The role of advanced glycation end products in patogenesis of diabetic nephropathy

Diabetes mellitus (DM) and chronic kidney disease are the diseases that have exceeded epidemic thresholds in terms of prevalence all over the world. That made it possible to classify them as non-communicable epidemics of the XXI century. Diabetic nephropathy (DN) is implicated with high levels of disablement and mortality. Advanced glycation end products (AGE) play a key role in the progression of DN. Increased formation of AGE occurs due to hyperglycemia under the conditions of diabetes. Moreover, there are additional factors in DN that increase the elaboration of AGE, such as high levels of oxidative stress and decreased renal clearance which slows down the AGE excretion. Both immediate effects of AGE and interaction of AGE with its cell-bound receptor (RAGE) result in a сascade of events that lead to further progression of DN. Thus, the research of the new therapeutic approaches targeted on the AGE-RAGE system is of great interest to slow progression of DN and improve the prognosis.

What Should the Earliest Age be for Clinical Trials of Corneal Crosslinking for Keratoconus?

Keratoconus is often diagnosed in the second or third decade of life, with a younger mean age at diagnosis more likely among those of Middle Eastern and Asian descent (1). Studies have shown that patients with severe forms of keratoconus present at a younger age (usually in the second decade of life), and these patients have more rapid progression of disease (2-6). Pediatric keratoconus is generally attributed to disease manifesting in those less than 18 years of age, however studies that looked at progression in different age groups used varying age criteria. Léoni-Mesplié et al. found that at diagnosis, keratoconus is often more advanced in children (defined as ?15 years) than in adults (?27 years), while Tuft et al. found that patients ?18 years at time of diagnosis progressed to transplantation faster than patients >18 years of age (5-6). McMahon et al. found that the rate of change in corneal curvature was substantially greater in patients <20 years old and slowed down dramatically in those ?20 years old (7). Until the late 1990s when corneal crosslinking (CXL) was initially developed (8) there were no effective means to halt or slow progression, and keratoplasty was the definitive treatment. There was some assertion in the literature that certain contact lenses and intracorneal rings may help slow progression, but no definitive evidence was ever presented (9-11). Ring segments have been shown to improve best corrected visual acuity as well as contact lens tolerance, but do not alter progression of disease (9, 11).

Orthogonality-Constrained CNMF-Based Noise Reduction with Reduced Degradation of Biological Sound

The number of deaths due to cardiovascular and respiratory diseases is increasing annually. Cardiovascular diseases with high mortality rates, such as strokes, are frequently caused by atrial fibrillation without subjective symptoms. Chronic obstructive pulmonary disease is another condition in which early detection is difficult owing to the slow progression of the disease. Hence, a device that enables the early diagnosis of both diseases is necessary. In our previous study, a sensor for monitoring biological sounds such as vascular and respiratory sounds was developed and a noise reduction method based on semi-supervised convolutive non-negative matrix factorization (SCNMF) was proposed for the noisy environments of users. However, SCNMF attenuated part of the biological sound in addition to the noise. Therefore, this paper proposes a novel noise reduction method that achieves less distortion by imposing orthogonality constraints on the SCNMF. The effectiveness of the proposed method was verified experimentally using the biological sounds of 21 subjects. The experimental results showed an average improvement of 1.4 dB in the signal-to-noise ratio and 2.1 dB in the signal-to-distortion ratio over the conventional method. These results demonstrate the capability of the proposed approach to measure biological sounds even in noisy environments.

Radiation Treatment for Inoperable Local Relapse of Parathyroid Carcinoma With Symptomatic Hypercalcemia: A Case Report

BackgroundParathyroid carcinoma (PC) is an extremely rare malignancy, characterized by slow progression, frequent recurrences and difficult-to-control hypercalcemia which is typically the main contributor to the morbidity and mortality of these patients. Patients often undergo repeated surgical resections, whether or not in combination with adjuvant radiation treatment. The role of radiation therapy within the symptomatic treatment of PC currently remains unclear.Case descriptionWe describe a 30-year-old male patient with an inoperable local relapse of PC and secondary symptomatic hypercalcemia, maximally pharmacologically treated. After a local radiation treatment to a total dose of 70 Gray in 35 fractions serum calcium and parathyroid hormone (PTH) levels decreased, accompanied by improvement of the severe gastro-intestinal disturbances.ConclusionFor patients with inoperable symptomatic PC despite maximal medical treatment who are in a good overall condition, radiation treatment can be considered in well-defined cases to decrease symptoms and improve quality of life.

Individual Oligogenic Background in p.D91A-SOD1 Amyotrophic Lateral Sclerosis Patients

The p.D91A is one of the most common ALS-causing SOD1 mutations and is known to be either recessive or dominant. The homozygous phenotype is characterized by prolonged survival and slow progression of disease, whereas the affected heterozygous phenotypes can vary. To date, no genetic protective factors located close to SOD1 have been associated with the mild progressive homozygous phenotype. Using Next Generation Sequencing (NGS), we characterized a small cohort of sporadic and familial p.D91A-SOD1 heterozygous (n = 2) or homozygous (n = 5) ALS patients, to reveal any additional contributing variant in 39 ALS-related genes. We detected unique sets of non-synonymous variants, four of which were of uncertain significance and several in untranslated regions of ALS-related genes. Our results supported an individual oligogenic background underlying both sporadic and familial p.D91A cases irrespective of their p.D91A mutant alleles. We suggest that a comprehensive genomic view of p.D91A-SOD1 ALS patients may be useful in identifying emerging variants and improving disease diagnosis as well as guiding precision medicine.

Collagen 1a1 Expression by Airway Macrophages Increases In Fibrotic ILDs and Is Associated With FVC Decline and Increased Mortality

Within the Interstitial Lung Diseases (ILD), patients with idiopathic pulmonary fibrosis (IPF) and a subset of those with non-IPF fibrotic ILD have a distinct clinical phenotype of progression despite management. This group of patients has been collectively termed the progressive fibrotic phenotype (PFP). Their early recognition may facilitate access to antifibrotic therapies to prevent or slow progression. Macrophages/monocytes within the lung orchestrate the progression and maintenance of fibrosis. A novel role for monocyte-derived macrophages during tissue damage and wound healing is the expression of collagens. We examined Collagen 1a1 expression in airway macrophages from ILD patients at diagnosis. COL1A1 mRNA levels from BAL cells were elevated in IPF and Non-IPF patients. The presence of a UIP pattern and a subsequent progressive phenotype were significantly associated with the higher BAL COL1A1 levels. In Non-IPF patients, higher COL1A1 levels were associated with a more than twofold increase in mortality. The intracellular localisation of COL1A1 in airway macrophages was demonstrated by confocal microscopy in CD45 and CD163 co-staining assays. Additionally, airway macrophages co-expressed COL1A1 with the profibrotic SPP1 gene product osteopontin. The levels of SPP1 mRNA and OPN in the BAL were significantly higher in IPF and Non-IPF patients relative to healthy. Our results suggest that profibrotic airway macrophages are increased in the BAL of patients with IPF and other ILDs and co-express COL1A1 and OPN. Importantly, COL1A1 expression by pro-fibrotic airway macrophages could be a marker of disease progression and poor survival in ILDs.

Anal canal epithelioid sarcoma: Case report and literature review

Soft tissue tumors account for less than 0.1% of colon and rectum malignant neoplasms. Epithelioid sarcoma is a subtype of undifferentiated soft tissue neoplasia that makes up 1% of this category; it is characterized by a slow progression, commonly affecting young male adults, with little or no response to chemotherapy and radiotherapy, leaving surgical resection their main therapeutic option to reduce recurrence. We here present the case of a 71-year-old male patient admitted for major rectorrhagia after evacuations and anal pain. During physical examination, a posterior anal sphincter induration was noted, which extended to the puborectal muscle. Anoscopy was performed where a thrombosed hemorrhoidal bundle was detected adjacent to a mass. In the later biopsy with immunohistochemistry, a proximal ulcer type, histological grade three epithelioid sarcoma was diagnosed. Subsequently, traditional abdominal perineal resection with colostomy was performed, resulting in favorable postoperative evolution and discharge after six days of the procedure. Keywords: soft tissue tumors; epithelioid sarcoma.

Adaptive and pathological connectivity responses in Parkinson’s disease brain networks

Functional imaging has been used extensively to identify and validate disease-specific networks as biomarkers in neurodegenerative disorders. It is not known, however, if connectivity patterns in these networks differ with disease progression compared to the beneficial adaptations that may also occur over time. To distinguish the two responses, we focused on assortativity, the tendency for network connections to link nodes with similar properties. High assortativity is associated with unstable, inefficient flow through the network. Low assortativity, by contrast, involves more diverse connections that are also more robust and efficient. We found that in Parkinson’s disease (PD), network assortativity increased with over time. Assoratitivty was high in clinically aggressive genetic variants, but low for genes associated with slow progression. Dopaminergic treatment increased assortativity despite improving motor symptoms, but subthalamic gene therapy, which remodels PD networks, reduced this measure compared to sham surgery. Assortativity may therefore be useful in evaluating disease-modifying therapies.