Reliability of the pre-operative imaging to assess neck nodal involvement in oral cancer patients, a single-center study

Background: Primary sites for the metastasis of oral cancer are the cervical lymph nodes. Although there has been considerable technical advancement in the radiological imaging, capability to recognize all metastatic lymph nodes pre-operatively has remained as a challenge. Thus elective neck dissection (END) has remained as reli-able practice to treat cervical lymph nodes. This study evaluated the accuracy of pre-operative imaging in pre-operative diagnostics of cervical lymph node status using computed tomography or magnetic resonance imaging in patients with oral squamous cell carcinoma (OSCC). We have also considered the reasons for the difficulties to recognise metastatic nodes in cervical area. Material and Methods: Patient charts of patients who had had elective neck dissection as a treatment for primary OSCC in the Department of Oral and Maxillofacial Surgery, Helsinki University Hospital between 2016 and 2017 were assessed retrospectively. The outcome variable was post-operatively histologically confirmed lymph node metastasis in the neck area. The primary predictor variable was radiologically confirmed metastasis in the neck area. The explanatory variables were age, sex, pT-class, imaging modality, delay and location of the tumour. De-scriptive statistics, sensitivity, specificity and Youden-J index were computed. Results: Eighty-three patients were included in the study. The sensitivity to detect pathological lymph nodes was 44.8%, and the specificity for the examination was 87.0%. 19.3% of cN0 patients had metastasis in the cervical nodes, whereas of the cN+ patients 8.4% were actually pN0. Patients having cN0, the largest neck metastasis was over 10 mm in 12.5%, whereas cN1-3 patients the corresponding rate was 45.5%. The computational threshold to diagnose a metastatic node was 7 mm. Conclusions: Especially small metastases are difficult to diagnose. Limitations of radiological diagnostics must be considered when treating OSCC.Peer reviewe

Oxidative Spin-Spray-Assembled Coordinative Multilayers as Platforms for Capacitive Films

The spin-spray-assisted layer-by-layer (LbL) assembly technique was used to prepare coordinative oxidative multilayers from Ce(IV), inorganic polyphosphate (PP), and graphene oxide (GO). The films consist of successive tetralayers and have a general structure (PP/Ce/GO/Ce)(n). Such oxidative multilayers have been shown to be a general platform for the electrodeless generation of conducting polymer and melanin-type films. Although the incorporation of GO enhances the film growth, the conventional dip LbL method is very time consuming. We show that the spin-spray method reduces the time required to grow thick multilayers by the order of magnitude and the film growth is linear from the beginning, which implies a stratified structure. We have deposited poly(3,4-ethylenedioxothiophene), PEDOT, on the oxidative multilayers and studied these redox-active films as models for melanin-type capacitive layers for supercapacitors to be used in biodegradable electronics, both before and after the electrochemical reduction of GO to rGO. The amount of oxidant and PEDOT scales linearly with the film thickness, and the charge transfer kinetics is not mass transfer-limited, especially after the reduction of GO. The areal capacitance of the films grows linearly with the film thickness, reaching a value of ca. 1.6 mF cm(-2) with 20 tetralayers, and the specific volumetric (per film volume) and mass (per mass of PEDOT) capacitances are ca. 130 F cm(-3) and 65 F g(-1), respectively. 5,6-Dihydroxyindole can also be polymerized to a redox-active melanin-type film on these oxidative multilayers, with even higher areal capacitance values

Understanding variability in root zone storage capacity in boreal regions

The root zone storage capacity (Sr) of vegetation is an important parameter in the hydrological behaviour of a catchment. Traditionally, Sr is derived from soil and vegetation data. However, more recently a new method has been developed that uses climate data to estimate Sr based on the assumption that vegetation adapts its root zone storage capacity to overcome dry periods. This method also enables one to take into account temporal variability of derived Sr values resulting from changes in climate or land cover. The current study applies this new method in 64 catchments in Finland to investigate the reasons for variability in Sr in boreal regions. Relations were assessed between climate-derived Sr values and climate variables (precipitation-potential evaporation rate, mean annual temperature, max snow water equivalent, snow-off date), detailed vegetation characteristics (leaf cover, tree length, root biomass), and vegetation types. The results show that in particular the phase difference between snow-off date and onset of potential evaporation has a large influence on the derived Sr values. Further to this it is found that (non-)coincidence of snow melt and potential evaporation could cause a division between catchments with a high and a low Sr value. It is concluded that the climate-derived root zone storage capacity leads to plausible Sr values in boreal areas and that, apart from climate variables, catchment vegetation characteristics can also be directly linked to the derived Sr values. As the climate-derived Sr enables incorporating climatic and vegetation conditions in a hydrological parameter, it could be beneficial to assess the effects of changing climate and environmental conditions in boreal regions.</p

Dysregulation of glucose metabolism is an early event in sporadic Parkinson's disease

AbstractUnlike most other cell types, neurons preferentially metabolize glucose via the pentose phosphate pathway (PPP) to maintain their antioxidant status. Inhibiting the PPP in neuronal cell models causes cell death. In rodents, inhibition of this pathway causes selective dopaminergic cell death leading to motor deficits resembling parkinsonism. Using postmortem human brain tissue, we characterized glucose metabolism via the PPP in sporadic Parkinson's disease (PD), Alzheimer's disease (AD), and controls. AD brains showed increased nicotinamide adenine dinucleotide phosphate (NADPH) production in areas affected by disease. In PD however, increased NADPH production was only seen in the affected areas of late-stage cases. Quantifying PPP NADPH-producing enzymes glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase by enzyme-linked immunosorbent assay, showed a reduction in the putamen of early-stage PD and interestingly in the cerebellum of early and late-stage PD. Importantly, there was no decrease in enzyme levels in the cortex, putamen, or cerebellum of AD. Our results suggest that down-regulation of PPP enzymes and a failure to increase antioxidant reserve is an early event in the pathogenesis of sporadic PD

Polydopamine Nanoparticles Prepared Using Redox-Active Transition Metals

Autoxidation of dopamine to polydopamine by dissolved oxygen is a slow process that requires highly alkaline conditions. Polydopamine can be formed rapidly also in mildly acidic and neutral solutions by using redox-active transition-metal ions. We present a comparative study of polydopamine nanoparticles formed by autoxidation and aerobic or anaerobic oxidation in the presence of Ce(IV), Fe(III), Cu(II), and Mn(VII). The UV-vis spectra of the purified nanoparticles are similar, and dopaminechrome is an early intermediate species. At low pH, Cu(II) requires the presence of oxygen and chloride ions to produce polydopamine at a reasonable rate. The changes in dispersibility and surface charge take place at around pH 4, which indicates the presence of ionizable groups, especially carboxylic acids, on their surface. X-ray photoelectron spectroscopy shows the presence of three different classes of carbons, and the carbonyl/carboxylate carbons amount to 5-15 atom %. The N 1s spectra show the presence of protonated free amino groups, suggesting that these groups may interact with the pi-electrons of the intact aromatic dihydroxyindole moieties, especially in the metal-induced samples. The autoxidized and Mn(VII)-induced samples do not contain metals, but the metal content is 1-2 atom % in samples prepared with Ce(IV) or Cu(II), and ca. 20 atom % in polydopamine prepared in the presence of Fe(III). These differences in the metal content can be explained by the oxidation and complexation properties of the metals using the general model developed. In addition, the nitrogen content is lower in the metal-induced samples. All of the metal oxidants studied can be used to rapidly prepare polydopamine at room temperature, but the possible influence of the metal content and nitrogen loss should be taken into account

Neurological symptoms and natural course of xeroderma pigmentosum

We have prospectively followed 16 Finnish xeroderma pigmentosum (XP) patients for up to 23 years. Seven patients were assigned by complementation analysis to the group XP-A, two patients to the XP-C group and one patient to the XP-G group. Six of the seven XP-A patients had the identical mutation (Arg228Ter) and the seventh patient had a different mutation (G283A). Further patients were assigned to complementation groups on the basis of their consanguinity to an XP patient with a known complementation group. The first sign of the disease in all the cases was severe sunburn with minimal sun exposure in early infancy. However, at the time the diagnosis was made in only two cases. The XP-A patients developed neurological and cognitive dysfunction in childhood. The neurological disease advanced in an orderly fashion through its successive stages, finally affecting the whole nervous system and leading to death before the age of 40 years. Dermatological and ocular damage of the XP-A patients tended to be limited. The two XP-C patients were neurologically and cognitively intact despite mild brain atrophy as seen by neuroimaging. The XP-G patients had sensorineural hearing loss, laryngeal dystonia and peripheral neuropathy. The XP-C patients had severe skin and ocular malignancies that first presented at pre-school age. They also showed immunosuppression in cell-mediated immunity. Neurological disease appears to be associated with the complementation group and the failure of fibroblasts to recover RNA synthesis following UV irradiation, but not necessarily to the severity of the dermatological symptoms, the hypersensitivity of fibroblasts to UVB killing or the susceptibility of keratinocytes to UVB-induced apoptosis

Mutation update and genotype-phenotype correlations of novel and previously described mutations in TPM2 and TPM3 causing congenital myopathies

Mutations affecting skeletal muscle isoforms of the tropomyosin genes may cause nemaline myopathy, cap myopathy, core-rod myopathy, congenital fiber-type disproportion, distal arthrogryposes, and Escobar syndrome. We correlate the clinical picture of these diseases with novel (19) and previously reported (31) mutations of the TPM2 and TPM3 genes. Included are altogether 93 families: 53 with TPM2 mutations and 40 with TPM3 mutations. Thirty distinct pathogenic variants of TPM2 and 20 of TPM3 have been published or listed in the Leiden Open Variant Database (http://www.dmd.nl/). Most are heterozygous changes associated with autosomal-dominant disease. Patients with TPM2 mutations tended to present with milder symptoms than those with TPM3 mutations, DA being present only in the TPM2 group. Previous studies have shown that five of the mutations in TPM2 and one in TPM3 cause increased Ca2+ sensitivity resulting in a hypercontractile molecular phenotype. Patients with hypercontractile phenotype more often had contractures of the limb joints (18/19) and jaw (6/19) than those with nonhypercontractile ones (2/22 and 1/22), whereas patients with the non-hypercontractile molecular phenotype more often (19/22) had axial contractures than the hypercontractile group (7/19). Our in silico predictions show that most mutations affect tropomyosin–actin association or tropomyosin head-to-tail binding

Quantifying groundwater fluxes from an aapa mire to a riverside esker formation

Water flows in peatland margins is an under-researched topic. This study examines recharge from a peatland to an esker aquifer in an aapa mire complex of northern Finland. Our objective was to study how the aapa mire margin is hydrogeologically connected to the riverside aquifer and spatial and temporal variations in the recharge of peatland water to groundwater (GW). Following geophysical studies and monitoring of the saturated zone, a GW model (MODFLOW) was used in combination with stable isotopes to quantify GW flow volumes and directions. Peatland water recharge to the sandy aquifer indicated a strong connection at the peatland–aquifer boundary. Recharge volumes from peatland to esker were high and rather constant (873 m3 d−1) and dominated esker recharge at the study site. The peat water recharging the esker boundary was rich in dissolved organic carbon (DOC). Stable isotope studies on water (δ18O, δ2H, and d-excess) from GW wells verified the recharge of DOC-rich water from peatlands to mineral soil esker. Biogeochemical analysis revealed changes from DOC to dissolved inorganic carbon in the flow pathway from peatland margin to the river Kitinen. This study highlights the importance of careful investigation of aapa mire margin areas and their potential role in regional GW recharge patterns. HIGHLIGHTS Peatland water recharge to aquifer showed connection at the peatland–aquifer boundary.; Analysis revealed changes from dissolved organic carbon to dissolved inorganic carbon in groundwater flow pathway from peatland.; Connection between an aapa mire margin and riverside esker was documented.

Obesity accelerates epigenetic aging in middle-aged but not in elderly individuals

Background: Human aging is associated with profound changes in one of the major epigenetic mechanisms, DNA methylation. Some of these changes occur in a clock-like fashion, i.e., correlating with the calendar age of an individual, thus providing a new aging biomarker. Some reports have identified factors associated with the acceleration of the epigenetic age. However, it is also important to analyze the temporal changes in the epigenetic age, i.e., the duration of the observed acceleration, and the effects of the possible therapeutic and lifestyle modifications.Methods: To address this issue, we determined the epigenetic age for a cohort of 183 healthy individuals using blood samples derived from two time points that were 25 years apart (between 15-24 and 40-49 years of age). Additionally, we also determined the epigenetic ages of 119 individuals in a cohort consisting of 90-year-old participants (nonagenarians). These were determined by using the Horvath algorithm based on the methylation level of 353 CpG sites. The data are indicated as the deviation of the epigenetic age from the calendar age (calendar age minus epigenetic age = delta age, Delta AGE). As obesity is often associated with accelerating aging and degenerative phenotypes, the correlation of the body mass index (BMI) with the Delta AGE was analyzed in the following three age groups: young adults, middle-aged, and nonagenarian.Results: The data showed that BMI is associated with decreased Delta AGE, i.e., increased epigenetic age, in middle-aged individuals. This effect is also seen during the 25-year period from early adulthood to middle age, in which an increase in the BMI is significantly associated with a decrease in the Delta AGE. We also analyzed the association between BMI and epigenetic age in young and elderly individuals, but these associations were not significant.Conclusion: Taken together, the main finding on this report suggests that association between increased BMI and accelerated epigenetic aging in the blood cells of middle-aged individuals can be observed, and this effect is also detectable if the BMI has increased in adulthood. The fact that the association between BMI and epigenetic age can only be observed in the middle-aged group does not exclude the possibility that this association could be present throughout the human lifespan; it might just be masked by confounding factors in young adults and nonagenarian individuals