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Abstract Background Myeloma‐related disorders (MRDs) are rare and poorly documented neoplasms of cats. Hypothesis/Objectives To describe clinical, clinicopathologic, and imaging findings, response to treatment, and survival time and to identify factors associated with shorter outcomes in cats with MRD. Animals Fifty cats with a diagnosis of MRD. Methods Cats with paraproteinemia confirmed by serum protein electrophoresis (SPE) and either intramedullary plasmacytosis >10%, marked cytonuclear atypia with intramedullary plasmacytosis that ranged between 5% and 10%, or cytologically or histologically confirmed visceral infiltration were retrospectively included from several veterinary referral centers. Results Bone marrow plasmacytosis and splenic or hepatic involvement were present in 17/27 cats (63%), 36/42 cats (86%), and 27/38 cats (71%), respectively. Anemia was reported in 33/49 cats (67%) and thrombocytopenia in 16/47 cats (34%). Some of the treatments that the cats received included melphalan and prednisolone (n = 19), cyclophosphamide and prednisolone (n = 10), chlorambucil and prednisolone (n = 4), prednisolone (n = 4), or other (n = 4). The overall response rates to melphalan, cyclophosphamide, and chlorambucil in combination with prednisolone were 87%, 90%, and 100%, respectively. Adverse events to melphalan or cyclophosphamide occurred in 65% and 23% of cats, respectively. Median survival time was 122 days (range, 0‐1403) and was not significantly associated with chemotherapy protocol. Anemia (hazard ratio [HR], 3.1; 95% confidence interval [CI], 1.0‐9.8) and thrombocytopenia (HR, 2.7; 95% CI, 1.2‐6.0) were risk factors for shorter survival. Conclusions and Clinical Importance Our study confirmed the guarded prognosis of MRD in cats and identified risk factors for shorter survival times.

Abstract Background Cholelithiasis is an uncommon and mainly incidental finding in dogs; current literature on this topic is scarce in cats. Hypothesis Report prevalence, clinical presentation, management, and outcome of cholelithiasis in cats. Animals Ninety‐eight cats with cholelithiasis. Methods Retrospective multicenter case series. Electronic databases from 3 hospitals were searched for cats diagnosed with cholelithiasis by ultrasonography (US). Cholelithiasis was classified as incidental (IC) or symptomatic (SC) depending on clinicopathological signs, biliary tract US appearance, and presence of another disease potentially explaining the clinical presentation. Multivariate analysis was used to investigate factors associated with clinical expression of cholelithiasis and, within the SC group, survival. Results The observed prevalence of cholelithiasis was 0.99% (95% confidence interval [CI], 0.79%‐1.19%) among cats that underwent abdominal US. Cholelithiasis was classified as IC in 41% and SC in 59%. Choleliths found in multiple locations within the biliary tract (odds ratio [OR], 8.11; 95% CI, 2.32‐34.15; P = .001) or associated with US signs of obstruction (OR, 18.47; 95% CI, 2.13‐2413.34; P = .004) were significantly associated with SC. Concurrent hepatobiliary diseases were suspected or confirmed in 83% of cases with SC. Forty‐three cats (74%) with SC survived to discharge. Biliary tract obstruction (BTO) was negatively associated with survival (OR, 13.87; 95% CI, 1.54‐124.76; P = .001). None of the cats with IC that had available follow‐up (47%) developed clinicopathological signs related to cholelithiasis. Conclusions and Clinical Importance Cholelithiasis is uncommon and can be asymptomatic in cats. Symptomatic cholelithiasis frequently is associated with another hepatobiliary disease or BTO or both. Biliary tract obstruction is associated with poorer outcome.

Abstract Triclabendazole is an effective and well‐tolerated treatment for human fascioliasis. A placebo‐ and positive‐controlled, four‐sequence by four‐period crossover study was conducted in 45 healthy participants to assess the effect of therapeutic (10 mg/kg twice daily [b.i.d.] for 1 day) and supratherapeutic (10 mg/kg b.i.d. for 3 days) oral doses of triclabendazole on corrected QT (QTc) interval prolongation. Moxifloxacin (400 mg, oral) was used as a positive control. The highest mean placebo‐corrected change from baseline in QTcF (ΔΔQTcF) on day 4 with triclabendazole was 9.2 at therapeutic dose ms and 21.7 ms at supratherapeutic dose, at 4 h postdose. The upper limit of the two‐sided 90% confidence interval exceeded 10 ms across all timepoints, except at predose timepoint on day 4 in the therapeutic group indicating that an effect of triclabendazole on cardiac repolarization could not be excluded. However, triclabendazole had no clinically significant effects on heart rate and cardiac conduction at the studied doses. In the moxifloxacin group, the mean ΔΔQTcF peak value was 13.7 ms at 3 h on day 4. The assay sensitivity was confirmed. Maximum plasma concentration of triclabendazole, sulfoxide metabolite, and sulfone metabolite occurred at ~3‐, 4‐, and 6‐h postdose, respectively. No deaths, serious adverse events, study discontinuations due to treatment‐emergent adverse events, or clinically relevant abnormalities in laboratory evaluations and vital sign values were observed. This study showed that triclabendazole had no clinically relevant effects on heart rate and cardiac conduction; however, an effect on cardiac repolarization (ΔΔQTcF >10 ms) could not be excluded.

Recent studies have shown that certain nutrients, specific food groups, or general dietary patterns (DPs) can promote health and prevent noncommunicable chronic diseases (NCCDs). Both developed and developing countries experience a high prevalence of NCCDs due to poor lifestyle habits, DPs, and low physical activity levels. This study aims to examine the dietary, physical activity, sociodemographic, and lifestyle patterns of Uruguayan State Electrical Company workers (the IN-UTE study). A total of 2194 workers participated in the study, providing information about their sociodemographics, lifestyles, and dietary habits through different questionnaires. To identify DPs from 16 food groups, principal component analysis (PCA) was performed. A hierarchical cluster algorithm was used to combine food groups and sociodemographic/lifestyle variables. Four DPs were extracted from the data; the first DP was related to the intake of energy-dense foods, the second DP to the characteristics of the job, the third DP to a Mediterranean-style diet, and the fourth DP to age and body mass index. In addition, cluster analysis involving a larger number of lifestyle variables produced similar results to the PCA. Lifestyle and sociodemographic factors, including night work, working outside, and moderate and intense PA, were significantly correlated with the dietary clusters, suggesting that working conditions, socioeconomic status, and PA may play an important role in determining DPs to some extent. Accordingly, these findings should be used to design lifestyle interventions to reverse the appearance of unhealthy DPs in the UTE population.

This study reviews the many uses for waste generated from acerola (Malpighia spp.) production, a tropical fruit renowned for its nutrient-rich content. Traditionally considered an environmental burden, this waste is now gaining attention for its sustainable applications in green technology. This review outlines the extraction of valuable bioactive compounds, like polyphenols, carotenoids, and pectin, that can be extracted from the acerola fruit and acerola waste, and it also delves into its potential in materials science, particularly in the creation of pharmaceutical formulations, nanomaterials, composites, biofuels, and energy applications. On the medical front, the paper highlights the promise that acerola waste holds in anti-inflammatory, antihyperglycemic, and anticancer therapies. By outlining challenges and opportunities, the review emphasizes the untapped potential of acerola waste as a resource for high-value products. These findings suggest a paradigm shift, turning what has been considered waste into a sustainable asset, thereby encouraging environmentally responsible practices within the fruit industry.

The objective of this work was to formulate PVA films with the addition of modified phenols, chitosan, silver, or copper nanoparticles with fungistatic and bacteriostatic activity. The films were characterized by Fourier transform infrared spectroscopy, thermogravimetry analysis, differential scanning calorimetry, and scanning electron microscopy. The bacteriostatic activity against Salmonella gallinarum and Lactobacillus acidophilus, and the fungistatic activity against Penicillium acidophilus were determined. The results indicated that the addition of phenols enhanced the effect on the stability of the chemical structure of the PVA film. PVA films with modified bioactives and nanoparticles inhibited the colonization of the microorganisms tested, indicating germicidal control.

Abstract In recent years, nanocarriers have been studied as promising pharmaceutical tools for controlled drug-delivery, treatment-efficacy follow-up and disease imaging. Among them, X-shaped amphiphilic polymeric micelles (Tetronic®, poloxamines) display great potential due to their biocompatibility and non-toxic effects, among others. In the present work, polymeric micelles based on the T1307 copolymer were initially decorated with a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-fluorophore in order to determinate its in vivo biodistribution on 4T1 tumor-bearing mice. However, unfavorable results with this probe led to two different strategies. On the one hand, the BODIPY-micelle-loaded, L-T1307-BODIPY, and on the other hand, the 99mTc-micelle-radiolabeled, L-T1307- 99m Tc, were analyzed separately in vivo. The results indicated that T1307 accumulates mainly in the stomach, the kidneys, the lungs and the tumor, reaching the maximum organ-accumulation 2 hours after intravenous injection. Additionally, and according to the results obtained for L-T1307- 99m Tc, the capture of the polymeric micelles in organs could be observed up to 24 hours after injection. The results obtained in this work were promising towards the development of new radiotracer agents for breast cancer based on X-shaped polymeric micelles.

Cellular senescence is an established tumour-suppressive mechanism that prevents the proliferation of premalignant cells. However, several lines of evidence show that senescent cells, which often persist in vivo, can also promote tumour progression in addition to other age-related pathologies via the senescence-associated secretory phenotype (SASP). Moreover, new insights suggest the SASP can facilitate tissue repair. Here, we review the beneficial and detrimental roles of senescent cells, highlighting conditions under which the senescence response does and does not promote pathology, particularly cancer. By better understanding the context-dependent effects of cellular senescence, it may be feasible to limit its detrimental properties while preserving its beneficial effects, and develop novel therapeutic strategies to prevent or treat cancer and possibly other age-associated diseases.

Cellular senescence permanently arrests cell proliferation, often accompanied by a multi-faceted senescence-associated secretory phenotype (SASP). Loss of mitochondrial function can drive age-related declines in the function of many post-mitotic tissues, but little is known about how mitochondrial dysfunction affects mitotic tissues. We show here that several manipulations that compromise mitochondrial function in proliferating human cells induce a senescence growth arrest with a modified SASP that lacks the IL-1-dependent inflammatory arm. Cells that underwent mitochondrial dysfunction-associated senescence (MiDAS) had lower NAD+/NADH ratios, which caused both the growth arrest and prevented the IL-1-associated SASP through AMPK-mediated p53 activation. Progeroid mice that rapidly accrue mtDNA mutations accumulated senescent cells with a MiDAS SASP in vivo, which suppressed adipogenesis and stimulated keratinocyte differentiation in cell culture. Our data identify a distinct senescence response and provide a mechanism by which mitochondrial dysfunction can drive aging phenotypes.

Postoperative recurrence after ileocaecal resection for fibrostenotic terminal ileal Crohn's disease is a significant issue for patients as it can result in symptom recurrence and requirement for further surgery. There are very few modifiable factors, aside from smoking cessation, that can reduce the risk of postoperative recurrence. Until relatively recently, the surgical technique used for resection and anastomosis had little or no impact on postoperative recurrence rates. Novel surgical techniques such as the Kono-S anastomosis and extended mesenteric excision have shown promise as ways to reduce postoperative recurrence rates. This manuscript will review and discuss the evidence regarding a range of surgical techniques and their potential role in reducing disease recurrence. Some of the techniques have been shown to be associated with significant benefits for patients and have already been integrated into the routine clinical practice of some surgeons, while other techniques remain under investigation. Current techniques such as resection of the mesentery close to the intestine and stapled side to side anastomosis are being challenged. It is looking more likely that surgeons will have a major role to play when it comes to reducing recurrence rates for patients undergoing ileocaecal resection for Crohn's disease.

Abstract Background Workplace Health Promotion Programs (WHPP) have been shown to be an efficient way of improving workers’ health. These programs can be incorporated in the worker’s daily schedule and improve their productivity at work. Improving employees’ health also benefits the employers by increasing their return on investment and lowering healthcare costs. The Activate Your Health program, created by Capsana in 2015, is a WHPP targeting multiple lifestyle habits for a three-year period. This WHPP includes tailored web-based interventions and the support of different health professionals throughout the years. We hypothesize that this approach will yield long-term lifestyle changes. The objective of the current paper is to describe the Activate Your Health program’s design. Methods/design Eleven companies are taking part in this WHPP and had to choose among five different options of this program and all their employees were encouraged to participate. Each option differs by the number and type of interventions included. The limited option, which is considered the control group, only consists in completing a questionnaire regarding their health status, lifestyle habits and behaviors. On the other end, the extensive option receives a combination of multiple interventions: online menus, health challenges, support in creating a healthy work environment, coaching by health professionals (nurse, nutritionist, and kinesiologist), health screening and flexibility assessment, online resources, social health platform, and activity tracking. The remaining options are in between these options and vary by the amount of intervention. Baseline data are already gathered; two other data collection periods will take place after one and 2 years into the program. The primary outcomes of the current program are physical activity and fitness measures, nutritional data, smoking habits, stress and intention to change. Discussion The Activate Your Health program will allow us to compare which combinations of interventions are the most effective. It is expected that the extensive option will be the most advantageous to improve lifestyle habits. The results will indicate the strength and weakness of each intervention and how it could be improved. Trial registration Clinicaltrails.gov, registration number: NCT02933385 (updated on the 26th of March 2019, initially registered on the 5th of October 2016).

2-Amino-7-fluorophenazine 5,10-dioxide (FNZ) is a bioreducible prodrug, poorly soluble in water, with potential anticancer activity on hypoxic-tumors. This poor solubility limits its potential applications in clinic. Amphiphilic pristine polymeric micelles (PMs) based on triblock copolymers Pluronic® and Tetronic®, glycosylated derivatives and their mixtures with preformed-liposomes (LPS), were analyzed as strategies to improve the bioavailability of FNZ. FNZ encapsulations were performed and the obtaining nanostructures were characterized using UV-visible spectroscopy (UV-VIS), Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS). The most promising nanoformulations were analyzed for their potential toxicity and pharmacologically, at 20 mg/kg FNZ-doses, in a stage-IV murine metastatic-breast tumor model. The results revealed that the solubility of the encapsulated-FNZ increased up to 14 times and the analysis (UV-VIS, DLS and TEM) confirmed the interaction between vehicles and FNZ. In all the cases appropriate encapsulation efficiencies (greater than 75%), monodisperse nanometric particle sizes (PDI = 0.180–0.335), adequate Z-potentials (−1.59 to −26.4 mV), stabilities and spherical morphologies were obtained. The in vitro profile of FNZ controlled releases corresponded mainly to a kinetic Higuchi model. The in vitro/in vivo biological studies revealed non-toxicity and relevant tumor-weight diminution (up to 61%).

Noncommunicable diseases are the main cause of death globally, and most are potentially preventable; they are long term diseases and generally evolve slowly. In Uruguay 64.9% of the population between 25 and 64 years of age are either overweight or obese. The available scientific data show that workplaces are good for developing food-intake interventions for a healthier life. The present study aims to report the design, protocol and methodology for the evaluation of the food intake and physical activity patterns of the Uruguayan State Electrical Company (UTE) workers, as it is distributed across the whole country, and has established associations with overweight and obesity in order to establish institutional strategies to improve the situation. This study uses a population and a cross-sectional, randomized, representative sample of UTE workers with a precision of 3% and a confidence level of 95%. The considered anthropometric variables are weight, height, waist circumference, percentage of fat mass and percentage of visceral fat. A questionnaire on frequency of consumption of different foods and two 24-h dietary recalls (24-h DR) will be performed to evaluate the food intake. Accelerometry will be used to evaluate physical activity, and the International physical activity questionnaire (IPAQ) will be applied. Clinical data will be obtained from the UTE clinical charts. This is the first study of its kind that will be undertaken in Uruguay. It is registered under ClinicalTrials.gov Identifier nº NCT04509908.

Neutrophils have been extensively described in the pathophysiology of autoimmune and infectious diseases. Accumulating evidence also suggests the important role of neutrophils in cancer progression through their interaction with cancer and immune cells in blood and in the tumor microenvironment (TME). Most studies have described neutrophils as key drivers of cancer progression, due to their involvement in various tumor promoting functions including proliferation, aggressiveness, and dissemination, as well as in immune suppression. However, such studies were focusing on late-stages of tumorigenesis, in which chronic inflammation had already developed. The role of tumor-associated neutrophils (TANs) at early stages of tumor development remains poorly described, though recent findings indicate that early-stage TANs may display anti-tumor properties. Beyond their role at tumor site, evidence supported by NLR retrospective studies and functional analyses suggest that blood neutrophils could also actively contribute to tumorigenesis. Hence, it appears that the phenotype and functions of neutrophils vary greatly during tumor progression, highlighting their heterogeneity. The origin of pro- or anti-tumor neutrophils is generally believed to arise following a change in cell state, from resting to activated. Moreover, the fate of neutrophils may also involve distinct differentiation programs yielding various subsets of pro or anti-tumor neutrophils. In this review, we will discuss the current knowledge on neutrophils heterogeneity across different tissues and their impact on tumorigenesis, as well as neutrophil-based therapeutic strategies that have shown promising results in pre-clinical studies, paving the way for the design of neutrophil-based next generation immunotherapy.

Clinical hantavirus infection was diagnosed in five Argentine children ages 5 to 11 years by immunoglobulin M (IgM)- capture enzyme-linked immunosorbent assay using Sin Nombre virus (SNV) antigens. Death in three of the children was associated with absence of detectable IgG to SNV antigens. An additional two cases in healthy children were studied: one, a breast-fed 15-month-old whose mother died of suspected hantavirus pulmonary syndrome (HPS) 8 months previously, had hantavirus IgG(> 1:6400); a second, whose mother survived HPS during month three of pregnancy, apparently had maternal antibodies no longer detectable 1 year after birth.

Les syndromes mycotoxiques de latence courte apparaissent dans les six heures qui suivent l'ingestion de champignons. Ils entraînent principalement des signes digestifs rapidement résolutifs et sont généralement banalisés. Une étude réalisée grâce aux données du centre antipoison et de toxicovigilance d'Angers permet de mettre en exergue leur gravité potentielle. Il est important de sensibiliser les professionnels de santé à leur prévention et à une prise en charge adéquate des patients. Short-latency mycotoxic syndromes appear within six hours after ingestion of mushrooms. They mainly lead to digestive signs that resolve quickly and are generally trivialized. A study carried out with data from the Angers Poison and Toxicovigilance Center highlights their potential seriousness. It is important to raise awareness among health professionals about their prevention and proper management of patients. [ABSTRACT FROM AUTHOR]

Objectives The aim was to estimate the long-term results and patency rates of totally laparoscopic aortobifemoral bypass in aorto-iliac occlusive disease (AIOD). Methods All 87 patients who received a laparoscopic aortobifemoral bypass for AIOD on an intention to treat basis between October 2003 and October 2013 were identified. All operations were performed by the same surgical team using a totally laparoscopic technique. Demographic, pre-operative, peri-operative, and follow up variables were collected and analyzed. Patients were followed up at 1 month post-operatively and annually thereafter. Patency rates were calculated in accordance with published patency reporting standards. Results The median age was 57 years (range 40–78 years). The conversion rate was 20.6% overall. The thirty-day post-operative mortality was 1.1%. Six patients required early re-intervention. There were no graft infections. The median length hospital stay was 6 days (range 4–39 days). The mean follow up was 58.0 months (range 1–133 months). Graft limb based primary, primary assisted, and secondary patency rates were respectively 96.1%, 98.1% and 99.4% at 1 year, and 83.0%, 92.0% and 97.0% at 5 years. Conclusion Totally laparoscopic aortobifemoral bypass is a safe alternative to open surgery in selected patients, with excellent long-term patency rates, albeit at the cost of a steep learning curve. [ABSTRACT FROM AUTHOR]