Low nuclear expression of HIF-hydroxylases PHD2/EGLN1 and PHD3/EGLN3 are associated with poor recurrence-free survival in clear cell renal cell carcinoma.

BACKGROUND: Hypoxia inducible factors, HIF-1α and HIF-2α, and their main regulators, the prolyl hydroxylase domain proteins (PHDs), mediate cellular response to hypoxia and contribute to tumor progression in clear cell renal cell carcinoma (ccRCC). These biomarkers may improve the value of traditional histopathological features in predicting disease progression after nephrectomy for localized ccRCC and guide patient selection for adjuvant treatments. PATIENTS AND METHODS: In this study, we analyzed the associations of PHD2 and PHD3 with histopathological tumor features and recurrence-free survival (RFS) in a retrospective cohort of 173 patients who had undergone surgery for localized ccRCC at Helsinki University Hospital (HUH), Finland. An external validation cohort of 191 patients was obtained from Turku University Hospital (TUH), Finland. Tissue-microarrays (TMA) were constructed using the primary tumor samples. Clinical parameters and follow-up information from 2006 to 2019 were obtained from electronic medical records. The cytoplasmic and nuclear expression of PHD2, and PHD3 were scored based on immunohistochemical staining and their associations with histopathological features and RFS were evaluated. RESULTS: Nuclear PHD2 and PHD3 expression in cancer cells were associated with lower pT-stage and Fuhrman grade compared with negative nuclei. Patients with positive nuclear expression of PHD2 and PHD3 in cancer cells had favorable RFS compared with patients having negative tumors. The nuclear expression of PHD2 was independently associated with a decreased risk of disease recurrence or death from RCC in multivariable analysis. These results were observed in both cohorts. CONCLUSIONS: The absence of nuclear PHD2 and PHD3 expression in ccRCC was associated with poor RFS and the nuclear expression of PHD2 predicted RFS regardless of other known histopathological prognostic factors. Nuclear PHD2 and PHD3 are potential prognostic biomarkers in patients with localized ccRCC and should be further investigated and validated in prospective studies.

High prevalence of neurological sequelae and multiple chemical sensitivity among occupants of a Finnish police station damaged by dampness microbiota.

Objectives: The aim of the study was to estimate the risks of different symptoms after the exposure to indoor air dampness microbiota (DM).Methods: This cross-sectional retrospective cohort-based study compared morbidity risks in DM exposed (n = 116) vs. unexposed cohort (n = 45). Gender-adjusted log-binomial regression models were used to calculate risk ratios (RR). The analysis of indoor dust toxicity was based on the inhibition of the motion of boar spermatozoa in vitro. Conventional microbiological work-up was performed in an accredited laboratory.Results: Compared to the unexposed cohort, the study cohort had statistically significant (p < 0.05) risks to develop symptoms of the central nervous system RR = 2.85 (95% CI 1.19-6.85), fatigue RR = 2.82 (1.55-5.11), Multiple Chemical Sensitivity (MCS) RR = 2.81 (1.06-7.46), cardiac arrhythmia RR = 9.58 (1.33-68.81) and respiratory symptoms RR = 2.66 (1.58-4.48).Conclusions: The results of this study corroborate our earlier findings that toxic indoor air may cause a plethora of neurological symptoms. Higher than in the control group the prevalence of MCS associated with the exposure to DM. Bad indoor air is therefore not only a risk for respiratory problems and asthma but should be viewed broader as a systemic biotoxicosis. Therefore, psychologization of this disorder without mentioning the underlying insulting mechanisms should be discouraged.

Moist and Mold Exposure is Associated With High Prevalence of Neurological Symptoms and MCS in a Finnish Hospital Workers Cohort.

BACKGROUND: Indoor air dampness microbiota (DM) is a big health hazard. Sufficient evidence exists that exposure to DM causes new asthma or exacerbation, dyspnea, infections of upper airways and allergic alveolitis. Less convincing evidence has yet been published for extrapulmonary manifestations of dampness and mold hypersensitivity syndrome ). METHODS: We investigated the prevalence of extrapulmonary in addition to respiratory symptoms with a questionnaire in a cohort of nurses and midwives (n = 90) exposed to DM in a Helsinki Obstetric Hospital. The corresponding prevalence was compared with an unexposed cohort (n = 45). Particular interest was put on neurological symptoms and multiple chemical sensitivity. RESULTS: The results show that respiratory symptoms were more common among participants of the study vs. control cohort, that is, 80 vs 29%, respectively (risk ratio [RR]: 2.56, p < 0.001). Symptoms of the central or peripheral nervous system were also more common in study vs. control cohort: 81 vs 11% (RR: 6.63, p < 0.001). Fatigue was reported in 77 vs. 24%, (RR: 3.05, p < 0.001) and multiple chemical sensitivity in 40 vs. 9%, (RR: 3.44, p = 0.01), the so-called "brain fog", was prevalent in 62 vs 11% (RR: 4.94, p < 0.001), arrhythmias were reported in 57 vs. 2.4% (RR: 19.75, p < 0.001) and musculoskeletal pain in 51 vs 22% (RR: 2.02, p = 0.02) among participants of the study vs. control cohort, respectively. CONCLUSION: The results indicate that the exposure to DM is associated with a plethora of extrapulmonary symptoms. Presented data corroborate our recent reports on the health effects of moist and mold exposure in a workplace.

Association of toxic indoor air with multi-organ symptoms in pupils attending a moisture-damaged school in Finland.

BACKGROUND: There is an on-going debate on how best to test toxic indoor air. Toxicological methods based on condensed water samples and cell culture technique are newly introduced research tools which were tested in this study. METHODS: Pupils (n=47) from a water-damaged and (n=56) healthy schools were interviewed using a questionnaire. Indoor air was collected with a novel condensed water sampling technique and human THP-1 macrophages were exposed to the condensate. The cytotoxicity of cotton wool swab samples was tested using human BJ fibroblasts. Conventional microbiological culture methods were also performed. RESULTS: Gastrointestinal problems (GI) were reported by 51% from the study cohort but only 4% of the control cohort, relative risk RR=14.30. For any neurological or neuropsychological symptoms, the RR was 63.04, muscular-skeletal pain RR=58.28, headache RR=31.00, respiratory symptoms RR=22.64, fatigue RR=21.45, sub febrility RR=15.49, ear infections RR=7.74, skin rash RR=5.96, all being statistically significant (P<0.001). All indoor air (n=7) and cotton wool samples (n=2) taken from the water-damaged classroom or in proximity of the problematic classrooms were toxic in cell culture assays. Low numbers of moisture-damage indicators were recovered from wall, passive air, and swab samples, namely Aspergillus ochraceus species group, Aspergillus, Eurotium species group, Fusarium, Tritirachium, Scopulariopsis genus group and Aspergillus versicolores species group. CONCLUSIONS: Indoor air toxicity and dampness-related microbiota recovered from the classrooms were associated with multi-organ morbidity of the school occupants. These results corroborated our previous reports from two adult cohorts i.e. evidence of causality. These new toxicological methods based on condensed water and cell culturing techniques seem to be superior to conventional microbiological methods in correlating with clinical symptoms.

Natural coniferous resin lacquer in treatment of toenail onychomycosis: an observational study.

In in vitro tests, natural coniferous resin from the Norway spruce (Picea abies) is strongly antifungal. In this observational study, we tested the clinical effectiveness of a lacquer composed of spruce resin for topical treatment of onychomycosis. Thirty-seven patients with clinical diagnosis of onychomycosis were enrolled into the study. All patients used topical resin lacquer treatment daily for 9 months. A mycological culture and potassium hydroxide (KOH) stain were done from nail samples in the beginning and in the end of the study. Treatment was considered effective, if a mycological culture was negative and there was an apparent clinical cure. At study entry, 20 patients (20/37; 54%; 95% CI: 38-70) had a positive mycological culture and/or positive KOH stain for dermatophytes. At study end, the result of 13 patients was negative (13/19; 68%; 95% CI: 48-89). In one case (1/14; 7%; 95% CI: 0-21) the mycological culture was initially negative, but it turned positive during the study period. By 14 compliant patients (14/32; 44%; 95% CI: 27-61), resin lacquer treatment was considered clinically effective: complete healing took place in three cases (9%) and partial healing in 11 cases (85%). The results indicate some evidence of clinical efficacy of the natural coniferous resin used for topical treatment of onychomycosis.

Effects of Norway spruce (Picea abies) resin on cell wall and cell membrane of Staphylococcus aureus.

Resin salve prepared from Norway spruce (Picea abies) has been used for centuries in traditional medicine to treat skin diseases. The authors studied with transmission and scanning electron microscopy, and with electron physiology, changes in cell wall and cell membrane of Staphylococcus aureus after exposure of the bacterial cultures to resin. After exposure, cell wall thickening, cell aggregation, changed branching of fatty acids, and dissipation of membrane potential of the bacterial cells were observed. The authors conclude that spruce resin affects the cell viability via changes in the cell wall and membrane, and impairs, thereby, the synthesis of energy in the bacteria.

Occupational exposure to solvents and gasoline and risk of cancers in the urinary tract among Finnish workers.

BACKGROUND: Bladder cancer (BC) is generally considered as an occupational disease, and some chemical exposures may also be associated with renal cell cancer (RCC). The aim of this study was to estimate the risk of cancers of the urinary tract in relation to occupational exposure to solvents and gasoline. METHODS: A cross-sectional cohort of all economically active Finns from the 1970 population census was followed up for BC (10,277 cases) and RCC (9,954 cases). Census occupations were assigned estimates of exposure to hydrocarbon (HC) solvents and gasoline with a job exposure matrix. Relative risk (RR) estimates were defined using Poisson regression models, adjusted for smoking and obesity. RESULTS: Exposure to solvents was positively associated with the incidence of BC in women but not in men. The RR estimates were above 1.2 in nearly all exposure categories of all exposures studied but a statistically significant excess was only seen for middle levels of chlorinated HC solvents (1.7; 95% CI = 1.2-2.5) and a low level of aromatic HC solvents (1.6; 95% CI = 1.3-2.1). The RR estimates for RCC were close to unity in all categories of exposure. CONCLUSIONS: Our findings suggest that occupational exposure to certain solvents may have an impact on BC risk. The risk of RCC does not appear to be altered by exposure to HC solvents or gasoline.

Effect of caffeine on simulator flight performance in sleep-deprived military pilot students.

Caffeine has been suggested to act as a countermeasure against fatigue in military operations. In this randomized, double-blind, placebo-controlled study, the effect of caffeine on simulator flight performance was examined in 13 military pilots during 37 hours of sleep deprivation. Each subject performed a flight mission in simulator four times. The subjects received either a placebo (six subjects) or 200 mg of caffeine (seven subjects) 1 hour before the simulated flights. A moderate 200 mg intake of caffeine was associated with higher axillary temperatures, but it did not affect subjectively assessed sleepiness. Flight performance was similar in both groups during the four rounds flown under sleep deprivation. However, subjective evaluation of overall flight performance in the caffeine group tended to be too optimistic, indicating a potential flight safety problem. Based on our results, we do not recommend using caffeine pills in military flight operations.

Resin-salve from Norway spruce--a potential method to treat infected chronic skin ulcers?

The home-made resin salve from Norway spruce is traditionally and widely used in folk medicine to heal various skin infections and wounds in Northern Finland. We have performed laboratory studies to solve the mechanism of resin salve. The resin salve exhibited a bacteriostatic effect against all tested Gram-positive bacteria important in human medicine including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE), but was not effective against Gram-negative bacteria. An exception among the Gram-negative bacteria was Proteus vulgaris against which resin salve was effective. High amounts of lipophilic extractives, like resin acids were dissolved into water from the resin salve. Also, a large proportion of lignans and cinnamic acid were found in the water extract.