Recent studies suggest excessive complement activation in severe coronavirus disease-19 (COVID-19). The latter shares common characteristics with complement-mediated thrombotic microangiopathy (TMA). We hypothesized that genetic susceptibility would be evident in patients with severe COVID-19 (similar to TMA) and associated with disease severity. We analyzed genetic and clinical data from 97 patients hospitalized for COVID-19. Through targeted next-generation-sequencing we found an ADAMTS13 variant in 49 patients, along with two risk factor variants (C3, 21 patients; CFH,34 patients). 31 (32%) patients had a combination of these, which was independently associated with ICU hospitalization (p = 0.022). Analysis of almost infinite variant combinations showed that patients with rs1042580 in thrombomodulin and without rs800292 in complement factor H did not require ICU hospitalization. We also observed gender differences in ADAMTS13 and complement-related variants. In light of encouraging results by complement inhibitors, our study highlights a patient population that might benefit from early initiation of specific treatment.
Matched MeSH terms: Genetic Predisposition to Disease/genetics*
Vertical transmission may contribute to the maintenance of arthropod-borne viruses, but its existence in chikungunya virus (CHIKV) is unclear. Experimental vertical transmission of infectious clones of CHIKV in Aedes aegypti mosquitoes from Malaysia was investigated. Eggs and adult progeny from the second gonotrophic cycles of infected parental mosquitoes were tested. Using polymerase chain reaction (PCR), 56.3% of pooled eggs and 10% of adult progeny had detectable CHIKV RNA, but no samples had detectable infectious virus by plaque assay. Transfected CHIKV RNA from PCR-positive eggs did not yield infectious virus in BHK-21 cells. Thus, vertical transmission of viable CHIKV was not demonstrated. Noninfectious CHIKV RNA persists in eggs and progeny of infected Ae. aegypti, but the mechanism and significance are unknown. There is insufficient evidence to conclude that vertical transmission exists in CHIKV, as positive results reported in previous studies were almost exclusively based only on viral RNA detection.
The objective of this article is to describe the organisation of an international, clinical registry, the Chronic Kidney Disease Observational Database (CKDOD), the processes of enrolling patients and entering data and preliminary results to date.
Between September 1998 to May 1999, Malaysia and Singapore were hit by an outbreak of fatal encephalitis caused by a novel virus from the paramyxovirus family. This virus was subsequently named as Nipah virus, after the Sungei Nipah village in Negeri Sembilan, where the virus was first isolated. The means of transmission was thought to be from bats-topigs and subsequently pigs-to-human. Since 2001, almost yearly outbreak of Nipah encephalitis has been reported from Bangladesh and West Bengal, India. These outbreaks were characterized by direct bats-to-human, and human-to-human spread of infection. Nipah virus shares many similar characteristics to Hendra virus, first isolated in an outbreak of respiratory illness involving horses in Australia in 1994. Because of their homology, a new genus called Henipavirus (Hendra + Nipah) was introduced. Henipavirus infection is a human disease manifesting most often as acute encephalitis (which may be relapsing or late-onset) or pneumonia, with a high mortality rate. Pteropus bats act as reservoir for the virus, which subsequently lead to human spread. Transmission may be from consumption of food contaminated by bats secretion, contact with infected animals, or human-to-human spread. With wide geographical distribution of Pteropus bats, Henipavirus infection has become an important emerging human infection with worldwide implication.
Corroborating evidence related to the role of aberrations on one-carbon metabolism (OCM) genes has been inconsistent. We evaluated the association between polymorphisms in 12 single nucleotide polymorphisms (SNPs) in 8 OCM genes (CBS, FPGS, FTHFD, MTRR, SHMT1, SLC19A1, TCN1, and TYMS), and non-Hodgkin lymphoma (NHL) risk in a multi-ethnic population which includes Malay, Chinese and Indian ethnic subgroups. Cases (N = 372) and controls (N = 722) were genotyped using the Sequenom MassARRAY platform. Our results of the pooled subjects showed a significantly enhanced NHL risk for CBS Ex9 + 33C > T (T versus C: OR 1.55, 95% CI 1.22-1.96, P = 0.0003), CBS Ex18-319G > A (A versus G: OR 1.15, 95% CI 1.14-1.83; P = 0.002), SHMT1 Ex12 + 236 T > C (T versus C: OR 1.44, 95% CI 1.15-1.81, P = 0.002), and TYMS Ex8 + 157C > T (T versus C: OR 1.29, 95% CI 1.06-1.57, P = 0.01). Haplotype analysis for CBS SNPs showed a significantly decreased risk of NHL in subjects with haplotype CG (OR 0.69, 95% CI 0.56-0.86, P = <0.001). The GG haplotype for the FTHFD SNPs showed a significant increased risk of NHL (OR 1.40, 95% CI 1.12-1.76, P = 0.002). For the TYMS gene, haplotype CAT at TYMS (OR 0.67, 95% CI 0.49-0.90, P = 0.007) was associated with decreased risk of NHL, while haplotype TAC (OR 1.29, 95% CI 1.05-1.58, P = 0.01) was found to confer increased risk of NHL. Our study suggests that variation in several OCM genes (CBS, FTHFD, SHMT1, TCN1, and TYMS) may influence susceptibility to NHL.
Matched MeSH terms: Genetic Predisposition to Disease
To describe the clinical findings, diagnostics, and differential diagnosis in a patient with retinopathy in acute systemic Epstein-Barr virus (EBV) infection.
Basaloid squamous cell carcinoma (BSCC) is a rare subtype of squamous cell carcinoma. To date, only 95 cases of sinonasal BSCC have been reported in the English-language literature, and they account for 5% of all cases of head and neck BSCC. We describe what we believe is only the second reported case of a sinonasal tract BSCC that metastasized to the liver. The patient was a 36-year-old woman who presented with right-sided nasal obstruction and a foul-smelling discharge. Clinical examination and imaging identified a large, lobulated, enhancing mass in the right nasal cavity. Following excision of the mass, the patient was scheduled for radiotherapy. However, before it could be administered, follow-up imaging detected a metastasis to the liver and lung, and the patient was switched to chemotherapy. Initially, she responded well clinically, but at 5 months postoperatively, a follow-up CT showed an increasing metastatic presence in the liver and bone. The patient died of her disease 1 year after surgery.
Matched MeSH terms: Glycogen Storage Disease Type VI
This article is a traditional literature review on caries levels in aggressive periodontitis. Aggressive periodontitis generally affects systemically healthy individuals aged <30 years (older individuals can also be affected) and is characterized by a young age of onset, rapid rate of disease progression, and familial aggregation of cases. Dental caries is caused by the dissolution of enamel by acid-producing bacteria present in the plaque biofilm, especially when the biofilm reaches critical mass due to improper oral hygiene. The association between caries level and aggressive periodontitis has long been debated. Initial research indicated that caries levels were high in patients with aggressive periodontitis, but high-quality studies have consistently shown that caries and aggressive periodontitis are inversely related. A recent in vitro study showed that Streptococcus mutans was killed more readily in the saliva of patients with aggressive periodontitis and Aggregatibacter actinomycetemcomitans positivity than in patients with A. actinomycetemcomitans negativity. Other mechanisms possibly explaining the inverse relationship between caries and aggressive periodontitis in cases of Down's syndrome are also discussed in this literature review. The usefulness of caries level in the diagnosis of aggressive periodontitis in developing countries such as India, where the disease is diagnosed primarily on the basis of clinical and radiographic features and familial history is also discussed.
Rutoside (rutin; quercetin rutinoside) is a glycoside found in various plant products, including apples, citrus fruits and cranberries. Hydroxyethylrutosides (HR) are semisynthetic derivatives sold as standardized products for the treatment of chronic venous insufficiency (CVI). Commercially available products include Relvène(®) (France), Venoruton(®) (Switzerland) and Paroven(®) (United Kingdom). However, the evidence for their efficacy is inconclusive. The aim of this systematic review was to evaluate the evidence of efficacy and tolerability of hydroxyethylrutosides for CVI.
UI is a worldwide chronic condition among postmenopausal women. Little is known about the meaning of lived experiences of urinary incontinence of these women's viewpoints in their context.
AIM: Prolonged depression during the post-partum period is associated with maternal and infant mortality and morbidity. Less attention has been given to factors that predict the persistence of depression beyond the first 3 months post-partum.
METHODS: From a longitudinal cohort of 2279 women who attended Mazandaran's primary health centres in 2009, 478 women with an Edinburgh Postnatal Depression Scale (EPDS) score of 12 or greater in the third trimester of pregnancy were recruited. Persistently depressed women (depressed at all three occasions: during pregnancy, and at 2 and 12 weeks post-partum) were compared with those without depression to determine demographic, cultural, obstetric and biopsychosocial predictors for persistence of depression. Data were analysed using chi-square test, t-test and logistic regression models.
RESULTS: The stability of depression was found in 193 (46.2 %) of 418 depressed cases who were followed up over the study period. Of those mothers who scored more than the threshold of 12 during the third trimester of pregnancy, 277 (66.3%) and 221 (52.9%) had high EPDS at 2 and 12 weeks post-partum. Psychological distress (based upon the General Health Questionnaire), low maternal parental self-efficacy (based upon the Parental Expectation Survey) and perceived social isolation (based upon the Network Orientation Scale) were independent predictors of persistent depression.
CONCLUSION: Fewer depressed mothers in this study were found to recover during the first 3 months after giving birth. Psychosocial factors predicted sustained depression from pregnancy to 3 months post-partum. The findings highlight the significance of support in enhancing maternal mental health.
Chikungunya virus (CHIKV) is an alphavirus of the Togaviridae family that causes chronic and incapacitating arthralgia in human populations. Since its discovery in 1952, CHIKV was responsible for sporadic and infrequent outbreaks. However, since 2005, global Chikungunya outbreaks have occurred, inducing some fatalities and associated with severe and chronic morbidity. Chikungunya is thus considered as an important re-emerging public health problem in both tropical and temperate countries, where the distribution of the Aedes mosquito vectors continues to expand. This review highlights the most recent advances in our knowledge and understanding of the epidemiology, biology, treatment and vaccination strategies of CHIKV.
Pediatric movement disorders are still a diagnostic challenge, as many patients remain without a (genetic) diagnosis. Magnetic resonance imaging (MRI) pattern recognition can lead to the diagnosis. MEGDEL syndrome (3-MethylGlutaconic aciduria, Deafness, Encephalopathy, Leigh-like syndrome MIM #614739) is a clinically and biochemically highly distinctive dystonia deafness syndrome accompanied by 3-methylglutaconic aciduria, severe developmental delay, and progressive spasticity. Mutations are found in SERAC1, encoding a phosphatidylglycerol remodeling enzyme essential for both mitochondrial function and intracellular cholesterol trafficking. Based on the homogenous phenotype, we hypothesized an accordingly characteristic MRI pattern. A total of 43 complete MRI studies of 30 patients were systematically reevaluated. All patients presented a distinctive brain MRI pattern with five characteristic disease stages affecting the basal ganglia, especially the putamen. In stage 1, T2 signal changes of the pallidum are present. In stage 2, swelling of the putamen and caudate nucleus is seen. The dorsal putamen contains an "eye" that shows no signal alteration and (thus) seems to be spared during this stage of the disease. It later increases, reflecting progressive putaminal involvement. This "eye" was found in all patients with MEGDEL syndrome during a specific age range, and has not been reported in other disorders, making it pathognomonic for MEDGEL and allowing diagnosis based on MRI findings.
To determine how tuberculosis (TB) treatment affects the health-related quality of life (HRQL) of patients with pulmonary TB and to identify the predictors of favourable TB treatment outcomes in Baghdad, Iraq.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Evidence suggests that miRNAs play an important role in progression, recurrence, metastasis and postoperative survival of HNSCC. Studies have investigated the utility of miRNAs as diagnostic/prognostic tools and as potential therapeutic targets and biomarkers that may improve the management and outcomes of HNSCC. The aim of this article is to review the current literature on aberrant expression profiles of miRNAs in biopsy samples of HNSCC and their role in cancer development, metastasis, prognosis and survival of these patients. This review gives an overview that miRNAs deregulation play major role in the development of HNSCC. They offer the potential to be used as biomarkers or novel therapeutic targets. Future research is required to test their use in both of these fields.
To describe 2 cases of spontaneous corneal clearing after Descemetorhexis: 1 after iatrogenic trauma (Case 1) and 1 as an intentional surgical intervention for Fuchs endothelial dystrophy (Case 2).
Animal models, particularly rodents, are major translational models for evaluating novel anticancer therapeutics. In this review, different types of nanostructure-based photosensitizers that have advanced into the in vivo evaluation stage for the photodynamic therapy (PDT) of cancer are described. This article focuses on the in vivo efficacies of the nanostructures as delivery agents and as energy transducers for photosensitizers in animal models. These materials are useful in overcoming solubility issues, lack of tumor specificity, and access to tumors deep in healthy tissue. At the end of this article, the opportunities made possible by these multiplexed nanostructure-based systems are summarized, as well as the considerable challenges associated with obtaining regulatory approval for such materials. The following questions are also addressed: (1) Is there a pressing demand for more nanoparticle materials? (2) What is the prognosis for regulatory approval of nanoparticles to be used in the clinic?
BACKGROUND: Environmental enrichment (EE) exposure is known to influence the structural changes in the neuronal network of hippocampus. In the present study, we evaluated the effects of EE exposure on the streptozotocin (STZ)-induced diabetic and stressed rat hippocampus.
METHODS: Male albino rats of Wistar strain (4-5 weeks old) were grouped into normal control (NC), vehicle control (VC), diabetes (DI), diabetes + stress (DI + S), diabetes + EE (DI + E), and diabetes + stress + EE (DI + S + E) groups (n = 8 in each group). Rats were exposed to stress and EE after inducing diabetes with STZ (40 mg/kg). Rats were sacrificed on Day 30 and brain sections were processed for cresyl violet staining to quantify the number of surviving neurons in the CA1, CA3, and dentate hilus (DH) regions of hippocampus.
RESULTS: A significant (p < 0.001) decrease in the number of survived neurons was noticed in DI (CA1, 34.06 ± 3.2; CA3, 36.1 ± 3.62; DH, 9.83 ± 2.02) as well as DI + S (CA1, 14.03 ± 3.12; CA3, 20.27 ± 4.09; DH, 6.4 ± 1.21) group rats compared to NC rats (CA1, 53.64 ± 2.96; CA3, 62.1 ± 3.34; DH, 21.11 ± 1.03). A significant (p < 0.001) increase in the number of survived neurons was observed in DI + E (CA1, 42.3 ± 3.66; CA3, 46.73 ± 4.74; DH, 17.03 ± 2.19) and DI + S + E (CA1, 29.69 ± 4.47; CA3, 36.73 ± 3.89; DH, 12.23 ± 2.36) group rats compared to DI and DI + S groups, respectively.
CONCLUSIONS: EE exposure significantly reduced the amount of neuronal damage caused by complications of diabetes and stress to the neurons of hippocampus.
The current study evaluates the impact of high fructose feeding in rat model of gentamicin induced nephrotoxicity. Sprague-Dawley rats weighing 180-200 g were randomized into four groups; (C) received standard rodents chow with free access to ad libitum drinking water for 8 weeks and was considered as control, (F) received standard rodents chow with free access to drinking water supplemented with 20% (W/V) fructose for the same abovementioned period, (FG) was fed as group F and was given 80 mg/kg (body weight)/day gentamicin sulphate intraperitoneally during the last 20 days of the feeding period, and (G) was given gentamicin as above and fed as group C. Renal function was assessed at the end of the treatment period through measuring serum creatinine, uric acid and albumin, creatinine clearance, absolute and fractional excretion of both sodium and potassium, twenty-four-hour urinary excretion of albumin, and renal histology. For metabolic syndrome assessment, fasting plasma glucose and insulin were measured and oral glucose tolerance test was performed throughout the treatment period. Results showed that gentamicin enhances progression of fructose induced metabolic syndrome. On the other hand, fructose pretreatment before gentamicin injection produced a comparable degree of renal dysfunction to those which were given fructose-free water but the picture of nephrotoxicity was somewhat altered as it was characterized by higher extent of glomerular congestion and protein urea. Overall, more vigilance is required when nephrotoxic drugs are prescribed for patients with fructose induced metabolic syndrome.