Spontaneous Remission of Blastic Plasmacytoid Dendritic Cell Neoplasm: A Case Report.

Spontaneous remissions (SRs) in blastic plasmacytoid dendritic cell neoplasms (BPDCNs) are infrequent, poorly documented, and transient. We report a 40-year-old man presenting with bycitopenia and soft tissue infection. The bone marrow exhibited 3% abnormal cells. Immunophenotyping of these cells revealed the antigens CD45+ (dim), CD34+, CD117+, CD123+ (bright), HLA-DR+ (bimodal), CD56+ (bright), CD33+, CD13+, CD2+, and CD22+ (dim) and the partial expression of the CD10+, CD36+, and CD7+ antigens. All other myeloid, monocytic, and lymphoid antigens were negative. Genetic studies showed a complex karyotype and mutations in the TP53R337C and KRASG12D genes. On hospital admission, the patient showed a subcutaneous nodule on the right hand and left lower limb. Flow cytometry multiparameter (FCM) analysis showed the presence of 29% abnormal cells with the previously described immunophenotype. The patient was diagnosed with BPDCN. The patient was treated with broad-spectrum antibiotics for soft tissue infection, which delayed therapy for BPDCN. No steroids or chemotherapeutic or hypomethylating agents were administered. His blood cell counts improved and skin lesions disappeared, until the patient relapsed five months after achieving spontaneous remission. About 60% of abnormal cells were identified. No changes in immunophenotype or the results of genetic studies were observed. The patient underwent a HyperCVAD chemotherapy regimen for six cycles. Consolidation therapy was performed via allogeneic bone marrow transplantation with an HLA-unrelated donor. One year after the bone marrow transplant, the patient died due to the progression of his underlying disease, coinciding with a respiratory infection caused by SARS-CoV-2. In the available literature, SRs are often linked to infections or other stimulators of the immune system, suggesting that powerful immune activation could play a role in controlling the leukemic clone. Nevertheless, the underlying mechanism of this phenomenon is not clearly understood. We hypothesize that the immune system would force the leukemic stem cell (LSC) to undergo a state of quiescence. This loss of replication causes the LSC progeny to die off, resulting in the SR of BPDCN.

Proteoglycans in Articular Cartilage and Their Contribution to Chondral Injury and Repair Mechanisms.

Proteoglycans are vital components of the extracellular matrix in articular cartilage, providing biomechanical properties crucial for its proper functioning. They are key players in chondral diseases, specifically in the degradation of the extracellular matrix. Evaluating proteoglycan molecules can serve as a biomarker for joint degradation in osteoarthritis patients, as well as assessing the quality of repaired tissue following different treatment strategies for chondral injuries. Despite ongoing research, understanding osteoarthritis and cartilage repair remains unclear, making the identification of key molecules essential for early diagnosis and effective treatment. This review offers an overview of proteoglycans as primary molecules in articular cartilage. It describes the various types of proteoglycans present in both healthy and damaged cartilage, highlighting their roles. Additionally, the review emphasizes the importance of assessing proteoglycans to evaluate the quality of repaired articular tissue. It concludes by providing a visual and narrative description of aggrecan distribution and presence in healthy cartilage. Proteoglycans, such as aggrecan, biglycan, decorin, perlecan, and versican, significantly contribute to maintaining the health of articular cartilage and the cartilage repair process. Therefore, studying these proteoglycans is vital for early diagnosis, evaluating the quality of repaired cartilage, and assessing treatment effectiveness.

Identification of seasonal variation in the diagnosis of acute myeloid leukaemia: a population-based study.

Until now, the role that seasonal factors play in the aetiology of acute myeloid leukaemia (AML) has been unclear. Demonstration of seasonality in AML diagnosis would provide supportive evidence of an underlying seasonal aetiology. To investigate the potential seasonal and long-term trends in AML diagnosis in an overall population and in subgroups according to sex and age, we used population-based data from a Spanish hospital discharge registry. We conducted a larger study than any to date of 26 472 cases of AML diagnosed in Spain between 2004 and 2015. Using multivariable Poisson generalized linear autoregressive moving average modelling, we found an upward long-term trend, with monthly incidence rates of AML annually increasing by 0.4% [95% confidence interval (CI), 0.2%-0.6%; p = 0.0011]. January displayed the highest incidence rate of AML, with a minimum average difference of 7% when compared to February (95% CI, 2%-12%; p = 0.0143) and a maximum average difference of 16% compared to November (95% CI, 11%-21%; p < 0.0001) and August (95% CI, 10%-21%; p < 0.0001). Such seasonal effect was consistent among subgroups according to sex and age. Our finding that AML diagnosis is seasonal strongly implies that seasonal factors, such as infectious agents or environmental triggers, influence the development and/or proliferation of disease, pointing to prevention opportunities.

Single-cell transcriptomics of the ventral posterolateral nucleus-enriched thalamic regions from HSV-1-infected mice reveal a novel microglia/microglia-like transcriptional response.

BACKGROUND: Microglia participate in the immune response upon central nervous system (CNS) infections. However, the role of these cells during herpes simplex encephalitis (HSE) has not been fully characterized. We sought to identify different microglia/microglia-like cells and describe the potential mechanisms and signaling pathways involved during HSE. METHODS: The transcriptional response of CD11b+ immune cells, including microglia/microglia-like cells, was investigated using single-cell RNA sequencing (scRNA-seq) on cells isolated from the ventral posterolateral nucleus (VPL)-enriched thalamic regions of C57BL/6 N mice intranasally infected with herpes simplex virus-1 (HSV-1) (6 × 105 PFUs/20 µl). We further performed scanning electronic microscopy (SEM) analysis in VPL regions on day 6 post-infection (p.i.) to provide insight into microglial functions. RESULTS: We describe a novel microglia-like transcriptional response associated with a rare cell population (7% of all analyzed cells), named "in transition" microglia/microglia-like cells in HSE. This new microglia-like transcriptional signature, found in the highly infected thalamic regions, was enriched in specific genes (Retnlg, Cxcr2, Il1f9) usually associated with neutrophils. Pathway analysis of this cell-type transcriptome showed increased NLRP3-inflammasome-mediated interleukin IL-1ß production, promoting a pro-inflammatory response. These cells' increased expression of viral transcripts suggests that the distinct "in transition" transcriptome corresponds to the intrinsic antiviral immune signaling of HSV-1-infected microglia/microglia-like cells in the thalamus. In accordance with this phenotype, we observed several TMEM119+/IBA-I+ microglia/microglia-like cells immunostained for HSV-1 in highly infected regions. CONCLUSIONS: A new microglia/microglia-like state may potentially shed light on how microglia could react to HSV-1 infection. Our observations suggest that infected microglia/microglia-like cells contribute to an exacerbated CNS inflammation. Further characterization of this transitory state of the microglia/microglia-like cell transcriptome may allow the development of novel immunomodulatory approaches to improve HSE outcomes by regulating the microglial immune response.

Spontaneous Remission of Acute Myeloid Leukemia: A Case Report.

Spontaneous remissions (SRs) in acute myeloid leukemia (AML) are infrequent, poorly documented and transient. Similarly, morphological and cytogenetic complete remissions (CR) under azacitidine treatment are scarce. We report a 71-year-old man with a secondary AML arising from essential thrombocythemia (ET), who developed an SR after discontinuation of azacitidine following a respiratory infection (four courses were administered). The distinctive feature of our case is the depth of the achieved CR, documented by next-generation sequencing (NGS) techniques. We also detected persistence of molecular lesions that might already have been present in the previous ET clone. Our patient relapsed 5 months after achieving CR. We conclude that our patient showed a spontaneous remission of his AML rather than an exquisite response to azacitidine. We hypothesize that the concurrent respiratory infection, or any other unknown trigger, might have activated his immune system forcing the leukemic stem cell to enter a quiescent state through a yet unexplained mechanism.

Congenital dyserythropoietic anemia types Ib, II, and III: novel variants in the CDIN1 gene and functional study of a novel variant in the KIF23 gene.

Congenital dyserythropoietic anemias (CDA) are disorders characterized by ineffective erythropoiesis and morphological anomalies in erythrocytes and erythroblasts. The purpose of this study is to identify the gene variants in patients diagnosed with CDA. We analyzed five unrelated patients and two siblings with a targeted panel of genes to CDA: CDAN1, CDIN1, SEC23B, KIF23, KLF1, and GATA1 genes. We found three novel variants in the CDIN1 gene (p.Leu136Val, p.Tyr247Cys, and p.Ile273Thr), four known variants in the SEC23B gene (p.Arg14Trp, p.Arg554Ter, p.Asp239Gly, and p.Ser436Leu), and one novel variant in the KIF23 gene (p.Leu945Trpfs*31). The in silico analysis of novel variants predict that they are pathogenic and, the in vitro study confirms the functional impact of the KIF23 variant on the protein location.

Assessment of effects of methylene blue on intestinal ischemia and reperfusion in a rabbit model: hemodynamic, histological and immunohistochemical study.

BACKGROUND: Intestinal ischemia-reperfusion (IR) is an important clinical occurrence seen in common diseases, such as gastric dilatation-volvulus in dogs or colic in horses. Limited data is available on the use of methylene blue in veterinary medicine for intestinal ischemia-reperfusion. The present study aimed to compare the hemodynamic, histopathological, and immunohistochemical effects of two doses of methylene blue in two rabbit model groups In one group, 5 mg/kg IV was administered, and in another, 20 mg/kg IV was administered following a constant rate infusion (CRI) of 2 mg/kg/h that lasted 6 h. All the groups, including a control group had intestinal ischemia-reperfusion. Immunohistochemical analysis was performed using caspase-3. RESULTS: During ischemia, hemodynamic depression with reduced perfusion and elevated lactate were observed. During reperfusion, methylene blue (MB) infusion generated an increase in cardiac output due to a positive chronotropic effect, an elevation of preload, and an intense positive inotropic effect. The changes in heart rate and blood pressure were significantly greater in the group in which methylene blue 5 mg/kg IV was administered (MB5) than in the group in which methylene blue 20 mg/kg IV dose was administered (MB20). In addition, lactate and stroke volume variations were significantly reduced, and vascular resistance was significantly elevated in the MB5 group compared with the control group and MB20 group. The MB5 group showed a significant decrease in the intensity of histopathological lesion scores in the intestines and a decrease in caspase-3 areas, in comparison with other groups. CONCLUSIONS: MB infusion produced improvements in hemodynamic parameters in rabbits subjected to intestinal IR, with increased cardiac output and blood pressure. An MB dosage of 5 mg/kg IV administered at a CRI of 2 mg/kg/h exhibited the most protective effect against histopathological damage caused by intestinal ischemia-reperfusion. Further studies with MB in clinical veterinary pathologies are recommended to fully evaluate these findings.

Inflammatory Cells in Atypical Eruption of Lymphocyte Recovery Carry the Same Mutations as Neoplastic Myeloid Cells.

Cutaneous eruption of lymphocyte recovery (ELR) during bone marrow (BM) aplasia recovery after intensive chemotherapy has been reported in very few patients. The presence of skin rashes in patients with acute leukemia who are undergoing intensive chemotherapy and BM transplantation is a diagnostic challenge because of the clinical similarity between drug eruptions, infiltrates related to the relapse of the underlying disease, cutaneous graft-versus-host disease, and ELR. IDH1 mutations have been identified as a recurrent genetic anomaly in acute myeloid leukemia and myelodysplastic syndromes. However, until now, this IDH1 mutation has not been reported as being shared by myeloid cells and non-neoplastic inflammatory cells in this clinical setting. Here, we present the rare case of a woman diagnosed with myelodysplastic syndrome that evolved into an acute myelogenous leukemia with leukemic cutaneous infiltrate. The patient developed ELR after the intensive chemotherapy administered before BM transplantation. The IDH1 mutation was identified in BM cells and in myeloid and inflammatory cells in skin biopsies before allogeneic BM transplantation. We discuss the main aspects of the differential diagnosis of these cutaneous reactions in leukemic patients and the biological significance of the IDH1 mutation.

Northern pigtailed macaques rely on old growth plantations to offset low fruit availability in a degraded forest fragment.

Space-use and foraging strategies are important facets to consider in regard to the ecology and conservation of primates. For this study, we documented movement, ranging, and foraging patterns of northern pigtailed macaques (Macaca leonina) for 14 months in a degraded habitat with old growth Acacia and Eucalyptus plantations at the Sakaerat Biosphere Reserve in northeastern Thailand. We used hidden Markov models and characteristic hull polygons to analyze these patterns in regard to fruit availability. Macaques' home range (HR) was 599 ha and spanned through a natural dry-evergreen forest (DEF), and plantation forest. Our results showed that active foraging increased with higher fruit availability in DEF. Macaques changed to a less continuous behavioral state during periods of lower fruit availability in DEF, repeatedly moving from foraging to transiting behavior, while extending their HR further into plantation forest and surrounding edge areas. Concomitantly, macaques shifted their diet from fleshy to dry fruit such as the introduced Acacia species. Our results showed that the diet and movement ecology adaptations of northern pigtailed macaques were largely dependent on availability of native fruits, and reflected a "high-cost, high-yield" foraging strategy when fresh food was scarce and dry fruit was available in plantation forest. Conversely, wild-feeding northern pigtailed macaque populations inhabiting pristine habitat approached a "low-cost, low-yield" foraging strategy. Our results outline the effects of habitat degradation on foraging strategies and show how a flexible species can cope with its nutritional requirements.

Intraoperative nociception-antinociception monitors: A review from the veterinary perspective.

OBJECTIVE: To review monitors currently available for the assessment of nociception-antinociception in veterinary medicine. DATABASES USED: PubMed, Web of Science and Google Scholar. The results were initially filtered manually based on the title and the abstract. CONCLUSIONS: The provision of adequate antinociception is difficult to achieve in veterinary anaesthesia. Currently, heart rate and arterial blood pressure are used to monitor the response to a noxious stimulus during anaesthesia, with minimum alveolar concentration-sparing effect and stress-related hormones used for this purpose in research studies. However, since none of these variables truly assess intraoperative nociception, several alternative monitoring devices have been developed for use in humans. These nociceptive-antinociceptive monitoring systems derive information from variables, such as electroencephalography, parasympathetic nervous system (PNS) response, sympathetic nervous system response and electromyography. Several of these monitoring systems have been investigated in veterinary medicine, although few have been used to assess intraoperative nociception in animals. There is controversy regarding their effectiveness and clinical use in animals. A nociceptive-antinociceptive monitoring system based on the PNS response has been developed for use in cats, dogs and horses. It uses the parasympathetic tone activity index, which is believed to detect inadequate intraoperative nociception-antinociception balance in veterinary anaesthesia. Nonetheless, there are limited published studies to date, and cardiovascular variables remain the gold standard. Consequently, further studies in this area are warranted.

Determination of acute tolerance and hyperalgesia to remifentanil constant rate infusion in dogs undergoing sevoflurane anaesthesia.

OBJECTIVE: To determine if acute opioid tolerance (AOT) or opioid-induced hyperalgesia (OIH) could develop and limit the remifentanil-induced reduction in the sevoflurane minimum alveolar concentration (MAC). The response to mechanical nociceptive threshold (MNT) was evaluated and related to OIH. STUDY DESIGN: A crossover, randomized, experimental animal study. ANIMALS: A total of nine Beagle dogs. METHODS: The dogs were anaesthetized with sevoflurane in 50% oxygen. Baseline sevoflurane MAC was measured (MACb1). Remifentanil (0.3 µg kg-1 minute-1) or 0.9% saline constant rate infusion (CRI) was administered intravenously (IV). Sevoflurane MAC was determined 20 minutes after CRI was initiated (MACpostdrug1), 30 minutes after MACpostdrug1 determination (MACpostdrug2) and after 1 week (MACb2). The MNT was determined at baseline (before anaesthesia), 3 and 7 days after anaesthesia. An increase of MACpostdrug2 ≥0.25% compared to MACpostdrug1 was considered evidence of AOT. A decrease in MNT at 3 and 7 days or an increase in MACb2 or both with respect to MACb1 were considered evidence of OIH. RESULTS: Remifentanil CRI reduced sevoflurane MACpostdrug1 by 43.7% with respect to MACb1. MACpostdrug2 was no different from MACpostdrug1 with the saline (p = 0.62) or remifentanil (p = 0.78) treatments. No significant differences were observed in the saline (p = 0.99) or remifentanil (p = 0.99) treatments between MACb1 and MACb2, or for MNT values between baseline, 3 and 7 days. CONCLUSION AND CLINICAL RELEVANCE: In dogs, under the study conditions, remifentanil efficacy in reducing sevoflurane MAC did not diminish in the short term, suggesting remifentanil did not induce AOT. Hyperalgesia was not detected 3 or 7 days after the administration of remifentanil. Contrary to data from humans and rodents, development of AOT or OIH in dogs is not supported by the findings of this study.

Comparative pharmacokinetics and a clinical laboratory evaluation of intravenous acetaminophen in Beagle and Galgo Español dogs.

OBJECTIVE: To assess the pharmacokinetics (PK) and conduct a clinical laboratory evaluation of acetaminophen in Beagle and Galgo Español (GE) dogs. STUDY DESIGN: Prospective randomized experimental trial. ANIMALS: A total of 20 healthy dogs - 10 Beagles and 10 GE (six males and four females in both groups). METHODS: Acetaminophen (10 and 20 mg kg-1) was administered intravenously (IV) to the dogs on two different occasions. Plasma concentrations were analysed by high-performance liquid chromatography. PK analysis was undertaken using compartmental modelling with ADAPT 5 software. Simulations after multiple IV doses were investigated. Clinical laboratory values such as red blood cell (RBC) count, haemoglobin (Hb), haematocrit (Ht), white blood cell (WBC) count, platelet count, total proteins, alanine aminotransferase (ALT), aspartate aminotransferase, urea and creatinine were measured before and 24 hours after acetaminophen administration in combination with clinical examination to assess side effects resulting from the drug. RESULTS: A two-compartmental model best described time-concentration profiles of acetaminophen. PK parameters were different as a result of a breed effect. For doses of 10 and 20 mg kg-1, respectively, clearance values were 1.70 (1.15-2.27) and 1.62 (1.06-2.86) L kg-1 hour-1 for Beagles and 1.18 (0.70-1.39) and 1.08 (0.67-1.35) L kg-1 hour-1 for GE; elimination half-life values were 2.64 (0.52-4.46) and 2.86 (0.87-4.63) hours for Beagles and 3.49 (1.89-7.80) and 4.57 (2.08-8.90) hours for GE. Significant differences were also found between GE and Beagles in the RBC count, Ht, Hb, WBC count and serum ALT before drug administration, and these differences were maintained 24 hours later, independent of the dosage used. For each breed, no side effects resulting from IV acetaminophen administration were observed at doses of either 10 or 20 mg kg-1. CONCLUSIONS AND CLINICAL RELEVANCE: IV PK of acetaminophen was different between Beagles and GE dogs. Side effects were not detected. Further studies are necessary to evaluate the PK in a clinical context.

Binding of eEF1A2 to the RNA-dependent protein kinase PKR modulates its activity and promotes tumour cell survival.

BACKGROUND: Through several not-fully-characterised moonlighting functions, translation elongation factor eEF1A2 is known to provide a fitness boost to cancer cells. Furthermore, eEF1A2 has been demonstrated to confer neoplastic characteristics on preneoplastic, nontumourigenic precursor cells. We have previously shown that eEF1A2 is the target of plitidepsin, a marine drug currently in development for cancer treatment. Herein, we characterised a new signalling pathway through which eEF1A2 promotes tumour cell survival. METHODS: Previously unknown binding partners of eEF1A2 were identified through co-immunoprecipitation, high-performance liquid chromatography-mass spectrometry and proximity ligation assay. Using plitidepsin to release eEF1A2 from those protein complexes, their effects on cancer cell survival were analysed in vitro. RESULTS: We uncovered that double-stranded RNA-activated protein kinase (PKR) is a novel eEF1A2-interacting partner whose pro-apoptotic effect is hindered by the translation factor, most likely through sequestration and inhibition of its kinase activity. Targeting eEF1A2 with plitidepsin releases PKR from the complex, facilitating its activation and triggering a mitogen-activated protein kinase signalling cascade together with a nuclear factor-κB-dependent activation of the extrinsic apoptotic pathway, which lead to tumour cell death. CONCLUSIONS: Through its binding to PKR, eEF1A2 provides a survival boost to cancer cells, constituting an Achilles heel that can be exploited in anticancer therapy.

Bioconjugation through Mesitylene Thiol Alkylation.

The design and generation of complex multifunctional macromolecular structures by bioconjugation is a hot topic due to increasing interest in conjugates with therapeutic applications. In this regard, the development of efficient, selective, and safe conjugation methods is a major objective. In this report, we describe the use of the bis(bromomethyl)benzene scaffold as a linker for bioconjugation with special emphasis on antibody conjugation. We first performed the monothioalkylation of 1,3,5-tris(bromomethyl)benzene, which rendered the reactive dibromotrimethylbenzyl derivatives to be used in thiol bis-alkylation. Next, we introduced into the linker either a bis(Cys)-containing peptide or anti-CD4 and -CD13 monoclonal antibodies, previously subjected to partial reduction of disulfide bonds. Mass spectrometry, UV-vis spectra, and SDS-PAGE experiments revealed that this bis-alkylating agent for bioconjugation preserved both antibody integrity and antibody-antigen binding affinity, as assessed by flow cytometry. Taken together, our results show that the mesitylene scaffold is a suitable linker for thiol-based bioconjugation reactions. This linker could be applicable in the near future for the preparation of antibody drug conjugates.

The ecology of white-handed and pileated gibbons in a zone of overlap and hybridization in Thailand.

OBJECTIVES: The study of related species in contact zones can elucidate what factors mediate species coexistence and geographical distributions. We investigated niche overlap and group interactions of two gibbon species and their hybrids co-occurring in a zone of overlap and hybridization. METHODS: The location, composition and behavior of white-handed, pileated, and mixed-species gibbon groups were studied by following them during 31 consecutive months in a relatively large part of the contact zone. RESULTS: Twenty groups of white-handed gibbon were mapped followed by nine groups of pileated gibbons and five mixed-species groups. White-handed, pileated and mixed-species groups had similar sizes and composition, ate a high proportion of fruits, shared a large number of species in their diets, and presented similar habitat preferences. Group home range sizes did not differ between species and overlapped little with neighboring groups irrespective of species, and intraspecific and interspecific encounter rates were similar. DISCUSSION: Ecological similarities support that competition between the gibbon species exists and takes the form of interspecific territoriality. However, we could not find any clear mechanism of niche partitioning favoring coexistence between species. Our findings suggest that the contact zone is unstable and is maintained by dispersal inward from groups of the parental species. The relatively low numbers of mixed-species groups and hybrids found suggests a high degree of premating reproductive isolation, perhaps mediated by interspecific miscommunication. The existence of hybrids and backcrosses potentially undetectable from phenotypic characters alone raises the possibility of more widespread introgression than has been evident. Hence, while interspecific territoriality should reduce the rate of gene transfer, it would not necessarily present a barrier to introgression into contiguous populations of the opposite species.

Cut-Off Values of Hematologic Parameters to Predict the Number of Alpha Genes Deleted in Subjects with Deletional Alpha Thalassemia.

Most α-thalassemia cases are caused by deletions of the structural α-globin genes. The degree of microcytosis and hypochromia has been correlated with the number of affected α-globin genes, suggesting a promising role of hematologic parameters as predictive diagnostic tools. However, cut-off points for these parameters to discriminate between the different subtypes of α-thalassemia are yet to be clearly defined. Six hematologic parameters (RBC, Hb, MCV, MCH, MCHC and RDW) were evaluated in 129 cases of deletional α-thalassemia (56 heterozygous α⁺ thalassemia, 36 homozygous α⁺ thalassemia, 29 heterozygous α° thalassemia and 8 cases of Hb H disease). A good correlation between the number of deleted alpha genes and MCV (r = -0.672, p < 0.001), MCH (r = -0.788, p < 0.001) and RDW (r = 0.633, p < 0.001) was observed. The presence of an α° allele should be discarded in individuals with microcytosis without iron deficiency and normal values of Hb A2 and Hb F with MCH < 23.40 pg. Furthermore, MCH < 21.90 pg and/or MCV < 70.80 fL are strongly suggestive of the presence of one α° allele. Finally, an accurate presumptive diagnosis of Hb H disease can be made if both RDW ≥ 20% and MCH < 19 pg are seen.

Ranging and site fidelity in northern pigtailed macaques (Macaca leonina) over different temporal scales.

Space-use patterns are crucial to understanding the ecology, evolution, and conservation of primates, but detailed ranging data are scarce for many species, especially those in Southeast Asia. Researchers studying site fidelity to either home ranges or core areas have focused mainly on territorial species, whereas less information is available for non-territorial species. We analyzed the ranging patterns and site fidelity of one wild troop of northern pigtailed macaques over 16 months at different temporal scales. We used characteristic hull polygons in combination with spatial statistics to estimate home ranges and core areas. The total home range and core areas were 449 ha and 190 ha, respectively. Average daily path length was 2,246 m. The macaques showed a high defendabili--ty index according to the expected ranging of a non-territorial species in which movement does not theoretically permit the defense of a large territory. Overall, the study troop ranged more extensively than conspecific groups and closely related species studied elsewhere. These differences may reflect variable troop size, degree of terrestriality and habitat characteristics, but could also reflect methodological differences. The location, size and shape of home ranges and core areas, and extent of daily path lengths changed on a monthly basis resulting in low site fidelity between months. The macaques also showed clear shifts in the location of daily home ranges with low site fidelity scores between consecutive days. Daily home range and daily path length were related to seasonality, with greater values during the fruit-abundant period. Low site fidelity associated with lack of territoriality is consistent with macaques structuring their movement based on available food sources. However, ranging patterns and site fidelity can also be explained by macaques feeding on the move, a foraging strategy that hinders frequent and long visits to the same location.

Hip osteoarthritis in dogs: a randomized study using mesenchymal stem cells from adipose tissue and plasma rich in growth factors.

PURPOSE: The aim of this study was to compare the efficacy and safety of a single intra-articular injection of adipose mesenchymal stem cells (aMSCs) versus plasma rich in growth factors (PRGF) as a treatment for reducing symptoms in dogs with hip osteoarthritis (OA). METHODS: This was a randomized, multicenter, blinded, parallel group. Thirty-nine dogs with symptomatic hip OA were assigned to one of the two groups, to receive aMSCs or PRGF. The primary outcome measures were pain and function subscales, including radiologic assessment, functional limitation and joint mobility. The secondary outcome measures were owners' satisfaction questionnaire, rescue analgesic requirement and overall safety. Data was collected at baseline, then, 1, 3 and 6 months post-treatment. RESULTS: OA degree did not vary within groups. Functional limitation, range of motion (ROM), owner's and veterinary investigator visual analogue scale (VAS), and patient's quality of life improved from the first month up to six months. The aMSCs group obtained better results at 6 months. There were no adverse effects during the study. Our findings show that aMSCs and PRGF are safe and effective in the functional analysis at 1, 3 and 6 months; provide a significant improvement, reducing dog's pain, and improving physical function. With respect to basal levels for every parameter in patients with hip OA, aMSCs showed better results at 6 months.

Characteristics and risk factors associated with mortality during the first cycle of prone secondary to ARDS due to SARS-CoV-2 pneumonia.

OBJECTIVE: To analyze characteristics, changes in oxygenation, and pulmonary mechanics, in mechanically ventilated patients with ARDS due to SARS-CoV-2 treated with prone position and evaluate the response to this maneuver. DESIGN: Cohort study including patients with PaO2/FiO2 <150mmHg requiring prone position over 18 months. We classified patients according to PaO2/FiO2 changes from basal to 24h after the first prone cycle as: 1) no increase 2) increase <25%, 3) 25%-50% increase 4) increase >50%. SETTING: 33-bed medical-surgical Intensive Care Unit (ICU) in Argentina. PATIENTS: 273 patients. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Epidemiological characteristics, respiratory mechanics and oxygenation were compared between survivors and non-survivors. Independent factors associated with in-hospital mortality were identified. RESULTS: Baseline PaO2/FiO2 was 116 [97-135]mmHg (115 [94-136] in survivors vs. 117 [98-134] in non-survivors; p=0.50). After prone positioning, 22 patients (8%) had similar PaO2/FiO2 values; 46(16%) increased PaO2/FiO2 ≤25%; 55 (21%) increased it 25%-50%; and 150 (55%), >50%. Mortality was 86%, 87%, 72% and 50% respectively (p<0.001). Baseline PaO2/FiO2, <100mmHg did not imply that patients were refractory to prone position. Factors independently associated with mortality were age, percentage increase in PaO2/FiO2 after 24h being in prone, and number of prone cycles. CONCLUSIONS: Older patients unable to improve PaO2/FiO2 after 24h in prone position and who require >1 cycle might early receive additional treatments for refractory hypoxemia. After the first 24h in the prone position, a low percentage of PaO2/FiO2 increase over baseline, beyond the initial value, was independently associated with higher mortality.