Transitions and Long-Term Clinical Outcomes in Patients Admitted in Intensive Care Units Receiving Continuous Renal Replacement Therapy.

Introduction: Acute kidney injury (AKI) significantly disrupts vital renal functions and is a common and serious condition in intensive care units (ICUs). AKI leads to extended hospital stays, increases mortality rates, and often necessitates nephrology consultations. Continuous renal replacement therapy (CRRT) plays a central role in managing AKI, requiring a multidisciplinary approach involving nephrologists, intensivists, and anesthesiologists. This study examines the clinical profile and progression of AKI in ICU patients requiring CRRT, with a focus on CRRT indications and modalities. Materials and Methods: We conducted a single-center retrospective observational study on ICU patients with AKI requiring CRRT from January to December 2019. AKI diagnosis followed the RIFLE criteria, and patients who received CRRT for less than 36 h were excluded. Data collected included demographics, hemodynamic parameters, and renal function parameters, with follow-ups at 1 week, 1 month, 6 months, and 12 months. Statistical analyses evaluated outcomes and transitions between CRRT and other renal replacement therapies. Results: Among 123 evaluated patients, 95 met inclusion criteria. Fifteen patients received CRRT for less than 36 h, with an early mortality rate of 80%. The final cohort comprised 80 patients who underwent CRRT for over 36 h, with a mean age of 65.3 years (SD = 13.6) and a Charlson index of 6.4. Patients were categorized based on primary diagnosis into heart failure, cardiac surgery, sepsis, other surgeries, and miscellanea groups. Mortality rates were highest in the heart failure and miscellanea groups. Significant variability was observed in therapy transitions and long-term outcomes. Continuous venovenous hemodiafiltration (CVVHDF) was the most frequently used CRRT modality. Conclusions: This study highlights the variability in CRRT practices and the poor prognosis for critically ill patients with AKI requiring CRRT. Timely nephrology consultation and tailored treatment plans may improve patient outcomes and optimize CRRT utilization. Future research should focus on refining CRRT protocols and exploring preventive strategies for AKI.

Efficacy and Safety in a Real-World Study of the New Oral Formulation of Semaglutide in Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus.

Background/Objectives: GLP-1 receptor agonists (GLP-1RAs) have emerged as fundamental components in the treatment of type 2 diabetic patients (T2DM) with chronic kidney disease (CKD). The oral formulation represents a novel therapeutic tool but may affect drug efficacy. This study sought to compare the effectiveness of subcutaneous versus oral semaglutide formulations in patients with CKD. Methods: A retrospective study in a real-world setting compared type 2 diabetes and chronic kidney disease patients, initiating oral semaglutide treatment to a historically matched control group treated with subcutaneous semaglutide. The matching considered factors such as estimated glomerular filtration rate (eGFR), age, and sex. Results: Nineteen patients were included in both groups, with a mean age of 68.0. Seventy-two percent were males with a CKD-EPI eGFR of 49.9 mL/min/1.73 m2 and a median urine albumin-to-creatinine ratio of 12.7 mg/g. Of the study participants, 94% and 79% of patients were on the maximum semaglutide sbc vs. oral dose, while 5.3% and 15.8% were on the sbc vs. oral low dose. Oral semaglutide significantly reduced HbA1C and BMI, identical to the control group (-0.9 and -1.4, p > 0.05). Renal function parameters and blood pressure remained stable throughout the follow-up in both groups. The main side effect was digestive intolerance (affecting three patients in the oral group and two patients in the subcutaneous group, p = 0.6), although the treatment abandonment percentage was similar. Conclusions: The oral formulation of semaglutide demonstrated equivalent effectiveness in glucose control and body weight management in patients with T2DM and CKD, even with a higher proportion of patients receiving low to medium doses. Gastrointestinal side effects were comparable between both oral and subcutaneous formulations.

Zoonosis screening in Spanish immunocompromised children and their pets.

Introduction: Although pets provide several social-emotional benefits for children, the risk of zoonosis must be considered among immunocompromised individuals. Methods: A prospective study was conducted in a tertiary hospital including immunocompromised patients younger than 20 years owning dogs and/or cats. Colonization and/or infection was evaluated by stool studies, bacterial swabs, blood polymerase chain reaction and serological studies in both patients and their pets, to evaluate potential zoonotic transmission occurrence. Results: We included 74 patients and their 92 pets (63 dogs, 29 cats). Up to 44.6% of the patients and 31.5% of the pets had at least 1 positive result. Up to 18.4% of pets' fecal samples were positive (bacteria, parasites or hepatitis E virus). No helminths were observed despite the high frequency of incorrect intestinal deworming practices. Among children, gastrointestinal microorganisms were found in 37.3% (primarily Clostridium difficile). Colonization by Staphylococcus pseudintermedius was common among pets (8.0%) but not among children (0.0%). No shared colonization between owners and pets was observed, except in one case (Blastocystis in both patient and pet feces). Among patients, serologies were positive for Strongyloides stercoralis (14.8%), Toxocara canis (3.2%), Bartonella henselae (19.1%) and hepatitis E (5.6%). Serology was positive for Rickettsia spp. (22.6%) and Babesia spp. (6.5%) in dogs and for Leishmania spp. (14.3%) and Toxoplasma spp. (14.3%) in cats. Conclusion: Exposure to zoonotic agents was detected in both patients and pets; however, shared colonization events were almost nonexistent. In our cohort, dogs and cats do not appear to entail high zoonosis transmission risk for immunocompromised patients.

Impact of chromosomally encoded resistance mechanisms and transferable ß-lactamases on the activity of cefiderocol and innovative ß-lactam/ß-lactamase inhibitor combinations against Pseudomonas aeruginosa.

OBJECTIVES: We aimed to compare the stability of the newly developed ß-lactams (cefiderocol) and ß-lactam/ß-lactamase inhibitor combinations (ceftazidime/avibactam, ceftolozane/tazobactam, aztreonam/avibactam, cefepime/taniborbactam, cefepime/zidebactam, imipenem/relebactam, meropenem/vaborbactam, meropenem/nacubactam and meropenem/xeruborbactam) against the most clinically relevant mechanisms of mutational and transferable ß-lactam resistance in Pseudomonas aeruginosa. METHODS: We screened a collection of 61 P. aeruginosa PAO1 derivatives. Eighteen isolates displayed the most relevant mechanisms of mutational resistance to ß-lactams. The other 43 constructs expressed transferable ß-lactamases from genes cloned in pUCP-24. MICs were determined by reference broth microdilution. RESULTS: Cefiderocol and imipenem/relebactam exhibited excellent in vitro activity against all of the mutational resistance mechanisms studied. Aztreonam/avibactam, cefepime/taniborbactam, cefepime/zidebactam, meropenem/vaborbactam, meropenem/nacubactam and meropenem/xeruborbactam proved to be more vulnerable to mutational events, especially to overexpression of efflux operons. The agents exhibiting the widest spectrum of activity against transferable ß-lactamases were aztreonam/avibactam and cefepime/zidebactam, followed by cefepime/taniborbactam, cefiderocol, meropenem/xeruborbactam and meropenem/nacubactam. However, some MBLs, particularly NDM enzymes, may affect their activity. Combined production of certain enzymes (e.g. NDM-1) with increased MexAB-OprM-mediated efflux and OprD deficiency results in resistance to almost all agents tested, including last options such as aztreonam/avibactam and cefiderocol. CONCLUSIONS: Cefiderocol and new ß-lactam/ß-lactamase inhibitor combinations show promising and complementary in vitro activity against mutational and transferable P. aeruginosa ß-lactam resistance. However, the combined effects of efflux pumps, OprD deficiency and efficient ß-lactamases could still result in the loss of all therapeutic options. Resistance surveillance, judicious use of new agents and continued drug development efforts are encouraged.

Management of Pediatric Mild Traumatic Brain Injury Patients: S100b, Glial Fibrillary Acidic Protein, and Heart Fatty-Acid-Binding Protein Promising Biomarkers.

Children are highly vulnerable to mild traumatic brain injury (mTBI). Blood biomarkers can help in their management. This study evaluated the performances of biomarkers, in discriminating between children with mTBI who had intracranial injuries (ICIs) on computed tomography (CT+) and (1) patients without ICI (CT-) or (2) both CT- and in-hospital-observation without CT patients. The aim was to rule out the need of unnecessary CT scans and decrease the length of stay in observation in the emergency department (ED). Newborns to teenagers (≤16 years old) with mTBI (Glasgow Coma Scale > 13) were included. S100b, glial fibrillary acidic protein (GFAP), and heart fatty-acid-binding protein (HFABP) performances to identify patients without ICI were evaluated through receiver operating characteristic curves, where sensitivity was set at 100%. A total of 222 mTBI children sampled within 6 h since their trauma were reported. Nineteen percent (n = 43/222) underwent CT scan examination, whereas the others (n = 179/222) were kept in observation at the ED. Sixteen percent (n = 7/43) of the children who underwent a CT scan had ICI, corresponding to 3% of all mTBI-included patients. When sensibility (SE) was set at 100% to exclude all patients with ICI, GFAP yielded 39% specificity (SP), HFABP 37%, and S100b 34% to rule out the need of CT scans. These biomarkers were even more performant: 52% SP for GFAP, 41% for HFABP, and 39% for S100b, when discriminating CT+ versus both in-hospital-observation and CT- patients. These markers can significantly help in the management of patients in the ED, avoiding unnecessary CT scans, and reducing length of stay for children and their families.

Seizures in Children With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

BACKGROUND: Although respiratory symptoms are the most prominent manifestations of coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and especially the omicron variant, may cause neurological manifestations such as seizures. It remains unclear if specific variants of the virus increase the risk of seizures more than others. MATERIAL AND METHODS: This was a retrospective multicenter study of pediatric (zero to 16 years) patients with COVID-19 who attended five pediatric emergency departments in Madrid, Spain, between March 2020 and July 2022. An analysis of demographics, medical history, and seizure characteristics was conducted. The data obtained were correlated with the incidence of the different strains of SARS-CoV-2 in the Community of Madrid. RESULTS: A total of 2411 seizures (infectious and noninfectious) were recorded, and 35 of them (1.4%) were positive for SARS-CoV-2. Of those 35 patients, 18 (51.4%) reported a history of previous seizures. The highest percentage of cases occurred when the omicron variant was the most prevalent (28 [80%] vs 7 [20%] before omicron variant). Typical febrile seizures accounted for 52.9% of the cases. No treatment was required in more than half (57.1%) of the cases. CONCLUSION: during the emergence of the omicron variant, there has been an increase in the number of COVID-19-associated seizures. These findings highlight the need for SARS-CoV-2 screening in patients with febrile and afebrile seizures, in addition to other microbiological, biochemical, or neuroimaging tests, depending on the patient's age and clinical presentation.

A newborn Screening Programme for Inborn errors of metabolism in Galicia: 22 years of evaluation and follow-up.

BACKGROUND: There is a notable lack of harmonisation in newborn screening (NBS) programmes worldwide. The Galician programme for early detection of inborn errors of metabolism (IEM) was one of the first NBS programmes in Europe to incorporate mass spectrometry (July 2000). This programme currently screens for 26 IEMs in dried blood and urine samples collected 24-72 h after birth. RESULTS: In its 22-year history, this programme has analysed samples from 440,723 neonates and identified 326 cases of IEM with a prevalence of 1:1351. The most prevalent IEMs were hyperphenylalaninaemia (n = 118), followed by medium chain acyl-CoA dehydrogenase deficiency (MCADD, n = 26), galactosaemia (n = 20), and cystinurias (n = 43). Sixty-one false positives and 18 conditions related to maternal pathologies were detected. Urine samples have been identified as a useful secondary sample to reduce the rate of false positives and identify new defects. There were 5 false negatives. The overall positive value was 84.23%. The fatality rate over a median of 12.1 years of follow-up was 2.76%. The intelligence quotient of patients was normal in 95.7% of cases, and school performance was largely optimal, with pedagogic special needs assistance required in < 10% of cases. Clinical onset of disease preceded diagnosis in 4% of cases. The age at which first NBS report is performed was reduced by 4 days since 2021. CONCLUSIONS: This study highlights the benefits of collecting urine samples, reduce NBS reporting time and expanding the number of IEMs included in NBS programmes.

Retrospective study of acute mastoiditis in children in Spain attended in a Pediatric Emergency department.

OBJECTIVE: To analyze the cases of acute mastoiditis, characteristics, management and complications in children attended in the emergency department. METHODS: Retrospective study of acute mastoiditis in a Spanish tertiary hospital over a 6-year period (2018-2023). RESULTS: One hundred two episodes of acute mastoiditis were analyzed (54% males, median age 1.8 years). Microorganisms were isolated in one third of cases, mainly Streptococcus pyogenes (64% of ear secretion cultures). Complications occurred in 27.5%, primarily subperiosteal abscess. A younger age, absence of vaccination schedule, previous history of otitis, cochlear implant carriers or white blood cell counts and C-reactive protein levels were not associated with complications. Complicated cases had longer hospitalizations. Treatment included antibiotics, corticosteroids, and surgery in 50% of cases. CONCLUSIONS: This study shows an increase of acute mastoiditis during 2023, with a relevant role of S. pyogenes. A younger age, absence of vaccination, personal history of otitis or cochlear implant, blood cell counts and C-reactive protein levels were not associated with complications.

The Uricosuric Effect of SGLT2 Inhibitors Is Maintained in the Long Term in Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus.

(1) Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2is) increase uric acid excretion. The intensity of uricosuria is linked to glycosuria. (2) Methods: We aim to analyze the effect of SGLT2 inhibitors on urinary fractional excretion (FE) of uric acid and glucose in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in a single-center retrospective study with patients with T2DM and CKD who started on treatment with SGLT2is. Patients on renal replacement therapy or with glucagon-like peptide-1 (GLP1) analogs were excluded. Subgroup analysis was performed according to the estimated glomerular filtration rate (eGFR), the SGLT2i molecule, the main comorbidities, and concomitant treatment. As a secondary objective, the study analyzed the effect of SGLT2 inhibitors on uricemia levels. (3) Results: Seventy-three patients were analyzed, with a mean follow-up of 1.2 years. Uric acid and glucose FE significantly increased after the initiation of SGLT2is. This increase remained stable during the follow-up without differences among eGFR groups. No significant reduction in uricemia was observed. However, a trend towards a decrease was observed. (4) Conclusion: The use of SGLT2is in patients with CKD and T2DM is associated with an increase in uric acid FE, which maintains stability irrespective of glomerular filtration loss at least during 24 months of follow-up.

Epidemiology, resistance genomics and susceptibility of Acinetobacter species: results from the 2020 Spanish nationwide surveillance study.

BackgroundAs increasing antibiotic resistance in Acinetobacter baumannii poses a global healthcare challenge, understanding its evolution is crucial for effective control strategies.AimWe aimed to evaluate the epidemiology, antimicrobial susceptibility and main resistance mechanisms of Acinetobacter spp. in Spain in 2020, and to explore temporal trends of A. baumannii.MethodsWe collected 199 single-patient Acinetobacter spp. clinical isolates in 2020 from 18 Spanish tertiary hospitals. Minimum inhibitory concentrations (MICs) for nine antimicrobials were determined. Short-read sequencing was performed for all isolates, and targeted long-read sequencing for A. baumannii. Resistance mechanisms, phylogenetics and clonality were assessed. Findings on resistance rates and infection types were compared with data from 2000 and 2010.ResultsCefiderocol and colistin exhibited the highest activity against A. baumannii, although colistin susceptibility has significantly declined over 2 decades. A. non-baumannii strains were highly susceptible to most tested antibiotics. Of the A. baumannii isolates, 47.5% (56/118) were multidrug-resistant (MDR). Phylogeny and clonal relationship analysis of A. baumannii revealed five prevalent international clones, notably IC2 (ST2, n = 52; ST745, n = 4) and IC1 (ST1, n = 14), and some episodes of clonal dissemination. Genes bla OXA-23, bla OXA-58 and bla OXA-24/40 were identified in 49 (41.5%), eight (6.8%) and one (0.8%) A. baumannii isolates, respectively. ISAba1 was found upstream of the gene (a bla OXA-51-like) in 10 isolates.ConclusionsThe emergence of OXA-23-producing ST1 and ST2, the predominant MDR lineages, shows a pivotal shift in carbapenem-resistant A. baumannii (CRAB) epidemiology in Spain. Coupled with increased colistin resistance, these changes underscore notable alterations in regional antimicrobial resistance dynamics.

Wastewater treatment from a science faculty during the COVID-19 pandemic by using ammonium-oxidising and heterotrophic bacteria.

During and after the pandemic caused by the SARS-CoV-2 virus, the use of personal care products and disinfectants increased in universities worldwide. Among these, quaternary ammonium-based products stand out; these compounds and their intermediates caused substantial changes in the chemical composition of the wastewater produced by these institutions. For this reason, improvements and environmentally sustainable biological alternatives were introduced in the existing treatment systems so that these institutions could continue their research and teaching activities. For this reason, the objective of this study was to develop an improved culture medium to cultivate ammonium oxidising bacteria (AOB) to increase the biomass and use them in the treatment of wastewater produced in a faculty of sciences in Bogotá, D.C., Colombia. A Plackett Burman Experimental Design (PBED) and growth curves served for oligotrophic culture medium, and production conditions improved for the AOB. Finally, these bacteria were used with total heterotrophic bacteria (THB) for wastewater treatment in a pilot plant. Modification of base ammonium broth and culture conditions (6607 mg L-1 of (NH4)2SO4, 84 mg L-1 CaCO3, 40 mg L-1 MgSO4·7H2O, 40 mg L-1 CaCl2·2H2O and 200 mg L-1 KH2PO4, 10% (w/v) inoculum, no copper addition, pH 7.0 ± 0.2, 200 r.p.m., 30 days) favoured the growth of Nitrosomonas europea, Nitrosococcus oceani, and Nitrosospira multiformis with values of 8.23 ± 1.9, 7.56 ± 0.7 and 4.2 ± 0.4 Log10 CFU mL-1, respectively. NO2- production was 0.396 ± 0.0264, 0.247 ± 0.013 and 0.185 ± 0.003 mg L-1 for Nitrosomonas europea, Nitrosococcus oceani and Nitrosospira multiformis. After the 5-day wastewater treatment (WW) by co-inoculating the three studied bacteria in the wastewater (with their self-microorganisms), the concentrations of AOB and THB were 5.92 and 9.3 Log10 CFU mL-1, respectively. These values were related to the oxidative decrease of Chemical Oxygen Demand (COD), (39.5 mg L-1), Ammonium ion (NH4+), (6.5 mg L-1) Nitrite (NO2-), (2.0 mg L-1) and Nitrate (NO3-), (1.5 mg L-1), respectively in the five days of treatment. It was concluded, with the improvement of a culture medium and production conditions for three AOB through biotechnological strategies at the laboratory scale, being a promising alternative to bio-augment of the biomass of the studied bacteria under controlled conditions that allow the aerobic removal of COD and nitrogen cycle intermediates present in the studied wastewater. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03961-4.

Legal abortion requests and outcomes for women when the law is restrictive - experience from a referral centre in south-eastern Brazil.

METHODS: Retrospective cohort study with review of medical records of women assisted between 2015 and 2020. The variables were socio-demographic and SV characteristics, gestational age, reactions towards pregnancy and outcome. We compared outcome groups using the chi-square test, Fisher's exact test and the Kruskal-Wallis test. The significance level was 5%. RESULTS: We evaluated the medical records of 235 women, of which 153(65%) had undergone to abortion; 17(7.2%) had a spontaneous abortion; 19(8%) remained pregnant; 25(10.6%) had an abortion denied; and 21(8.9%) had been lost to follow-up. Out of the total number of women, 44(18.7%) were adolescents, 152(65.2%) were white and 201(88.5%) had an education ≥9 years. Women who remained pregnant had a known aggressor, disclosed the pregnancy (p < 0.001) and were more ambivalent (p < 0.001) than the other groups. Gestational age was higher in the denied abortion group than in the performed abortion group (p < 0.001). CONCLUSION: Feelings related to decision-making about abortion affected all groups, with differences. It is important to give women space to be heard, so they can make their own decisions.

Abortion care is possible in places with restrictive laws; however, women with more vulnerable characteristics did not seek the service. Legal restrictions interfere with women's decision-making about abortion and can promote inequality in gaining access to health services.

Activity of cefiderocol and innovative ß-lactam/ß-lactamase inhibitor combinations against isogenic strains of Escherichia coli expressing single and double ß-lactamases under high and low permeability conditions.

OBJECTIVES: To analyse the impact of the most clinically relevant ß-lactamases and their interplay with low outer membrane permeability on the activity of cefiderocol, ceftazidime/avibactam, aztreonam/avibactam, cefepime/enmetazobactam, cefepime/taniborbactam, cefepime/zidebactam, imipenem/relebactam, meropenem/vaborbactam, meropenem/xeruborbactam and meropenem/nacubactam against recombinant Escherichia coli strains. METHODS: We constructed 82 E. coli laboratory transformants expressing the main ß-lactamases circulating in Enterobacterales (70 expressing single ß-lactamase and 12 producing double carbapenemase) under high (E. coli TG1) and low (E. coli HB4) permeability conditions. Antimicrobial susceptibility testing was determined by reference broth microdilution. RESULTS: Aztreonam/avibactam, cefepime/zidebactam, cefiderocol, meropenem/xeruborbactam and meropenem/nacubactam were active against all E. coli TG1 transformants. Imipenem/relebactam, meropenem/vaborbactam, cefepime/taniborbactam and cefepime/enmetazobactam were also highly active, but unstable against most of MBL-producing transformants. Combination of ß-lactamases with porin deficiency (E. coli HB4) did not significantly affect the activity of aztreonam/avibactam, cefepime/zidebactam, cefiderocol or meropenem/nacubactam, but limited the effectiveness of the rest of carbapenem- and cefepime-based combinations. Double-carbapenemase production resulted in the loss of activity of most of the compounds tested, an effect particularly evident for those E. coli HB4 transformants in which MBLs were present. CONCLUSIONS: Our findings highlight the promising activity that cefiderocol and new ß-lactam/ß-lactamase inhibitors have against recombinant E. coli strains expressing widespread ß-lactamases, including when these are combined with low permeability or other enzymes. Aztreonam/avibactam, cefiderocol, cefepime/zidebactam and meropenem/nacubactam will help to mitigate to some extent the urgency of new compounds able to resist MBL action, although NDM enzymes represent a growing challenge against which drug development efforts are still needed.

Biomass gasification, catalytic technologies and energy integration for production of circular methanol: New horizons for industry decarbonisation.

The Intergovernmental Panel on Climate Change (IPCC) recognises the pivotal role of renewable energies in the future energy system and the achievement of the zero-emission target. The implementation of renewables should provide major opportunities and enable a more secure and decentralised energy supply system. Renewable fuels provide long-term solutions for the transport sector, particularly for applications where fuels with high energy density are required. In addition, it helps reducing the carbon footprint of these sectors in the long-term. Information on biomass characteristics feedstock is essential for scaling-up gasification from the laboratory to industrial-scale. This review deals with the transformation biogenic residues into a valuable bioenergy carrier like biomethanol as the liquid sunshine based on the combination of modified mature technologies such as gasification with other innovative solutions such as membranes and microchannel reactors. Tar abatement is a critical process in product gas upgrading since tars compromise downstream processes and equipment, for this, membrane technology for upgrading syngas quality is discussed in this paper. Microchannel reactor technology with the design of state-of-the-art multifunctional catalysts provides a path to develop decentralised biomethanol synthesis from biogenic residues. Finally, the development of a process chain for the production of (i) methanol as an intermediate energy carrier, (ii) electricity and (iii) heat for decentralised applications based on biomass feedstock flexible gasification, gas upgrading and methanol synthesis is analysed.

An Open One-Step RT-qPCR for SARS-CoV-2 detection.

The COVID-19 pandemic has resulted in millions of deaths globally, and while several diagnostic systems were proposed, real-time reverse transcription polymerase chain reaction (RT-PCR) remains the gold standard. However, diagnostic reagents, including enzymes used in RT-PCR, are subject to centralized production models and intellectual property restrictions, which present a challenge for less developed countries. With the aim of generating a standardized One-Step open RT-qPCR protocol to detect SARS-CoV-2 RNA in clinical samples, we purified and tested recombinant enzymes and a non-proprietary buffer. The protocol utilized M-MLV RT and Taq DNA pol enzymes to perform a Taqman probe-based assay. Synthetic RNA samples were used to validate the One-Step RT-qPCR components, demonstrating sensitivity comparable to a commercial kit routinely employed in clinical settings for patient diagnosis. Further evaluation on 40 clinical samples (20 positive and 20 negative) confirmed its comparable diagnostic accuracy. This study represents a proof of concept for an open approach to developing diagnostic kits for viral infections and diseases, which could provide a cost-effective and accessible solution for less developed countries.

The role of veterinarians in zoonosis prevention: Advising families of immunocompromised children with pets.

Background: Pet ownership is widespread, offering numerous benefits to individuals and families. However, the risk of zoonotic diseases must be carefully considered, especially for immunosuppressed patients. Knowledge gaps in preventive measures for zoonoses have been identified, underscoring the vital role of veterinarians in addressing this issue. Objectives: This study aimed to assess the knowledge and recommendations of veterinarians regarding pet ownership by immunocompromised individuals. Additionally, we compared these insights with responses from European healthcare professionals specializing in pediatric transplant recipients. Methods: We conducted an observational, cross-sectional study involving small animal veterinarians in Spain. An online survey was administered to gather information on veterinarians' knowledge of zoonoses and their recommendations for immunocompromised pet owners. Results: A survey of 514 individuals was collected from experienced veterinarians mainly working in primary care clinics. Surprisingly, 63% of respondents did not routinely inquire about the presence of immunocompromised individuals among pet owners, although 54% offered specific recommendations for this group. Most respondents adhered to deworming guidelines for pets owned by immunocompromised individuals and demonstrated sound practices in Leishmania and Leptospira prevention, as well as the avoidance of raw food. However, gaps were noted concerning Bordetella bronchiseptica vaccination. Notably, veterinarians outperformed medical professionals in their knowledge of zoonotic cases and identification of zoonotic microorganisms. The presence of specific recommendations in veterinary clinics was viewed positively by nearly all respondents. Conclusions: Our findings indicate that veterinarians possess a superior understanding of zoonotic pathogens and exhibit greater proficiency in diagnosing zoonoses compared with physicians. They stay well-informed about recommendations outlined in established guidelines and are more likely to provide written recommendations in their clinics than physicians. Nevertheless, knowledge gaps among veterinarians emphasize the need for enhanced communication between medical and veterinary professionals. Reinforcing the "One Health" concept is imperative, with veterinarians playing a pivotal role in this collaborative effort.

Molecular portraits of patients with intrahepatic cholangiocarcinoma who diverge as rapid progressors or long survivors on chemotherapy.

OBJECTIVE: Cytotoxic agents are the cornerstone of treatment for patients with advanced intrahepatic cholangiocarcinoma (iCCA), despite heterogeneous benefit. We hypothesised that the pretreatment molecular profiles of diagnostic biopsies can predict patient benefit from chemotherapy and define molecular bases of innate chemoresistance. DESIGN: We identified a cohort of advanced iCCA patients with comparable baseline characteristics who diverged as extreme outliers on chemotherapy (survival <6 m in rapid progressors, RP; survival >23 m in long survivors, LS). Diagnostic biopsies were characterised by digital pathology, then subjected to whole-transcriptome profiling of bulk and geospatially macrodissected tissue regions. Spatial transcriptomics of tumour-infiltrating myeloid cells was performed using targeted digital spatial profiling (GeoMx). Transcriptome signatures were evaluated in multiple cohorts of resected cancers. Signatures were also characterised using in vitro cell lines, in vivo mouse models and single cell RNA-sequencing data. RESULTS: Pretreatment transcriptome profiles differentiated patients who would become RPs or LSs on chemotherapy. Biologically, this signature originated from altered tumour-myeloid dynamics, implicating tumour-induced immune tolerogenicity with poor response to chemotherapy. The central role of the liver microenviroment was confrmed by the association of the RPLS transcriptome signature with clinical outcome in iCCA but not extrahepatic CCA, and in liver metastasis from colorectal cancer, but not in the matched primary bowel tumours. CONCLUSIONS: The RPLS signature could be a novel metric of chemotherapy outcome in iCCA. Further development and validation of this transcriptomic signature is warranted to develop precision chemotherapy strategies in these settings.

Relationship between cholestasis and altered progesterone metabolism in the placenta-maternal liver tandem.

BACKGROUND: In intrahepatic cholestasis of pregnancy (ICP), there are elevated maternal serum levels of total bile acids, progesterone, and some sulfated metabolites, such as allopregnanolone sulfate, which inhibits canalicular function. AIM: To investigate the relationship between cholestasis and the expression of crucial enzymes involved in progesterone metabolism in the liver and placenta. METHODS: Obstructive cholestasis was induced by bile duct ligation (BDL). RT-qPCR (mRNA) and western blot (protein) were used to determine expression levels. Srd5a1 and Akr1c2 enzymatic activities were assayed by substrate disappearance (progesterone and 5α-dihydroprogesterone, respectively), measured by HPLC-MS/MS. RESULTS: BDL induced decreased Srd5a1 and Akr1c2 expression and activity in rat liver, whereas both enzymes were up-regulated in rat placenta. Regarding sulfotransferases, Sult2b1 was also moderately up-regulated in the liver. In placenta from ICP patients, SRD5A1 and AKR1C2 expression was elevated, whereas both genes were down-regulated in liver biopsies collected from patients with several liver diseases accompanied by cholestasis. SRD5A1 and AKR1C2 expression was not affected by incubating human hepatoma HepG2 cells with FXR agonists (chenodeoxycholic acid and GW4064). Knocking-out Fxr in mice did not reduce Srd5a1 and Akr1c14 expression, which was similarly down-regulated by BDL. CONCLUSION: SRD5A1 and AKR1C2 expression was markedly altered by cholestasis. This was enhanced in the placenta but decreased in the liver, which is not mediated by FXR. These results suggest that the excess of progesterone metabolites in the serum of ICP patients can involve both enhanced placental production and decreased hepatic clearance. The latter may also occur in other cholestatic conditions.

Menstrual health: Inequities in a cohort of menstruating people in the Brazilian southeastern region.

OBJECTIVE: To assess menstrual hygiene management (MHM) and period poverty in a group of low- and medium-income menstruating people. METHODS: A cross-sectional study was conducted at the University of Campinas, Brazil, from January to June 2022 with 535 participants aged 18-49. For data collection, we used the abbreviated version of the WHO Quality-of-Life questionnaire (WHOQOL-BREF) and a pre-tested questionnaire with items regarding MHM and period poverty. RESULTS: We found an inverse relationship between the risk of no access to supplies to perform menstrual hygiene, which increased by 2.5% and each point less in the environmental domain of quality of life (QoL), and this risk increased by up to 3.1 times among participants who reported difficulty making ends meet. The risk of not having adequate conditions to perform menstrual hygiene at home increased by up to 2.6% for every one-point drop in the environmental domain of QoL. The risk of not having adequate conditions to perform menstrual hygiene outside the home increased by up to 1.3% for less points in the psychological domain of QoL, and 44.4% of those who indicated inadequate conditions for menstrual hygiene reported two or more childbirths. CONCLUSIONS: Menstruating people who have an increased risk of lacking menstrual supplies and have an increased risk of inadequate conditions for MHM at home and outside the home, as well as those who have two or more deliveries and those having difficulties making ends meet, scored low on the QoL, especially in the environmental and psychological dimensions.