23; 95% CI [0.03,  1.98]; P < 0.18), although these findings were not statistically significant. CONCLUSIONS: Despite a limited number of studies comparing SC versus CRC/F in overriding DRF in children under 11 years, this study suggests that anatomical reduction is not necessary. Treating these fractures with SC, even when presenting with an overriding position, leads to reduced complications, shows a trend towards fewer reinterventions, improved sagittal alignment, and less limitation in patient motion. LEVEL OF EVIDENCE: Level III, Systematic review of Level-III studies.

Convergent evolution of ventral adaptations for enrolment in trilobites and extant euarthropods.

The ability to enrol for protection is an effective defensive strategy that has convergently evolved multiple times in disparate animal groups ranging from euarthropods to mammals. Enrolment is a staple habit of trilobites, and their biomineralized dorsal exoskeleton offered a versatile substrate for the evolution of interlocking devices. However, it is unknown whether trilobites also featured ventral adaptations for enrolment. Here, we report ventral exoskeletal adaptations that facilitate enrolment in exceptionally preserved trilobites from the Middle Ordovician Walcott-Rust Quarry in New York State, USA. Walcott-Rust trilobites reveal the intricate three-dimensional organization of the non-biomineralized ventral anatomy preserved as calcite casts, including the spatial relationship between the articulated sternites (i.e. ventral exoskeletal plates) and the wedge-shaped protopodites. Enrolment in trilobites is achieved by ventrally dipping the anterior margin of the sternites during trunk flexure, facilitated by the presence of flexible membranes, and with the close coupling of the wedge-shaped protopodites. Comparisons with the ventral morphology of extant glomerid millipedes and terrestrial isopods reveal similar mechanisms used for enrolment. The wedge-shaped protopodites of trilobites closely resemble the gnathobasic coxa/protopodite of extant horseshoe crabs. We propose that the trilobites' wedge-shaped protopodite simultaneously facilitated tight enrolment and gnathobasic feeding with the trunk appendages.

Three-dimensional morphology of the biramous appendages in Isoxys from the early Cambrian of South China, and its implications for early euarthropod evolution.

Early euarthropod evolution involved a major transition from lobopodian-like taxa to organisms featuring a segmented, well-sclerotized trunk (arthrodization) and limbs (arthropodization). However, the precise origin of a completely arthrodized trunk and arthropodized ventral biramous appendages remain controversial, as well as the early onset of anterior-posterior limb differentiation in stem-group euarthropods. New fossil material and micro-computed tomography inform the detailed morphology of the arthropodized biramous appendages in the carapace-bearing euarthropod Isoxys curvirostratus from the early Cambrian Chengjiang biota. In addition to well-developed grasping frontal appendages, I. curvirostratus possesses two batches of morphologically and functionally distinct biramous limbs. The first batch consists of four pairs of short cephalic appendages with robust endites with a feeding function, whereas the second batch has more elongate trunk appendages for locomotion. Critically, our new material shows that the trunk of I. curvirostratus was not arthrodized. The results of our phylogenetic analyses recover isoxyids as some of the earliest branching sclerotized euarthropods, and strengthens the hypothesis that arthropodized biramous appendages evolved before full body arthrodization.

Platinum(IV)-Gold(I) Agents with Promising Anticancer Activity: Selected Studies in 2D and 3D Triple-Negative Breast Cancer Models.

New heterometallic binuclear and trinuclear platinum(IV)-gold(I) compounds of the type [Pt(L)n Cl2 (OH){(OOC-4-C6 H4 -PPh2 )AuCl}x ] (L=NH3 , n=2; x=1, 2; L=diaminocyclohexane, DACH, n=1; x=2) are described. These compounds are cytotoxic and selective against a small panel of renal, bladder, ovarian, and breast cancer cell lines. We selected a trinuclear PtAu2 compound containing the PtIV core based on oxaliplatin, to further investigate its cell-death pathway, cell and organelle uptake and anticancer effects against the triple-negative breast cancer (TNBC) MDA-MB-231 cell line. This compound induces apoptosis and accumulates mainly in the nucleus and mitochondria. It also exerts remarkable antimigratory and antiangiogenic properties, and has a potent cytotoxic effect against TNBC 3D spheroids. Trinuclear compounds do not seem to display relevant interactions with calf thymus (CT) DNA and plasmid (pBR322) even in the presence of reducing agents, but inhibit pro-angiogenic enzyme thioredoxin reductase (TrxR) in TNBC cells.

Underwater versus conventional EMR of large nonpedunculated colorectal lesions: a multicenter randomized controlled trial.

BACKGROUND AND AIMS: Underwater EMR (UEMR) is an alternative procedure to conventional EMR (CEMR) to treat large, nonpedunculated colorectal lesions (LNPCLs). In this multicenter, randomized controlled clinical trial, we aimed to compare the efficacy and safety of UEMR versus CEMR on LNPCLs. METHODS: We conducted a multicenter, randomized controlled clinical trial from February 2018 to February 2020 in 11 hospitals in Spain. A total of 298 patients (311 lesions) were randomized to the UEMR (n = 149) and CEMR (n = 162) groups. The main outcome was the lesion recurrence rate in at least 1 follow-up colonoscopy. Secondary outcomes included technical aspects, en bloc resection rate, R0 resection rates, and adverse events, among others. RESULTS: There were no differences in the overall recurrence rate (9.5% UEMR vs 11.7% CEMR; absolute risk difference, -2.2%; 95% CI, -9.4 to 4.9). However, considering polyp sizes between 20 and 30 mm, the recurrence rate was lower for UEMR (3.4% UEMR vs 13.1% CEMR; absolute risk difference, -9.7%; 95% CI, -19.4 to 0). The R0 resection showed the same tendency, with significant differences favoring UEMR only for polyps between 20 and 30 mm. Overall, UEMR was faster and easier to perform than CEMR. Importantly, the techniques were equally safe. CONCLUSIONS: UEMR is a valid alternative to CEMR for treating LNPCLs and could be considered the first option of treatment for lesions between 20 and 30 mm due to its higher en bloc and R0 resection rates. (Clinical trial registration number: NCT03567746.).

Fresh perspectives on the River Continuum Concept require trophic ecology approaches focussed on food web structure and energy mobilisation routes.

Stream-dwelling communities are expected to show a gradual replacement of the dominant feeding types following the type of resources found along the river continuum. Yet, the underlying longitudinal gradients in food web structure and energy flow-paths remain poorly understood. Here, I synthesise novel research on the River Continuum Concept (RCC) and identify promising areas for future research linked to longitudinal changes in food-chain length and energy mobilisation routes. For example, feeding links and connectance should reach maximum values in mid-order rivers and then decrease to river mouths following uncovered longitudinal diversity patterns. Regarding energy mobilisation routes, a gradual replacement in the food web fuelling between allochthonous (leaf litter) and autochthonous (periphyton) resources should be expected. Beyond longitudinal changes in primary basal resource to consumer paths, other allochthonous (e.g. riparian arthropod inputs) and autochthonous (e.g. fish prey) inputs subsidising higher level consumers may show longitudinal changes, that is, terrestrial invertebrates decreasing but piscivory increasing downstream. However, the role of these inputs, that can alter predator niche variation and have indirect community-based effects, on both food web structure and energy flow-paths along the river continuum is not clear yet. Incorporating energy mobilisation and food web structure into RCC principles is necessary for a broad understanding of ecosystem functioning and trophic diversity in riverine systems, driving the emergence of novel insights. How function and structure of riverine food webs adapt to longitudinal changes in physical and biological environments represent a challenge for next generation of stream ecologists.

A regioselective synthesis of 3,4-diaryl-1H-pyrazoles through a 1,3-dipolar cycloaddition of tosylhydrazones and nitroalkenes.

A procedure for the selective synthesis of 3,4-diaryl-1H-pyrazoles through a 1,3-dipolar cycloaddition is reported. The transformation occurred under mild conditions using affordable tosylhydrazones and nitroalkenes commencing from benzaldehydes/heteroaromatic aldehydes as starting materials. Due to the versatility of this protocol, we prepared a vast collection of 3,4-diaryl-1H-pyrazoles, which included the incorporation of heterocyclic rings at the pyrazole core. Two-dimensional NMR techniques (2D-NOESY and HMBC) confirmed the regioselectivity of the transformation and correlated well with DFT calculations. Accordingly, the analysis of the transition states indicated that the 3,4-diaryl product corresponded to the product with the lowest activation energy and led to the most stable product. Finally, the series was evaluated against three cancer cell lines, with compound 8f being the most remarkable analog in terms of activity and extraordinary selectivity towards PC-3 compared to the other cell lines (including COS-7).

Contrast-enhanced Mammography Artifacts and Pitfalls: Tips and Tricks to Avoid Misinterpretation.

Contrast-enhanced mammography (CEM) involves addition of intravenous iodinated contrast material at digital mammography, thus increasing the ability to detect breast cancer owing to tumor contrast enhancement. After image acquisition, interpretation includes careful assessment of the technique, artifacts, and pitfalls and reporting with a standard lexicon category and appropriate follow-up recommendations. Artifacts and pitfalls that may cause image misinterpretation should be detected and distinguished from pathologic conditions. Different artifacts apparent on CEM images are usually caused during image acquisition and include CEM-specific and contrast agent-related artifacts, apart from the typical digital mammography artifacts. The pitfalls are related to technical and diagnostic difficulties. One disadvantage of CEM that MRI does not have is a technical factor related to a mammography technique that consists of blind spots that may not be included in the imaging field of mammography views, including the axilla, medial region of the breast, or areas close to the breast wall. Normal breast tissue enhancement called background parenchymal enhancement is also present at CEM and may affect interpretation performance. Diagnostic pitfalls are caused by minimally enhancing lesions, such as invasive lobular carcinomas and mucinous carcinomas, which are difficult to detect with CEM, resulting in false-negative findings. Benign lesions can show enhancement at CEM and represent false-positive lesions that should also be recognized. The authors discuss image interpretation of CEM studies and focus on the artifacts and pitfalls that may be encountered. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Protective ileostomy creation after anterior resection of the rectum: Shared decision-making or still subjective?

AIM: The choice of whether to perform protective ileostomy (PI) after anterior resection (AR) is mainly guided by risk factors (RFs) responsible for the development of anastomotic leakage (AL). However, clear guidelines about PI creation are still lacking in the literature and this is often decided according to the surgeon's preferences, experiences or feelings. This qualitative study aims to investigate, by an open-ended question survey, the individual surgeon's decision-making process regarding PI creation after elective AR. METHOD: Fifty four colorectal surgeons took part in an electronic survey to answer the questions and describe what usually led their decision to perform PI. A content analysis was used to code the answers. To classify answers, five dichotomous categories (In favour/Against PI, Listed/Unlisted RFs, Typical/Atypical, Emotions/Non-emotions, Personal experience/No personal experience) have been developed. RESULTS: Overall, 76% of surgeons were in favour of PI creation and 88% considered listed RFs in the question of whether to perform PI. Atypical answers were reported in 10% of cases. Emotions and personal experience influenced surgeons' decision-making process in 22% and 49% of cases, respectively. The most frequently considered RFs were the distance of the anastomosis from the anal verge (96%), neoadjuvant chemoradiotherapy (88%), a positive intraoperative leak test (65%), blood loss (37%) and immunosuppression therapy (35%). CONCLUSION: The indications to perform PI following rectal cancer surgery lack standardization and evidence-based guidelines are required to inform practice. Until then, expert opinion can be helpful to assist the decision-making process in patients who have undergone AR for adenocarcinoma.