Acute Ischemic Stroke Infarct Topology: Association with Lesion Volume and Severity of Symptoms at Admission and Discharge.
Acute stroke presentation and outcome depend on both ischemic infarct volume and location. We aimed to determine the association between acute ischemic infarct topology and lesion volume and stroke severity at presentation and discharge. Patients with acute ischemic stroke who underwent MR imaging within 24 hours of symptom onset or last seen well were included. Infarcts were segmented and coregistered on the Montreal Neurological Institute-152 brain map. Voxel-based analyses were performed to determine the distribution of infarct lesions associated with larger volumes, higher NIHSS scores at admission and discharge, and greater NIHSS/volume ratios. A total of 238 patients were included. Ischemic infarcts involving the bilateral lentiform nuclei, insular ribbons, middle corona radiata, and right precentral gyrus were associated with larger infarct volumes (average, 76.7 ± 125.6 mL versus 16.4 ± 24.0 mL, P < .001) and higher admission NIHSS scores. Meanwhile, brain stem and thalami infarctions were associated with higher admission NIHSS/volume ratios. The discharge NIHSS scores were available in 218 patients, in whom voxel-based analysis demonstrated that ischemic infarcts of the bilateral posterior insular ribbons, middle corona radiata, and right precentral gyrus were associated with more severe symptoms at discharge, whereas ischemic lesions of the brain stem, bilateral thalami, and, to a lesser extent, the middle corona radiata were associated with higher ratios of discharge NIHSS score/infarct volume. Acute ischemic infarcts of the insulae, lentiform nuclei, and middle corona radiata tend to have larger volumes, more severe presentations, and worse outcomes, whereas brain stem and thalamic infarcts have greater symptom severity relative to smaller lesion volumes.


Clinical Manifestations Associated with Overweight/Obesity in Puerto Ricans with Fibromyalgia Syndrome.
Objective. To determine the clinical manifestations associated with overweight/obesity in Hispanics from Puerto Rico with fibromyalgia syndrome (FMS). Methods. A cross-sectional study was performed in 144 patients with FMS (per American College of Rheumatology (ACR) classification criteria). Sociodemographic features, FMS-related symptoms, tender points (per ACR criteria), comorbidities, and FMS treatment were examined. BMI was calculated and patients were grouped into two categories: BMI ≤ 24.9 kg/m(2) (nonoverweight/obese) and BMI ≥ 25 kg/m(2) (overweight/obese). Bivariate and multivariate analyses were used to evaluate differences between the study groups. Results. The mean (standard deviation (SD)) age of patients was 50.2 (9.9) years; 95.1% were females and 75.7% were overweight/obese. In the bivariate analysis, overweight/obese patients were more likely to have self-reported memory impairment, anxiety, shortness of breath, and urinary frequency than nonoverweight/obese patients. In addition, the tender point count was higher in the overweight/obese group. In the logistic regression analyses, self-reported memory impairment and urinary frequency differences remained significant after adjusting for confounding variables. Conclusion. In this population of Puerto Ricans with FMS, overweight/obese patients experienced more FMS-related manifestations than nonoverweight/obese individuals. However, prospective studies are needed to confirm these associations and to elucidate if weight reduction interventions could favorably impact the severity of FMS.


Diagnostic and prognostic accuracy of Protein C in adult patients with sepsis: protocol for a systematic review and meta-analysis.
Sepsis is a dysregulated host response to infection characterised by activation of proinflammatory and procoagulant mechanisms. Protein C (PC)'s activity as an anticoagulant and antiinflammatory molecule makes it an appealing target for sepsis biomarker studies. To date, there has been no systematic review of PC as a sepsis biomarker. To evaluate the diagnostic accuracy and prognostic strength of PC as a biomarker for adult sepsis. Medline, Embase, Cochrane Library, PubMed and Cumulative Index to Nursing and Allied Health Literature (CINAHL) will be searched from inception through 20 January 2021 for prospective observational studies that evaluate the use of PC as a diagnostic or prognostic biomarker for adult sepsis. Title and abstract screening, full-text screening and data extraction will be conducted in duplicate. Risk of bias will be assessed using the Quality Assessment of Diagnostic Accuracy Studies and Quality in Prognostic Studies tools. If sufficient data are available, a meta-analysis will be conducted. The standardised mean difference and 95% CI will be calculated for prognostic and diagnostic studies. If possible, a hierarchical summary receiver operator characteristic curve will be generated to assess overall prognostic and diagnostic biomarker accuracy. I2 statistics will be used to assess heterogeneity. Sensitivity analysis will be performed by removing studies with a high risk of bias and re-examining the meta-analysis results. Given this is a systematic review and meta-analysis, there is no requirement for ethics approval. Findings will be disseminated through a peer-reviewed publication and social media. CRD42021229786.


Trends in biological joint resurfacing.
The treatment of osteochondral lesions and osteoarthritis remains an ongoing clinical challenge in orthopaedics. This review examines the current research in the fields of cartilage regeneration, osteochondral defect treatment, and biological joint resurfacing, and reports on the results of clinical and pre-clinical studies. We also report on novel treatment strategies and discuss their potential promise or pitfalls. Current focus involves the use of a scaffold providing mechanical support with the addition of chondrocytes or mesenchymal stem cells (MSCs), or the use of cell homing to differentiate the organism's own endogenous cell sources into cartilage. This method is usually performed with scaffolds that have been coated with a chemotactic agent or with structures that support the sustained release of growth factors or other chondroinductive agents. We also discuss unique methods and designs for cell homing and scaffold production, and improvements in biological joint resurfacing. There have been a number of exciting new studies and techniques developed that aim to repair or restore osteochondral lesions and to treat larger defects or the entire articular surface. The concept of a biological total joint replacement appears to have much potential. Cite this article: Bone Joint Res 2013;2:193-9.


Misdiagnosis of prolonged psychogenic non-epileptic seizures as status epilepticus: epidemiology and associated risks.
To determine the epidemiology of prolonged psychogenic non-epileptic seizures (pPNES) misdiagnosed as status epilepticus, as well as the risks associated with non-indicated treatment. We performed an individual patient data analysis from the Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) and the Established Status Epilepticus Treatment Trial (ESETT) to assess incidence, patient characteristics and clinical course of misdiagnosed pPNES. Among 980 patients aged 8 years or older diagnosed and treated for status epilepticus in RAMPART and ESETT, 79 (8.1%) were discharged with a final diagnosis of pPNES. The relative incidence was highest in adolescents and young adults (20.1%). The typical female preponderance seen in that age bracket was not evident in children and older adults. Adverse effects, including respiratory depression and intubation, were documented in 26% of patients with pPNES receiving benzodiazepines in RAMPART and 33% of patients receiving additional second-line medication in ESETT. In ESETT, patients who were treated with benzodiazepines before hospital admission had higher rates of unresponsiveness and severe adverse effects than those treated after admission, suggesting cumulative effects of accelerated treatment momentum. Across trials, one in five patients with pPNES were admitted to an intensive care unit. Misdiagnosis and treatment of pPNES as status epilepticus are a common and widespread problem with deleterious consequences. Mitigating it will require training of emergency staff in semiological diagnosis. Status epilepticus response protocols should incorporate appropriate diagnostic re-evaluations at each step of treatment escalation, especially in clinical trials.


Charge manipulation for improved mass determination of high-mass species and mixture components by electrospray mass spectrometry.
The manipulation of the charge states of high-mass ions can facilitate mass determination in electrospray (ES) mass spectrometry. Specifically, the reduction of charge (which leads to ions of higher mass-to-charge ratios) can significantly reduce peak overlap. Signals associated with various charge states of high-mass ions are more easily resolved at low charge states and chemical noise tends to be significantly lower at high mass-to-charge ratios than in the normal mass-to-charge window typically associated with electrospray. Algorithms that transform ES mass spectra to zero-charge spectra are most likely to yield unambiguous results when charge states are clearly resolved and when signal-to-noise ratios are relatively high. Charge manipulation can enhance the value of the transformation algorithms in cases in which compromises their utility. Such situations include ES mass spectra of high-mass species that yield charge states that are not baseline resolved, mixtures with many components and mixtures in which the signals from major components overwhelm signals from minor components. Examples of improved mass determination are illustrated for proteins using ion-ion chemistry as the means for charge state manipulation and the quadrupole ion trap as the mass analyzer.


Heterogeneous UV/Fenton catalytic degradation of wastewater containing phenol with Fe-Cu-Mn-Y catalyst.
The heterogeneous UV/Fenton process with the appropriate amount of Fe-Mn-Cu-Y as catalyst was developed and various operation conditions for the degradation of phenol were evaluated. The results indicated that by using the heterogeneous UV/Fenton process, the COD(cr) removal rate reached almost 100% for wastewater containing phenol. Compared with the homogeneous process, the developed catalyst could be used at wider pH range in the UV/Fenton process. Comparison of various heterogeneous process showed that heterogeneous UV/Fenton process was best. The heterogeneous UV/Fenton process with Fe-Mn-Cu-Y catalyst is highly efficient in degrading various organic pollutants.


Expectant care versus surgical treatment for miscarriage.
Miscarriage is a common complication of early pregnancy that can have both medical and psychological consequences such as depression and anxiety. The need for routine surgical evacuation with miscarriage has been questioned because of potential complications such as cervical trauma, uterine perforation, hemorrhage, or infection. To compare the safety and effectiveness of expectant management versus surgical treatment for early pregnancy failure. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (9 February 2012), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2011, Issue 4 of 4), PubMed (2005 to 11 January 2012), POPLINE (inception to 11 January 2012), LILACS (2005 to 11 January 2012) and reference lists of retrieved studies. Randomized trials comparing expectant care and surgical treatment (vacuum aspiration or dilation and curettage) for miscarriage were eligible for inclusion. Two review authors assessed trial quality and extracted data. We contacted study authors for additional information. For dichotomous data, we calculated the Mantel-Haenszel risk ratio (RR) with 95% confidence interval (CI). For continuous data, we computed the mean difference (MD) and 95% CI. We entered additional data such as medians into 'Other data' tables. We included seven trials with 1521 participants in this review. The expectant-care group was more likely to have an incomplete miscarriage by two weeks (RR 3.98; 95% CI 2.94 to 5.38) or by six to eight weeks (RR 2.56; 95% CI 1.15 to 5.69). The need for unplanned surgical treatment was greater for the expectant-care group (RR 7.35; 95% CI 5.04 to 10.72). The mean percentage needing surgical management in the expectant-care group was 28%, while 4% of the surgical-treatment group needed additional surgery. The expectant-care group had more days of bleeding (MD 1.59; 95% CI 0.74 to 2.45). Further, more of the expectant-care group needed transfusion (RR 6.45; 95% CI 1.21 to 34.42). The mean percentage needing blood transfusion was 1.4% for expectant care compared with none for surgical management. Results were mixed for pain. Diagnosis of infection was similar for the two groups (RR 0.63; 95% CI 0.36 to 1.12), as were results for various psychological outcomes. Pregnancy data were limited. Costs were lower for the expectant-care group (MD -499.10; 95% CI -613.04 to -385.16; in UK pounds sterling). Expectant management led to a higher risk of incomplete miscarriage, need for unplanned (or additional) surgical emptying of the uterus, bleeding and need for transfusion. Risk of infection and psychological outcomes were similar for both groups. Costs were lower for expectant management. Given the lack of clear superiority of either approach, the woman's preference should be important in decision making. Pharmacological ('medical') management has added choices for women and their clinicians and has been examined in other reviews.


Treatment of depression with antidepressants is primarily a psychological treatment.
Depression treatment with antidepressants is generally described as evidence-based. However, generalizations to practice recommendations seem to us to rest on the tacit assumption that treatment outcome in research trials is the sum of three factors: specific effects of the drug, expectancy effects (placebo), and spontaneous recovery. Because randomization isolates the specific effects of the drug, trials showing significant drug effects are used as evidence for prescribing the drug regardless of context. Drawing on Wampold's (2001) description of two metamodels of psychotherapy, the authors argue that available empirical evidence indicates that depression treatment with antidepressants is primarily a psychological treatment. This conclusion has far-reaching consequences for the scientific status of contemporary treatments for depression. It also affects what the doctor should focus on in a treatment with antidepressants and how to act when the patient is treatment resistant. In order to achieve the results obtained in clinical trials, the quantity and quality of support from the doctor is more important than pharmacological concerns, such as adequate doses of medicine. When faced with a treatment resistant patient, relationship factors rather than pharmacological factors should be in focus. (PsycINFO Database Record (c) 2010 APA, all rights reserved).


Mutations in c-Ki-ras oncogenes in diseased livers of winter flounder from Boston Harbor.
Livers of a natural population of winter flounder from a contaminated site in Boston Harbor were examined for the presence of oncogenes by transfection of DNA into NIH 3T3 mouse fibroblasts. Tissues analyzed contained histopathologic lesions including abnormal vacuolation, biliary proliferation, and, in many cases, hepatocellular and cholangiocellular carcinomas. Fibroblasts transfected with liver DNA samples from 7 of 13 diseased animals were effective in the induction of subcutaneous sarcomas in nude mice. Further analysis revealed the presence of flounder c-Ki-ras oncogenes in all 10 nude mouse subcutaneous tumors analyzed. Direct DNA sequencing and allele-specific oligonucleotide hybridization following amplification of the tumor DNA by the polymerase chain reaction showed mutations in the 12th codon in this gene. Analysis of DNA from all nude mouse tumors as well as the livers from which they were derived showed mutations at this codon. The mutations comprised G.C----A.T or G.C----T.A base changes resulting in substitution of serine, valine, or cysteine for glycine. Liver DNA samples from five histologically normal livers of animals from a less polluted site were ineffective in the transfection assay and showed only wild-type DNA sequences (GGT) at the 12th codon of c-Ki-ras. The prevalence of mutations in this gene region was associated with the presence of liver lesions and could signify DNA damage resulting from environmental chemical exposure.


Acute gallstone pancreatitis with pseudocyst as a complication.
Gallstone disease as the etiology of pancreatitis is much more common in private hospital patients than was once described. Common duct stones (choledocholithiasis) have been proven not to coexist in the majority of cases. The objectives of surgery for gallstone pancreatitis therefore should be adequate drainage of the pancreas, evaluation of the common duct, and cholecystectomy. Common duct exploration usually is not warranted or advised.A pseudocyst may occur subsequent to the acute phase of pancreatitis, or subsequent to surgery for pancreatitis if the pancreas is not adequately and widely drained. The collection of fluid adjacent to or within the pancreas must be determined to be either a pancreatic abscess or a pancreatic pseudocyst. The management of the pseudocyst, which is usually diagnosed by the ultrasonographic finding of a thickened wall, is adjacent internal drainage. By contrast, the pancreatic abscess must have wide, radical, external drainage.Mature judgement must be exercised in the approach to, the timing of, and the management of surgery for gallstone pancreatitis or pseudocyst formation.


Structural organization of the human folypoly-gamma-glutamate synthetase gene: evidence for a single genomic locus.
The cytotoxicity, and probably the selectivity, of folate antimetabolites depend upon the expression of the enzyme folylpoly-gamma-glutamate synthetase in tumor cells. Evidence for the existence of multiple forms of this enzyme and the need to define the control mechanisms determinant of expression levels in normal and neoplastic cells has focused attention on the gene(s) encoding these forms. The organization of the genomic locus for the human folylpoly-gamma-glutamate synthetase (FPGS) gene has been determined. The complete 2256 nucleotides of cDNA for the 5'-untranslated region, mitochondrial leader sequence, coding region, and 3'-untranslated region were distributed on 15 exons stretching over 11.2 kb of genomic DNA. All of the restriction fragments found in diploid human genomic DNA could be accounted for by fragments contained on the isolated genomic clones. Likewise, Southern analysis of the transfected human genomic DNA that complemented the FPGS- phenotype of a hamster cell line indicated that the same gene had been integrated in all of three independently derived transfectants. We conclude that the genomic locus that we now report appears to be the only gene encoding FPGS-related sequences in the human complement.


Peer-led healthy lifestyle program in supportive housing: study protocol for a randomized controlled trial.
The risk for obesity is twice as high in people with serious mental illness (SMI) compared to the general population. Racial and ethnic minority status contribute additional health risks. The aim of this study is to describe the protocol of a Hybrid Trial Type 1 design that will test the effectiveness and examine the implementation of a peer-led healthy lifestyle intervention in supportive housing agencies serving diverse clients with serious mental illness who are overweight or obese. The Hybrid Trial Type 1 design will combine a randomized effectiveness trial with a mixed-methods implementation study. The effectiveness trial will test the health impacts of a peer-led healthy lifestyle intervention versus usual care in supportive housing agencies. The healthy lifestyle intervention is derived from the Group Lifestyle Balanced Program, lasts 12 months, and will be delivered by trained peer specialists. Repeated assessments will be conducted at baseline and at 6, 12, and 18 months post randomization. A mixed-methods (e.g., structured interviews, focus groups, surveys) implementation study will be conducted to examine multi-level implementation factors and processes that can inform the use of the healthy lifestyle intervention in routine practice, using data from agency directors, program managers, staff, and peer specialists before, during, and after the implementation of the effectiveness trial. This paper describes the use of a hybrid research design that blends effectiveness trial methodologies and implementation science rarely used when studying the physical health of people with SMI and can serve as a model for integrating implementation science and health disparities research. Rigorously testing effectiveness and exploring the implementation process are both necessary steps to establish the evidence for large-scale delivery of peer-led healthy lifestyle intervention to improve the physical health of racial/ethnic minorities with SMI. www.clinicaltrials.gov; NCT02175641, registered 24 June 2014.


Increased frequency of travel in the presence of cross-immunity may act to decrease the chance of a global pandemic.
The high frequency of modern travel has led to concerns about a devastating pandemic since a lethal pathogen strain could spread worldwide quickly. Many historical pandemics have arisen following pathogen evolution to a more virulent form. However, some pathogen strains invoke immune responses that provide partial cross-immunity against infection with related strains. Here, we consider a mathematical model of successive outbreaks of two strains-a low virulence (LV) strain outbreak followed by a high virulence (HV) strain outbreak. Under these circumstances, we investigate the impacts of varying travel rates and cross-immunity on the probability that a major epidemic of the HV strain occurs, and the size of that outbreak. Frequent travel between subpopulations can lead to widespread immunity to the HV strain, driven by exposure to the LV strain. As a result, major epidemics of the HV strain are less likely, and can potentially be smaller, with more connected subpopulations. Cross-immunity may be a factor contributing to the absence of a global pandemic as severe as the 1918 influenza pandemic in the century since. This article is part of the theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes'. This issue is linked with the subsequent theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control'.


Using Historical Biogeography Models to Study Color Pattern Evolution.
Color is among the most striking features of organisms, varying not only in spectral properties like hue and brightness, but also in where and how it is produced on the body. Different combinations of colors on a bird's body are important in both environmental and social contexts. Previous comparative studies have treated plumage patches individually or derived plumage complexity scores from color measurements across a bird's body. However, these approaches do not consider the multivariate nature of plumages (allowing for plumage to evolve as a whole) or account for interpatch distances. Here, we leverage a rich toolkit used in historical biogeography to assess color pattern evolution in a cosmopolitan radiation of birds, kingfishers (Aves: Alcedinidae). We demonstrate the utility of this approach and test hypotheses about the tempo and mode of color evolution in kingfishers. Our results highlight the importance of considering interpatch distances in understanding macroevolutionary trends in color diversity and demonstrate how historical biogeography models are a useful way to model plumage color pattern evolution. Furthermore, they show that distinct color mechanisms (pigments or structural colors) spread across the body in different ways and at different rates. Specifically, net rates are higher for structural colors than pigment-based colors. Together, our study suggests a role for both development and selection in driving extraordinary color pattern diversity in kingfishers. We anticipate this approach will be useful for modeling other complex phenotypes besides color, such as parasite evolution across the body.


New sterilisation technologies--are they applicable for endoscopic surgical instruments?
It has been well established that instruments for minimally invasive surgery (MIS) must be treated like ordinary surgical instruments when they are intended for use within sterile areas of the human body. Due to the special design of most MIS instruments autoclaving (i.e. application of heat) may damage these delicate items. Therefore, low temperature sterilisation processes are essential. Gas sterilisation with ethylene oxide and formaldehyde may pose significant health hazards to workers exposed to these gases and to patients due to residues remaining on the surface of the instruments. Their general use in hospitals is more and more discouraged. However, with the advent of hydrogen peroxide gas plasma sterilisation there is a true alternative available for the sterilisation of MIS instruments. In contrast, the use of immersion sterilants such as liquid glutaraldehyde or peracetic acid cannot be considered as adequate because it is almost impossible to keep the processed instruments sterile until their intended use.


Cladribine and bendamustine exhibit inhibitory activity in dexamethasone-sensitive and -resistant multiple myeloma cells.
Cladribine (2-CDA) is a well-known purine nucleoside analog with activities against lymphoproliferative disorders such as hairy cell leukemia (HCL). Bendamustine, a hybrid molecule of purine analog and alkylator, induces apoptosis via DNA damage response and inhibition of mitotic checkpoint. Their therapeutic potential in patients with multiple myeloma (MM), particularly those become resistant to traditional chemotherapeutic agents, remains unclear. Here we study the effects of cladribine or bendamustine on dexamethasone-sensitive (MM1.S) and -resistant (MM1.R) MM cells. MTS-based proliferation assays showed that cladribine and bendamustine exhibited similar anti-proliferation/anti-survival effects on MM1.S and MM1.R cells in a dose-dependent manner. The IC50s of cladribine were approximately 35.3 nmol/L and 58 nmol/L for MM1.S and MM1.R cells, respectively. The IC50s of bendamustine were approximately 119.8 μmol/L (MM1.S) and 138 μmol/L (MM1.R). An apoptotic-ELISA and western blot assays of PARP cleavage and activation of caspase-8 and caspase-3 indicated that cladribine or bendamustine induced apoptosis in both cell lines. Similar results were obtained with flow cytometric analysis showing that cladribine or bendamustine increased the sub-G1 population. Treatment with bendamustine but not cladribine also resulted in cell cycle S-phase arrest. Either cladribine or bendamustine led to a remarkable increase of the phosphorylated H2A.X, CHK1 and CHK2 in both MM1.S and MM1.R cells, suggesting an induction of DNA damage response. Collectively, we demonstrate that cladribine and bendamustine exert potent inhibitory effects on dexamethasone-sensitive and -resistant MM cells in vitro. Our data suggest that MM patients, including those with dexamethasone resistance, may particularly benefit from cladribine or bendamustine.


Polarization phase shifting dispersed fringe sensor.
The dispersed fringe sensor (DFS) has been demonstrated as an effective means of measuring mirror segment piston error for telescopes with primary mirror apertures below 10 meters. With larger proposed telescopes such as The Thirty Meter Telescope (TMT) and The European Large Telescope (ELT) including ever more segments, there is a need for improvement in the co-phasing capability for segmented primary mirrors. In this paper a novel DFS that employs polarization phase shifting technology is introduced. This novel technology provides system designers and engineers with a new tool to extend the dynamic range of a DFS.


The evolution of scale sensilla in the transition from land to sea in elapid snakes.
Scale sensilla are small tactile mechanosensory organs located on the head scales of many squamate reptiles (lizards and snakes). In sea snakes and sea kraits (Elapidae: Hydrophiinae), these scale organs are presumptive scale sensilla that purportedly function as both tactile mechanoreceptors and potentially as hydrodynamic receptors capable of sensing the displacement of water. We combined scanning electron microscopy, silicone casting of the skin and quadrate sampling with a phylogenetic analysis to assess morphological variation in sensilla on the postocular head scale(s) across four terrestrial, 13 fully aquatic and two semi-aquatic species of elapids. Substantial variation exists in the overall coverage of sensilla (0.8-6.5%) among the species sampled and is broadly overlapping in aquatic and terrestrial lineages. However, two observations suggest a divergent, possibly hydrodynamic sensory role of sensilla in sea snake and sea krait species. First, scale sensilla are more protruding (dome-shaped) in aquatic species than in their terrestrial counterparts. Second, exceptionally high overall coverage of sensilla is found only in the fully aquatic sea snakes, and this attribute appears to have evolved multiple times within this group. Our quantification of coverage as a proxy for relative 'sensitivity' represents the first analysis of the evolution of sensilla in the transition from terrestrial to marine habitats. However, evidence from physiological and behavioural studies is needed to confirm the functional role of scale sensilla in sea snakes and sea kraits.


Precision and accuracy of point-of-care testing coagulometers used for self-testing and self-management of oral anticoagulation therapy.
Oral anticoagulation therapy is monitored by the use of the International Normalized Ratio (INR). Patients who perform self-testing or self-management use a point-of-care testing (POCT) coagulometer (INR monitor) to estimate their INRs. A precondition for a correct dosage of coumarins is a correct INR estimation, and the method and apparatus used for providing the INR measurements are crucial in this context. Several studies have been published regarding the precision and accuracy of these POCT coagulometers, and have led to diverse conclusions. It is difficult and challenging to perform an overview of the literature, owing to the vast amount of papers, with differences in design, statistical analysis, etc. The aim of this systematic review was to analyze the current literature, especially regarding the precision and accuracy of the POCT coagulometers, to provide recommendations for clinical use and quality control, and to point out areas for future research. We included a total of 22 studies, of which four were characterized as high-quality studies. The precision of the POCT coagulometers was generally adequate for clinical use. Their performance in terms of accuracy has to be viewed in the context of the inherent inaccuracies of INR measurements. The accuracy of POCT coagulometers seems, in this respect, to be generally acceptable, and they can be used in a clinical setting.


Comparison of CHROMagar, polymerase chain reaction-restriction fragment length polymorphism, and polymerase chain reaction-fragment size for the identification of Candida species.
The epidemiological alteration in the distribution of Candida species, as well as the significantly increasing trend of either intrinsic or acquired resistance of some of these fungi highlights the need for a reliable method for the identification of the species. Polymerase chain reaction (PCR) is one of the methods facilitating the quick and precise identification of Candida species. The aim of this study was to compare the efficiency of CHROMagar, PCR-restriction fragment length polymorphism (PCR-RFLP), and PCR-fragment size polymorphism (PCR-FSP) assays in the identification of Candida species to determine the benefits and limitations of these methods. This study was conducted on 107 Candida strains, including 20 standard strains and 87 clinical isolates. The identification of the isolates was accomplished by using CHROMagar as a conventional method. The PCR-RFLP assay was performed on the entire internal transcribed spacer (ITS) region of ribosomal DNA (rDNA), and the consequent enzymatic digestion was compared with PCR-FSP results in which ITS1 and ITS2 regions were separately PCR amplified. In both molecular assays, yeast identification was carried out through the specific electrophoretic profiles of the PCR products. According to the results, the utilization of CHROMagar resulted in the identification of 29 (33.3%) Candida isolates, while the PCR-RFLP and PCR-FSP facilitated the identification of 83 (95.4%) and 80 (91.9%) clinical isolates, respectively. The obtained concordances between CHROMagar and PCR-RFLP, between CHROMagar and PCR-FSP, as well as between PCR-RFLP and PCR-FSP were 0.23, 0.20, and 0.77, respectively. The recognition of the benefits and limitations of PCR methods allows for the selection of the most efficient technique for a fast and correct differentiation. The PCR-RFLP and PCR-FSP assays had satisfactory concordance. The PCR-FSP provides a rapid, technically simple, and cost-effective method for the identification of Candida species. Nevertheless, to accurately differentiate among the taxonomically related species, PCR-RFLP should be implemented.


Dynamic contrast-enhanced MRI analysis for prognosis of intracranial dissecting aneurysm with intramural haematoma after endovascular treatment: an observational registry study.
Intracranial dissecting aneurysm (IDA) with intramural haematoma (IMH) is an intractable cerebrovascular disease. The outcome of IDA with IMH after endovascular treatment varies across different individuals: some IMHs stop growing after endovascular treatment, while others continue to grow, even after embolisation of the parent artery. Currently, the mechanism for the continuous growth of IMH after endovascular treatment is still unclear. Continuous haemorrhage of the vasa vasorum in the IMH is considered to be associated with continuous enlargement of the IMH; however, this theory has not been proved by in vivo imaging. This study will establish a prospective cohort of 80 patients who had an IDA with IMH and received endovascular treatment. Demographic characteristics, IDA morphological characteristics and treatment characteristics will be collected prospectively. All patients will undergo dynamic contrast-enhanced MRI (DCE-MRI) before and 6 months after the endovascular treatment. According to the follow-up results of the MRI, the IDAs will be divided into two groups: a haematoma stabilisation group and a haematoma enlargement group. Then, quantitative analysis of the vasa vasorum in the IMH will be performed, and differences between the two groups will be compared with determine the association between DCE-MRI related parameters and the outcomes of IMH changes. The research was approved by the ethics committee of Beijing Tian Tan Hospital (KY 2019-024-03) and written informed consents would be obtained from all patients included in this study. The results of this study will be disseminated in professional printed media. NCT03940859. Registered: 7 May, 2019. https://clinicaltrials.gov/ct2/show/NCT03940859.


Farnesol prevents Fe-NTA-mediated renal oxidative stress and early tumour promotion markers in rats.
Excess iron deposition in tissues leads to organ dysfunction and impairment. In this study, the protective effects of farnesol (FL), an isoprenoid, against Fe-NTA (9 mg iron/kg body weight i.p.)-induced oxidative damage and early tumour promotion markers are evaluated. The pretreatment of iron-intoxicated rats with 1% and 2%/kg body weight oral dose of FL for 7 consecutive days significantly reversed the iron-induced increase in H2O2 content (P < 0.001), malondialdehyde formation, xanthine oxidase activity (P < 0.001), ornithine decarboxylase activity (P < 0.001) and 3[H]thymidine incorporation in renal DNA (P < 0.005) with simultaneous significant depletion in serum toxicity markers blood urea nitrogen (BUN) and creatinine (P < 0.001). Significant dose-dependent restoration was recorded in renal glutathione content, its dependent enzymes and other phase II metabolizing enzymes viz., catalase, glutathione-S-transferase and quinone reductase (P < 0.001) with prophylactic treatment of FL. Present results support that FL markedly lowers the oxidative damage and appearance of tumour markers, which precludes its development as a chemopreventive tool.


Enhanced magnetism in lightly doped manganite heterostructures: strain or stoichiometry?
Lattice mismatch induced epitaxial strain has been widely used to tune functional properties in complex oxide heterostructures. Apart from the epitaxial strain, a large lattice mismatch also produces other effects including modulations in microstructure and stoichiometry. However, it is challenging to distinguish the impact of these effects from the strain contribution to thin film properties. Here, we use La0.9Sr0.1MnO3 (LSMO), a lightly doped manganite close to the vertical phase boundary, as a model system to demonstrate that both epitaxial strain and cation stoichiometry induced by strain relaxation contribute to functionality tuning. The thinner LSMO films are metallic with a greatly enhanced TC which is 97 K higher than the bulk value. Such anomalies in TC and transport cannot be fully explained by the epitaxial strain alone. Detailed microstructure analysis indicates La deficiency in thinner films and twin domain formation in thicker films. Our results have revealed that both epitaxial strain and strain relaxation induced stoichiometry/microstructure modulations contribute to the modified functional properties in lightly doped manganite perovskite thin films.


Interventional vitamin C: A strategy for attenuation of coagulopathy and inflammation in a swine multiple injuries model.
Coagulopathy and inflammation induced by hemorrhagic shock and traumatic injury are associated with increased mortality and morbidity. Vitamin C (VitC) is an antioxidant with potential protective effects on the proinflammatory and procoagulant pathways. We hypothesized that high-dose VitC administered as a supplement to fluid resuscitation would attenuate inflammation, coagulation dysfunction, and end-organ tissue damage in a swine model of multiple injuries and hemorrhage. Male Sinclair swine (n = 24; mean body weight, 27 kg) were anesthetized, intubated, mechanically ventilated, and instrumented for physiologic monitoring. Following stabilization, swine were subjected to shock/traumatic injury (hypothermia, liver ischemia and reperfusion, comminuted femur fracture, hemorrhagic hypotension), resuscitated with 500 mL of hydroxyethyl starch, and randomized to receive either intravenous normal saline (NS), low-dose VitC (50 mg/kg; LO), or high-dose VitC (200 mg/kg; HI). Hemodynamics, blood chemistry, hematology, and coagulation function (ROTEM) were monitored to 4 hours postresuscitation. Histological and molecular analyses were obtained for liver, kidney, and lung. Compared with VitC animals, NS swine showed significant histological end-organ damage, elevated acute lung injury scores, and increased mRNA expression of tissue proinflammatory mediators (IL-1β, IL-8, TNFα), plasminogen activation inhibitor-1 and tissue factor. There were no statistically significant differences between treatment groups on mean arterial pressure or univariate measures of coagulation function; however, NS showed impaired multivariate clotting function at 4 hours. Although correction of coagulation dysfunction was modest, intravenous high-dose VitC may mitigate the proinflammatory/procoagulant response that contributes to multiple organ failure following acute severe multiple injuries. Prospective randomized controlled blinded trial study, Preclinical (animal-based).


Site of penetrating brain lesions causing chronic acquired stuttering.
Ten subjects exhibited acquired stuttering that had persisted for 10 to 15 years following penetrating missile wounds sustained during the Vietnam War. None had a history of developmental or chronic adult stuttering. In comparison with other head-injured subjects and normal control subjects, the subjects with acquired stuttering had significant deficits in skilled rapid hand movements and oral and speech movements, suggesting a motor control disorder. The identified brain lesions of the acquired stuttering group were on the right in 5 subjects, on the left in 4, and bilateral in 1. The internal and external capsules, the frontal white matter, and the striatum were more frequently involved in the acquired stuttering group than in other head-injured subjects (p less than or equal to 0.05). This speech rhythm and rate disorder was not associated with evident cortical lesions in either hemisphere but with predominantly unilateral lesions of the subcortical pyramidal and extrapyramidal systems.


[Functional evaluation of an experimental model of cutaneous microcirculation and pO2 after surgical excision: traditional method vs laser CO2].
Within an experimental study project about the interaction between Laser and biological tissues, the authors utilized a Laser Doppler Flowmeter device and a Polarographic method to study the cutaneous microcirculation and the tissue pO2. Under standardized conditions, the experimental model considered the microcirculation measurement and the ptiO2 before and after the exsection of a cutaneous lozenge on the animals back realized with traditional surgical methods (scalpel and electrotome) or with a last generation CO2 Laser in continuous and in pulsed mode. The Laser Doppler Flowmeter showed that the largest perturbation of the microcirculatory flux occurred after the exsection realized with the scalpel and the electrotome. The CO2 Laser utilized in continuous mode showed an influence slightly lower on the microcirculation while in pulsed mode the perturbation was absent. The ptiO2 measurement showed similar results emphasizing that the CO2 surgical Laser technique is less invasive than the traditional. To sum up, these functional methods allowed a careful microcirculation an ptiO2 evaluation and provided useful information about vasal and metabolic alterations, showing that the CO2 surgical Laser utilized in pulsed mode appears to be the less harmful surgical technique for the tissues surrounding the exsection site.


New insights into chasmosaurine (Dinosauria: Ceratopsidae) skulls from the Upper Cretaceous (Campanian) of Alberta, and an update on the distribution of accessory frill fenestrae in Chasmosaurinae.
Chasmosaurine ceratopsids are well documented from the Upper Cretaceous (Campanian) Dinosaur Park Formation (DPF) of southern Alberta and Saskatchewan, and include Chasmosaurus belli, Chasmosaurus russelli, Mercuriceratops gemini, Vagaceratops irvinensis, and material possibly referable to Spiclypeus shipporum. In this study, we describe three recently prepared chasmosaurine skulls (CMN 8802, CMN 34829, and TMP 2011.053.0046) from the DPF, and age-equivalent sediments, of Alberta. CMN 8802 and CMN 34829 are both referred to Chasmosaurus sp. based on the size and shape of the preserved parietal fenestrae. TMP 2011.053.0046 is referred to Vagaceratops sp. based on the position and orientation of its preserved epiparietals. Each skull is characterized by the presence of an accessory fenestra in either the squamosal (CMN 8802 and TMP 2011.053.0046) or parietal (CMN 34829). Such fenestrae are common occurrences in chasmosaurine squamosals, but are rare in the parietal portion of the frill. The origin of the fenestrae in these three specimens is unknown, but they do not appear to exhibit evidence of pathology, as has been previously interpreted for the accessory fenestrae in most other chasmosaurine frills. These three skulls contribute to a better understanding of the morphological variation, and geographic and stratigraphic distribution, of chasmosaurines within the DPF and age-equivalent sediments in Western Canada.


Electrical impedance of muscle during isometric contraction.
Non-invasive measurements of the 50 kHz impedance of the anterior forearm show that the resistance and reactance increase under voluntary isometric contraction of the finger flexor muscles. The relationship between impedance and force is nonlinear, dependent on the type of test, the history of prior exercise, and the health status of the subject. Nevertheless, useful dynamic response parameters betaR = deltaR/R0deltaF and betax = deltaX/X0deltaF can be defined, typically a few hundredths of a per cent per newton. Evidence is presented for the view that these effects reflect dominantly physiological as opposed to morphological changes in the muscle. In particular, (a) the impedance changes many milliseconds before the force is generated, (b) betaR and betaX change substantially during a series of repetitions of the same exercise, and (c) the impedance does not return to its original value following relaxation of the muscle. Supporting data are presented for six healthy men and women, with ages ranging from 19 to 70 years. A preliminary study of patients with various neuromuscular diseases was also performed, amongst whom marked quantitative and qualitative contrasts with the healthy group were found. Further research aimed at assessing the clinical potential of such measurements is discussed, as are studies to elucidate the underlying mechanisms for the impedance changes. We propose the name 'dynamic electrical impedance myography' for this new technique.


Agricultural intensification in Brazil and its effects on land-use patterns: an analysis of the 1975-2006 period.
Does agricultural intensification reduce the area used for agricultural production in Brazil? Census and other data for time periods 1975-1996 and 1996-2006 were processed and analyzed using Geographic Information System and statistical tools to investigate whether and if so, how, changes in yield and stocking rate coincide with changes in cropland and pasture area. Complementary medium-resolution data on total farmland area changes were used in a spatially explicit assessment of the land-use transitions that occurred in Brazil during 1960-2006. The analyses show that in agriculturally consolidated areas (mainly southern and southeastern Brazil), land-use intensification (both on cropland and pastures) coincided with either contraction of both cropland and pasture areas, or cropland expansion at the expense of pastures, both cases resulting in farmland stability or contraction. In contrast, in agricultural frontier areas (i.e., the deforestation zones in central and northern Brazil), land-use intensification coincided with expansion of agricultural lands. These observations provide support for the thesis that (i) technological improvements create incentives for expansion in agricultural frontier areas; and (ii) farmers are likely to reduce their managed acreage only if land becomes a scarce resource. The spatially explicit examination of land-use transitions since 1960 reveals an expansion and gradual movement of the agricultural frontier toward the interior (center-western Cerrado) of Brazil. It also indicates a possible initiation of a reversed trend in line with the forest transition theory, i.e., agricultural contraction and recurring forests in marginally suitable areas in southeastern Brazil, mainly within the Atlantic Forest biome. The significant reduction in deforestation that has taken place in recent years, despite rising food commodity prices, indicates that policies put in place to curb conversion of native vegetation to agriculture land might be effective. This can improve the prospects for protecting native vegetation by investing in agricultural intensification.


Analysis of the covariance structure of digital ridge counts in the offspring of monozygotic twins.
Improved methods for analysis of covariance structures now permit the rigorous testing of multivariate genetic hypotheses. Using Jöreskog's Lisrel IV computer program we have conducted a confirmatory factor analysis of dermal ridge counts on the individual fingers of 509 offspring of 107 monozygotic twin pairs. Prior to the initiation of the model-fitting procedure, the sex-adjusted ridge counts for the offspring of male and female twins were partitioned by a multivariate nested analysis of variance yielding five 10 X 10 variance-covariance matrices containing a total of 275 distinctly observed parameters with which to estimate latent sources of genetic and environmental variation and test hypotheses about the factor structure of those latent causes. To provide an adequate explanation for the observed patterns of covariation, it was necessary to include additive genetic, random environmental, epistatic and maternal effects in the model and a structure for the additive genetic effects which included a general factor and allowed for hand asymmetry and finger symmetry. The results illustrate the value of these methods for the analysis of interrelated metric traits.


Subcutaneous immunoglobulins in patients with multiple myeloma and secondary hypogammaglobulinemia: a randomized trial.
Multiple myeloma is commonly associated with a reduction of non-paraprotein immunoglobulins, resulting in a higher risk of infections that represent the leading cause of the patients' death. Therefore, immunoglobulin replacement therapy appears a logical approach. A total number of 46 myeloma patients were randomly enrolled: 24 of them were assigned to receive subcutaneous immunoglobulins, and 22 were controls. The primary endpoint was the evaluation of the annual rate of severe infections in immunoglobulins-receiving patients as compared with those untreated. Subcutaneous immunoglobulins-treated patients showed a significantly lower number of severe infections per year. Adverse events were limited to the site of infusion and were easily manageable. Health-related quality of life was significantly better in subcutaneous immunoglobulins-receiving patients. By decreasing the rate of infections, the prophylactic administration of SCIg improves both adherence to chemotherapy and health-related quality of life, and is cost-effective by reducing the need of hospitalization and the use of antibiotics.


Prayer and Faith: Spiritual Coping among American Indian Women Cancer Survivors.
Although cancer disparities among American Indian (AI) women are alarming, research on spiritual coping among this population is virtually nonexistent. This is particularly problematic, given the importance of medical practitioners' discussing the topic with cancer patients, along with the centrality of spirituality to many AI patients. The purpose of this article was to explore AI women cancer survivors' spiritual coping with their experiences. Using a community-based participatory research approach, this qualitative descriptive study included a sample of 43 AI women cancer survivors (n = 14 breast cancer, n = 14 cervical cancer, and n = 15 colon and other types of cancer). Qualitative content analysis revealed that most participants (76 percent, n = 32) cited prayer as an important part of their cancer recovery and coping strategies. Many participants expressed how prayer and spirituality connected them to family, to faith communities, and to others. In addition to prayer, over a third (36 percent, n = 15) of participants emphasized faith as a recovery and coping strategy. Results indicate that most women drew great comfort, strength, hope, and relief from their spiritual and faith traditions, indicating that religious and spiritual practices may be an important protective factor against the strain of the cancer experience.


Pediatric extracorporeal life support in specialized situations.
The purpose of this review was to provide a systematic review of the literature regarding the use of extracorporeal life support (ECLS) in various specialized conditions, as part of the Pediatric Cardiac Intensive Care Society/Extracorporeal Life Support Organization Joint Statement on Mechanical Circulatory Support. MEDLINE and PubMed. Searches for published abstracts and articles were conducted using the following MeSH terms: extracorporeal life support, extracorporeal membrane oxygenation, or mechanical support, and pediatric or children. Abstracts of all articles including case reports were reviewed; the full article was reviewed if the abstract indicated that it focused on extracorporeal life support for conditions other than primary respiratory disease or persistent pulmonary hypertension of the newborn and described outcomes such as survival to hospital discharge. Studies with potential overlapping patients were highlighted in the review process and summary results. Classification of recommendations and level of evidence are expressed in the American College of Cardiology Foundation/American Heart Association format. The majority of specialized situations where extracorporeal life support is used fall into the category of class II-III evidence. Class I indications for extracorporeal life support in the pediatric population include myocarditis and in the context of acute interventions in the cardiac catheterization laboratory.


Young Netherlands Twin Register (Y-NTR): a longitudinal multiple informant study of problem behavior.
The Netherlands Twin Register (NTR) was established around 1987 at the Vrije Universiteit in Amsterdam, the Netherlands. The current article summarizes the longitudinal genetic analyses of maternal and paternal ratings of twins' behavior as a function of the sex of the children for the traits of aggression (AGG), attention problems (AP), anxious/depression (ANX), internalizing behavior (INT) and externalizing behavior (EXT). We found that genetic influences are the most important factor in explaining individual differences in these traits. For most phenotypes, influences of genetic factors fluctuate throughout development, with the exception of AP, for which genetic influences remain of similar magnitude. Changes in genetic influences parallel those in shared environmental influences, while nonshared environmental influences remain relatively constant. Around 10% to 20% of the variance is accounted for by parent-specific shared environment, which includes rater bias. For all phenotypes, stability throughout childhood is accounted for by genetic and shared environmental factors, while nonshared environmental influences are mainly age/measurement specific. About 15% of the phenotypic stability is accounted for by rater-specific shared environmental influences, which include rater bias. In conclusion, between ages 3 and 12 genetic factors are the most important cause of individual differences in emotional and behavioral problems.


Hamilton-Jacobi-Bellman equations and approximate dynamic programming on time scales.
The time scales calculus is a key emerging area of mathematics due to its potential use in a wide variety of multidisciplinary applications. We extend this calculus to approximate dynamic programming (ADP). The core backward induction algorithm of dynamic programming is extended from its traditional discrete case to all isolated time scales. Hamilton-Jacobi-Bellman equations, the solution of which is the fundamental problem in the field of dynamic programming, are motivated and proven on time scales. By drawing together the calculus of time scales and the applied area of stochastic control via ADP, we have connected two major fields of research.


Atomistic modeling of La3+ doping segregation effect on nanocrystalline yttria-stabilized zirconia.
The effect of La3+ doping on the structure and ionic conductivity change in nanocrystalline yttria-stabilized zirconia (YSZ) was studied using a combination of Monte Carlo and molecular dynamics simulations. The simulation revealed the segregation of La3+ at eight tilt grain boundary (GB) structures and predicted an average grain boundary (GB) energy decrease of 0.25 J m-2, which is close to the experimental values reported in the literature. Cation stabilization was found to be the main reason for the GB energy decrease, and energy fluctuations near the grain boundary are smoothed out with La3+ segregation. Both dynamic and energetic analysis on the Σ13(510)/[001] GB structure revealed La3+ doping hinders O2- diffusion in the GB region, where the diffusion coefficient monotonically decreases with increasing La3+ doping concentration. The effect was attributed to the increase in the site-dependent migration barriers for O2- hopping caused by segregated La3+, which also leads to anisotropic diffusion at the GB.


Alterations of excitatory amino acid receptors in the brain of manganese-treated mice.
An excessive activation of excitatory amino acid (EAA) receptors has been associated with oxidative stress, which is considered the primary cause of manganese (Mn) poisoning neurotoxicity. Therefore, the EAA receptor distribution was analyzed by autoradiographic methods in several brain regions during Mn intoxication. We found that chronic treatment of mice with MnCl2 during 8 wk significantly alters the L-[3H]glutamate (L-[3H]Glu) binding to total glutamate (Glu) receptors, as well as to N-methyl-D-aspartate (NMDA) and quisqualate (QA) receptor subtypes. A generalized decrease of 16-24% of the L-[3H]Glu binding to total Glu receptors was found in all cortex, hippocampus, basal ganglia (except globus pallidus), and cerebellum. Saturation studies showed a significant reduction of the maximal number of receptors (Bmax) in Mn-treated mice, whereas the affinity (Kd) was not altered. L-[3H]Glu binding to NMDA sites was mainly decreased (10-21%) in a few cortical regions, basal ganglia (except globus pallidus), and hippocampus, whereas binding to QA receptor subtype was diminished (16-30%) in cortex, hippocampus, and cerebellum. The decrease of Glu receptor binding sites during Mn poisoning could reflect a receptor downregulation more than neuronal loss, since these reductions are moderate and diffuse. Thus, this down-regulation might mean a protection mechanism against an excitotoxic process associated with Mn toxicity.


Demineralized Bone Matrix in Spine Surgery: A Review of Current Applications and Future Trends.
Graft augmentation for spinal fusion is an area of continued interest, with a wide variety of available products lacking clear recommendations regarding appropriate use. While iliac crest autograft has long been considered the "gold standard", suboptimal fusion rates along with harvest-related concerns continue to drive the need for graft alternatives. There are now multiple options of products with various characteristics that are available. These include demineralized bone matrix (DBM) and demineralized bone fibers (DBF), which have been used increasingly to promote spine fusion. The purpose of this review is to provide an updated narrative on the use of DBM/DBF in spine surgery. Literature review. The clinical application of DBM in spine surgery has evolved since its introduction in the mid-1900s. Early preclinical studies demonstrated its effectiveness in promoting fusion. When used in the cervical, thoracic, and lumbar spine, more recent clinical data suggest similar rates of fusion compared with autograft, although clinical studies are primarily limited to level III or IV evidence with few level I studies. However, significant variability in surgical technique and type of product used in the literature limits its interpretation and overall application. DBM and DBF are bone graft options in spine surgery. Most commonly used as graft extenders, they have the ability to increase the volume of traditional grafting techniques while potentially inducing new bone formation. While the literature supports good fusion rates when used in the lumbar spine and when used with adjuvant cages or additional grafting techniques in the cervical spine, care should be taken when using as a stand-alone product. As new literature emerges, DBM and DBF can be a useful method in a surgeon's armamentarium for fusion-based procedures.


Confronting Deep-Learning and Biodiversity Challenges for Automatic Video-Monitoring of Marine Ecosystems.
With the availability of low-cost and efficient digital cameras, ecologists can now survey the world's biodiversity through image sensors, especially in the previously rather inaccessible marine realm. However, the data rapidly accumulates, and ecologists face a data processing bottleneck. While computer vision has long been used as a tool to speed up image processing, it is only since the breakthrough of deep learning (DL) algorithms that the revolution in the automatic assessment of biodiversity by video recording can be considered. However, current applications of DL models to biodiversity monitoring do not consider some universal rules of biodiversity, especially rules on the distribution of species abundance, species rarity and ecosystem openness. Yet, these rules imply three issues for deep learning applications: the imbalance of long-tail datasets biases the training of DL models; scarce data greatly lessens the performances of DL models for classes with few data. Finally, the open-world issue implies that objects that are absent from the training dataset are incorrectly classified in the application dataset. Promising solutions to these issues are discussed, including data augmentation, data generation, cross-entropy modification, few-shot learning and open set recognition. At a time when biodiversity faces the immense challenges of climate change and the Anthropocene defaunation, stronger collaboration between computer scientists and ecologists is urgently needed to unlock the automatic monitoring of biodiversity.


Airway pressure release and biphasic intermittent positive airway pressure ventilation: are they ready for prime time?
Airway pressure release ventilation and biphasic positive airway pressure ventilation are being used increasingly as alternative strategies to conventional assist control ventilation for patients with acute respiratory distress syndrome (ARDS) and acute lung injury. By permitting spontaneous breathing throughout the ventilatory cycle, these modes offer several advantages over conventional strategies to improve the pathophysiology in these patients, including gas exchange, cardiovascular function, and reducing or eliminating the need for heavy sedation and paralysis. Whether these surrogate outcomes will translate into better patient outcomes remains to be determined. The purpose of this review is to summarize the rationale behind the use of these ventilatory strategies in ARDS, the clinical experience with the use of these modes, and their future applications in trauma patients.


Detection of Mycobacterium avium subsp. paratuberculosis in bovine manure using Whatman FTA card technology and Lightcycler real-time PCR.
A modified forensic DNA extraction and real-time fluorescent polymerase chain reaction assay has been evaluated for the detection of Mycobacterium avium subsp. paratuberculosis (MAP) in bovine fecal samples using primers and fluorescent resonance energy transfer (FRET) probes targeting the IS900 gene sequence of MAP. DNA was successfully extracted from manure samples by utilizing the Whatman FTA card technology, which allows for simple processing and storage of samples at room temperature. The FTA cards were washed and subjected to a Chelex-100 incubation to remove any remaining polymerase chain reaction (PCR) inhibitors and to elute the DNA from the FTA card. This isolated DNA was then subjected to direct real time fluorescent PCR analysis. Detection of MAP DNA from bovine fecal samples spiked with known concentrations of viable MAP cells was obtained. The detection limits of the assay was consistently found to be between 10(2) and 10(4) colony forming units [CFU]/g, with some samples containing as low as 10 CFU/g, yielding positive assay results. This cost-efficient assay allows reporting of results as early as 4 h after fecal collection, which can be particularly useful in highthroughput herd screening.


Estimating conflict losses and reporting biases.
Determining the number of casualties and fatalities suffered in militarized conflicts is important for conflict measurement, forecasting, and accountability. However, given the nature of conflict, reliable statistics on casualties are rare. Countries or political actors involved in conflicts have incentives to hide or manipulate these numbers, while third parties might not have access to reliable information. For example, in the ongoing militarized conflict between Russia and Ukraine, estimates of the magnitude of losses vary wildly, sometimes across orders of magnitude. In this paper, we offer an approach for measuring casualties and fatalities given multiple reporting sources and, at the same time, accounting for the biases of those sources. We construct a dataset of 4,609 reports of military and civilian losses by both sides. We then develop a statistical model to better estimate losses for both sides given these reports. Our model accounts for different kinds of reporting biases, structural correlations between loss types, and integrates loss reports at different temporal scales. Our daily and cumulative estimates provide evidence that Russia has lost more personnel than has Ukraine and also likely suffers from a higher fatality to casualty ratio. We find that both sides likely overestimate the personnel losses suffered by their opponent and that Russian sources underestimate their own losses of personnel.


Improved Database Filtering Technology Enables More Efficient Ab Initio Design of Potent Peptides against Ebola Viruses.
The rapid mutations of viruses such as SARS-CoV-2 require vaccine updates and the development of novel antiviral drugs. This article presents an improved database filtering technology for a more effective design of novel antiviral agents. Different from the previous approach, where the most probable parameters were obtained stepwise from the antimicrobial peptide database, we found it possible to accelerate the design process by deriving multiple parameters in a single step during the peptide amino acid analysis. The resulting peptide DFTavP1 displays the ability to inhibit Ebola virus. A deviation from the most probable peptide parameters reduces antiviral activity. The designed peptides appear to block viral entry. In addition, the amino acid signature provides a clue to peptide engineering to gain cell selectivity. Like human cathelicidin LL-37, our engineered peptide DDIP1 inhibits both Ebola and SARS-CoV-2 viruses. These peptides, with broad antiviral activity, may selectively disrupt viral envelopes and offer the lasting efficacy required to treat various RNA viruses, including their emerging mutants.


Contemporary use of perioperative cisplatin-based chemotherapy in patients with muscle-invasive bladder cancer.
Level I evidence indicates that neoadjuvant cisplatin-based chemotherapy, in combination with radical cystectomy (RC), is associated with a significant survival advantage for patients with muscle-invasive bladder cancer. Despite this, neoadjuvant chemotherapy is not uniformly used. Our objective was to determine the patterns of utilization of neoadjuvant chemotherapy in patients undergoing RC for muscle invasive bladder cancer in a contemporary cohort in a tertiary care center. A retrospective review was performed of patients with bladder cancer who underwent RC between 2003 and 2008 at our institution. Clinical stage, pathologic stage, renal function, and perioperative chemotherapy treatments were tabulated. Primary outcome measures were the type and use of neoadjuvant chemotherapy among eligible patients. Secondary measures were the utilization patterns of adjuvant chemotherapy, renal function, pathologic outcomes, and disease specific and overall survival. Reasons for nonutilization of chemotherapy were also examined. Among 238 patients who underwent RC for bladder cancer, 145 had a preoperative clinical stage ≥T2. Only 17% (25 of 145) of these patients received cisplatin-based neoadjuvant chemotherapy. The renal function was adequate (CrCl > 60 ml/min) in 97 (67%) of these patients. Patients who received neoadjuvant chemotherapy had higher p0 rates (29% vs 8%) than patients who did not receive neoadjuvant therapy. Advanced patient age, comorbidities, concerns over toxicity of chemotherapy, and the modest nature of benefit from neoadjuvant chemotherapy may explain why this treatment is not often used. Despite level I evidence, neoadjuvant cisplatin-based chemotherapies continue to be underutilized in the management of bladder cancer, even at a high-volume tertiary center. A prospective evaluation of management choices, including the patient and physician factors involved in the use of perioperative cisplatin-based chemotherapy in bladder cancer, is indicated.


Neuroprotective Effect of Swertiamarin in a Rotenone Model of Parkinson's Disease: Role of Neuroinflammation and Alpha-Synuclein Accumulation.
Parkinson's disease (PD) is a progressive neurodegenerative disease with no permanent cure affecting around 1% of the population over 65. There is an urgency to search for a disease-modifying agent with fewer untoward effects. PD pathology involves the accumulation of toxic alpha-synuclein (α-syn) and neuronal inflammation leading to the degeneration of dopaminergic (DAergic) neurons. Swertiamarin (SWE), a well-studied natural product, possesses a strong anti-inflammatory effect. It is a secoiridoid glycoside isolated from Enicostemma littorale Blume. SWE showed a reversal effect on the α-syn accumulation in the 6-hydroxydopamine (6-OHDA)-induced Caenorhabditis elegans model of PD. However, there are no reports in the literature citing the effect of SWE as a neuroprotective agent in rodents. The present study aimed to evaluate the anti-inflammatory activity of SWE against lipopolysaccharide (LPS)-induced C6 glial cell activation and its neuroprotective effect in the intrastriatal rotenone mouse PD model. SWE treatment showed a significant reduction in interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) levels in LPS-induced C6 glial cell activation. Further, our studies demonstrated the suppression of microglial and astroglial activation in substantia nigra (SN) after administration of SWE (100 mg/kg, intraperitoneally) in a rotenone mouse model. Moreover, SWE alleviated the rotenone-induced α-syn overexpression in the striatum and SN. SWE ameliorated the motor impairment against rotenone-induced neurotoxicity and mitigated the loss of DAergic neurons in the nigrostriatal pathway. Therefore, SWE has the potential to develop as an adjunct therapy for PD, but it warrants further mechanistic studies.


Impact of Optical Cavity on Refractive Index Sensitivity of Gold Nanohole Arrays.
Refractive index sensing based on surface plasmon resonance (SPR) is a highly efficient label-free technique for biomolecular detection. The performance of this method is defined by the dielectric properties of a sensing layer and its structure. Nanohole arrays in thin metal films provide good refractive index sensitivity but often suffer from a large resonance linewidth, which limits their broad practical application in biosensorics. Coupling the broad plasmon modes to sharp resonances can reduce the peak widths, but at the same time it can also degrade the sensitivity. Here, we use Finite-Difference Time Domain simulations to study the factors affecting the sensing performance of gold-silica-gold optical cavities with nanohole arrays in the dielectric and top metal layers. We demonstrate that by tuning resonator size and inter-hole spacing, the performance of the biosensor can be optimized and the figure of merit of the order of 5-7 is reached.


Proteome-wide analysis of protein abundance and turnover remodelling during oncogenic transformation of human breast epithelial cells.
Background: Viral oncogenes and mutated proto-oncogenes are potent drivers of cancer malignancy. Downstream of the oncogenic trigger are alterations in protein properties that give rise to cellular transformation and the acquisition of malignant cellular phenotypes. Developments in mass spectrometry enable large-scale, multidimensional characterisation of proteomes. Such techniques could provide an unprecedented, unbiased view of how oncogene activation remodels a human cell proteome. Methods: Using quantitative MS-based proteomics and cellular assays, we analysed how transformation induced by activating v-Src kinase remodels the proteome and cellular phenotypes of breast epithelial (MCF10A) cells. SILAC MS was used to comprehensively characterise the MCF10A proteome and to measure v-Src-induced changes in protein abundance across seven time-points (1-72 hrs). We used pulse-SILAC MS ( Boisvert et al., 2012), to compare protein synthesis and turnover in control and transformed cells. Follow-on experiments employed a combination of cellular and functional assays to characterise the roles of selected Src-responsive proteins. Results: Src-induced transformation changed the expression and/or turnover levels of ~3% of proteins, affecting ~1.5% of the total protein molecules in the cell. Transformation increased the average rate of proteome turnover and disrupted protein homeostasis. We identify distinct classes of protein kinetics in response to Src activation. We demonstrate that members of the polycomb repressive complex 1 (PRC1) are important regulators of invasion and migration in MCF10A cells. Many Src-regulated proteins are present in low abundance and some are regulated post-transcriptionally. The signature of Src-responsive proteins is highly predictive of poor patient survival across multiple cancer types. Open access to search and interactively explore all these proteomic data is provided via the EPD database ( www.peptracker.com/epd). Conclusions: We present the first comprehensive analysis measuring how protein expression and protein turnover is affected by cell transformation, providing a detailed picture at the protein level of the consequences of activation of an oncogene.


Small RNAs in the animal gonad: guarding genomes and guiding development.
Germ cells must safeguard, apportion, package, and deliver their genomes with exquisite precision to ensure proper reproduction and embryonic development. Classical genetic approaches have identified many genes controlling animal germ cell development, but only recently have some of these genes been linked to the RNA interference (RNAi) pathway, a gene silencing mechanism centered on small regulatory RNAs. Germ cells contain microRNAs (miRNAs), endogenous siRNAs (endo-siRNAs), and Piwi-interacting RNAs (piRNAs); these are bound by members of the Piwi/Argonaute protein family. piwi genes were known to specify germ cell development, but we now understand that mutations disrupting germline development can also affect small RNA accumulation. Small RNA studies in germ cells have revealed a surprising diversity of regulatory mechanisms and a unifying function for germline genes in controlling the spread of transposable elements. Future challenges will be to understand the production of germline small RNAs and to identify the full breadth of gene regulation by these RNAs. Progress in this area will likely impact biomedical goals of manipulating stem cells and preventing diseases caused by the transposition of mobile DNA elements.


Prominent T lymphocyte response to Borrelia burgdorferi from peripheral blood of unexposed donors.
The proliferative response of peripheral blood T cells to the spirochete, Borrelia burgdorferi, can be as pronounced in unexposed normal individuals as it is in Lyme disease patients. This finding was observed using three geographically distinct isolates of B. burgdorferi. The response is not due to a lipopolysaccharide effect of the spirochete, is sensitive to Proteinase K, and requires antigen processing. It does not result from cross-reactivity of memory T cells that may be reactive to another antigen; the proliferative response to B. burgdorferi is equally distributed between naive (CD29-, CD45RO-) and memory (CD29+, CD45RO+) T cells, whereas the tetanus response is confined to the memory subset. In support of this notion, cord blood specimens that contain almost entirely naive T cells, respond as vigorously to B. burgdorferi as T cells from normal adult peripheral blood. A large panel of CD4+ T cell clones has been derived that are specific for B. burgdorferi. The majority of these clones are reactive to B. burgdorferi in the presence only of autologous HLA-DR molecules. Collectively, these data suggest that the T cell response from normal individuals is more likely due to multiple antigenic epitopes within Borrelial proteins than a superantigen response.


Coronavirus Disease 2019 Hospitalizations Attributable to Cardiometabolic Conditions in the United States: A Comparative Risk Assessment Analysis.
BACKGROUND Risk of coronavirus disease 2019 (COVID-19) hospitalization is robustly linked to cardiometabolic health. We estimated the absolute and proportional COVID-19 hospitalizations in US adults attributable to 4 major US cardiometabolic conditions, separately and jointly, and by race/ethnicity, age, and sex. METHODS AND RESULTS We used the best available estimates of independent associations of cardiometabolic conditions with a risk of COVID-19 hospitalization; nationally representative data on cardiometabolic conditions from the National Health and Nutrition Examination Survey 2015 to 2018; and US COVID-19 hospitalizations stratified by age, sex, and race/ethnicity from the Centers for Disease Control and Prevention's Coronavirus Disease 2019-Associated Hospitalization Surveillance Network database and from the COVID Tracking Project to estimate the numbers and proportions of COVID-19 hospitalizations attributable to diabetes mellitus, obesity, hypertension, and heart failure. Inputs were combined in a comparative risk assessment framework, with probabilistic sensitivity analyses and 1000 Monte Carlo simulations to jointly incorporate stratum-specific uncertainties in data inputs. As of November 18, 2020, an estimated 906 849 COVID-19 hospitalizations occurred in US adults. Of these, an estimated 20.5% (95% uncertainty interval [UIs], 18.9-22.1) of COVID-19 hospitalizations were attributable to diabetes mellitus, 30.2% (UI, 28.2-32.3) to total obesity (body mass index ≥30 kg/m2), 26.2% (UI, 24.3-28.3) to hypertension, and 11.7% (UI, 9.5-14.1) to heart failure. Considered jointly, 63.5% (UI, 61.6-65.4) or 575 419 (UI, 559 072-593 412) of COVID-19 hospitalizations were attributable to these 4 conditions. Large differences were seen in proportions of cardiometabolic risk-attributable COVID-19 hospitalizations by age and race/ethnicity, with smaller differences by sex. CONCLUSIONS A substantial proportion of US COVID-19 hospitalizations appear attributable to major cardiometabolic conditions. These results can help inform public health prevention strategies to reduce COVID-19 healthcare burdens.


Zooprophylaxis: impact of breeding rabbits around houses on reducing the indoor abundance of Phlebotomus papatasi.
Zooprophylaxis is the use of animals to deviate vectors from humans. The indoor abundance of Phlebotomus papatasi in houses with rabbit holes in the peridomestic areas are significantly lower than the indoor abundance in houses without rabbit holes in their peridomestic areas. Introduction of rabbits in artificial underground holes in peridomestic areas reduced significantly the indoor abundance of P. papatasi. Cleaning rabbit holes in peridomestic area by removing all rabbit feces induced a significant increase in the abundance of P. papatasi inside bedrooms. The ecologic niche made around houses in endemic areas by creating active rabbit holes is a major source of attractiveness of P. papatasi, and therefore it may deviate the vector from humans to rabbits. Although rabbit holes are breeding sites for P. papatasi, rabbits are not competent reservoirs for Leishmania major. Our overall findings strongly suggest that zooprophylaxis could be effective in reducing the indoor abundance of P. papatasi and subsequently may be used to control the transmission L. major in rural areas.


Differential effects of the APOE e4 allele on different domains of cognitive ability across the life-course.
The association between APOE genotype and cognitive function suggests a positive role for the e2 allele and a negative role for the e4 allele. Both alleles have relatively low frequencies in the general population; hence, meta-analyses have been based on many small, heterogeneous studies. Here, we report the APOE-cognition associations in the largest single analysis to date. APOE status and cognitive ability were measured in 18 337 participants from the Generation Scotland study between 2006 and 2011. The age range was 18-94 years with a mean of 47 (SD 15). Four cognitive domains were assessed: verbal declarative memory (paragraph recall), processing speed (digit symbol substitution), verbal fluency (phonemic verbal fluency), and vocabulary (Mill Hill synonyms). Linear regression was used to assess the associations between APOE genetic status and cognition. Possession of the e4 allele was associated with lower scores on the measures of memory and processing speed in subjects aged >60. Across all age ranges, the e4 allele was linked to better verbal fluency scores. In younger subjects (≤60 years) the e4 allele was linked to higher vocabulary scores. There were no associations between the e2 allele and cognitive ability. As seen in previous meta-analyses, the APOE e4 allele is linked to poorer cognitive performance in the domains of memory and processing speed. By contrast, positive associations were seen between the e4 allele and measures of verbal fluency and vocabulary. All associations were relatively small and, in many cases, nominally significant despite the very large sample size.


Digestive enzymes of three teleost fishes.
The activity of amylase, sucrase, protease and lipase has been examined in Wallago attu, Clarias batrachus and Labeo rohita. The optimum pH value for carbohydrases ranges from 5.0 to 7.0 and that for trypsin between pH 6.8 and 7.8. Lipase is active at a slightly more alkaline medium. The optimum pH for a given enzyme varies in different sections of the alimentary canal of the same fish and also from species to species. Variations are also found in the optimum substrate concentration for a given enzyme in the different sections of the alimentary canal. The activity of carbohydrases is higher in the herbivorous fish Labeo, than in the carnivorous fish Wallago, and the omnivorous fish Clarias. As for protease, maximum activity is found in Wallago. The difference is not so well marked for the activity of lipase. There is a correlation between the normal diet of the fishes and the relative activity of the digestive enzymes.


Expression of a microinjected porcine class I major histocompatibility complex gene in transgenic mice.
A porcine class I major histocompatibility complex (SLA) gene has been introduced into the genome of a C57BL/10 mouse. This transgenic mouse expressed SLA antigen on its cell surfaces and transmitted the gene to offspring, in which the gene is also expressed. Skin grafts of such transgenic mice were rejected by normal C57BL/10 mice, suggesting that the foreign SLA antigen expressed in the transgenic mice is recognized as a functional transplantation antigen.


Nonenzymatic glycosylation reduces the susceptibility of fibrin to degradation by plasmin.
The effect of nonenzymatic glycosylation on the susceptibility of fibrin to degradation by the specific fibrinolytic enzyme plasmin was evaluated using both a fibrin plate assay and a fluorogenic synthetic plasmin substrate assay. Data from both types of experiments demonstrate that nonenzymatic glycosylation reduces the susceptibility of fibrin to plasmin degradation. Acetylation and carbamylation have qualitatively similar effects, indicating that chemical modification of lysine amino groups is the underlying phenomenon responsible for the observed degradative defect produced by glucose. Experimental conditions that increased the rate of nonenzymatic protein glycosylation (higher monosaccharide concentration, glucose-6-phosphate) were associated with correspondingly greater degrees of resistance to degradation by plasmin. Such reduced degradation of nonenzymatically glycosylated proteins in vivo may contribute to the accumulation of fibrin and several other proteins observed in those tissues most frequently affected by the complications of diabetes.


Peri-infarct zone pacing to prevent adverse left ventricular remodelling in patients with large myocardial infarction.
We sought to determine whether peri-infarct pacing prevents left ventricular (LV) remodelling and improves functional and clinical outcomes in patients with large first myocardial infarction (MI). A total of 126 patients at 27 international sites within 10 days of onset of anterior or non-anterior MI with creatine phosphokinase >3000 U/L and QRS duration ≤120 ms were randomized 1:1:1 to dual-site biventricular pacing vs. single-site LV only pacing vs. non-implanted control. The primary endpoint was the echocardiographic core laboratory-assessed change in LV end-diastolic volume (ΔLVEDV) from baseline to 18 months between the pooled pacing therapy groups and the control group. ΔLVEDV increased by 15.3 ± 28.6 mL in the control group and by 16.7 ± 30.5 mL in the pooled pacing groups during follow-up (adjusted mean difference (95% CI) = 0.6 (-12.3, 13.5) mL, P = 0.92). There were also no significant between-group differences in the change in LV end-systolic volume or ejection fraction over time. Quality of life, as assessed by the Minnesota Living with Heart Failure (HF) and European Quality of Life-5 Dimension questionnaires and New York Heart Association class, was also similar between groups during 18-month follow-up. Six-minute walk distance improved during follow-up to an equal degree between groups, and there were no significant differences in the 18-month rates of death or HF hospitalization between the pooled pacing therapy vs. control groups (17.4 vs. 21.7% respectively, P = 0.59). In the present multicentre, randomized trial, peri-infarct pacing did not prevent LV remodelling or improve functional or clinical outcomes during 18-month follow-up in patients with large first MI. NCT01213251.


Male inbreeding status affects female fitness in a seed-feeding beetle.
Inbreeding generally reduces male mating activity such that inbred males are less successful in male-male competition. Inbred males can also have smaller accessory glands, transfer less sperm and produce sperm that are less motile, less viable or have a greater frequency of abnormalities, all of which can reduce the fertilization success and fitness of inbred males relative to outbred males. However, few studies have examined how male inbreeding status affects the fitness of females with whom they mate. In this study, we examine the effect of male inbreeding status (inbreeding coefficient f = 0.25 vs. f = 0) on the fecundity, adult longevity and the fate of eggs produced by outbred females in the seed-feeding beetle, Callosobruchus maculatus. Females mated to inbred males were less likely to lay eggs. Of those that laid eggs, females mated to inbred males laid 6-12% fewer eggs. Females mated to inbred males lived on average 5.4% longer than did females mated to outbred males, but this effect disappeared when lifetime fecundity was used as a covariate in the analysis. There was no effect of male inbreeding status on the proportion of a female's eggs that developed or hatched, and no evidence that inbred males produced smaller nuptial gifts. However, ejaculates of inbred males contained 17-33% fewer sperm, on average, than did ejaculates of outbred males. Our study demonstrates that mating with inbred males has significant direct consequences for the fitness of female C. maculatus, likely mediated by effects of inbreeding status on the number of sperm in male ejaculates. Direct effects of male inbreeding status on female fitness should be more widely considered in theoretical models and empirical studies of mate choice.


Role of rat alpha adducin in angiogenesis: null effect of the F316Y polymorphism.
Rat alpha adducin point mutation (F316Y) has been associated with primary systemic arterial hypertension. As microcirculatory abnormalities are present in most forms of hypertension, the aim of the present study was to investigate whether rat alpha adducin may regulate endothelial cell (EC) functions in vitro and in vivo. The overexpression of rat wild type alpha adducin (WT-Add1) in ECs induced capillary-like structure development in Matrigel in vitro and enhanced capillary formation in Matrigel implants in vivo in CD1 mice. In contrast, the overexpression of the mutated form (MUT-Add1) of rat alpha adducin had a Null effect in vitro and lacked any significant activity in vivo. Further, adenovirus-mediated rat WT-Add1 but not MUT-Add1 gene transfer to murine ischemic hindlimb enhanced capillary formation in skeletal muscles. Gene profiling of human umbilical vein endothelial cells overexpressing alpha adducin was performed in order to identify putative effector molecules of alpha adducin-mediated activities on ECs. Interestingly, among a number of genes involved in angiogenesis regulation, retinoic acid-induced protein (RAI17) was found to be upregulated in WT-Add1 vs MUT-Add1 overexpressing cells, possibly representing a key molecule/axis for the functional Add1-induced effect. Rat WT alpha adducin enhanced EC functions both in vitro and in vivo. The expression of the F316Y variant, associated with the hypertensive phenotype, had a Null effect and might contribute to endothelial rarefaction/dysfunction in hypertension. RAI17 was found to be a putative effector molecule differentially regulated by the overexpression of the two forms of Add1 in endothelial cells.


Spinal Motion and Muscle Activity during Active Trunk Movements - Comparing Sheep and Humans Adopting Upright and Quadrupedal Postures.
Sheep are used as models for the human spine, yet comparative in vivo data necessary for validation is limited. The purpose of this study was therefore to compare spinal motion and trunk muscle activity during active trunk movements in sheep and humans. Three-dimensional kinematic data as well as surface electromyography (sEMG) of spinal flexion and extension was compared in twenty-four humans in upright (UR) and 4-point kneeling (KN) postures and in 17 Austrian mountain sheep. Kinematic markers were attached over the sacrum, posterior iliac spines, and spinous and transverse processes of T5, T8, T11, L2 and L5 in humans and over the sacrum, tuber sacrale, T5, T8, T12, L3 and L7 in sheep. The activity of erector spinae (ES), rectus abdominis (RA), obliquus externus (OE), and obliquus internus (OI) were collected. Maximum sEMG (MOE) was identified for each muscle and trial, and reported as a percentage (MOE%) of the overall maximally observed sEMG from all trials. Spinal range of motion was significantly smaller in sheep compared to humans (UR / KN) during flexion (sheep: 6-11°; humans 12-34°) and extension (sheep: 4°; humans: 11-17°). During extension, MOE% of ES was greater in sheep (median: 77.37%) than UR humans (24.89%), and MOE% of OE and OI was greater in sheep (OE 76.20%; OI 67.31%) than KN humans (OE 21.45%; OI 19.34%), while MOE% of RA was lower in sheep (21.71%) than UR humans (82.69%). During flexion, MOE% of RA was greater in sheep (83.09%) than humans (KN 47.42%; UR 41.38%), and MOE% of ES in sheep (45.73%) was greater than KN humans (14.45%), but smaller than UR humans (72.36%). The differences in human and sheep spinal motion and muscle activity suggest that caution is warranted when ovine data are used to infer human spine biomechanics.


Form processing modules in primate area V4.
Area V4 occupies a central position among the areas of the primate cerebral cortex involved with object recognition and analysis. Consistent with this role, neurons in V4 are selective for many visual attributes including color, orientation, and binocular disparity. However, it is uncertain whether cells within V4 are organized with respect to these properties. In this study we used in vivo optical imaging and electrophysiology in macaque visual cortex to show that cells that share certain physiological properties are indeed grouped together in V4. Our results revealed regions containing cells with common orientation selectivity. These regions were similar in size to those seen in V2 and much larger than those seen in V1 and were confirmed by appropriately targeted single-unit recording. Surprisingly, orientation organization visible through imaging was limited to the portion of V4 representing the central visual fields. Optical imaging also revealed a functional organization related to stimulus size. Size-sensitive regions (S regions) contained cells that were strongly suppressed by large stimuli. In contrast to V2, S regions in V4 contain orientation domains. These results suggest that V4 contains modular assemblies of cells related to particular aspects of form analysis. Such organization may contribute to the construction of object-based representations.


Efficacy of a school-based intervention to influence attitudes about future parenting among Swedish youth with intellectual disability: An RCT study.
The study aim was to investigate the efficacy of an intervention designed to provide a basis for informed choices about future parenthood to special upper secondary school students with intellectual disabilities. A randomised trial with a waiting list control group was used. In total, 108 special upper secondary school students with mild or moderate intellectual disabilities, age 16-21 years, provided informed consent and participated. The intervention included education using the Parenting Toolkit and a Real Care Baby simulator. The analyses included 91 students (intervention group n = 46, 24F/22M; control group n = 45, 26F/19M). The result showed that intervention group changed their attitudes to future parenting, from 'do not know' to 'know', significantly more than control group. The intervention increased knowledge levels in the intervention group. The intervention group showed increased ability to make informed choices and decisions about parenthood.


Epigenetic modifier alpha-ketoglutarate modulates aberrant gene body methylation and hydroxymethylation marks in diabetic heart.
Diabetic cardiomyopathy (DCM) is a leading cause of death in diabetic patients. Hyperglycemic myocardial microenvironment significantly alters chromatin architecture and the transcriptome, resulting in aberrant activation of signaling pathways in a diabetic heart. Epigenetic marks play vital roles in transcriptional reprogramming during the development of DCM. The current study is aimed to profile genome-wide DNA (hydroxy)methylation patterns in the hearts of control and streptozotocin (STZ)-induced diabetic rats and decipher the effect of modulation of DNA methylation by alpha-ketoglutarate (AKG), a TET enzyme cofactor, on the progression of DCM. Diabetes was induced in male adult Wistar rats with an intraperitoneal injection of STZ. Diabetic and vehicle control animals were randomly divided into groups with/without AKG treatment. Cardiac function was monitored by performing cardiac catheterization. Global methylation (5mC) and hydroxymethylation (5hmC) patterns were mapped in the Left ventricular tissue of control and diabetic rats with the help of an enrichment-based (h)MEDIP-sequencing technique by using antibodies specific for 5mC and 5hmC. Sequencing data were validated by performing (h)MEDIP-qPCR analysis at the gene-specific level, and gene expression was analyzed by qPCR. The mRNA and protein expression of enzymes involved in the DNA methylation and demethylation cycle were analyzed by qPCR and western blotting. Global 5mC and 5hmC levels were also assessed in high glucose-treated DNMT3B knockdown H9c2 cells. We found the increased expression of DNMT3B, MBD2, and MeCP2 with a concomitant accumulation of 5mC and 5hmC, specifically in gene body regions of diabetic rat hearts compared to the control. Calcium signaling was the most significantly affected pathway by cytosine modifications in the diabetic heart. Additionally, hypermethylated gene body regions were associated with Rap1, apelin, and phosphatidyl inositol signaling, while metabolic pathways were most affected by hyperhydroxymethylation. AKG supplementation in diabetic rats reversed aberrant methylation patterns and restored cardiac function. Hyperglycemia also increased 5mC and 5hmC levels in H9c2 cells, which was normalized by DNMT3B knockdown or AKG supplementation. This study demonstrates that reverting hyperglycemic damage to cardiac tissue might be possible by erasing adverse epigenetic signatures by supplementing epigenetic modulators such as AKG along with an existing antidiabetic treatment regimen.


Impact of PEGDA photopolymerization in micro-stereolithography on 3D printed hydrogel structure and swelling.
3D printing complex architectures of responsive-hydratable polymers are enabled by stereolithography via photopolymerization. Yet, insufficient crosslinking leads to compromised structural integrity of the photopolymerized samples, which affects the functionality and reliability of hydrogel devices significantly. Here we investigate how curing parameters and ink formulation affect 3D printed PEGDA samples by using a combination of microfabrication, structural characterization, and reactive coarse-grained molecular dynamics simulation. Our findings show that the degree of curing exhibits a graded profile from confocal Raman spectroscopy and submicron pores from atomic force microscopy, both of which are also observed in our molecular simulations. Moreover, with environmental scanning electron microscopy, we probe the microscopic swelling and bending dynamics of 3D printed hydratable PEGDA structures as well as their structural integrity. Our in-depth characterization results reveal how hydrogel elasticity and irreversible densification due to pore formation highly depends on the exposure time, light intensity and the associated degree of crosslinking. This work provides new molecular insights into processing-structure relation in stereolithography 3D printing.