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Weekly paclitaxel (WP) is a chemotherapeutic cornerstone in the management of patients with platinum-resistant ovarian carcinoma. Multiple WP dosing regimens have been used clinically and studied individually. However, no formal comparison of these regimens is available to provide objective guidance in clinical decision making. The primary objective of this study was to compare the cumulative dose of paclitaxel delivered using 80 mg/m2/week, administered using either a 3 weeks out of 4 (WP3) or a 4 weeks out of 4 (WP4) regimen. The secondary objective was to evaluate the clinical outcomes associated with both regimens, including efficacy and toxicity parameters. Our retrospective cohort comprised 149 patients harboring platinum-resistant ovarian cancer treated at the CHU de Québec from January 2012 to January 2023. WP3 and WP4 reached a similar cumulative dose (1353.7 vs. 1404.2 mg/m2; p = 0.29). No significant differences in the clinical outcomes were observed. The frequency of dose reduction was significantly higher for WP4 than WP3 (44.7% vs. 4.9%; p < 0.01), mainly due to treatment intolerance from toxicity (34.0% vs. 3.9%; p < 0.01). Our data suggest that a WP3 regimen delivers a similar cumulative dose to WP4, hence offering a better efficacy profile without compromising efficacy.

An infection with the tick-borne Rickettsia helvetica has been associated with a broad spectrum of clinical manifestations in humans, but patients are only seldomly reported. Understanding its disease etiology necessitates well-stablished infection models, improving to recognize and diagnose patients with R. helvetica infection and facilitating the development of effective control strategies. In this study, we used C3H/HeN mice as a model to establish R. helvetica infection, achieving a high infection prevalence (89–100 %). While the liver and the spleen DNA consistently tested positive for infection in all challenged mice, additional infected organs included the kidneys, heart, and the lungs. Notably, a low prevalence of infection was observed in I. ricinus nymphs fed on R. helvetica-challenged mice. In addition, larvae were refractory to infection, suggesting that ticks exhibit low susceptibility to the pathogen. To the best of our knowledge, this is the first study of an animal model for R. helvetica infection. It serves as a valuable tool for advancing research on the interactions among the bacterium and its vertebrate host.

Since the beginning of the industrial revolution, atmospheric carbon dioxide (CO2) concentrations have risen steadily and have induced a decrease of the averaged surface ocean pH by 0.1 units, corresponding to an increase in ocean acidity of about 30 %. In addition to ocean warming, ocean acidification poses a tremendous challenge to some marine organisms, especially calcifiers. The need for long-term oceanic observations of pH and temperature is a key element to assess the vulnerability of marine communities and ecosystems to these pressures. Nearshore productive environments, where a large majority of shellfish farming activities are conducted, are known to present pH levels as well as amplitudes of daily and seasonal variations that are much larger than those observed in the open ocean. Yet, to date, there are very few coastal observation sites where these parameters are measured simultaneously and at high frequency. To bridge this gap, an observation network was initiated in 2021 in the framework of the CocoriCO2 project. Six sites were selected along the French Atlantic and Mediterranean coastlines based on their importance in terms of shellfish production and the presence of high- and low-frequency monitoring activities. At each site, autonomous pH sensors were deployed, both inside and outside shellfish production areas, next to high-frequency CTD (conductivity–temperature–depth) probes operated through two operating monitoring networks. pH sensors were set to an acquisition rate of 15 min, and discrete seawater samples were collected biweekly in order to control the quality of pH data (laboratory spectrophotometric measurements) as well as to measure total alkalinity and dissolved inorganic carbon concentrations for full characterization of the carbonate system. While this network has been up and running for more than 2 years, the acquired dataset has already revealed important differences in terms of pH variations between monitored sites related to the influence of diverse processes (freshwater inputs, tides, temperature, biological processes). Data are available at https://doi.org/10.17882/96982 (Petton et al., 2023a).

Abstract Background Muscle aging is associated with a consistent decrease in the ability of muscle tissue to regenerate following intrinsic muscle degradation, injury or overuse. Age‐related imbalance of protein synthesis and degradation, mainly regulated by AKT/mTOR pathway, leads to progressive loss of muscle mass. Maintenance of anabolic and regenerative capacities of skeletal muscles may be regarded as a therapeutic option for sarcopenia and other muscle wasting diseases. Our previous studies have demonstrated that BIO101, a pharmaceutical grade 20‐hydroxyecdysone, increases protein synthesis through the activation of MAS receptor involved in the protective arm of renin‐angiotensin‐aldosterone system. The purpose of the present study was to assess the anabolic and pro‐differentiating properties of BIO101 on C2C12 muscle cells in vitro and to investigate its effects on adult and old mice models in vivo. Methods The effects of BIO101 on C2C12 differentiation were assessed using myogenic transcription factors and protein expression of major kinases of AKT/mTOR pathway by Western blot. The in vivo effects of BIO101 have been investigated in BIO101 orally‐treated (50 mg/kg/day) adult mice (3 months) for 28 days. To demonstrate potential beneficial effect of BIO101 treatment in a sarcopenic mouse model, we use orally treated 22‐month‐old C57Bl6/J mice, for 14 weeks with vehicle or BIO101. Mice body and muscle weight were recorded. Physical performances were assessed using running capacity and muscle contractility tests. Results Anabolic properties of BIO101 were confirmed by the rapid activation of AKT/mTOR, leading to an increase of C2C12 myotubes diameters (+26%, P

Tick paralysis is a potentially fatal condition caused by toxins produced and secreted by tick salivary glands. This survey presents clinical and epidemiological observations of tick paralysis cases in domestic animals in Cyprus. Local veterinarians report typical tick paralysis cases occurring in goats, sheep, dogs, and cats. The animals suffering from paralysis are free from other neurological diseases, have blood and biochemical parameters within normal ranges, and recover fast by simply removing the ticks found predominantly on the head and around the neck. Tick paralysis cases occur in a specific geographic area of Cyprus (Akamas peninsula), from September through March, but not every year. Instead, the phenomenon has 2 periodic cycles of occurrence, a 3- and a 7-year cycle. The 2 cycles are differentiated by severity based on the number of affected animals and the resulting losses. As described for other tick-borne diseases, these cyclic patterns may be attributed to external factors, self-oscillations of the disease system, or the combined action of these mechanisms. Ticks collected from a recent paralysis case in a goat were morphologically and molecularly identified as Ixodes gibbosus. Efforts should be made to characterize the specific toxins involved in tick paralysis and to develop a vaccine, which could prevent significant losses of small ruminants, especially in free-ranging farming systems, a prevalent management approach observed in Cyprus and various regions worldwide.

Despite the significant health risks associated with Dermanyssus gallinae infestations in humans, they are often overlooked. This study investigated a household case of D. gallinae infestation and explored the resulting clinical manifestations and risk of infection in family members. Microfluidic PCR was employed for high-throughput screening of pathogens in collected mites and blood samples from both chickens and family members. Morphological and molecular examinations confirmed the identity of the mites as D. gallinae sensu stricto (s.s.), with evidence indicating recent blood feeding. Results indicated that the mites exclusively harbored various pathogens, including Bartonella spp., Ehrlichia spp., Apicomplexa, and Theileria spp. Blood samples from family members and poultry tested negative for these pathogens, suggesting a potential reservoir role for D. gallinae. The study further identified haplotypes of D. gallinae, classifying them into D. gallinae s.s., cosmopolitan haplogroup A. Serological analysis revealed elevated IgE seroreactivity against mite proteins in the family member with bite lesions. Antibodies against Bartonella spp. were detected in this individual, indicating exposure to the pathogen. In summary, this study sheds light on the clinical manifestations, pathogen detection, and genetic characterization of D. gallinae infestations, underscoring the necessity of adopting comprehensive approaches to manage such infestations effectively.

Abstract Background Ixodid ticks, particularly Rhipicephalus sanguineus s.l., are important vectors of various disease-causing agents in dogs and humans in Cuba. However, our understading of interactions among tick-borne pathogens (TBPs) in infected dogs or the vector R. sanguineus s.l. remains limited. This study integrates microfluidic-based high-throughput real-time PCR data, Yule's Q statistic, and network analysis to elucidate pathogen-pathogen interactions in dogs and ticks in tropical western Cuba. Methods A cross-sectional study involving 46 client-owned dogs was conducted. Blood samples were collected from these dogs, and ticks infesting the same dogs were morphologically and molecularly identified. Nucleic acids were extracted from both canine blood and tick samples. Microfluidic-based high-throughput real-time PCR was employed to detect 25 bacterial species, 10 parasite species, 6 bacterial genera, and 4 parasite taxa, as well as to confirm the identity of the collected ticks. Validation was performed through end-point PCR assays and DNA sequencing analysis. Yule's Q statistic and network analysis were used to analyse the associations between different TBP species based on binary presence-absence data. Results The study revealed a high prevalence of TBPs in both dogs and R. sanguineus s.l., the only tick species found on the dogs. Hepatozoon canis and Ehrlichia canis were among the most common pathogens detected. Co-infections were observed, notably between E. canis and H. canis. Significant correlations were found between the presence of Anaplasma platys and H. canis in both dogs and ticks. A complex co-occurrence network among haemoparasite species was identified, highlighting potential facilitative and inhibitory roles. Notably, H. canis was found as a highly interconnected node, exhibiting significant positive associations with various taxa, including A. platys, and E. canis, suggesting facilitative interactions among these pathogens. Phylogenetic analysis showed genetic diversity in the detected TBPs. Conclusions Overall, this research enhances our understanding of TBPs in Cuba, providing insights into their prevalence, associations, and genetic diversity, with implications for disease surveillance and management. Graphical abstract

Abstract Background Transitional hospital-to-home care programs support safe and timely transition from acute care settings back into the community. Case-mix systems that classify transitional care clients into groups based on their resource utilization can assist with care planning, calculating reimbursement rates in bundled care funding models, and predicting health human resource needs. This study evaluated the fit and relevance of the Resource Utilization Groups version III for Home Care (RUG-III/HC) case-mix classification system in transitional care programs in Ontario, Canada. Methods We conducted a retrospective analysis of clinical assessment data and administrative billing records from a cohort of clients (n = 1,680 care episodes) in transitional home care programs in Ontario. We classified care episodes into established RUG-III/HC groups based on clients’ clinical and functional characteristics and calculated four case-mix indices to describe care relative resource utilization in the study sample. Using these indices in linear regression models, we evaluated the degree to which the RUG-III/HC system can be used to predict care resource utilization. Results A majority of transitional home care clients are classified as being Clinically complex (41.6%) and having Reduced physical functions (37.8%). The RUG-III/HC groups that account for the largest share of clients are those with the lowest hierarchical ranking, indicating low Activities of Daily Living limitations but a range of Instrumental Activities of Daily Living limitations. There is notable heterogeneity in the distribution of clients in RUG-III/HC groups across transitional care programs. The case-mix indices reflect decreasing hierarchical resource use within but not across RUG-III/HC categories. The RUG-III/HC predicts 23.34% of the variance in resource utilization of combined paid and unpaid care time. Conclusions The distribution of clients across RUG-III/HC groups in transitional home care programs is remarkably different from clients in long-stay home care settings. Transitional care programs have a higher proportion of Clinically complex clients and a lower proportion of clients with Reduced physical function. This study contributes to the development of a case-mix system for clients in transitional home care programs which can be used by care managers to inform planning, costing, and resource allocation in these programs.

Abstract Background Dirofilarioses are widespread diseases caused by mosquito-borne nematodes of the family Onchocercidae, genus Dirofilaria. The major etiologic agent of canine dirofilariosis in the American continent is the zoonotic parasite Dirofilaria immitis. Existing reports of filarioid nematodes in Cuba are based solely on morphological and immunological analysis which do not allow unambiguous identification and/or direct detection of causal agents. Results Here we present the molecular characterization of filarioid nematodes found in a dog in Cuba. Based on the molecular and phylogenetic analysis of the 5.8S-ITS2-28S region and cox1 gene fragments, the worms were unambiguously classified as D. immitis. Sequence analysis showed high identity of the gene fragments in this study with others previously obtained from D. immitis found in dogs, wolfs and jackals but also from mosquito vectors of D. immitis. Conclusions Further studies are guarantee to better understand the epidemiological impact of canine dirofilariosis in Cuba as well as the competence of different species of culicid mosquitoes as vectors of Dirofilaria in the country.

Abstract Interactions within the tick microbiome involving symbionts, commensals, and tick‐borne pathogens (TBPs) play a pivotal role in disease ecology. This study explored temporal changes in the microbiome of Rhipicephalus microplus, an important cattle tick vector, focusing on its interaction with Anaplasma marginale. To overcome limitations inherent in sampling methods relying on questing ticks, which may not consistently reflect pathogen presence due to variations in exposure to infected hosts in nature, our study focused on ticks fed on chronically infected cattle. This approach ensures continuous pathogen exposure, providing a more comprehensive understanding of the nesting patterns of A. marginale in the R. microplus microbiome. Using next‐generation sequencing, microbiome dynamics were characterized over 2 years, revealing significant shifts in diversity, composition, and abundance. Anaplasma marginale exhibited varying associations, with its increased abundance correlating with reduced microbial diversity. Co‐occurrence networks demonstrated Anaplasma's evolving role, transitioning from diverse connections to keystone taxa status. An integrative approach involving in silico node removal unveils the impact of Anaplasma on network stability, highlighting its role in conferring robustness to the microbial community. This study provides insights into the intricate interplay between the tick microbiome and A. marginale, shedding light on potential avenues for controlling bovine anaplasmosis through microbiome manipulation.

Summary: Germinal activity persists throughout life within the ventricular-subventricular zone (V-SVZ) of the postnatal forebrain due to the presence of neural stem cells (NSCs). Accumulating evidence points to a recruitment for these cells following early brain injuries and suggests their amenability to manipulations. We used chronic hypoxia as a rodent model of early brain injury to investigate the reactivation of cortical progenitors at postnatal times. Our results reveal an increased proliferation and production of glutamatergic progenitors within the dorsal V-SVZ. Fate mapping of V-SVZ NSCs demonstrates their contribution to de novo cortical neurogenesis. Transcriptional analysis of glutamatergic progenitors shows parallel changes in methyltransferase 14 (Mettl14) and Wnt/β-catenin signaling. In agreement, manipulations through genetic and pharmacological activation of Mettl14 and the Wnt/β-catenin pathway, respectively, induce neurogenesis and promote newly-formed cell maturation. Finally, labeling of young adult NSCs demonstrates that pharmacological NSC activation has no adverse effects on the reservoir of V-SVZ NSCs and on their germinal activity.