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The article titled "Decentralized cooperation alliances for animal welfare, the case of World Horse Welfare" talks about the importance of global cooperation alliances to achieve animal welfare and meet the Sustainable Development Goals (SDGs). World Horse Welfare, a European organization, established strategies to implement animal welfare policies through awareness of the human-animal relationship and international cooperation. Surveys and training were conducted, research was carried out, and participation in events related to the 2030 Agenda took place. As a result, 3 SDGs were established within the organization and 4 SDGs within each of the 14 counterparts. These alliances have improved operational processes and impact on communities in terms of animal welfare, economic growth, and sustainability. [Extracted from the article]

Genital lymphedema is a challenging condition often refractory to conservative treatments. This case report presents a novel surgical approach combining a lymphatic system transfer based on a pedicled superficial circumflex iliac perforator flap with nanofibrillar collagen scaffolds to address genital lymphedema secondary to hidradenitis suppurativa. A 47-year-old man with hidradenitis suppurativa-related genital lymphedema, unresponsive to conservative measures, underwent the procedure. Indocyanine green lymphography and ultrahigh-frequency ultrasound were used for preoperative flap planning, including lymphatic vessels in the skin paddle. Nanofibrillar collagen scaffolds were placed to enhance lymphangiogenesis in distal genital areas. The patient experienced significant improvement, with a reduction in lymphedema severity from 5 of 9 to 1 of 9 on the Genital Lymphedema Score and substantial relief of symptoms. Single-photon emission computed tomography demonstrated uptake of 18 F-fluorodeoxyglucose at the right inguinal lymph nodes, ipsilateral to the lymphatic flap. This case demonstrates the potential of this combined approach in managing complex genital lymphedema., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Accurately assessing flap volume and thickness is a crucial aspect of breast reconstruction using the deep inferior epigastric perforator (DIEP) flap, especially in challenging cases such as thin or large-breasted women or bilateral reconstruction. To address this, we present an innovative image processing tool utilizing computed tomography angiography (CTA) to measure DIEP flap volume and thickness. Our approach incorporates an elliptical equation validated on DIEP reconstruction patients. Preoperative abdominal CTA images were obtained from 70 patients who underwent DIEP flap breast reconstruction at Hospital Universitari de Bellvitge from 2017 to 2021. The image processing tool was employed for preoperative quantification, utilizing elliptical approximations, to determine the volume to be harvested and assess the central thickness of the flap. Subsequently, a non-parametric statistical retrospective analysis was conducted to examine these parameters in relation to immediate complications. The mean maximum recruitable volume (MRV) was 1017.15 ± 325.51 cm³, with a mean thickness of 3.65 ± 1.14 cm. No significant correlation was found between postoperative complications and MRV or thickness values. The processing tool offers a reliable solution for accurately measuring the volume and thickness of the DIEP flap from CTA images, aiding surgeons in breast reconstruction decision-making. This innovative approach enhances surgical planning by addressing quantitative values of thickness and volume of the DIEP flap, which is critical for accurate flap assessment., Competing Interests: All authors declare no financial tie or conflict of interest related directly or indirectly to the current work., (© 2024 The Author(s).)

Hunga Tonga-Hunga Ha'apai had a large eruption (VEI 5-6) on 15 January 2022, which caused a tsunami recorded in all ocean basins. Costa Rica has made many advances in tsunami preparation over the past 9 years since the creation of SINAMOT ( Sistema Nacional de Monitoreo de Tsunamis , National Tsunami Monitoring System), both on watch and warning protocols and on community preparedness. For the Hunga Tonga-Hunga Ha'apai event, the government declared a low-threat warning, suspending all in-water activities, even though the country did not receive any official warning from PTWC (Pacific Tsunami Warning Center) due to the lack of procedures for tsunamis generated by volcanoes. The tsunami was observed at 24 locations on both the Pacific and Caribbean coasts of Costa Rica, becoming the second most recorded tsunami in the country, after the 1991 Limon tsunami along the Caribbean coast. At 22 of those locations along the continental Pacific coast, observations were made by eyewitnesses, including one collocated with the sea level station at Quepos, which registered the tsunami. At Cocos Island (~ 500 km southwest of the continental Costa Rica, in the Pacific Ocean), several eyewitnesses reported the tsunami at two locations, and it was recorded at the sea level station. The tsunami was also recorded at the sea level station on the Caribbean coast. The tsunami effects reported were a combination of sea level fluctuations, strong currents, and coastal erosion, proving that the response actions were adequate for the size of the tsunami. Tsunami preparedness and the largest waves arriving during a dry season Saturday afternoon allowed the large number of eyewitness reports. This event then increased tsunami awareness in the country and tested protocols and procedures. Still, many people along the coast were not informed of the tsunami during the alert due to their remote location, the short notice of the warning, and a lack of procedures for some communities. There is thus still much work to do, particularly about warning dissemination, a direction in which communities should take an active role., Supplementary Information: The online version contains supplementary material available at 10.1007/s00445-023-01648-x., Competing Interests: Conflict of interestThe authors declare no competing interests., (© International Association of Volcanology & Chemistry of the Earth's Interior 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

We hypothesize that dosage compensation of critical genes arises from systems-level properties for cancer cells to withstand the negative effects of aneuploidy. We identified several candidate genes in cancer multiomics data and developed a biocomputational platform to construct a mathematical model of their interaction network with micro-RNAs and transcription factors, where the property of dosage compensation emerged for MYC and was dependent on the kinetic parameters of its feedback interactions with three micro-RNAs. These circuits were experimentally validated using a genetic tug-of-war technique to overexpress an exogenous MYC , leading to overexpression of the three microRNAs involved and downregulation of endogenous MYC. In addition, MYC overexpression or inhibition of its compensating miRNAs led to dosage-dependent cytotoxicity in MYC -amplified colon cancer cells. Finally, we identified negative correlation of MYC dosage compensation with patient survival in TCGA breast cancer patients, highlighting the potential of this mechanism to prevent aneuploid cancer progression., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Explaining the maintenance of tropical forest diversity under the countervailing forces of drift and competition poses a major challenge to ecological theory. Janzen-Connell effects, in which host-specific natural enemies restrict the recruitment of juveniles near conspecific adults, provide a potential mechanism. Janzen-Connell is strongly supported empirically, but existing theory does not address the stable coexistence of hundreds of species. Here we use high-performance computing and analytical models to demonstrate that tropical forest diversity can be maintained nearly indefinitely in a prolonged state of transient dynamics due to distance-responsive natural enemies. Further, we show that Janzen-Connell effects lead to community regulation of diversity by imposing a diversity-dependent cost to commonness and benefit to rarity. The resulting species-area and rank-abundance relationships are consistent with empirical results. Diversity maintenance over long time spans does not require dispersal from an external metacommunity, speciation, or resource niche partitioning, only a small zone around conspecific adults in which saplings fail to recruit. We conclude that the Janzen-Connell mechanism can explain the maintenance of tropical tree diversity while not precluding the operation of other niche-based mechanisms such as resource partitioning., Competing Interests: Conflict of interest statement: J.T. and S.A.L. are coauthors on a 2016 retrospective article.

Background: The differential diagnosis between patients with essential tremor (ET) and those with Parkinson's disease (PD) whose main manifestation is tremor may be difficult unless using complex neuroimaging techniques such as 123I-FP-CIT SPECT. We considered that using smartphone's accelerometer to stablish a diagnostic test based on time-frequency differences between PD an ET could support the clinical diagnosis., Methods: The study was carried out in 17 patients with PD, 16 patients with ET, 12 healthy volunteers and 7 patients with tremor of undecided diagnosis (TUD), who were re-evaluated one year after the first visit to reach the definite diagnosis. The smartphone was placed over the hand dorsum to record epochs of 30 s at rest and 30 s during arm stretching. We generated frequency power spectra and calculated receiver operating characteristics curves (ROC) curves of total spectral power, to establish a threshold to separate subjects with and without tremor. In patients with PD and ET, we found that the ROC curve of relative energy was the feature discriminating better between the two groups. This threshold was then used to classify the TUD patients., Results: We could correctly classify 49 out of 52 subjects in the category with/without tremor (97.96% sensitivity and 83.3% specificity) and 27 out of 32 patients in the category PD/ET (84.38% discrimination accuracy). Among TUD patients, 2 of 2 PD and 2 of 4 ET were correctly classified, and one patient having PD plus ET was classified as PD., Conclusions: Based on the analysis of smartphone accelerometer recordings, we found several kinematic features in the analysis of tremor that distinguished first between healthy subjects and patients and, ultimately, between PD and ET patients. The proposed method can give immediate results for the clinician to gain valuable information for the diagnosis of tremor. This can be useful in environments where more sophisticated diagnostic techniques are unavailable.

Background: Matrix metalloproteinases (MMPs) are associated with Kaposi's sarcoma (KS) tumorigenesis. To date, only a few MMPs have been studied in KS lesions. Their role in KS regression has not been investigated. The aim of this study was to evaluate the expression of multiple MMPs in developing and pharmacologically regressed KS lesions., Methods: Nine samples of acquired immune deficiency syndrome (AIDS)-related and classic cutaneous KS lesions at various histological stages were studied. Regressing KS lesions from three patients treated with systemic therapy were procured after one and two cycles of chemotherapy. Tissue sections from all specimens were immunostained using monoclonal antibodies to MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, and MMP-14., Results: KS lesional cells were immunoreactive for all MMPs, except MMP-14. Admixed inflammatory cells were immunoreactive for MMP-1, MMP-2, MMP-7, MMP-9, and MMP-13. The MMP immunoprofile in residual KS lesional cells was unaltered in regressed lesions. Increased extracellular matrix (ECM) and macrophage immunoreactivity for MMPs was identified in regressed specimens., Conclusions: These data show that developing KS lesional cells express collagenases (MMP-1, MMP-13), gelatinases (MMP-2, MMP-9), stromelysin-1 (MMP-3), and matrilysin (MMP-7) but not the membrane-type MMP-14. This MMP expression profile is retained by residual KS cells and also expressed by infiltrating macrophages in regressed KS lesions. Pantanowitz L, Dezube BJ, Hernandez-Barrantes S, Tahan SR, Dabbous MK. Matrix metalloproteinases in the progression and regression of Kaposi's sarcoma.

MMP-9 (gelatinase B) is produced in a latent form (pro-MMP-9) that requires activation to achieve catalytic activity. Previously, we showed that MMP-2 (gelatinase A) is an activator of pro-MMP-9 in solution. However, in cultured cells pro-MMP-9 remains in a latent form even in the presence of MMP-2. Since pro-MMP-2 is activated on the cell surface by MT1-MMP in a process that requires TIMP-2, we investigated the role of the MT1-MMP/MMP-2 axis and TIMPs in mediating pro-MMP-9 activation. Full pro-MMP-9 activation was accomplished via a cascade of zymogen activation initiated by MT1-MMP and mediated by MMP-2 in a process that is tightly regulated by TIMPs. We show that TIMP-2 by regulating pro-MMP-2 activation can also act as a positive regulator of pro-MMP-9 activation. Also, activation of pro-MMP-9 by MMP-2 or MMP-3 was more efficient in the presence of purified plasma membrane fractions than activation in a soluble phase or in live cells, suggesting that concentration of pro-MMP-9 in the pericellular space may favor activation and catalytic competence.

Membrane type 1 matrix metalloproteinase (MT1-MMP) is a type I transmembrane MMP shown to play a critical role in normal development and in malignant processes. Emerging evidence indicates that MT1-MMP is regulated by a process of ectodomain shedding. Active MT1-MMP undergoes autocatalytic processing on the cell surface, leading to the formation of an inactive 44-kDa fragment and release of the entire catalytic domain. Analysis of the released MT1-MMP forms in various cell types revealed a complex pattern of shedding involving two major fragments of 50 and 18 kDa and two minor species of 56 and 31-35 kDa. Protease inhibitor studies and a catalytically inactive MT1-MMP mutant revealed both autocatalytic (18 kDa) and non-autocatalytic (56, 50, and 31-35 kDa) shedding mechanisms. Purification and sequencing of the 18-kDa fragment indicated that it extends from Tyr(112) to Ala(255). Structural and sequencing data indicate that shedding of the 18-kDa fragment is initiated at the Gly(284)-Gly(285) site, followed by cleavage between the conserved Ala(255) and Ile(256) residues near the conserved methionine turn, a structural feature of the catalytic domain of all MMPs. Consistently, a recombinant 18-kDa fragment had no catalytic activity and did not bind TIMP-2. Thus, autocatalytic shedding evolved as a specific mechanism to terminate MT1-MMP activity on the cell surface by disrupting enzyme integrity at a vital structural site. In contrast, functional data suggest that the non-autocatalytic shedding generates soluble active MT1-MMP species capable of binding TIMP-2. These studies suggest that ectodomain shedding regulates the pericellular and extracellular activities of MT1-MMP through a delicate balance of active and inactive enzyme-soluble fragments.

Pericellular proteolysis is a hallmark of tumor cell metastasis. The membrane type (MT)-matrix metalloproteinases (MMPs) constitute a distinctive group of membrane-bound MMPs that are central mediators of surface proteolytic events that regulate tumor cell motility, metastasis and angiogenesis. As membrane-tethered proteases, the MT-MMPs exhibit unique regulatory mechanisms and interactions with metalloproteinase inhibitors and other relevant molecules. This review will focus on new emerging information on the mechanisms that regulate MT-MMP processing, activity and inhibition, and their significance for enzyme function in the tumor microenvironment., (Copyright 2002 Elsevier Science Ltd. All rights reserved.)

The tissue inhibitors of metalloproteinases (TIMPs) are specific inhibitors of MMP enzymatic activity. However, TIMP-2 can promote the activation of pro-MMP-2 by MT1-MMP. This process is mediated by the formation of a complex between MT1-MMP, TIMP-2, and pro-MMP-2. Binding of TIMP-2 to active MT1-MMP also inhibits the autocatalytic turnover of MT1-MMP on the cell surface. Thus, under certain conditions, TIMP-2 is a positive regulator of MMP activity. TIMP-4, a close homologue of TIMP-2 also binds to pro-MMP-2 and can potentially participate in pro-MMP-2 activation. We coexpressed MT1-MMP with TIMP-4 and investigated its ability to support pro-MMP-2 activation. TIMP-4, unlike TIMP-2, does not promote pro-MMP-2 activation by MT1-MMP. However, TIMP-4 binds to MT1-MMP inhibiting its autocatalytic processing. When coexpressed with TIMP-2, TIMP-4 competitively reduced pro-MMP-2 activation by MT1-MMP. A balance between TIMP-2 and TIMP-4 may be a critical factor in determining the degradative potential of cells in normal and pathological conditions.