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International Journal of Molecular... Jun 2024Varicose veins (VVs) are the most common manifestation of chronic venous disease (CVD) and appear as abnormally enlarged and tortuous superficial veins. VVs result from...
Varicose veins (VVs) are the most common manifestation of chronic venous disease (CVD) and appear as abnormally enlarged and tortuous superficial veins. VVs result from functional abnormalities in the venous circulation of the lower extremities, such as venous hypertension, venous valve incompetence, and venous reflux. Previous studies indicate that enhanced angiogenesis and inflammation contribute to the progression and onset of VVs; however, dysregulations in signaling pathways associated with these processes in VVs patients are poorly understood. Therefore, in our study, we aimed to identify key regulators of angiogenesis and inflammation that are dysregulated in patients with VVs. Expression levels of 18 genes were analyzed in peripheral blood mononuclear cells (PBMC) using real-time PCR, as well as plasma levels of 6 proteins were investigated using ELISA. Higher levels of , , , TGF-alpha, TGF-beta 1, and VEGF-A, as well as lower levels of and VEGF-C, were found to be statistically significant in the VV group compared to the control subjects without VVs. None of the analyzed factors was associated with the venous localization of the varicosities. The presented study identified dysregulations in key angiogenesis- and inflammation-related factors in PBMC and plasma from VVs patients, providing new insight into molecular mechanisms that could contribute to the development of VVs and point out promising candidates for circulatory biomarkers of this disease.
Topics: Humans; Varicose Veins; Female; Male; Middle Aged; Neovascularization, Pathologic; Inflammation; Leukocytes, Mononuclear; Adult; Aged; Gene Expression Regulation; Angiogenesis
PubMed: 38928491
DOI: 10.3390/ijms25126785 -
Antibiotics (Basel, Switzerland) May 2024(group B streptococci, GBS) is responsible for severe infections in both neonates and adults. Currently, empiric antimicrobial therapy for sepsis and meningitis is the...
(group B streptococci, GBS) is responsible for severe infections in both neonates and adults. Currently, empiric antimicrobial therapy for sepsis and meningitis is the combined use of penicillin and gentamicin due to the enhanced bactericidal activity. However, high-level gentamicin resistance (HLGR) abrogates the synergism. The rate of HLGR was investigated within a dataset of 433 GBS strains collected from cases of invasive disease in both adults and neonates as well as from pregnant carriers. GBS isolates (n = 20, 4.6%) presented with HLGR (gentamicin MIC breakpoint >1024 mg/L) that was differently diffused between strains from adults or neonates (5.2% vs. 2.8%). Notably, 70% of HLGR GBS strains (14 isolates) were serotype IV. Serotype IV HLGR-GBS isolates were susceptible to all antibiotics tested, exhibited the alpha-C/HvgA/PI-2b virulence string, and belonged to sequence type 1010 (clonal complex (CC) 452). The mobile element that harbored the HLGR (6')-(2)″ gene is a novel integrative and conjugative element (ICE) about 45 kb long, derived from GBS 515 ICE tRNA. The clonal expansion of this HLGR hypervirulent serotype IV GBS CC452 sublineage may pose a threat to the management of infections caused by this strain type.
PubMed: 38927158
DOI: 10.3390/antibiotics13060491 -
Malaria Journal Jun 2024Although Tanzania adopted and has been implementing effective interventions to control and eventually eliminate malaria, the disease is still a leading public health...
High prevalence and risk of malaria among asymptomatic individuals from villages with high prevalence of artemisinin partial resistance in Kyerwa district of Kagera region, north-western Tanzania.
BACKGROUND
Although Tanzania adopted and has been implementing effective interventions to control and eventually eliminate malaria, the disease is still a leading public health problem, and the country experiences heterogeneous transmission. Recent studies reported the emergence of parasites with artemisinin partial resistance (ART-R) in Kagera region with high prevalence (> 10.0%) in two districts of Karagwe and Kyerwa. This study assessed the prevalence and predictors/risk of malaria infections among asymptomatic individuals living in a hyperendemic area where ART-R has emerged in Kyerwa District of Kagera region, north-western Tanzania.
METHODS
This was a community-based cross-sectional survey which was conducted in July and August 2023 and involved individuals aged ≥ 6 months from five villages in Kyerwa district. Demographic, anthropometric, clinical, parasitological, type of house inhabited and socio-economic status (SES) data were collected using electronic capture tools run on Open Data Kit (ODK) software. Predictors/risks of malaria infections were determined by univariate and multivariate logistic regression, and the results were presented as crude (cORs) and adjusted odds ratios (aORs), with 95% confidence intervals (CIs).
RESULTS
Overall, 4454 individuals were tested using rapid diagnostic tests (RDTs), and 1979 (44.4%) had positive results. The prevalence of malaria infections ranged from 14.4% to 68.5% and varied significantly among the villages (p < 0.001). The prevalence and odds of infections were significantly higher in males (aOR = 1.28, 95% CI 1.08 -1.51, p = 0.003), school children (aged 5-≤10 years (aOR = 3.88, 95% CI 3.07-4.91, p < 0.001) and 10-≤15 years (aOR = 4.06, 95% CI 3.22-5.13, p < 0.001)) and among individuals who were not using bed nets (aOR = 1.22, 95% CI 1.03-1.46, p = 0.024). The odds of malaria infections were also higher in individuals with lower SES (aOR = 1.42, 95% CI 1.17-1.72, p < 0.001), and living in houses without windows (aOR = 2.08, 95% CI 1.46-2.96, p < 0.001), partially open (aOR = 1.33, 95% CI 1.11-1.58, p = 0.002) or fully open windows (aOR = 1.30, 95%CI 1.05-1.61, p = 0.015).
CONCLUSION
The five villages had a high prevalence of malaria infections and heterogeneity at micro-geographic levels. Groups with higher odds of malaria infections included school children, males, and individuals with low SES, living in poorly constructed houses or non-bed net users. These are important baseline data from an area with high prevalence of parasites with ART-R and will be useful in planning interventions for these groups, and in future studies to monitor the trends and potential spread of such parasites, and in designing a response to ART-R.
Topics: Tanzania; Male; Prevalence; Female; Humans; Artemisinins; Cross-Sectional Studies; Child; Child, Preschool; Adolescent; Adult; Young Adult; Antimalarials; Middle Aged; Infant; Drug Resistance; Malaria; Aged; Malaria, Falciparum; Risk Factors; Plasmodium falciparum
PubMed: 38926854
DOI: 10.1186/s12936-024-05019-5 -
BMC Microbiology Jun 2024Enterocytozoon bieneusi is the most common species found in humans. Although E. bieneusi has been investigated in humans, genotype profile of E. bieneusi is not known in...
BACKGROUND
Enterocytozoon bieneusi is the most common species found in humans. Although E. bieneusi has been investigated in humans, genotype profile of E. bieneusi is not known in Türkiye.
METHODS
In this study, we screened E. bieneusi in patients (n = 94) with different types of malignant solid tumors by Real Time PCR and then sequenced E. bieneusi positive samples. All cancer patients were undergoing chemotherapy and had diarrhea. Moreover, as control groups, we also screened E. bieneusi in patients with diarrhea (n = 50) and without diarrhea (n = 50).
RESULTS
Among all patients analyzed, 33 (17%) were found to be E. bieneusi-positive. As the patients were categorized, the molecular prevalence of E. bieneusi increased to 25.5% among cancer patients with diarrhea. However, the molecular prevalence of E. bieneusi was found to be lower in patients with presenting only diarrhea (8%) and patients without diarrhea (10%). The high molecular prevalence value detected among cancer patients with diarrhea was also statistically significant compared to other patient groups (P = 0.00112 and P = 0.0269). Among the 33 Real Time PCR positive samples, 10 of them were amplified by nested PCR and among these 10 samples, 6 of them were successfully genotyped. The phylogenetic tree showed the presence of D and Type IV which were also identified in stray cats living in İzmir in our previous study.
CONCLUSIONS
High molecular prevalence value indicates the importance of screening stool samples of cancer patients with diarrhea for E. bieneusi and genotyping results indicate that D and Type IV are circulating between humans and cats.
Topics: Humans; Enterocytozoon; Microsporidiosis; Neoplasms; Genotype; Male; Female; Diarrhea; Middle Aged; Prevalence; Adult; Aged; Real-Time Polymerase Chain Reaction; Young Adult; Phylogeny; Sequence Analysis, DNA; Antineoplastic Agents; DNA, Fungal; Aged, 80 and over; Feces
PubMed: 38926815
DOI: 10.1186/s12866-024-03369-3 -
Parasites & Vectors Jun 2024Trichomonosis is a common infection in small animals, mostly manifesting in gastrointestinal symptoms such as diarrhea. Although oral trichomonads are also known, the...
BACKGROUND
Trichomonosis is a common infection in small animals, mostly manifesting in gastrointestinal symptoms such as diarrhea. Although oral trichomonads are also known, the species found colonizing the large intestine are more frequently detected protozoa.
METHODS
In the present study, four wildcats, 94 domestic cats, and 25 dogs, originating from 18 different locations in Hungary, were investigated for the presence of oral and large intestinal trichomonads based on the 18S rRNA gene and ITS2.
RESULTS
All oral swabs were negative by polymerase chain reaction (PCR). However, Tritrichomonas foetus was detected in a high proportion among tested domestic cats (13.8%) and dogs (16%), and Pentatrichomonas hominis only in two domestic cats. In addition, a novel Tritrichomonas genotype was identified in one cat, probably representing a new species that was shown to be phylogenetically most closely related to Tritrichomonas casperi described recently from mice. All positive dogs and half of the positive cats showed symptoms, and among cats, the most frequent breed was the Ragdoll.
CONCLUSIONS
With molecular methods, this study evaluated the prevalence of oral and intestinal trichomonads in clinical samples of dogs and cats from Hungary, providing the first evidence of T. foetus in dogs of this region. In contrast to literature data, P. hominis was more prevalent in cats than in dogs. Finally, a hitherto unknown large intestinal Tritrichomonas species (closely related to T. casperi) was shown to be present in a cat, raising two possibilities. First, this novel genotype might have been a rodent-associated pseudoparasite in the relevant cat. Otherwise, the cat was actually infected, thus suggesting the role of a predator-prey link in the evolution of this trichomonad.
Topics: Animals; Cats; Dogs; Cat Diseases; Dog Diseases; Phylogeny; Protozoan Infections, Animal; Hungary; RNA, Ribosomal, 18S; Tritrichomonas; DNA, Protozoan; Female; Male; Genotype; Prevalence; Polymerase Chain Reaction; Tritrichomonas foetus
PubMed: 38926778
DOI: 10.1186/s13071-024-06343-0 -
BMJ Case Reports Jun 2024This report describes a male in his late 20s who presented with a 2-month history of recurrent haemoptysis and chest pain. A chronic infection, such as tuberculosis, was...
This report describes a male in his late 20s who presented with a 2-month history of recurrent haemoptysis and chest pain. A chronic infection, such as tuberculosis, was suspected. He had undergone surgical resection of an intrapericardial hydatid cyst in the past. His blood investigations showed peripheral eosinophilia, and his chest X-ray showed a cystic oval lesion in the left upper zone. A CT pulmonary angiogram revealed filling defects in the bilateral segmental and subsegmental arteries with a cystic lesion in the left upper lobe. Further workup, including bronchoalveolar lavage culture and MRI of the thorax, confirmed the diagnosis of a hydatid cyst of pulmonary echinococcosis. This case illustrates the presentation of multisystemic echinococcosis in a young male with no other risk factors, initially treated with surgical resection and antihelminthic therapy. The disease later recurred, which required prolonged medications, which brought the patient into remission.
Topics: Humans; Male; Echinococcosis, Pulmonary; Adult; Albendazole; Hemoptysis; Anthelmintics; Recurrence; Chest Pain; Heart Diseases; Tomography, X-Ray Computed; Magnetic Resonance Imaging; Follow-Up Studies
PubMed: 38926123
DOI: 10.1136/bcr-2023-256689 -
International Immunopharmacology Jun 2024Leishmaniasis, caused by Leishmania (L.) species, remains a neglected infection. Therapeutic vaccination presents a promising strategy for its treatment. In this study,...
Leishmaniasis, caused by Leishmania (L.) species, remains a neglected infection. Therapeutic vaccination presents a promising strategy for its treatment. In this study, we aimed to develop a therapeutic vaccine candidate using Leishmaniaantigens (SLA) and Toll-like receptor (TLR) 7/8 agonist (R848) encapsulated into the poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). Moreover, TLR1/2 agonist (Pam3CSK4) was loaded onto the NPs. The therapeutic effects of these NPs were evaluated in L. major-infected BALB/c mice. Footpad swelling, parasite load, cellular and humoral immune responses, and nitric oxide (NO) production were analyzed. The results demonstrated that the PLGA NPs (SLA-R848-Pam3CSK4) therapeutic vaccine effectively stimulated Th1 cell responses, induced humoral responses, promoted NO production, and restricted parasite burden and lesion size.Our findings suggest that vaccination with SLA combined with TLR1/2 and TLR7/8 agonists in PLGA NPs as a therapeutic vaccine confers strong protection againstL. majorinfection. These results represent a novel particulate therapeutic vaccine against Old World cutaneous leishmaniasis.
PubMed: 38924865
DOI: 10.1016/j.intimp.2024.112538 -
Clinical Pharmacology in Drug... Jun 2024AWZ1066S has been developed as a potential treatment for the neglected tropical diseases lymphatic filariasis and onchocerciasis. AWZ1066S targets the Wolbachia...
AWZ1066S has been developed as a potential treatment for the neglected tropical diseases lymphatic filariasis and onchocerciasis. AWZ1066S targets the Wolbachia bacterial endosymbiont present in the causative nematode parasites. This phase 1, first-in-human study aimed to assess the safety and pharmacokinetics of AWZ1066S in healthy human participants. In a randomized double-blind, placebo-controlled, single ascending dose study, healthy adults received a single oral dose of AWZ1066S (or placebo) and were followed up for 10 days. The planned single doses of AWZ1066S ranged from 100 to 1600 mg, and each dose was administered to a cohort of 8 participants (6 AWZ1066S and 2 placebo). In total 30 people participated, 18 (60%) female, median age 30.0 years (minimum 20, maximum 61). The cohorts administered 100, 200, 300, and 400 mg of AWZ1066S progressed unremarkably. After single 700-mg doses all 4 participants developed symptoms of acute gastritis and transient increases in liver enzymes. The severity of these adverse events ranged from mild to severe, with 1 participant needing hospital admission. Pharmacokinetic analysis indicated that AWZ1066S is rapidly absorbed with predictable pharmacokinetics. In conclusion, safety concerns prevented this study from reaching the human exposures needed for AWZ1066S to be clinically effective against lymphatic filariasis and onchocerciasis.
PubMed: 38924387
DOI: 10.1002/cpdd.1441 -
Journal of Experimental Zoology. Part... Jun 2024Honey bees play a pivotal role in shaping ecosystems and sustaining human health as both pollinators and producers of health-promoting products. However, honey bee...
Honey bees play a pivotal role in shaping ecosystems and sustaining human health as both pollinators and producers of health-promoting products. However, honey bee colony mortality is on the rise globally, driven by various factors, including parasites, pesticides, habitat loss, poor nutrition, and climate change. This has far-reaching consequences for the environment, economy, and human welfare. While efforts to address these issues are underway, the current progress in electron paramagnetic resonance (EPR) instrumentation affords using the immense potential of this magnetic resonance technique to study small samples such as honey bees. This paper presents the pioneering 2D in vivo EPR imaging experiment on a honey bee, revealing the ongoing redox-status of bees' intestines. This way, by monitoring the spatio-temporal changes of the redox-active spin-probes' EPR signal, it is possible to gain access to valuable information on the course of ongoing bees' pathologies and the prospect of following-up on the efficiency of applied therapies. Employing a selection of diverse spin-probes could further reveal pH levels and oxygen concentrations in bee tissues, allowing a noninvasive assessment of bee physiology. This approach offers promising strategies for safeguarding pollinators and understanding their biology, fostering their well-being and ecological harmony.
PubMed: 38924358
DOI: 10.1002/jez.2845 -
ChemMedChem Jun 2024This study introduces further insights from the hit-to-lead optimization process involving a series of benzimidazole derivatives acting as inhibitors of the cruzain...
This study introduces further insights from the hit-to-lead optimization process involving a series of benzimidazole derivatives acting as inhibitors of the cruzain enzyme, which targets Trypanosoma cruzi, the causative parasite of Chagas disease. Here, we present the design, synthesis and biological evaluation of 30 new compounds as a third generation of benzimidazole analogues with trypanocidal activity, aiming to enhance our understanding of their pharmacokinetic profiles and establish a structure-metabolism relationships within the series. The design of these new analogues was guided by the analysis of previous pharmacokinetic results, considering identified metabolic sites and biotransformation studies. This optimization resulted in the discovery of two compounds (42e and 49b) exhibiting enhanced metabolic stability, anti-Trypanosoma cruzi activity compared to benznidazole (the reference drug for Chagas disease), as well as being non-cruzain inhibitors, and demonstrating a satisfactory in vitro pharmacokinetic profile. These findings unveil a new subclass of aminobenzimidazole and rigid compounds, which offer potential for further exploration in the quest for discovering novel classes of antichagasic compounds.
PubMed: 38924252
DOI: 10.1002/cmdc.202400293