Diffusion tensor imaging analysis of rheumatoid arthritis patients with neuropsychiatric features to determine the alteration of white matter integrity due to vascular events

Clinical Rheumatology - The pathophysiology of neuropsychiatric manifestations in rheumatoid arthritis is not well known. The magnetic resonance imaging of the brain in rheumatoid arthritis...     

Primary drug resistance in South Africa: data from 10 years of surveys

HIV-1 transmitted drug resistance (TDR) could reverse the gains of antiretroviral rollout. To ensure that current first-line therapies remain effective, TDR levels in recently infected treatment-naive patients need to be monitored. A literature review and data mining exercise was carried out to determine the temporal trends in TDR in South Africa. In addition, 72 sequences from seroconvertors identified from Africa Centre's 2010 HIV surveillance round were also examined for TDR. Publicly available data on TDR were retrieved from GenBank, curated in RegaDB, and analyzed using the Calibrated Population Resistance Program. There was no evidence of TDR from the 2010 rural KwaZulu Natal samples. Ten datasets with a total of 1618 sequences collected between 2000 and 2010 were pooled to provide a temporal analysis of TDR. The year with the highest TDR rate was 2002 [6.67%, 95% confidence interval (CI): 3.09-13.79%; n=6/90]. After 2002, TDR levels returned to <5% (WHO low-level threshold) and showed no statistically significant increase in the interval between 2002 and 2010. The most common mutations were associated with NNRTI resistance, K103N, followed by Y181C and Y188C/L. Five sequences had multiple resistance mutations associated with NNRTI resistance. There is no evidence of TDR in rural KwaZulu-Natal. TDR levels in South Africa have remained low following a downward trend since 2003. Continuous vigilance in monitoring of TDR is needed as more patients are initiated and maintained onto antiretroviral therapy.     

Accuracy of four dental age estimation methods in determining the legal age threshold of 18 years among South Indian adolescents and young

The aim of this study was to compare the accuracy, specificity and sensitivity of four commonly used methods of dental age estimation in a sample of south Indian adolescents and young adults aged between 14 and 30 years, with an age threshold of 18 years, using receiver operating characteristic curves (ROC) and the area under the curve (AUC). A total of 1070 orthopantomograms (535 males and 535 females) of adolescents and young adults of south Indian origin were collected retrospectively and interpreted. The effectiveness of each method was evaluated by using sensitivity (Se), specificity (Sp), likelihood ratios (LR+ and LR-) and AUC. Among all methods, I3M< 0.08 resulted in better values of AUC, Se and Sp which were 0.950, 91.5%, 97.8% and 0.950, 88.5% and 98.6% in males and females, respectively. For “stage H” of Demirjian’s system, the AUC, Se and Sp were 0.940, 84.9%, 97.7% and 0.930, 79.9% and 98.5% in males and females, respectively. The use of the Olze et al “stage 1 (or higher)” root pulp visibility and “stage D” of third molar eruption were not recommended in the studied population due to the greater percentage of third molars with incomplete mineralization in younger age groups and impaction. Taking into account the values of Se, Sp, both positive and negative LRs, we recommend the use of the cut-off value of I3M< 0.08 to discriminate adults and minors in south Indian adolescents and young adults.     

Waste to white light: a sustainable method for converting biohazardous waste to broadband white LEDs

The Covid-19 pandemic has generated a lot of non-degradable biohazardous plastic waste across the globe in the form of disposable surgical and N95 masks, gloves, face shields, syringes, bottles and plastic storage containers. In the present work we address this problem by recycling plastic waste to single system white light emitting carbon dots (CDs) using a pyrolytic method. The synthesized CDs have been embedded into a transparent polymer to form a carbon dot phosphor. This CD phosphor has a broad emission bandwidth of 205 nm and is stable against photo degradation for about a year. A white LED with CRI ∼70 and CIE co-ordinates of (0.25, 0.32) using the fabricated CD phosphor is reported. Further our phosphor is scalable and is environmentally sustainable, and will find wide application in next generation artificial lighting systems.

Recycling of plastic waste to white LEDs.     

Mutation and Methylation Analysis of the Chromodomain-Helicase-DNA Binding 5 Gene in Ovarian Cancer

Chromodomain, helicase, DNA binding 5 (CHD5) is a member of a subclass of the chromatin remodeling Swi/Snf proteins and has recently been proposed as a tumor suppressor in a diverse range of human cancers. We analyzed all 41 coding exons of CHD5 for somatic mutations in 123 primary ovarian cancers as well as 60 primary breast cancers using high-resolution melt analysis. We also examined methylation of the CHD5 promoter in 48 ovarian cancer samples by methylation-specific single-stranded conformation polymorphism and bisulfite sequencing. In contrast to previous studies, no mutations were identified in the breast cancers, but somatic heterozygous missense mutations were identified in 3 of 123 ovarian cancers. We identified promoter methylation in 3 of 45 samples with normal CHD5 and in 2 of 3 samples with CHD5 mutation, suggesting these tumors may have biallelic inactivation of CHD5. Hemizygous copy number loss at CHD5 occurred in 6 of 85 samples as assessed by single nucleotide polymorphism array. Tumors with CHD5 mutation or methylation were more likely to have mutation of KRAS or BRAF (P = .04). The aggregate frequency of CHD5 haploinsufficiency or inactivation is 16.2% in ovarian cancer. Thus, CHD5 may play a role as a tumor suppressor gene in ovarian cancer; however, it is likely that there is another target of the frequent copy number neutral loss of heterozygosity observed at 1p36.     

Tat-induced deregulation of neuronal differentiation and survival by nerve growth factor pathway

HIV-1 enters the brain at the early stage of infection and resides primarily in a limited number of macrophages/microglia and astrocytes. Infection of these cells, however, may not explain the massive neuronal pathology which is seen in AIDS-associated dementia, suggesting a role for factors released from HIV-1 infected cells that trigger a cascade of events leading to neurodegeneration. Our results indicate that Tat, the potent regulatory protein of HIV-1 which is secreted by infected cells and can affect neighboring uninfected cells by transcellular means, can influence multiple biological events that lead to neuronal injury. These findings demonstrate that treatment of neuronal cells with Tat affects MAPK/ERK1/2 activity, the downstream central component of the nerve growth factor (NGF) signaling pathway. Furthermore, our data indicate that treatment of cells with Tat severely decreases expression of p35, a neuron-specific activator of cdk5, a cyclin dependent kinase that phosphorylates several neuronal proteins including neurofilament, and plays an important role in neuronal differentiation and survival. In parallel, Tat can bind to the cellular protein, Puralpha, which associates with cdk5. Further, results from Puralpha knockout animals revealed a decrease in p35 activity, pointing to the importance of Puralpha association with cdk5 in the activity of cdk5:p35 complex. These data demonstrate the cooperativity between HIV-1 Tat and the Puralpha in deregulation of the NGF signal transduction pathway in neuronal cells.     

Application of the woodchuck animal model for the treatment of hepatitis B virus-induced liver cancer

This review describes woodchucks chronically infected with the woodchuck hepatitis virus (WHV) as an animal model for hepatocarcinogenesis and treatment of primary liver cancer or hepatocellular carcinoma (HCC) induced by the hepatitis B virus (HBV). Since laboratory animal models susceptible to HBV infection are limited, woodchucks experimentally infected with WHV, a hepatitis virus closely related to HBV, are increasingly used to enhance our understanding of virus-host interactions, immune response, and liver disease progression. A correlation of severe liver pathogenesis with high-level viral replication and deficient antiviral immunity has been established, which are present during chronic infection after WHV inoculation of neonatal woodchucks for modeling vertical HBV transmission in humans. HCC in chronic carrier woodchucks develops 17 to 36 mo after neonatal WHV infection and involves liver tumors that are comparable in size, morphology, and molecular gene signature to those of HBV-infected patients. Accordingly, woodchucks with WHV-induced liver tumors have been used for the improvement of imaging and ablation techniques of human HCC. In addition, drug efficacy studies in woodchucks with chronic WHV infection have revealed that prolonged treatment with nucleos(t)ide analogs, alone or in combination with other compounds, minimizes the risk of liver disease progression to HCC. More recently, woodchucks have been utilized in the delineation of mechanisms involved in innate and adaptive immune responses against WHV during acute, self-limited and chronic infections. Therapeutic interventions based on modulating the deficient host antiviral immunity have been explored in woodchucks for inducing functional cure in HBV-infected patients and for reducing or even delaying associated liver disease sequelae, including the onset of HCC. Therefore, woodchucks with chronic WHV infection constitute a well-characterized, fully immunocompetent animal model for HBV-induced liver cancer and for preclinical evaluation of the safety and efficacy of new modalities, which are based on chemo, gene, and immune therapy, for the prevention and treatment of HCC in patients for which current treatment options are dismal.