Unusual overlap of systemic sclerosis with Takayasu arteritis.

Overlap syndromes are diseases that meet the criteria of two or more rheumatic diseases. In this case report, a woman in her 20s presented with a constellation of symptoms, including skin thickening, Raynaud's phenomenon, hypertension, absent pulse in both lower limbs with bilateral renal artery bruit. The antinuclear antibody profile revealed Scl-70 positivity. CT thorax identified early interstitial lung disease, and nailfold capillaroscopy showed severe capillary loss. CT angiogram features were suggestive of Takayasu arteritis. Notably, there have been only four documented cases of systemic sclerosis coexisting with Takayasu arteritis, highlighting the rarity of this overlap syndrome. The diagnosis of overlap syndrome was made after a thorough history recording and clinical examination. In the presence of bilateral renal artery stenosis, managing the scleroderma renal crisis may be challenging . This patient received treatment with mycophenolate mofetil and oral corticosteroids, aiming to address both systemic sclerosis and Takayasu arteritis effectively.

Haemorrhage diagnosis in colour fundus images using a fast-convolutional neural network based on a modified U-Net.

Retinal haemorrhage stands as an early indicator of diabetic retinopathy, necessitating accurate detection for timely diagnosis. Addressing this need, this study proposes an enhanced machine-based diagnostic test for diabetic retinopathy through an updated UNet framework, adept at scrutinizing fundus images for signs of retinal haemorrhages. The customized UNet underwent GPU training using the IDRiD database, validated against the publicly available DIARETDB1 and IDRiD datasets. Emphasizing the complexity of segmentation, the study employed preprocessing techniques, augmenting image quality and data integrity. Subsequently, the trained neural network showcased a remarkable performance boost, accurately identifying haemorrhage regions with 80% sensitivity, 99.6% specificity, and 98.6% accuracy. The experimental findings solidify the network's reliability, showcasing potential to alleviate ophthalmologists' workload significantly. Notably, achieving an Intersection over Union (IoU) of 76.61% and a Dice coefficient of 86.51% underscores the system's competence. The study's outcomes signify substantial enhancements in diagnosing critical diabetic retinal conditions, promising profound improvements in diagnostic accuracy and efficiency, thereby marking a significant advancement in automated retinal haemorrhage detection for diabetic retinopathy.

Synchronization of the neurons coupled with sequential developing electrical and chemical synapses.

There is some evidence representing the sequential formation and elimination of electrical and chemical synapses in particular brain regions. Relying on this feature, this paper presents a purely mathematical modeling study on the synchronization among neurons connected by transient electrical synapses transformed to chemical synapses over time. This deletion and development of synapses are considered consecutive. The results represent that the transient synapses lead to burst synchronization of the neurons while the neurons are resting when both synapses exist constantly. The period of the transitions and also the time of presence of electrical synapses to chemical ones are effective on the synchronization. The larger synchronization error is obtained by increasing the transition period and the time of chemical synapses' existence.

Clinical Outcomes among Asymptomatic or Mildly Symptomatic COVID-19 Patients in an Isolation Facility in Chennai, India.

Globally, India has reported the third highest number of COVID-19 cases. Chennai, the capital of Tamil Nadu state, witnessed a huge surge in COVID-19 cases, resulting in the establishment of isolation facilities named COVID Care Center (CCC). In our study, we describe the demographic, epidemiological, and clinical characteristics; clinical progression; and outcome of 1,263 asymptomatic/mildly symptomatic COVID-19 patients isolated in one such CCC between May 4, 2020 and June 4, 2020. Around 10.5% of the patients progressed to moderate/severe illness, requiring referral for tertiary care, and three died. Nearly half (49.5%) of the patients were symptomatic at the time of admission, 2.2% of the patients developed symptoms post-testing, and 48.5% patients remained asymptomatic during the entire course of illness. Most common presenting symptoms were fever (69.9%) and cough (29.6%), followed by generalized body pain, breathlessness, and loss of smell and taste. On multivariate analysis, we identified that symptomatic patients with comorbidities and higher neutrophil-lymphocyte ratio (NLR) were more likely to progress to severe illness warranting referral for tertiary care. COVID Care Center ensured case isolation and monitoring of asymptomatic/mildly symptomatic patients, thereby providing hospital beds for sick patients. COVID Care Center isolation facilities are safe alternatives for medical institutions to isolate and monitor COVID-19 patients. Older symptomatic patients with comorbidities and a high NLR admitted in an isolation facility must be frequently monitored for prompt identification of clinical progression and referral to higher center for advanced medical care.

The Borrelia burgdorferi flaB promoter has an extended -10 element and includes a T-rich -35/-10 spacer sequence that is essential for optimal activity.

In this study, we investigated the functional elements of the flaB promoter of Borrelia burgdorferi. Promoter function was examined in a high-passage variant of strain JD1 using a set of 5' deletions and mutations within the flaB promoter. Expression from the modified flaB promoters was assayed using the gene for green fluorescent protein (gfp) as a reporter. Although the -35 element of the promoter stimulated promoter activity, its disruption did not negate expression. Sequences upstream of the -35 had no effect on expression. The -35/-10 spacer region composed of a T-rich sequence was critical for optimal promoter function. Surprisingly, a cytosine at the -13 site was found to be more favorable for transcription compared with a guanosine at the same site. Based on these results and other characteristics, we propose that the B. burgdorferi flaB promoter is an example of an extended -10 promoter. Further, the T-rich spacer is a key element of the flaB promoter that contributes to the abundance of the flagellar core protein in Borrelia species.

Interaction of the Lyme disease spirochete Borrelia burgdorferi with brain parenchyma elicits inflammatory mediators from glial cells as well as glial and neuronal apoptosis.

Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi, often manifests by causing neurocognitive deficits. As a possible mechanism for Lyme neuroborreliosis, we hypothesized that B. burgdorferi induces the production of inflammatory mediators in the central nervous system with concomitant neuronal and/or glial apoptosis. To test our hypothesis, we constructed an ex vivo model that consisted of freshly collected slices from brain cortex of a rhesus macaque and allowed live B. burgdorferi to penetrate the tissue. Numerous transcripts of genes that regulate inflammation as well as oligodendrocyte and neuronal apoptosis were significantly altered as assessed by DNA microarray analysis. Transcription level increases of 7.43-fold (P = 0.005) for the cytokine tumor necrosis factor-alpha and 2.31-fold (P = 0.016) for the chemokine interleukin (IL)-8 were also detected by real-time-polymerase chain reaction array analysis. The immune mediators IL-6, IL-8, IL-1beta, COX-2, and CXCL13 were visualized in glial cells in situ by immunofluorescence staining and confocal microscopy. Concomitantly, significant proportions of both oligodendrocytes and neurons undergoing apoptosis were present in spirochete-stimulated tissues. IL-6 production by astrocytes in addition to oligodendrocyte apoptosis were also detected, albeit at lower levels, in rhesus macaques that had received in vivo intraparenchymal stereotaxic inoculations of live B. burgdorferi. These results provide proof of concept for our hypothesis that B. burgdorferi produces inflammatory mediators in the central nervous system, accompanied by glial and neuronal apoptosis.

Analysis of the determinants of bba64 (P35) gene expression in Borrelia burgdorferi using a gfp reporter.

The bba64 (P35) gene of Borrelia burgdorferi, the agent of Lyme disease, encodes a surface-exposed lipoprotein. The expression of bba64 in vitro is tightly regulated and dependent on several environmental factors. In nature, its expression is induced in the tick vector during feeding and maintained during infection of the vertebrate host. The pattern of expression of bba64 suggests that it imparts a critical function to the pathogen. A previous study has shown that the expression of bba64 is down-regulated in the absence of RpoS, suggesting that the alternative sigma factor may be involved in its expression. A DNA-binding protein has also been shown to specifically recognize a sequence in the 5' regulatory region of the gene. Therefore, the contribution of these putative determinants to the differential expression of bba64 was investigated. The role of RpoS was critically evaluated by genetic complementation of the rpoS mutant using a chromosomally targeted copy of the wild-type gene. The results confirm that RpoS is indeed required for the expression of bba64. The role of the upstream DNA-binding site was examined using bba64 promoter-gfp transcriptional fusions in a shuttle vector. The DNA-binding site was studied by targeting mutations to an inverted repeat sequence (IRS), the most prominent feature within the binding site, as well as by deletion of the entire sequence upstream of the basal promoter. Quantitative assessment of gene expression demonstrated that neither the IRS nor the sequence upstream of the promoter was essential for expression. Moreover, the expression of the reporter (GFP) appeared to remain RpoS-dependent in all cases, based on the co-expression of GFP and OspC in a subpopulation of spirochaetes and the selective expression of GFP in the stationary phase. Collectively, the data indicate that RpoS is the sole determinant of differential bba64 expression in cultured spirochaetes.

Expression of the bmpB gene of Borrelia burgdorferi is modulated by two distinct transcription termination events.

bmp gene family 36 of Borrelia burgdorferi, the agent of Lyme disease, comprises four paralogs: bmpA, bmpB, bmpC, and bmpD. The bmpA and bmpB genes constitute an operon. All four genes have been found to be transcribed in cultured spirochetes. Expression from the bmpAB operon results in three distinct transcripts of 1.1, 1.6, and 2.4 kb, and the relative expression of bmpA mRNA is three- to fourfold greater than that of bmpB mRNA. However, thus far only expression of the BmpA protein has been demonstrated. Therefore, in this study we characterized the origins of the three transcripts and compared the relative expression of the BmpA and BmpB proteins. Northern blotting revealed that the three distinct transcripts originated from a single promoter located upstream of bmpA but terminated either 3' to the bmpA (1.1-kb RNA) or bmpB (2.4-kb RNA) gene or, most unusually, within the bmpB gene (1.6-kb RNA). Termination within the bmpB gene was associated with a functional Rho-independent transcription terminator. At the protein level, we also observed a 4.3-fold greater abundance of BmpA compared to that of BmpB. These studies identify a transcription termination mechanism in B. burgdorferi resulting in the disparate expression of the two genes of the bmpAB operon.

Survival strategies of Borrelia burgdorferi, the etiologic agent of Lyme disease.

To fight, flee or hide are the imperatives of long-term survival by an infectious microbe. Active immune suppression, induction of immune tolerance, phase and antigenic variation, intracellular seclusion, and incursion into immune privileged sites are examples of survival strategies of persistent pathogens. Here we critically review the supporting evidence for possible stratagems utilized by Borrelia burgdorferi, the spirochete that causes Lyme disease, to persist in the mammalian host.