Genomic epidemiology of third-generation cephalosporin-resistant Escherichia coli from Argentinian pig and dairy farms reveals animal-specific patterns of co-resistance and resistance mechanisms.

Control measures are being introduced globally to reduce the prevalence of antibiotic resistance (ABR) in bacteria on farms. However, little is known about the current prevalence and molecular ecology of ABR in bacterial species with the potential to be key opportunistic human pathogens, such as Escherichia coli, on South American farms. Working with 30 dairy cattle farms and 40 pig farms across two provinces in central-eastern Argentina, we report a comprehensive genomic analysis of third-generation cephalosporin-resistant (3GC-R) E. coli, which were recovered from 34.8% (cattle) and 47.8% (pigs) of samples from fecally contaminated sites. Phylogenetic analysis revealed substantial diversity suggestive of long-term horizontal and vertical transmission of 3GC-R mechanisms. CTX-M-15 and CTX-M-2 were more often produced by isolates from dairy farms, while CTX-M-8 and CMY-2 and co-carriage of amoxicillin/clavulanate resistance and florfenicol resistance were more common in isolates from pig farms. This suggests different selective pressures for antibiotic use in these two animal types. We identified the ß-lactamase gene blaROB, which has previously only been reported in the family Pasteurellaceae, in 3GC-R E. coli. blaROB was found alongside a novel florfenicol resistance gene, ydhC, also mobilized from a pig pathogen as part of a new composite transposon. As the first comprehensive genomic survey of 3GC-R E. coli in Argentina, these data set a baseline from which to measure the effects of interventions aimed at reducing on-farm ABR and provide an opportunity to investigate the zoonotic transmission of resistant bacteria in this region. IMPORTANCE: Little is known about the ecology of critically important antibiotic resistance among bacteria with the potential to be opportunistic human pathogens (e.g., Escherichia coli) on South American farms. By studying 70 pig and dairy cattle farms in central-eastern Argentina, we identified that third-generation cephalosporin resistance (3GC-R) in E. coli was mediated by mechanisms seen more often in certain species and that 3GC-R pig E. coli were more likely to be co-resistant to florfenicol and amoxicillin/clavulanate. This suggests that on-farm antibiotic usage is key to selecting the types of E. coli present on these farms. 3GC-R E. coli and 3GC-R plasmids were diverse, suggestive of long-term circulation in this region. We identified the de novo mobilization of the resistance gene blaROB from pig pathogens into E. coli on a novel mobile genetic element, which shows the importance of surveying poorly studied regions for antibiotic resistance that might impact human health.

The Spontaneous Incidence of Neurological Clinical Signs in Preclinical Species Using Cage-side Observations or High-definition Video Monitoring: A Retrospective Analysis.

When conducting toxicology studies, the interpretation of drug-related neurological clinical signs such as convulsions, myoclonus/myoclonic jerks, tremors, ataxia, and salivation requires an understanding of the spontaneous incidence of those observations in commonly used laboratory animal species. The spontaneous incidence of central nervous system clinical signs in control animals from a single facility using cage-side observations or high definition video monitoring was retrospectively analyzed. Spontaneous convulsions were observed at low incidence in Beagle dogs and Sprague-Dawley rats but were not identified in cynomolgus monkeys and Göttingen minipigs. Spontaneous myoclonic jerks and muscle twitches were observed at low incidence in Beagle dogs, cynomolgus monkeys, and Sprague-Dawley rats but were not seen in Göttingen minipigs. Spontaneous ataxia/incoordination was identified in all species and generally with a higher incidence when using video monitoring. Salivation and tremors were the two most frequent spontaneous clinical signs and both were observed in all species. Data from the current study unveil potential limitations when using control data obtained from a single study for toxicology interpretation related to low incidence neurological clinical signs while providing historical control data from Beagle dogs, cynomolgus monkeys, Sprague-Dawley rats, and Göttingen minipigs.

Soluble ST2, BCN-Bio-HF calculator and MAGGIC-HF score in long-term risk prediction after an urgent visit for heart failure.

Soluble ST2 (sST2) is the expression of a pathogenic process related to adverse remodeling that ultimately leads to increased mortality in heart failure (HF). Risk score models provide a comprehensive approach for mortality prediction, beyond the use of biomarkers alone. The objective was to determine the additional value of sST2 and two well-validated contemporary risk scores, BCN-Bio-HF and MAGGIC-HF, in predicting mortality and readmission in the acute setting. This prospective study included 129 patients (mean age 75 ± 9 years; 52% males) after an urgent HF visit. Baseline sST2 levels were measured and the two risk scores were calculated. The primary endpoint was all-cause mortality, and the secondary endpoint was HF readmissions. The follow-up period was 3.6 ± 1.9 years. Patients who died (46%) had higher sST2 concentrations (80.5 vs. 42.7 ng/ml; p < 0.001). The BCN-Bio-HF calculator with sST2 demonstrated the best discriminative ability for mortality prediction (area under the ROC curve: 0.792; p < 0.001). In multivariate analysis for each risk score, the MAGGIC-HF score retained its predictive value only in the model without sST2 (3-year risk: HR = 1.036; 95% CI 1.019-1.054; p < 0.001). However, the BCN-Bio-HF score maintained its prognostic value with sST2 (HR = 1.032; 95%CI 1.020-1.044; p < 0.001), as well as without sST2 (HR = 1.035; 95% CI 1.021-1.049; p < 0.001). sST2 was not associated with readmission, and only the BCN-Bio-HF risk of HF hospitalization showed independent predictive value (OR = 1.040; 95% CI 1.005-1.076; p = 0.023). For predicting long-term mortality in HF in the emergency department, the BCN-Bio-HF calculator with sST2 demonstrated superior discrimination and allows estimation of the risk of HF hospitalizations.

Pilot testing the EARS-Vet surveillance network for antibiotic resistance in bacterial pathogens from animals in the EU/EEA.

Introduction: As part of the EU Joint Action on Antimicrobial Resistance (AMR) and Healthcare-Associated Infections, an initiative has been launched to build the European AMR Surveillance network in veterinary medicine (EARS-Vet). So far, activities included mapping national systems for AMR surveillance in animal bacterial pathogens, and defining the EARS-Vet objectives, scope, and standards. Drawing on these milestones, this study aimed to pilot test EARS-Vet surveillance, namely to (i) assess available data, (ii) perform cross-country analyses, and (iii) identify potential challenges and develop recommendations to improve future data collection and analysis. Methods: Eleven partners from nine EU/EEA countries participated and shared available data for the period 2016-2020, representing a total of 140,110 bacterial isolates and 1,302,389 entries (isolate-antibiotic agent combinations). Results: Collected data were highly diverse and fragmented. Using a standardized approach and interpretation with epidemiological cut-offs, we were able to jointly analyze AMR trends of 53 combinations of animal host-bacteria-antibiotic categories of interest to EARS-Vet. This work demonstrated substantial variations of resistance levels, both among and within countries (e.g., between animal host species). Discussion: Key issues at this stage include the lack of harmonization of antimicrobial susceptibility testing methods used in European surveillance systems and veterinary diagnostic laboratories, the absence of interpretation criteria for many bacteria-antibiotic combinations of interest, and the lack of data from a lot of EU/EEA countries where little or even surveillance currently exists. Still, this pilot study provides a proof-of-concept of what EARS-Vet can achieve. Results form an important basis to shape future systematic data collection and analysis.

An Overview of Gene Editing Modalities and Related Non-clinical Testing Considerations.

Gene therapy has become an important modality for a wide range of therapeutic indications with a rapid increase in the number of therapeutic candidates being developed in this field. Understanding the molecular biology underlying the gene therapy is often critical to develop appropriate safety assessment strategies. We aimed to discuss some of the commonly used gene therapy modalities and common preclinical toxicology testing considerations when developing gene therapies. Non-viral gene delivery methods such as electroporation, microinjection, peptide nanoparticles and lipid nanoparticles are deployed as innovative molecular molecular construct which are included in the design of novel gene therapies and the associated molecular biology mechanisms have become relevant knowledge to non-clinical toxicology. Viral gene delivery methodologies including Adenovirus vectors, Adeno-Associated virus vectors and Lentivirus gene therapy vectors have also advanced considerably across numerous therapeutic areas, raising unique non-clinical toxicology and immunological considerations. General toxicology, biodistribution and tumorigenicity are the pillars of non-clinical safety testing in gene therapies. Evaluating the tumorigenicity potential of a gene editing therapy often leverages molecular pathology while some translational challenges remain. Toxicology study design is entering a new era where science-driven customized approaches and program specific considerations have become the norm.

Resting metabolic rate in relation to incident disability and mobility decline among older adults: the modifying role of frailty.

BACKGROUND: Alterations in resting metabolic rate (RMR), the largest component of daily total energy expenditure, with aging have been shown in various studies. However, little is known about the associations between RMR and health outcomes in later life. AIMS: To analyze whether RMR is associated with incident disability and mobility decline in a 10-year longitudinal study, as well as the moderating role of frailty in these associations. METHODS: Data from 298 older adults aged 70 and over from the Frailty and Dependence in Albacete (FRADEA) study in Spain were used, including a baseline measurement in 2007-2009 and a follow-up measurement 10 years later. RMR was measured by indirect calorimetry. Outcomes were incident disability in basic activities of daily living (BADL, Barthel Index), incident disability in instrumental ADL (IADL, Lawton index), and mobility decline (Functional Ambulation Categories scores). Fried's frailty phenotype was used as an indicator of frailty. Logistic regression analyses were conducted. RESULTS: Fully adjusted and stratified analyses revealed that only in the pre-frail/frail group, a higher RMR was associated with a lower risk of incident BADL disability (OR = 0.47, 95% CI = 0.23-0.96, p = 0.037), incident IADL disability (OR = 0.39, 95% CI = 0.18-0.84, p = 0.017), and mobility decline (OR = 0.30, 95% CI = 0.14-0.64, p = 0.002). CONCLUSIONS: To our knowledge, this is the first study looking at the associations between RMR and functional health using a longitudinal research design. The results suggest that RMR could be used as an early identifier of a specific resilient group within the pre-frail and frail older population, with a lower risk of further health decline.

Model Characterization: Total Body Irradiation or Busulfan for Conditioning in Human Cell Therapy Toxicology and Tumorigenicity Studies using NOD/SCID/IL2Rγnull (NSG) Mice.

The NOD/SCID/IL2Rγnull (NSG) mouse is a relevant model for toxicology and tumorigenicity studies evaluating human cell therapies. Data was compiled from toxicology study control NSG mice exposed to gamma irradiation (0 or 200 cGy) or busulfan. Retrospective data evaluation included mortality, clinical observations, body weights, hematology, and external and internal macroscopic observations. There was no mortality in any of the 129 toxicology control (irradiated and non-irradiated) mice up to the 20-week observation period. Mortalities occurred between Days 1 and 25 among animals given busulfan ≥25 mg/kg/day at 1 or 2 doses via intraperitoneal (i.p.) injection. There were 4/10, 6/10 and 4/10 deaths at 25, 30 and 35 mg/kg/day busulfan, respectively. Busulfan-treated mice presented with dose-dependent clinical signs including signs of anemia in some individuals. Hematology, including white blood cell (WBC) and neutrophil (NEUT) counts, from irradiated mice at Weeks 12 and 20 revealed comparable values to non-irradiated animals. In contrast, irradiated mice treated with a positive control (HL-60) were euthanized prior to Week 12. There were no irradiation-related differences in macroscopic observations with lymphoid atrophy identified comparably in irradiated and non-irradiated groups. These results suggest that irradiation was suitable for conditioning to enable cell engraftment in NSG mice in the context of regulatory toxicology and tumorigenicity studies. Busulfan administered at 20 mg/kg/day for 2 days, i.p. was also well-tolerated, and it could be considered for toxicology studies of genetically modified human cells.

Nonclinical Safety Assessment of Lipid Nanoparticle-and Emulsion-Based Self-Amplifying mRNA Vaccines in Rats.

Vaccines containing mRNA with the capacity to self-amplify represent an alternative to the mRNA vaccines that came to prominence during the COVID-19 pandemic. To gain further insights on the safety profile of self-amplifying mRNA- (SAM-) vaccines, this preclinical toxicology study in rats evaluated the effect of (i) the type of delivery system (lipid nanoparticle [LNP] vs cationic nano-emulsion [CNE]); (ii) antigen-encoding sequence (rabies glycoprotein G vs SARS-CoV-2 Spike); and (iii) RNA amplification. Further analyses also evaluated gene expression in peripheral blood after vaccination, and the biodistribution of vaccine RNA. The SAM vaccines administered as two doses 2-weeks apart had acceptable safety profiles in rats, with respect to clinical signs, blood biochemistry, and macroscopic and microscopic pathology. A transient increase in ALT/AST ratio occurred only in female rats and in the absence of muscle and liver damage was dependent on RNA amplification and appeared related to the greater quantities of vaccine RNA in the muscle and livers of female rats vs male rats. The RNA and delivery-vehicle components, but not the nature of the antigen-coding sequence or the requirement for RNA amplification, affected aspects of the stimulation of innate-immune activity, which was consistent with the transient activation of type I and type II interferon signaling. The delivery vehicle, LNP, differed from CNE as vaccine RNA in CNE compositions appeared independently to stimulate innate-immune activity at 4 hours after vaccination. Our analysis supports further studies to assess whether these differences in innate-immune activity affect safety and efficacy of the SAM vaccine.

Limits of stability and falls during a multicomponent exercise program in faller older adults: A retrospective cohort study.

BACKGROUND/OBJETIVES: Multicomponent exercise programs have been demonstrated to prevent falls in older adults. However, the underlying responsible mechanisms are not clear. We aimed to analyze the association between changes in the limits of stability (LOS) as a relevant balance component, and falls occurrence during a multicomponent physical exercise program. METHODS: Retrospective study, including ninety-one participants who had experienced a fall in the previous year, and were attended in a falls unit. All of them were included in a twice-a-week multicomponent exercise program during 16 weeks. Pre- and post-program measurements were collected for leg press, gait speed, the short physical performance battery (SPPB), and LOS (point of excursion [POE] and maximal excursion [MEX]) with posturography. Falls occurrence was assessed between the beginning and the completion of the exercise program (16 week). RESULTS: The mean age was 77.2 years, and 72 were female. Thirty-two participants fell at least once during the exercise period. The global baseline POE was 47.6 %, and the MEX was 64.7 %, and there were no differences between fallers and nonfallers. Nonfallers presented greater improvements in POE (6.3 % versus 1.3 %; p < .05) and MEX (9.2 % versus 3.0 %; p < .01) than fallers. The POE and MEX were independently associated with a reduced probability of having had a fall, OR: 0.95 (95 % CI: 0.91 to 0.99) and 0.94 (95 % CI: 0.90 to 0.99), respectively. Changes in SPPB results or leg press strength were not associated with decreased falls. Adjusted probability of fall occurrence decreased by 5 % and 6 % per 1 % improvement in absolute values in POE and MEX, respectively. CONCLUSIONS: Improvements in LOS after a multicomponent physical exercise program in older adults with previous falls may be associated with a decreased occurrence of falls.

Field and Laboratory Procedures for Fusarium circinatum Identification and Diagnosis.

Fusarium circinatum is a serious invasive pathogen affecting conifers and causes the disease commonly known as pine pitch canker. Due to the outbreak in European countries, regulations stipulate that Member States must conduct annual official surveys for the fungus on their territory and report the results to the European Commission. Here, we describe the field and laboratory protocols used for the identification and diagnostic of the pathogen.

Frailty, depression risk and 10-year hospitalization in older adults. The FRADEA study.

OBJECTIVES: To determine whether the interaction between frailty status and depression risk is associated with hospitalization density in older adults. METHODS: Ongoing cohort study in 794 subjects aged over 70 years from Albacete (Spain). Data were collected on depression risk, frailty, hospitalizations, and covariates. Participants were categorized into six groups. RESULTS: Adjusted hospitalization risk was higher for groups of prefrail/-non depression risk (HR 1.48; 95% confidence interval (CI) 1.16-1.89), prefrail/depression risk (HR 1.73; 95% CI 1.29-2.30), frail/non depression risk (HR 1.79; 95% CI 1.22-2.62), and frail/depression risk (HR 2.12; 95% CI 1.49-3.02), compared with robust/non depression risk group (p<0.01). Frail and prefrail groups presented increased hospitalization density in the first four follow-up years. CONCLUSIONS: Depression risk changes the yearly probabilities of hospitalization in prefrail and frail groups, increasing them in the first years. Depression risk should be monitored in prefrail and frail older adults as an independent risk factor for hospitalization.

Genome-wide identification and characterization of Fusarium circinatum-responsive lncRNAs in Pinus radiata.

BACKGROUND: One of the most promising strategies of Pine Pitch Canker (PPC) management is the use of reproductive plant material resistant to the disease. Understanding the complexity of plant transcriptome that underlies the defence to the causal agent Fusarium circinatum, would greatly facilitate the development of an accurate breeding program. Long non-coding RNAs (lncRNAs) are emerging as important transcriptional regulators under biotic stresses in plants. However, to date, characterization of lncRNAs in conifer trees has not been reported. In this study, transcriptomic identification of lncRNAs was carried out using strand-specific paired-end RNA sequencing, from Pinus radiata samples inoculated with F. circinatum at an early stage of infection. RESULTS: Overall, 13,312 lncRNAs were predicted through a bioinformatics approach, including long intergenic non-coding RNAs (92.3%), antisense lncRNAs (3.3%) and intronic lncRNAs (2.9%). Compared with protein-coding RNAs, pine lncRNAs are shorter, have lower expression, lower GC content and harbour fewer and shorter exons. A total of 164 differentially expressed (DE) lncRNAs were identified in response to F. circinatum infection in the inoculated versus mock-inoculated P. radiata seedlings. The predicted cis-regulated target genes of these pathogen-responsive lncRNAs were related to defence mechanisms such as kinase activity, phytohormone regulation, and cell wall reinforcement. Co-expression network analysis of DE lncRNAs, DE protein-coding RNAs and lncRNA target genes also indicated a potential network regulating pectinesterase activity and cell wall remodelling. CONCLUSIONS: This study presents the first comprehensive genome-wide analysis of P. radiata lncRNAs and provides the basis for future functional characterizations of lncRNAs in relation to pine defence responses against F. circinatum.

Psychological and Functional Impact of COVID-19 in Long-Term Care Facilities: The COVID-A Study.

OBJECTIVE: To analyze the psychological and functional sequelae of the COVID-19 pandemic among older adults living in long term care facilities (LTCFs). DESIGN: Cohort longitudinal study SETTING ANT PARTICIPANTS: A total of 215 residents ≥ 65 years without moderate-to-severe cognitive impairment, living in five LTCFs in Albacete (Spain). MEASUREMENTS: Baseline on-site data were collected between March - June 2020 and three-month follow-up between June to September 2020. Symptoms of depression, anxiety, posttraumatic stress disorder (PTSD), and sleep disturbances were measured as psychological variables. Disability in basic activities of daily living (BADL), ambulation and frailty were assessed as functional variables. Differences were analyzed in relation to level of comorbidity and test positivity for COVID-19. RESULTS: At baseline, residents with COVID-19 presented worse functionality, higher frailty levels and malnutrition risk compared to non-COVID-19 residents. At three-month follow-up, higher rates of clinically significant depressive symptoms (57.7%), anxiety symptoms (29.3%), PTSD symptoms (19.1%) and sleep disturbances (93.0%) were found among residents regardless of COVID status. Thus, among 215 residents, 101 (47%) experienced a decline in BADL from baseline to the 3-month follow-up (median functional loss = 5 points in Barthel Index). In multivariate analyses, COVID-19 status did not explain either the functional or the ambulation loss. By contrast, residents with low comorbidity and COVID-19 presented higher PTSD symptoms (effect 2.58; 95% CI 0.93 to 4.23) and anxiety symptoms (effect 2.10; 95% CI 0.48 to 3.73) compared to the low comorbidity/non-COVID19 group. CONCLUSION: COVID-19 pandemic was associated, after three-months, with high psychological impact in older adults in LTCFs., specifically with higher post-traumatic stress and anxiety symptoms. Functional decline did not differ in relation to COVID-19 status but could be related to isolation strategies used for pandemic control.

Co-Infections by Fusarium circinatum and Phytophthora spp. on Pinus radiata: Complex Phenotypic and Molecular Interactions.

This study investigated the complex phenotypic and genetic response of Monterey pine (Pinus radiata) seedlings to co-infections by F. circinatum, the causal agent of pine pitch canker disease, and the oomycetes Phytophthora xcambivora and P. parvispora. Monterey pine seedlings were wound-inoculated with each single pathogen and with the combinations F. circinatum/P. xcambivora and F. circinatum/P. parvispora. Initially, seedlings inoculated only with F. circinatum showed less severe symptoms than seedlings co-inoculated or inoculated only with P. xcambivora or P. parvispora. However, 30 days post-inoculation (dpi), all inoculated seedlings, including those inoculated only with F. circinatum, showed severe symptoms with no significant differences among treatments. The transcriptomic profiles of three genes encoding pathogenesis-related proteins, i.e., chitinase (PR3), thaumatin-like protein (PR5), phenylalanine ammonia-lyase (PAL), and the pyruvate decarboxylase (PDC)-encoding gene were analyzed at various time intervals after inoculation. In seedlings inoculated with single pathogens, F. circinatum stimulated the up-regulation of all genes, while between the two oomycetes, only P. xcambivora induced significant up-regulations. In seedlings co-inoculated with F. circinatum and P.xcambivora or P. parvispora none of the genes showed a significant over-expression 4 dpi. In contrast, at 11 dpi, significant up-regulation was observed for PR5 in the combination F. circinatum/P.xcambivora and PDC in the combination F. circinatum/P. parvispora, thus suggesting a possible synergism of multiple infections in triggering this plant defense mechanism.

Mining nematode protein secretomes to explain lifestyle and host specificity.

Parasitic nematodes are highly successful pathogens, inflicting disease on humans, animals and plants. Despite great differences in their life cycles, host preference and transmission modes, these parasites share a common capacity to manipulate their host's immune system. This is at least partly achieved through the release of excretory/secretory proteins, the most well-characterized component of nematode secretomes, that are comprised of functionally diverse molecules. In this work, we analyzed published protein secretomes of parasitic nematodes to identify common patterns as well as species-specific traits. The 20 selected organisms span 4 nematode clades, including plant pathogens, animal parasites, and the free-living species Caenorhabditis elegans. Transthyretin-like proteins were the only component common to all adult secretomes; many other protein classes overlapped across multiple datasets. The glycolytic enzymes aldolase and enolase were present in all parasitic species, but missing from C. elegans. Secretomes from larval stages showed less overlap between species. Although comparison of secretome composition across species and life-cycle stages is challenged by the use of different methods and depths of sequencing among studies, our workflow enabled the identification of conserved protein families and pinpointed elements that may have evolved as to enable parasitism. This strategy, extended to more secretomes, may be exploited to prioritize therapeutic targets in the future.

Developing and validating a rapid assessment tool for small ruminant reproduction and production in pastoralist flocks in Kajiado, Kenya.

The collection of production performance data in small ruminants pastoralists flocks is essential to evaluate their efficiency and assess how different challenges, such as diseases, droughts or changes in land use, affect their sustainability. Although different methodologies exist, capturing these data is difficult, particularly in nomadic pastoral flocks. In this study, a method for rapid assessment of flock production performance based on farmer recall was designed, implemented and tested. Through literature review and consultation with pastoralists and key informants, a questionnaire was developed to capture small ruminant flock data disaggregated by age (≤2 years old and >2 years old), species and sex. Data on flock dynamics and on reproduction parameters were collected for a period of 12 months. A survey of 130 pastoralists with medium to large flocks was then conducted in Kajiado County (Kenya). Values were calculated for 12 reproduction performance indicators and 7 additional production performance indicators. In addition, a flock efficiency indicator (FEI) is proposed that classifies mixed flocks (i.e., with sheep and goats) into low, medium or high efficiency. Results showed that in flocks with low efficiency, the median value for net fecundity rate was 0.43 lambs/ewe (range 0.08-1.00) and 0.41 kids/doe (range 0.07-0.73), and the median production rate was 6% (range [-47%] to 20%) for sheep and 11% (range [-38%] to 0.21%) for goats. In flocks with high efficiency the median net fecundity rate was 0.77 lambs/ewe (range 0.48-2.73) and 0.88 kids/doe (range 0.49-1.80), and the median production rate was 25% (range 11-47) for sheep and 28% (range 15-46) for goats. Sixty-two (47.7%) of the pastoralists surveyed reported usually buying animals into their flocks, and, consequently were considered as 'pastoralists and traders'. Their flocks had significantly lower FEI scores (median = 7.5, interquartile range [IQR] 6-9), compared with "pastoralists only" flocks (median = 8, IQR 6-10, Kruskal-Wallis rank sum test, p-value <0.001). Since this method is based on pastoralist recall, values obtained should be considered as approximations. Nonetheless, the proposed assessment tool can be used by individuals with low resources or recording capacity, and in large scale programmes to monitor pastoralist flock dynamics, set-up benchmarking programmes, estimate the impact of diseases and shocks, identify those flocks which are most vulnerable to these shocks and evaluate the effectiveness of policies and interventions on herd performance.

Baricitinib reduces 30-day mortality in older adults with moderate-to-severe COVID-19 pneumonia.

BACKGROUND: Older adults are at the highest risk of severe disease and death due to COVID-19. Randomized data have shown that baricitinib improves outcomes in these patients, but focused stratified analyses of geriatric cohorts are lacking. Our objective was to analyze the efficacy of baricitinib in older adults with COVID-19 moderate-to-severe pneumonia. METHODS: This is a propensity score [PS]-matched retrospective cohort study. Patients from the COVID-AGE and Alba-Score cohorts, hospitalized for moderate-to-severe COVID-19 pneumonia, were categorized in two age brackets of age <70 years old (86 with baricitinib and 86 PS-matched controls) or ≥70 years old (78 on baricitinib and 78 PS-matched controls). Thirty-day mortality rates were analyzed with Kaplan-Meier and Cox proportional hazard models. RESULTS: Mean age was 79.1 for those ≥70 years and 58.9 for those <70. Exactly 29.6% were female. Treatment with baricitinib resulted in a significant reduction in death from any cause by 48% in patients aged 70 or older, an 18.5% reduction in 30-day absolute mortality risk (n/N: 16/78 [20.5%] baricitinib, 30/78 [38.5%] in PS-matched controls, p < 0.001) and a lower 30-day adjusted fatality rate (HR 0.21; 95% CI 0.09-0.47; p < 0.001). Beneficial effects on mortality were also observed in the age group <70 (8.1% reduction in 30-day absolute mortality risk; HR 0.14; 95% CI 0.03-0.64; p = 0.011). CONCLUSIONS: Baricitinib is associated with an absolute mortality risk reduction of 18.5% in adults older than 70 years hospitalized with COVID-19 pneumonia.

Symptomatic and Asymptomatic Protist Infections in Hospital Inpatients in Southwestern China.

Cryptosporidium spp., Entamoeba histolytica, Giardia duodenalis, and Blastocystis sp. infections have been frequently reported as etiological agents for gastroenteritis, but also as common gut inhabitants in apparently healthy individuals. Between July 2016 and March 2017, stool samples (n = 507) were collected from randomly selected individuals (male/female ratio: 1.1, age range: 38-63 years) from two sentinel hospitals in Tengchong City Yunnan Province, China. Molecular (PCR and Sanger sequencing) methods were used to detect and genotype the investigated protist species. Carriage/infection rates were: Blastocystis sp. 9.5% (95% CI: 7.1-12.4%), G. duodenalis 2.2% (95% CI: 1.1-3.8%); and E. histolytica 2.0% (95% CI: 0.9-3.6%). Cryptosporidium spp. was not detected at all. Overall, 12.4% (95% CI: 9.7-15.6) of the participants harbored at least one enteric protist species. The most common coinfection was E. histolytica and Blastocystis sp. (1.0%; 95% CI: 0.3-2.2). Sequence analyses revealed that 90.9% (10/11) of the genotyped G. duodenalis isolates corresponded to the sub-assemblage AI. The remaining sequence (9.1%, 1/11) was identified as sub-assemblage BIV. Five different Blastocystis subtypes, including ST3 (43.7%, 21/48), ST1 (27.1%, 13/48), ST7 (18.8%, 9/48), ST4 (8.3%, 4/48), and ST2 (2.1%, 1/48) were identified. Statistical analyses confirmed that (i) the co-occurrence of protist infections was purely random, (ii) no associations were observed among the four protist species found, and (iii) neither their presence, individually or jointly, nor the patient's age was predictors for developing clinical symptoms associated with these infections. Overall, these protist mono- or coinfections are asymptomatic and do not follow any pattern.

Dual RNA-Sequencing Analysis of Resistant (Pinus pinea) and Susceptible (Pinus radiata) Hosts during Fusarium circinatum Challenge.

Fusarium circinatum causes one of the most important diseases of conifers worldwide, the pine pitch canker (PPC). However, no effective field intervention measures aiming to control or eradicate PPC are available. Due to the variation in host genetic resistance, the development of resistant varieties is postulated as a viable and promising strategy. By using an integrated approach, this study aimed to identify differences in the molecular responses and physiological traits of the highly susceptible Pinus radiata and the highly resistant Pinus pinea to F. circinatum at an early stage of infection. Dual RNA-Seq analysis also allowed to evaluate pathogen behavior when infecting each pine species. No significant changes in the physiological analysis were found upon pathogen infection, although transcriptional reprogramming was observed mainly in the resistant species. The transcriptome profiling of P. pinea revealed an early perception of the pathogen infection together with a strong and coordinated defense activation through the reinforcement and lignification of the cell wall, the antioxidant activity, the induction of PR genes, and the biosynthesis of defense hormones. On the contrary, P. radiata had a weaker response, possibly due to impaired perception of the fungal infection that led to a reduced downstream defense signaling. Fusarium circinatum showed a different transcriptomic profile depending on the pine species being infected. While in P. pinea, the pathogen focused on the degradation of plant cell walls, active uptake of the plant nutrients was showed in P. radiata. These findings present useful knowledge for the development of breeding programs to manage PPC.

The Functional Continuum Scale in Relation to Hospitalization Density in Older Adults: The FRADEA Study.

BACKGROUND: There is a need to know the relationship between function and hospitalization risk in older adults. We aimed at investigating whether the Functional Continuum Scale (FCS), based on basic (BADL) and instrumental (IADL) activities of daily living and frailty, is associated with hospitalization density in older adults across 12 years of follow-up. METHODS: Cohort study, with a follow-up of 12 years. A total of 915 participants aged 70 years and older from the Frailty and Dependence in Albacete (FRADEA) study, a population-based study in Spain, were included. At baseline, the FCS, sociodemographic characteristics, comorbidity, number of medications, and place of residence were assessed. Associations with first hospitalization, number of hospitalizations, and 12-year density of hospitalizations were assessed using Kaplan-Meier curves, Poisson regression analyses, and density models. RESULTS: The median time until the first hospitalization was shorter toward the less functionally independent end of the FCS, from 3917 days (95% confidence interval [CI] 3701-3995) to 1056 days (95% CI 785-1645) (p < .001). The incidence rate ratio (IRR) for all hospitalizations increased from the robust category until the frail one (IRR 1.89), and thereafter it decreased until the worse functional category. Those who were BADL dependent presented an increased hospitalization density in the first 4 follow-up years (58%), those who were frail in the third-to-sixth follow-up years (55%), while in those prefrail or robust the hospitalization density was homogeneous during the complete follow-up. CONCLUSIONS: The FCS is useful for stratifying the risk of hospitalization and for predicting the density of hospitalizations in older adults.