Oral Changes in Chronic Renal Failure Patients in One of the Regional Hospitals in Kosovo

Chronic kidney disease (CKD) patients have a higher tendency to have oral diseases such as periodontitis, saliva flow changes, bleeding gums, dry mouth, and bad breath. Malnutrition, oxidative stress, and vitamin deficiency, such as complex vitamin B and vitamin C, are the main factors that may cause oral changes. This study aimed to evaluate the subjective oral health of a sample of 90 patients with chronic renal failure (CRF) in dialysis and determine the relationship between renal failure and oral changes. As a result, the most frequent answer was dry mouth after dialysis at around 73.3% of the patients, whereas 41.1% had tooth decay, 52% had bad breath, 35% had gingival bleeding and 22.2% have noticed tooth coloring. The comparison between male and female patients found significant differences in uremic fetor: male patients had an average score of 1.58, while female patients had 1.36 (P=0.0371). Another significant difference was found for tooth discoloration: the average score for males was 1.67 and for females, 1.90 (p=0.0082). Patients in urban areas had an average score for caries after dialysis of 1.40, while those in rural areas had 1.68 (P=0.01). Patients with CRF should get multidisciplinary treatment. These patients require special consideration not only about dental treatment but also because of the side effects of the treatments they receive. A detailed evaluation and provision of good oral care after diagnosis of end-stage renal disease is more than necessary

Improved genetic testing for monogenic diabetes using targeted next-generation sequencing

addresses: Institute for Biomedical and Clinical Science, University of Exeter Medical School, Barrack Road, Exeter EX2 5DW, UK. [email protected]: PMCID: PMC3737433types: Journal Article; Research Support, Non-U.S. Gov'tOpen Access ArticleCurrent genetic tests for diagnosing monogenic diabetes rely on selection of the appropriate gene for analysis according to the patient's phenotype. Next-generation sequencing enables the simultaneous analysis of multiple genes in a single test. Our aim was to develop a targeted next-generation sequencing assay to detect mutations in all known MODY and neonatal diabetes genes

GCK gene mutations are a common cause of childhood-onset MODY (maturity-onset diabetes of the young) in Turkey.

Inactivating heterozygous mutations in the GCK gene are a common cause of MODY and result in mild fasting hyperglycaemia, which does not require treatment. We aimed to identify the frequency, clinical and molecular features of GCK mutations in a Turkish paediatric cohort.This article is freely available via PubMed Central, click on the Additional Link above to access the full-text

Androgen-regulated transcription of ESRP2 drives alternative splicing patterns in prostate cancer

Prostate is the most frequent cancer in men. Prostate cancer progression is driven by androgen steroid hormones, and delayed by androgen deprivation therapy (ADT). Androgens control transcription by stimulating androgen receptor (AR) activity, yet also control pre-mRNA splicing through less clear mechanisms. Here we find androgens regulate splicing through AR-mediated transcriptional control of the epithelial-specific splicing regulator ESRP2. Both ESRP2 and its close paralog ESRP1 are highly expressed in primary prostate cancer. Androgen stimulation induces splicing switches in many endogenous ESRP2-controlled mRNA isoforms, including splicing switches correlating with disease progression. ESRP2 expression in clinical prostate cancer is repressed by ADT, which may thus inadvertently dampen epithelial splice programmes. Supporting this, treatment with the AR antagonist bicalutamide (Casodex) induced mesenchymal splicing patterns of genes including FLNB and CTNND1. Our data reveals a new mechanism of splicing control in prostate cancer with important implications for disease progression.This article is freely available via Open Access. Click on the Publisher URL to access the full-text via the publisher's site

The role of GCNT1 mediated O-glycosylation in aggressive prostate cancer

Prostate cancer is the most common cancer in men and a major cause of cancer related deaths worldwide. Nearly all affected men develop resistance to current therapies and there is an urgent need to develop new treatments for advanced disease. Aberrant glycosylation is a common feature of cancer cells implicated in all of the hallmarks of cancer. A major driver of aberrant glycosylation in cancer is the altered expression of glycosylation enzymes. Here, we show that GCNT1, an enzyme that plays an essential role in the formation of core 2 branched O-glycans and is crucial to the final definition of O-glycan structure, is upregulated in aggressive prostate cancer. Using in vitro and in vivo models, we show GCNT1 promotes the growth of prostate tumours and can modify the glycome of prostate cancer cells, including upregulation of core 2 O-glycans and modifying the O-glycosylation of secreted glycoproteins. Furthermore, using RNA sequencing, we find upregulation of GCNT1 in prostate cancer cells can alter oncogenic gene expression pathways important in tumour growth and metastasis. Our study highlights the important role of aberrant O-glycosylation in prostate cancer progression and provides novel insights regarding the mechanisms involved

Physical therapy intervention studies on idiopathic scoliosis-review with the focus on inclusion criteria1

<p>Abstract</p> <p>Background</p> <p>Studies investigating the outcome of conservative scoliosis treatment differ widely with respect to the inclusion criteria used. This study has been performed to investigate the possibility to find useful inclusion criteria for future prospective studies on physiotherapy (PT).</p> <p>Materials and methods</p> <p>A PubMed search for outcome papers on PT was performed in order to detect study designs and inclusion criteria used.</p> <p>Results</p> <p>Real outcome papers (start of treatment in immature samples/end results after the end of growth; controlled studies in adults with scoliosis with a follow-up of more than 5 years) have not been found. Some papers investigated mid-term effects of exercises, most were retrospective, few prospective and many included patient samples with questionable treatment indications.</p> <p>Conclusion</p> <p>There is no outcome paper on PT in scoliosis with a patient sample at risk for being progressive in adults or in adolescents followed from premenarchial status until skeletal maturity. However, papers on bracing are more frequently found and bracing can be regarded as evidence-based in the conservative management and rehabilitation of idiopathic scoliosis in adolescents.</p

ST6GAL1-mediated aberrant sialylation promotes prostate cancer progression

Aberrant glycosylation is a universal feature of cancer cells, and cancer-associated glycans have been detected in virtually every cancer type. A common change in tumour cell glycosylation is an increase in α2,6 sialylation of N-glycans, a modification driven by the sialyltransferase ST6GAL1. ST6GAL1 is overexpressed in numerous cancer types, and sialylated glycans are fundamental for tumour growth, metastasis, immune evasion, and drug resistance, but the role of ST6GAL1 in prostate cancer is poorly understood. Here, we analyse matched cancer and normal tissue samples from 200 patients and verify that ST6GAL1 is upregulated in prostate cancer tissue. Using MALDI imaging mass spectrometry (MALDI-IMS), we identify larger branched α2,6 sialylated N-glycans that show specificity to prostate tumour tissue. We also monitored ST6GAL1 in plasma samples from >400 patients and reveal ST6GAL1 levels are significantly increased in the blood of men with prostate cancer. Using both in vitro and in vivo studies, we demonstrate that ST6GAL1 promotes prostate tumour growth and invasion. Our findings show ST6GAL1 introduces α2,6 sialylated N-glycans on prostate cancer cells and raise the possibility that prostate cancer cells can secrete active ST6GAL1 enzyme capable of remodelling glycans on the surface of other cells. Furthermore, we find α2,6 sialylated N-glycans expressed by prostate cancer cells can be targeted using the sialyltransferase inhibitor P-3FAX-Neu5Ac. Our study identifies an important role for ST6GAL1 and α2,6 sialylated N-glycans in prostate cancer progression and highlights the opportunity to inhibit abnormal sialylation for the development of new prostate cancer therapeutics

Upregulation of GALNT7 in prostate cancer modifies O-glycosylation and promotes tumour growth

Prostate cancer is the most common cancer in men and it is estimated that over 350,000 men worldwide die of prostate cancer every year. There remains an unmet clinical need to improve how clinically significant prostate cancer is diagnosed and develop new treatments for advanced disease. Aberrant glycosylation is a hallmark of cancer implicated in tumour growth, metastasis, and immune evasion. One of the key drivers of aberrant glycosylation is the dysregulated expression of glycosylation enzymes within the cancer cell. Here, we demonstrate using multiple independent clinical cohorts that the glycosyltransferase enzyme GALNT7 is upregulated in prostate cancer tissue. We show GALNT7 can identify men with prostate cancer, using urine and blood samples, with improved diagnostic accuracy than serum PSA alone. We also show that GALNT7 levels remain high in progression to castrate-resistant disease, and using in vitro and in vivo models, reveal that GALNT7 promotes prostate tumour growth. Mechanistically, GALNT7 can modify O-glycosylation in prostate cancer cells and correlates with cell cycle and immune signalling pathways. Our study provides a new biomarker to aid the diagnosis of clinically significant disease and cements GALNT7-mediated O-glycosylation as an important driver of prostate cancer progression

The COVID-19 pandemic and its global effects on dental practice. An international survey

Objectives A multicentre survey was designed to evaluate the impact of COVID-19 outbreak on dental practice worldwide, estimate the COVID-19 related symptoms/signs, work attitudes and behaviour and the routine use of protective measures and personal protective equipment (PPE). Methods A global survey using a standardized questionnaire with research groups from 36 countries was designed. The questionnaire was developed and pretested during April 2020 and contained three domains: 1) personal data; 2) COVID-19 positive rate and symptoms/signs presumably related to the coronavirus; 3) working conditions and PPE adopted after the outbreak. Countries’ data were grouped by the country positive rate (CPR) during the survey period and by Gross-National-Income per capita. An ordinal multinomial logistic regression model was carried out with COVID-19 self-reported rate referred by dental professionals as dependent variable to assess the association with questionnaire items. Results A total of 52,491 questionnaires were returned with a male/female ratio of 0.63. Out of the total respondents, 7,859 dental professionals (15%) reported symptoms/signs compatible with COVID-19. More than half of the sample (n=27,818; 53%) stated to use FFP2/N95 masks, while 21,558 (41.07%) used eye protection. In the bivariate analysis, CPR and N95/FFP2 were significantly associated (OR=1.80 95%CI=1.60/2.82 and OR=5.20 95%CI=1.44/18.80, respectively), while Gross-National-Income was not statistically associated with CPR (OR=1.09 95%CI=0.97/1.60). The same significant associations were observed in the multivariate analysis. Conclusions Oral health service provision has not been significantly affected by COVID-19, although access to routine dental care was reduced due to country-specific temporary lockdown periods. While the dental profession has been identified at high-risk, the reported rates of COVID-19 for dental professionals were not significantly different to those reported for the general population in each country. These findings may help to better plan oral health care for future pandemic events