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Continental aquatic environments have undergone chemical pollution due to increased anthropogenic activities. Among those substances, petroleum hydrocarbons are a potential hazard for the aquatic animals. Additionally, alterations in the abiotic characteristics of the water, such as temperature and pH, can impose additional stress when those substances are present. We evaluate how alterations in water temperature and pH modified the acute (96 h) toxicity of the water-soluble fraction of gasoline (WSF G ) to Astyanax altiparanae through physiological analysis. We also investigated the physiological responses after the fish recovery from exposure (96 h) in clean water. Both isolated and combined exposures to WSF G resulted in significant physiological changes. Alone, WSF G altered energetic metabolism and haematopoietic functions, potentially due to metabolic hypoxia. When combined with changes in water temperature (30 °C) and pH (4.0), A. altiparanae activated additional physiological mechanisms to counterbalance osmoregulatory and acid-base imbalances, likely exacerbated by severe metabolic hypoxia. In both isolated and combined exposure scenarios, A. altiparanae maintained cellular hydration, suggesting a robust capacity to uphold homeostasis under environmental stress conditions. Following a recovery in clean water, energetic metabolism returned to control levels. Nevertheless, plasmatic Na + and Cl - levels and haematological parameters remained affected by WSF G exposure. Our findings underscore the impact of interactions between WSF G contaminants, temperature and pH, leading to additional biological damage in A. altiparanae., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To evaluate the physiological ability to adjust to environmental variations of salinity, Carcinus maenas were maintained in 10, 20, 32 (control), 40, and 50 ppt (13.8 ± 0.6 °C) for 7 days. Closed respirometry systems were used to evaluate oxygen consumption ([Formula: see text]), ammonia excretion (Jamm), urea-N excretion (Jurea-N) and diffusive water fluxes (with 3 H 2 O). Ions, osmolality, metabolites, and acid-base status were determined in the hemolymph and seawater, and transepithelial potential (TEP) was measured. At the lowest salinity, there were marked increases in [Formula: see text] and Jamm, greater reliance on N-containing fuels to support aerobic metabolism, and a state of internal metabolic alkalosis (increased [HCO 3 - ]) despite lower seawater pH. At higher salinities, an activation of anaerobic metabolism and a state of metabolic acidosis (decreased [HCO 3 - ] and increased [lactate]), in combination with respiratory compensation (decreased PCO 2 ), were detected. TEP became more negative with decreasing salinity. Osmoregulation and osmoconformation occurred at low and high salinities, respectively, with complex patterns in individual ions; hemolymph [Mg 2+ ] was particularly well regulated at levels well below the external seawater at all salinities. Diffusive water flux rates increased at higher salinities. Our results show that C. maenas exhibits wide plasticity of physiological responses when acclimated to different salinities and tolerates substantial disturbances of physiological parameters, illustrating that this species is well adapted to invade and survive in diverse habitats., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: A brief bedside test has recently been introduced by Hoche et al. (Brain, 2018) to screen for the Cerebellar Cognitive Affective Syndrome (CCAS) in patients with cerebellar disease., Objective: This multicenter study tested the ability of the CCAS-Scale to diagnose CCAS in individual patients with common forms of hereditary ataxia., Methods: A German version of the CCAS-Scale was applied in 30 SCA3, 14 SCA6 and 20 FRDA patients, and 64 healthy participants matched for age, sex, and level of education. Based on original cut-off values, the number of failed test items was assessed, and CCAS was considered possible (one failed item), probable (two failed items) or definite (three failed items). In addition a total sum raw score was calculated., Results: On a group level, failed items were significantly higher and total sum scores were significantly lower in SCA3 patients compared to matched controls. SCA6 and FRDA patients performed numerically below controls, but respective group differences failed to reach significance. The ability of the CCAS-Scale to diagnose CCAS in individual patients was limited to severe cases failing three or more items. Milder cases failing one or two items showed a great overlap with the performance of controls exhibiting a substantial number of false-positive test results. The word fluency test items differentiated best between patients and controls., Conclusions: As a group, SCA3 patients performed below the level of SCA6 and FRDA patients, possibly reflecting additional cerebral involvement. Moreover, the application of the CCAS-Scale in its present form results in a high number of false-positive test results, that is identifying controls as patients, reducing its usefulness as a screening tool for CCAS in individual patients., (© 2022. The Author(s).)

Purpose: We aimed to determine the value of laparoscopy to assess the intra-abdominal tumor extent and predict complete cytoreduction., Methods: All patients at our department in the period from 2017 to 2021 that underwent laparoscopy to assess peritoneal metastasis and subsequent open exploration with the intention to perform cytoreductive surgery (CRS) with HIPEC were retrospectively identified in a continuously maintained database., Results: Forty-three patients were analyzed. Peritoneal cancer index (PCI) determination by laparoscopy compared to open surgery was overestimated in five patients (11.6%), identical in eleven patients (25.6%), and underestimated in 27 patients (62.8%). PCI differences were independent of surgeons, tumor entities, and prior chemotherapy. Thirty-four patients (79.1%) were determined eligible for CRS with HIPEC during open exploration, whereas nine patients (20.9%) underwent a non-therapeutic laparotomy. Complete or almost complete cytoreduction was achieved in 33 patients (76.7%). In one patient, completeness of cytoreduction was not documented., Conclusions: We demonstrate a moderate agreement according to weighted Cohen's kappa analysis of PCI values calculated during laparoscopy and subsequent open exploration for CRS with HIPEC. Uncertainty of PCI assessment should therefore be kept in mind when performing laparoscopy in patients with peritoneal metastasis., (© 2022. The Author(s).)

We consider the following dynamic load-balancing process: given an underlying graph G with n nodes, in each step t ≥ 0 , a random edge is chosen, one unit of load is created, and placed at one of the endpoints. In the same step, assuming that loads are arbitrarily divisible, the two nodes balance their loads by averaging them. We are interested in the expected gap between the minimum and maximum loads at nodes as the process progresses, and its dependence on n and on the graph structure. Peres et al. (Random Struct Algorithms 47(4):760-775, 2015) studied the variant of this process, where the unit of load is placed in the least loaded endpoint of the chosen edge, and the averaging is not performed. In the case of dynamic load balancing on the cycle of length n the only known upper bound on the expected gap is of order O ( n log n ) , following from the majorization argument due to the same work. In this paper, we leverage the power of averaging and provide an improved upper bound of O ( n log n ) . We introduce a new potential analysis technique, which enables us to bound the difference in load between k -hop neighbors on the cycle, for any k ≤ n / 2 . We complement this with a "gap covering" argument, which bounds the maximum value of the gap by bounding its value across all possible subsets of a certain structure, and recursively bounding the gaps within each subset. We also show that our analysis can be extended to the specific instance of Harary graphs. On the other hand, we prove that the expected second moment of the gap is lower bounded by Ω ( n ) . Additionally, we provide experimental evidence that our upper bound on the gap is tight up to a logarithmic factor., (© The Author(s) 2021.)

Epigenetic mechanisms regulate gene expression, without changing the DNA sequence, and establish cell-type-specific temporal and spatial expression patterns. Alterations of epigenetic marks have been observed in several pathological conditions, including cancer and neurological disorders. Emerging evidence indicates that a variety of environmental factors may cause epigenetic alterations and eventually influence disease risks. Humans are increasingly exposed to extremely low-frequency magnetic fields (ELF-MFs), which in 2002 were classified as possible carcinogens by the International Agency for Research on Cancer. This review summarizes the current knowledge of the link between the exposure to ELF-MFs and epigenetic alterations in various cell types. In spite of the limited number of publications, available evidence indicates that ELF-MF exposure can be associated with epigenetic changes, including DNA methylation, modifications of histones and microRNA expression. Further research is needed to investigate the molecular mechanisms underlying the observed phenomena., (© 2021. The Author(s).)

Long INterspersed Element-1 (L1) is a transposable element that can insert copies of itself in new genomic locations causing genomic instability. In somatic cells, L1 retrotransposition activity is usually repressed but somatic L1 retrotransposition has recently been observed during neuronal differentiation. In this study, we evaluate whether L1 elements are differentially active in rat tissues during postnatal development. To this purpose, we quantified L1 in genomic DNA extracted from the olfactory bulb (OB), cerebellum (CE), cortex (CO) and heart (H). Each analysis was repeated on rats aged 7, 21 and 60 days. We found that L1 content in OB and CE tissue was significantly higher than H tissue, in rats of all three ages studied, suggesting that L1 activity could be modulated in postnatal development and neurogenesis.

Extremely low frequency magnetic fields (ELF-MF) have been classified as "possibly carcinogenic", but their genotoxic effects are still unclear. Recent findings indicate that epigenetic mechanisms contribute to the genome dysfunction and it is well known that they are affected by environmental factors. To our knowledge, to date the question of whether exposure to ELF-MF can influence epigenetic modifications has been poorly addressed. In this paper, we investigated whether exposure to ELF-MF alone and in combination with oxidative stress (OS) can affect DNA methylation, which is one of the most often studied epigenetic modification. To this end, we analyzed the DNA methylation levels of the 5'untranslated region (5'UTR) of long interspersed nuclear element-1s (LINE-1 or L1), which are commonly used to evaluate the global genome methylation level. Human neural cells (BE(2)C) were exposed for 24 and 48 h to extremely low frequency pulsed magnetic field (PMF; 50 Hz, 1 mT) in combination with OS. The methylation levels of CpGs located in L1 5'UTR region were measured by MassARRAY EpiTYPER. The results indicate that exposures to the single agents PMF and OS induced weak decreases and increases of DNA methylation levels at different CpGs. However, the combined exposure to PMF and OS lead to significant decrease of DNA methylation levels at different CpG sites. Most of the changes were transient, suggesting that cells can restore homeostatic DNA methylation patterns. The results are discussed and future research directions outlined.

Epilepsy is a devastating condition with a considerable increase in mortality compared to the general population. Few studies have focused on cause-specific mortality which we analyse in detail in over 4,000 well-characterized epilepsy patients. The cohort comprised of epilepsy patients ≥ 18, treated between 1970 and 2009 at the epilepsy clinic of Innsbruck Medical University, Austria, and living in the province of Tyrol, Austria. Epilepsy diagnosis was based on ILAE guidelines (1989); patients with brain tumor were excluded. Deceased patients and causes of death (ICD-codes) were obtained via record linkage to the national death registry. We computed age-, sex-, and period-adjusted standardized mortality rates (SMR) for 36 diagnoses subgroups in four major groups. Additional analyses were performed for an incidence cohort. Overall cohort: 4,295 patients, 60,649.1 person-years, 822 deaths, overall SMR 1.7 (95 % CI 1.6-1.9), highest elevated cause-specific SMR: congenital anomalies [7.1 (95 % CI 2.3-16.6)], suicide [4.2 (95 % CI 2.0-8.1)], alcohol dependence syndrome [3.9 (95 % CI 1.8-7.4)], malignant neoplasm of esophagus [3.1 (95 % CI 1.2-6.4)], pneumonia [2.7 (95 % CI 1.6-4.2)]. Incidence cohort: 1,299 patients, 14,215.4 person-years, 267 deaths, overall SMR 1.8 (95 % CI 1.6-2.1), highest elevated cause-specific SMR congenital anomalies [10.8 (95 % CI 1.3-39.3)], suicide [6.8 (95 % CI 1.4-19.8)], alcohol dependence syndrome (6.4 [95 % CI 1.8-16.5)], pneumonia [3.9 (95 % CI 1.8-7.4)], cerebrovascular disease at 3.5 (95 % CI 2.6-4.6). Mortality due to mental health problems, such as suicide or alcohol dependence syndrome, malignant neoplasms, and cerebrovascular diseases was highly increased in our study. In addition to aim for seizure freedom, we suggest improving general health promotion, including cessation of smoking, lowering of alcohol intake, and reduction of weight as well as early identification of psychiatric comorbidity in patients with epilepsy.

Purpose: We retrospectively analyzed our results in thoracolumbar and lumbar adolescent idiopathic scoliosis treated during adulthood., Methods: Fifty-two thoracolumbar and 30 lumbar idiopathic scoliosis surgically treated were reviewed. Mean follow-up was 9.5 ± 6.6 years. All the subjects were analyzed by visual analog scale, Oswestry Disability Index (ODI), and SF-36 scores before and after surgery and at follow-up. The scoliotic curve, thoracic kyphosis, lumbar lordosis, pelvic incidence (PI), pelvic tilt (PT), sacral slope, and C7 plumb line were measured. For the statistical analysis, multivariate multiple regression models were formulated, considering as significative a P < 0.05., Results: A statistically significant clinical and radiological amelioration was noted after surgery and at final follow-up. According to the logistic regression model, ODI was related to lumbar lordosis and spino-pelvic parameters at follow-up. The only determinant of failure was age., Conclusions: Spino-pelvic recovery is easier in patients aged less than 60 years with PI < 55° and PT < 25°.

Objective: The aim of this study was to evaluate the effectiveness of Chêneau brace in the management of idiopathic scoliosis., Methods: This is a retrospective observational study according to SOSORT and SRS (Scoliosis Research Society) recommendations involving 48 girls with documented progressive idiopathic scoliosis, treated with Chêneau brace. A statistical analysis was performed with STATA MP11.2 to validate the obtained results., Results: No patient needed surgery. The average curve angle measured in Cobb degrees passed from 27° ± 6.7° at the beginning (T0), to 7.6° ± 7.4° in brace (T1) (72 % of correction), to 8.5° ± 8.6° (69 % of correction) at the end of treatment (T2), to 11.0° ± 7.4° (59.3 % of correction) at final follow-up (mean 5 years and 5 months) (T3)., Conclusion: Conservative treatment with Chêneau brace and physiotherapy was effective in our hands for halting scoliosis progression in 100 % of patients.

Recent neuroimaging studies have reported structural and functional brain abnormalities in patients with juvenile myoclonic epilepsy (JME), which may also involve cortical and subcortical networks that are important for decision making. This study is the first attempt to examine decision making in JME. Twenty-two patients with JME (median age 26.00, range 18-50) and 33 healthy controls (median age 26.00, range 18-57) participated in the study. For the JME group, the median age at seizure onset was 14.00 years (range 1-20); the median epilepsy duration was 11.50 years (range 3-45). Eleven patients (50 %) had pharmacoresistant seizures. All participants completed the Iowa Gambling Task (IGT), a widely used standard task of decision making. In this task, contingencies are not explained and feedback on previous decisions has to be used in order to learn to choose the advantageous alternatives. In the IGT, patients with JME showed difficulty in learning to choose advantageously compared to healthy controls. Difficulty was enhanced for the patients with pharmacoresistant seizures. A correlation analysis revealed an association between decision-making performance of patients with JME and executive functions. Results indicate that patients with JME have difficulty in making advantageous decisions and that persistence of seizures might be a critical factor for cognitive functioning. Findings of this study add a new aspect to the neuropsychological profile of JME. Difficulty in decision making may impair functioning of patients with JME in everyday life and affect their adherence to treatment plans.

Long interspersed element-1s (LINE-1 or L1s) are abundant retrotransposons that occur in mammalian genomes and that can cause insertional mutagenesis and genomic instability. L1 activity is generally repressed in most cells and tissues but has been found in some embryonic cells and, in particular, in neural progenitors. Moreover, L1 retrotransposition can be induced by several DNA-damaging agents. We have carried out experiments to verify whether L1 retrotransposition is affected by oxidative DNA damage, which plays a role in a range of human diseases, including cancer and inflammatory and neurodegenerative disease. To this purpose, BE(2)C neuroblastoma cells, which are thought to represent embryonic precursors of sympathetic neurons, have been treated with hydrogen peroxide and subjected to an in vitro retrotransposition assay involving an episomal L1(RP) element tagged with enhanced green fluorescent protein. Our results indicate that hydrogen peroxide treatment induces an increase in the retrotransposition of transiently transfected L1(RP) and an increase in the expression of endogenous L1 transcripts. An increase of γ-H2AX foci and changes in the mRNA levels of MRE11, RAD50, NBN and ERCC1 (all involved in DNA repair) have also been found. Thus, oxidative stress can cause L1 dysregulation.

Cyclic nucleotide phosphodiesterase (PDE) isoenzymes are key proteins regulating intracellular cyclic nucleotide turnover and thus smooth muscle tension. Several in vitro studies have indicated that the cyclic GMP and cyclic AMP-mediated signaling may play a role in the control of human ureteral muscle. The aim of the present study was to evaluate the functional effects of PDE5 inhibitors sildenafil (Sil), vardenafil (Var) and tadalafil (Tad), as well as nitric oxide (NO)-donating agent sodium nitroprusside (SNP) and non-selective muscarinic antagonist butylscopolamine (BSC) on the tension induced by KCl and the turnover of cyclic nucleotides in isolated human ureteral smooth muscle. In vitro relaxant responses of human ureteral smooth muscle to the PDE5 inhibitors mentioned above were investigated using the organ bath technique. Cyclic nucleotides cAMP and cGMP were determined by means of specific radioimmunoassay following incubation of the tissue with Sil, Var, Tad and SNP. The tension induced by KCl of the ureteral tissue was dose dependently reversed by the drugs with the following rank order of efficacy: SNP > Var >or= Sil > Tad > BSC. R(max) values ranged from 25 +/- 9% (SNP) to 5 +/- 3% (BSC). Relaxant responses were paralleled by threefold to fourfold increase in tissue levels of cGMP. Our results indicate that PDE5 inhibitors can reverse the tension of isolated human ureteral smooth muscle via cGMP-mediated pathways. Nevertheless, further studies are indicated in order to evaluate as to whether there might be a use for PDE5 inhibitors in the treatment of ureteral stone disease.

The cellular sites of insulin-like growth factor I (IGF-I) synthesis in the early developing tilapia (0-140 days post fertilization, DPF) were investigated. IGF-I mRNA and peptide appeared in liver as early as 4 DPF and in gastro-intestinal epithelial cells between 5-9 DPF. In exocrine pancreas, the expression of IGF-I started at 4 DPF and continued until 90 DPF. IGF-I production was detected in islets at 6 DPF in non-insulin cells and occurred throughout life. In renal tubules and ducts, IGF-I production started at 8 DPF. IGF-I production in chondrocytes had its onset at 4 DPF, was more pronounced in growing regions and was also found in adults. IGF-I mRNA and peptide appeared in the cytoplasm of skeletal muscle cells at 4 DPF. In gill chloride cells, IGF-I production started at 6 DPF. At 13 DPF, IGF-I was detected in cardiac myocytes. IGF-I-producing epidermal cells appeared at 5 DPF. In brain and ganglia, IGF-I was expressed in virtually all neurones from 6 to 29 DPF, their number decreasing with age. Neurosecretory IGF-I-immunoreactive axons were first seen in the neurohypophysis around 17 DPF. Endocrine cells of the adenohypophysis exhibited IGF-I mRNA at 28 DPF and IGF-I immunoreactivity at 40 DPF. Thus, IGF-I appeared early (4-5 DPF), first in liver, the main source of endocrine IGF-I, and then in organs involved in growth or metabolism. The expression of IGF-I was more pronounced during development than in juvenile and adult life. Local IGF-I therefore seems to have a high functional impact in early growth, metabolism and organogenesis.

Our objective was to determine if urinary bladder distention modifies the sensitivity of the baroreceptor-heart rate reflex in hypertensive and control subjects. The baroreceptor-heart rate reflex sensitivity was measured in 15 male patients (mean age 37+/-8 years) with mild untreated hypertension (mean 163+/-8/ 95+/-12 mmHg) and 17 age- and sex-matched control subjects before and after urinary bladder distention. Bladder filling was performed infusing saline heated to 37 degrees C via a urinary catheter; the volume infused in each patient corresponded to that which caused the urge to void without reaching the pain threshold. The baroreceptor-heart rate reflex sensitivity was determined correlating the variations of the systolic pressure and of the peak blood flow velocity in the common carotid artery with the variations of the ECG RR' interval of the following heart beat, both during spontaneous and phenylephrine-induced fluctuations of the haemodynamic variables. After bladder distention the diastolic pressure of the hypertensive subjects increased significantly (95+/-12 vs. 100+/-12 mmHg: P < 0.02), whereas the heart rate decreased (RR= 873+/-70 vs. 926+/-80 ms; P < 0.005). These parameters were unchanged in the normotensive subjects (84+/-9 vs. 83+/-8 mmHg and 914+/-158 vs. 913+/-140 ms, respectively). The baroreceptor-heart rate reflex sensitivity, measured on the basis of spontaneous pressure and carotid blood flow velocity fluctuations in relationship to RR changes, decreased in the normotensive subjects after bladder distention (10.7+/-4.6 vs. 9.4+/-2.7 ms/mmHg; P < 0.05 and 423+/-99 vs. 356+/-102 ms/kHz; P < 0.01, respectively), whereas it increased in the hypertensive patients (6.9 +/- 3.6 vs. 8.3 +/- 2.8 ms/mmHg; P < 0.03, and 332 +/- 86 vs. 381+/-97 ms/kHz; P < 0.03 respectively). After bladder distention and phenylephrine administration the baroreceptor-heart rate reflex sensitivity, measured by the correlation between systolic pressure and RR interval, increased only in the hypertensive group (10.2+/-5.4 vs. 15.2+/-7.7 ms/mmHg; P < 0.005). In conclusion urinary bladder distention provokes in hypertensives but not normotensive controls a brisk parasympathetic response of the component of the baroreceptor-heart rate reflex which controls heart rate.