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Frontiers in Behavioral Neuroscience 2015Alzheimer's disease (AD) is the major cause of dementia in Western societies. It progresses asymptomatically during decades before being belatedly diagnosed when... (Review)
Review
Alzheimer's disease (AD) is the major cause of dementia in Western societies. It progresses asymptomatically during decades before being belatedly diagnosed when therapeutic strategies have become unviable. Although several genetic alterations have been associated with AD, the vast majority of AD cases do not show strong genetic underpinnings and are thus considered a consequence of non-genetic factors. Epigenetic mechanisms allow for the integration of long-lasting non-genetic inputs on specific genetic backgrounds, and recently, a growing number of epigenetic alterations in AD have been described. For instance, an accumulation of dysregulated epigenetic mechanisms in aging, the predominant risk factor of AD, might facilitate the onset of the disease. Likewise, mutations in several enzymes of the epigenetic machinery have been associated with neurodegenerative processes that are altered in AD such as impaired learning and memory formation. Genome-wide and locus-specific epigenetic alterations have also been reported, and several epigenetically dysregulated genes validated by independent groups. From these studies, a picture emerges of AD as being associated with DNA hypermethylation and histone deacetylation, suggesting a general repressed chromatin state and epigenetically reduced plasticity in AD. Here we review these recent findings and discuss several technical and methodological considerations that are imperative for their correct interpretation. We also pay particular focus on potential implementations and theoretical frameworks that we expect will help to better direct future studies aimed to unravel the epigenetic participation in AD.
PubMed: 26734709
DOI: 10.3389/fnbeh.2015.00347 -
Revue Medicale Suisse Sep 2020Diaphragmatic paresis/paralysis can be unilateral or bilateral. Its manifestations range from completely asymptomatically to global respiratory failure. Respiratory... (Review)
Review
Diaphragmatic paresis/paralysis can be unilateral or bilateral. Its manifestations range from completely asymptomatically to global respiratory failure. Respiratory functional tests will reveal lowered respiratory pressures with a restrictive syndrome, and a decrease in vital capacity when lying in the supine position compared to sitting. Unilateral paresis is most often self-limited and mainly post-surgical. The bilateral dysfunction, observed in neuromuscular diseases, is often permanent. The treatment consists in the management of specific causes, the optimization of the treatment of comorbidities, and in some cases, diaphragmatic plication, ventilatory support or pacing of phrenic nerves.
Topics: Diaphragm; Humans; Paresis; Phrenic Nerve; Respiratory Insufficiency; Respiratory Paralysis
PubMed: 32914596
DOI: No ID Found -
The Surgical Clinics of North America Apr 2019The management of autoimmune hepatobiliary disorders remains a challenging and emerging area of investigation. An awareness of cholestatic liver diseases is critical to... (Review)
Review
The management of autoimmune hepatobiliary disorders remains a challenging and emerging area of investigation. An awareness of cholestatic liver diseases is critical to appropriate recognition and management of these challenging diseases, because patients often present asymptomatically, and diagnosis is limited by the lack of disease-specific markers and diagnostic studies. Furthermore, there is a paucity of treatment options because the pathophysiology underlying autoimmune biliary diseases remains largely unknown. This article discusses the natural history, clinical presentation, diagnosis, and medical and surgical management strategies for three dominant autoimmune biliary diseases: primary biliary cirrhosis, primary sclerosing cholangitis, and immunoglobulin G4-related hepatobiliary disease.
Topics: Autoimmune Diseases; Biliary Tract Diseases; Humans
PubMed: 30846029
DOI: 10.1016/j.suc.2018.11.003 -
Journal of the Pediatric Infectious... Nov 2021Clostridioides difficile is a spore-forming, obligate anaerobe, and ubiquitous nosocomial pathogen. While C. difficile infection in adults causes a spectrum of disease,... (Review)
Review
Clostridioides difficile is a spore-forming, obligate anaerobe, and ubiquitous nosocomial pathogen. While C. difficile infection in adults causes a spectrum of disease, including pseudomembranous colitis and toxic megacolon, healthy infants are asymptomatically colonized at high rates. The mechanisms leading to high colonization rates and infant protection from C. difficile are currently unknown; however, the ecology and metabolic state of the intestinal microbiome are factors known to influence C. difficile pathogenesis. In this review, we will examine the aspects of the early-life microbiome that may contribute to the incidence of C. difficile and protection from disease manifestation in infants. We will also discuss whether features of the adult microbiota that enable and restrict C. difficile are prevalent during early-life colonization.
Topics: Adult; Clostridioides; Clostridioides difficile; Clostridium Infections; Enterocolitis, Pseudomembranous; Humans; Infant; Microbiota
PubMed: 34791400
DOI: 10.1093/jpids/piab063 -
Malaria Journal Jan 2021Plasmodium falciparum causes the majority of malaria cases worldwide and children in sub-Saharan Africa are the most vulnerable group affected. Non-sterile clinical...
BACKGROUND
Plasmodium falciparum causes the majority of malaria cases worldwide and children in sub-Saharan Africa are the most vulnerable group affected. Non-sterile clinical immunity that protects from symptoms develops slowly and is relatively short-lived. Moreover, current malaria vaccine candidates fail to induce durable high-level protection in endemic settings, possibly due to the immunomodulatory effects of the malaria parasite itself. Because dendritic cells play a crucial role in initiating immune responses, the aim of this study was to better understand the impact of cumulative malaria exposure as well as concurrent P. falciparum infection on dendritic cell phenotype and function.
METHODS
In this cross-sectional study, the phenotype and function of dendritic cells freshly isolated from peripheral blood samples of Malian adults with a lifelong history of malaria exposure who were either uninfected (n = 27) or asymptomatically infected with P. falciparum (n = 8) was assessed. Additionally, plasma cytokine and chemokine levels were measured in these adults and in Malian children (n = 19) with acute symptomatic malaria.
RESULTS
With the exception of lower plasmacytoid dendritic cell frequencies in asymptomatically infected Malian adults, peripheral blood dendritic cell subset frequencies and HLA-DR surface expression did not differ by infection status. Peripheral blood myeloid dendritic cells of uninfected Malian adults responded to in vitro stimulation with P. falciparum blood-stage parasites by up-regulating the costimulatory molecules HLA-DR, CD80, CD86 and CD40 and secreting IL-10, CXCL9 and CXCL10. In contrast, myeloid dendritic cells of asymptomatically infected Malian adults exhibited no significant responses above the uninfected red blood cell control. IL-10 and CXCL9 plasma levels were elevated in both asymptomatic adults and children with acute malaria.
CONCLUSIONS
The findings of this study indicate that myeloid dendritic cells of uninfected adults with a lifelong history of malaria exposure are able to up-regulate co-stimulatory molecules and produce cytokines. Whether mDCs of malaria-exposed individuals are efficient antigen-presenting cells capable of mounting an appropriate immune response remains to be determined. The data also highlights IL-10 and CXCL9 as important factors in both asymptomatic and acute malaria and add to the understanding of asymptomatic P. falciparum infections in malaria-endemic areas.
Topics: Adult; Asymptomatic Infections; Chemokines; Child; Child, Preschool; Cross-Sectional Studies; Cytokines; Dendritic Cells; Erythrocytes; Female; Humans; Malaria; Malaria, Falciparum; Male; Mali; Middle Aged; Phenotype; Plasmodium falciparum
PubMed: 33407502
DOI: 10.1186/s12936-020-03533-w -
Journal of the National Comprehensive... Aug 2023Immune checkpoint inhibitor-induced pancreatic injury (ICI-PI) ranges from asymptomatic hyperlipasemia to symptomatic acute pancreatitis (AP). The proportion of...
BACKGROUND
Immune checkpoint inhibitor-induced pancreatic injury (ICI-PI) ranges from asymptomatic hyperlipasemia to symptomatic acute pancreatitis (AP). The proportion of pancreatic injury while receiving ICIs that is attributable to therapy remains unclear. We evaluated the etiology of hyperlipasemia in patients receiving ICIs, and the clinical characteristics, management, and outcomes of ICI-PI.
PATIENTS AND METHODS
We assessed 6,450 consecutive adult patients with cancer who received ICI doses between 2011 and 2019, 364 of whom had at least 1 instance of elevated serum lipase after ICI initiation and were included in our trial. Primary outcomes were the development of ICI-PI and ICI-induced acute pancreatitis (ICI-AP).
RESULTS
Pancreatic injury was attributable to ICI use in 105 individuals (29% of those with hyperlipasemia; 1.6% overall). Of 27 patients with ICI-AP, 4 (15%) presented asymptomatically with hyperlipasemia and pancreatic inflammation on imaging. In multivariable regression, the presence of other immune-related adverse events was positively associated with ICI-AP (≥2 events: odds ratio, 5.43; 95% CI, 1.47-26.03). Compared with patients with other ICI-PI, those with ICI-AP more frequently required steroids (74% vs 4%), intravenous fluids (85% vs 10%), hospitalization (89% vs 9%), and permanent cessation of ICIs due to pancreatic injury (70% vs 3%), and less frequently continued therapy uninterrupted (0% vs 40%) (P<.01 for all). Of the 105 patients, 3 (3%) developed exocrine insufficiency and 9 (9%) developed endocrine insufficiency, which were concentrated among those with ICI-AP.
CONCLUSIONS
A minority of occurrences of pancreatitis and hyperlipasemia in patients receiving ICIs are due to these therapies, supporting NCCN recommendations to exclude alternative etiologies. Because a notable proportion of patients with ICI-AP were asymptomatic but warranted treatment per current guidelines, abdominal imaging is diagnostically valuable in those with significant hyperlipasemia. Patients with ICI-AP should be monitored for exocrine pancreatic insufficiency. Many with hyperlipasemia who do not meet the criteria for AP can continue therapy uninterrupted.
Topics: Adult; Humans; Pancreatitis; Immune Checkpoint Inhibitors; Acute Disease; Radioimmunotherapy; Neoplasms; Retrospective Studies
PubMed: 37549912
DOI: 10.6004/jnccn.2023.7034 -
Ortopedia, Traumatologia, Rehabilitacja Oct 2021Enchondromas are the most common benign bone tumours found in the hand. They are usually accidentally diagnosed on an X-ray, because they grow asymptomatically. In some...
BACKGROUND
Enchondromas are the most common benign bone tumours found in the hand. They are usually accidentally diagnosed on an X-ray, because they grow asymptomatically. In some cases, a pathological fracture of the involved phalanx may be the first sign. The objective of this study was to assess the results of operative treatment of enchondromas involving hand phalanges and metacarpals.
MATERIAL AND METHODS
The study group consisted of 24 patients, 16 women (67%) and 8 men, (33%), aged a mean of 31 years, who were operated on at our centre. The surgery consisted in curettage, and - in most cases - filling the bone defect with either a bone graft or a bone substitute. Follow-up assessment was performed over the telephone in 17 patients (79% of the group) at a mean of 2 years after surgery.
RESULTS
Half of the patients were asymptomatic and fully recovered functionally, whereas the other half complained of some not troublesome symptoms such as scar discomfort, limitation of finger movement or cold sensitivity. No differences were observed with regard to the material used for filling of the bone defect following curettage. Two cases of recurrence were noted after surgery: one in the bone substitute group and one in the bone graft group.
CONCLUSIONS
1. Enchondromas are the most common benign bone tumours encountered in bones of the hand. 2. The first line treatment in these lesions is curettage and filling of the bone defect with a bone sub-stitute or cancellous bone graft. 3. Both the results of the present study and literature data show that the approach to managing the tu-mour cavity after curettage has no significant effect on outcomes, which are essentially satisfactory.
Topics: Aged; Bone Neoplasms; Chondroma; Curettage; Female; Hand; Humans; Male; Neoplasm Recurrence, Local; Retrospective Studies
PubMed: 34734563
DOI: 10.5604/01.3001.0015.4344 -
Allergy Feb 2021The missing asymptomatic COVID-19 infections have been overlooked because of the imperfect sensitivity of the nucleic acid testing (NAT). Globally understanding the...
BACKGROUND
The missing asymptomatic COVID-19 infections have been overlooked because of the imperfect sensitivity of the nucleic acid testing (NAT). Globally understanding the humoral immunity in asymptomatic carriers will provide scientific knowledge for developing serological tests, improving early identification, and implementing more rational control strategies against the pandemic.
MEASURE
Utilizing both NAT and commercial kits for serum IgM and IgG antibodies, we extensively screened 11 766 epidemiologically suspected individuals on enrollment and 63 asymptomatic individuals were detected and recruited. Sixty-three healthy individuals and 51 mild patients without any preexisting conditions were set as controls. Serum IgM and IgG profiles were further probed using a SARS-CoV-2 proteome microarray, and neutralizing antibody was detected by a pseudotyped virus neutralization assay system. The dynamics of antibodies were analyzed with exposure time or symptoms onset.
RESULTS
A combination test of NAT and serological testing for IgM antibody discovered 55.5% of the total of 63 asymptomatic infections, which significantly raises the detection sensitivity when compared with the NAT alone (19%). Serum proteome microarray analysis demonstrated that asymptomatics mainly produced IgM and IgG antibodies against S1 and N proteins out of 20 proteins of SARS-CoV-2. Different from strong and persistent N-specific antibodies, S1-specific IgM responses, which evolved in asymptomatic individuals as early as the seventh day after exposure, peaked on days from 17 days to 25 days, and then disappeared in two months, might be used as an early diagnostic biomarker. 11.8% (6/51) mild patients and 38.1% (24/63) asymptomatic individuals did not produce neutralizing antibody. In particular, neutralizing antibody in asymptomatics gradually vanished in two months.
CONCLUSION
Our findings might have important implications for the definition of asymptomatic COVID-19 infections, diagnosis, serological survey, public health, and immunization strategies.
Topics: Adult; Aged; Antibodies, Neutralizing; Antibodies, Viral; COVID-19; COVID-19 Testing; Carrier State; Female; Humans; Immunoglobulin G; Immunoglobulin M; Male; Middle Aged; SARS-CoV-2
PubMed: 33040337
DOI: 10.1111/all.14622 -
Malaria Journal Sep 2021Further reductions in malaria incidence as more countries approach malaria elimination require the identification and treatment of asymptomatic individuals who carry...
BACKGROUND
Further reductions in malaria incidence as more countries approach malaria elimination require the identification and treatment of asymptomatic individuals who carry mosquito-infective Plasmodium gametocytes that are responsible for furthering malaria transmission. Assessing the relationship between total parasitaemia and gametocytaemia in field surveys can provide insight as to whether detection of low-density, asymptomatic Plasmodium falciparum infections with sensitive molecular methods can adequately detect the majority of infected individuals who are potentially capable of onward transmission.
METHODS
In a cross-sectional survey of 1354 healthy children and adults in three communities in western Kenya across a gradient of malaria transmission (Ajigo, Webuye, and Kapsisywa-Kipsamoite), asymptomatic P. falciparum infections were screened by rapid diagnostic tests, blood smear, and quantitative PCR of dried blood spots targeting the varATS gene in genomic DNA. A multiplex quantitative reverse-transcriptase PCR assay targeting female and male gametocyte genes (pfs25, pfs230p), a gene with a transcriptional pattern restricted to asexual blood stages (piesp2), and human GAPDH was also developed to determine total parasite and gametocyte densities among parasitaemic individuals.
RESULTS
The prevalence of varATS-detectable asymptomatic infections was greatest in Ajigo (42%), followed by Webuye (10%). Only two infections were detected in Kapsisywa. No infections were detected in Kipsamoite. Across all communities, children aged 11-15 years account for the greatest proportion total and sub-microscopic asymptomatic infections. In younger age groups, the majority of infections were detectable by microscopy, while 68% of asymptomatically infected adults (> 21 years old) had sub-microscopic parasitaemia. Piesp2-derived parasite densities correlated poorly with microscopy-determined parasite densities in patent infections relative to varATS-based detection. In general, both male and female gametocytaemia increased with increasing varATS-derived total parasitaemia. A substantial proportion (41.7%) of individuals with potential for onward transmission had qPCR-estimated parasite densities below the limit of microscopic detection, but above the detectable limit of varATS qPCR.
CONCLUSIONS
This assessment of parasitaemia and gametocytaemia in three communities with different transmission intensities revealed evidence of a substantial sub-patent infectious reservoir among asymptomatic carriers of P. falciparum. Experimental studies are needed to definitively determine whether the low-density infections in communities such as Ajigo and Webuye contribute significantly to malaria transmission.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asymptomatic Infections; Child; Child, Preschool; Cross-Sectional Studies; Female; Humans; Infant; Kenya; Malaria, Falciparum; Male; Middle Aged; Prevalence; Rural Population; Young Adult
PubMed: 34535134
DOI: 10.1186/s12936-021-03905-w -
Acta Clinica Belgica Feb 2016Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by vasculopathy and progressive fibrosis of the skin and visceral organs... (Review)
Review
Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by vasculopathy and progressive fibrosis of the skin and visceral organs (gastrointestinal tract, heart, kidneys and lungs). Although the prevalence is low, SSc is a disease with high morbidity and mortality. Since pulmonary arterial hypertension (PAH) associated with SSc (SSc-PAH) and clinically evident cardiac involvement is associated with increased mortality, the cardiac complications and PAH in SSc are reviewed. Both diffuse cutaneous (DcSSc) and limited cutaneous (LcSSc) subgroups are at risk for cardiac involvement and SSc-PAH. Cardiac involvement can be divided in pericardial involvement, myocardial involvement and rhythm disturbances and mostly occurs asymptomatically. However, when symptomatic, it is associated with a poor prognosis. Screening for asymptomatic cardiac involvement should be considered in SSc in order to initiate treatment in an early stage. However, there are no randomized controlled trials on treatment options for cardiac involvement in SSc. SSc-PAH is a devastating complication of SSc, which can develop early in DcSSc and LcSSc. Screening for PAH should be performed since screening leads to earlier diagnosis and earlier treatment is associated with a better prognosis. Today, screening is performed by clinical judgement and echocardiography. Recently the DETECT algorithm, a 2-step screening algorithm is proposed in a SSc-subgroup at increased risk for PAH, but further validation is needed. Despite current treatment options with prostacyclins, endothelin-1 receptor antagonists and phosphodiesterase type-5 inhibitors, mortality remains high. Several promising new treatment options for PAH are evaluated in phase II and III clinical trials.
Topics: Heart; Humans; Hypertension, Pulmonary; Scleroderma, Systemic
PubMed: 27075793
DOI: 10.1080/17843286.2015.1108538