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Pressure distribution during gait was markedly changed in fallers. Differences between fallers and non-fallers as well as cut off values for increased fall risk in the ROC analysis could be determined. The introduced measurement protocol suggests that patients at risk for falling can be detected without any additional office visits. Based on the introduced protocol in a limited patient setting, further large scale studies should now determine the effect of prevention measures triggered by gait analysis, the specific risk reduction and the associated personal and socioeconomic advantages.Visually guided decision-making requires integration of information from distributed brain areas, necessitating a brain-wide approach to examine its neural mechanisms. New tools in Drosophila melanogaster enable circuits spanning the brain to be charted with single cell-type resolution. Here, we highlight recent advances uncovering the computations and circuits that transform and integrate visual information across the brain to make behavioral choices. Visual information flows from the optic lobes to three primary central brain regions a sensorimotor mapping area and two 'higher' centers for memory or spatial orientation. Rapid decision-making during predator evasion emerges from the spike timing dynamics in parallel sensorimotor cascades. Goal-directed decisions may occur through memory, navigation and valence processing in the central complex and mushroom bodies.The ribbed mussel has been demonstrated to tolerate high levels of urban pollution and inhabits intertidal regions of the New York City estuary. The ability of this bivalve to filter bacteria raises the question of whether it can remove from the water column the fecal bacteria introduced to urban waterways by septic system leakage or sewer overflow. The study here addresses the hypothesis that ribbed mussel filters bacteria introduced by combined sewer overflow (CSO) discharge. Mussels and water were collected from a highly polluted region of the NYC estuary in order to conduct two sets of five trials for filtration of coliform and coccoid fecal indicator bacteria, respectively, Escherichia coli and Enterococcus species. Mussels and water samples were collected in proximity to a major CSO outfall within 1-2 days of a rainfall event to ensure high baseline values of bacterial contamination for filtration trials. For any given Enterococcus or E. coli trial, equal volume water samples were serially distributed across aerated tanks either containing a mussel or not. Comparison of with-mussel versus no-mussel tank water contamination across pooled trials showed significant (P less then 0.05) reduction in water exposed to mussel filtration for both, Enterococcus and E. coli trials. For Enterococcus trials, measures of turbidity (suspended particle density) were taken concurrently with measures of bacterial contamination. Regression of contamination against turbidity, with measures standardized across trials, yielded a significant positive association (n = 50, P less then 0.0001) across all tank water with a mussel. Thus, contamination reduction was associated with particle removal by mussel filtration.In this study, components, concentrations, distribution characteristics and sources of low molecular weight organic acids (LMWOAs) in seawater of the Changjiang Estuary and its adjacent East China Sea were investigated in March 2015. Lactic, acetic and formic acids were identified with their concentration range of 0-16.7, 0-42.7 and 0-6.7 μmol·L-1, respectively. In the surface seawater, high concentrations of LMWOAs appeared in the sea area close to the estuary and along the coast. LMWOAs were important fractions of dissolved organic carbon and acetic acid was dominant component of LMWOAs. Riverine, terrestrial input, phytoplankton and sediment release were important sources for the LMWOAs, and human activities were considered as dominant sources for them in sampling period. The consistency of regions with high concentrations of LMWOAs, eutrophication, seasonal hypoxia and frequent red tide occurrence suggested LMWOAs as potential indicators for evaluating pollution status in coastal areas.The stochastic switching between microtubule growth and shrinkage is a fascinating and unique process in the regulation of the cytoskeleton. To understand it, almost all attention has been focused on the microtubule ends. However, recent research has revived the idea that tubulin dimers can also be exchanged in protofilaments along the microtubule shaft, thus repairing the microtubule and protecting it from disassembly. Here, we review the research describing this phenomenon, the mechanisms regulating the removal and insertion of tubulin dimers, as well as the potential implications for key functions of the microtubule network, such as intracellular transport and cell polarization.

The COVID-19 pandemic is putting healthcare workers across the world in an unprecedented situation. The purpose of this study was to evaluate the levels of depression, anxiety, and stress among Hubei pediatric nurses during the COVID-19 pandemic and to analyze the potential factors associated with them.

A self-designed online questionnaire survey, which consisted of the demographic and selected features, the occupational protection knowledge, attitudes, and practices of COVID-19, and the Chinese version of Depression, Anxiety, and Stress Scale, were used to assess the levels of depression, anxiety, and stress among Hubei pediatric nurses during COVID-19 pandemic. The logistic regression analyses were performed to analyze the potential factors associated with depression, anxiety, and stress.

A total of 617 pediatric nurses were included in the survey. A considerable proportion of pediatric nurses reported symptoms of depression (95 [15.4%]), anxiety (201 [32.6%]), and stress (111 [18.0%]). Results of mulork requirements and intensifying occupational protection practices might help safeguard pediatric nurses from depression, anxiety, and stress.In this work, three series of ω-3 polyunsaturated fatty acid-alkanolamine derivatives (PUFA-AAs) were synthesized, characterized and their anti-inflammatory activity in vivo was evaluated. Compounds 4a, 4f, and 4k exhibited marked anti-inflammatory activity in LPS-stimulated RAW 264.7 cells. The most promising compound 4k dose-dependently suppressed the cytokines with IC50 values in the low micromolar range. Further, 4k exhibited potential in vitro Nur77-binding affinity (Kd = 6.99 × 10-6 M) which is consistent with the result of docking studies. Next, the anti-inflammatory mechanism of 4k was found to be through NF-κB signal pathway in a Nur77-dependent manner. Moreover, we also observed 4k significantly inhibited LPS-induced expression of cytokines (IL-6, TNF-α, and IL-1β) through suppressing NF-κB activation and attenuated LPS-induced inflammation in mouse acute lung injury (ALI) model. In conclusion, the study strongly suggests that the PUFA-AA derivatives can be particularly as new Nur77 mediators for further treatment in inflammatory diseases.The indole scaffold has been recognized, over the years, as a model for the synthesis of compounds with anticancer activity by dint of its substantiated ability to act via multiple mechanisms, which also involves the inhibition of enzymes engaged in DNA replication. In this regard, a new series of indole and pyranoindole derivatives have been prepared, some of which showed good antitumor activity and proved their inhibitory effects on the tubulin target. The anticancer activity of the newly synthesized compounds has been evaluated on breast cancer cell lines, as MCF-7 and MDA-MB231, cervical cancer cells line HeLa and Ishikawa endometrial cancer cell line. Among the compounds under study, 7 exhibited a good antitumor activity on HeLa cell line (IC50 = 3.6 ± 0.5), leading to cell death by apoptosis due to the inhibition of tubulin polymerization, which demonstrated that the compound can explicate its function in a similar way to Vinblastine, a well-known inhibitor of tubulin polymerization. The data were also confirmed by in silico assays. No cytotoxicity against normal cells has been detected. Furthermore, in order to investigate the antioxidant properties, DPPH and ABTS tests were performed, together with fluorescence assays on 3T3-L1 cells. All our findings taken together led us to consider compound 7 a favourable candidate for the battle against cancer.In the present study, the titanium decorated iron oxide (Ti@Fe2O3) nanocomposites are synthesized using the chemical method. The as-prepared nanocomposite was characterized for successful formulation and the elemental spectra showed the composition of Fe (44%), Ti (0.71%) and O (55%) is confirmed the homogenous distribution. Crystallographic spectra depict the strong peaks corresponding to the of TiO2 and Fe2O3 nanoparticles planes with minor shift variation due to the formulation of Ti on the surface of Fe2O3 nanoparticles and it is also confirmed with SAED analysis. The X-ray photoelectron spectroscopy (XPS) analysis of Ti@Fe2O3) nanocomposite confirms the existence of elements such as Fe, O and Ti. Further, the morphology of the composite showed the well-defined encapsulation and aggregation of TiO2 nanoparticles on the surface of Fe2O3 nanoparticles. Further, the TiO2 nanoparticles showed less cytotoxic activity against bovine satellite cells, as well the nanocomposite increased the growth of bovine satellite cells comparing with control cells. Further, the morphological analysis showed the significant changes in TiO2 nanoparticles treated cells and the nanocomposite induces the myotube formation due to the increased ROS level in bovine satellite cells. Moreover, the nanocomposite regulates the expression of genes IGF-1, TGF-β, MSTN, CASP3, CASP2 and proteins such as CALP1, CALP2, MyoD, MyoG which are responsible for the growth, proliferation, and differentiation of satellite cells. Together, the prepared Ti@Fe2O3 nanocomposites afford additional support for the applications of nanomaterials in skeletal muscle repair and tissue regeneration engineering.The literature on "missing girls" suggests a net preference for sons both in China and among Chinese immigrants to the West. Perhaps surprisingly, we find that newborn Chinese-American girls are treated more intensively in US hospitals they are kept longer following delivery, have more medical procedures performed, and have more hospital charges than predicted (by the non-Chinese gender difference). What might explain more aggressive medical treatment? We posit that hospitals are responding to worse health at birth of Chinese-American girls. We document higher rates of low birth weight, congenital anomalies, maternal hypertension, and lower APGAR scores among Chinese American girls - outcomes recorded prior to intensive neonatal medical care and relative to the non-Chinese gender gap. To the best of our knowledge, we are the first to find that son preference may also compromise "survivor" health at birth. On net, compromised newborn health seems to outweigh the benefit of more aggressive neonatal hospital care for girls. Relative to non-Chinese gender differences, death on the first day of life and in the post-neonatal period is more common among Chinese-American girls, i.e. later than sex selection is typically believed to occur.

The objective of this study was to explore serum levels of differentially abundant proteins between women with hypertensive disorders of pregnancy (HDP) and women with normal-term pregnancy, and to explore the contribution of SH3BGRL3 to the pathogenesis of HDP.

At 6-20 weeks gestation 48 pregnant women who later developed HDP (HDP group) and 48 women with normal-term pregnancy (normal group) were recruited based on maternal age and gestational age at a 11 ratio. Total serum protein was extracted, denatured, deoxidized, and subjected to enzymolysis. The sample was labeled with Tandem Mass Tags and analyzed via mass spectroscopy to identify differentially abundant proteins. The role of SH3BGRL3 in trophoblast invasion, proliferation and apoptosis was examined using the HTR-8/SVneo cell line and primary isolates of extravillous trophoblast (EVT) cells.

In the proteomic profiling analysis, there were 19 proteins that showed significant differential abundance (P<0.05). Among them, 13 proteins were more abundant and 6 proteins were less abundant in the serum from the HDP group compared with the normal group. The function of one of the more abundant proteins, SH3BGRL3, in trophoblast cell invasion, proliferation and apoptosis was investigated. Treatment of the EVT cells or the HTR-8/SVneo cell line with anti-SH3BGRL3 inhibited proliferation, but stimulated both apoptosis and invasion. MMP2 and p-ERK levels were also decreased in EVT after anti-SH3BGRL3 treatment.

The SH3BGRL3 protein can regulate various aspects of trophoblast biology, and may be useful in the clinical diagnosis of HDP.

The SH3BGRL3 protein can regulate various aspects of trophoblast biology, and may be useful in the clinical diagnosis of HDP.The powerful and intriguing idea that drives the emerging technology of microneedles-shrinking the standard needle to a micron scale-has fostered an entire field of microneedle study and subsequent exponential growth in research and product development. Originally enabled by microfabrication tools derived from the microelectronic industry, microneedles are now produced through a number of methods in a variety of forms including solid, coated, dissolvable, and hollow microneedles. They are used to deliver a broad spectrum of molecules, including small molecules, biomolecules, and vaccines, as well as various forms of energy into the skin, eye, and other tissues. Microneedles are also being exploited for use in diagnostics, as well as additional medical, cosmetic, and other applications. This review elucidates the relative roles of different aspects of microneedle technology development, as shown through scientific papers, patents, clinical studies, and internet/social media activity. Considering >1000 papers, 750 patents, and almost 80 clinical trials, we analyze different attributes of microneedles such as usage of microneedles, types of microneedles, testing environment, types of patent claims, and phases of clinical trials, as well as which institutions and people in academia and industry from different locations and in different journals are publishing, patenting, and otherwise studying the potential of microneedles. We conclude that there is robust and growing activity in the field of microneedles; the technology is rapidly developing and being used for novel applications to benefit human health and well-being.Pulsed electromagnetic field (PEMF) treatments stimulate bone formation activities though further work is needed to optimize its therapeutic benefit. PEMF can generate local potential gradients and electric currents that have been suggested to mimic bone electrochemical responses to load. In line with this reasoning, a recent publication reported that PEMF application on isolated bone tissue induced detectable micro-vibrations (doihttps//doi.org/10.1109/TMAG.2016.2515069). To determine the ability of PEMF to intervene in a rat model of osteoporosis, we tested its effect on trabecular and cortical bone following ovariectomy. Four PEMF treatments, with increasing sinusoidal amplitude rise with time (3850 Hz pulse frequency and 15 Hz repetition rate at 10 tesla/sec (T/s), 30 T/s, 100 T/s, or 300 T/s), were compared to the efficacy of an osteoporosis drug, alendronate, in reducing levels of trabecular bone loss in the proximal tibia. Herein, the novel findings from our study are (1) 30 T/s PEMF treatment approached the efficacy of alendronate in reducing trabecular bone loss, but differed from it by not reducing bone formation rates; and (2) 30 T/s and 100 T/s PEMF treatments imparted measurable alterations in lacunocanalicular features in cortical bone, consistent with osteocyte sensitivity to PEMF in vivo. The efficacy of specific PEMF doses may relate to their ability to modulate osteocyte function such that the 30 T/s, and to a lesser extent 100 T/s, doses preferentially antagonize trabecular bone resorption while stimulating bone formation. Thus, PEMF treatments of specific magnetic field magnitudes exert a range of measurable biological effects in trabecular and cortical bone tissue in osteoporotic rats.Bone metastases occur in 70% of patients with advanced breast cancer, causing severe morbidity and increased mortality due to osteolytic lesions driven by osteoclasts (OCs) inside the bone marrow (BM) microenvironment. A reciprocal vicious cycle between bone remodeling system and the tumor itself is established by the release of growth factors stored in the mineralized matrix, which in turn feed the tumor, changing tumor behavior and growth. However, BM is not a passive host microenvironment for circulating tumor cells, but instead can be actively modified by the primary tumor before metastatic spread occurs. Indeed, we have shown that T cells specific for the 4T1 mammary carcinoma cell line, are characteristically RANKL+ IL-17F+ CD4+ T cells. Those cells arrive in the BM before metastatic cells and set the pre-metastatic niche. In the absence of T cell derived RANKL, there is no pre-metastatic osteolytic disease and bone metastases do not take place. Recently, dendritic cells (DCs), the main T cell partner alysis, maintaining the pro-osteoclastogenic T cell phenotype in the BM.The present study was designed to evaluate luteinization rates subsequent to aspiration of dominant follicles (≥25 mm) in the absence of a functional CL (progesterone 0.05) among groups on Day 23. Thus, the present study provided novel information that the luteinization rate is relatively high (83%) and consistent following aspiration of dominant follicles (≥25 mm) in the absence of a functional CL and that the increase in progesterone reaches sustainable progestational concentrations (≥2 ng/mL) in accord with the length of the estrous cycle that may potentially support development and maintenance of early pregnancy in recipient mares involved in an embryo transfer program.Accumulating evidence has demonstrated the role of microRNAs (miRs) in the avian ovary. In this study, high-throughput transcriptome analyses were employed to study the differential miR expression profiles in the chicken ovary, aiming to reveal miR-targeting matrix metalloproteinase (MMP) expression during follicular growth, maturation, and atresia. Using tissues of chicken ovarian follicles at key steps of development (slow growing - white, the most recently recruited - small yellow, and preovulatory - F2) and regression (the third postovulatory), 14 small RNA (sRNA) libraries were constructed. The 25 most highly expressed known miRs were identified along with eight significantly differentially expressed (DE) miRs (gga-miR-let-7d, gga-miR-31-3p, gga-miR-138-1-3p, gga-miR-1552-5p, gga-miR-92-3p, gga-miR-31-5p, gga-miR-202-3p, and gga-miR-6648-3p) which were further examined by quantitative real time-PCR (qRT-PCR) in white, yellowish, small yellow, and atretic follicles as well as in the granulosa and theca layer of yellow preovulatory F3-F1 follicles (n = 6 hens). These miRs were mainly associated with four pathways inhibition of MMPs, axonal guidance signaling, HIF1α signaling, and GP6 signaling. Four predicted target genes (i.e. MMP-16, ADAM10, COL4A2, and COL4A5) were examined by qRT-PCR and negatively correlated with DE miRs. The identified candidate miRmRNA target pairs include gga-miR-31-5p or gga-miR-92-3pMMP-16, gga-miR-31-5p or gga-miR-92-3pADAM10, let-7dCOL4A2, and gga-miR-138-1-3pCOL4A5 are potentially associated with MMP modulation in the hen ovary, mostly in the granulosa and theca cells of the largest preovulatory follicles. These results provide a novel insight to the role of miRs in follicle development by identifying a miR target network that is putatively engaged in remodeling of the extracellular matrix during ovarian follicle development in chickens.MicroRNAs (miRNAs) are endogenous non-coding RNAs in eukaryotic cells that modulate apoptosis of ovarian granulosa cells (GCs), which is an important cause of mammalian follicular atresia. In the present study, associations were evaluated between miR-21-5p and the extent of Smad7 protein production in regulation of ovarian granulosa cell (pGC) apoptosis. There was detection of miR-21-5p and Smad7 primarily in the cytoplasm and nucleus of pGCs, respectively. When there was an enhanced abundance of miR-21-5p and decreased abundance of Smad7 there were similar effects in pGCs, including inducing proliferation, inhibiting apoptosis, increasing the number of cells in S and G2/M phases, increasing serum estradiol, and decreasing serum progesterone concentrations. Furthermore, the Smad7 mRNA transcript was identified as a target for miR-21-5p actions, with enhanced abundances of miR-21-5p being associated with a lesser abundance of Smad7 mRNA transcript and protein in pGCs. Overall, results from the present study indicate that miR-21-5p has actions on the Smad7 mRNA transcript during the process of ovarian granulosa cell apoptosis in pigs.

To determine clearance of levetiracetam in patients requiring continuous renal replacement therapy (CRRT) or sustained low efficiency dialysis (SLED).

Adult patients with acute kidney injury or end stage renal disease requiring either CRRT or SLED and levetiracetam were eligible for inclusion. Simultaneous arterial, venous, and effluent samples for analysis of levetiracetam concentrations were collected every two hours for up to 6-8h. Levetiracetam clearance (CL) and half-life (t

) were calculated for each modality.

Eight CRRT patients and 4 SLED patients completed the study 67% male, mean age 50±13years, and 83% had AKI. Seven CRRT patients received continuous venovenous hemodiafiltration (CVVHDF) [median pre-replacement rate 700mL/h (range 500-1000), post-replacement rate 500mL/h (range 200-1000), effluent rate 2500mL/h (range 1700-3650) and delivered CRRT dose 27mL/kg/h (range 19-54)] and one patient received CVV hemofiltration (CVVH). The mm mean levetiracetam CL during CVVHDF was 31.2±8.5mL/min, and the and the mean t

was 10.4±2.2h. For the patient requiring CVVH, clearance and t

were 22.5mL/min and 9.5h, respectively. Mean levetiracetam CL during SLED performed at a blood flow rate of 250mL/min and a dialysate flow rate of 100mL/min was 74.0±25.3mL/min and t

was 4.8±2.3h.

Levetiracetam clearance was substantial with both modalities under the operating conditions reported. There is the potential for subtherapeutic concentrations with current recommended dosing strategies that account only for kidney function and not these extracorporeal routes of elimination.

Levetiracetam clearance was substantial with both modalities under the operating conditions reported. There is the potential for subtherapeutic concentrations with current recommended dosing strategies that account only for kidney function and not these extracorporeal routes of elimination.Guidelines suggest broad use of pharmacologic prophylaxis to prevent venous thromboembolism (VTE) in hospitalized medical patients, however little 'real-world' data exists to support this. Our goal was to describe the use of thromboprophylaxis among general medical and cancer patients admitted to hospital, compare VTE and bleeding outcomes according to use of thromboprophylaxis, and to determine what variables influence prescribing patterns and outcomes. Patients admitted to the general medical and oncology services at The Ottawa Hospital between 2010 and 2015 were retrospectively reviewed and classified according to whether they received initial, delayed, or no pharmacologic thromboprophylaxis during their first hospitalization. Patients with an alternate indication for anticoagulation or those admitted with a bleeding event were excluded from analysis. The primary efficacy outcome was any symptomatic VTE during index hospitalization or within 90 days of discharge, and the primary safety outcome was clinically relevant bleeding during the index hospitalization. 17,262 patients were included in our final analysis. General medical patients selected to receive no, initial, or delayed thromboprophylaxis had 0.4%, 0.7%, and 2.4% rates of VTE; and 0.2%, 0.7%, and 1.5% rates of clinically relevant bleeding complications, respectively. Cancer patients had significantly higher rates of VTE 3.3%, 3.9%, and 5.0%; and 0.9%, 0.7%, and 3.0% rates of clinically relevant bleeding among those selected to receive no, initial, or delayed thromboprophylaxis, respectively. Overall, our study suggests that broad use of pharmacologic thromboprophylaxis may be unnecessary in select low-risk general medical patients and may be less effective in cancer patients in whom new studies are indicated.The intention of the study was to establish the activity concentrations and the annual committed effective dose due to ingestion of medicinal plants and soils by pregnant women and their probable effects to infants. The samples of medicinal plants and soils were collected from Osukuru, Tororo District (Uganda). The naturally occurring radionuclides investigated were 226Ra, 232Th and 40K and their activity concentrations were determined using NaI gamma detector. In the medicinal plants, the average activity concentrations of 226Ra, 232Th and 40K were found to be 6.04 Bq/kg, 9.65 Bq/kg and 359.59 Bq/kg respectively. African Basil registered the highest activity concentration of 226Ra of 10.02 Bq/kg, spider plant had the highest activity concentration of 232Th of 18.60 Bq/kg whereas the pumpkin registered the highest activity concentrations of 40K of 437.92 Bq/kg. The average activity concentrations of 226Ra, 232Th and 40K in 'medicinal soils' were 68.87 Bq/kg, 78.20 Bq/kg and 477.44 Bq/kg respectively. The soil values higher 0.3 mSv/y in infants. The results of this study show that there is inherent danger to the infants in consuming soils during pregnancy and this should be discouraged.

To report the end-of-study results from the Ladder clinical trial of the Port Delivery System with ranibizumab (PDS) for the treatment of neovascular age-related macular degeneration (nAMD).

Multicenter, randomized, active treatment-controlled phase 2 clinical trial.

Patients diagnosed with nAMD with a documented response to anti-vascular endothelial growth factor treatment who received study treatment (N= 220).

Patients were randomized 3332 to treatment with the PDS filled with ranibizumab 10-mg/ml, 40-mg/ml, and 100-mg/ml formulations or monthly intravitreal ranibizumab 0.5-mg injections.

End-of-study results for the time to first meeting refill criteria (first refill), mean change from baseline for best-corrected visual acuity (BCVA) and central foveal thickness (CFT), and safety.

At study end, the mean time on study was 22.1 months (range, 10.8-37.6 months) for all PDS patients. Median time to first refill was 8.7 months, 13.0 months, and 15.8 months, and 28.9%, 56.0%, and 59.4% of patients weod. The PDS has the potential to reduce treatment burden in patients with nAMD while maintaining vision.

Over a mean of 22 months on study, vision and anatomic outcomes were comparable between the PDS 100-mg/ml and monthly intravitreal ranibizumab 0.5-mg arms, with a lower total number of ranibizumab treatments with the PDS. The Ladder end-of-study findings were consistent with the primary analysis, and the PDS generally was well tolerated throughout the entire study period. The PDS has the potential to reduce treatment burden in patients with nAMD while maintaining vision.

To determine histologic correlates for stages of drusen-associated atrophy observed with fundus autofluorescence (FAF) and color fundus photography (CFP), of eyes with advanced age-related macular degeneration (AMD).

Case study and clinicopathologic correlation.

A white woman with AMD findings of inactive subretinal fibrosis (right eye) and untreated nonexudative type 1 macular neovascularization (left eye) was followed for 9 years before death at 90 years of age.

Eyes preserved 6.25 hours after death were postfixed in osmium tannic acid paraphenylenediamine and were prepared for submicrometer epoxy resin sections (115 and 90 from the right and left eye, respectively), with 19 aligned to clinical B-scans. Drusen visible by CFP at the last visit were assigned to 4 stages ofFAF stage 1, isoautofluorescence; stage 2, mildly uniform hyperautofluorescence; stage 3, a ring of hyperautofluorescence around a center of the hypoautofluorescence; and stage 4, uniform hypoautofluorescence.

Light microscopic morStages 3 and 4 comport with incomplete RPE and outer retinal atrophy as defined by the Classification of Atrophy Meetings group. Loss of RPE, ONL, and ELM in stage 4 indicates that atrophy can begin over individual drusen. Findings will help the identification of new therapeutic approaches and clinical study end points.

We present the first direct clinicopathologic correlation for FAF imaging of drusen-associated atrophy. Our data support 4 FAF stages of drusen-associated atrophy. Stage 2 is the earliest detected stage in which loss of screening by photoreceptor photopigment contributes to uniform hyperautofluorescence. Stages 3 and 4 comport with incomplete RPE and outer retinal atrophy as defined by the Classification of Atrophy Meetings group. Loss of RPE, ONL, and ELM in stage 4 indicates that atrophy can begin over individual drusen. Findings will help the identification of new therapeutic approaches and clinical study end points.

Tree nut allergies affect an estimated 1% of the US population and is lifelong in 90% of allergic individuals. Oral immunotherapy (OIT) for food allergies is an effective method to induce desensitization in a majority of participants in trials of peanut, egg, and milk OIT. Limited trials using tree nut OIT have been reported, possibly due to the lack of standardized drug products.

Food products used in OIT are considered drugs by the Food and Drug Administration (FDA) because they are intended to modulate the individuals' immune responses to the food allergens. As such, OIT drug products must meet FDA standards for acceptable levels of microbes and undergo testing for allergenic proteins. We aimed to determine the suitability of walnut, cashew, hazelnut, and almond flours for use in OIT trials.

We employed gamma irradiation on commercially available walnut, cashew, hazelnut, and almond flours and tested their levels of microbial contamination, total protein, and allergen content, along with stability of these parameters over time.

Our results demonstrate that irradiation of tree nut flours greatly diminishes the levels of total aerobic bacteria, mold, yeast, Escherichia coli, and Salmonella, whereas there are no substantial changes in total protein or allergen content. Importantly, the microbial levels, protein, and allergen content remained stable over a 24-month period.

Irradiation of tree nut flours is a safe and effective method of processing to allow tree nut products to meet the FDA standards for OIT drug products.

Irradiation of tree nut flours is a safe and effective method of processing to allow tree nut products to meet the FDA standards for OIT drug products.

Gain-of-function mutations in STING1 underlie a type I interferonopathy termed SAVI (STING-associated vasculopathy with onset in infancy). This severe disease is variably characterized by early-onset systemic inflammation, skin vasculopathy, and interstitial lung disease (ILD).

To describe a cohort of patients with SAVI.

Assessment of clinical, radiological and immunological data from 21 patients (17 families) was carried out.

Patients carried heterozygous substitutions in STING1 previously described in SAVI, mainly the p.V155M. Most were symptomatic from infancy, but late onset in adulthood occurred in 1 patient. Systemic inflammation, skin vasculopathy, and ILD were observed in 19, 18, and 21 patients, respectively. Extensive tissue loss occurred in 4 patients. Severity of ILD was highly variable with insidious progression up to end-stage respiratory failure reached at teenage in 6 patients. Lung imaging revealed early fibrotic lesions. Failure to thrive was almost constant, with severe growth failuronopathies.

The largest worldwide cohort of SAVI patients yet described, illustrates the core features of the disease and extends the clinical and immunological phenotype to include overlap with other monogenic interferonopathies.

Recognizing anaphylaxis in infants and toddlers can be challenging for health care providers and caregivers, and current diagnostic criteria and anaphylaxis action plans do not specifically address this younger population.

To describe symptoms and signs observed by primary caregivers of infants and toddlers during severe food-induced allergic reactions.

We conducted a national online survey among primary caregivers of children who experienced a severe food-induced allergic reaction when less than 36 months of age. Respondents who were present during the child's most severe reaction were asked to report symptoms and signs observed. The survey asked about infant- and toddler-specific symptoms and signs in lay language for caregivers. Data were compared with patient-reported data from past studies to identify distinct patterns among the younger population.

The survey was completed for 374 children (193 infants, 181 toddlers). The most common symptoms and signs reported were skin reactions (90%), facial ariteria, clinical guidelines, and anaphylaxis action plans may be enhanced to address this young, often nonverbal, population.

White matter hyperintensities (WMH) are estimated to occur in greater than 63% of older adults over the age of 60 years. WMH identified in the T2-weighted FLAIR images can be combined with T1-weighted images to enhance individualized current flow models of older adults by accounting for the presence of WMH and its effects on delivered tES current in the aging brain.

Individualized head models were derived from T1-weighted images of 130 healthy older adults (mean=71 years). Lesions segmented from FLAIR acquisition were added to individualized models. Current densities were computed in the brain and compared between models with and without lesions.

Integrating WMH into the models resulted in an overall decrease (up to 7%) in median current densities in the brain outside lesion regions. Changes in current density and total lesion volume was positively correlated (R

=0.31, p<0.0001).

Incorporating WMH into individualized models may increase the accuracy of predicted tES current flow in the aging brain.

Incorporating WMH into individualized models may increase the accuracy of predicted tES current flow in the aging brain.

Electrical stimulation applied to individual organs, peripheral nerves, or specific brain regions has been used to treat a range of medical conditions. In cardiovascular disease, autonomic dysfunction contributes to the disease progression and electrical stimulation of the vagus nerve has been pursued as a treatment for the purpose of restoring the autonomic balance. However, this approach lacks selectivity in activating function- and organ-specific vagal fibers and, despite promising results of many preclinical studies, has so far failed to translate into a clinical treatment of cardiovascular disease.

Here we report a successful application of optogenetics for selective stimulation of vagal efferent activity in a large animal model (sheep).

Twelve weeks after viral transduction of a subset of vagal motoneurons, strong axonal membrane expression of the excitatory light-sensitive ion channel ChIEF was achieved in the efferent projections innervating thoracic organs and reaching beyond the level of the diaphragm. Blue laser or LED light (>10mWmm

 ; 1ms pulses) applied to the cervical vagus triggered precisely timed, strong bursts of efferent activity with evoked action potentials propagating at speeds of ∼6ms

.

These findings demonstrate that in species with a large, multi-fascicled vagus nerve, it is possible to stimulate a specific sub-population of efferent fibers using light at a site remote from the vector delivery, marking an important step towards eventual clinical use of optogenetic technology for autonomic neuromodulation.

These findings demonstrate that in species with a large, multi-fascicled vagus nerve, it is possible to stimulate a specific sub-population of efferent fibers using light at a site remote from the vector delivery, marking an important step towards eventual clinical use of optogenetic technology for autonomic neuromodulation.

Transcranial electrical stimulation at an appropriate dose may demonstrate intracranial effects, including neuronal stimulation and cerebral blood flow responses.

We performed invivo experiments on mouse cortex using transcranial alternating current [AC] stimulation to assess whether cerebral blood flow can be reliably altered by extracranial stimulation.

We performed transcranial AC electrical stimulation transversely across the closed skull in anesthetized mice, measuring transcranial cerebral blood flow with a laser Doppler probe and intracranial electrical responses as endpoint biomarkers. We calculated a stimulation dose-response function between intracranial electric field and cerebral blood flow.

Stimulation at electric field amplitudes of 5-20mV/mm at 10-20Hz rapidly increased cerebral blood flow (within 100ms), which then quickly decreased with no residual effects. The time to peak and blood flow shape varied with stimulation intensity and duration, showing a linear correlation between stimullood flow (i.e., in stroke recovery) will require significant modification, potentially to pericranial, focused, multi-electrode application or intracranial stimulation.

To evaluate protocols of root canal irrigation and dentin pretreatment in a cell culture model simulating immature teeth. Cytotoxic, migration, and angiogenic effects of Sodium hypochlorite associated with EDTA (NaOCl/EDTA), NaOCl associated with Smear Clear (NaOCl/SC), and QMix were compared.

Three roots of mandibular first premolars had their length and root canal diameter standardized. Root canals were irrigated, and the resulting solutions were diluted in culture medium. Sulforhodamine B (SRB) assay was performed with apical papilla cells and with endothelial cells (HUVECs) to assess cytotoxicity. Polarity index and migration assays of apical papilla cells and sprouting of HUVECs were evaluated. Data were analyzed by ANOVA and Tukey post-hoc tests (p < .05).

In apical papilla cells, NaOCl/SC and QMix promoted higher cytotoxicity, decreased fraction of elongated cells, and had lower migration speed and shorter migration distance of cells compared to NaOCl/EDTA. Also, HUVECs treated with NaOCl/SC and QMix showed decreased tubule formation in comparison with NaOCl/EDTA.

NaOCl/SC and QMix showed unfavorable biological responses of cells involved in revascularization in comparison to NaOCl/EDTA. Further studies with other intracanal irrigants should be performed to improve the balance of root canal disinfection with biological responses.

NaOCl/SC and QMix showed unfavorable biological responses of cells involved in revascularization in comparison to NaOCl/EDTA. Further studies with other intracanal irrigants should be performed to improve the balance of root canal disinfection with biological responses.

This study investigated circRNA and lncRNA expression profile in exosomes derived from periodontal ligament stem cell (PDLSC) before and after its osteogenic differentiation.

Exosomes derived from PDLSCs before (EX0) and after osteogenic induction for 5 (EX5) and 7 (EX7) days were harvested and exosomal circRNAs and lncRNAs were analyzed by RNA sequencing. Certain RNAs showing significantly altered expression were selected for qRT-PCR verification. The circRNA-miRNA-mRNA network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed.

All groups of exosomes showed typical characteristics under nanoparticle tracking analysis, flow cytometry assay and transmission electron microscopy. 69-557 circRNAs and 2907-11581 lncRNAs were found in EX0, EX5 and EX7, which were broadly distributed across the 24 pairs of human chromosomes. Compared with EX0, 3 circRNAs and 2 lncRNAs were up-regulated and 39 circRNAs and 5 lncRNAs down-regulated consistently through out of EX5 and EX7, p < 0.05. qRT-PCR confirmed certain those consistently expressed RNAs, such as circ lysophosphatidic acid receptor 1 (LPAR1). KEGG analysis showed that those consistent expressed RNAs closely related to TGF-beta pathway, MAPK pathway, mTOR pathway and FoxO signaling pathways regulating pluripotency of stem cells.

Exosomal circRNAs and lncRNAs had significant expression changes during the early phase of osteogenic differentiation of PDLSCs. Further study would be taken for understanding the roles of exosomal circRNAs and lncRNAs playing in osteogenic differentiation of PDLSCs.

Exosomal circRNAs and lncRNAs had significant expression changes during the early phase of osteogenic differentiation of PDLSCs. Further study would be taken for understanding the roles of exosomal circRNAs and lncRNAs playing in osteogenic differentiation of PDLSCs.

The aim of this study is evaluation of pregnancy outcomes of the asymptomatic cases with vaginal progesterone treatment for the 20-30 mm cervical length detected in the transvaginal ultrasonography for fetal abnormality screening and cervical cerclage after cervical length detected <20 mm in weekly cervical length measures; and present the treatment algorithm of progesterone treatment combined with cervical cerclage application.

Patients who have the inclusion criteria and cervical length more than 30 mm were categorized as group 1(n = 1948). Group 2 were included patients with cervical length shorter than 30 mm (n = 95). All patients of group 2 started to use vaginal natural progesterone 400 mg/day(n = 87). Pregnancies which progressed with cervical length above 20 mm were continued vaginal progesterone until 34. Gestational week and they were named as group 2A (n = 78). Cervical cerclage were applied to patients with cervical length below than 20 mm measured via transvaginal ultrasonography and they were categorized as group 2B (n = 9).

Excluding 8 cases (8.42 %) which cervical cerclage were applied, 87 patients were administered vaginal progesterone and in 9 cases (10.34 %) cervical shortening were continued despite progesterone treatment. Four out of these nine cases (44.44 %) had cervical cerclage and their deliveries were delayed after 34 th gestational week. Vaginal progesterone treatment prevented cervical shortening in 89.66 % of patients who had cervical length between 20-30 mm and out of these patients.

Cervical cerclage application algorithm in continued cervical shortening cases despite vaginal progesterone is beneficial to delay the delivery after 34 th gestational week and related to low complication rate.

Cervical cerclage application algorithm in continued cervical shortening cases despite vaginal progesterone is beneficial to delay the delivery after 34 th gestational week and related to low complication rate.

To determine the incidence of occult uterine sarcomas and other unexpected pathologies in patients undergoing hysterectomies or myomectomies with a pre-operative diagnosis of uterine leiomyomas.

Retrospective study.

Tertiary hospital in Santiago, Chile.

921 women who underwent surgery for presumed myomas. Database analysis of surgical and pathological notes, from January 2007 to December 2017 with a preoperative diagnosis of uterine leiomyoma.

number of patients with uterine sarcoma confirmed on histology.

During this period, a total of 921 gynecological surgeries were performed for benign uterine fibroids of which 787 were hysterectomies and 134 were myomectomies. We found four cases of malignant neoplasms (0,43 %). Two were uterine leiomyosarcoma (LMS), one mixed epithelial and mesenchymal tumor, and one case of incidental cervical cancer. This gives an LMS incidence of 1 in 460 and 1 in 921 of mixed epithelial and mesenchymal tumor. There were seven cases of unexpected benign pathology. This included six atypical myomas and one leiomyoblastoma epithelioid myoma. If we combine the malignant and benign cases, we would have an incidence of 1.2 % of unexpected pathology.

In our series of patients undergoing myomectomies or hysterectomies for presumed myomas the incidence of LMS was 1 in 460. The incidence of any unexpected pathology including benign ones in presumed myomas was 1 in 83 (six atypical myomas, one leiomyoblastoma epithelioid myoma, two LMS, one mixed epithelial and mesenchymal tumor, one incidental cervical cancer).

In our series of patients undergoing myomectomies or hysterectomies for presumed myomas the incidence of LMS was 1 in 460. The incidence of any unexpected pathology including benign ones in presumed myomas was 1 in 83 (six atypical myomas, one leiomyoblastoma epithelioid myoma, two LMS, one mixed epithelial and mesenchymal tumor, one incidental cervical cancer).

Induction of labour in women with an unfavourable cervix is associated with a risk of caesarean delivery. When a diagnosis of fetal growth restriction (FGR) is also involved, the risk of intrapartum fetal acidosis increases. The main objective was to identify prognostic factors for the risk of caesarean delivery after induction for suspected FGR after 36 weeks of gestation with an unripe cervix.

This was a retrospective, single-centre (Port Royal, Paris, France) study of women with a singleton fetus in cephalic presentation, with labour induced at or after 36 weeks for suspected FGR diagnosed during second or third trimester of pregnancy with an unripe cervix (Bishop score under 6) who gave birth between 1 January 2015 and 31 December 2019. A multivariable analysis was performed to identify the factors related to an increased risk of caesarean section.

Of the 146 women included, 56 (38.4 %) had caesarean deliveries. After adjustment, the factors significantly associated with the risk of caesarean were maternal age greater than 39 years (ORa = 4.33 [1.22-17.2], reference 25-39 years), nulliparity (ORa = 3.49 [1.25-11.2]), and an abnormal fetal umbilical artery Doppler velocimetry (ORa = 3.50 [1.47-8.70]). The risk of poor neonatal condition did not differ significantly between women with vaginal and caesarean deliveries (2.3 % vs 7.3 %, P = 0.21).

When FGR is suspected at 36 weeks of gestation and later, induction of labour is a reasonable option, even if the cervix is unripe, as the risk of caesarean delivery appears acceptable and neonatal status is good and similar with both modes of delivery.

When FGR is suspected at 36 weeks of gestation and later, induction of labour is a reasonable option, even if the cervix is unripe, as the risk of caesarean delivery appears acceptable and neonatal status is good and similar with both modes of delivery.

To evaluate a thrombin gel matrix (TGM), Floseal, for the prevention of lymphocele in patients with endometrial cancer who underwent pelvic lymphadenectomy.

A total of 79 consecutive patients with endometrial cancer were randomly allocated to one of two groups the TGM group and control group. After completion of the lymphadenectomy, 5 mL of Floseal was applied to the bilateral pelvic sidewalls, especially the femoral canal, obturator, and common iliac vessels areas. Computed tomography scans were obtained for lymphocele evaluation 2 months after the surgery.

Three patients from the TGM group, and four patients from the control group were lost during follow-up, and data from 36 participants from each group were analyzed. As the primary outcome, lymphocele developed in 12 patients in both groups (33 %). There was no significant difference between the groups in terms of lymphocele and symptomatic lymphocele development. Lymphocele localization was also not different between the two groups, but the diameter of the lymphoceles detected in the TGM group was significantly greater (p = 0.021). The mean drainage days was significantly shorter in the TGM group (p = 0.015). The amount of drainage was also less in the TGM group, but the difference was not statistically significant.

Thrombin gel matrix applied to the pelvic sidewalls does not reduce the incidence of symptomatic or asymptomatic lymphoceles after pelvic lymphadenectomy in endometrial cancer. However, it can reduce the amount of drainage and the number of drainage days so it can help to shorten hospitalization.

Thrombin gel matrix applied to the pelvic sidewalls does not reduce the incidence of symptomatic or asymptomatic lymphoceles after pelvic lymphadenectomy in endometrial cancer. However, it can reduce the amount of drainage and the number of drainage days so it can help to shorten hospitalization.Breast cancer is the leading cause of cancer death in women, and most breast cancer related deaths are due to metastases. Uterine metastases from breast cancer are uncommon and rarely reported in the literature. We described the case of a 50 years-old-woman who developed a uterine metastasis, 6 years after the diagnosis of an invasive ductal breast carcinoma. Indeed, although the patient was asymptomatic, the monitoring imaging examinations, particularly the computed tomography (CT) and the positron emission tomography/computed tomography (PET/CT), showed a myometrial lesion. Non-conservative total hysterectomy was performed. The anatomo-pathological examination revealed a myometrial metastasis from an invasive ductal breast carcinoma. Seventeen months after surgery, the patient had no pelvic recurrence, but lungs and bones metastases progressed despite chemotherapy. In the lack of guidelines of uterine metastases from breast cancer's management, we reviewed the existing literature with the aim to provide a rational framework for clinical presentation, diagnostic approach, histological findings and treatment of this rare and heterogeneous pathology. Uterine metastases of breast cancer are frequently revealed with metrorrhagia. They occur preferentially in tumours with initial lobular carcinoma, initial lymph node involvement and positive hormonal receptors.Hyperbranched polymers (HBPs), such as hyperbranched polyglycerols (HPGs) with a dendritic configuration, have been recognized for their excellent biocompatibility and multifunctionalization. HPGs have been studied for use in the delivery diagnostic, imaging and therapeutic molecules in the area of nanobiomedicine. They show superior characteristics to linear polymers and dendrimers, such as compact structure, a simple manufacturing process with easy functionalization ability, low viscosity, and high stability. Owing to these advantages, HPGs are now considered promising carriers for drug delivery, diagnostics, imaging, and theranostics applications for cancer treatment. In this review, we also discuss safety aspects of HPG-based nanoformulations in various animal models and the clinical translation status of such polymers for real-time applications.