Parasitism-Induced Changes in Microbial Eukaryotes of Peruvian Alpaca Gastrointestinal Tract.

Alpacas, important genetic resources in the Andean region of Peru, are vulnerable to diarrhea caused by pathogenic parasites such as Eimeria lamae and Giardia sp., which can be fatal, especially in neonates, due to their physiological immaturity and limited adaptability. The study investigated the diversity and abundance of intestinal fungi and protists in alpacas infected with Eimeria lamae and Giardia sp. compared to healthy alpacas. A total of 19 alpacas, aged between one and two months, were included. They were divided into two groups, one with pathological conditions (nine) and the other healthy (ten). Parasitological analyses for the detection of parasites and subsequent molecular analysis were performed on the collected fecal samples. The results revealed a greater diversity and abundance of protists in infected alpacas in comparison with healthy alpacas, while the fungal composition did not show significant changes. Therefore, parasitic infections affect the protist component of the alpaca gut microbiota. Also, it was observed that Blastocystis was identified in all healthy alpacas, serving as a possible marker of the health of the intestinal microbiota; in addition, Prussia and Pichia are beneficial fungi that help control diseases. This groundbreaking study in neonatal alpacas is the first to explore potential changes in the intestinal microbiota during an infectious state, underscoring the importance of further research to comprehend its effects on alpaca health and immune responses.

Synergistic Combination of Antimicrobial Peptides and Cationic Polyitaconates in Multifunctional PLA Fibers.

Combining different antimicrobial agents has emerged as a promising strategy to enhance efficacy and address resistance evolution. In this study, we investigated the synergistic antimicrobial effect of a cationic biobased polymer and the antimicrobial peptide (AMP) temporin L, with the goal of developing multifunctional electrospun fibers for potential biomedical applications, particularly in wound dressing. A clickable polymer with pendent alkyne groups was synthesized by using a biobased itaconic acid building block. Subsequently, the polymer was functionalized through click chemistry with thiazolium groups derived from vitamin B1 (PTTIQ), as well as a combination of thiazolium and AMP temporin L, resulting in a conjugate polymer-peptide (PTTIQ-AMP). The individual and combined effects of the cationic PTTIQ, Temporin L, and PTTIQ-AMP were evaluated against Gram-positive and Gram-negative bacteria as well as Candida species. The results demonstrated that most combinations exhibited an indifferent effect, whereas the covalently conjugated PTTIQ-AMP displayed an antagonistic effect, potentially attributed to the aggregation process. Both antimicrobial compounds, PTTIQ and temporin L, were incorporated into poly(lactic acid) electrospun fibers using the supercritical solvent impregnation method. This approach yielded fibers with improved antibacterial performance, as a result of the potent activity exerted by the AMP and the nonleaching nature of the cationic polymer, thereby enhancing long-term effectiveness.

Cumulative Dissipated Energy (CDE) in Three Phaco-Fragmentation Techniques for Dense Cataract Removal.

Purpose: To determine the energy expenditure in phacoemulsification surgery expressed as cumulative dissipated energy (CDE) among the divide and conquer, ultrachopper-assisted divide and conquer, and phaco-chop techniques for dense cataract removal. Patients and Methods: The clinical data were obtained from the medical charts of dense cataracts patients undergoing routine phacoemulsification employing any of three phaco-fragmentation techniques, including divide and conquer using the Kelman 0.9 mm tip, the ultrachopper tip, and the phaco-chop technique using the Kelman 0.9 mm tip. Cumulated dissipated energy (CDE), longitudinal ultrasound time (UST), and endothelial cell loss were compared among groups at the one-month postoperative. Results: Surgeries from 90 eyes were analyzed, among whom the conventional divide-and-conquer technique group included 30 patients, 32 in the ultrachopper group, and 28 in the phaco-chop technique group. The average CDE in the conventional divide and conquer group was 44.52 ± 23.00, the ultrachopper technique was 43.27 ± 23.18, and 20.11 ± 11.06 in the phaco-chop group. Phaco-fragmentation chop demonstrated significantly lower CDE than the other techniques (p= <0.0001). The phaco-chop technique showed statistically significantly lower CDE when compared to the other two groups (p=<0.0001) with 93.96 ± 39.71 seconds. There were no statistically significant differences in postoperative endothelial cell density between groups (p=0.4916). Conclusion: The use of the phaco-chop technique in hard cataract phacoemulsification represents a lower energy expenditure than divide and conquer and ultrachopper techniques; nevertheless, no differences regarding endothelial density loss were evidenced.

Effect of Intranodally Administered Dendritic Cell-Based HIV Vaccine in Combination With Pegylated Interferon α-2a on Viral Control Following ART Discontinuation: A Phase 2A Randomized Clinical Trial.

Introduction: Functional cure has been proposed as an alternative to lifelong antiretroviral therapy and therapeutic vaccines represent one of the most promising approaches. Materials and Methods: We conducted a double-blind randomized placebo-controlled clinical trial to evaluate the safety, immunogenicity, and effect on viral dynamics of a therapeutic vaccine produced with monocyte-derived dendritic cells (MD-DC) loaded with a high dose of heat-inactivated autologous (HIA) HIV-1 in combination with pegylated interferon alpha 2a (IFNα-2a) in people with chronic HIV-1. Results: Twenty-nine male individuals on successful ART and with CD4+ ≥450 cells/mm3 were randomized 1:1:1:1 to receive three ultrasound-guided inguinal intranodal immunizations, one every 2 weeks: (1) vaccine ~107 MD-DC pulsed with HIA-HIV-1 (1010 HIV RNA copies) (n = 8); (2) vaccine plus three doses of 180 mcg IFNα-2a at weeks 4-6 (n = 6); (3) placebo = saline (n = 7); and (4) placebo plus three doses of 180 mcg IFNα-2a (n = 8). Thereafter, treatment was interrupted (ATI). Vaccines, IFNα-2a, and the administration procedures were safe and well tolerated. All patients' viral load rebounded during the 12-week ATI period. According to groups, changes in viral set-point between pre-ART and during ATI were not significant. When comparing all groups, there was a tendency in changes in viral set-point between the vaccine group vs. vaccine + IFNα-2a group (>0.5log10p = 0.05). HIV-1-specific T-cell responses (IFN-Æ´ Elispot) were higher at baseline in placebo than in the vaccine group (2,259 ± 535 vs. 900 ± 200 SFC/106 PBMC, p = 0.028). A significant difference in the change of specific T-cell responses was only observed at week 4 between vaccine and placebo groups (694 ± 327 vs. 1,718 ± 282 SFC/106 PBMC, p = 0.04). No effect on T-cell responses or changes in viral reservoir were observed after INFα-2a administration. Discussion: Results from this study show that intranodally administered DC therapeutic vaccine in combination with IFNα-2a was safe and well-tolerated but had a minimal impact on viral dynamics in HIV-1 chronic infected participants. Clinical Trial Registration: (www.ClinicalTrials.gov), identifier NCT02767193.

Efficacy and Safety of Sarilumab in patients with COVID19 Pneumonia: A Randomized, Phase III Clinical Trial (SARTRE Study).

INTRODUCTION: SARS-CoV-2 pneumonia is often associated with hyper-inflammation. The cytokine-storm-like is one of the targets of current therapies for coronavirus disease 2019 (COVID-19). High Interleukin-6 (IL6) blood levels have been identified in severe COVID-19 disease, but there are still uncertainties regarding the actual role of anti-IL6 antagonists in COVID-19 management. Our hypothesis was that the use of sarilumab plus corticosteroids at an early stage of the hyper-inflammatory syndrome would be beneficial and prevent progression to acute respiratory distress syndrome (ARDS). METHODS: We randomly assigned (in a 1:1 ratio) COVID-19 pneumonia hospitalized patients under standard oxygen therapy and laboratory evidence of hyper-inflammation to receive sarilumab plus usual care (experimental group) or usual care alone (control group). Corticosteroids were given to all patients at a 1 mg/kg/day of methylprednisolone for at least 3 days. The primary outcome was the proportion of patients progressing to severe respiratory failure (defined as a score in the Brescia-COVID19 scale ≥ 3) up to day 15. RESULTS: A total of 201 patients underwent randomization: 99 patients in the sarilumab group and 102 patients in the control group. The rate of patients progressing to severe respiratory failure (Brescia-COVID scale score ≥ 3) up to day 15 was 16.16% in the Sarilumab group versus 15.69% in the control group (RR 1.03; 95% CI 0.48-2.20). No relevant safety issues were identified. CONCLUSIONS: In hospitalized patients with Covid-19 pneumonia, who were under standard oxygen therapy and who presented analytical inflammatory parameters, an early therapeutic intervention with sarilumab plus standard of care (including corticosteroids) was not shown to be more effective than current standard of care alone. The study was registered at EudraCT with number: 2020-002037-15.

In vitro activity of ceftaroline in combination with other antimicrobials active against Staphylococcus spp. / Actividad in vitro de la combinación de ceftarolina con otros antimicrobianos activos frente a Staphylococcus spp.

INTRODUCTION: We evaluated the in vitro activity of the combination of ceftaroline with daptomycin, linezolid and vancomycin against methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus (CNS). MATERIAL AND METHODS: We analysed 70 staphylococcal strains (31 S. aureus and 39 CNS) with the Etest using the MIC:MIC ratio method and calculation of fractional inhibitory concentration indexes. RESULTS: The combination of ceftaroline with daptomycin showed an additive effect (53.2%) and synergy (6.6%) against methicillin-susceptible S. aureus, and an additive effect (81.2%) against methicillin-resistant S. aureus (MRSA). This combination also showed an additive effect against 33% of linezolid-susceptible CNS and was not synergistic against linezolid-resistant CNS. The combination of ceftaroline with vancomycin was synergistic (87%) and ceftaroline with linezolid was additive (37%) against MRSA. CONCLUSIONS: The combinations of ceftaroline with daptomycin, vancomycin or linezolid showed additive and/or synergistic effects against methicillin-resistant Staphylococcus.

Listeria monocytogenes infections: Analysis of 41 patients.

OBJECTIVE: We describe and analyze Listeria-related demographics and clinical features to determine the predisposing conditions for severe infections. METHODS: We performed a retrospective study using positive isolation of Listeria monocytogenes from blood, cerebrospinal fluid, and other organic fluids. Electronic health records were used to determine the epidemiological and clinical features of infections caused by L. monocytogenes. Mortality and sepsis were considered dependent variables in the statistical analyses. RESULTS: We included 41 patients in an observation period of 15 years (2003-2018), with an annual incidence rate of 1.3 cases per 100,000 population. Three main population profiles were identified: newborns, pregnant women, and other adults (17.1%, 12.2%, and 82.9%, respectively). Neuroinvasive infection was present in 17 patients (41.5%). In both univariate and multivariate analyses, neurological infections, whether meningoencephalitis, rhombencephalitis, or brain abscesses, were the main risk factors for severe forms of Listeria-related infections (odds ratio 1.8, 95% CI 1.52-2.14, p=0.01). Malignancies, whether solid tumors or hematological neoplasms, immunosuppression, and chronic diseases were not related to either mortality or severe clinical syndromes. CONCLUSION: Infections caused by L. monocytogenes were uncommon but could cause severe sepsis and mortality, especially in susceptible populations. Our study focused on neurological involvement and severe invasive forms of listeriosis. Neuroinvasive forms were the most important risk factors for severe illness but not for mortality.

Belief in a Just World and Emotional Intelligence in Subjective Well-Being of Cancer Patients.

The study of coping strategies has provided valuable insights about the process of helping cancer patients adapt to their disease. However, new approaches must be explored to increase the knowledge of this adjustment. In this study, we will analyze the relationship between patients' psychological well-being and quality of life and less well-studied constructs such as the belief in a just world (BJW) and emotional intelligence (EI). Sixty-eight cancer patients (35 men, 33 women; mean age 53.5 years; range: 20-86) were asked about their personal and general BJW, EI, Perception of Quality of Life, Anxiety, and Depression. Different multiple regression analyses showed that patients' personal BJW negatively predicted their anxiety (p < .05) and a trend to a better quality of life. In addition, patients with high scores in the Mood Repair subfactor of EI showed better quality of life (p < .05), and those with higher Attention to Feelings exhibited more Anxiety (p < .01) and a trend to more Depression. These results underline the need to take into consideration new factors, such as BJW and EI, in clinical interventions for cancer patients.

Exogenous fatty acids and niacin on acute prostaglandin D2 production in human myeloid cells.

Niacin activates HCA2 receptor that results in the release of PGD2. However, little is known on PGD2-producing cells and the role of fatty acids. Notably M-CSF macrophages exhibited a timely dependent PGD2 production upon niacin challenge. Short pretreatment of M-CSF macrophages with autologous postprandial TRLs induced the down-regulation of HCA2 gene and up-regulation of genes encoding COX1 and COX2 enzymes in a fatty acid-dependent manner. These effects were paralleled by a higher PGD2 production with postprandial TRL-SFAs. The niacin-mediated transcriptional activity of all genes involved in PGD2 biosynthesis was desensitized in a time-dependent manner by postprandial TRLs, leading to a decreased PGD2 release. In vivo, the net excursions of PGD2 in plasma followed similar fatty acid-dependent patterns as those found for PGD2 release in vitro. The predominant fatty acid class in the diet acutely modulates PGD2 biosynthetic pathway both in vitro and in vivo.

Risk factors, clinical presentation and prognosis of mixed candidaemia: a population-based surveillance in Spain.

The low incidence of mixed candidaemia (MC) may have precluded a better knowledge of its clinical presentation. The aim of the study was to analyse the risk factors, clinical presentation and prognosis of MC episodes. A comparison between MC and monomicrobial candidaemia within a prospective programme on candidaemia was performed in 29 hospitals between April 2010 and May 2011. In fifteen episodes of candidaemia corresponding to 15 patients, out of 752, two species of Candida (1.9%) were isolated. MC was more frequent in patients with HIV infection (12%, P = 0.038) and those admitted due to extensive burns (23%, P = 0.012). The Candida species most frequently identified in MC were C. albicans 12 patients (40%), C. glabrata seven patients (23.3%) and C. parapsilosis six patients (20%). Early mortality was higher (nine patients, 60%) in patients with MC than in patients with MMC (223 patients, 30.3%, P = 0.046). In conclusion, MC was was independently associated with increased mortality even after considering other prognostic factors. MC is an infrequent event that is more common in HIV infection and in patients suffering from burns, and is associated with increased mortality.

[In vitro activity of fosfomycin, alone or in combination, against clinical isolates of carbapenem resistant Pseudomonas aeruginosa]. / Actividad in-vitro de fosfomicina, sola o en combinaciones, frente a aislamientos clínicos de Pseudomonas aeruginosa resistentes a carbapenémicos.

INTRODUCTION: The increase in microorganisms showing patterns of multi-drug resistance or even pan-drug resistance is of growing concern. Fosfomycin (FO) is well known to be active against a wide variety of microorganisms, including highly resistant strains of Pseudomonas aeruginosa (P. aeruginosa), and can also synergistically act with other molecules. METHODS: This study examines the in vitro activity shown by FO against 120 strains of carbapenem-resistant P. aeruginosa using an agar dilution and a gradient diffusion test. Possible synergistic effects of the combinations of FO/amikacin and FO/ciprofloxacin were also examined using E-test and time-kill techniques. RESULTS: According to the epidemiological cut-off value (ECOFF) issued by the European Committee on Antimicrobial Susceptibility Testing (EUCAST), our results indicate that over three-quarters of the strains tested would be susceptible to FO treatment, especially if combined with another antimicrobial. The FO/ciprofloxacin combination had a synergistic effect on 40% of the clinical isolates, while for FO/amikacin this effect was only observed in 12% of the isolates. CONCLUSION: The appearance of carbapenem-resistant P. aeruginosa strains requires the evaluation by combination therapy. This report suggests that the FO/ciprofloxacin combination can be useful, showing a synergistic effect in 40% of the isolates.

[Assessment of 2 automated microdilution techniques compared to an agar dilution method in determining sensitivity to fosfomycin in strains of carbapenem-resistant Pseudomonas aeruginosa]. / Valoración de 2 técnicas automatizadas de microdilución frente a dilución en agar en la determinación de la sensibilidad a fosfomicina en cepas de Pseudomonas aeruginosa resistentes a carbapenémicos.

Carbapenems-resistance in Pseudomonas aeruginosa isolates has been widely reported. Fosfomycin has been shown to act synergistically with other antimicrobials. The agar dilution method was approved for susceptibility testing for fosfomycin and Pseudomonas aeruginosa. However, broth microdilution methods are the basis of systems currently used in clinical microbiology laboratories. The results of this study indicate that these methods are acceptable as susceptibility testing methods for fosfomycin against these organisms.

Difficulties in differential diagnosis of COPD and asthma in primary care.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and asthma treatment must be based on appropriate diagnosis. However, patients receiving inhaled therapy in primary care may not be accurately diagnosed according to current guidelines. AIM: To analyse the characteristics of patients treated with inhaled medication, the concordance of tools for differential diagnosis, and the adequacy of prescription of inhaled corticosteroids (ICs) in primary care. DESIGN AND SETTING: Cross-sectional, multicentre, non-interventional study conducted in 10 primary care centres in Barcelona, Spain. METHOD: Patients with chronic respiratory disease, aged >40 years were treated with ICs. They provided sociodemographic and clinical information and performed forced spirometry with a bronchodilator test (BDT). The diagnostic accuracy of asthma and COPD diagnoses were tested using two differential diagnosis questionnaires. RESULTS: A total of 328 patients were initially classified as having COPD (64.8%), asthma (15.4%), or indeterminate (19.8%) by their GPs. After spirometry, 40% of patients had moderate-severe airflow obstruction according to the GOLD classification; mean reversibility of forced expiratory volume in 1 second (FEV1) was 8.4%; 18.6% had a positive BDT; and 39.8% had post-bronchodilator FEV1/forced vital capacity >0.7. Concordance of the differential diagnosis tools was moderate (clinical diagnosis versus spirometry and between the two questionnaires), low (clinical diagnosis versus questionnaires), and very low (spirometry versus differential diagnosis). Of the patients diagnosed with COPD, 71.4% were treated with ICs, and 12% of those classified as having asthma were not receiving ICs. CONCLUSION: Most patients can be classified as having COPD or asthma by primary care physicians. The use of the two questionnaires did not provide a better differential diagnostic compared with symptoms and spirometry with a BDT. Misdiagnosis may lead to inadequate treatment.

[Primary percutaneous angioplasty. An analysis of reperfusion delays, their determining factors and their prognostic implications]. / Angioplastia primaria en nuestro medio. Análisis de los retrasos hasta la reperfusión, sus condicionantes y su implicación pronóstica.

INTRODUCTION AND OBJECTIVES: The optimum treatment for patients with ST-segment elevation acute myocardial infraction (AMI) is primary percutaneous coronary intervention (PCI), provided that the door-to-balloon time is less than 90 min. The aims of this study were to determine actual treatment times in our patients, to investigate the effect of different factors in reducing those times, and to evaluate the impact of any delay on prognosis. METHODS: The study involved patients who underwent primary or rescue PCI at our center between January 2005 and October 2007. Treatment times, clinical and angiographic characteristics, and follow-up findings at 1 and 12 months were recorded prospectively. RESULTS: Overall, 389 PCIs were performed: 361 primary and 28 rescue interventions. The median total duration of ischemia was 235 [interquartile range, 170-335] min. The median door-to-balloon time was 79 [53-104] min. The door-to-balloon time was shorter when the ambulance service was able to notify the on-duty cardiologist, who alerted the interventional cardiology team. The difference was 30 [60-90] min (P< .01). Patients who arrived at the emergency department by their own means had the longest door-to-balloon time (100 min vs. 74 min; P< .01). A door-to-balloon time >120 min was associated with higher mortality at 30 days; multivariate analysis showed a clearly increasing trend. CONCLUSIONS: The door-to-balloon time at our center was in line with current recommendations, with the time being markedly shorter for patients for whom the ambulance service was able to give advanced warning. A shorter time was associated with a trend towards lower 30-day mortality.

Prognostic value of neutrophils and NK cells in bronchoalveolar lavage of sarcoidosis.

BACKGROUND: Not all the patients with sarcoidosis need pharmacological therapy, and the decision to start therapy is based mainly on clinical conditions. The aim of this study was to evaluate the prognostic value of the leukocyte and lymphocyte subpopulations in the bronchoalveolar lavage fluid from these patients. METHODS: Thirty-three nonsmoking patients with sarcoidosis were included and classified based on the presence of Löfgren's syndrome (n = 11), the radiological stage (12 at Stage I, 17 at Stage II, and 4 at Stage III), and their follow-up. Differential leukocyte subsets and the lymphocyte subpopulations were determined by flow cytometry. RESULTS: The percentage of neutrophils was lower in patients with Löfgren's syndrome (P = 0.038) and in patients at Stage I (P = 0.002). Patients with a poor outcome had a higher percentage of neutrophils (P = 0.004) and NK cells (P = 0.023) than those with a stable disease. Finally, a higher percentage of NK cells was found in those patients who needed a steroid treatment (P = 0.012). CONCLUSIONS: Increased percentages of neutrophils and NK cells in the bronchoalveolar lavage fluid from patients with sarcoidosis are associated with a poor outcome and a higher probability to need steroids treatment. The percentage of neutrophils was also lower in patients with Löfgren's syndrome.