A rare large duplication of MLH1 identified in Lynch syndrome.

BACKGROUND: The most frequently identified strong cancer predisposition mutations for colorectal cancer (CRC) are those in the mismatch repair (MMR) genes in Lynch syndrome. Laboratory diagnostics include testing tumors for immunohistochemical staining (IHC) of the Lynch syndrome-associated DNA MMR proteins and/or for microsatellite instability (MSI) followed by sequencing or other techniques, such as denaturing high performance liquid chromatography (DHPLC), to identify the mutation. METHODS: In an ongoing project focusing on finding Mendelian cancer syndromes we applied whole-exome/whole-genome sequencing (WES/WGS) to 19 CRC families. RESULTS: Three families were identified with a pathogenic/likely pathogenic germline variant in a MMR gene that had previously tested negative in DHPLC gene variant screening. All families had a history of CRC in several family members across multiple generations. Tumor analysis showed loss of the MMR protein IHC staining corresponding to the mutated genes, as well as MSI. In family A, a structural variant, a duplication of exons 4 to 13, was identified in MLH1. The duplication was predicted to lead to a frameshift at amino acid 520 and a premature stop codon at amino acid 539. In family B, a 1 base pair deletion was found in MLH1, resulting in a frameshift and a stop codon at amino acid 491. In family C, we identified a splice site variant in MSH2, which was predicted to lead loss of a splice donor site. CONCLUSIONS: We identified altogether three pathogenic/likely pathogenic variants in the MMR genes in three of the 19 sequenced families. The MLH1 variants, a duplication of exons 4 to 13 and a frameshift variant, were novel, based on the InSiGHT and ClinVar databases; the MSH2 splice site variant was reported by a single submitter in ClinVar. As a variant class, duplications have rarely been reported in the MMR gene literature, particularly those covering several exons.

Selenium and Arsenic Levels, Prevalence of Common Variants of Genes Involved in Their Metabolism, and Psoriasis Disease.

Using an Inductively Coupled Plasma Mass Spectrometer we measured the concentration of selenium and arsenic in serum and blood samples from 336 unselected psoriatic patients and 336 matched healthy controls to evaluate any associations with the clinical course of the disease. We genotyped 336 patients and 903 matched controls to evaluate the prevalence of SOD2 (rs4880), CAT (rs1001179), GPX1 (rs1050450), and DMGDH (rs921943) polymorphisms using Taqman assays. The mean selenium (Se) level in serum was 74 µg/L in patients and 86 µg/L in controls (p < 0.001). The mean Se level in blood was 95 µg/L in patients and 111 µg/L in controls (p < 0.001). Psoriasis risk was greatest among participants with the lowest serum (<68.75 µg/L, OR: 8.30; p < 0.001) and lowest blood concentrations of Se (<88.04 µg/L, OR: 10.3; p < 0.001). Similar results were observed in subgroups of males and females. We found an inverse correlation of selenium levels with PASI, NAPSI, and BSA scores. There was no significant difference in the distribution of the CAT, GPX1, DMGDH, and SOD2 polymorphisms. Among carriers of rs4880, rs1001179, and rs921943 polymorphisms, blood selenium levels were significantly lower. The mean arsenic level in serum was 0.79 µg/L in patients and 0.7 µg/L in controls (p = 0.2). The mean concentration in blood was 1.1 µg/L in patients and 1.3 µg/L in controls (p < 0.001). In conclusion, we found that lower selenium levels, in blood and serum, are associated with psoriasis risk and its more severe course. Future prospective studies should focus on the optimalisation of the concentration of this trace element not only for prophylactic guidance but also to support the treatment of this disease.

Microbiological Hazards Associated with the Use of Oligocene Waters: A Study of Water Intakes in Warsaw, Poland.

Oligocene waters are widely recognized as excellent sources of drinking water. Due to the belief in their good quality, the water from Oligocene intakes in Warsaw, Poland, is made available to users without prior treatment or disinfection. The present study aimed at assessing possible microbiological risks associated with the use of this water. The occurrence of microbiological contaminants in selected intakes was evaluated, in addition to an assessment of possible changes in the microbiological quality of the water under typical storage conditions. The possibility of antibiotic resistance in bacteria isolated from Oligocene water samples was also investigated, as was their sensitivity to selected disinfectants. A small number of bacteria-27.0 ± 60.8 CFU/cm3 and 3.0 ± 3.0 CFU/cm3-were found in Oligocene water intakes for psychrophilic and mesophilic bacteria, respectively. Fecal bacteria were not detected. Bacteria present in Oligocene waters showed the ability to multiply intensively during standard water storage; this was especially true for mesophilic bacteria in water stored at room temperature. In some samples, bacterial counts reached 103-104 CFU/cm3 after 48 h. Almost all bacterial isolates were resistant to the commonly used antibiotics: ampicillin, vancomycin and rifampicin. The bacteria were also insensitive to some disinfectants.

Water - A life-giving toxin - A nephrological oxymoron. Health consequences of water and sodium balance disorders. A review article.

BACKGROUND: This article aims to reveal misconceptions about methods of assessment of hydration status and impact of the water disorders on the progression of kidney disease or renal dysfunction. MATERIALS AND METHODS: The PubMed database was searched for reviews, meta-analyses and original articles on hydration, volume depletion, fluid overload and diagnostic methods of hydration status, which were published in English. RESULTS: Based on the results of available literature the relationship between the amount of fluid consumed, and the rate of progression of chronic kidney disease, autosomal dominant polycystic kidney disease, and kidney stones disease was discussed. Selected aspects of the assessment of the hydration level in clinical practice based on physical examination, laboratory tests, and imaging are presented. The subject of in-hospital fluid therapy is discussed. Based on available randomized studies, an attempt was made to assess, which fluids should be selected for intravenous treatment. CONCLUSIONS: There is some evidence for the beneficial effect of increased water intake in preventing recurrent cystitis and kidney stones, but there are still no convincing data for chronic kidney disease and autosomal dominant polycystic kidney disease. Further studies are needed to clarify the aforementioned issues and establish a reliable way to assess the volemia and perform suitable fluid therapy.

Polish version of the Brief Negative Symptom Scale (BNSS). / Polska wersja Krótkiej Skali Objawów Negatywnych (Brief Negative Symptom Scale ­ BNSS).

OBJECTIVES: To create a Polish adaptation of the Brief Negative Symptom Scale (BNSS), to assess the internal consistency of the Polish version of the BNSS, and to make correlations between the BNSS scores and the Positive and Negative Syndrome Scale (PANSS) in the group of patients with schizophrenia. METHODS: The procedure of Polish adaptation of the assessment form (Scoresheet) of the BNSS, comprising 13 items organized in 6 subscales (anhedonia, lack of proper distress, asociality, avolition, blunted affect, and alogia), as well as the Manual and the Workbook of the scale was carried out. Psychometric tests were performed in 40 patients with paranoid schizophrenia (20 men and 20 women), aged 44±13 years, with illness duration of 17±10 years, and severity of symptoms on the PANSS 56±16 points, receiving unchanged pharmacological treatment in the last three months. RESULTS: The Polish version was accepted by the authors of the scale. The reliability analysis showed high values of the Cronbach's alpha coefficient both for the whole scale (0.97) and for individual subscales (0.74-0.93). The BNSS and its subscales showed a high significant correlation with the total PANSS score and with the PANSS negative symptom subscale, both original and modified. CONCLUSIONS: The obtained results indicate good psychometric properties of the Polish version of the BNSS and its possible usefulness in the study of negative symptoms of schizophrenia conducted in Poland.

Symptoms of depression among adults in rural areas of western Poland.

OBJECTIVE: To measure the intensity of depressive symptoms in the populations residing in rural areas of western Poland, and to delineate the putative association between the intensity of depression and selected socio-demographic and clinical factors. MATERIALS AND METHOD: The study covered 445 adults recruited from one family physician practice in the rural area of Wielkopolska region. The following tools were applied: Beck Depression Inventory (BDI), the WHO WHOQoL-Bref quality of life assessment scale, and a socio-demographic and clinical questionnaire elaborated by the authors. RESULTS: Depressive symptoms were observed in approx. 30% of the patients. The intensity of symptoms correlated with age, female gender, and inversely correlated with the quality of life. There was no association between depressive symptoms and level of education (counted as years of education), number of somatic illnesses, and family burden of psychiatric disorders. CONCLUSION: Symptoms of depression were noted in approx. 30% of patients who consulted their family physician. The Beck questionnaire is a simple tool whose application could decidedly improve the recognition of depression. It is worth taking note of factors that may be connected with the intensity of depressive symptoms - gender, the number of diagnosed somatic illnesses, and the quantity of drugs administered.