Sandbergwilliford8074

In this work, a series of Biotin-substituted B-nor-cholesteryl benzimidazole compounds were synthesized. The antiproliferativeactivities of these compounds were evaluated in vitro using a series of human cancer cell lines, including HeLa (cervical cancer), SKOV3 (ovarian cancer), T-47D (thymus gland cancer), MCF-7 (human breast cancer) and HEK293T (normal renal epithelial) cells. These compounds displayed distinct antiproliferative activities against the currently tested cancer cells. The apoptotic properties induced by compound 6d were further investigated. Our results showed that compound 6d could induce the apoptosis of SKOV3 cells, blocking the cell growth in S-phase. Western blotting analyses revealed that compound 6d can induce cell apoptosis via the mitochondria-dependent pathway.When Russel et al. first introduced the term 'super-recogniser' (SR), they observed that 'super-recognizers are about as good as many developmental prosopagnosics are bad', with regard to both face perception and recognition (Russell et al., 2009). As Meike Ramon reports in her Viewpoint in this issue (Ramon, 2021), SRs have since been the focus of considerable media attention and some 25 papers. Still, the term lacks a uniform operational definition, risking the comparison of apples and oranges. Thus, Ramon proposes a clear rule for qualifying someone as SR, which is precise enough for standardisation but at the same time affords flexibility. She also makes a strong case for open research practices and documentation, underscored by her exemplary presentation of 70 cases.Peripersonal space (PPS) represents the region of space surrounding the body. A pivotal function of PPS is to coordinate defensive responses to threat. We have previously shown that a centrally-presented, looming fearful face, signalling a potential threat in one's surroundings, modulates spatial processing by promoting a redirection of sensory resources away from the face towards the periphery, where the threat may be expected - but only when the face is presented in near, rather than far space. Here, we use electrophysiological measures to investigate the neural mechanism underlying this effect. Participants made simple responses to tactile stimuli delivered on the cheeks, while watching task-irrelevant neutral or fearful avatar faces, looming towards them either in near or far space. Simultaneously with the tactile stimulation, a ball with a checkerboard pattern (probe) appeared to the left or right of the avatar face. Crucially, this probe could either be close to the avatar face, and thus more central in the participant's vision, or further away from the avatar face, and thus more peripheral in the participant's vision. Electroencephalography was continuously recorded. Behavioural results confirmed that in near space only, and for fearful relative to neutral faces, tactile processing was facilitated by the peripheral compared to the central probe. This behavioural effect was accompanied by a reduction of the N1 mean amplitude elicited by the peripheral probe for fearful relative to neutral faces. Moreover, the faster the participants responded to tactile stimuli with the peripheral probe, relative to the central, the smaller was their N1. Together these results, suggest that fearful faces intruding into PPS may increase expectation of a visual event occurring in the periphery. This fear-induced effect would enhance the defensive function of PPS when it is most needed, i.e., when the source of threat is nearby, but its location remains unknown.Pharmacologic inhibition of PARP is the primary therapeutic strategy for BRCA mutant ovarian cancer. However, most of patients carry wild-type BRCA1/2 with no significant clinical benefits from PARP inhibitors, calling for the needs to further understanding and developing new strategy when employing PARP inhibitors to treat ovarian cancer. Here, we show that ferroptosis, a form of regulated cell death driven by iron-dependent phospholipid peroxidation, is partly responsible for the efficacy of PARP inhibitor olaparib. Mechanistically, pharmacological inhibition or genetic deletion of PARP downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Furthermore, ferroptosis perturbation results in significant resistance to olaparib without affecting DNA damage response, while boosting ferroptosis by ferroptosis inducers (FINs) synergistically sensitizes BRCA-proficient ovarian cancer cells and xenografts to PARP inhibitor. Together, our results reveal a previously unappreciated mechanism coupling ferroptosis to PARP inhibition and suggest the combination of PARP inhibitor and FINs in the treatment of BRCA-proficient ovarian cancer.The bacterial cytosol is generally a reducing environment with protein cysteine residues maintained in their thiol form. The low molecular weight thiol bacillithiol (BSH) serves as a general thiol reductant, analogous to glutathione, in a wide range of bacterial species. Proteins modified by disulfide bond formation with BSH (S-bacillithiolation) are reduced by the action of bacilliredoxins, BrxA and BrxB. Here, the YtxJ protein is identified as a monothiol bacilliredoxin, renamed BrxC, and is implicated in BSH removal from oxidized cytosolic proteins, including the glyceraldehyde 3-phosphate dehydrogenases GapA and GapB. BrxC can also debacillithiolate the mixed disulfide form of the bacilliredoxin BrxB. Bdr is a thioredoxin reductase-like flavoprotein with bacillithiol-disulfide (BSSB) reductase activity. Here, Bdr is shown to additionally function as a bacilliredoxin reductase. Bdr and BrxB function cooperatively to debacillithiolate OhrR, a transcription factor regulated by S-bacillithiolation on its sole cysteine residue. Collectively, these results expand our understanding of the BSH redox network comprised of three bacilliredoxins and a BSSB reductase that serve to counter the widespread protein S-bacillithiolation that results from conditions of disulfide stress.

Residential long-term care (LTC) facilities may be key settings for the prevention of suicide among older adults; however, little is known about the relationship between statewide policies determining characteristics of LTC facilities and suicide mortality. The primary goal of this study was to evaluate the association between state policies regarding availability, regulation, and cost of LTC and suicide mortality among adults aged 55 and older in the United States over a 5-year period.

Longitudinal ecological study.

LTC residents from 16 states reporting mortality data to the National Violent Death Reporting System (NVDRS) from 2010 to2015.

We linked suicide data from the NVDRS and data sources on LTC services and regulations for 16 states. We applied a natural language-processing algorithm to identify suicide deaths related to LTC. We used fixed effect regression models to assess whether state variation in LTC characteristics is related to variation in the rate of suicide (both overall and related telated suicide incidence among older adults. Given the challenges of preventing suicide among older adults through facility- or individual-level interventions, policies governing the features and provision of LTC services may therefore serve as a means for public health suicide prevention.Controversy exists as to whether high test anxiety (HTA) individuals, when completing an inhibition task, increase or decrease top-down attentional control resources to maintain high task performance. In a flanker task experiment, individuals were confronted with a threat or no threat context in combination with a low or a high working memory load. The N2 measured top-down attentional control resource allocation. The results showed that, in comparison to low test anxiety (LTA) individuals, HTA individuals had larger N2 amplitudes in a no threat condition, especially for incongruent trials. Also, in a threat condition when under high working memory load, HTA individuals had smaller incongruent N2 amplitudes. These findings support the conclusion that HTA individuals tend to enhance recruitment of top-down attentional control of inhibition. Additionally, they may also fail to compensate for impaired inhibition as indicated by impoverished top-down attentional control resources when demands on attentional control are high.Testosterone (T) has been linked to poorer social cognition in younger adults. Because social cognition and T both decline with normal aging, a different type of relationship may exist between T and social cognition in late adulthood. To test this possibility, younger and older adults provided a salivary T sample and completed two social cognition tasks. The results showed that age-group was a significant moderator in the relationship between T and theory of mind (ToM) performance for males, such that T was a negative predictor of ToM in younger males and a positive predictor of ToM in older age. No relationships were identified for females. These findings show for the first time that T is differentially related to ToM in the early and later stages of the male adult lifespan, and are discussed in relation to prior work that suggests T may have neuroprotective effects in older age.

To evaluate the effects and safety of therapeutic ultrasound in patients with neck pain.

The PubMed, EMBASE, CENTRAL, and Physiotherapy Evidence databases were searched for articles published before December 1, 2020.

Randomized controlled trials that compared the effects of therapeutic ultrasound on neck pain were included in this review. The included studies compared therapeutic ultrasound plus other treatments with the other treatments alone or compared therapeutic ultrasound with sham or no treatment. Outcome measures involved the effects on pain, disability, and quality of life. Other treatments included all nonultrasonic therapies (eg, various exercises, massage, electrotherapy).

Data on the study population, therapeutic ultrasound intervention, combined intervention, outcome measures, and follow-up were extracted.

Twelve randomized controlled trials (705 patients) fulfilled the inclusion criteria. Seven studies compared therapeutic ultrasound plus other treatments vs the other treatments alonesity of pain more than sham or no treatment, and it is a safe treatment. Whether therapeutic ultrasound in combination with other conventional treatments produced additional benefits on pain intensity, disability, or quality of life is not clear. The randomized trials included in this review had different levels of quality and high heterogeneity. A large trial using a valid methodology is warranted.A 70-year-old man with back pain presented with a tumor invading the chest wall of his right upper lobe. Three-dimensional computed tomography revealed an aberrant right lower bronchus originating from the left main bronchus. Open thoracotomy right upper lobectomy with combined resection of the chest wall was performed under ventilation for the left and right lower lobes. The aberrant bronchus was defined as a bridging bronchus, a rare congenital anomaly. For such cases, careful planning is necessary to manage ventilation during operation. The area and extent of lymph node dissection are debatable.Perfluoroctanesulfonate (PFOS) belongs to a larger family of compounds known as Per- and polyfluoroalkyl substances (PFAS). The strength of the carbon-fluorine bond makes PFOS extremely resistant to environmental degradation. Due to its persistent nature, research has been directed to elucidating possible health effects of PFOS on humans and laboratory animals. Here we have explored the effects of PFOS exposure on immune development and function in mice. We exposed adult mice to 3 and 1.5 μg/kg/day of PFOS for 2 and 4 weeks, respectively, and examined the effects of PFOS exposure on populations of T cells, B cells, and granulocytes. These doses of PFOS resulted in serum levels of approximately 100 ng/mL with no weight loss during exposure. We find that PFOS does not affect T-cell development during this time. However, while PFOS exposure reduced immune cell populations in some organs, it also led to an increase in the numbers of cells in others, suggesting possible relocalization of cells. We also examined the effect of PFOS on the response to influenza virus infection. We find that exposure to PFOS at 1.5 μg/kg/day of PFOS for 4 weeks does not affect weight loss or survival, nor is viral clearance affected. Analysis of antibody and T cell specific antiviral responses indicate that at this concentration, PFOS does not suppress the immune cell development or antigen specific immune response.Two new aporphine alkaloids, (R)-1,2-methylenedioxy-3,9-dimethoxy-11-hydroxy-N- carbamoyl-noraporphine (1) and 3,10,11-trimethoxy-1,2-methylenedioxy-7-oxoaporphine(2), and one new dihydrochalcone, 4',5'-dimethoxy-2'-hydroxy-3',6'-quinodihydrochalcone (3), along with five known alkaloids were isolated from the ethanol extracts of the stems of Fissistigma oldhamii var. longistipitatum. The compounds were obtained by various classical column chromatographic methods, and the structure elucidation was completed primarily on the basis of spectroscopic analysis, such as UV, NMR and HR-ESI-MS. The isolated compounds were subjected to evaluate cytotoxic activities in vitro, compound 1 had activity against HL-60 and HELA (IC50 value of 8.4 μM and 5.2 μM, respectively), compound 2 against MCF-7 (IC50 value of 3.7 μM), compound 3 against HEPG2 (IC50 value of 10.8 μM), respectively.Changes in the environment from the drug product to the human physiology might lead to physical and/or chemical modifications of the protein drug, such as in vivo aggregation and fragmentation. Although subcutaneous (SC) injection is a common route of administration for therapeutic proteins, knowledge on in vivo stability in the SC tissue is limited. In this study, we developed a physiologic in vitro model simulating the SC environment in patients. We assessed the stability of two monoclonal antibodies (mAbs) in four different protein-free fluids under physiologic conditions. We monitored protein stability over two weeks using a range of analytical methods, in analogy to testing purposes of a drug product. Both mAbs showed an increase of protein aggregates, fragments, and acidic species. mAb1 was consistently more stable in this in vitro model than mAb2, highlighting the importance of comparing the stability of different mAbs under physiologic conditions. Throughout the study, both mAbs were substantially less stable in bicarbonate buffers as compared to phosphate-buffered saline. In summary, our developed model was able to differentiate stability between molecules. Bicarbonate buffers were more suitable compared to phosphate-buffered saline in regards to simulating the in vivo conditions and evaluating protein liabilities.Epidemiological and experimental studies indicate that a number of aromatic solvents widely used in the industry can affect hearing and balance following chronic exposure. Animal studies demonstrated that long-term exposure to aromatic solvents directly damages the auditory receptor within the inner ear the cochlea. However, no information is available on their effect on the vestibular receptor, which shares many structural features with the cochlea and is also localized in inner ear. The aim of this study was to use an in vitro approach to assess and compare the vestibular toxicity of different aromatic solvents (toluene, ethylbenzene, styrene and ortho-, meta-, para-xylene), all of which have well known cochleotoxic properties. We used a three-dimensional culture model of rat utricles ("cysts") with preserved functional sensory and secretory epithelia, and containing a potassium-rich (K+) endolymph-like fluid for this study. Variations in K+ concentrations in this model were considered as biomarkers of toxicity of the substances tested. After 72 h exposure, o-xylene, ethylbenzene and styrene decreased the K+ concentration by 78 %, 37 % and 28 %, respectively. O- xylene and styrene both caused histopathological alterations in secretory and sensory epithelial areas after 72 h exposure, whereas no anomalies were observed in ethylbenzene-exposed samples. These in vitro results suggest that some widely used aromatic solvents might have vestibulotoxic properties (o-xylene, styrene and ethylbenzene), whereas others may not (p-xylene, m-xylene, toluene). Our results also indicate that variations in endolymphatic K+ concentration may be a more sensitive marker of vestibular toxicity than histopathological events. Finally, this study suggests that cochleotoxic solvents might not be necessarily vestibulotoxic, and vice versa.ErbB4 loss-of-function in catecholaminergic neurons induces catecholamine dyshomeostasis. Despite ErbB4's significant role in neuropathology, the signaling pathways that regulate these changes are still widely unknown. In this study, we attempt to identify the downstream pathway of ErbB4 that regulates catecholamine homeostasis. The SH-SY5Y human neuroblastoma cell line was used as the in vitro model for catecholaminergic neurons. Western blotting, enzyme-linked immunosorbent assay, and pharmacological and genetic manipulations by agonist/antagonist or small interference RNA were used to investigate the relationship between ErbB4 and extracellular catecholamines. We confirmed that ErbB4 is abundantly expressed in undifferentiated and retinoic acid-differentiated catecholaminergic cells from the SH-SY5Y cell line. ErbB4 inhibition increase the ratio of phosphorylated p38 to total p38 in SH-SY5Y human neuroblastoma cells. Consistent with previous in vivo observations in mice, ErbB4 deficiency led to increases in extracellular dopamine and norepinephrine levels. However, the resulting increase in extracellular dopamine, but not norepinephrine, could be suppressed by p38 inhibitor SB202190. Our results suggest that both extracellular dopamine and norepinephrine homeostasis could be regulated by ErbB4 in human catecholaminergic cells, and ErbB4 may regulate extracellular dopamine, but not norepinephrine, through the p38 MAPK signaling pathway, thus indicating different regulatory pathways of dopamine and norepinephrine by ErbB4 in catecholaminergic neurons.

In the United States, medication errors are considered to be the cause of 7000 deaths annually. Continuous quality improvement (CQI) is a management process that focuses on continually and systematically evaluating the organization's work process. In community pharmacy, CQI leads to enhanced patient safety through a reduction in medication errors and quality-related events (QREs). There is limited information about the variations in CQI regulations required by State Boards of Pharmacy (SBPs) for community pharmacy across the country. The objective of this study is to comprehensively describe CQI regulations required by SBPs for community pharmacy practice in the United States.

This was a cross-sectional study. Information regarding SBPs community pharmacy CQI regulations was collected electronically by surveying a representative of each SBP. In addition, a review of State Pharmacy Laws published online complemented the survey data. The percentage of states with CQI regulations for community pharmacy was estimated.

Of the 50 Boards, 16 require pharmacies to maintain CQI programs to monitor and prevent QREs in community pharmacy. The most common elements of CQI programs include the management of known, alleged, and suspected medication errors that reach the patient (73%) and regular reviews of the pharmacy's aggregate data of medication errors or incidents (73%). The North Dakota SBP regulation is the most comprehensive, followed by that of Iowa, Maryland, Massachusetts, and Montana.

There is wide variation among SBP CQI regulations for community pharmacy practice. Standardization of CQI programs across Boards, including a national database for reporting medication errors and QREs would enhance patient safety.

There is wide variation among SBP CQI regulations for community pharmacy practice. Standardization of CQI programs across Boards, including a national database for reporting medication errors and QREs would enhance patient safety.

Increasing attention has been drawn to poor working conditions in community pharmacy, the impact on patient safety, and the role of pharmacy benefit managers (PBMs) in the United States. This study assessed community pharmacists' perceptions of potential solutions to improve working conditions.

This mixed-methods, survey-based study explored pharmacists' proposed solutions for improving working conditions. The participants' perceptions of solutions at the company and state or national levels were assessed using a 7-point Likert-type response format (from 1= strongly disagree to 7= strongly agree). Multiple regression assessed the relationships between participant perceptions and pharmacy type (e.g., national chain, grocery, or independent), pharmacy degree, age, average number of prescriptions processed daily (prescription volume), and years of experience. The participants' perceptions of how to improve working conditions were explored to provide more depth and nuance to the understanding of these issues.g conditions in community pharmacy are influenced by multiple factors that often are dependent on one another. Thus, a multifaceted approach will likely be required to improve working conditions.

Identifying solutions from employee stakeholders may be an effective way to inform actions that both employers and extraorganizational entities can take to improve pharmacist working conditions and patient care. Restricting PBMs was the most preferred solution, followed by direct and indirect reimbursement for nondispensing services. However, working conditions in community pharmacy are influenced by multiple factors that often are dependent on one another. Thus, a multifaceted approach will likely be required to improve working conditions.

The use of direct oral anticoagulants (DOAC) in preference to vitamin K antagonists (VKA) as a treatment of left ventricle (LV) thrombus is controversial.

Literature search for full-text articles and conference abstracts was performed using PubMed, EMBASE databases search was performed to identify articles that compared use of DOAC vs. VKA in patients with LV thrombus. The primary outcome was composite failure or adverse effects of DOAC and VKA. Other outcomes were resolution of thrombus, systemic thromboembolism, major bleeding, and mortality. Pooled odds ratio (OR) with 95% confidence interval (CI) were computed using random effects model.

Seven studies with 1003 patients (mean age DOAC=58.8years and VKA=58.9year, 55.5% males) were included in this study. There were 306 (30.5%) patients that were treated with DOAC and 697 (69.5%) patients were treated with VKA. Overall, there were no significant differences between both agents in terms of composite failure/adverse effects, resolution of thrombus, systemic embolism, major bleeding, or mortality.

In this pooled analysis, outcomes in patients on DOAC were comparable to VKA. The hypothesis generated could suggest DOAC could be used interchangeably with VKA in patients with LV thrombus. Randomized trials are needed for generalization of results.

In this pooled analysis, outcomes in patients on DOAC were comparable to VKA. The hypothesis generated could suggest DOAC could be used interchangeably with VKA in patients with LV thrombus. Randomized trials are needed for generalization of results.

Treatment for multiple myeloma (MM) has continued to evolve with second generation immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and monoclonal antibodies (mAbs). This study aims to evaluate the epidemiology and risks of infection in patients with MM managed with these therapies.

Clinical and microbiological records were reviewed to capture patient demographics, disease characteristics, treatment received, episodes of infection, and outcomes. Infections were classified as microbiologically defined (MDI), clinically defined (CDI), and fever of unknown focus (FUF). Univariate and multivariate analyses were performed to determine risk factors for infection, with a P value< .05 considered statistically significant.

A total of 148 patients with MM with 345 infection episodes were identified. Of these, 29.0% (100/345), 58.0% (200/345), and 13.0% (45/345) were defined as MDI, CDI, and FUF, respectively. Of 100 MDIs, 50.0% were owing to viruses, whereas 45.0% were owing to bacterial infection. The most common infection site was the respiratory tract (56.8%). Hospital admission occurred in 41.7% of infection episodes, and the 30-day all-cause mortality rate was 5.4%. On multivariate regression, receipt of a PI (odds ratio [OR], 16.80; 95% confidence interval [CI], 2.47-114.52), combination of IMiD and PI (OR, 13.44; 95% CI, 2.39-75.76), mAb-combination (OR, 10.44; 95% CI, 1.99-54.51), and lines of therapy (> 4) (OR, 7.72; 95% CI, 1.25-47.81) were associated with increased risk of infection (all P< .05).

Viral infections now constitute the majority of infections in patients with MM treated with newer agents. Receipt of a PI and lines of therapy (> 4) were associated with higher risk for infection.

4) were associated with higher risk for infection.Capsids of several RNA viruses are reported to have unconventional roles attributed to their subcellular trafficking property. The capsid of CHIKV is also found to localize in the nucleus, but the rationale is not yet clear. To understand the role of the nuclear-localized capsid, we examined the nucleic acid binding and cargo delivery activity of the CHIKV capsid. We used bacterially purified capsid protein to probe the binding affinity with CHIKV genome-specific and non-specific nucleic acids. We found that the capsid was able to bind non-specifically to different forms of nucleic acids. The successful transfection of GFP-tagged plasmid DNA by CHIKV capsid protein shows the DNA delivery ability of the protein. Further, we selected and investigated the DNA binding and cargo delivery activity of commercially synthesized Nuclear Localization Signal sequences (NLS 1 and NLS2) of capsid protein. Both peptides showed comparable DNA binding affinity, however, only the NLS1 peptide was capable of delivering plasmid DNA inside the cell. Furthermore, the cellular uptake study using the FITC-labelled NLS1 peptide was performed to highlight the membrane penetrating ability. Structural analysis was performed using circular dichroism and NMR spectroscopy to elucidate the transfection ability of the NLS1 peptides. Our findings suggest that the capsid of CHIKV might influence cellular trafficking in the infected cell via non-specific interactions. Our study also indicates the significance of NLS sequences in the multifunctionality of CHIKV capsid protein.Dipeptidyl peptidase (DPP)-4 inhibitors are a class of orally available, small molecule inhibitors that prolong the insulinotropic activity of the incretin hormone glucagon-like peptide-1 (GLP-1) and are highly effective for the treatment of Type-2 diabetes. DPP4 can also cleave several immunoregulatory peptides including chemokines. Emerging evidence continues to implicate DPP4 inhibitors as immunomodulators, with recent findings suggesting DPP4 inhibitors modify specific aspects of innate immunity. This review summarises recent insights into how DPP4 inhibitors could be implicated in endothelial, neutrophil and monocyte/macrophage mediated immunity. Additionally, this review highlights additional avenues of research with DPP4 inhibitors in the context of the COVID-19 pandemic.

Polycystic ovary syndrome (PCOS) is the most common metabolic and endocrine disorder among reproductive-age women, and the leading cause of anovulatory infertility. 11β-hydroxysteroid dehydrogenases-1 (11β-HSD1) catalysing the conversion of inactive cortisone to active cortisol plays a crucial role in various metabolic diseases. However, whether 11β-HSD1 is associated with the pathogenesis of PCOS and whether 11β-HSD1 can be a treating target of PCOS remain unknown.

This study was first designed to explore the role of 11β-HSD1 in PCOS development and the effect of selective 11β-HSD1 inhibitor administration on PCOS treatment. Follicular fluid and granulosa cells (GCs) were collected from 32 non-PCOS patients and 37 patients with PCOS to measure cortisol and 11β-HSDs levels. Female Sprague-Dawley rats (3-week-old) were injected with dehydroepiandrosterone (DHEA) to induce PCOS and their ovaries were collected to measure the abundance of corticosterone (CORT) and 11β-HSDs. To determine the role of 11β-HSD1 vated 11β-HSD1 abundance in ovarian is involved in the pathogenesis of PCOS by impairing insulin signalling pathway and ECM remodelling. Selective inhibition of 11β-HSD1 ameliorates a cluster of PCOS phenotypes. Our study demonstrates the selective 11β-HSD1 inhibitor as a novel and promising strategy for the treatment of PCOS.

Henoch-Schönlein purpura is a systemic vasculitis that mainly occurs in children. Renal impairment is a major complication of Henoch-Schönlein purpura, but there is no established predictive marker for renal involvement. Thus, in this study, we investigated the risk factors for renal involvement in children with Henoch-Schönlein purpura.

The medical records of children newly diagnosed as having Henoch-Schönlein purpura between 2005 and 2020 were reviewed retrospectively. Selected laboratory data were recorded before treatment initiation. The date and the age at diagnosis; sex; and the presence of arthralgia, gastrointestinal and renal involvement were obtained retrospectively.

This study included a total of 186 patients with Henoch-Schönlein purpura. Among them, 36.0% had renal involvement; 28.4% had only microscopic hematuria, 53.7% had non-nephrotic range proteinuria, and 17.9% had nephrotic-range proteinuria during follow-up. The mean age was higher (p = 0.016) and female sex was predominant (p = 0.001) in patients with renal involvement than in those without renal involvement. Blood neutrophil/lymphocyte ratio (p = 0.002) and platelet/lymphocyte ratio (p = 0.002) were significantly higher than that of the patients without renal involvement. No statistically significant differences were observed in the hemoglobin concentration, platelet count, presence of arthralgia, and gastrointestinal involvement between patients with and without renal involvement. Logistic regression analysis revealed female sex (odd ratio = 3.213) and neutrophil/lymphocyte ratio (odd ratio = 1.329) as risk factors for renal involvement.

Female sex and high neutrophil/lymphocyte ratio were risk factors for renal involvement in Henoch-Schönlein purpura.

Female sex and high neutrophil/lymphocyte ratio were risk factors for renal involvement in Henoch-Schönlein purpura.

To determine the sodium concentration in cow milk available for sale and to estimate its consumption by infants up to 6 months of age.

Sodium level was determined by flame emission spectrophotometry in eight different lots of five brands of liquid ultra-high temperature milk and three brands of powdered milk. To estimate sodium consumption via cow milk, orientations for exceptional situations when neither breastfeeding nor infant formula is possible were considered. Inferential statistics were performed and results were compared with critical parameters at a 5% significance level.

The mean sodium content per portion found in liquid milk (162.5±16.2) mg/200mL was higher than that in powdered milk (116.8±3.0) mg/26g. Estimated sodium consumption by infants through powdered milk varied from 149.8 to 224.7% of adequate intake, and via liquid milk can be more than 500% of the adequate intake, reaching 812.4% of it if dilution is not applied. Seven of the eight brands of milk studied had declared, on their labels, that the sodium content was 13-30% lower than that found in chemical analysis.

Liquid and powdered whole cow milk have high sodium content, and the content per portion is higher in liquid milk than in powdered milk. The estimated consumption of sodium through these products can far exceed the adequate intake for infants from 0 to 6 months old, even when the recommended dilution and maximum daily volumes are followed.

Liquid and powdered whole cow milk have high sodium content, and the content per portion is higher in liquid milk than in powdered milk. The estimated consumption of sodium through these products can far exceed the adequate intake for infants from 0 to 6 months old, even when the recommended dilution and maximum daily volumes are followed.

In recreational snow sports activities, safety mattresses are placed on obstacles to prevent injuries from a collision with users. However, the performances of these devices in field conditions remain unclear. The objective of this study is to evaluate the effect of mattress thickness, impact speed, impacting mass and atmospheric conditions on head acceleration during an in-field impact on safety mattress.

42 in-field experimental drop tests of a normative metallic head were conducted on safety mattress to assess the influence of impact speed (5.8m/s or 7.3m/s), impacting mass (6kg or 11.6kg), outside conditions (3 conditions) and mattress thickness (24cm, 32cm, 44cm) on head acceleration at impact.

Linear accelerations were measured and Head Injury Criteria 15ms (HIC

) was computed. A statistical analysis (ANOVA) was used to characterize the effects of the varying parameters on maximal acceleration and HIC

.

Reduced impact speed, increased mattress thickness and change in the outside conditions significantly decreased the head acceleration and HIC

(p<0.001). The effect of the impacting mass on head acceleration was not significant.

This study highlights the influence of impact speed, atmospheric condition and mattress construction on absorption capacities of safety mattresses. It is a first step toward a better understanding and evaluation of safety mattresses performances.

This study highlights the influence of impact speed, atmospheric condition and mattress construction on absorption capacities of safety mattresses. It is a first step toward a better understanding and evaluation of safety mattresses performances.

Phthalate exposure is associated with altered reproductive function, but little is known about associations of phthalate exposure with risk of hot flashes.

To investigate associations of urinary phthalate metabolite levels with four hot flash outcomes in midlife women.

A cross-sectional study of the first year of a prospective cohort of midlife women, the Midlife Women's Health Study (2006-2015), a convenience sample from an urban setting.

728 multi-racial/ethnic pre- and perimenopausal women aged 45-54 years.

Women completed questionnaires about hot flash experience and provided 1-4 urine samples over four consecutive weeks that were pooled for analysis. Phthalate metabolites were assessed individually and as molar sums representative of common compounds (all phthalates ƩPhthalates; DEHP ƩDEHP), exposure sources (plastics ƩPlastic; personal care products ƩPCP), and modes of action (anti-androgenic ƩAA). Covariate-adjusted logistic regression models were used to assess associations of continuous natble to experiencing hot flashes.

Several studies have indicated that prenatal exposure to ambient air pollution is associated with an increased risk of gestational diabetes mellitus, hypertensive disorder during pregnancy, preterm birth, and stillbirth. However, no previous study has focused on the association between the number of pregnancy complications and exposure to ambient air pollution.

To investigate the association between prenatal exposure to ambient air pollutants and the number of pregnancy complications in high-risk pregnancies.

We collected data on gestational diabetes mellitus, hypertensive disorder during pregnancy, preterm birth, and stillbirth from the National Health Information Databases, provided by the Korean National Health Insurance Service.R To assess individual-level exposure to air pollutants, a spatial prediction model and area-averaging approach were used.

From 2015 to 2018, data of 789,595 high-risk pregnancies were analyzed. The ratio of gestational diabetes mellitus in the country was the highest, folls is positively associated with the exposure to the high concentrations of PM10, PM2.5, CO, NO2, and SO2.

Polychlorinated biphenyls (PCB) are persistent and bioaccumulative lipophilic substances, mostly used in the past by industry. Known to be cancerogenic, PCB are suspected to increase Non-Hodgkin's Lymphoma (NHL) risk in the general population mainly due to evidence from cases-controls studies. Since their interdiction in 1987, diet represents the main route of exposure for the general population, nevertheless no study has assessed the relationship between PCB dietary exposure and NHL risk. The aim of this study was to analyze the association between dietary exposures to dioxin like PCB (DL PCB) and non-dioxin like PCB (NDL PCB) and NHL risk in the E3N prospective cohort of French women.

Among 67,879 women included in this study, 457 cases of NHL were confirmed during 21 years of follow-up. Dietary exposure to PCB was estimated combining food consumption data collected in E3N and food contamination data provided by French Agency for Food, Environmental and Occupational Health & Safety (ANSES) in the secohort study. Overall, the findings suggest a lack of association between dietary exposure to DL or NDL PCB and NHL risk. Additional studies are needed to reproduce these findings.

This is the first study to evaluate the association between dietary exposure to DL and NDL PCB and the risk of NHL in a prospective cohort study. Overall, the findings suggest a lack of association between dietary exposure to DL or NDL PCB and NHL risk. Additional studies are needed to reproduce these findings.The high toxicity of persistent pollutants limits the phytoremediation of pollutants-contaminated soil. In this study, heterologous expressing Halorhodospira halophila single-stranded DNA binding protein gene (HhSSB) improves tolerance to 2,4,6-trinitrotoluene (TNT), 2,4,6-trichlorophenol (2,4,6-TCP), and thiocyanate (SCN-) in A. thaliana and tall fescue (Festuca arundinacea). The HhSSB transformed Arabidopsis, and tall fescue also exhibited enhanced phytoremediation of TNT, 2,4,6-TCP, and SCN- separately contaminated soil and co-contaminated soil compared to control plants. TNT assay was selected to explore the mechanism of how HhSSB enhances the phytoremediation of persistent pollutants. Our result indicates that HhSSB enhances the phytoremediation of TNT by enhancing the transformation of TNT in Arabidopsis. Moreover, transcriptomics and comet analysis revealed that HhSSB improves TNT tolerance through three pathways strengthening the defense system, enhancing the ROS scavenging system, and reducing DNA damage. These results presented here would be particularly useful for further studies in the remediation of soil contaminated by organic and inorganic pollutants.Silver (Ag) nanocomposites were prepared via a facile and eco-friendly route using microbial extracellular polymer substances (EPSs) as green substrates for the catalytic reduction of 4-nitrophenol. Batch adsorption experiments demonstrated the binding of microbial EPSs to silver ions (Ag+), which was promoted by UV light, as was evident in the kinetics and thermodynamics analyses. The assembly mechanism of Ag nanocomposites prepared using microbial EPSs in the presence of UV light was investigated using the spectral analysis. The results showed that Ag+ was reduced and transformed into Ag0 by the hemiacetal groups in the microbial EPSs, and that UV light accelerated the nucleation and growth of Ag0 to form Ag nanoparticles (diameter about 12 nm), followed by loading on the surface of microbial EPSs. Catalytic reduction of 4-nitrophenol over Ag nanocomposites was almost completed within 60 s without stirring, and the kinetic rate constant (k) was 49.9 × 10-3 s-1. The recyclability test showed that Ag nanocomposites stably maintained the efficiency of catalytic reduction through five repeated reaction cycles. This work proved that Ag nanocomposites assembled using microbial EPSs have great catalytic activity in the reduction of 4-nitrophenol, providing the green and efficient catalyst for the reduction of organic pollutants in the environment.

Since 2000, more than 6000 Burmese refugees were resettled in Wisconsin. The Burmese diet is traditionally rich in fish and fish products, and studies show that Burmese refugees continue to rely on local waterbodies for food. Given that Wisconsin has five Areas of Concern (AOC) that are severely affected by pollution, long-term exposure to contaminants in sport-caught fish is a health concern. To better understand fish consumption among Burmese refugees, we conducted a biomonitoring study in Milwaukee. The present study examined Burmese refugees' fish consumption habits and awareness of fish advisories.

We used respondent-driven sampling (RDS) methodology to recruit Burmese refugees in Milwaukee. RDS Analysis Tool 7.1 was used to obtain adjusted population estimates for demographic characteristics, fish consumption habits, and awareness of fish advisories. Homophily and equilibrium were investigated to evaluate the effectiveness of RDS in recruitment.

Initiated by five active seeds, we recruited 103 resthe Burmese population more likely to be exposed to contaminants. Health education efforts should be focused in this vulnerable population, particularly among Burmese WCBA.

RDS is an effective methodology to recruit hard-to-reach populations, such as the Burmese surveyed in this study. High percentages of WCBA eating potentially contaminated sportfish meals, low awareness of consumption advisories, and limited economic resources make the Burmese population more likely to be exposed to contaminants. Health education efforts should be focused in this vulnerable population, particularly among Burmese WCBA.

The differential diagnostic role of plasma developmental endothelial locus-1 (Del-1) was proposed in our previous study. Therefore the current study aimed to confirm the diagnostic role and explore the prognostic role of exosomal Del-1 in a prospective cohort of female patients with breast cancer.

To determine the optimal sampling time for the postoperative Del-1 measurements, blood was serially collected on days 1, 3, 5, and 7 after surgery in 22 patients (cohort 1). Thereafter, 111 female patients with breast cancer were prospectively enrolled (cohort 2) to compare exosomal Del-1 levels before and after surgery.

Among the subsequent prospective cohort, 107 patients (96.4%) showed a high exosomal Del-1 level (optical density [OD] value > 0.5) at the time of diagnosis. Of these patients, 101 (94.6%) in this high-level group showed normalized Del-1 levels postoperatively, representing a significant difference (mean OD value, 1.232 vs. 0.196; P < .00001). High postoperative Del-1 level was significantly associated with a worse disease-free survival adjusted to the clinicopathological characteristics (hazard ratio, 24.0; P=.0011).

This study confirmed the normalization of exosomal Del-1 after surgery, indicating exosomal Del-1 as a potent diagnostic biomarker for breast cancer. In addition, because a high Del-1 level after surgery was associated with early relapse, this suggests exosomal Del-1 as a potential prognostic marker by identifying the existence of residual cancer.

This study confirmed the normalization of exosomal Del-1 after surgery, indicating exosomal Del-1 as a potent diagnostic biomarker for breast cancer. In addition, because a high Del-1 level after surgery was associated with early relapse, this suggests exosomal Del-1 as a potential prognostic marker by identifying the existence of residual cancer.

Providing patient safety is a central matter in health care requiring complex treatment processes containing many risks. In hospital care, adverse events and patient harm occur frequently. In this context, the safety sciences investigate causes and contributing factors of such events as well as improvement measures. With Safety-I and Safety-II, two complementary approaches come into play. While Safety-I aims to minimize adverse events, the Safety-II approach focuses on understanding the system as a whole whose normal operations can result in both desired and adverse events. With the implementation of the Critical Incident Report System (CIRS), the Safety-I approach (with a focus on errors and correction of negative consequences for patient safety) has become an integral part of the university hospital chosen for this study. The subject matter of this study is to determine if and how the Safety-II approach (focussing on normal operation and the understanding of positive effects for patient safety) is alreadyg of how the system of daily clinical practice with all its subsystems works will make it possible to proactively counteract unwanted occurrences, for example through regular feedback sessions and debriefings, and to increase patient safety.

The standard management of orbital cellulitis is to administer a combination of intravenous broad-spectrum antibiotics along with treatment of associated sinusitis.

The purpose of this study was to evaluate whether the addition of corticosteroids could lead to earlier resolution of inflammation and improve disease outcome.

We independently searched five databases (PubMed, SCOPUS, Embase, the Web of Science, and the Cochrane database) for studies published as recent as December 2019. Of the included studies, we reviewed orbital cellulitis and disease morbidity through lengths of hospitalization, incidence of surgical drainage, periorbital edema, vision, levels or C-reactive protein, and serum WBC levels in order to focus on comparing steroid with antibiotics treated group and only antibiotics treated group.

Lengths of hospitalization after admission as diagnosed as orbital cellulitis (SMD=-4.02 [-7.93; -0.12], p-value=0.04, I

=96.9%) decrease in steroid with antibiotics treated group compared to antibiotics only treated group. Incidence of surgical drainage (OR=0.78 [0.27; 2.23], p-value=0.64, I

=0.0%) was lower in the steroid with antibiotics treated group compared to the antibiotics only treated group.

Use of systemic steroids as an adjunct to systemic antibiotic therapy for orbital cellulitis may decrease orbital inflammation with a low risk of exacerbating infection. Based on our analysis, we concluded that early use of steroids for a short period can help shorten hospitalization days and prevent inflammation progression.

Use of systemic steroids as an adjunct to systemic antibiotic therapy for orbital cellulitis may decrease orbital inflammation with a low risk of exacerbating infection. Based on our analysis, we concluded that early use of steroids for a short period can help shorten hospitalization days and prevent inflammation progression.

The diagnosis of vestibular neuritis is based on clinical and laboratory findings after exclusion of other disease. There are occasional discrepancies between clinical impressions and laboratory results. It could be the first vertigo episode caused by other recurrent vestibular disease, other than vestibular neuritis.

This study aimed to analyze the clinical features and identify the diagnostic evolution of patients with clinically suspected vestibular neuritis.

A total of 201 patients clinically diagnosed with vestibular neuritis were included in this study. Clinical data on the symptoms and signs of vertigo along with the results of vestibular function test were analyzed retrospectively. Patients were categorized in terms of the results of caloric testing (CP - canal paresis) group; canal paresis ≥25%; (MCP -minimal canal paresis) group; canal paresis <25%). Clinical features were compared between the two groups and the final diagnosis was reviewed after long-term follow up of both groups.

Out of 201 patients, 57 showed minimal canal paresis (CP<25%) and 144 showed definite canal paresis (CP≥25%). A total of 48 patients (23.8%) experienced another vertigo episode and were re-diagnosed. Recurring vestibular symptoms were seen more frequently in patients with minimal canal paresis (p=0.027). Repeated symptoms were observed on the same affected side more frequently in the CP group. The proportion of final diagnosis were not different between two groups.

Patients with minimal CP are more likely to have recurrent vertigo than patients with definite CP. There was no significant difference in the distribution of the final diagnoses between two groups when the vertigo recurs.

Patients with minimal CP are more likely to have recurrent vertigo than patients with definite CP. There was no significant difference in the distribution of the final diagnoses between two groups when the vertigo recurs.

Vestibular migraine is the most common cause of spontaneous episodic vertigo in adult patients and the second most common cause of vertigo in patients of all ages.

To assess the effectiveness of oral medication type (propranolol, flunarizine, and amitriptyline) and botulinum toxin A application on vestibular symptoms, headache severity and attack frequency for vestibular migraine patients.

Sixty patients with vestibular migraine were enrolled. Thirty patients received botulinum toxin A treatment (B+ group) in addition to the oral medication, whereas 30 patients received only oral medication (B- group). Headache severity was evaluated with Migraine Disability Assessment Scale and vertigo severity was evaluated with Dizziness Handicap Inventory scale. Vestibular migraine attack frequencies in the last three months were also evaluated.

There was a statistically significant decrement in mean Dizziness Handicap Inventory scores, Migraine Disability Assessment Scale scores and vertigo attack frequencies aftability Assessment Scale score gain values.

Both B+ and B- group patients exhibited significant improvement in vestibular migraine attack frequencies, Dizziness Handicap Inventory score and Migraine Disability Assessment Scale score values. However, botulinum toxin A application had a more pronounced effect for Migraine Disability Assessment Scale score gain and vestibular migraine attack frequency values, but not for Dizziness Handicap Inventory score gain values. Thus, botulinum toxin A application should be considered for vestibular migraine patients whose headache severity degrees are more profound. The oral medication type (propranolol, flunarizine or amitriptyline) did not differ in influencing the vestibular migraine attack frequency, Dizziness Handicap Inventory score gain and Migraine Disability Assessment Scale score gain values.