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The Korean Journal of Gastroenterology... Jun 2024Toxocariasis, a zoonotic infection transmitted by (from dogs) and (from cats) larvae, poses rare but severe risks to humans. We present a case of hepatic visceral... (Review)
Review
Toxocariasis, a zoonotic infection transmitted by (from dogs) and (from cats) larvae, poses rare but severe risks to humans. We present a case of hepatic visceral larva migrans (VLM) caused by in a 21-year-old male with a history of close contact with a pet dog. Initial symptoms and imaging findings mimicked a pyogenic liver abscess. The initial laboratory investigations revealed neutrophilia and elevated levels of IgE. Despite broad-spectrum antibiotics, persistent fever prompted further investigation. Subsequent serological testing for Toxocara antibodies and histopathological analysis of liver tissue demonstrating eosinophil infiltrates and Charcot-Leyden crystals led to a confirmed diagnosis of a liver abscess caused by . Serological testing for Toxocara antibodies and histopathological analysis of liver tissue confirmed a -induced liver abscess. Albendazole treatment yielded significant clinical improvement. This case highlights the necessity of considering toxocariasis in liver abscess differentials, particularly in high-seroprevalence regions like Vietnam. Relying solely on serological tests may be insufficient, emphasizing the need for corroborative evidence, including invasive procedures like liver biopsy, for accurate hepatic toxocariasis diagnosis.
Topics: Humans; Toxocara canis; Larva Migrans, Visceral; Male; Animals; Young Adult; Albendazole; Tomography, X-Ray Computed; Dogs; Liver; Antibodies, Helminth; Ultrasonography; Liver Abscess; Toxocariasis; Immunoglobulin E; Anthelmintics
PubMed: 38918038
DOI: 10.4166/kjg.2024.051 -
PloS One 2024Visceral Leishmaniasis (VL) is a neglected tropical disease (NTD) with the highest regional burden in East Africa. Relapse and Post Kala-azar Dermal Leishmaniasis (PKDL)...
BACKGROUND
Visceral Leishmaniasis (VL) is a neglected tropical disease (NTD) with the highest regional burden in East Africa. Relapse and Post Kala-azar Dermal Leishmaniasis (PKDL) contribute to the spread of VL in endemic areas, making their surveillance imperative for control and elimination. Little is known about long-term patient outcomes in Kenya through follow-up after VL treatment, despite its requirement for control and elimination by the World Health Organization (WHO) and the Kenya Ministry of Health (KMOH).
METHODOLOGY/PRINCIPAL FINDINGS
36 follow-up patients in Tiaty East and West, sub-counties, Kenya, and records from 248 patients at the regional Chemolingot Sub-county Hospital (CSCH) were analyzed separately using Fisher's Exact Tests, two-sample t-tests, and Welch's t-tests in R (Version 4.3.0). The study found a prevalence rate of 88.89% (n = 32) final cure, 5.56% (n = 2) relapse, and 5.56% (n = 2) PKDL in follow-up patients and 92.74% (n = 230) initial cure, 6.86% (n = 17) relapse, and 0.80% (n = 2) PKDL in overall CSCH patients. The mean lengths of time at which follow-up patients relapsed and developed PKDL were 4.5 and 17 months, respectively. Young age (p = 0.04, 95% CI 0.63-24.31), shorter length of time from initial treatment to follow-up (p = 0.002, 95% CI 1.03-∞), lower Hb level at primary treatment (p = 0.0002, 95% CI 1.23-3.24), and living in Tiaty East sub-county (p = 0.04, 95% CI 0.00-1.43) were significantly associated (p<0.05) with VL relapse in follow-up study patients. Female sex (p = 0.04, 95% CI 0.84-∞) and living in Tiaty East sub-county (p = 0.03, 95% CI 0.00-1.43) were significantly associated with PKDL in follow-up study patients.
CONCLUSIONS/SIGNIFICANCE
More research should be done on PKDL in Kenya with active follow-up to understand its true burden. These results on prevalence and risk factors for PKDL and relapse in Kenya should inform knowledge of patient outcomes and interventions in the region.
Topics: Humans; Leishmaniasis, Visceral; Kenya; Male; Female; Adult; Recurrence; Adolescent; Follow-Up Studies; Child; Treatment Outcome; Young Adult; Child, Preschool; Leishmaniasis, Cutaneous; Middle Aged; Antiprotozoal Agents; Prevalence
PubMed: 38917127
DOI: 10.1371/journal.pone.0306067 -
Arthritis Research & Therapy Jun 2024Treatments for rheumatoid arthritis (RA) are associated with complex changes in lipids and lipoproteins that may impact cardiovascular (CV) risk. The objective of this... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Treatments for rheumatoid arthritis (RA) are associated with complex changes in lipids and lipoproteins that may impact cardiovascular (CV) risk. The objective of this study was to examine lipid and lipoprotein changes associated with two common RA treatment strategies, triple therapy or tumor necrosis factor inhibitor (TNFi), and association with CV risk.
METHODS
In this secondary data analysis of the TARGET trial, methotrexate (MTX) inadequate responders with RA were randomized to either add sulfasalazine and hydroxychloroquine (triple therapy), or TNFi for 24-weeks. The primary trial outcome was the change in arterial inflammation measured in the carotid arteries or aorta by FDG-PET/CT at baseline and 24-weeks; this change was described as the target-to-background ratio (TBR) in the most diseased segment (MDS). Routine lipids and advanced lipoproteins were measured at baseline and 24-weeks; subjects on statin therapy at baseline were excluded. Comparisons between baseline and follow-up lipid measurements were performed within and across treatment arms, as well as change in lipids and change in MDS-TBR.
RESULTS
We studied 122 participants, 61 in each treatment arm, with median age 57 years, 76% female, and 1.5 year median RA disease duration. When comparing treatment arms, triple therapy had on average a larger reduction in triglycerides (15.9 mg/dL, p = 0.01), total cholesterol to HDL-C ratio (0.29, p-value = 0.01), and LDL particle number (111.2, p = 0.02) compared to TNFi. TNFi had on average a larger increase in HDL particle number (1.6umol/L, p = 0.006). We observed no correlation between change in lipid measurements and change in MDS-TBR within and across treatment arms.
CONCLUSIONS
Both treatment strategies were associated with improved lipid profiles via changes in different lipids and lipoproteins. These effects had no correlation with change in CV risk as measured by vascular inflammation by FDG-PET/CT.
TRIAL REGISTRATION
ClinicalTrials.gov ID NCT02374021.
Topics: Humans; Arthritis, Rheumatoid; Female; Middle Aged; Male; Antirheumatic Agents; Hydroxychloroquine; Lipids; Drug Therapy, Combination; Methotrexate; Aged; Sulfasalazine; Adult; Tumor Necrosis Factor Inhibitors; Treatment Outcome; Positron Emission Tomography Computed Tomography; Vasculitis
PubMed: 38915065
DOI: 10.1186/s13075-024-03352-3 -
Scientific Reports Jun 2024Antibiotic resistance among bacteria is recognized as the primary factor contributing to the failure of treatment. In this research, our objective was to examine the...
Antibiotic resistance among bacteria is recognized as the primary factor contributing to the failure of treatment. In this research, our objective was to examine the prevalence of antibiotic resistance in H. pylori bacteria in Palestine. We enlisted 91 individuals suffering from dyspepsia, comprising 49 females and 42 males. These participants underwent esophagogastroduodenoscopy procedures with gastric biopsies. These biopsies were subsequently subjected to microbiological assessments and tested for their susceptibility to various antimicrobial drugs. Among the 91 patients, 38 (41.7%) exhibited the presence of H. pylori. Notably, Ciprofloxacin displayed the highest efficacy against H. pylori, followed by Levofloxacin, Moxifloxacin, and Amoxicillin, with resistance rates of 0%, 0%, 2.6%, and 18.4%, respectively. On the contrary, Metronidazole and Clarithromycin demonstrated the lowest effectiveness, with resistance percentages of 100% and 47.4%, respectively. The outcomes of this investigation emphasize that H. pylori strains within the Palestinian patient group exhibit substantial resistance to conventional first-line antibiotics like clarithromycin and metronidazole. However, alternative agents such as fluoroquinolones and amoxicillin remain efficacious choices. Consequently, we recommend favoring quinolone-based treatment regimens for H. pylori infections and adopting a more judicious approach to antibiotic usage among the Palestinian population.
Topics: Humans; Helicobacter pylori; Female; Male; Helicobacter Infections; Cross-Sectional Studies; Anti-Bacterial Agents; Adult; Prevalence; Middle Aged; Drug Resistance, Bacterial; Hospitals, University; Microbial Sensitivity Tests; Amoxicillin; Clarithromycin; Metronidazole; Levofloxacin
PubMed: 38914675
DOI: 10.1038/s41598-024-63982-0 -
Frontiers in Immunology 2024Vitamin E, which is also known as tocopherol, is a compound with a polyphenol structure. Its esterified derivative, Vitamin E succinate (VES), exhibits unique anticancer...
BACKGROUND
Vitamin E, which is also known as tocopherol, is a compound with a polyphenol structure. Its esterified derivative, Vitamin E succinate (VES), exhibits unique anticancer and healthcare functions as well as immunomodulatory effects. Natural polysaccharides are proved to be a promising material for nano-drug delivery systems, which show excellent biodegradability and biocompatibility. In this study, we employed a novel polysaccharide-vitamin E succinate polymer (BSP-VES) micelles to enhance the tumor targeting and anti-colon cancer effect of andrographolide (AG).
METHODS
BSP-VES polymer was synthesized through esterification and its structure was confirmed using 1H NMR. AG@BSP-VES was prepared via the dialysis method and the drug loading, entrapment efficiency, stability, and safety were assessed. Furthermore, the tumor targeting ability of AG@BSP-VES was evaluated through targeted cell uptake and imaging. The antitumor activity of AG@BSP-VES was measured using MTT assay, Live&Dead cell staining, and cell scratch test.
RESULTS
In this study, we successfully loaded AG into BSP-VES micelles (AG@BSP-VES), which exhibited good stability, biosafety and sustained release effect. In addition, AG@BSP-VES also showed excellent internalization capability into CT26 cells compared with NCM460 cells . Meanwhile, the specific delivery of AG@BSP-VES micelles into subcutaneous and colon tumors was observed compared with normal colon tissues during the whole experiment process (1-24 h). What's more, AG@BSP-VES micelles exhibited significant antitumor activities than BSP-VES micelles and free AG.
CONCLUSION
The study provides a meaningful new idea and method for application in drug delivery system and targeted treatment of colon cancer based on natural polysaccharides.
Topics: Micelles; Animals; Colonic Neoplasms; Diterpenes; Humans; Mice; Cell Line, Tumor; Polysaccharides; Antineoplastic Agents; Drug Delivery Systems; Xenograft Model Antitumor Assays; Drug Carriers; Nanoparticles; Nanoparticle Drug Delivery System; Mice, Nude; Mice, Inbred BALB C
PubMed: 38911867
DOI: 10.3389/fimmu.2024.1380229 -
BMC Infectious Diseases Jun 2024Nocardia is an ubiquitous soil organism. As an opportunistic pathogen, inhalation and skin inoculation are the most common routes of infection. Lungs and skin are the... (Review)
Review
BACKGROUND
Nocardia is an ubiquitous soil organism. As an opportunistic pathogen, inhalation and skin inoculation are the most common routes of infection. Lungs and skin are the most frequent sites of nocardiosis. Testis is a highly unusual location for nocardiosis.
CASE PRESENTATION
We report the case of an immunocompromised 75-year-old-man admitted for fever of unknown origin. He presented with skin lesions after gardening and was first suspected of Mediterranean spotted fever, but he did not respond to doxycycline. Then, physical examination revealed new left scrotal swelling that was compatible with a diagnosis of epididymo-orchitis. The patient's condition did not improve despite empirical antibiotic treatment with the onset of necrotic scrotal abscesses requiring surgery. Nocardia brasiliensis yielded from the removed testis culture. High-dose trimethoprim-sulfamethoxazole and ceftriaxone were started. Multiple micro-abscesses were found in the brain and spinal cord on imaging studies. After 6 weeks of dual antibiotic therapy for disseminated nocardiosis, slight regression of the brain abscesses was observed. The patient was discharged after a 6-month course of antibiotics and remained relapse-free at that time of writing these lines. Trimethoprim-sulfamethoxazole alone is meant to be pursued for 6 months thereafter. We undertook a literature review on previously reported cases of genitourinary and urological nocardiosis; to date, only 36 cases have been published with predominately involvement of kidney, prostate and testis.
CONCLUSIONS
To the best of our knowledge, this is the first case of Nocardia brasiliensis simultaneously infecting skin, testis, brain and spinal cord in an immunocompromised patient. Knowledge on uncommon forms of nocardiosis remains scarce. This case report highlights the difficulty of diagnosing atypical nocardiosis and the importance of prompt bacteriological sampling in case of empirical antibiotics failure.
Topics: Humans; Male; Nocardia Infections; Aged; Anti-Bacterial Agents; Nocardia; Fever of Unknown Origin; Immunocompromised Host; Trimethoprim, Sulfamethoxazole Drug Combination; Testis; Orchitis
PubMed: 38907186
DOI: 10.1186/s12879-024-09521-8 -
Medicine Jun 2024Scrub typhus is a naturally occurring acute febrile disease caused by Orientia tsutsugamushi. Although it can cause multiple organ dysfunction, central nervous system... (Review)
Review
RATIONALE
Scrub typhus is a naturally occurring acute febrile disease caused by Orientia tsutsugamushi. Although it can cause multiple organ dysfunction, central nervous system infections are uncommon.
PATIENT CONCERNS
A 17-year-old male presented with a 5-day history of fever and headaches. The MRI of the head revealed thickness and enhancement of the left temporal lobe and tentorium cerebelli, indicating potential inflammation.
DIAGNOSES
The patient was diagnosed with a central nervous system infection.
INTERVENTIONS
Ceftriaxone and acyclovir were administered intravenously to treat the infection, reduce fever, restore acid-base balance, and manage electrolyte disorders.
OUTCOMES
Despite receiving ceftriaxone and acyclovir as infection therapy, there was no improvement. Additional multipathogen metagenomic testing indicated the presence of O tsutsugamushi infection, and an eschar was identified in the left axilla. The diagnosis was changed to scrub typhus with meningitis and the therapy was modified to intravenous doxycycline. Following a 2-day therapy, the body temperature normalized, and the fever subsided.
CONCLUSIONS
The patient was diagnosed with scrub typhus accompanied by meningitis, and doxycycline treatment was effective.
LESSION
Rarely reported cases of scrub typhus with meningitis and the lack of identifiable symptoms increase the chance of misdiagnosis or oversight. Patients with central nervous system infections presenting with fever and headache unresponsive to conventional antibacterial and antiviral treatment should be considered for scrub typhus with meningitis. Prompt multipathogen metagenomic testing is recommended to confirm the diagnosis and modify the treatment accordingly.
Topics: Humans; Scrub Typhus; Male; Adolescent; Anti-Bacterial Agents; Doxycycline; Orientia tsutsugamushi; Meningitis, Bacterial
PubMed: 38905360
DOI: 10.1097/MD.0000000000038613 -
PloS One 2024Syphilis, caused by Treponema pallidum, is resurging globally. Molecular typing allows for the investigation of its epidemiology. In Pakistan and other nations, T....
Syphilis, caused by Treponema pallidum, is resurging globally. Molecular typing allows for the investigation of its epidemiology. In Pakistan and other nations, T. pallidum subsp. pallidum has developed widespread macrolide resistance in the past decade. A study at the Peshawar Regional Blood Centre from June 2020-June 2021 analyzed serum samples from 32,812 blood donors in Khyber Pakhtunkhwa, Pakistan, to assess circulating T. pallidum strains and antibiotic resistance. Blood samples were initially screened for T. pallidum antibodies using a chemiluminescent microparticle immunoassay (CMIA). CMIA-reactive samples underwent polymerase chain reaction (PCR) targeted the polA, tpp47, bmp, and tp0319 genes. PCR-positive samples were further analyzed for molecular subtyping using a CDC-developed procedure and tp0548 gene examination. All PCR-positive samples were analyzed for the presence of point mutations A2058G and A2059G in 23S rRNA, as well as the G1058C mutation in 16S rRNA. These mutations are known to impart antimicrobial resistance to macrolides and doxycycline, respectively. Out of 32,812 serum samples, 272 (0.83%) were CMIA-reactive, with 46 being PCR-positive. Nine T. pallidum subtypes were identified, predominantly 14d/f. The A2058G mutation in 23S rRNA was found in 78% of cases, while G1058C in 16S rRNA and A2059G in 23S rRNA were absent. The research found donor blood useful for assessing T. pallidum molecular subtypes and antibiotic resistance, especially when chancres are not present. The prevalent subtype was 14d/f (51.85%), and the high macrolide resistance of 36 (78%) indicates caution in using macrolides for syphilis treatment in Khyber Pakhtunkhwa, Pakistan.
Topics: Treponema pallidum; Humans; Pakistan; Syphilis; Blood Donors; Anti-Bacterial Agents; Drug Resistance, Bacterial; Male; Female; Adult; Macrolides; RNA, Ribosomal, 23S; RNA, Ribosomal, 16S; Middle Aged; Doxycycline; Young Adult
PubMed: 38905249
DOI: 10.1371/journal.pone.0305720 -
International Journal of Biological... 2024N-methyladenosine (mA) methylation plays a crucial role in various biological processes and the pathogenesis of human diseases. However, its role and mechanism in kidney...
N-methyladenosine (mA) methylation plays a crucial role in various biological processes and the pathogenesis of human diseases. However, its role and mechanism in kidney fibrosis remain elusive. In this study, we show that the overall level of mA methylated RNA was upregulated and the mA methyltransferase METTL3 was induced in kidney tubular epithelial cells in mouse models and human kidney biopsies of chronic kidney disease (CKD). Proximal tubule-specific knockout of METTL3 in mice protected kidneys against developing fibrotic lesions after injury. Conversely, overexpression of METTL3 aggravated kidney fibrosis . Through bioinformatics analysis and experimental validation, we identified β-catenin mRNA as a major target of METTL3-mediated mA modification, which could be recognized by a specific mA reader, the insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3). METTL3 stabilized β-catenin mRNA, increased β-catenin protein and induced its downstream profibrotic genes, whereas either knockdown of IGF2BP3 or inhibiting β-catenin signaling abolished its effects. Collectively, these results indicate that METTL3 promotes kidney fibrosis by stimulating the mA modification of β-catenin mRNA, leading to its stabilization and its downstream profibrotic genes expression. Our findings suggest that targeting METTL3/IGF2BP3/β-catenin pathway may be a novel strategy for the treatment of fibrotic CKD.
Topics: beta Catenin; Animals; Mice; Fibrosis; Humans; Methylation; Methyltransferases; Signal Transduction; Adenosine; Kidney; Male; Mice, Inbred C57BL; Up-Regulation; Renal Insufficiency, Chronic; Mice, Knockout; RNA Methylation
PubMed: 38904026
DOI: 10.7150/ijbs.96233 -
Journal of Translational Medicine Jun 2024KIAA1429, a regulatory subunit of the N-methyladenosine (mA) methyltransferase complex, has been implicated in the progression of various cancers. However, the role of...
BACKGROUND
KIAA1429, a regulatory subunit of the N-methyladenosine (mA) methyltransferase complex, has been implicated in the progression of various cancers. However, the role of KIAA1429 in gastric cancer (GC) and its underlying mechanisms remain elusive. This study aimed to investigate the role of KIAA1429 in GC and to elucidate the underlying mechanisms.
METHODS
The expression patterns and clinical relevance of KIAA1429 in GC were assessed using quantitative real-time PCR (qRT-PCR), Western blotting, immunohistochemistry (IHC), and bioinformatic analysis. In vitro and in vivo loss- and gain-of-function assays, mA dot blot assays, methylated RNA immunoprecipitation sequencing (MeRIP-seq), RNA-seq, MeRIP-qPCR, dual luciferase reporter assays, RNA stability assays, RNA immunoprecipitation (RIP) assays, and RNA pull-down assays were performed to investigate the biological functions and underlying molecular mechanisms of KIAA1429 in GC.
RESULTS
Both the mRNA and protein expression of KIAA1429 were greater in GC tissues than in normal gastric tissues. High KIAA1429 expression correlated positively with poor prognosis in GC patients. KIAA1429 not only promoted GC cell proliferation, colony formation, G2/M cell cycle transition, migration, and invasion in vitro but also enhanced GC tumor growth and metastasis in vivo. Mechanistically, KIAA1429 increased the mA level of RASD1 mRNA and enhanced its stability in an mA-YTHDF2-dependent manner, thereby upregulating its expression. RASD1 knockdown partially rescued the KIAA1429 knockdown-induced impairment of pro‑oncogenic ability in GC cells. The expression levels of KIAA1429 and RASD1 were negatively correlated in GC tissues.
CONCLUSIONS
KIAA1429 plays a pro‑oncogenic role in GC by downregulating RASD1 expression through destabilizing RASD1 mRNA in an mA-YTHDF2-dependent manner. KIAA1429 may serve as a prognostic biomarker and therapeutic target for GC.
Topics: Stomach Neoplasms; Humans; RNA, Messenger; Disease Progression; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; RNA-Binding Proteins; Cell Proliferation; Animals; RNA Stability; Adenosine; Male; Mice, Nude; Female; Middle Aged; Cell Movement; Mice; Prognosis; Mice, Inbred BALB C
PubMed: 38902717
DOI: 10.1186/s12967-024-05375-5