Variability of bovine conceptus-related volumes in early pregnancy measured with transrectal 3-dimensional ultrasonography.

Up until now, bovine fetometry has been entirely based on 2-dimensional ultrasonography. Fetal size is estimated by several linear measurements such as crown-rump length (CRL). However, the advent of 3-dimensional ultrasonography (3D-US) provides in vivo access to the volumes of the fetus and its amniotic sac. The objective of this preliminary observational study was to determine the variability of conceptus-related volumes using transrectal 3D-US in dairy cows and to identify factors affecting them. Furthermore, relationships between the gained measurements and calf birth weight were investigated. In total, 315 Simmental and Holstein-Friesian dairy cows were transrectally examined at d 42 after breeding using a portable ultrasound device (Voluson I, GE Healthcare). Gestational volumes including fetal volume (FV) and amniotic sac volume (ASV) were determined with the software tool VOCAL (Virtual Organ Computer-Aided Analysis, GE Healthcare), whereas amniotic fluid volume (AFV) values were derived from the subtraction of FV from ASV. The CRL was determined by means of 3-dimensional data. The mean values and standard deviations for FV, ASV, AFV, and CRL were 1.47 ± 0.25 cm3, 5.86 ± 1.22 cm3, 4.38 ± 1.02 cm3, and 2.38 ± 0.18 cm, respectively. All gestational volumes and CRL values were affected by breed. In Simmental cattle, larger concepti were observed compared with pregnancies derived from Holstein-Friesian animals. Parity affected only ASV and AFV, with heifers showing greater values than lactating cows. The CRL was positively associated with milk protein content. It was not possible to predict calf weight at birth by using FV, ASV, or AFV; however, tendencies were found for ASV and AFV. The present study was the first to adopt 3D-US volumetry to assess early pregnancy development in dairy cattle. Our results showed that this method could be used successfully to identify minor variations in conceptus growth.

Correction to: Induced surface proteins of Staphylococcus epidermidis adhering to titanium implant substrata.

There is a mistake in the original published version of this article. The word 'Streptococcus' in the article title should have been 'Staphylococcus'.

Induced surface proteins of Staphylococcus [corrected] epidermidis adhering to titanium implant substrata.

OBJECTIVE: Staphylococcus epidermidis, as a primary colonizer, is strongly associated with infections of (dental) implants (i.e., peri-implantitis), but little is known about the surface proteome of this bacterium. For the identification of bacterial adhesins, this study investigated the surface proteome of S. epidermidis adhering directly to titanium implant substrata. MATERIALS AND METHODS: S. epidermidis strain ATTC 35984 was cultured either planktonically or on titanium implant specimens. The surface proteomes were isolated by mutanolysin digestion, and proteins were separated by 2D gel electrophoreses to reveal highly expressed proteins only. Protein spots were visualized by silver staining and proteins were identified by mass spectrometry. RESULTS: Surface proteome analyses of S. epidermidis on titanium identified six expressed proteins. Three proteins were highly expressed on the titanium implants including accumulation-associated protein Q8CQD9. These specific proteins could be potential pathogenicity factors of bacteria in peri-implant biofilms. CONCLUSION: For the first time, our study identified S. epidermidis surface proteins, which are expressed after adhesion to titanium implant materials. CLINICAL RELEVANCE: Our study reveals possible candidates for a newly protein-based vaccine against peri-implantitis.

Implications of recent epidemiologic studies for the linear nonthreshold model and radiation protection.

The recently published NCRP Commentary No. 27 evaluated the new information from epidemiologic studies as to their degree of support for applying the linear nonthreshold (LNT) model of carcinogenic effects for radiation protection purposes (NCRP 2018 Implications of Recent Epidemiologic Studies for the Linear Nonthreshold Model and Radiation Protection, Commentary No. 27 (Bethesda, MD: National Council on Radiation Protection and Measurements)). The aim was to determine whether recent epidemiologic studies of low-LET radiation, particularly those at low doses and/or low dose rates (LD/LDR), broadly support the LNT model of carcinogenic risk or, on the contrary, demonstrate sufficient evidence that the LNT model is inappropriate for the purposes of radiation protection. An updated review was needed because a considerable number of reports of radiation epidemiologic studies based on new or updated data have been published since other major reviews were conducted by national and international scientific committees. The Commentary provides a critical review of the LD/LDR studies that are most directly applicable to current occupational, environmental and medical radiation exposure circumstances. This Memorandum summarises several of the more important LD/LDR studies that incorporate radiation dose responses for solid cancer and leukemia that were reviewed in Commentary No. 27. In addition, an overview is provided of radiation studies of breast and thyroid cancers, and cancer after childhood exposures. Non-cancers are briefly touched upon such as ischemic heart disease, cataracts, and heritable genetic effects. To assess the applicability and utility of the LNT model for radiation protection, the Commentary evaluated 29 epidemiologic studies or groups of studies, primarily of total solid cancer, in terms of strengths and weaknesses in their epidemiologic methods, dosimetry approaches, and statistical modelling, and the degree to which they supported a LNT model for continued use in radiation protection. Recommendations for how to make epidemiologic radiation studies more informative are outlined. The NCRP Committee recognises that the risks from LD/LDR exposures are small and uncertain. The Committee judged that the available epidemiologic data were broadly supportive of the LNT model and that at this time no alternative dose-response relationship appears more pragmatic or prudent for radiation protection purposes.

Selective Probing of Hidden Spin-Polarized States in Inversion-Symmetric Bulk MoS_{2}.

Spin- and angle-resolved photoemission spectroscopy is used to reveal that a large spin polarization is observable in the bulk centrosymmetric transition metal dichalcogenide MoS_{2}. It is found that the measured spin polarization can be reversed by changing the handedness of incident circularly polarized light. Calculations based on a three-step model of photoemission show that the valley and layer-locked spin-polarized electronic states can be selectively addressed by circularly polarized light, therefore providing a novel route to probe these hidden spin-polarized states in inversion-symmetric systems as predicted by Zhang et al. [Nat. Phys. 10, 387 (2014).NPAHAX1745-247310.1038/nphys2933].

The hedgehog-signaling pathway is repressed during the osteogenic differentiation of dental follicle cells.

Dental follicle stem cells (DFCs) are precursor cells of alveolar osteoblasts, and previous studies have shown that the growth factor bone morphogenetic protein (BMP)2 induces the osteogenic differentiation of DFCs. However, the molecular mechanism down-stream of the induction of the osteogenic differentiation by BMP2 remains elusive. We investigated therefore the phosphoproteome of DFCs after the induction of the osteogenic differentiation with BMP2. In this study, phosphoproteins of the hedgehog "off" state were differentially expressed. Further analyses revealed that BMP2 induced the expression of repressors of the hedgehog-signaling pathway such as Patched 1 (PTCH1), Suppressor of Fused (SUFU), and Parathyroid Hormone-Related Peptide (PTHrP). Previous studies suggested that hedgehog proteins induce the osteogenic differentiation of mesenchymal stem cells via a paracrine pathway. Indian hedgehog (IHH) induced the expression of the osteogenic transcription factor RUNX2. However, a supplementation of the BMP2-based osteogenic differentiation medium with IHH did not induce the expression of RUNX2. Moreover, IHH inhibited slightly the ALP activity and the mineralization of osteogenic-differentiated DFCs. In conclusion, our results suggest that BMP2 inhibits the hedgehog signaling after the induction of the osteogenic differentiation in DFCs.

Feasibility of an exercise programme in elderly patients undergoing allogeneic stem cell transplantation - a pilot study.

It has been demonstrated that physical exercise benefits younger patients undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT). We designed a prospective pilot study investigating whether elderly patients (>60 years) would also be able to participate in such a programme. It consisted of physiotherapist-supervised alternating endurance and resistance workouts on 6 of 7 days a week. Sixteen consecutive patients undergoing allo-HSCT were enrolled into the study. The median age was 64.5 years. Twelve patients participated in the programme until the time of discharge (75%) from the transplant unit. Therefore, the predefined criteria regarding feasibility were met. The reason for drop out was transplantation associated mortality in all patients (n = 4). Adherence was very good with a median of 85% attended training sessions. No adverse events were recorded. The endurance capacity dropped by 7% and lower extremity strength improved by 2% over time. Quality of life decreased during the study period, with global health being significantly worse at the time of discharge. In conclusion, a combined and intensified strength and endurance exercise programme is feasible and safe in a population of elderly patients undergoing allo-HSCT. Further research should focus on exploring effect sizes of such an intervention by conducting randomised controlled trials.

Impact of electron-hole correlations on the 1T-TiSe_{2} electronic structure.

Several experiments have been performed on 1T-TiSe_{2} in order to identify whether the electronic structure is semimetallic or semiconducting without reaching a consensus. In this Letter, we theoretically study the impact of electron-hole and electron-phonon correlations on the bare semimetallic and semiconducting electronic structure. The resulting electron spectral functions provide a direct comparison of both cases and demonstrate that 1T-TiSe_{2} is of predominant semiconducting character with some spectral weight crossing the Fermi level.

Outcomes for split-thickness skin transplantation in high-risk patients using octenidine.

Skin transplantation is a commonly used surgical technique; however, the complication rate, including postoperative infection and delayed wound healing due to inefficient perfusion, is significantly higher in patients suffering from comorbidities. Hence, a subsequent repeat procedure is often necessary. In this report, two case studies are presented in which an octenidine-based antiseptic is used with a tie-over dressing (TOD) instead of povidone iodine (PVP-iodine), following a split-thickness skin graft. The two patients selected were deemed to be at high risk of impaired wound healing due to comorbidities. The first patient, a confirmed smoker with diabetes, presented with a nodular melanoma that was resected and covered with a split-thickness skin graft. After 5 days of negative pressure wound therapy as a TOD, in combination with PVP-iodine, the graft became necrotic. A second split-thickness skin graft was performed and an antiseptic regimen with octenidine in combination with the same TOD resulted in a completely healed transplant. The second patient, also a confirmed smoker with diabetes and receiving oral corticosteroid treatment, was diagnosed with a skin necrosis on her leg. Following the split-thickness skin graft, octenidine and TOD were applied. The patient's skin graft completely healed without any adverse events. These two case studies indicate that the combination of octenidine and TOD following split-thickness skin transplantation is safe, well-tolerated and appears to have positive benefits in the reconstruction of defects in patients with impaired wound healing.

Comparative study of elbow disorders in young high-performance gymnasts.

The study aimed to investigate the prognosis of osteochondral affection (e.g., osteochondritis dissecans (OCD), cartilage lesions, fractures and bone edema in the elbows of high-performance gymnasts (n=30) compared to prognosis results with athletes not undergoing excessive stress on the upper extremity (n=29). The study also tested a novel isotropic 3D-FSE-sequence (CUBE) technique as an early diagnostic modality. Standard protocol was used to conduct the MRI examinations, which were then compared to results from the CUBE - sequence. The gymnast group (p=0.012) presented a significantly higher prevalence of complaints in the elbow joint compared to the other athlete group. Furthermore, osteochondral lesions in MRIs appeared more frequently in the group of gymnasts (n=10, 33%, p=0.033), including 7 cases (23%) of OCD. In the control athlete group 2 asymptomatic cases of OCD and one case of bone edema were detected. The MRI investigation with the CUBE - sequence showed similar results as the standard MRI protocol in terms of the diagnosis sensitivity. The current study indicates that juvenile gymnasts are at a higher risk for osteochondral lesions of the elbow than athletes without excessive stress on the upper extremities.

Clinical and dermoscopic characteristics of Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy with a high mortality rate. Diagnosis is often delayed. OBJECTIVES: To characterize the dermoscopic features of MCC. METHODS: Clinical and dermoscopic images of 12 biopsy-proven MCCs were analysed in a retrospective manner, with existing dermoscopic criteria being scored independently by three dermatologists. RESULTS: The four most frequent clinical features were cherry red colour, shiny surface, sharp circumscription and nodular morphology. Significant dermoscopic features included linear irregular and polymorphous vessels, poorly focused vessels, milky pink areas, white areas, structureless areas and architectural disorder. Pigmented structures were absent from all lesions. CONCLUSIONS: The dermoscopic features described herein help the clinician to distinguish MCC from other benign and malignant red nodules. Increasing recognition of the presenting features will facilitate earlier diagnosis of MCC and reduced mortality.

Enzyme replacement therapy for alpha-mannosidosis: 12 months follow-up of a single centre, randomised, multiple dose study.

BACKGROUND: Alpha-mannosidosis (OMIM 248500) is a rare lysosomal storage disease (LSD) caused by alpha-mannosidase deficiency. Manifestations include intellectual disabilities, facial characteristics and hearing impairment. A recombinant human alpha-mannosidase (rhLAMAN) has been developed for weekly intravenous enzyme replacement therapy (ERT). We present the preliminary data after 12 months of treatment. METHODS: This is a phase I-II study to evaluate safety and efficacy of rhLAMAN. Ten patients (7-17 y) were treated. We investigated efficacy by testing motor function (6-minutes-Walk-Test (6-MWT), 3-min-Stair-Climb-Test (3-MSCT), The Bruininks-Oseretsky Test of Motor Proficiency (BOT2), cognitive function (Leiter-R), oligosaccharides in serum, urine and CSF and Tau- and GFA-protein in CSF. RESULTS: Oligosaccharides: S-, U- and CSF-oligosaccharides decreased 88.6% (CI -92.0 -85.2, p < 0.001), 54.1% (CI -69.5- -38.7, p < 0,001), and 25.7% (CI -44.3- -7.1, p < 0.05), respectively. Biomarkers: CSF-Tau- and GFA-protein decreased 15%, p < 0.009) and 32.5, p < 0.001 respectively. Motor function: Improvements in 3MSCT (31 steps (CI 6.8-40.5, p < 0.01) and in 6MWT (60.4 m (CI -8.9 -51.1, NS) were achieved. Cognitive function: Improvement in the total Equivalence Age of 4 months (0.34) was achieved in the Leiter R test (CI -0.2-0.8, NS). CONCLUSIONS: These data suggest that rhLAMAN may be an encouraging new treatment for patients with alpha-mannosidosis.The study is designed to continue for a total of 18 months. Longer-term follow-up of patients in this study and the future placebo-controlled phase 3 trial are needed to provide greater support for the findings in this study.

Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration.

Hypoxia stimulates angiogenesis through the binding of hypoxia-inducible factors to the hypoxia-response element in the vascular endothelial growth factor (Vegf) promotor. Here, we report that deletion of the hypoxia-response element in the Vegf promotor reduced hypoxic Vegf expression in the spinal cord and caused adult-onset progressive motor neuron degeneration, reminiscent of amyotrophic lateral sclerosis. The neurodegeneration seemed to be due to reduced neural vascular perfusion. In addition, Vegf165 promoted survival of motor neurons during hypoxia through binding to Vegf receptor 2 and neuropilin 1. Acute ischemia is known to cause nonselective neuronal death. Our results indicate that chronic vascular insufficiency and, possibly, insufficient Vegf-dependent neuroprotection lead to the select degeneration of motor neurons.

The magnitude of variability produced by methods used to estimate annual stormwater contaminant loads for highly urbanised catchments.

Stormwater contaminant loading estimates using event mean concentration (EMC), rainfall/runoff relationship calculations and computer modelling (Model of Urban Stormwater Infrastructure Conceptualisation--MUSIC) demonstrated high variability in common methods of water quality assessment. Predictions of metal, nutrient and total suspended solid loadings for three highly urbanised catchments in Sydney estuary, Australia, varied greatly within and amongst methods tested. EMC and rainfall/runoff relationship calculations produced similar estimates (within 1 SD) in a statistically significant number of trials; however, considerable variability within estimates (∼50 and ∼25 % relative standard deviation, respectively) questions the reliability of these methods. Likewise, upper and lower default inputs in a commonly used loading model (MUSIC) produced an extensive range of loading estimates (3.8-8.3 times above and 2.6-4.1 times below typical default inputs, respectively). Default and calibrated MUSIC simulations produced loading estimates that agreed with EMC and rainfall/runoff calculations in some trials (4-10 from 18); however, they were not frequent enough to statistically infer that these methods produced the same results. Great variance within and amongst mean annual loads estimated by common methods of water quality assessment has important ramifications for water quality managers requiring accurate estimates of the quantities and nature of contaminants requiring treatment.

Mapping of electron-hole excitations in the charge-density-wave system 1T-TiSe2 using resonant inelastic x-ray scattering.

In high-resolution resonant inelastic x-ray scattering at the Ti L edge of the charge-density-wave system 1T-TiSe(2), we observe sharp low energy loss peaks from electron-hole pair excitations developing at low temperature. These excitations are strongly dispersing as a function of the transferred momentum of light. We show that the unoccupied bands close to the Fermi level can effectively be probed in this broadband material. Furthermore, we extract the order parameter of the charge-density-wave phase from temperature-dependent measurements.

Large-scale population disappearances and cycling in the white-lipped peccary, a tropical forest mammal.

Many vertebrate species undergo population fluctuations that may be random or regularly cyclic in nature. Vertebrate population cycles in northern latitudes are driven by both endogenous and exogenous factors. Suggested causes of mysterious disappearances documented for populations of the Neotropical, herd-forming, white-lipped peccary (Tayassu pecari, henceforth "WLP") include large-scale movements, overhunting, extreme floods, or disease outbreaks. By analyzing 43 disappearance events across the Neotropics and 88 years of commercial and subsistence harvest data for the Amazon, we show that WLP disappearances are widespread and occur regularly and at large spatiotemporal scales throughout the species' range. We present evidence that the disappearances represent 7-12-year troughs in 20-30-year WLP population cycles occurring synchronously at regional and perhaps continent-wide spatial scales as large as 10,000-5 million km2. This may represent the first documented case of natural population cyclicity in a Neotropical mammal. Because WLP populations often increase dramatically prior to a disappearance, we posit that their population cycles result from over-compensatory, density-dependent mortality. Our data also suggest that the increase phase of a WLP cycle is partly dependent on recolonization from proximal, unfragmented and undisturbed forests. This highlights the importance of very large, continuous natural areas that enable source-sink population dynamics and ensure re-colonization and local population persistence in time and space.

Exciton condensation driving the periodic lattice distortion of 1T-TiSe2.

We address the lattice deformation of 1T-TiSe2 within the exciton condensate phase. We show that, at low temperature, condensed excitons influence the lattice through electron-phonon interaction. It is found that at zero temperature, in the exciton condensate phase of 1T-TiSe2, this exciton condensate exerts a force on the lattice generating ionic displacements comparable in amplitude to what is measured in experiment. This is thus the first quantitative estimation of the amplitude of the periodic lattice distortion observed in 1T-TiSe2 as a consequence of the exciton condensate phase.

Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions.

Vascular endothelial growth factor (VEGF) stimulates angiogenesis by activating VEGF receptor-2 (VEGFR-2). The role of its homolog, placental growth factor (PlGF), remains unknown. Both VEGF and PlGF bind to VEGF receptor-1 (VEGFR-1), but it is unknown whether VEGFR-1, which exists as a soluble or a membrane-bound type, is an inert decoy or a signaling receptor for PlGF during angiogenesis. Here, we report that embryonic angiogenesis in mice was not affected by deficiency of PlGF (Pgf-/-). VEGF-B, another ligand of VEGFR-1, did not rescue development in Pgf-/- mice. However, loss of PlGF impaired angiogenesis, plasma extravasation and collateral growth during ischemia, inflammation, wound healing and cancer. Transplantation of wild-type bone marrow rescued the impaired angiogenesis and collateral growth in Pgf-/- mice, indicating that PlGF might have contributed to vessel growth in the adult by mobilizing bone-marrow-derived cells. The synergism between PlGF and VEGF was specific, as PlGF deficiency impaired the response to VEGF, but not to bFGF or histamine. VEGFR-1 was activated by PlGF, given that anti-VEGFR-1 antibodies and a Src-kinase inhibitor blocked the endothelial response to PlGF or VEGF/PlGF. By upregulating PlGF and the signaling subtype of VEGFR-1, endothelial cells amplify their responsiveness to VEGF during the 'angiogenic switch' in many pathological disorders.

Interventional management of intractable sympathetically mediated pain by computed tomography-guided catheter implantation for block and neuroablation of the thoracic sympathetic chain: technical approach and review of 322 procedures.

We retrospectively evaluated the safety and efficacy of computed tomography-guided placement of percutaneous catheters in close proximity to the thoracic sympathetic chain by rating pain intensity and systematically reviewing charts and computed tomography scans. Interventions were performed 322 times in 293 patients of mean (SD) age 59.4 (17.0) years, and male to female ratio 105:188, with postherpetic neuralgia (n = 103, 35.1%), various neuralgias (n = 88, 30.0%), complex regional pain syndrome (n = 69, 23.6%), facial pain (n = 17, 5.8%), ischaemic limb pain (n = 7, 2.4%), phantom limb pain (n = 4, 1.4%), pain following cerebrovascular accident (n = 2, 0.7%), syringomyelia (n = 2, 0.7%) and palmar hyperhidrosis (n = 1, 0.3%). The interventions were associated with a total of 23 adverse events (7.1% of all procedures): catheter dislocation (n = 9, 2.8%); increase in pain intensity (n = 8, 2.5%); pneumothorax (n = 3, 0.9%); local infection (n = 2, 0.6%); and puncture of the spinal cord (n = 1, 0.3%). Continuous infusion of 10 ml.h(-1) ropivacaine 0.2% through the catheters decreased median (IQR [range]) pain scores from 8 (6-9 [2-10]) to 2 (1-3 [0-10]) (p < 0.0001). Chemical neuroablation was necessary in 137 patients (46.8%). We conclude that this procedure leads to a significant reduction of pain intensity in otherwise obstinate burning or stabbing pain and is associated with few hazards.