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Cureus Apr 2024Lyme disease progresses through three distinct clinical phases: early localized, early disseminated, and late disseminated. Lyme arthritis is characterized by attacks of...
Lyme disease progresses through three distinct clinical phases: early localized, early disseminated, and late disseminated. Lyme arthritis is characterized by attacks of joint swelling lasting for weeks to months, potentially causing permanent joint damage in late disseminated disease. Our case focuses on a 63-year-old, obese, type 2 diabetic, wheelchair-bound, Caucasian male with severe bilateral knee pain. Our patient had previously undergone bilateral knee arthroscopies for meniscal tears and also had knee injections performed previously without the desired level of pain alleviation. He indicated a recent cough that was treated with erythromycin and noted his knees felt better during the course of the antibiotic. The patient recreationally enjoyed hunting and mentioned that his dog had Lyme Disease. Laboratory confirmation of Lyme disease prompted our patient to be treated with doxycycline. Upon completion of doxycycline therapy, our patient noted significant improvement in his knee pain. The improvement was significant enough that the patient canceled a planned bilateral knee replacement with his orthopedic surgeon, and no longer required the use of a wheelchair as he was able to return to ambulating independently. The patient's quality of life improved significantly, and he could also return to work. Lyme disease should be a consideration in the differential diagnosis of patients in areas endemic to the disease, and patients who tend to have outdoor lifestyles.
PubMed: 38817479
DOI: 10.7759/cureus.59318 -
Cureus Apr 2024Ehrlichiosis is a tick-borne illness that has been recognized as a source of human infection with increased incidence in the United States over the last decade. The...
Ehrlichiosis is a tick-borne illness that has been recognized as a source of human infection with increased incidence in the United States over the last decade. The usual presentation is with acute febrile illness, myalgia, malaise with confusion, and central nervous system abnormalities, along with laboratory data concerning transaminitis and hematological abnormalities. Though many complications have been associated with Ehrlichiosis, very few cardiac complications have been reported. We report a rare presentation of Ehrlichiosis in a 63-year-old female who presented with acute fever, transaminitis, and renal failure followed by the development of myocarditis. As part of the diagnostic work-up, an examination of the peripheral smear revealed intracytoplasmic granules in monocytes, which were later confirmed through serology to have Ehrlichia chaffeensis (E. chaffeensis). Given the high degree of initial clinical suspicion, the patient was started on empiric doxycycline and fully recovered with no disease-associated sequelae.
PubMed: 38817458
DOI: 10.7759/cureus.59369 -
Frontiers in Cellular and Infection... 2024Brucellosis is a zoonotic disease caused by a Gram-negative coccus a facultative intracellular pathogen. Neurobrucellosis has an incidence rate of 3-7% among all... (Review)
Review
Brucellosis is a zoonotic disease caused by a Gram-negative coccus a facultative intracellular pathogen. Neurobrucellosis has an incidence rate of 3-7% among all patients with brucellosis, while spinal cord involvement is rare and carries a significant mortality risk. This report describes a case of brucellosis myelitis in a 55-year-old male patient who presented with recurrent paralysis, incontinence, and damage to the visual and auditory nerves. The diagnosis of neurobrucellosis involves a serum tube agglutination test, cerebrospinal fluid analysis, a physical examination of the nervous system, and a comprehensive review of the patient's medical history. The presence of brucellosis was confirmed in cerebrospinal fluid using MetaCAP™ sequencing. Treatment with a combination of rifampicin, doxycycline, ceftriaxone sodium, amikacin, compound brain peptide ganglioside, and dexamethasone resulted in significant improvement of the patient's clinical symptoms and a decrease in the brucellosis sequence count in cerebrospinal fluid. For the first time, MetaCAP™ sequencing has been used to treat pathogenic microbial nucleic acids, which could be a valuable tool for early diagnosis and treatment of neurobrucellosis.
Topics: Humans; Male; Brucellosis; Middle Aged; Myelitis; Anti-Bacterial Agents; Treatment Outcome; Magnetic Resonance Imaging
PubMed: 38817447
DOI: 10.3389/fcimb.2024.1378331 -
Breast Cancer Research : BCR May 2024Despite progress understanding the mechanisms underlying tumor spread, metastasis remains a clinical challenge. We identified the choline-producing...
BACKGROUND
Despite progress understanding the mechanisms underlying tumor spread, metastasis remains a clinical challenge. We identified the choline-producing glycerophosphodiesterase, EDI3 and reported its association with metastasis-free survival in endometrial cancer. We also observed that silencing EDI3 slowed cell migration and other cancer-relevant phenotypes in vitro. Recent work demonstrated high EDI3 expression in ER-HER2+ breast cancer compared to the other molecular subtypes. Silencing EDI3 in ER-HER2+ cells significantly reduced cell survival in vitro and decreased tumor growth in vivo. However, a role for EDI3 in tumor metastasis in this breast cancer subtype was not explored. Therefore, in the present work we investigate whether silencing EDI3 in ER-HER2+ breast cancer cell lines alters phenotypes linked to metastasis in vitro, and metastasis formation in vivo using mouse models of experimental metastasis.
METHODS
To inducibly silence EDI3, luciferase-expressing HCC1954 cells were transduced with lentiviral particles containing shRNA oligos targeting EDI3 under the control of doxycycline. The effect on cell migration, adhesion, colony formation and anoikis was determined in vitro, and significant findings were confirmed in a second ER-HER2+ cell line, SUM190PT. Doxycycline-induced HCC1954-luc shEDI3 cells were injected into the tail vein or peritoneum of immunodeficient mice to generate lung and peritoneal metastases, respectively and monitored using non-invasive bioluminescence imaging. Metabolite levels in cells and tumor tissue were analyzed using targeted mass spectrometry and MALDI mass spectrometry imaging (MALDI-MSI), respectively.
RESULTS
Inducibly silencing EDI3 reduced cell adhesion and colony formation, as well as increased susceptibility to anoikis in HCC1954-luc cells, which was confirmed in SUM190PT cells. No influence on cell migration was observed. Reduced luminescence was seen in lungs and peritoneum of mice injected with cells expressing less EDI3 after tail vein and intraperitoneal injection, respectively, indicative of reduced metastasis. Importantly, mice injected with EDI3-silenced cells survived longer. Closer analysis of the peritoneal organs revealed that silencing EDI3 had no effect on metastatic organotropism but instead reduced metastatic burden. Finally, metabolic analyses revealed significant changes in choline and glycerophospholipid metabolites in cells and in pancreatic metastases in vivo.
CONCLUSIONS
Reduced metastasis upon silencing supports EDI3's potential as a treatment target in metastasizing ER-HER2+ breast cancer.
Topics: Animals; Female; Humans; Mice; Cell Line, Tumor; Receptor, ErbB-2; Breast Neoplasms; Receptors, Estrogen; Disease Models, Animal; Cell Movement; Gene Knockdown Techniques; Tumor Burden; Neoplasm Metastasis; Lung Neoplasms; Cell Proliferation
PubMed: 38816770
DOI: 10.1186/s13058-024-01849-y -
Cureus Apr 2024Syphilis is a sexually transmitted disease that impacts multiple organ systems and can mimic various diseases and is an extremely rare cause of proctitis in men who...
Syphilis is a sexually transmitted disease that impacts multiple organ systems and can mimic various diseases and is an extremely rare cause of proctitis in men who have sex with men and transgender females. We present a case of a 49-year-old transgender female with a medical history significant for diabetes mellitus and hyperlipidemia who presented to the emergency department with dull abdominal pain in the left upper and lower quadrants for two days. She had non-bloody, nonbilious emesis, 10-pound weight loss over 1 month, and constipation for 2 weeks. Laboratory results showed a cholestatic pattern. Computed tomography of the abdomen showed rectal wall thickening, multiple enlarged perirectal adenopathy, and mild inflammatory infiltration around the rectum suggesting superimposed proctitis. On colonoscopy, a possible rectal mass or severe proctitis with near complete obstruction was seen with initial pathology concerning for lymphoma or a rare type of colitis. The patient was empirically started on ceftriaxone and doxycycline leading to improvement in inflammation. Special stains requested were positive for Treponema pallidum confirming the diagnosis of syphilitic proctitis and highly suggestive syphilitic hepatitis. Few cases of syphilitic proctitis imitating rectal malignancy and syphilitic hepatitis have been reported. Syphilis requires exclusion as well as confirmation of spirochetes for high-risk populations with special staining. It is important to diagnose syphilis in special populations that are at high risk of contraction.
PubMed: 38807842
DOI: 10.7759/cureus.59222 -
Journal of Cutaneous Medicine and... May 2024Rosacea is a chronic inflammatory skin condition affecting approximately 5.5% of the global population. Patients present heterogeneously with a mix of features in the...
INTRODUCTION
Rosacea is a chronic inflammatory skin condition affecting approximately 5.5% of the global population. Patients present heterogeneously with a mix of features in the central facial region, of which papules and pustules are considered to be a major feature. The identification of effective treatments for reducing inflammatory lesions in rosacea can alleviate the psychosocial burden that many rosacea patients experience, including reduced self-esteem, anxiety, and social withdrawal. The objective of this systematic review is to determine the effectiveness of topical and systemic therapies in reducing lesion count in rosacea patients.
METHODS/RESULTS
Medline, Embase, and Cochrane CENTRAL databases were searched, resulting in the inclusion of 43 clinical trials reporting on a total of 18,347 rosacea patients. The most well-studied treatments include ivermectin, metronidazole, azelaic acid, minocycline, and doxycycline. Oral isotretinoin was the most effective treatment in reducing inflammatory lesions and may be recommended for severe recalcitrant cases of rosacea.
CONCLUSIONS
Several topical and systemic therapies have demonstrated efficacy in reducing inflammatory lesion count in rosacea patients, with mechanisms of action centred around suppressing inflammation and killing mites. Additional research is required to determine effective combination therapies in rosacea.
PubMed: 38807451
DOI: 10.1177/12034754241253195 -
Cureus Apr 2024Background Pulp necrosis in incomplete root formation halts dentine development, resulting in larger canals with fragile walls and an open apex, complicating canal...
Histologic Assessment of a Fast-Set Mineral Trioxide Aggregate (MTA) and Two Novel Antibacterial-Enhanced Fast-Set MTAs for Apexification and Periapical Healing of Teeth With Incomplete Root Formation in a Rat Model: An In Vivo Animal Study.
Background Pulp necrosis in incomplete root formation halts dentine development, resulting in larger canals with fragile walls and an open apex, complicating canal instrumentation and apical stop formation. Bioactive endodontic cements such as mineral trioxide aggregate (MTA) are crucial for creating artificial apical barriers or inducing apical foramen closure, but challenges remain regarding their antimicrobial efficacy and cytotoxicity. Modifications to MTA formulations aim to address these concerns. Methods This in vivo animal study involved 80 Wistar albino rats, with incomplete root formation induced by pulp exposure. Rats were divided into four groups receiving different MTA formulations for apexification: conventional MTA, modified MTA, and MTA enhanced with metronidazole or doxycycline. Histopathological evaluations were conducted at seven and 28 days post-treatment to assess calcific barrier formation, inflammatory reactions, and antimicrobial efficacy. Results By day 7, modified MTA formulations exhibited enhanced antibacterial activity compared to conventional MTA (p = 0.000), with fewer inflammatory reactions and microorganisms. By day 28, modified formulations showed superior calcific barrier formation, particularly in the metronidazole- and doxycycline-enhanced groups compared to conventional MTA (p = 0.000). These outcomes suggest that modifications to MTA formulations improve antimicrobial efficacy and calcific barrier formation in vivo. Conclusion Novel modified MTA formulations, particularly those enhanced with metronidazole or doxycycline, exhibit superior antibacterial efficacy and calcific barrier formation compared to conventional MTA. Further long-term studies are warranted to validate these findings for potential clinical translation.
PubMed: 38800318
DOI: 10.7759/cureus.59064 -
Pharmaceuticals (Basel, Switzerland) May 2024Brucellosis is an infection widely distributed around the world, and in some countries it is considered a public health problem. Brucellosis causes insidious symptoms...
Brucellosis is an infection widely distributed around the world, and in some countries it is considered a public health problem. Brucellosis causes insidious symptoms that make it difficult to diagnose. Infection can also trigger chronic pain and neuropsychiatric complications. Antibiotics are not always effective to eradicate infection, contributing to chronicity. We aimed to investigate the effects of antibiotic treatment on proinflammatory cytokines, neurotransmitters, corticosterone, and behavior in a murine model of infecrion of strain 2308. Four study groups were created: (a) control; (b) antibiotic control; (c) infected with 2308; and (d) infected and treated with rifampicin and doxycycline. We determined 2308 colony-forming units (CFUs), the count of dendritic cells, and macrophages in the spleen; serum levels of cytokines and corticosterone; levels of serotonin, dopamine, epinephrine, and norepinephrine in the brain; and equilibrium, physical strength, anxiety, and hopelessness tests. The infected and treated mice group was compared with the control and infected mice to assess whether treatment is sufficient to recover neuroimmunoendocrine parameters. Our results showed that despite the treatment of brucellosis with rifampicin and doxycycline, antibiotic-treated mice showed a persistence of 2308 CFUs, an increased count in macrophage number, and higher circulating levels of corticosterone. Furthermore, the levels of IL-12, IL-6, and TNF-α remained higher. We found a decrease in muscular strength and equilibrium concomitant to changes in neurotransmitters in the hippocampus, cerebellum, and frontal cortex. Our data suggest that the remaining bacterial load after antibiotic administration favors inflammatory, neurochemical, and behavioral alterations, partly explaining the widespread and paradoxical symptomatology experienced by patients with chronic brucellosis.
PubMed: 38794208
DOI: 10.3390/ph17050638 -
Microorganisms May 2024B13, selected from fermentation chili, has been proven to promote animal growth by previous studies, but it belongs to opportunistic pathogens, so a comprehensive...
B13, selected from fermentation chili, has been proven to promote animal growth by previous studies, but it belongs to opportunistic pathogens, so a comprehensive evaluation of its probiotic properties and safety is necessary. In this study, the probiotic properties and safety of B13 were evaluated at the genetic and phenotype levels in vitro and then confirmed in vivo. The genome of B13 contains one chromosome and two plasmids. The average nucleotide identity indicated that B13 was most closely related to the fermentation-plant-derived strain. The strain does not carry the major virulence genes of the clinical strains but contains , , genes. The strain had a higher tolerance to acid at pH 3.0, 4.0, and 0.3% bile salt and a 32.83% free radical DPPH clearance rate. It can adhere to Caco-2 cells and reduce the adhesion of to Caco-2 cells. The safety assessment revealed that the strain showed no hemolysis and did not exhibit gelatinase, ornithine decarboxylase, lysine decarboxylase, or tryptophanase activity. It was sensitive to twelve antibiotics but was resistant to erythromycin, rifampicin, tetracycline, doxycycline, and minocycline. Experiments in vivo have shown that B13 can be located in the ileum and colon and has no adverse effects on experiment animals. After 28 days of feeding, B13 did not remarkable change the α-diversity of the gut flora or increase the virulence genes. Our study demonstrated that B13 may be used as a probiotic candidate.
PubMed: 38792822
DOI: 10.3390/microorganisms12050994 -
Microorganisms Apr 2024() is a zoonotic pathogen capable of causing severe diseases in humans and pigs, including meningitis, sepsis, polyserositis, arthritis, and endocarditis. This study...
() is a zoonotic pathogen capable of causing severe diseases in humans and pigs, including meningitis, sepsis, polyserositis, arthritis, and endocarditis. This study aimed to investigate the biological characteristics of 19 strains of isolated from diseased pigs in Hubei Province between 2021 and 2023. Through bioinformatics analysis, we investigated the serotype, MLST, pan-genome characteristics, SNP, AMR, and ICE of the 19 isolates. Among the 19 strains, ten serotypes were identified, and serotype 9 was the most prevalent (21.05%). Ten new alleles and nine new sequence types (STs) were discovered, with ST28 and ST243 emerging as the predominant STs. The results of the pan-genomic analysis of indicate that there are 943 core genes, 2259 shell genes, and 5663 cloud genes. Through SNP evolutionary analysis, we identified a strong genetic similarity between SS31 and the reference genome P1/7. The analysis of antibiotic resistance genes revealed widespread presence of (B) and (O) genes among 19 strains of . This association may be linked to the high resistance of to lincosamides, macrolides, and tetracyclines. Integrative and conjugative elements (ICEs) and integrative and mobilizable elements (IMEs) were identified in 16 strains, with a carriage rate of 84.21%, and resistance genes were identified within the ICE/IME elements of 8 strains. Antimicrobial susceptibility testing revealed that all strains showed sensitivity to vancomycin and lincomycin but resistance to tilmicosin, tiamulin, amoxicillin, and doxycycline. This study contributes to our understanding of the genomic diversity of in Hubei Province of China, providing essential data for the comprehensive prevention and control of infections in China.
PubMed: 38792744
DOI: 10.3390/microorganisms12050917