Adcockhickman1737

Side effects of radiation therapy may include skin damage. The surface dose is of great interest and contains the buildup effect. In particular, the proton therapy community requires further experimental data to quantify doses in the surface region. This specification includes the skin dose, which is defined according to ICRU Report No. 39 at 70μm water equivalent depth. The aim of this study is to gather more knowledge of the skin dose by varying key parameters defined by the patient treatment plan. This consists of clinical aspects such as the influence of the air gap, the application of a range shifter (RS), or the proton delivery technique.

Skin doses were determined with a PTW 23391 extrapolation chamber with three thin Kapton® entrance windows operated as a conventional ionization chamber. The impact on the skin dose for quasi-monoenergetic pencil beam scanning (PBS) proton beams was evaluated for clinical air gaps between 3.5 and 51.1cm. The differences in skin dose were assessed by irradiating equer of 4.0% for the skin dose at the depth of 70 μm. The increases in skin dose are the effects of the contribution of the increased electron fluence at small air gaps and the emitted hadronic particles produced by the RS.

The Spectra Optia allows automated performance of red blood cell reduction and isovolemic hemodilution (IHD) prior to standard red cell exchange (RCE), and is primarily intended for patients with sickle cell disease (SCD) undergoing chronic RCE. Data on the safety of inducing transient further anemia and the benefits of IHD-RCE is limited and occasionally contradictory.

In this retrospective crossover analysis of six patients with SCD who underwent chronic exchange with standard RCE (Cobe Spectra) followed by IHD-RCE (Spectra Optia), we compared safety and benefit outcomes with IHD-RCE vs standard RCE.

There were statistically but not clinically significant drops in blood pressure in the post-IHD phase. With IHD-RCE, there were significant reductions in red blood cell (RBC) usage and/or lower fraction of cells and significant increases in postprocedure hematocrit (Hct) associated with increased preprocedure Hct. There were no differences achieved in the time interval between procedures or in the net RBC gain with IHD-RCE. Overall, there were also no significant differences in pre- and postprocedure percentage of hemoglobin S, reticulocyte count, interval daily hemoglobin A decrement, or postprocedure white blood cell, neutrophil, or platelet counts.

Our study supports that IHD-RCE can be safely used in patients with stroke risk and compared to standard RCE, results in benefits of lower RBC usage and/or fraction of cells remaining and higher postprocedure Hct associated with higher preprocedure Hct. These findings support wider use of IHD-RCE, especially in the current environment with reduced availability of minority units.

Our study supports that IHD-RCE can be safely used in patients with stroke risk and compared to standard RCE, results in benefits of lower RBC usage and/or fraction of cells remaining and higher postprocedure Hct associated with higher preprocedure Hct. These findings support wider use of IHD-RCE, especially in the current environment with reduced availability of minority units.

To examine multiprofessionals' views on patient involvement in acute psychiatric wards.

The study was conducted in four hospital districts in Finland. The data were collected between December 2016 and March 2017 by means of four focus group interviews and analyzed with inductive content analysis.

The five main themes emerged Patient-, carer-, professional-, hospital-, and healthcare system-related factors enhancing or preventing patient involvement in acute psychiatric wards.

The findings confirm that many obstacles need to be removed in wardpractice before patient involvement can really be made a part of the daily routine.

The findings confirm that many obstacles need to be removed in ward practice before patient involvement can really be made a part of the daily routine.At leaf level, elevated atmospheric CO2 concentration (eCO2 ) results in stimulation of carbon net assimilation and reduction of stomatal conductance. However, a comprehensive understanding of the impact of eCO2 at larger temporal (seasonal and annual) and spatial (from leaf to whole-tree) scales is still lacking. Here, we review overall trends, magnitude and drivers of dynamic tree responses to eCO2 , including carbon and water relations at the leaf and the whole-tree level. Spring and early season leaf responses are most susceptible to eCO2 and are followed by a down-regulation towards the onset of autumn. At the whole-tree level, CO2 fertilization causes consistent biomass increments in young seedlings only, whereas mature trees show a variable response. Elevated CO2 -induced reductions in leaf stomatal conductance do not systematically translate into limitation of whole-tree transpiration due to the unpredictable response of canopy area. Reduction in the end-of-season carbon sink demand and water-limiting strategies are considered the main drivers of seasonal tree responses to eCO2 . These large temporal and spatial variabilities in tree responses to eCO2 highlight the risk of predicting tree behavior to eCO2 based on single leaf-level point measurements as they only reveal snapshots of the dynamic responses to eCO2 .

To describe multidimensional quality of life (QOL) outcomes in patients with sinonasal malignancies (SNM). To elucidate factors predicting worse QOL in this population.

Retrospective chart review at tertiary institution.

A retrospective chart review on patients treated for SNM from 2006 to 2019 at a tertiary medical center was conducted. QOL outcomes were measured using the Hospital Anxiety and Depression Scale (HADS) and the Functional Assessment Cancer Therapy - Nasopharynx (FACT-NP) score. A stepwise multiple linear regression analysis was conducted to assess factors predicting worse QOL.

Eighty-one patients met inclusion criteria. Twelve (14.8%) patients had a subscale score >11 for anxiety (HADS-A) or depression (HADS-D) indicating significant anxiety or depression, at a median of 24 (8-68.5) months post treatment. The median FACT-NP total score was 136 (110-152). On multivariable analysis, advanced T classification, single status, and worse social support survey score were significant predictors of worse HADS score. Worse social support survey score was a significant predictor of worse total FACT-NP score.

After adjusting for confounders, at a median of 24 months after completion of definitive therapy for SNM, advanced T classification and single relationship status were found to be significant predictors of anxiety and depression (based on HADS). A worse social support survey score was associated with worse anxiety, depression, and QOL (based on HADS and FACT-NP). Identifying these factors early may help to guide treatment and psychiatric referral to at-risk individuals after the treatment of SNM.

3. Laryngoscope, 2020.

3. Laryngoscope, 2020.

The dosages of valaciclovir used for herpes zoster treatment recommended by Chinese pharmaceutical companies can differ considerably from those reported in the literature. This randomized clinical study compares the efficacy and safety of different oral valaciclovir doses for the treatment of herpes zoster in adults.

A total of 214 patients with herpes zoster were enrolled and randomized into two groups according to age 98 patients in the 18-44-year group (younger patients) and 116 patients in the 45-74-year group (middle-aged and elderly patients). Patients in the two age groups were then prescribed different doses of valaciclovir. The high-dose group was administered 900mg of valaciclovir, three times daily for 10days, whereas the low-dose group was administered 300mg of valaciclovir, two times daily for 10days. The efficacy and side effects of these regimens were recorded on days 6, 11 and 30.

In total, 207 (of 214 enrolled) patients completed the study. Of the seven patients who discontinued the stue difference in the incidence of adverse reactions between the high-dose and low-dose groups was not statistically significant (p>0.05). Overall, the main side effect was headache.

The present study indicates that early treatment with high-dose valaciclovir can significantly reduce pain in patients, especially in elderly patients, in whom it can also reduce the incidence of PHN. In terms of safety, no significant difference was noted in the incidence of adverse reactions between high- and low-dose groups.

The present study indicates that early treatment with high-dose valaciclovir can significantly reduce pain in patients, especially in elderly patients, in whom it can also reduce the incidence of PHN. In terms of safety, no significant difference was noted in the incidence of adverse reactions between high- and low-dose groups.In spite of multiple program efforts in Ghana, progress in reducing the burden of anemia is slow. The objective was to conduct multilevel assessments of existing childhood ( less then 5 years) anemia prevention and treatment programs according to UNICEF's conceptual framework of malnutrition, and to elucidate implementation gaps in Ghana. Purposive and snowball sampling strategies recruited 25 program personnel from 20 organizations to participate in audiorecorded interviews conducted through in-person, telephone, or email correspondence in August 2018. Interview guides constructed around UNICEF's conceptual framework of malnutrition identified context-specific immediate, underlying, and basic causes of anemia, and corresponding programs. Interviews were transcribed, coded, and analyzed using the Dedoose software version 8.1.8. Few programs addressed identified basic causes of anemia, such as inadequate human resources, housing/water/toilet facilities, and poverty/poor access to financial resources. Organizations implemented programs addressing ≥1 underlying cause. Five organizations provided food rations and/or supplements to address immediate causes. A key food-based gap identified was minimal education on fruit intake or antinutritive factors in foods; however, no interventions included vitamin C supplements. Food manufacturers mainly used cereals and grains in commercial food products. Multiple organizations worked in the same region on anemia with instances of an overlapping program focus. Food sources of vitamin C or supplements could be promoted in food-based interventions to increase the absorption of nonheme iron consumed.

Current management guidelines recognize the impact of hepatic versus peritoneal sided gallbladder cancers (GBC) on survival. However, no data exist regarding the significance of anatomic tumor location within the gallbladder.

We retrospectively analyzed all GBC that underwent surgical resection with curative intent in our health system from 2007 to 2017. We evaluated the effect of anatomic pathologic tumor location (fundus/body, neck, and multifocal) on clinicopathologic, perioperative, and oncologic outcomes.

About 97 patients met criteria; 63% fundus/body, 22% multifocal, and 15% neck. Compared with fundus/body, neck tumors more frequently presented with preoperative jaundice (53% vs. 13%, p < .001), were smaller (20 mm vs. 30 mm, p = .068) and had significantly more biliary tree invasion (33% vs. 13%, p = .030) on histopathology. Although tumor characteristics (pTNM stage, liver invasion, lymphovascular invasion, prognostic nutritional index, and grade) were similar, neck tumors had significantly higher rates of R0 resection (53% vs. 11%, p < .001). Rates of adjuvant therapy were similar. Median PFS was similar between cohorts (p = .356). However, median overall survival (OS) was significantly shorter in neck (21 months) than fundus/body tumors (NR > 109 months), p = .015.

Neck tumors were rare, small and more likely to result in jaundice secondary to biliary tree invasion. Despite higher R0 resection rates, these tumors had significantly worse OS.

Neck tumors were rare, small and more likely to result in jaundice secondary to biliary tree invasion. Despite higher R0 resection rates, these tumors had significantly worse OS.

Japan is endemic for human T-cell leukemia virus type 1 (HTLV-1), and the horizontal transmission of HTLV-1 is often reported. However, the window period (WP) for serologic or molecular screening is unclear.

Results for anti-HTLV-1 screening and confirmatory tests obtained from 648 591 repeated blood donors in the Kyushu district, one of the most endemic areas of HTLV-1 in the world, were evaluated. A lookback study was conducted for seroconverters.

During 2012 to 2019, 436 seroconverters (155 men, 281women) were identified with use of a screening chemiluminescence enzyme-immunoassay (CLEIA) and multiple confirmatory tests. Because the period between the latest seronegative donation and seroconversion was highly variable (2.1-276.7 months), 19 cases that seroconverted within 6 months were subjected to the analysis. The WP of the particle agglutination assay and CLEIA was estimated to be 2.2 ± 0.6 and 2.6 ± 1.7 months, respectively. The WP of the indirect immunofluorescence assay was 4.8 ± 6.5 months. Although the WP of western blotting was estimated to be 6.3 ± 8.7 months, four cases were still indeterminate through the study period. Chemiluminescence and line immunoassays, the current screening and confirmatory tests used in the Japanese blood program, showed the shortest WP of 2.2 ± 0.6 months. The WP of real-time polymerase chain reaction for HTLV-1 was estimated to be 4.1 ± 7.8 months.

The WP in commercially available testing systems for HTLV-1/2 was determined for natural infection among repeated blood donors. Considering the HTLV-1 WP will help increase transfusion safety and facilitate the accurate diagnosis of HTLV-1 infection.

The WP in commercially available testing systems for HTLV-1/2 was determined for natural infection among repeated blood donors. Considering the HTLV-1 WP will help increase transfusion safety and facilitate the accurate diagnosis of HTLV-1 infection.This study compared the repulsive effects of sound playbacks of intermittent 30, 150, 300, 600 and 900 Hz tones on two fish with different auditory capabilities juvenile chum salmon (Oncorhynchus keta) and common carp (Cyprinus carpio). When 150 and 300 Hz tones were emitted from an underwater speaker, O. keta exhibited a moderate repulse reaction. Conversely, C. carpio exhibited a moderate repulse reaction to a tone with a frequency of 30 Hz, which indicates that a low-frequency component in complex broadband sound may be important for inducing a repulse reaction in cyprinids.Diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) cases is based on the count of real-time reverse transcription-plymerase chain reaction (RT-PCR) positive people. Viral load by real-time RT-PCR has been suggested as a biomarker of the SARS-CoV-2 infection. However, the association of viral load and severity of the disease is not yet resolved. Nasopharyngeal samples from 458 patients were tested by RT-PCR for SARS-CoV-2 diagnosis. Relative quantitation was made by the comparative threshold cycle (ΔΔCt ) formula between ORF1ab viral and RNase P housekeeping genes. Absolute viral load was calculate using a reference positive control. Most prevalent clinical signs were cough (75.8%), myalgia (66.7%), and fever (48.5%). Hypertension (18.2%), neurological diseases (15.1%), and asthma and hypothyroidism (12.1%) were most frequent comorbidities. Fever, either as an exclusive symptom or combined with others, was associated with high viral loads ( 2 - ∆ ∆ C t range, 35.65-155.16; 4.25-4.89 log10 RNA copies/test]). During the first week after onset of symptoms in mild patients up to 60 years-old was detected the peak of viral load. Children under 10 years old have a high viral load (313.84; 2.50) in the first 2 days postinfection with a sharp decline thereafter. Cases between 10 and 49 years old mostly showed low and moderate viral load during the first 2 days postinfection (range, 0.03 to 17.24; -1.50 to 1.24). Patients over 60 years old have high viral load up to the second week after the onset of symptoms (range, 25.32-155.42; 1.40-2.19), indicating the longer presence of the virus in them. These findings suggest the viral load in nasopharyngeal swabs would help to monitor the SARS-CoV-2 infection in mild coronavirus disease 2019 cases.

Immune modulation by vitamin D3 through dendritic cells (DCs) remains controversial. Human DCs exposed in vitro counteract type-1 T-helper (Th1) differentiation and induce regulatory T cells. However, cutaneous application on mice promotes Th2-driven inflammation resembling atopic dermatitis and relying on thymic stromal lymphopoietin (TSLP) from keratinocytes and T-cell orientation by TSLP-stimulated skin DCs. We studied the effects of vitamin D3 in human skin, focusing on TSLP production and the role of skin DCs in T-cell differentiation.

Human healthy skin explants were exposed in vitro to vitamin D3 analogs. Migrating DCs were analyzed and TSLP quantified in the supernatant. Allogeneic naïve CD4+ T cells were cocultured with DCs to assess their proliferation and cytokine production.

Vitamin D3 induced skin DCs to differentiate Th2 cells producing IL-4 and IL-13. Vitamin D3 triggered TSLP release in ~30% of skin explants, correlating with IL-13 detection in Th2 cells. In these donors, blocking TSLP receptor during skin explant cultures abrogated IL-13 production, yet IL-4+ Th2 cells were unaffected. Among skin DCs emerged CD14+ cells that had responded directly to vitamin D3 and differed from classical CD14+ dermal emigrants. Vitamin D3-elicited CD14+ DCs sufficed to promote IL-4+ Th2 cells in a TSLP-independent manner.

Vitamin D3, despite inducing TSLP in some donors, had a direct influence on skin DCs, affecting their phenotype and ability to drive Th2 responses independently of TSLP. Our findings pave the way toward in vitro systems that accurately model human cutaneous Th2 responses, notably involved in atopic dermatitis.

Vitamin D3, despite inducing TSLP in some donors, had a direct influence on skin DCs, affecting their phenotype and ability to drive Th2 responses independently of TSLP. Our findings pave the way toward in vitro systems that accurately model human cutaneous Th2 responses, notably involved in atopic dermatitis.Sinbaglustat (ACT-519276), a brain-penetrating inhibitor of glucosylceramide synthase and nonlysosomal glucosylceramidase, is developed as a new therapy for lysosomal storage disorders. In the first-in-human study, sinbaglustat was primarily excreted unchanged in urine. This study was conducted to evaluate the effect of mild, moderate, and severe renal function impairment on the safety, tolerability, and pharmacokinetics (PK) of sinbaglustat. In this single-center, open-label study, 32 subjects (8 per renal function group, assessed by the Cockcroft-Gault formula, and 8 healthy subjects) received a single oral dose of 200 mg sinbaglustat. Plasma PK parameters of sinbaglustat were derived by noncompartmental analysis. Standard safety and tolerability evaluations were analyzed descriptively. When compared with healthy subjects, Cmax did not present clinically relevant differences in subjects with impaired renal function, but median tmax was slightly longer in subjects with moderate and severe renal function impairment. Overall, when compared with healthy subjects, exposure to sinbaglustat based on AUC0-t (geometric mean and 90% confidence interval) increased in subjects with mild, moderate, and severe renal function impairment by 1.2-fold (1.08- to 1.36-fold), 1.8-fold (1.47- to 2.17-fold), and 2.6-fold (2.23- to 3.00-fold), respectively. There were no clinically relevant findings on electrocardiogram, vital signs, and clinical laboratory variables. Headache was reported by 2 of 24 subjects with renal function impairment and by 2 of 8 healthy subjects. In conclusion, 200 mg of sinbaglustat was well tolerated in all groups. In future studies, a 2- and 3-fold dose reduction is needed for subjects with moderate and severe renal function impairment, respectively.The bacterial pathogen Borrelia burgdorferi is the causative agent of Lyme disease and is transmitted to humans through an Ixodes tick vector. B. burgdorferi is able to survive in both mammalian and tick hosts through careful modulation of its gene expression. This allows B. burgdorferi to adapt to the environmental and nutritional changes that occur when it is transmitted between the two hosts. Distinct interactions between the spirochete and its host occur at every step of the enzootic cycle and dictate the ability of the spirochete to survive until the next stage of the cycle. Studying the interface between B. burgdorferi, the Ixodes tick vector and the natural mammalian reservoirs has been made significantly more feasible through the complete genome sequences of the organisms and the advent of high throughput screening technologies. Ultimately, a thorough investigation of the interplay between the two domains (and two phyla within one domain) is necessary in order to completely understand how the pathogen is transmitted.The oral prodrug fostemsavir (GSK3684394, formerly BMS-663068) is an antiretroviral treatment for HIV-1. Fostemsavir is metabolized to its active moiety, temsavir, a first-in-class HIV-1 attachment inhibitor that binds to the viral envelope glycoprotein 120. Long-term antiretroviral therapy, the resulting longer life expectancy, and/or certain coinfections can increase the risk of chronic liver and kidney disease in HIV-1-infected individuals. Two studies were conducted to collectively evaluate the impact of renal and hepatic impairment on temsavir pharmacokinetics (PK) and safety following a single dose of a 600-mg extended-release fostemsavir tablet. There was no clinically meaningful effect of renal or hepatic impairment on temsavir PK, although renal clearance decreased with increasing renal impairment from moderate to severe, and exposure (maximum concentration and area under the plasma concentration-time curve from time 0 to infinity) tended to increase with increasing severity of hepatic impairment. No clinically meaningful effect of hemodialysis on temsavir PK parameters was observed. Fostemsavir was generally safe and well tolerated by treated subjects. Most adverse events (AEs) were mild, with the exception of 1 patient in the renal impairment study who discontinued due to 2 serious AEs unrelated to the study drug. No other treatment-emergent serious AEs occurred, and no other AEs leading to discontinuation were reported. Overall, these results suggest that fostemsavir can be used without dose modification in subjects with mild to severe renal impairment, including those with end-stage renal disease on hemodialysis, and in subjects with mild to severe hepatic impairment.A new species of Poptella is described from the Río Putumayo, Upper Río Amazon basin, Peru. The new species is distinguished from congeners by having a dense field of dark chromatophores homogeneously spread over the posterior half of the body, posterior humeral blotch extending to three to four horizontal scale rows below the lateral line, and a higher number of branched dorsal-fin rays. The new species can be readily distinguished from P. paraguayensis by having a comparatively shorter predorsal spine.Breast cancer is a heterogeneous disease where the tumor microenvironment, including extracellular components, plays a crucial role in tumor progression, potentially modulating treatment response. Different approaches have been used to develop three-dimensional models able to recapitulate the complexity of the extracellular matrix. Here, we use cell-free patient-derived scaffolds (PDSs) generated from breast cancer samples that were recellularized with cancer cell lines as an in vivo-like culture system for drug testing. We show that PDS cultured MCF7 cancer cells increased their resistance against the front-line chemotherapy drugs 5-fluorouracil, doxorubicin and paclitaxel in comparison to traditional two-dimensional cell cultures. The gene expression of the environmentally adapted cancer cells was modulated in different ways depending on the drug and the concentration used. High doses of doxorubicin reduced cancer stem cell features, whereas 5-fluorouracil increased stemness and decreased the proliferative phenotype. By using PDSs repopulated with other breast cancer cell lines, T-47D and MDA-MB-231, we observed both general and cell line specific drug responses. In summary, PDSs can be used to examine the extracellular matrix influence on cancer drug responses and for testing novel compounds in in vivo-like microenvironments.

This prospective study examines the test-retest reliability of touchscreen DriveSafe DriveAware (DSDA). In a future study, the authors intend assessing the usefulness of DSDA to measure progress of patients undergoing treatment for neurological conditions. Evidence of test-retest reliability is required first.

Australian adults with current driver's licences (N=39) aged 20 to 91years (M

=58) recruited from a convenience sample were assessed with DSDA. The assessment was repeated 6weeks, 6months, and 12months later to match planned assessments of patients undergoing neurosurgical treatment in future research. DSDA classification, DriveSafe subtest score, and DriveAware subtest scores were analysed as a whole sample, and in three age groups.

DSDA classification and DriveAware scores were consistent over repeated tests. DriveSafe scores increased between test 1 and 2 (p=.006), and thereafter no significant change from test 2 to 4. DriveSafe scores of older participants (70+ years) increased between test A classification and DriveAware scores demonstrated test-retest reliability for all age groups. DriveSafe scores did not demonstrate test-retest reliability between test 1 and 2 for participants 70+ years. However, DriveSafe scores demonstrated test-retest reliability after test 2, possibly indicating an initial learning effect for the DriveSafe score only. The authors posit that this result may have been influenced by older adults' reduced familiarity with iPad technology at first assessment. Further longitudinal research is required to confirm whether these results are consistent in a sample population with diagnosed cognitive impairment. Future research will assess whether repeated assessment of DSDA may be useful for monitoring and screening cognitive fitness to drive in patients who have undergone neurosurgical treatment and whether declining scores may indicate cognitive changes in ability to drive.

Pymetrozine is a widely used pesticide. It is challenging to analyze and difficult to manage due to the large gap in its global maximum residue limits (MRLs) in tea. The development of a high-efficiency detection method for the evaluation of the transfer of residual pymetrozine from tea plantations to tea cups is therefore of prime significance.

An analytical method for the determination of pymetrozine residues in tea was established based on Cleanert PCX solid-phase extraction. The average recoveries were 72.2-93.7%, with relative standard deviations (RSDs) of less than 12%. The limits of quantification (LOQs) were 0.005 mg·kg

in fresh tea leaves and dry tea, and 0.00025 mg·L

in tea brew. Pymetrozine degraded rapidly in tea plants with a half-life (t

) of 1.9 days in open tea plantations, and decreased by 9.4-23.7% in the green tea-processing procedure, which was concentration dependent. The residual pymetrozine levels in green tea collected at 6 and 21 days were below the MRLs in China and EU at a dosage of 30 g a.i. ha

, respectively. The leaching rates of pymetrozine from dry tea to tea brew were 58.7-96.3%. Hazard quotient (HQ) values of pymetrozine were significantly <100% when tea shoots were plucked in 6 days, which indicated a negligible risk to humans.

This work allows the determination of residual pymetrozine in tea and illustrates a low intake risk with the use of pymetrozine in tea plantations. It could serve as reference for further regulation consideration for maximum residue limits (MRLs). © 2020 Society of Chemical Industry.

This work allows the determination of residual pymetrozine in tea and illustrates a low intake risk with the use of pymetrozine in tea plantations. It could serve as reference for further regulation consideration for maximum residue limits (MRLs). © 2020 Society of Chemical Industry.Senescent cells can secrete a plethora of cytokines which induce senescent phenotype of neighboring cells and was called senescence-associated secretory phenotype. Previously, it was believed that cancer was caused by the infinite division and uncontrolled proliferation of cells. Based on this, anticancer treatments were all aimed at killing cancer cells. Cancer is now considered an age-related disease. Cancer cells are not exogenous, but one of the worst results of injuries which initially induce cell senescence. Therefore, reversing cell senescence can fundamentally prevent and treat cancer. Though current anticancer treatments induce the cancer cells apoptosis, they induce senescence of normal cells at the same time, thus promoting the occurrence and development of cancer and forming a vicious circle. Extracellular vesicles (EVs) are nano-sized vesicles which partially mirror their parent cells. In the tumor microenvironment, EVs of senescent cells can change the expression profile of cancer cells, contributing to their resistance to chemotherapy. There is growing evidence indicates that stem cell EVs exert effective antiaging and anticancer actions by transferring functional microRNAs and proteins. This review will summarize the therapeutic role of stem cell EVs in reversing aging and cancer, which suggests the broad clinical application perspective.

The optimal transfusion threshold for most patient populations has been defined as hematocrit (HCT) <21%. However, some specific patient populations are known to benefit from higher transfusion thresholds. To date, the optimal postoperative transfusion threshold for patients undergoing liver transplant has not been determined. To define the ideal transfusion threshold for liver transplant patients, we designed a retrospective study of 496 liver transplant recipients.

Using HCT prior to discharge as a surrogate marker for transfusion thresholds we grouped patients into three groups of transfusion thresholds (HCT <21%, <24%, and >30%). Transfusion rates (intra- and postoperative), graft and patient survival, and complications requiring readmission were compared between groups.

Ninety-two percent of patients were transfused during their hospital stay. Graft survival, patient survival, and rates of readmission within 30 days of discharge were no different between the three discharge HCT groups. Patients discharged with HCT >30% were less likely to be readmitted with infectious complications; however, this group also had the lowest model of end-stage liver (MELD) score at time of transplantation and were less likely to have received a transfusion during their hospital stay.

Transfusion thresholds of HCT <24%, and potentially as low as 21% are acceptable in postoperative liver transplant recipients. The conduct of a randomized clinical trial, as supported by these data, will be necessary to support the use of lower thresholds.

Transfusion thresholds of HCT less then 24%, and potentially as low as 21% are acceptable in postoperative liver transplant recipients. The conduct of a randomized clinical trial, as supported by these data, will be necessary to support the use of lower thresholds.

Exhausted sugar beet pulp pellets (ESBPP) were used as raw material for lactic acid (LA) fermentation. The enzymatic hydrolysis of ESBPP was performed with the solid obtained after the fungal solid-state fermentation of ESBPP as a source of hydrolytic enzymes. Subsequently, a medium rich in glucose and arabinose was obtained, which was used to produce LA by fermentation. For LA production, two Lactobacillus strains were assayed and the effects of the supplementation of the hydrolysate with a nitrogen source and the mode of pH regulation of the fermentation were investigated. Moreover, a kinetic model for LA fermentation by Lactobacillus plantarum of ESBPP hydrolysates was developed.

L. plantarum produced a LA concentration 34% higher than that produced by L. casei. The highest LA concentration (30 g L

) was obtained with L. plantarum when the hydrolysate was supplemented with 5 g L

yeast extract and the pH was controlled with CaCO

. The concentration of acetic acid differed depending on the concentration of CaCO

added, producing its maximum value with 27 g L

CaCO

. The proposed kinetic model was able to predict the evolution of substrates and products depending on the variation of the pH in the hydrolysate, according to the amount of CaCO

added.

ESBPP can be revalorised to produce LA. A pure LA stream or a mixture of LA and acetic acid, depending on the pH control method of the fermentation, can be produced. Thus, this control is of great interest depending on the destination of the effluent. © 2020 Society of Chemical Industry.

ESBPP can be revalorised to produce LA. A pure LA stream or a mixture of LA and acetic acid, depending on the pH control method of the fermentation, can be produced. Thus, this control is of great interest depending on the destination of the effluent. © 2020 Society of Chemical Industry.

Few studies have rigorously assessed the impact of red blood cell (RBC) transfusion on oxygen delivery. Several large trials demonstrated no clinical outcome differences between transfusion of shorter-storage vs prolonged-storage RBCs. These trials did not directly assess functional measures of oxygen delivery. Therefore, it is not clear if 42-day stored RBCs deliver oxygen as effectively as 7-day stored RBCs.

Leukocyte-reduced RBCs were collected by apheresis in AS-3. Thirty subjects were randomized (111) to receive 2 units of autologous RBCs at either 7, 28, or 42 days following donation. VO

max testing, using a standardized protocol to exhaustion, was performed 2 days before (Monday) and 2 days after (Friday) the transfusion visit (Wednesday). The primary endpoint was the percent increase in VO

max between Monday and Friday. The secondary endpoint was the percent change in duration of exercise for the same time points.

Hemoglobin levels decreased by 2.8 ± 1.4 g/dL after donation and increased by 2.1 ± 0.6 g/dL after transfusion. This change in hemoglobin was associated with expected decreases (then increases after transfusion) in VO

max and exercise duration. No differences were observed between 7-day and 42-day RBC transfusion for percent increase in median [IQR] VO

max (10.5 [0.2-17.3] vs 10.9 [5.7-16.8], P = .41) or for percent increase in exercise duration (5.4 [4.1-6.9] vs 4.9 [2.0-7.2], P = .91), respectively. Results were similar for 28-day RBCs and were consistent across the ITT and per-protocol analysis populations.

These data indicate that 42-day, 28-day, and 7-day RBCs have similar ability to deliver oxygen.

These data indicate that 42-day, 28-day, and 7-day RBCs have similar ability to deliver oxygen.

To investigate the potential association between periodontitis and arterial stiffness among the older Japanese population.

The prevalence of periodontitis is increasing in Japanese older adults. Arterial stiffness increases the risks of cardiovascular events and death, morbidity, and dementia.

This secondary analysis of data from a cross-sectional study evaluated the periodontal inflamed surface area (PISA), reflecting the amount of inflamed periodontal tissue that was estimated by a full-mouth periodontal examination. Severe periodontitis was defined per the parameters provided by the Centers for Disease Control/American Academy of Periodontology. The Cardio-Ankle Vascular Index (CAVI) was used for measuring the overall stiffness of the artery, and higher CAVI indicated increased arterial stiffness. An ordinal logistic regression model was used to evaluate the association between periodontitis and arterial stiffness.

The analysis included 185 Japanese adults [35% men; age, mean (standard deviation) 8ic diseases, including cardiovascular disease and dementia.The dielectric properties and specifically the complex relative permittivity of foods are key elements for the design of pasteurization processes with high frequency electromagnetic waves. Mexican sauces are recognized worldwide for their flavor and nutritional properties. In this work, the complex permittivity of four of the most representative sauces of Mexican cuisine (chipotle chili, habanero chili, red and green sauce) is presented. The permittivity was measured with the open coaxial probe method at temperatures of 25, 40, 55, 70, 85 °C and in the frequency range of 500 MHz to 6 GHz. Additionally, moisture content, specific heat, viscosity, water activity, density and electrical conductivity are reported, these last three at 25 °C. Dielectric properties were affected by the sauce formulation. The loss factor of each sauce sample at any temperature presents significant changes in relation to the frequency. At 915 and 2,450 MHz, d ε ' ' d T > 0 , which would cause a thermal runaway effect or the uncontrollcrowave-assisted pasteurization according to the penetration depth of the electromagnetic wave in the sauces and microwave dielectric heating speed of the sauces.

Patients with non-ST-elevation myocardial infarction (NSTEMI) have worse long-term prognoses than those with ST-elevation myocardial infarction (STEMI).

It may be attributable to more extended coronary atherosclerotic disease burden in patients with NSTEMI.

This study consisted of consecutive 231 patients who underwent coronary intervention for myocardial infarction (MI). To assess the extent and severity of atherosclerotic disease burden of non-culprit coronary arteries, two scoring systems (Gensini score and synergy between percutaneous coronary intervention with Taxus and cardiac surgery [SYNTAX] score) were modified by subtracting the score of the culprit lesion the non-culprit Gensini score and the non-culprit SYNTAX score.

Patients with NSTEMI had more multi-vessel disease, initial thrombolysis in myocardial infarction (TIMI) flow grade 2/3, and final TIMI flow grade 3 than those with STEMI. As compared to STEMI, patients with NSTEMI had significantly higher non-culprit Gensini score (16.3 ± 19.8 vs. 31.2 ± 25.4, p < 0.001) and non-culprit SYNTAX score (5.8 ± 7.0 vs. 11.1 ± 9.7, p < 0.001).

Patients with NSTEMI had more advanced coronary atherosclerotic disease burden including non-obstruction lesions, which may at least in part explain higher incidence of cardiovascular events in these patients.

Patients with NSTEMI had more advanced coronary atherosclerotic disease burden including non-obstruction lesions, which may at least in part explain higher incidence of cardiovascular events in these patients.

Determine if diagnostic findings from pre-operative multidisciplinary evaluations are associated with single surgery or overall success rates in pediatric laryngotracheal reconstruction (LTR).

Retrospective cohort.

Retrospective cohort study of patients undergoing LTR at a tertiary care children's hospital between January 01, 2008 and December 31, 2017. Success is defined as decannulation rate if tracheostomy present, and resolution of symptoms if tracheostomy not present. Cohorts compared were those who did and did not receive pulmonary and gastrointestinal preoperative testing. Multivariate, logistic regression, and Kaplan Meier analyses performed.

About 165 children were included in the study. Median age was 3 years at the time of surgery; 73% of LTRs were double-stage procedures. Single surgery and overall success rates were 75% and 87%, respectively. After adjusting for severity of stenosis and surgical approach, performing esophagogastroduodenoscopy (EGD) and normal gross appearance on EGD were associated with increased single surgery (P = .01, .005) and overall success (P = .005, .0003). Performing pH probe and normal EGD biopsy results was associated with increased overall success (P = .03, .007). Asthma and musculoskeletal comorbidities, postoperative complications, and need for postoperative balloon dilation were associated with decreased success. No other comorbidities evaluated impacted success.

Aerodigestive comorbidities are common in children undergoing LTR, and preoperative multidisciplinary workup often results in changes in management. After adjusting for grade and level of stenosis and staged approach, performing EGD and pH/impedance probe as well as normal gross and microscopic EGD findings was independently associated with increased LTR surgical success.

4 (retrospective cohort study) Laryngoscope, 2020.

4 (retrospective cohort study) Laryngoscope, 2020.Hypercholesterolemia has been found to be closely linked with a significant increase in both cancer incidence and mortality. However, the exact correlation between serum cholesterol levels and cancer has not been completely deciphered. Here we analyzed the effect of low-density lipoprotein (LDL) cholesterol on prostate and pancreatic cancer cells. We noted that LDL induced a substantial STAT3 activation and JAK1, JAK2, Src activation in diverse prostate and pancreatic tumor cells. Moreover, LDL promoted cancer cell proliferation, migration, and invasion as well as upregulated the expression of diverse oncogenic gene products. However, deletion of LDL-activated STAT3 in LNCaP and PANC-1 cells and reduced LDL-induced cell viability. Simvastatin (SV) treatment also alleviated LDL-induced cell viability and migration ability in both the prostate and pancreatic tumor cells. These results demonstrate that LDL-induced STAT3 activation may exert a profound effect on the proliferation and survival of tumor cells.

Portable electronic devices are used regularly within the veterinary and medical environments. Use of these in clinical areas may predispose them to bacterial contamination and they could act as fomites, transmitting infection between clinicians and patients.

To determine the prevalence, origin and nature of Staphylococcal bacterial contamination on the surface of portable electronic devices used in a large small animal hospital.

Staff were surveyed on the frequency of portable electronic device use and device-cleaning routines. Portable electronic devices were swabbed for staphylococcus species. Cultured cocci were tested for antimicrobial resistance and identified at the species level to help determine the likely source (human or animal).

Forty one of 48 (85%) of staff used a portable electronic device every day within the hospital. Useable swabs were obtained from 47 portable electronic devices. Staphylococci were found on 68% of portable electronic devices. Vancomycin and Oxacillin resistance were seen in 17 of 46 (37%) and 1 of 46 (2%) isolated colonies respectively, including four vancomycin resistant, coagulase-positive staphylococci. 44% of staff never cleaned their device.

Portable electronic devices are commonly used in veterinary hospitals, but few staff routinely disinfect them. The use of disinfectant to reduce colony counts should be implemented when forming protocols for these devices in the hospital. The majority of staphylococci found were of likely human origin. It is suggested that contamination is therefore more likely to be originating from staff rather than patients.

Portable electronic devices are commonly used in veterinary hospitals, but few staff routinely disinfect them. The use of disinfectant to reduce colony counts should be implemented when forming protocols for these devices in the hospital. The majority of staphylococci found were of likely human origin. It is suggested that contamination is therefore more likely to be originating from staff rather than patients.

SR is a chemical agent developed for the treatment of osteoporosis. In vitro, SR enhanced replication of osteoprogenitor cells and bone formation. In vivo, in ovariectomized rats SR prevented the biomechanical deterioration of bone while in non-ovariectomized rats, enhanced bone architecture and increased trabecular and cortical bone mass. The aim of this study was to evaluate the effect of SR on bone healing of calvarial critical size defects treated with a deproteinized bovine bone mineral (DBBM) and a collagen barrier (CM), in healthy and osteoporotic rats.

Sixty-four, 4-month-old Wistar female rats were used. Osteoporosis was induced by ovariectomy and calcium-deficient diet in half of them. Sixteen ovariectomized (OSR) and 16 healthy (HSR) rats were treated with SR while no medication was administered in the remaining 16 healthy (H) and 16 ovariectomized (O) rats. At 6 weeks after ovariectomy, a 5mm defect was created in each parietal bone of every animal. One defect was treated with DBBM and CM, whiit in a moderate extent.Loss-of-function mutations in the deoxyguanosine kinase (DGUOK) gene result in a mitochondrial DNA (mtDNA) depletion syndrome. DGUOK plays an important role in converting deoxyribonucleosides to deoxyribonucleoside monophosphates via the salvage pathway for mtDNA synthesis. DGUOK deficiency manifests predominantly in the liver; the most common cause of death is liver failure within the first year of life and no therapeutic options are currently available. in vitro supplementation with deoxyguanosine or deoxyguanosine monophosphate (dGMP) were reported to rescue mtDNA depletion in DGUOK-deficient, patient-derived fibroblasts and myoblasts. CERC-913, a novel ProTide prodrug of dGMP, was designed to bypass defective DGUOK while improving permeability and stability relative to nucleoside monophosphates. To evaluate CERC-913 for its ability to rescue mtDNA depletion, we developed a primary hepatocyte culture model using liver tissue from DGUOK-deficient rats. DGUOK knockout rat hepatocyte cultures exhibit severely reduced mtDNA copy number (~10%) relative to wild type by qPCR and mtDNA content remains stable for up to 8 days in culture. CERC-913 increased mtDNA content in DGUOK-deficient hepatocytes up to 2.4-fold after 4 days of treatment in a dose-dependent fashion, which was significantly more effective than dGMP at similar concentrations. These early results suggest primary hepatocyte culture is a useful model for the study of mtDNA depletion syndromes and that CERC-913 treatment can improve mtDNA content in this model.

Periodontal ligament stem cells (PDLSCs) have potential for osteogenic differentiation and show a great foreground in treating bone diseases. Histone three lysine 27 (H3K27) demethylase lysine demethylase 6A (KDM6A) is a critical epigenetic modifier and plays an important role in regulating osteogenic differentiation. Multiple microRNAs have been found to play important roles in osteogenesis. The aim of this study was to explore the mechanisms underlying the roles of miR-153-3p and KDM6A in PDLSC osteogenesis.

The levels of the osteogenic markers alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), and osteopontin (OPN) were measured by western blotting. Osteoblast activity and mineral deposition were detected by ALP and Alizarin red S (ARS) staining. The levels of miR-153-3p and KDM6A were measured by quantitative real-time PCR (qRT-PCR). A luciferase reporter assay was used to confirm the interaction between KDM6A and miR-153-3p. Gain-of-function and loss-of-function assays were perf provide latent hope for PDLSCs application in periodontal therapy.

This study was to compare barbed reposition pharyngoplasty (BRP) and expansion sphincter pharyngoplasty (ESP) in the treatment of obstructive sleep apnea (OSA).

Relevant 907 articles were searched from various databases until August 2020, including PubMed, MEDLINE, EMBASE, Cochrane Library, Web of Science and Scopus, and reference lists.

Four studies with a total of 208 participants were included. The mean reduction of apnea-hypopnea index (AHI) in the BRP group was 74.03% and the mean reduction of AHI in the ESP group was 60.17%. The mean success rate in the BRP group and the ESP group was 84.96% and 79.87%, respectively. The mean difference (MD) of the change in AHI between groups was not significantly different (MD=-1.24 event/hr, 95% CI [-11.86, 9.36], P= .82). There was no significant difference in postoperative AHI, postoperative Epworth Sleepiness Scale, pain, hospital stay, time to oral diet, and the change in oxygen desaturation index in both groups whereas the analgesic requirement was lower in the BRP group. Operative time was lower in the BRP group (MD=21.72 minutes, 95% CI [18.85, 24.60], P < .0001).

The outcomes in both procedures are comparable in the improvement of OSA with palatal collapse. BRP is superior to ESP in term of surgical time. However, randomized clinical controlled trials with multicenter cooperation and long-term follow-up are essential to further demonstrate the efficacy of these procedures. Laryngoscope, 1311420-1428, 2021.

The outcomes in both procedures are comparable in the improvement of OSA with palatal collapse. BRP is superior to ESP in term of surgical time. However, randomized clinical controlled trials with multicenter cooperation and long-term follow-up are essential to further demonstrate the efficacy of these procedures. Laryngoscope, 1311420-1428, 2021.Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, an epithelial cytokine involved in asthma pathogenesis. In the phase 2b PATHWAY study (ClinicalTrials.gov identifier NCT02054130), tezepelumab significantly reduced exacerbations in adults with severe, uncontrolled asthma. We used pharmacokinetic (PK) and pharmacodynamic (PD) modeling to guide tezepelumab dose selection for phase 3 trials in patients with severe asthma. PK data from 7 clinical studies were used to develop a population PK model. Population PK-PD models were developed to characterize the relationship between tezepelumab PK and asthma exacerbation rate (AER) and fractional exhaled nitric oxide (FeNO) levels (using phase 2b PD data only). Tezepelumab PK were well described by a 2-compartment model with first-order absorption; PK parameter estimates were consistent with those of other immunoglobulin G2 antibodies. PK-PD models predicted that subcutaneous dosing at 210 mg every 4 weeks was associated with ≈90% of the maximum drug effect of tezepelumab on AER and FeNO; further dose increases were not expected to result in additional, clinically meaningful treatment benefit. No clinically significant covariates of treatment effects on AER and FeNO were identified. Population PK simulations, exposure-response relationships and safety profiles of tezepelumab at doses up to 280 mg every 2 weeks suggested that no dose adjustment based on body weight or for adolescents was required. These results support the selection of 210 mg every 4 weeks subcutaneously as the dose for phase 3 studies of tezepelumab in adults and adolescents with severe asthma.