Tatyana Markus: Hero of Ukraine

A dramatized telling of the story of Tatyana Markus, a young Jewish resistance fighter from Kiev, Ukraine. Under a false identity, she personally killed dozens of Nazis during WWII. Along the way she lost many people she cared about until she was captured herself. Tatyana has gone on virtually unknown throughout the world, so this play is an effort to spread word about this brave, amazing girl who was only in her early 20s. I think the themes are very relatable to today\u27s society with the struggle of whether to stand up to injustice, or stand by. Especially since she was such a young girl, and the young people of our world that are our future are also trying to stand up for what they believed in. Putting Tatyana\u27s story in a play makes it a much more personal experience

Serum anti-Müllerian hormone concentrations before and after treatment of an ovarian granulosa cell tumour in a cat

Case summary A 15-year-old female cat was presented for investigation of progressive behavioural changes, polyuria, polydipsia and periuria. An ovarian granulosa cell tumour was identified and the cat underwent therapeutic ovariohysterectomy (OHE). The cat’s clinical signs resolved, but 6 months later it was diagnosed as having an anaplastic astrocytoma and was euthanased. Serum anti-Müllerian hormone (AMH) concentration prior to OHE was increased vs a control group of entire and neutered female cats. Following OHE, serum AMH concentration decreased to <1% of the original value. Relevance and novel information Serum AMH measurement may represent a novel diagnostic and monitoring tool for functional ovarian neoplasms in cats

Proceedings of the Rank Forum on Vitamin D

The Rank Forum on Vitamin D was held on 2nd and 3rd July 2009 at the University of Surrey, Guildford, UK. The workshop consisted of a series of scene-setting presentations to address the current issues and challenges concerning vitamin D and health, and included an open discussion focusing on the identification of the concentrations of serum 25-hydroxyvitamin D (25(OH)D) (a marker of vitamin D status) that may be regarded as optimal, and the implications this process may have in the setting of future dietary reference values for vitamin D in the UK. The Forum was in agreement with the fact that it is desirable for all of the population to have a serum 25(OH)D concentration above 25 nmol/l, but it discussed some uncertainty about the strength of evidence for the need to aim for substantially higher concentrations (25(OH)D concentrations . 75 nmol/l). Any discussion of ‘optimal’ concentration of serum 25(OH)D needs to define ‘optimal’ with care since it is important to consider the normal distribution of requirements and the vitamin D needs for a wide range of outcomes. Current UK reference values concentrate on the requirements of particular subgroups of the population; this differs from the approaches used in other European countries where a wider range of age groups tend to be covered. With the re-emergence of rickets and the public health burden of low vitamin D status being already apparent, there is a need for urgent action from policy makers and risk managers. The Forum highlighted concerns regarding the failure of implementation of existing strategies in the UK for achieving current vitamin D recommendations

Vitamin A Metabolism by Dendritic Cells Triggers an Antimicrobial Response against Mycobacterium tuberculosis.

Epidemiological evidence correlates low serum vitamin A (retinol) levels with increased susceptibility to active tuberculosis (TB); however, retinol is biologically inactive and must be converted into its bioactive form, all-trans retinoic acid (ATRA). Given that ATRA triggers a Niemann-Pick type C2 (NPC2)-dependent antimicrobial response against Mycobacterium tuberculosis, we investigated the mechanism by which the immune system converts retinol into ATRA at the site of infection. We demonstrate that granulocyte-macrophage colony-stimulating factor (GM-CSF)-derived dendritic cells (DCs), but not macrophages, express enzymes in the vitamin A metabolic pathway, including aldehyde dehydrogenase 1 family, member a2 (ALDH1A2) and short-chain dehydrogenase/reductase family, member 9 (DHRS9), enzymes capable of the two-step conversion of retinol into ATRA, which is subsequently released from the cell. Additionally, mRNA and protein expression levels of ALDH1A2 and DC marker CD1B were lower in tuberculosis lung tissues than in normal lung. The conditioned medium from DCs cultured with retinol stimulated antimicrobial activity from M. tuberculosis-infected macrophages, as well as the expression of NPC2 in monocytes, which was blocked by specific inhibitors, including retinoic acid receptor inhibitor (RARi) or N,N-diethylaminobenzaldehyde (DEAB), an ALDH1A2 inhibitor. These results indicate that metabolism of vitamin A by DCs transactivates macrophage antimicrobial responses.IMPORTANCE Tuberculosis (TB) is the leading cause of death by a single infectious agent worldwide. One factor that contributes to the success of the microbe is the deficiency in immunomodulatory nutrients, such as vitamin A (retinol), which are prevalent in areas where TB is endemic. Clinical trials show that restoration of systemic retinol levels in active TB patients is ineffective in mitigating the disease; however, laboratory studies demonstrate that activation of the vitamin A pathway in Mycobacterium tuberculosis-infected macrophages triggers an antimicrobial response. Therefore, the goal of this study was to determine the link between host retinol levels and retinoic acid-mediated antimicrobial responses against M. tuberculosis By combining established in vitro models with in situ studies of lung tissue from TB patients, this study demonstrates that the innate immune system utilizes transcellular metabolism leading to activation between dendritic cells and macrophages as a means to combat the pathogen

A breathing zirconium metal-organic framework with reversible loss of crystallinity by correlated nanodomain formation

The isoreticular analogue of the metal-organic framework UiO-66(Zr), synthesized with the flexible trans-1,4-cyclohexanedicarboxylic acid as linker, shows a peculiar breathing behavior by reversibly losing long-range crystalline order upon evacuation. The underlying flexibility is attributed to a concerted conformational contraction of up to two thirds of the linkers, which breaks the local lattice symmetry. X-ray scattering data are described well by a nanodomain model in which differently oriented tetragonal-type distortions propagate over about 7-10 unit cells

pLG72 modulates intracellular D-serine levels through its interaction with D-amino acid oxidase - Effect on schizophrenia susceptibility

Human genes coding for pLG72 and d-amino acid oxidase have recently been linked to the onset of schizophrenia. pLG72 was proposed as an activator of the human FAD-containing flavoprotein d-amino acid oxidase (hDAAO). In the brain this oxidizes d-serine, a potent activator of N-methyl-d-aspartate receptor. We have investigated the mechanistic regulation of hDAAO by pLG72. Immunohistochemical analyses revealed that hDAAO and pLG72 are both expressed in astrocytes of the human cortex, where they most likely interact, considering their partial overlapping subcellular distribution and their coimmunoprecipitation. We demonstrated that the specific in vitro interaction of the two proteins yields a complex composed of 2 hDAAO homodimers and 2 pLG72 molecules. Binding of pLG72 did not affect the kinetic properties and FAD binding ability of hDAAO; instead, a time-dependent loss of hDAAO activity in the presence of an excess of pLG72 was found. The binding affects the tertiary structure of hDAAO, altering the amount of the active form. We finally demonstrated that overexpression of hDAAO in glioblastoma cells decreases the levels of d-serine, an effect that is null when pLG72 is coexpressed. These data indicate that pLG72 acts as a negative effector of hDAAO. Therefore, a decrease in the synaptic concentration of d-serine as the result of an anomalous increase in hDAAO activity related to hypoexpression of pLG72 may represent a molecular mechanism by which hDAAO and pLG72 are involved in schizophrenia susceptibility

Do Montana\u27s Sixmile Creek Cobbles Have Nevada Origins? Evidence for Headwaters of the Miocene Bell River Basin

The Miocene Sixmile Creek Formation in Montana contains distinctive river cobbles of coarse-grained sandstone and conglomerate that include small grains of black chert, but the source of these cobbles has not been confirmed. The Paleozoic Diamond Peak Formation of Nevada may be one possible source of these cobbles. It is widespread in central Nevada\u27s mountains but is unlike any bedrock formations found in Montana. If cobbles in the Sixmile Creek Formation were derived from central Nevada, the Miocene river that carried them would have had to have crossed the present positions of the Snake River Plain and the Idaho-Montana Continental Divide. The purpose of our study is to test the hypothesis by examining particularly distinctive cobbles along the proposed Miocene river path. We compared cobbles collected from the Sixmile Creek Formation at locations from Nevada to Great Falls, Montana, and compared these to each other and to samples collected from proposed source rocks at Pequot Summit, Nevada. We measured the percentage of black chert grains in each rock sample, as well as the shapes and size ranges of the chert grains. Our results support the hypothesis of a great Miocene river that flowed through Montana from headwaters as far south as central Nevada (Sears, 2014). This would have been possible in the Miocene because tectonics had not yet formed the Snake River Plain and modern Continental Divide. The river implied by this model would have been a tributary to the pre-ice age Bell River basin of Canada, which rivaled the modern Amazon River basin in scale. This research could lead to new understanding of the paleotopography and paleofluvial systems of the western interior of North America

"Sometimes it is difficult for us to stand up and change this": an analysis of power within priority-setting for health following devolution in Kenya

Background Practices of power lie at the heart of policy processes. In both devolution and priority-setting, actors seek to exert power through influence and control over material, human, intellectual and financial resources. Priority-setting arises as a consequence of the needs and demand exceeding the resources available, requiring some means of choosing between competing demands. This paper examines the use of power within priority-setting processes for healthcare resources at sub-national level, following devolution in Kenya. Methods We interviewed 14 national level key informants and 255 purposively selected respondents from across the health system in ten counties. These qualitative data were supplemented by 14 focus group discussions (FGD) involving 146 community members in two counties. We conducted a power analysis using Gaventa’s power cube and Veneklasen’s expressions of power to interpret our findings. Results We found Kenya’s transition towards devolution is transforming the former centralised balance of power, leading to greater ability for influence at the county level, reduced power at national and sub-county (district) levels, and limited change at community level. Within these changing power structures, politicians are felt to play a greater role in priority-setting for health. The interfaces and tensions between politicians, health service providers and the community has at times been felt to undermine health related technical priorities. Underlying social structures and discriminatory practices generally continue unchanged, leading to the continued exclusion of the most vulnerable from priority-setting processes. Conclusions Power analysis of priority-setting at county level after devolution in Kenya highlights the need for stronger institutional structures, processes and norms to reduce the power imbalances between decision-making actors and to enable community participation

Phase Aberration Correction for in vivo Ultrasound Localization Microscopy Using a Spatiotemporal Complex-Valued Neural Network

Ultrasound Localization Microscopy (ULM) can map microvessels at a resolution of a few micrometers ({\mu}m). Transcranial ULM remains challenging in presence of aberrations caused by the skull, which lead to localization errors. Herein, we propose a deep learning approach based on recently introduced complex-valued convolutional neural networks (CV-CNNs) to retrieve the aberration function, which can then be used to form enhanced images using standard delay-and-sum beamforming. Complex-valued convolutional networks were selected as they can apply time delays through multiplication with in-phase quadrature input data. Predicting the aberration function rather than corrected images also confers enhanced explainability to the network. In addition, 3D spatiotemporal convolutions were used for the network to leverage entire microbubble tracks. For training and validation, we used an anatomically and hemodynamically realistic mouse brain microvascular network model to simulate the flow of microbubbles in presence of aberration. We then confirmed the capability of our network to generalize to transcranial in vivo data in the mouse brain (n=2). Qualitatively, vascular reconstructions using a pixel-wise predicted aberration function included additional and sharper vessels. The spatial resolution was evaluated by using the Fourier ring correlation (FRC). After correction, we measured a resolution of 16.7 {\mu}m in vivo, representing an improvement of up to 27.5 %. This work leads to different applications for complex-valued convolutions in biomedical imaging and strategies to perform transcranial ULM

Associated Factors and Prognostic Implications of Stimulus-Induced Rhythmic, Periodic, or Ictal Discharges.

IMPORTANCE: The implications of stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs) sometimes found on prolonged electroencephalographic (EEG) recordings are uncertain. OBJECTIVE: To evaluate the incidence of SIRPIDs and their clinical implications in critically ill patients. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, international retrospective study was performed from October 1, 2012, through September 30, 2014, of consecutive adult patients hospitalized in intensive care units with alteration of consciousness who underwent EEG recordings at 3 separate centers. Demographic data, including admission diagnosis, age, sex, history of epilepsy, and EEG findings, were noted. Characteristics of SIRPIDs were documented. Data were evaluated for predictors of SIRPIDs and in-hospital mortality. Data analysis was performed from January 16, 2015, to June 15, 2015. MAIN OUTCOMES AND MEASURES: Incidence of SIRPIDs, association of SIRPIDs with mortality and other EEG characteristics, and EEG and clinical predictors of mortality. RESULTS: A total of 416 patients were studied. The median age of patients was 60 years (interquartile range, 46-71 years), and 252 (60.6%) were male. A total of 104 patients (25.0%) did not survive to hospital discharge. SIRPIDs were identified in 43 patients (10.3%). The proportion of patients with SIRPIDs was not significantly different across the 3 sites (P = .34). Anoxic brain injury (odds ratio [OR], 3.80; 95% CI, 1.73-8.33; P &lt; .001), the use of antiepileptic medications (OR, 3.24; 95% CI, 1.31-8.00; P = .01), electrographic seizures (OR, 2.85; 95% CI, 1.13-7.19; P = .03), generalized periodic discharges with triphasic morphologic features (OR, 3.66; 95% CI, 1.67-8.02; P = .001), and sporadic sharp waves and periodic discharges (OR, 2.59; 95% CI, 1.13-5.92; P = .02) were independently associated with the presence of SIRPIDs. Older age (OR, 1.02; 95% CI, 1.01-1.04; P = .005), anoxic brain injury (OR, 3.49; 95% CI, 1.96-6.21; P ≤ .001), and absence of EEG reactivity (OR, 8.14; 95% CI, 4.20-15.79; P &lt; .001) but not SIRPIDs (OR, 1.73; 95% CI, 0.79-3.78; P = .17) were independently associated with in-hospital mortality. CONCLUSIONS AND RELEVANCE: In critically ill patients undergoing EEG recordings, SIRPIDs occurred in 43 (10.3%) and were associated with other electrographic abnormalities previously reported to indicate poor prognosis. However, SIRPIDs were not independently associated with in-hospital mortality