The effect of fluvial avulsion on the Holocene chronostratigraphic record and the agricultural signal of the world's largest coastal lagoonal system.

This study identified the occurrence of Holocene chronology hiatuses in the sedimentary record of the Patos-Mirim system caused by river avulsion processes, as well as evidence of sharp anthropogenic changes in the surrounding region of the lagoon water bodies. The presence of chronology hiatuses demonstrates the importance of considering the disturbance effect of paleo-drainage processes on the paleoenvironmental resolution and expression of the sedimentary record of such coastal plains. Anthropogenic activities especially those related to agriculture and forestry have increased significantly during the great acceleration, resulting in modifications of both the landscape and the environmental conditions of the lagoon bodies. Such impacts were clearly reflected in the sedimentary record where abrupt changes in palynological trends, sedimentary DNA, isotopic and granulometric analyses were inferred. The climatic conditions combined with regressive sea level can explain the chronology hiatuses. Pollen analyses demonstrated changes in the landscape, particularly indicated by the shift from Cyperaceae to Poaceae dominance after the 1960 CE. Therefore, all proxies together demonstrate the modification in the landscape and changes in the environment, clearly influenced by anthropogenic action from unsustainable agricultural practices.

Generation of homozygous and heterozygous REEP1 knockout induced pluripotent stem cell lines by CRISPR/Cas9 gene editing.

REEP1 is a transmembrane protein in the endoplasmic reticulum (ER) membrane that is involved in shaping and remodeling of the ER. Mutations in REEP1 cause SPG31, an autosomal dominant form of hereditary spastic paraplegia (HSP). Here we show the generation of a homozygous and a heterozygous REEP1 knockout induced pluripotent stem cell line suitable for in vitro disease modelling using the CRISPR/Cas9 editing system.

Case report: Rhabdomyolysis in children in acute and chronic disease-a challenging condition in pediatric emergency medicine.

Rhabdomyolysis is a challenging condition in pediatric emergency departments (PED): It ranges from asymptomatic illness with isolated elevation of creatine kinase (CK) levels to a life-threatening condition associated with extreme elevations in CK, electrolyte imbalances, circulatory failure (CF), acute kidney injury (AKI), and multi-organ disease. Most common causes of rhabdomyolysis are viral myositis and trauma, hereditary metabolic myopathies must be considered when facing rhabdomyolysis in early childhood. We report two cases of severe rhabdomyolysis with CF in our PED, thereby summarizing first-line management of rhabdomyolysis.

The use of microplastics as a reliable chronological marker of the Anthropocene onset in Southeastern South America.

Microplastics (MPs) represent an emergent contamination marker. For this reason, we analyzed the vertical distribution of MPs in six sediment cores retrieved from the Patos-Mirim System, the world's largest coastal lagoonal system. The sediment cores span from mid Holocene to present times according to both radiocarbon and lead dating and are located close to both urban/industrial and agricultural regions. We identified a basal pre-disturbance MP-free zone in all cores and an uppermost contaminated 70-cm-zone, where a general increasing trend in MPs content resembling the human anthropization process was recorded. The predominant format of MPs was fiber, followed by fragments. The most commonly identified polymers were rayon, PVC, acrylate, polycarbonate and cellophane. Urban/industrial and agricultural activities were shown as clear sources of MPs, leading to comparable MPs concentration values in the sediment cores. Thus, MPs are collectively a reliable indicator of the Anthropocene onset, and in the Patos-Mirim System the most appropriate chronology can be assigned to the beginning of 1970s, matching the intensification of anthropogenic activities in the area.

First Direct Detection Constraints on Planck-Scale Mass Dark Matter with Multiple-Scatter Signatures Using the DEAP-3600 Detector.

Dark matter with Planck-scale mass (≃10^{19} GeV/c^{2}) arises in well-motivated theories and could be produced by several cosmological mechanisms. A search for multiscatter signals from supermassive dark matter was performed with a blind analysis of data collected over a 813 d live time with DEAP-3600, a 3.3 t single-phase liquid argon-based detector at SNOLAB. No candidate signals were observed, leading to the first direct detection constraints on Planck-scale mass dark matter. Leading limits constrain dark matter masses between 8.3×10^{6} and 1.2×10^{19} GeV/c^{2}, and ^{40}Ar-scattering cross sections between 1.0×10^{-23} and 2.4×10^{-18} cm^{2}. These results are interpreted as constraints on composite dark matter models with two different nucleon-to-nuclear cross section scalings.

Aspects of transition cow metabolomics-Part I: Effects of a metaphylactic butaphosphan and cyanocobalamin treatment on the metabolome in liver, blood, and urine in cows with different liver metabotypes.

Dairy cows in modern production systems are at risk to develop metabolic disorders during the transition period. Reasons for individual differences in susceptibility, as well as the underlying pathomechanisms, are still only partially understood. The development of metaphylactic treatment protocols is needed. In this context, an on-farm prospective 3-fold blinded randomized study involving 80 German Holstein cows was performed throughout 1 yr. The trial involved a thorough recording of the production and clinical traits, clinical chemistry, and liver biopsies and blood and urine sampling at d 14 (mean: 12 d, range: 1-26 d) antepartum (AP), and d 7 (7, 4-13) and 28 (28, 23-34) postpartum (PP) for metabolomics analyses. Two groups received a treatment with butaphosphan and cyanocobalamin (BCC) at either the dosage recommended by the manufacturer or the double dosage (5 or 10 mL/100 kg of body weight 10% butaphosphan and 0.005% cyanocobalamin (Catosal, Bayer Animal Health), n = 20 in each group, parity: 4.2 ± 2.0 and 3.4 ± 1.3, respectively (mean ± SD)] and one group a placebo treatment (NaCl 0.9%, n = 40, parity: 4.0 ± 1.9). The animals were treated at 6 time points (7, 6, and 5 d AP, and 1, 2, and 3 d PP) via intravenous injection. Mass spectroscopy-based targeted metabolomics analysis of blood plasma and liver samples were performed using the AbsoluteIDQ p180 kit (Biocrates Life Sciences), whereas the urine samples were analyzed by nuclear magnetic resonance spectroscopy. Statistical analysis was performed using multivariate [partial least squares discriminant analysis (PLS-DA)] and univariate methods (linear mixed model). Multivariate data analysis (PLS-DA plots) of the liver metabolome revealed 3 different metabotypes (A = medium, B = minor, C = large alterations in liver metabolome profile between AP and PP status). Metabotype B animals were characterized by higher PP lipomobilization (stronger PP body condition decrease and higher blood bilirubin, fatty acids, gamma-glutamyltransferase, and triglyceride levels) and a higher occurrence of transition cow diseases, compared with the animals in metabotype C. Analysis of the feeding data showed that the period of metabotype B animals (calving in a distinct time frame) was characterized by a decreased grass silage quality. The PP liver metabolome of the metabotype C animals was characterized by higher concentrations of AA, acylcarnitines, lysoPC and sphingomyelins compared with metabotype B. For the metaphylactic treatment with BCC a dose-dependent effect was confirmed, differing between the metabotypes. In all matrices and metabotypes at various time points significant treatment effects were observed, with different profiles in clinical chemistry and as well in metabolomics data. The most clear-cut treatment effect was observed in metabotype B in the liver at 7 d PP, characterized by an increase in several acylcarnitines and phosphatidylcholines, indicating a more efficient influx and oxidation of fatty acids in mitochondria and thereby an increase in energy supply and more efficient triglyceride export in the liver. The results from the liver metabolomics analysis support the application of an indication-based metaphylactic treatment with BCC.

Aspects of transition cow metabolomics-Part II: Histomorphologic changes in the liver parenchyma throughout the transition period, in cows with different liver metabotypes and effects of a metaphylactic butaphosphan and cyanocobalamin treatment.

The aims of this study were to evaluate histopathologic changes during the transition period, describe the histopathological features of the metabotypes identified in Part I (Schären et al., 2021b), and investigate effects of a metaphylactic treatment with butaphosphan and cyanocobalamin (BCC) on the liver parenchyma. Eighty German Holstein cows (mean 305-d production: 10,957 kg, range: 6,480-15,193 kg; mean lactation number: 3.9, range: 2-9) from a commercial dairy farm in Saxony, Germany, were enrolled in a randomized, prospective, triple-blinded study. Two groups received a treatment with BCC (5 or 10 mL/100 kg of body weight 10% butaphosphan and 0.005% cyanocobalamin, Catosal, Bayer Animal Health, n = 20 each) and one group a placebo treatment (NaCl 0.9%, n = 40). Liver biopsy specimens were collected 14 d antepartum (AP) and 7, 28, and 42 d postpartum (PP), routinely processed for histologic examination, and stained with hematoxylin and eosin, Sudan III, periodic acid-Schiff, and picrosirius red stains. The sections were assessed for fat and glycogen content and degenerative, inflammatory, fibrotic, and proliferative changes. The statistical analysis included the effects of the sampling day, the lactation number, the treatment, and the metabotype (A = medium, B = minor, C = large alterations in the liver metabolome profile between AP and PP status). There was mild to moderate fat infiltration in the liver of 37% of cows in the last 2 wk AP, and moderate to severe fat infiltration in 66% of cows in the first days PP. The degree of fat infiltration increased from 2 wk AP until the end of the first week PP, and then decreased until the end of the study period, at which time about 25% of cows had moderate to severe fatty infiltration. Lipidosis was positively correlated with the severity of liver cell degeneration, and negatively correlated with the degree of glycogen deposits. Complete glycogen depletion of hepatocytes was not observed in cows, even in the presence of severe hepatic lipidosis. Moderate to severe lymphocytic hepatitis was seen in 39% of cows throughout the study period, and cows with lactation numbers 5 or greater had perisinusoidal fibrosis more often than younger cows. Severe fibrosis and cirrhosis of the liver did not occur. Metabotype B animals exhibited a higher chance of fatty infiltration, lower glycogen storage, and perisinusoidal fibrosis and for this metabotype positive correlations were calculated between increased fat deposition in the liver and marked glycogen depletion, and increased degenerative, inflammatory, fibrotic, and proliferative changes of hepatic tissue. For the treatment with BCC, no significant effect was observed. In summary, during the transition period, the liver of dairy cows is characterized by fat accumulation and glycogen depletion and histologic signs of hepatitis and hepatocyte degeneration. These histomorphologic changes were accentuated in animals exhibiting little alterations in their liver metabolome profile across the transition period (metabotype B) and support the assumption of a decreased grass silage quality as a causative factor.

Morphology controlled NH4V3O8 microcrystals by hydrothermal synthesis.

Single crystalline ammonium trivanadate NH4V3O8 with variable morphologies, including shuttles, flowers, belts, and plates, was synthesized by the hydrothermal treatment of NH4VO3 with acetic acid. The crystals optimally grow under gentle conditions of 140 °C for 48 h. The resulting NH4V3O8 microcrystals were characterized by means of X-ray diffraction, scanning electron microscopy, infrared and Raman spectroscopy, static magnetization studies, and thermal analysis. The key factors to control the size and morphology of the crystals are the pH value and the vanadium concentration. A tentative microscopic growth mechanism is proposed and it is demonstrated how shape and morphology of the resulting microcrystalline material can be tuned by appropriate synthesis parameters.

Clinical and microbiological characteristics of peri-implantitis cases: a retrospective multicentre study.

OBJECTIVES: The aim of this study was to follow patient cases retrospectively in a longitudinal manner from the time of implant placement to the time they were diagnosed with peri-implant disease, and to identify associated clinical and microbiological features of peri-implant disease. MATERIAL AND METHODS: A total of 281 patient cases were chosen from the archives of the Oral Microbiological Diagnostic Laboratory, Gothenburg, Sweden, based on bacterial samples taken from diseased implants. A form was designed and filled in separately for each case including data on patient, implant and disease profile. RESULTS: Most cases were severe peri-implantitis cases (91.4%). In 41.3% of the patients, peri-implantitis was developed early, already after having implants in function less than 4 years. The type of implant surface was significantly associated with the time in years implants were in function, before disease was developed (P < 0.05). The microbiological results by both culture and checkerboard analysis, although failed to fully correspond to the severity of the disease in terms of magnitude, proved to show that peri-implantitis is a polymicrobial anaerobic infection with increased number of AGNB (aerobic Gram-negative bacilli) in 18.6% of the patients. CONCLUSIONS: Peri-implantitis is a biological complication of implants in function that poses a threat to their long-term survival. It may develop earlier around implants with rough surfaces and it may represent a true infection. Microbiological sampling methods should be improved and uniformed so as to fully unveil the microbiological profile of the disease.

Quantum oscillations and ferromagnetic hysteresis observed in iron filled multiwall carbon nanotubes.

We report on the electrical transport properties of single multiwall carbon nanotubes with and without an iron filling as a function of temperature and magnetic field. For the iron filled nanotubes the magnetoresistance shows a magnetic behavior induced by iron, which can be explained by taking into account a contribution of s-d hybridization. In particular, ferromagnetic-like hysteresis loops were observed up to 50 K for the iron filled multiwall carbon nanotubes. The magnetoresistance shows quantum interference phenomena such as universal conductance fluctuations and weak localization effects.

Quantitative magnetic force microscopy on permalloy dots using an iron filled carbon nanotube probe.

An iron filled carbon nanotube (FeCNT), a 10-40 nm ferromagnetic nanowire enclosed in a protective carbon tube, is an attractive candidate for a magnetic force microscopy (MFM) probe as it provides a mechanically and chemically robust, nanoscale probe. We demonstrate the probe's capabilities with images of the magnetic field gradients close to the surface of a Py dot in both the multi-domain and vortex states. We show the FeCNT probe is accurately described by a single magnetic monopole located at its tip. Its effective magnetic charge is determined by the diameter of the iron wire and its saturation magnetization 4πM(s) ≈ 2.2 × 10(4)G. A magnetic monopole probe is advantageous as it enables quantitative measurements of the magnetic field gradient close to the sample surface. The lateral resolution is defined by the diameter of the iron wire and the probe-sample separation.

Iron filled carbon nanotubes as novel monopole-like sensors for quantitative magnetic force microscopy.

We present a novel ultrahigh stability sensor for quantitative magnetic force microscopy (MFM) based on an iron filled carbon nanotube. In contrast to the complex magnetic structure of conventional MFM probes, this sensor constitutes a nanomagnet with defined properties. The long iron nanowire can be regarded as an extended dipole of which only the monopole close to the sample surface is involved in the imaging process. We demonstrate its potential for high resolution imaging. Moreover, we present an easy routine to determine its monopole moment and prove that this calibration, unlike other approaches, is universally applicable. For the first time this enables straightforward quantitative MFM measurements.

Delivery of carboplatin by carbon-based nanocontainers mediates increased cancer cell death.

Since the activity of several conventional anticancer drugs is restricted by resistance mechanisms and dose-limiting side-effects, the design of nanocarriers seems to be an efficient and promising approach for drug delivery. Their chemical and mechanical stability and their possible multifunctionality render tubular nanomaterials, such as carbon nanotubes (CNTs) and carbon nanofibres (CNFs), promising delivery agents for anticancer drugs. The goal of the present study was to investigate CNTs and CNFs in order to deliver carboplatin in vitro. No significant intrinsic toxicity of unloaded materials was found, confirming their biocompatibility. Carboplatin was loaded onto CNTs and CNFs, revealing a loading yield of 0.20 mg (CNT-CP) and 0.13 mg (CNF-CP) platinum per milligram of material. The platinum release depended on the carrier material. Whereas CNF-CP marginally released the drug, CNT-CP functioned as a drug depot, constantly releasing up to 68% within 14 days. The cytotoxicity of CNT-CP and CNF-CP in urological tumour cell lines was dependent on the drug release. CNT-CP was identified to be more effective than CNF-CP concerning the impairment of proliferation and clonogenic survival of tumour cells. Moreover, carboplatin, which was delivered by CNT-CP, exhibited a higher anticancer activity than free carboplatin.

Low-frequency rTMS of the premotor cortex reduces complex movement patterns in a patient with pantothenate kinase-associated neurodegenerative disease (PKAN).

INTRODUCTION: Pantothenate kinase-associated neurodegenerative disease (PKAN) is a secondary generalized dystonia associated with an accumulation of iron in the basal ganglia and increased motor cortex excitability. A pilot study in three patients with secondary generalized dystonia had reported a reduced frequency of painful axial spasms following inhibitory 1-Hz repetitive transcranial magnetic stimulation (rTMS) applied over the premotor cortex. PATIENT AND METHODS: We compared the effects of real versus sham rTMS on the frequency of the complex movement pattern and the need for additional benzodiazepine medication in a 6-year-old male patient with PKAN. A 20-minute session of left premotor 1-Hz rTMS was performed daily on 5 consecutive days. RESULTS: The occurrence of the complex movement pattern was gradually reduced from three to two attacks daily to one attack daily by real rTMS while sham rTMS had no effect. This reduction was obtained concomitantly with a similar reduction of additional benzodiazepines for both real and sham rTMS sessions. CONCLUSION: Inhibitory rTMS of the premotor cortex may be used to temporarily control motor symptoms in PKAN.

Structure and electronic properties of Li-doped vanadium oxide nanotubes.

The influence of Li-doping on the mixed-valent vanadium oxide nanotubes has been investigated using electron energy loss spectroscopy. In particular, the electron diffraction profiles and the vanadium L excitation edges have been studied. We observe that the structure of the vanadium oxide nanotubes is stable against electron transfer upon Li-doping. Excitations at the vanadium L edges show features which are associated with a reduction of the vanadium valency.

A new checkerboard panel for testing bacterial markers in periodontal disease.

BACKGROUND/AIMS: Various microbiological methods have been used for testing bacterial markers for periodontitis and periodontal disease progression. Most studies have used only a limited number of well recognized bacterial species. The purpose of the present study was to evaluate the association of 13 more recently identified bacterial species in a new panel in comparison with 12 previously more recognized periodontotopathogens ('old panel') using the 'checkerboard' DNA-DNA hybridization method. METHODS: Fifty individuals were chosen who showed at least one site with a probing pocket depth of 6 mm or more (disease) and bleeding on probing and at least one site with a probing pocket depth of 3 mm and without bleeding on probing (health). One diseased and one healthy site on each individual were sampled with the paperpoint technique and the samples were processed in the checkerboard technique against deoxigenin-labeled whole genomic probes to 25 subgingival species representing 12 well recognized and 13 newly identified periodontitis associated species. RESULTS: Twenty-four (out of 25) species were detected more frequently in the subgingival plaque of diseased than healthy sites both at score 1 (> 10(4)) and score 3 (> 10(5)). A significant difference at the higher score (score 3) was noticed for all species of the old panel except for three (Streptococcus intermedius, Selenomonas noxia, and Eikenella corrodens). Of the species in the new panel only Prevotella tannerae, Filifactor alocis, and Porphyromonas endodontalis showed a statistical significant difference between diseased and healthy sites. CONCLUSION: It was concluded that P. tannerae, F. alocis, and P. endodontalis should be added to the 12 species used for routine diagnostics of periodontitis-associated bacterial flora.

High efficacy and minor renal effects of indomethacin treatment during individualized fluid intake in premature infants with patent ductus arteriosus.

AIM: To determine the efficacy and the renal side effects of indomethacin treatment for closure of a patent ductus arteriosus (PDA) in premature infants during an individualized fluid regime that avoids hypovolaemia and subsequent prostaglandin-dependent renal perfusion. METHODS: Observational retrospective analysis of the efficacy of indomethacin in premature infants with PDA treated in a single institution from June 1992 to May 2000. The clinical course and renal effects were analysed in the subgroup of infants born from June 1995 to May 2000. The management of infants at risk and the treatment of infants with PDA followed a standardized protocol that included echocardiographic screening for PDA, indomethacin treatment before congestive failure develops (early symptomatic treatment) and an individualized fluid intake. RESULTS: In total, 412 infants with a gestational age < or = 32 wk were identified. Fifty-six infants with a PDA (14%) were treated with indomethacin [mean birthweight 936 (95% confidence interval 866-1006) g; gestational age 27.3 (26.8-27.9) wk]. Indomethacin treatment was successful in 52 infants (93%). The clinical course and renal effects were analysed in 41 infants. Most infants received three indomethacin doses of 0.2 mg kg(-1) every 12 h. Urine output transiently decreased from 5.6 (4.6-6.4) to 4.6 (3.9-5.3) ml kg(-1) (h(-1). Serum creatinine temporarily increased from 0.90 (0.83-0.98) to 1.06 (0.87-1.24)mg dl(-1). Fluid intake was 158 (148-168) ml kg(-1) d(-1) before indomethacin and decreased to 142 (131-154) ml kg(-1) d(-1). CONCLUSION: Indomethacin is very effective for closure of a PDA, even in very premature infants, and is not associated with clinically significant renal side effects.

Do we need another NSAID instead of indomethacin for treatment of ductus arteriosus in preterm infants?

UNLABELLED: Up until now indomethacin is the most extensively evaluated non-steroidal anti-inflammatory drug (NSAID) in neonatal medicine. If used with due consideration to the physiologic role of prostaglandins, a 90 success rate can be reached and serious adverse drug effects prevented. CONCLUSION: The results reported by Bellander et al. support the idea that we do not need to study other substances of the same therapeutic class, with the same target--cyclooxygenase--in the prostaglandin cascade and with a similar pharmacological profile. Instead, indomethacin treatment regimes should be further improved with respect to their efficacy and safety.

Self-expandable metal mesh stents for common bile duct stenosis in chronic pancreatitis: retrospective evaluation of long-term follow-up and clinical outcome pilot study.

BACKGROUND: Symptomatic common bile duct strictures are frequently seen in the course of severe chronic pancreatitis with a reported incidence of 10-30%. The exact role of endoscopic stenting with metal prostheses as definitive treatment has not yet been clearly defined. METHODS: Six patients with symptomatic distal common bile duct stricture in the setting of chronic pancreatitis were treated with a self-expandable metal stent in an attempt to achieve permanent drainage. All cases were approached non-operatively and underwent prior unsuccessful treatment with plastic prostheses. RESULTS: The patients received a self-expandable metal Wall stent after a median follow-up of 14 months of plastic stenting. The median follow-up time was 58 months and the stents remained open for a median time of 20 months, respectively. Overall, in 2 of 6 cases the metal stent therapy was successful while 4 of 6 patients required additional endoscopic procedures. CONCLUSIONS: Self-expandable metal stents could be useful and adequate in patients who suffer from symptomatic obstructive jaundice due to chronic pancreatitis. However, they provide acceptable dilation of the common bile duct for only a limited period of time. Overall, endoscopic stenting with self-expandable metal stents seems to be an advantageous treatment only for a subgroup of patients who are unfavorable candidates for surgical drainage. To clarify the role of the endoscopic approach, prospective trials with homogeneous and larger patient numbers are necessarily in the future.

Pancreatic endoscopic sphincterotomy in patients with chronic pancreatitis: a single-center experience in 171 consecutive patients.

BACKGROUND AND STUDY AIMS: In recent years, interest in endoscopic therapy techniques for pancreatic diseases has been constantly increasing. The aim of the present study was to assess the technical success, technique, and complications of endoscopic pancreatic sphincterotomy (EPS) in patients with chronic pancreatitis. PATIENTS AND METHODS: A total of 171 patients with chronic pancreatitis and abdominal complaints were identified in whom at least one attempt at EPS was carried out. During the procedure, sphincterotomy was carried out using a guide-wire sphincterotome or a needle-knife papillotome. Patients were followed up after EPS for at least 24 h, including clinical symptoms and laboratory data (pancreatic enzymes and hemoglobin/hematocrit). RESULTS: EPS was performed in 167 of the 171 patients (technical success rate: 97.7 %). In 24 patients (14 %), a precut technique was necessary using a needle-knife sphincterotome. Sphincterotomy-related complications were observed in seven of the 171 patients (4.1 %), including three cases of bleeding, three patients with mild pancreatitis, and one with retroduodenal perforation. All complications were managed medically. There was no treatment-related mortality. CONCLUSIONS: Endoscopic sphincterotomy of the pancreatic duct in patients with chronic pancreatitis is a fairly safe procedure with a high technical success rate.