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Ocular Immunology and Inflammation Sep 2023Endogenous endophthalmitis (EE) is an uncommon but potentially devastating ocular infection involving the inner layers of the eye. The global incidence of EE is on the...
Endogenous endophthalmitis (EE) is an uncommon but potentially devastating ocular infection involving the inner layers of the eye. The global incidence of EE is on the rise. Common ocular signs and symptoms associated with EE include conjunctival injection, ocular pain, and reduced visual acuity. On clinical examination, a history of prior or coexisting systemic infections, symptoms (e.g., fever, malaise), and localizing features may be noted. Clinical diagnosis is often challenging, resulting in critical delays that contribute to a poor prognosis. Blood cultures and ocular fluid samples can aid in conforming causative pathogen(s), after which empirical antibiotic therapy, both systemic and intravitreal, should be instated. The use of steroids to suppress inflammation remains controversial. Surgical options include pars plana vitrectomy. Overall prognosis varies depending on host and pathogen factors, and early diagnosis and initiation of appropriate treatment are crucial.
Topics: Humans; Vitreous Body; Retrospective Studies; Endophthalmitis; Vitrectomy; Eye Infections, Fungal; Anti-Bacterial Agents
PubMed: 36306406
DOI: 10.1080/09273948.2022.2126863 -
Mediterranean Journal of Rheumatology Sep 2023Rheumatoid arthritis (RA), a chronic inflammatory autoimmune disorder, is characterised by persistent synovial inflammation, erosion of bones and cartilage, leading to... (Review)
Review
Rheumatoid arthritis (RA), a chronic inflammatory autoimmune disorder, is characterised by persistent synovial inflammation, erosion of bones and cartilage, leading to joint destruction. Clinical manifestations are morning stiffness, pain in shoulder, neck and pelvic girdle, loss of mobility with fever, fatigue, malaise, loss of body weight, and development of rheumatoid nodules. Environmental and genetic factors are important contributors in its susceptibility. Association between RA and diet, cigarette smoking, hormones, alcohol, microbiota, infection, and coffee have also been reported. To diagnose patients with RA, American college of rheumatology (ACR, 2010) criteria, developed by European league against rheumatism (EULAR). Inflammation produced in RA patients is due to cell-mediated immune response. The rheumatoid synovium consists of a large number of CD T cells suggesting pathogenic nature of T cells in this disorder. B-cells may also participate in the pathogenesis by several means such as autoantibodies, by instigation of T-cells through expression of co-stimulatory molecules, by generating pro-inflammatory and anti-inflammatory cytokines and by organisation of other inflammatory cells. The conventional management of RA usually focuses over reducing pain and limiting the disability by medical therapies which include a number of classes of agents such as non-steroidal anti-inflammatory drugs (NSAIDs), non-biological and biological agents, disease-modifying anti rheumatic drugs (DMARDs), immunosuppressants, and corticosteroids. However, only proper rehabilitation can promote the objective to achieve the joint functionality and ease of motion which improves independence as well as quality of life in patient suffering from Rheumatoid Arthritis.
PubMed: 37941854
DOI: 10.31138/mjr.20230801.oo -
The Journal of Gene Medicine Sep 2023Monkeypox infection outbreaks have been observed sporadically in Africa, usually as a result of interaction with wildlife reservoirs. The genomes of the new strain range... (Review)
Review
Monkeypox infection outbreaks have been observed sporadically in Africa, usually as a result of interaction with wildlife reservoirs. The genomes of the new strain range in size from 184.7 to 198.0 kb and are identified with 143-214 open reading frames. Viral cores are rapidly carried on microtubules away from the cell's perimeter and deeper into the cytoplasm once the virus and cell membranes fuse. Depending on the kind of exposure, patients with monkeypox may experience a febrile prodrome 5-13 days after exposure, which frequently includes lymphadenopathy, malaise, headaches, and muscle aches. A different diagnostic approach is available for monkeypox, including histopathological analysis, electron microscopy, immunoassays, polymerase chain reaction, genome sequencing, microarrays, loop-mediated isothermal amplification technology and CRISPR (i.e., "clustered regularly interspaced short palindromic repeats"). There are currently no particular, clinically effective treatments available for the monkeypox virus. An initial treatment is cidofovir. As a monophosphate nucleotide analog, cidofovir is transformed into an inhibitor of viral DNA polymerase by cellular kinases, which is analogous to cidofovir's function in inhibiting viral DNA synthesis. The European Medicine Agency and the Food and Drug Administration have both granted permission for IMVAMUNE, a replication-deficient, attenuated third-generation modified vaccinia Ankara vaccine, to be used for the prevention of smallpox and monkeypox in adults.
Topics: United States; Humans; Mpox (monkeypox); Cidofovir; Vaccinia virus; Monkeypox virus; Clinical Laboratory Techniques
PubMed: 37132057
DOI: 10.1002/jgm.3521 -
Proceedings of the National Academy of... Oct 2023Travel can induce motion sickness (MS) in susceptible individuals. MS is an evolutionary conserved mechanism caused by mismatches between motion-related sensory...
Travel can induce motion sickness (MS) in susceptible individuals. MS is an evolutionary conserved mechanism caused by mismatches between motion-related sensory information and past visual and motion memory, triggering a malaise accompanied by hypolocomotion, hypothermia, hypophagia, and nausea. Vestibular nuclei (VN) are critical for the processing of movement input from the inner ear. Motion-induced activation of VN neurons recapitulates MS-related signs. However, the genetic identity of VN neurons mediating MS-related autonomic and aversive responses remains unknown. Here, we identify a central role of cholecystokinin (CCK)-expressing VN neurons in motion-induced malaise. Moreover, we show that CCK VN inputs onto the parabrachial nucleus activate -expressing neurons and are sufficient to establish avoidance to novel food, which is prevented by CCK-A receptor antagonism. These observations provide greater insight into the neurobiological regulation of MS by identifying the neural substrates of MS and providing potential targets for treatment.
Topics: Animals; Mice; Motion Sickness; Movement; Neurons; Vestibular Nuclei; Vestibule, Labyrinth
PubMed: 37847729
DOI: 10.1073/pnas.2304933120 -
Journal of Cardiopulmonary... Nov 2023The post-acute sequalae of SARS-CoV-2, also known as "Long COVID," is characterized by profound fatigue, impaired functional capacity with post-exertional malaise,... (Review)
Review
The post-acute sequalae of SARS-CoV-2, also known as "Long COVID," is characterized by profound fatigue, impaired functional capacity with post-exertional malaise, orthostatic intolerance, and tachycardia. At least 25-30% of individuals impacted by SARS-CoV-2 will go on to experience the Long COVID syndrome, underscoring the detrimental impact this condition has on society. Although efforts are underway to further understand risk factors for Long COVID and identify strategies to prevent disease development entirely, implementation of treatment strategies is warranted to alleviate symptom burden among those affected. This review provides a rationale for exercise prescriptions tailored to the Long COVID patient based on the pathophysiology underlying this syndrome, as well as the previously demonstrated benefits of exercise training in other similar populations whose clinical manifestations result from cardiac deconditioning. Herein, we discuss methods to tailor exercise protocols, accommodating exercise intolerance and post-exertional malaise that may otherwise limit the ability to participate in a training protocol, as well as data demonstrating that a focused exercise prescription may effectively alleviate symptom burden in these patients. Long COVID results, in large part, from deconditioning, which may result from as little as 20 hr of inactivity. Exercise prescriptions tailored to patients with Long COVID may effectively alleviate symptom burden associated with this condition and in the absence of overt contraindications should be considered in management.
Topics: Humans; Post-Acute COVID-19 Syndrome; COVID-19; SARS-CoV-2; Exercise Therapy; Exercise
PubMed: 37646620
DOI: 10.1097/HCR.0000000000000821 -
Journal of Clinical Medicine Jul 2023Fatigue is the most commonly reported and debilitating extraglandular symptom of primary Sjögren's syndrome (pSS). Fatigue and exertional intolerance are hallmark...
Fatigue is the most commonly reported and debilitating extraglandular symptom of primary Sjögren's syndrome (pSS). Fatigue and exertional intolerance are hallmark symptoms of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We aimed to characterize fatigue and further symptoms among pSS patients and to determine whether there is a symptom overlap in pSS and ME/CFS. In 19 patients with pSS, we assessed pSS symptom severity and disease activity via questionnaires as well as the Canadian Consensus Criteria (CCC) for ME/CFS. Hand grip strength (HGS) and levels of α1-, α2-, β1-, β2-, M3- and M4-receptor-autoantibodies were measured. A subgroup of pSS patients exhibited severe fatigue and had higher severity of pain ( = 0.045), depression ( = 0.021) and sleep disturbances ( = 0.020) compared to those with less fatigue. Four of eighteen pSS patients fulfilled the CCC. HGS parameters strongly correlated with fatigue severity ( < 0.05), but strength fully recovered one hour after exertion in contrast to ME/CFS. Levels of β1-, β2- and M4-receptor-autoantibodies were elevated and correlated significantly with disease activity assessed by the ESSDAI ( < 0.05), but not fatigue severity. Only a minor subgroup of pSS patients fulfills the CCC, and post exertional malaise (PEM) is atypical, as it is primarily triggered by mental/emotional but not physical exertion. HGS assessment is an objective measure to assess overall fatigue severity.
PubMed: 37568396
DOI: 10.3390/jcm12154994 -
EClinicalMedicine Sep 2023Post-COVID-19 syndrome (PCS) is characterised by a wide range of symptoms, primarily fatigue and exertion intolerance. While disease courses in the early months...
BACKGROUND
Post-COVID-19 syndrome (PCS) is characterised by a wide range of symptoms, primarily fatigue and exertion intolerance. While disease courses in the early months post-infection have been well-described, the long-term health consequences for patients with PCS with disabling fatigue remain unclear.
METHODS
In this prospective observational cohort study, we evaluated symptom severity and various biomarkers, including hand grip strength (HGS), cardiovascular function, and laboratory parameters, in 106 patients with PCS with moderate to severe fatigue and exertion intolerance at three time points after infection (3-8, 9-16, and 17-20 months). The study was conducted at the Charité's Fatigue Centre and the Charité's outpatient clinic for neuroimmunology at Berlin, Germany from July 16, 2020, to February 18, 2022. A subset of patients (PCS-ME/CFS) met the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome according to the Canadian Consensus Criteria (CCC). The aim was to determine differences in the disease course between the two patient groups (i.e., PCS vs PCS-ME/CFS) and identify correlating biomarkers.
FINDINGS
Patients with PCS-ME/CFS reported persistently high severity of most symptoms up to 20 months after infection, while patients with PCS showed overall health improvement. Although fatigue and post-exertional malaise (PEM), hallmarks of post-infectious fatigue syndromes, were still evident in both groups, they remained more pronounced in PCS-ME/CFS. Inflammatory biomarkers decreased in both groups, but not antinuclear antibodies. Lower HGS at onset correlated with symptom persistence, particularly in patients with PCS-ME/CFS.
INTERPRETATION
Our findings suggest that PCS can persist beyond 20 months post-infection and encompass the full scope of post-infectious ME/CFS as defined by the CCC. Sub-classifying patients with PCS based on the CCC can assist in the management and monitoring of patients with PCS-ME/CFS due to their persistently higher symptom severity.
FUNDING
C. S. was supported by a grant from the Weidenhammer-Zoebele Foundation. F. K. was supported by the Volkswagen Foundation.
PubMed: 37662515
DOI: 10.1016/j.eclinm.2023.102146 -
General Dentistry 2024The zoonotic infectious disease mpox (previously known as monkeypox) is caused by the monkeypox virus (MPXV) from the Poxviridae family. Presently, mpox is receiving...
The zoonotic infectious disease mpox (previously known as monkeypox) is caused by the monkeypox virus (MPXV) from the Poxviridae family. Presently, mpox is receiving worldwide attention because of its emergence in countries that have never previously documented the illness, resulting in a public health emergency. MPXV is transmitted via human-to-human contact, and sexual contact is especially implicated in spread of the disease. Affected individuals experience fever, headache, malaise, and early lymphadenopathy, followed by a secondary mucotaneous rash. Oral ulcers and perioral papules may be the first evidence of the disease. Although there are numerous articles in medical publications documenting the cutaneous presentations of mpox, there is limited information in the dental literature regarding oral lesions. The objective of this article is to review the oral manifestations of mpox and strategies for management of the disease.
Topics: Humans; Mpox (monkeypox); Oral Ulcer; Public Health
PubMed: 38411483
DOI: No ID Found -
World Journal of Gastroenterology Oct 2023Primary biliary cholangitis (PBC) is a chronic cholestatic progressive liver disease and one of the most important progressive cholangiopathies in adults. Damage to... (Review)
Review
Primary biliary cholangitis (PBC) is a chronic cholestatic progressive liver disease and one of the most important progressive cholangiopathies in adults. Damage to cholangiocytes triggers the development of intrahepatic cholestasis, which progresses to cirrhosis in the terminal stage of the disease. Accumulating data indicate that damage to biliary epithelial cells [(BECs), cholangiocytes] is most likely associated with the intracellular accumulation of bile acids, which have potent detergent properties and damaging effects on cell membranes. The mechanisms underlying uncontrolled bile acid intake into BECs in PBC are associated with pH change in the bile duct lumen, which is controlled by the bicarbonate (HCO) buffer system "biliary HCO umbrella". The impaired production and entry of HCO from BECs into the bile duct lumen is due to epigenetic changes in expression of the X-linked microRNA 506. Based on the growing body of knowledge on the molecular mechanisms of cholangiocyte damage in patients with PBC, we propose a hypothesis explaining the pathogenesis of the first morphologic (ductulopenia), immunologic (antimitochondrial autoantibodies) and clinical (weakness, malaise, rapid fatigue) signs of the disease in the asymptomatic stage. This review focuses on the consideration of these mechanisms.
Topics: Humans; Liver Cirrhosis, Biliary; Bile Ducts; Epithelial Cells; Cholestasis; Bile Acids and Salts; Cholangitis; MicroRNAs
PubMed: 37899787
DOI: 10.3748/wjg.v29.i37.5292 -
Frontiers in Immunology 2023Generalized pustular psoriasis (GPP) is a rare, chronic, inflammatory skin disorder characterized by recurrent flares associated with skin erythema, desquamation, and... (Review)
Review
Generalized pustular psoriasis (GPP) is a rare, chronic, inflammatory skin disorder characterized by recurrent flares associated with skin erythema, desquamation, and widespread superficial sterile pustules, which may be severe ("lakes of pus"). Systemic symptoms are often present, including malaise, fever, and skin pain. In GPP, innate immune responses are driven by abnormal activation of the interleukin (IL)-36-chemokine-neutrophil axis and excessive neutrophil infiltration. This review highlights the IL-36 pathway in the context of the IL-1 superfamily and describes how unopposed IL-36 signaling can lead to the development of GPP. Targeted inhibition of the IL-36 receptor (IL-36R) is an attractive therapeutic strategy in the treatment of GPP, including flare prevention and sustained disease control. Spesolimab is a first-in-class, humanized, monoclonal antibody that binds specifically to the IL-36R and antagonizes IL-36 signaling. Spesolimab was approved by the US Food and Drug Administration in September 2022 to treat GPP flares in adults and was subsequently approved for GPP flare treatment in other countries across the world. Anti-IL-36R therapy, such as spesolimab, can mitigate flares and address flare prevention in GPP, presumably through rebalancing IL-36 signaling and modulating the pro-inflammatory response of the downstream effectors.
Topics: United States; Adult; Humans; Psoriasis; Interleukins; Skin; Skin Diseases, Vesiculobullous
PubMed: 38077370
DOI: 10.3389/fimmu.2023.1292941