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PloS One 2024Human induced pluripotent stem cells (hiPSCs) derived into neurons offer a powerful in vitro model to study cellular processes. One method to characterize functional...
Human induced pluripotent stem cells (hiPSCs) derived into neurons offer a powerful in vitro model to study cellular processes. One method to characterize functional network properties of these cells is using multielectrode arrays (MEAs). MEAs can measure the electrophysiological activity of cellular cultures for extended periods of time without disruption. Here we used WTC11 hiPSCs with a doxycycline-inducible neurogenin 2 (NGN2) transgene differentiated into neurons co-cultured with primary human astrocytes. We achieved a synchrony index ∼0.9 in as little as six-weeks with a mean firing rate of ∼13 Hz. Previous reports show that derived 3D brain organoids can take several months to achieve similar strong network burst synchrony. We also used this co-culture to model aspects of blood-brain barrier breakdown by using human serum. Our fully human co-culture achieved strong network burst synchrony in a fraction of the time of previous reports, making it an excellent first pass, high-throughput method for studying network properties and neurodegenerative diseases.
Topics: Humans; Astrocytes; Induced Pluripotent Stem Cells; Coculture Techniques; Neurons; Cell Differentiation; Cells, Cultured; Nerve Tissue Proteins; Basic Helix-Loop-Helix Transcription Factors; Electrodes; Blood-Brain Barrier
PubMed: 38917115
DOI: 10.1371/journal.pone.0303901 -
International Journal of... Apr 2024Mycobacterium welchii (Mycobacterium w) vaccine was one of the many strategies used to both treat and prevent coronavirus disease 2019 (COVID-19) infection. We report...
BACKGROUND
Mycobacterium welchii (Mycobacterium w) vaccine was one of the many strategies used to both treat and prevent coronavirus disease 2019 (COVID-19) infection. We report the results of a retrospective analysis of 15 cases with vaccine-site granulomas after administration of prophylactic Mycobacterium w vaccine as part of a trial for COVID-19 and our experience in managing those cases.
METHODS
This was a retrospective analysis of 15 patients with vaccine-site granulomas who were given the vaccine as a prophylactic measure as part of a trial with informed consent.
RESULTS
The mean average age of cases was 37 and the male-to-female ratio was 1:0.87. All of the patients developed erythematous tender nodules over the injection sites within a month of receiving the inoculations. Mycobacterial cultures and cartridge-based nucleic acid amplification tests yielded negative results. Skin biopsy revealed granulomatous dermatitis with acid-fast bacilli positivity. A diagnosis of noninfective granulomatous dermatitis was made. Treatment started with analgesics and anti-inflammatory agents. Systemic antibiotics were required in 9/15 patients. Patients are being followed up with no reported recurrence till date.
CONCLUSION
The possibility of injection-site granuloma should be taken into the risk-benefit analysis for the administration of Mycobacterium w vaccine and the patients should be counseled as such. Patients with persistent ulceration respond to combinations of doxycycline, ofloxacin, and clarithromycin.
Topics: Humans; Female; Male; Retrospective Studies; Adult; Granuloma; Middle Aged; Bacterial Vaccines; COVID-19; Injection Site Reaction; Young Adult; Anti-Bacterial Agents
PubMed: 38916389
DOI: 10.4103/ijmy.ijmy_50_24 -
Heliyon Jun 2024A 71-year-old male had disseminated multiple organ dysfunction syndrome (MODS). Following treatment with cefotaxime and piperacillin-tazobactam, his symptoms have...
A 71-year-old male had disseminated multiple organ dysfunction syndrome (MODS). Following treatment with cefotaxime and piperacillin-tazobactam, his symptoms have worsened instead. Multiple organ failure caused by Japanese Spotted Fever (JSF) was diagnosed based on metagenomic next-generation sequencing (mNGS), we rapidly treated the patient with doxycycline. Thereafter, his symptoms gradually improved. In this report, we emphasized the importance of rapid microbial diagnostic tools and the early use of tetracyclines for the treatment of JSF.
PubMed: 38912444
DOI: 10.1016/j.heliyon.2024.e32647 -
The Indian Journal of Radiology &... Jul 2024A widely accepted set of imaging criteria or classification has not yet been adopted to evaluate response to treatment by percutaneous sclerotherapy for aneurysmal...
A widely accepted set of imaging criteria or classification has not yet been adopted to evaluate response to treatment by percutaneous sclerotherapy for aneurysmal bone cyst (ABC). In this article, we described and illustrated the Royal Orthopaedic Hospital (ROH) scoring system which is a new, reproducible, and objective tool to evaluate the radiological response. We also reported our institutional experience in the efficacy of computed tomography (CT)-guided sclerotherapy for treating such lesions. A retrospective analysis was conducted for 19 patients who underwent CT-guided sclerotherapy with doxycycline and albumin to treat ABC. Follow-up magnetic resonance imaging, at a minimum of 12 months, was assessed according to the four ROH scoring system parameters: cystic component, fluid-fluid level, presence of consolidation, and cortical integrity. The cumulative score was used to grade response as either: excellent, good, equivocal, or poor. Out of 19 patients with a mean age of 17.8 years, 11 cases occurred in the long bones, 5 cases in the pelvis, and 1 in each of the C3 vertebral body, scapula, and talus. The mean parameter of response score for cystic component was 2, fluid-fluid level was 1.3, consolidation was 2, and cortical integrity was 2.1. Four cases showed excellent response, 12 cases showed good response, 2 cases showed equivocal response, and 1 case showed poor response. Interrater reliability was excellent (κ = 0.9). The ROH scoring system provides the radiologist and surgeon with an objective method to score imaging parameters of response independently and achieve a grade based on the cumulative score.
PubMed: 38912248
DOI: 10.1055/s-0044-1779266 -
The Journal of Clinical and Aesthetic... Jun 2024Acne is a chronic inflammatory disease that involves the pilosebaceous follicle. Its pharmacological treatment involves topical and systemic medications, but a...
OBJECTIVE
Acne is a chronic inflammatory disease that involves the pilosebaceous follicle. Its pharmacological treatment involves topical and systemic medications, but a heterogeneous group of drugs may exacerbate or induce skin lesions. The aim of this study was to identify the pharmacological management and medications related to the exacerbation of skin lesions in patients diagnosed with acne.
METHODS
This was a cross-sectional study that identified the outpatient medication prescription patterns of patients with acne from a dispensing database of 8.5 million members of the Colombian Health System. Sociodemographic and pharmacological variables and the identification of prescriptions that were potentially inappropriate due to the risk of worsening acne were considered.
RESULTS
A total of 21,604 patients with acne were identified. Median age was 20.8 years (interquartile range: 17.3-27.3 years), and 60.7 percent were female. Treatment mainly involved antibiotics (79.9% of patients), especially doxycycline (66.0%), and retinoids (55.7%). A total of 17.2 percent of patients had potentially inappropriate prescriptions, predominantly progestogens with androgenic properties (8.9%). Female patients (odds ratio [OR]: 3.55; 95% confidence interval [CI]:3.24-3.90) and patients with pathologies such as systemic lupus erythematosus (OR: 18.61; 95% CI: 7.23-47.93) and rheumatoid arthritis (OR: 10.80; 95% CI: 5.02-23.23) were more likely to receive inappropriate prescriptions, and the risk increased with each year of life (OR: 1.02; 95% CI: 1.02-1.03).
LIMITATIONS
Access to medical records was not obtained to verify clinical characteristics of acne.
CONCLUSION
Patients with acne are excessively treated with systemic antibiotics, counter to clinical practice guidelines. Approximately one-fifth of these patients received some potentially inappropriate medication that could exacerbate their skin lesions.
PubMed: 38912194
DOI: No ID Found -
Urology Case Reports Jul 2024Brucellosis, a systemic infection, can affect various organs, including the genitourinary system, causing epididymo-orchitis in 2%-20 % of cases. This report details a...
Brucellosis, a systemic infection, can affect various organs, including the genitourinary system, causing epididymo-orchitis in 2%-20 % of cases. This report details a 34-year-old Thai male migrant worker with febrile orchitis. Initial gentamicin treatment failed, but serological tests confirmed brucellosis, likely from raw dairy consumption. The patient was successfully treated with gentamicin, doxycycline, and rifampicin, resulting in complete symptom resolution. Brucella orchitis, though rare, should be considered in patients from endemic areas. Conservative treatment with combined antibiotics is typically effective.
PubMed: 38911465
DOI: 10.1016/j.eucr.2024.102764 -
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 Biology Jun 2024Candida albicans is a commensal of the human microbiota that can form biofilms on implanted medical devices. These biofilms are tolerant to antifungals and to the host...
Candida albicans is a commensal of the human microbiota that can form biofilms on implanted medical devices. These biofilms are tolerant to antifungals and to the host immune system. To identify novel genes modulating C. albicans biofilm formation, we performed a large-scale screen with 2,454 C. albicans doxycycline-dependent overexpression strains and identified 16 genes whose overexpression significantly hampered biofilm formation. Among those, overexpression of the ZCF15 and ZCF26 paralogs that encode transcription factors and have orthologs only in biofilm-forming species of the Candida clade, caused impaired biofilm formation both in vitro and in vivo. Interestingly, overexpression of ZCF15 impeded biofilm formation without any defect in hyphal growth. Transcript profiling, transcription factor binding, and phenotypic microarray analyses conducted upon overexpression of ZCF15 and ZCF26 demonstrated their role in reprogramming cellular metabolism by regulating central metabolism including glyoxylate and tricarboxylic acid cycle genes. Taken together, this study has identified a new set of biofilm regulators, including ZCF15 and ZCF26, that appear to control biofilm development through their specific role in metabolic remodeling.
PubMed: 38905306
DOI: 10.1371/journal.pbio.3002693 -
PLoS Neglected Tropical Diseases Jun 2024Febrile illnesses that persist despite initial treatment are common clinical challenges in (sub)tropical low-resource settings. Our aim is to review infectious...
BACKGROUND
Febrile illnesses that persist despite initial treatment are common clinical challenges in (sub)tropical low-resource settings. Our aim is to review infectious etiologies of "prolonged fevers" (persistent febrile illnesses, PFI) and to quantify relative contributions of selected neglected target diseases with limited diagnostic options, often overlooked, causing inadequate antibiotic prescriptions, or requiring prolonged and potentially toxic treatments.
METHODS
We performed a systematic review of articles addressing the infectious etiologies of PFI in adults and children in sub-/tropical low- and middle-income countries (LMICs) using the PRISMA guidelines. A list of target diseases, including neglected parasites and zoonotic bacteria (e.g., Leishmania and Brucella), were identified by infectious diseases and tropical medicine specialists and prioritized in the search. Malaria and tuberculosis (TB) were not included as target diseases due to well-established epidemiology and diagnostic options. Four co-investigators independently extracted data from the identified articles while assessing for risk of bias.
RESULTS
196 articles from 52 countries were included, 117 from Africa (33 countries), 71 from Asia (16 countries), and 8 from Central and -South America (3 countries). Target diseases were reported as the cause of PFI in almost half of the articles, most frequently rickettsioses (including scrub typhus), relapsing fever borreliosis (RF-borreliosis), brucellosis, enteric fever, leptospirosis, Q fever and leishmaniasis. Among those, RF-borreliosis was by far the most frequently reported disease in Africa, particularly in Eastern Africa. Rickettsioses (including scrub typhus) were often described in both Africa and Asia. Leishmaniasis, toxoplasmosis and amoebiasis were the most frequent parasitic etiologies. Non-target diseases and non-tropical organisms (Streptococcus pneumoniae, Escherichia coli, and non-typhoidal Salmonella spp) were documented in a fifth of articles.
CONCLUSIONS
Clinicians faced with PFI in sub-/tropical LMICs should consider a wide differential diagnosis including enteric fever and zoonotic bacterial diseases (e.g., rickettsiosis, RF-borreliosis and brucellosis), or parasite infections (e.g., leishmaniasis) depending on geography and syndromes. In the absence of adequate diagnostic capacity, a trial of antibiotics targeting relevant intra-cellular bacteria, such as doxycycline or azithromycin, may be considered.
PubMed: 38905305
DOI: 10.1371/journal.pntd.0011978