Search Results (111)

Mycoplasmas are known respiratory pathogens in tortoises, but few studies exist in snakes. To better understand the correlation with clinical signs and co-infections, samples from mycoplasma-positive snakes with and without clinical respiratory disease were analyzed. Oral swabs from 15 snakes (pythons n = 12, boas n = 3) were examined using polymerase chain reaction (PCR) and third-generation sequencing (TGS). Additionally, mycoplasma isolation assays were performed. Pathogens detected by PCR included Mycoplasmas (15/15, 100%), serpentoviruses (9/15, 60%), and Chlamydia sp. (2/15, 13%); those detected by TGS included Mycoplasmas (14/15, 93%), serpentoviruses (10/15, 67%), Chlamydia sp. (1/15, 7%), and 15 different bacterial species. Sequencing of the mycoplasma PCR products revealed a close genetic relationship to Mycoplasmopsis agassizii. TGS identified genetically distinct mycoplasmas and three different serpentoviruses. While mycoplasmas could not be successfully propagated, Brucella intermedia comb. nov. was identified in eight cultures. Respiratory disease in snakes is often multifactorial, involving various pathogens and environmental influences. This study demonstrates that comprehensive diagnostics are essential for understanding disease processes in snakes and improving the detection of diverse pathogens. Further research is needed to improve laboratory diagnostics for infectious diseases in reptiles and to better understand the roles of various pathogens in respiratory diseases in snakes. Full article

Background/Objectives: This review aimed to compare the efficacy of antibiotic treatment vs. non-antibiotic treatment in mild and moderate clinical mastitis in lactating dairy cows, categorized by the causative pathogen. Methods: The initial systematic review plan, which resulted in only four relevant articles, was altered due to limited available studies and significant heterogeneity among them. Consequently, five additional articles, closely meeting our criteria with minor differences, were included to ensure comprehensive analysis, resulting in nine included articles. Due to these pragmatic constraints, this review represents a hybrid between a systematic and a narrative review. The outcome of interest was the bacteriological cure (BC). Results: The findings revealed that antibiotic treatment resulted in improved BC rates for cases caused by Streptococci. For cases caused by Escherichia (E.) coli, antibiotic therapy showed no significant improvement in BC rates compared to non-antibiotic treatment, suggesting that antibiotics may be often unnecessary for these cases due to self-limiting tendencies. However, severe E. coli mastitis warrants systemic antibiotic treatment due to potentially life-threatening complications. Klebsiella spp. mastitis showed better cure rates with antibiotic therapy. Conclusions: This study underscores the importance of regular pathogen diagnostics to guide appropriate treatment, advocating for the use of on-farm rapid tests to reduce unnecessary antibiotic use while ensuring effective treatment outcomes. Full article

Background/Objectives: We examined the association between dietary intake and blood concentrations of one-carbon metabolism (OCM)-related nutrients in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: Blood concentrations and dietary intake of the vitamins riboflavin (B2), Pyridoxal 5′-phosphate (PLP and B6), folate (B9), B12, and methionine, concentrations of homocysteine, and dietary intake of betaine, choline, and cysteine were pooled from 16,267 participants in nine EPIC nested case–control studies. Correlation analyses between dietary intakes and blood concentrations were carried out. Principal component (PC) analysis identified latent factors in the two sets of measurements. Results: Pearson correlations between dietary intakes and blood concentrations ranged from 0.08 for methionine to 0.12 for vitamin B2, 0.15 for vitamin B12, 0.17 for vitamin B6, and 0.19 for folate. Individual dietary intakes showed higher correlations (ranging from −0.14 to 0.82) compared to individual blood concentrations (from −0.31 to 0.29). Correlations did not vary by smoking status, case–control status, or vitamin supplement use. The first PC of dietary intakes was mostly associated with methionine, vitamin B12, cysteine, and choline, while the first PC of blood concentrations was associated with folate and vitamin B6. Conclusions: Within this large European study, we found weak to moderate associations between dietary intakes and concentrations of OCM-related nutrients. Full article

Little is known about the dysbiosis of the gut microbiome in patients with mild cognitive impairment (MCI) potentially at risk for the development of Alzheimer’s disease (AD). So far, only cross-sectional differences and not longitudinal changes and their prognostic significance have been in the scope of research in MCI. Therefore, we investigated the ability of longitudinal taxonomic and functional gut microbiome data from 100 healthy controls (HC) to predict the progression from normal cognition to MCI over a 4-year follow-up period (4yFU). Logistic regression models were built with baseline features that best discriminated between the two groups using an ANOVA-type statistical analysis. The best model for the discrimination of MCI converters was based on functional data using Gene Ontology (GO), which included 14 features. This model achieved an area under the receiver operating characteristic curve (AUROC) of 0.84 at baseline, 0.78 at the 1-year follow-up (1yFU), and 0.75 at 4yFU. This functional model outperformed the taxonomic model, which included 38 genera features, in terms of descriptive performance and showed comparable efficacy to combined analyses integrating functional, taxonomic, and clinical characteristics. Thus, gut microbiome algorithms have the potential to predict MCI conversion in HCs over a 4-year period, offering a promising innovative supplement for early AD identification. Full article

Background: Survivors of hematopoietic stem cell transplantation (HSCT) during childhood face significant late effects. This study aimed to map the dietary micronutrient intake of long-term survivors of pediatric HSCT and explore its associations with transplant outcomes, body composition, and physical capacity. Methods: We included 85 long-term survivors of HSCT (median age 30 years) The median time since HSCT was 19.9 years, reflecting a long-term survivor population. Dietary intake was assessed using a 3-day food record. Body composition was measured by DXA, and physical capacity was evaluated through cardiorespiratory fitness and physical performance tests. Results: We observed an inadequate intake of several vitamins and minerals including vitamins A, C, D, E, selenium, and potassium, with a median intake below recommendations. While dietary intake of vitamin D was reduced in patients with chronic graft versus host disease (cGvHD), the occurrence of cGvHD was not associated with overall micronutrient intake. Twelve percent of the participants had reduced skeletal muscle mass and 16% displayed a low bone mass density during DXA scans. These conditions were not related to the micronutrient intake. Likewise, reduced cardiorespiratory fitness and physical performance were unrelated to micronutrient intake. Total energy intake was found to significantly influence micronutrient intake (p = 0.001), explaining 66% of the variation. Conclusions: Long-term survivors of pediatric HSCT demonstrated inadequate intake of multiple micronutrients. These findings suggest that inclusion of comprehensive micronutrient assessment and nutritional guidance should be considered for inclusion in follow-up care protocols. Full article

Metacestodes of Echinococcus multilocularis are the causative agents of alveolar echinococcosis, a neglected, life-threatening, zoonotic disease. To study these metacestodes in vitro, a model system using a culture medium conditioned by rat hepatoma cells is available. A key question is how the parasite interacts with the host and, in particular, which host-derived compounds are taken up. In this study, we focus on the uptake of host-derived proteins. Studies with artificially labeled proteins suggest that this uptake may occur independently of protein size or charge. Closer investigation using proteomics draws, however, a different picture. Of 1170 host (i.e., rat or bovine) proteins as identified by LC-MS/MS-based proteomics present in the culture medium, only 225 are found in metacestode vesicle tissue or fluid. Moreover, their relative abundances differ. Serum albumin, the most abundant culture medium host protein, is only the third most abundant protein in vesicle fluid, where Alpha-2-HS-glycoprotein becomes the most abundant protein. In vesicle fluid obtained ex vivo from experimentally infected mice, the situation is again different, with histone isoforms as the most abundant proteins. This suggests that while maintaining their internal milieu constant, metacestodes may adjust the spectrum of host proteins taken up. Potential uptake mechanisms and functions are discussed. Full article

Background: The medical care of critically ill children requires special expertise in pediatric emergency and intensive care medicine. In Germany, this expertise is mainly available in specialized centers at maximum-care hospitals due to the small number of cases of critically ill children. Telemedical care networks, such as the Pediatric-Tele-Intensive-Care Network Saxony, offer a solution for networking these centers with regional hospitals providing basic or standard care. However, the evaluation of these networks represents a major challenge, especially because it involves a heterogeneous target group of patients with various diseases. This article reports on the evaluation design development process for such a network, under equal participation of all relevant stakeholders, and presents the resulting evaluation design. Methods: The methods used were a literature review, two workshops, and a survey of all relevant stakeholders (representatives of 17 partner clinics, 4 external experts in pediatric intensive care, and 2 patient representatives). Results: The evaluation design contained proposals for a care objective, outcomes, and the corresponding databases (project database, clinic database, and survey database) to investigate these. Conclusions: Our study can offer other researchers and stakeholders a methodological approach and template for their evaluation design. It is the first published, consented evaluation design for a telemedical care network in pediatric intensive care. When developing and realizing an evaluation design for (tele)medical interventions, including the perspectives of relevant stakeholders, from the outset, it is essential to achieve a high level of commitment to the implementation of the evaluation. Full article

Background: Major trauma is a leading cause of severe disability and mortality. The influence of patient sex on outcome after severe trauma is a topic of ongoing discussion. We present a prospective multicenter study on the effects of trauma severity on health-related quality of life (HRQoL) of female patients. We hypothesized that the impairment of HRQoL after major trauma between the sexes depends not only on sex itself but also on age. Methods: This multicenter prospective registry-based observational study compared sex-based differences in HRQoL of patients who sustained major trauma Injury Severity Score (ISS ≥ 16). The HRQoL was assessed using the EQ-5D-3L (European Quality of Life 5-Dimension 3-Level Version) score over 2 years post-trauma. Results: We included 416 patients (116 female/300 male) with an ISS > 16 (median ISS 22 IQR 18/30). All patients had a lower HRQoL after trauma than the population norm. Increased AIS (Abbreviated Injury Scale) face and extremity scores and ASA (American Society of Anesthesiologists) scores showed a significant decrease in HRQoL. Even though the groups of female and male patients were comparable in injury severity, female patients reported significantly more problems on the anxiety and depression scales than male patients 6 months (p = 0.003) and 24 months (p = 0.044) after trauma (6 months: female 46% vs. male 30%; 24 months: female 44% vs. male 32%). We observed the greatest improvement in the EQ Index over time in patients between 16 and 39 years of age, especially female patients (0.78 to 0.87 in females under 39 years of age, compared to males in the same age group 0.76 to 0.81). Females over 65 years of age initially presented the lowest EQ Index of 0.62. It remained significantly lower over time and was lower compared to male patients of the same age group (female EQ Index after 24 months was 0.68 compared to men over the age of 65 who presented an EQ Index of 0.75). Conclusions: All patients included in this study presented a lower HRQoL after trauma than the population norm. Female patients under 39 years of age reported the most improvement. Females over 65 years of age showed a limited HRQoL, which remained significantly lower over time. Female patients reported significantly more anxiety and depression after major trauma than male patients. Thus, further development and methodologically rigorous testing of ortho-geriatric initiatives, psychosocial support, and prevention measures are required to improve the care after major trauma, particularly for the female elderly. Full article

Background: Pelvic lymph node dissection during standard radical cystectomy (stdRC) for muscle invasive bladder cancer is performed as separate templates. In the modernized en bloc radical cystectomy (mEbRC), the bladder is removed together with all its associated lymphatic tissue as one specimen. Our aim was to evaluate the oncological and surgical outcomes of mEbRC with a propensity-matched national cohort of stdRC cases. Methods: 935 patients (mEbRC: 214 and stdRC: 721) were eligible for analysis, and 1:2 propensity score matching was performed regressing mEbRC treatment on the variables age, gender, neoadjuvant chemotherapy, Charlson Comorbidity Index, lymph node metastases at final pathology, carcinoma in situ, and pT-stage. The primary outcome was recurrence-free survival (RFS). Secondary endpoints were overall survival (OS) and cancer-specific survival (CSS), survival for female patients. and perioperative measures. Results: There were no significant differences between the groups regarding complications, 30-day readmission rates, and 30- and 90-day mortality rates. In the propensity score matched groups, the 5-year RFS was 83% in the mEbRC group vs. 67% in the stdRC group (p < 0.001), the CSS was 89% and 78% (p ≤ 0.001), and OS 81% vs. 68% (p < 0.001) in the same groups, respectively. The results were confirmed by Cox regression analyses with hazard ratios ranging from 0.41 to 0.50 and p-values ≤ 0.001, favoring mEbRC. The 5-year OS for female patients was 86% for mEbRC and 60% for stdRC (p = 0.022). Conclusions: Performing mEbRC over stdRC might yield significantly better oncological outcomes, with equal survival rates for both genders. Full article

Schistosomiasis affects over 250 million people worldwide, with the highest prevalence at the age of 10–14 years. The influence of the host’s age on the severity of liver damage is unclear. We infected male 8, 14, and 20-week-old mice with S. mansoni. Hepatic damage, inflammation, fibrosis, and metabolism were analyzed by RT-qPCR, Western blotting, ELISA, immunohistochemistry, and mechanistic transwell chamber experiments using S. mansoni eggs and human hepatic stellate cells (HSCs) or primary mouse hepatocytes. Major results were validated in human biopsies. We found that hepatosplenomegaly, granuloma size, egg load, inflammation, fibrosis, and glycogen stores all improved with the increasing age of the host. However, serum alanine transaminase (ALT) levels were lowest in young mice infected with S. mansoni. Hepatic carbohydrate exploitation was characterized by a shift towards Warburg-like glycolysis in S. mansoni-infected animals. Notably, S. mansoni eggs stimulated hepatic stellate cells to an alternatively activated phenotype (GFAP⁺/desmin⁺/αSMA⁻) that secretes IL-6 and MCP-1. The reduction of fibrosis in older age likely depends on the fine-tuning of regulatory and inflammatory cytokines, alternative HSC activation, and the age-dependent preservation of hepatic energy stores. The current results emphasize the significance of investigations on the clinical relevance of host age-dependent liver damage in patients with schistosomiasis. Full article

Thiosemicarbazones and their metal complexes have been studied for their biological activities against bacteria, cancer cells and protozoa. Short-term in vitro treatment with one gold (III) complex (C3) and its salicyl-thiosemicarbazone ligand (C4) selectively inhibited proliferation of T. gondii. Transmission Electron Microscopy (TEM) detected transient structural alterations in the parasitophorous vacuole membrane and the tachyzoite cytoplasm, but the mitochondrial membrane potential appeared unaffected by these compounds. Proteins potentially interacting with C3 and C4 were identified using differential affinity chromatography coupled with mass spectrometry (DAC-MS). Moreover, long-term in vitro treatment was performed to investigate parasitostatic or parasiticidal activity of the compounds. DAC-MS identified 50 ribosomal proteins binding both compounds, and continuous drug treatments for up to 6 days caused the loss of efficacy. Parasite tolerance to both compounds was, however, rapidly lost in their absence and regained shortly after re-exposure. Proteome analyses of six T. gondii ME49 clones adapted to C3 and C4 compared to the non-adapted wildtype revealed overexpression of ribosomal proteins, of two transmembrane proteins involved in exocytosis and of an alpha/beta hydrolase fold domain-containing protein. Results suggest that C3 and C4 may interfere with protein biosynthesis and that adaptation may be associated with the upregulated expression of tachyzoite transmembrane proteins and transporters, suggesting that the in vitro drug tolerance in T. gondii might be due to reversible, non-drug specific stress-responses mediated by phenotypic plasticity. Full article

In the coffee industry, approximately 60% of coffee fruit components are discarded after harvest, posing potential environmental challenges. To repurpose these organic by-products for human consumption, fresh coffee husks from wet coffee processing at a plantation in Tres Ríos, Cartago, Costa Rica, were used to prepare fruit spreads. Three formulations were developed, plain coffee pulp, coffee pulp with pectin, and coffee pulp with guava, each in high- and low-sugar versions (1:1 and 3:1 fruit-to-sugar ratio, respectively). The stability (moisture content, water activity, Brix, and pH), and key nutritional values (sugar profile, minerals, dietary fiber, and fat content) of these spreads were evaluated. Secondary plant metabolites, such as caffeine and tannins, and color were also analyzed. In addition, consumer acceptability was assessed using a hedonic test of the three formulations. The results showed that the high-sugar versions met stability requirements better than the low-sugar ones. Furthermore, both sugar variants had high mineral and dietary fiber contents, qualifying them for the “source of fiber” label according to European Union Food Regulation No. 1924/2006. Caffeine content was within safe limits for adult consumption at 60 mg per 20 g serving, with minimal tannin content (<0.7 mg/g dry basis). Sensory evaluation revealed a preference for the high-sugar guava formulation, followed by the high-sugar plain coffee pulp, and the lowest ratings were received for the low-sugar plain recipe. These results support the feasibility of converting coffee by-products into useful consumer products with potential health benefits and reduced environmental impact. Full article

Identification of drug targets and biochemical investigations on mechanisms of action are major issues in modern drug development. The present article is a critical review of the classical “one drug”—“one target” paradigm. In fact, novel methods for target deconvolution and for investigation of resistant strains based on protein mass spectrometry have shown that multiple gene products and adaptation mechanisms are involved in the responses of pathogens to xenobiotics rather than one single gene or gene product. Resistance to drugs may be linked to differential expression of other proteins than those interacting with the drug in protein binding studies and result in complex cell physiological adaptation. Consequently, the unraveling of mechanisms of action needs approaches beyond proteomics. This review is focused on protozoan pathogens. The conclusions can, however, be extended to chemotherapies against other pathogens or cancer. Full article

Macular edema (ME) remains a primary cause of visual deterioration in uveitis. Visual acuity (VA) can often be maintained using corticosteroid depot systems. This study evaluated the efficacy of a fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN^®) in treating non-infectious uveitis using real-world data. This retrospective analysis included 135 eyes subdivided into responders and non-responders. Central retinal thickness (CRT), VA, and intraocular pressure (IOP) were followed over time. A significant decrease in CRT and an increase in VA were observed in all eyes throughout the follow-up period (p < 0.01). An IOP increase (p = 0.028) necessitated treatment in 43% of eyes by Month 6. Non-responders were older (p = 0.004) and had been treated with more dexamethasone (DEX) implants (p = 0.04); 89.3% had a defect in the external limiting membrane (ELM) and inner/outer segment (IS/OS) zone (p < 0.001). Immunomodulatory therapy had no impact on treatment response. Pars plana vitrectomy (PPV) patients had a mean CRT reduction of 47.55 µm and a reduced effect by Month 24 (p = 0.046) versus non-PPV patients. We conclude that the FAc implant achieves long-term control of CRT and improves VA. Increases in IOP were manageable. Eyes with a previous PPV showed milder results. Data showed a correlation between older age, a damaged ELM and IS/OS zone, frequent DEX inserts, and poorer outcome measures. Full article

Coffee silverskin is a byproduct of the coffee industry, appearing in large quantities during the roasting step. In this work, a sober and simple water process is proposed, using extractions cycles, to produce valuable products including (a) an extract rich in caffeine, (b) possibly pure caffeine, and (c) insoluble fibers. The hypothetical number of necessary cycles was calculated and compared to the number of cycles used experimentally. Two types of cycles, with and without water compensation, were compared for their water consumption and the amount of caffeine extracted. The use of cycles, with the resulting product from a previous extraction as a solvent for fresh biomass, drove a significant rise in the content of caffeine determined by a UV–visible detector with a spectrophotometer and ultra-performance liquid chromatography (UPLC). After 11 extraction cycles with water compensation, we obtained an extract 4.5 times more concentrated in caffeine (4.25 mg/mL) than after a single extraction (1.03 mg/mL). Full article