3798; p < .001) had better prognostic performance than pN and better discriminatory ability than LND (AIC = 3902 vs. 3928). LODDS had better power of discrimination than LND and pN. LODDS could predict survival in lymph node yield (LNY) < 15 (p < .001).

LODDS is an independent predictor of OS in the SCC penis and has superior prognostic significance than the AJCC pN and LND classification systems.

LODDS is an independent predictor of OS in the SCC penis and has superior prognostic significance than the AJCC pN and LND classification systems.

The effectiveness of local therapy has been reported in non-small-cell lung cancer (NSCLC) patients with oligo-recurrence. However, there is still no clear consensus on the choice of local therapy. We aimed to examine the choice of local therapy in NSCLC patients with lung oligo-recurrence.

Among 1760 consecutive NSCLC patients who underwent complete resection between 1990 and 2008, 535 patients developed recurrence. Lung oligo-recurrence was defined as 1-5 metachronous recurrences limited to the lungs only; such recurrence was found in 97 patients. We examined the differences in the prognosis of each therapy for these patients.

The 5-year postrecurrence survival (PRS) rates in patients who underwent local therapy (n = 54) and those who did not (n = 43) were 55.6% and 31.1%, respectively; it was significantly higher in patients who underwent local therapy (p = 0.004). Among 47 patients who underwent resection or radiation therapy, the 5-year PRS rates were 61.5% and 47.6% (p = 0.258), and the 5-year postrecurrence progression-free survival rates were 30.3% and 24.7% (p = 0.665), respectively, without any significant difference.

Patients with lung oligo-recurrence should consider local therapy individually, depending on their general condition.

Patients with lung oligo-recurrence should consider local therapy individually, depending on their general condition.

Transanal total mesorectal excision (taTME) is a novel radical resection technique that may address the unsatisfactory functional and oncological outcomes of medium-low rectal cancers. Although its oncological safety remains unclear, taTME has demonstrable value in surgery, complications, and oncological outcomes. Here, we explore the short-term outcomes of rectal cancer after taTME and discuss the surgical experience. Twenty-two patients with medium-low rectal cancer who underwent taTMEwere retrospectively evaluated. Comprehensive demographic, oncological, and clinical data were analyzed and the perioperative state and postoperative follow-up were evaluated.

Over a median follow-up period of 24.4 (4-36) months, local recurrence occurred in one patient at 6 months postsurgery. Fecal incontinence was the most common postoperative complication, and 3-6 months of pelvic-floor-rehabilitation training greatly improved anal function CONCLUSIONS taTME achieved satisfactory short-term outcomes in oncological complications and postoperative functions. Accurate intraoperative anatomical location, identification of the rectovesical fascia, and neuroprotection are critical. However, this procedure has a steep learning curve, and large samples and multicenter studies are required to substantiate its effectiveness.

We retrospectively analyzed the oncological and functional prognosis of 22 patients with colorectal cancer undergoing taTME surgery and preliminarily concluded taTME can be regarded as a safe and feasible treatment.

We retrospectively analyzed the oncological and functional prognosis of 22 patients with colorectal cancer undergoing taTME surgery and preliminarily concluded taTME can be regarded as a safe and feasible treatment.Bone regeneration and remodeling are complex physiological processes that are regulated by key transcription factors. Understanding the regulatory mechanism of key transcription factors on the osteogenic differentiation of mesenchymal stem cells (MSCs) is a key issue for successful bone regeneration and remodeling. In the present study, we investigated the regulatory mechanism of the histone deacetylase Sirtuin 7 (SIRT7) on the key transcription factor OSX and osteogenesis of MSCs. In this study, we found that SIRT7 knockdown increased ALP activity and in vitro mineralization and promoted the expression of the osteogenic differentiation markers DSPP, DMP1, BSP, OCN, and the key transcription factor OSX in MSCs. In addition, SIRT7 could associate with RNA binding motif protein 6 (RBM6) to form a protein complex. Moreover, RBM6 inhibited ALP activity, the expression of DSPP, DMP1, BSP, OCN, and OSX in MSCs, and the osteogenesis of MSCs in vivo. Then, the SIRT7/RBM6 protein complex was shown to downregulate the level of H3K18Ac in the OSX promoter by recruiting SIRT7 to the OSX promoter and inhibiting the expression of OSX isoforms 1 and 2. Furthermore, lncRNA PLXDC2-OT could associate with the SIRT7/RBM6 protein complex to diminish its binding and deacetylation function in the OSX promoter and its inhibitory function on OSX isoforms 1 and 2 and to promote the osteogenic potential of MSCs.Mastocytosis is a heterogeneous group of diseases characterized by abnormal proliferation of neoplastic mast cells in the skin and/or other extracutaneous tissues. Most patients with skin involvement can be subclassified into one of the three subtypes of cutaneous mastocytosis currently recognized by the World Health Organization (i.e., mastocytoma, maculopapular cutaneous mastocytosis and diffuse cutaneous mastocytosis); however, some patients may occasionally present with atypical skin lesions that cannot be ascribed to any of these disease subtypes. Here, we report three patients diagnosed with mastocytosis and an unusual cutaneous involvement mimicking Kaposi’s sarcoma. Skin biopsies showed neoplastic mast cell infiltrates together with features commonly seen in acroangiodermatitis, and immunohistochemistry for human herpesvirus 8 was negative. One patient fulfilled the criteria for aggressive systemic mastocytosis, showed no response to cytoreductive therapy, and died because of disease progression. The remaining two patients had indolent and smoldering systemic mastocytosis, respectively, but they showed several features associated with an unfavorable prognosis such as extensive involvement of the hematopoiesis by the KIT D816V mutation, increased serum β2-microglobulin, and decreased serum lactate dehydrogenase. The presence of pseudo-Kaposi’s sarcoma skin lesions is an uncommon finding in mastocytosis which may alert physicians to the possible existence of underlying features indicative of a poor prognosis.Incidence of melanoma continues to rise in the United States with ~100,000 new cases diagnosed in 2019. While the 5-year survival rate of melanoma is 99% when localized, the rate of survival drops to 22.5% when distant disease is detected. As such, an area of great interest is understanding the mechanisms that promote melanoma metastasis so that better potential therapeutic targets can be discovered. Herein, we demonstrate that activation of NRF2 by FAM129B contributes to increased metastatic potential of BRAF V600E mutant melanoma cells. Specifically, FAM129B induces NRF2 by competing for Kelch-like ECH-associated protein 1 (KEAP1) binding (the negative regulator of NRF2) via an ETGE motif. Furthermore, we show that phosphorylation of FAM129B plays a role in mediating the interaction between FAM129B and KEAP1, as the phosphorylation status of FAM129B dictates its subcellular localization. When phosphorylated, FAM129B is found primarily in the cytosol where it can bind to KEAP1, but upon inhibition of mitogen-activated protein kinase kinase activity, FAM129B is localized to the cell membrane and no longer interacts with KEAP1. In BRAF V600E mutant melanoma, the mitogen-activated protein kinase pathway leads to hyperphosphorylation of FAM129B, and therefore FAM129B localizes to the cytosol, binds KEAP1, and upregulates NRF2. Importantly, genetic modulation or pharmacological inhibition that results in a decrease in FAM129B protein level or its phosphorylation decreases migration and invasion of mutant melanoma in an NRF2-dependent manner. Overall, these data indicate that phosphorylation of FAM129B plays a significant role in driving the metastatic potential of BRAF V600E melanoma via upregulation of the NRF2 signaling pathway.Loss of biodiversity and accumulation of contaminants in urban soils and water bodies cause serious issues in metropolitan areas. The Matanza-Riachuelo river basin (metropolitan area of Buenos Aires, Argentina) is one of the most environmentally degraded regions in the world. Senecio bonariensis Hook & Arn (Asteraceae) grows in the periodically flooded soils of this wetland. This plant concentrates potentially toxic trace elements (PTEs) in its tissues and establishes symbiosis with arbuscular mycorrhizal (AM) fungi that collaborate with PTE phytostabilization in soils. The objective of this work was to evaluate tolerance and stress alleviation of AM-colonized S. bonariensis when transplanting and exposing to highly polluted environmental conditions of the river basin. Plants were initially inoculated with different AM strains and maintained in greenhouse conditions. After 6 mo, they were transplanted to the field. These plants showed a more equal distribution between shoot and root biomass production in comparison to field spontaneous S. bonaerensis plants. Plants in earlier contact with native soil inoculum showed positive correlation with phosphorus content and a significant increase of vesicle frequency. Plants belatedly contacted with native inoculum in the field (control) showed a higher catalase level that was positively correlated with the total colonization frequency and chlorophyll content. The ability to establish symbiosis with Rhizophagus intraradices (strain GC3), commonly used in the formulation of biofertilizers, was also analyzed. Plants inoculated with GC3 at the beginning of the assay showed lower colonization and were less efficient in the field. The preservation of spontaneous native plants with ornamental value and bioaugmentation of their associated microbiome can contribute to the stabilization of contaminants in soils.

For patients with bilateral pulmonary metastases, staged resections have historically been the preferred surgical intervention. During the spring of 2020, the COVID-19 pandemic made patient travel to the hospital challenging and necessitated reduction in operative volume so that resources could be conserved. We report our experience with synchronous bilateral metastasectomies for the treatment of disease in both lungs.

Patients with bilateral pulmonary metastases who underwent simultaneous bilateral resections were compared with a cohort of patients who underwent staged resections. We used nearest-neighbor propensity score (11) matching to adjust for confounders. Perioperative outcomes were compared between groups using paired statistical analysis techniques.

Between 1998 and 2020, 36 patients underwent bilateral simultaneous metastasectomies. We matched 31 pairs of patients. The length of stay was significantly shorter in patients undergoing simultaneous resection (median 3 vs. 8 days, p < .001) and operative time was shorter (156 vs. 235.5 min, p < .001) when compared to the sum of both procedures in the staged group. The groups did not significantly differ with regard to postoperative complications.

In a carefully selected patient population, simultaneous bilateral metastasectomy is a safe option. A single procedure confers benefits for both the patient as well as the hospital resource system.

In a carefully selected patient population, simultaneous bilateral metastasectomy is a safe option. A single procedure confers benefits for both the patient as well as the hospital resource system.

Ischemic complications are still prevalent after distal pancreatectomy with en bloc celiac axis resection (DP-CAR) despite the use of preoperative arterial embolization. We described our institutional experience with arterial reconstruction during DP-CAR.

We retrospectively reviewed short- and long-term outcomes of all DP-CAR performed for pancreatic adenocarcinoma between January 1, 1995 and March 30, 2020. Outcomes were compared according to the presence of arterial reconstruction.

Sixty consecutive DP-CARs were reviewed. Most patients underwent induction chemotherapy (85%) based on FOLFIRINOX protocol (80.3%). The hepatic artery was reconstructed in 50 patients (83.3%). The left gastric artery was reconstructed in 4 and preserved in 14 patients. A venous resection was associated during 44 DP-CARs (36 segmental venous resections/8 lateral venous resections). Ninety days mortality was 5.0% with 48.3% (n = 29) overall rate of morbidity. Postoperative outcomes in term of mortality, morbidity, and ischemic events between patients with and without arterial reconstruction were similar despite a higher rate of venous resection (81% vs. 40%; p = 0.005) and more complex cases (Mayo clinic DP-CARs class1B, 2A, and 3A) in the reconstructed group.

Arterial reconstruction represents a safe surgical option during DP-CAR to lessen postoperative ischemic events. This technique, reserved to high volume centers expert in vascular resection during pancreatectomy, deserves further comparison with standard technique in a larger setting.

Arterial reconstruction represents a safe surgical option during DP-CAR to lessen postoperative ischemic events. This technique, reserved to high volume centers expert in vascular resection during pancreatectomy, deserves further comparison with standard technique in a larger setting.

The purpose of this study was to assess the utility of determining the biological features of synchronous axillary lymph node (syLN) metastasis of breast cancer in evaluating the efficacy of preoperative systemic chemotherapy (PST).

The retrospective subjects initially comprised 59 patients (T1c-4 N1-3 M0) diagnosed with syLN metastasis via core needle biopsy who received PST. The hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status in each patient was assessed in primary breast tumor (pBT) and syLNs using immunohistochemistry, and the patients were classified into HR(+), HER2(+), and triple negative breast cancer (TN) subtypes.

Subtype shift (SS) of pBT in syLNs was observed in 28% cases for HR(+), in 6% cases for the HER2(+), and in 16% cases for the TN. The pCR rate of the pBT and syLNs types were 45% and 36% in the HR(+), 45% and 39% in the TN, and 94% and 100% in the HER2(+), respectively. In SS cases, the pCR rate was significantly higher in 75% cases compared with 33% of the no-SS cases.

A SS in syLNs was more frequent in HR(+) than in other types.

A SS in syLNs was more frequent in HR(+) than in other types.Therapeutic antibodies blocking PD-1-/PD-L1 interaction have achieved remarkable clinical success in cancer. In addition to blocking a target molecule, some isotypes of antibodies can activate complement, NK cells or phagocytes, resulting in death of the cell expressing the antibody’s target. Human anti-PD-1 therapeutics use antibody isotypes designed to minimize such antibody-dependent lysis. In contrast, anti-PD-1 reagents used in mice are derived from multiple species, with different isotypes, and are not engineered to reduce target cell death few studies analyze or discuss how antibody species and isotype may impact data interpretation. We demonstrate here that anti-PD-1 therapy to promote activation and proliferation of murine PD-1-expressing CD8 T cells sometimes led instead to a loss of antigen specific cells. This phenomenon was seen in two tumor models and a model of virus infection, and varied with the clone of anti-PD-1 antibody. Additionally, we compared competition among anti-PD-1 clones to find a combination that allows detection of PD-1-expressing cells despite the presence of blocking anti-PD1 antibodies in vivo. These data bring attention to the possibility of unintended target cell depletion with some commonly used anti-mouse PD-1 clones, and should provide a valuable resource for the design and interpretation of anti-PD-1 studies in mice.Plastid metabolism is critical in both photoautotrophic and heterotrophic plant cells. In chloroplasts, fructose-1,6-bisphosphate aldolase (FBA) catalyses the formation of both fructose 1,6-bisphosphate and sedoheptulose 1,7-bisphosphate within the Calvin-Benson cycle. Three Arabidopsis genes, AtFBA1-AtFBA3, encode plastidial isoforms of FBA, but the contribution of each isoform is unknown. Phylogenetic analysis indicates that FBA1 and FBA2 derive from a recently duplicated gene, while FBA3 is a more ancient paralog. fba1 mutants are phenotypically indistinguishable from the wild type, while both fba2 and fba3 have reduced growth. We show that FBA2 is the major isoform in leaves, contributing most of the measurable activity. Partial redundancy with FBA1 allows both single mutants to survive, but combining both mutations is lethal, indicating a block of photoautotrophy. In contrast, FBA3 is expressed predominantly in heterotrophic tissues, especially the leaf and root vasculature, but not in the leaf mesophyll. We show that the loss of FBA3 affects plastidial glycolytic metabolism of the root, potentially limiting the biosynthesis of essential compounds such as amino acids. However, grafting experiments suggest that fba3 is dysfunctional in leaf phloem transport, and we suggest that a block in photoassimilate export from leaves causes the buildup of high carbohydrate concentrations and retarded growth.Recruitment of the mRNA capping enzyme (CE/RNGTT) to the site of transcription is essential for the formation of the 5′ mRNA cap, which in turn ensures efficient transcription, splicing, polyadenylation, nuclear export and translation of mRNA in eukaryotic cells. The CE GTase is recruited and activated by the Serine-5 phosphorylated carboxyl-terminal domain (CTD) of RNA polymerase II. Through the use of molecular dynamics simulations and enhanced sampling techniques, we provide a systematic and detailed characterization of the human CE-CTD interface, describing the effect of the CTD phosphorylation state, length and orientation on this interaction. Our computational analyses identify novel CTD interaction sites on the human CE GTase surface and quantify their relative contributions to CTD binding. We also identify, for the first time, allosteric connections between the CE GTase active site and the CTD binding sites, allowing us to propose a mechanism for allosteric activation. Through binding and activity assays we validate the novel CTD binding sites and show that the CDS2 site is essential for CE GTase activity stimulation. Comparison of the novel sites with cocrystal structures of the CE-CTD complex in different eukaryotic taxa reveals that this interface is considerably more conserved than previous structures have indicated.The genetic code of mammalian cells can be expanded to allow the incorporation of non-canonical amino acids (ncAAs) by suppressing in-frame amber stop codons (UAG) with an orthogonal pyrrolysyl-tRNA synthetase (PylRS)/tRNAPylCUA (PylT) pair. However, the feasibility of this approach is substantially hampered by unpredictable variations in incorporation efficiencies at different stop codon positions within target proteins. Here, we apply a proteomics-based approach to quantify ncAA incorporation rates at hundreds of endogenous amber stop codons in mammalian cells. With these data, we compute iPASS (Identification of Permissive Amber Sites for Suppression; available at http://www.bultmannlab.eu/tools/iPASS), a linear regression model to predict relative ncAA incorporation efficiencies depending on the surrounding sequence context. To verify iPASS, we develop a dual-fluorescence reporter for high-throughput flow-cytometry analysis that reproducibly yields context-specific ncAA incorporation efficiencies. We show that nucleotides up- and downstream of UAG synergistically influence ncAA incorporation efficiency independent of cell line and ncAA identity. Additionally, we demonstrate iPASS-guided optimization of ncAA incorporation rates by synonymous exchange of codons flanking the amber stop codon. This combination of in silico analysis followed by validation in living mammalian cells substantially simplifies identification as well as adaptation of sites within a target protein to confer high ncAA incorporation rates.Scribble is a critical cell polarity regulator that has been shown to work as either an oncogene or tumor suppressor in a context dependent manner, and also impacts cell migration, tissue architecture and immunity. Mutations in Scribble lead to neural tube defects in mice and humans, which has been attributed to a loss of interaction with the planar cell polarity regulator Vangl2. We show that the Scribble PDZ domains 1, 2 and 3 are able to interact with the C-terminal PDZ binding motif of Vangl2 and have now determined crystal structures of these Scribble PDZ domains bound to the Vangl2 peptide. Mapping of mammalian neural tube defect mutations reveal that mutations located distal to the canonical PDZ domain ligand binding groove can not only ablate binding to Vangl2 but also disrupt binding to multiple other signaling regulators. Our findings suggest that PDZ-associated neural tube defect mutations in Scribble may not simply act in a Vangl2 dependent manner but as broad-spectrum loss of function mutants by disrupting the global Scribble-mediated interaction network.Osteoporosis is a global health issue among the aging population. The effect of the acid or base interventions on bone health remains controversial. This study performed a systematic review and meta-analysis to investigate effects of acidic diets and alkaline supplements on bone health simultaneously. We conducted a comprehensive literature search in 5 available databases and 1 registered clinical trial system to identify randomized controlled trials (RCTs) that assessed effects of the acid-base intervention on bone health. Depending on heterogeneity across studies, the pooled effects were calculated by fixed-effects or random-effects models. The present study included 13 acidic diet intervention studies and 13 alkaline supplement studies for final quantitative assessments. The meta-analysis showed that acidic diets significantly increased net acid excretion [NAE; standardized mean difference (SMD) = 2.99; P = 0.003] and urinary calcium excretion (SMD = 0.47, P less then 0.00001) but had no significant effe by a larger RCT. In summary, through integrating evidence from RCTs, the present meta-analysis initially suggests that alkaline supplements may be beneficial to bone metabolism and acidic diets may not be harmful to bone health. This work may be clinically useful for both clinicians and patients with osteoporosis.Multi-compartment body-composition models that divide the body into its multiple constituents are the criterion method for measuring body fat percentage, fat mass, and fat-free mass. However, 2- and 3-compartment body-composition devices such as air displacement plethysmography (ADP), DXA, and bioelectrical impedance devices [bioelectrical impedance analysis (BIA)] are more commonly used. Accurate measures depend on several assumptions, including constant hydration, body proportion, fat-free body density, and population characteristics. Investigations evaluating body composition in racial and ethnic minorities have observed differences in the aforementioned components between cohorts. Consequently, for racial/ethnic minority populations, estimates of body composition may not be valid. The purpose of this review was to comprehensively examine the validity of common body-composition devices in multi-ethnic samples (samples including >1 race/ethnicity) and in African-American, Hispanic, Asian, and Native Americadiverse samples may improve our ability to select the appropriate method to accurately assess body composition in each racial/ethnic population.Reactive astrocytes are implicated in amyotrophic lateral sclerosis (ALS), although the mechanisms controlling reactive transformation are unknown. We show that decreased intron retention (IR) is common to human-induced pluripotent stem cell (hiPSC)-derived astrocytes carrying ALS-causing mutations in VCP, SOD1 and C9orf72. Notably, transcripts with decreased IR and increased expression are overrepresented in reactivity processes including cell adhesion, stress response and immune activation. This was recapitulated in public-datasets for (i) hiPSC-derived astrocytes stimulated with cytokines to undergo reactive transformation and (ii) in vivo astrocytes following selective deletion of TDP-43. We also re-examined public translatome sequencing (TRAP-seq) of astrocytes from a SOD1 mouse model, which revealed that transcripts upregulated in translation significantly overlap with transcripts exhibiting decreased IR. Using nucleocytoplasmic fractionation of VCP mutant astrocytes coupled with mRNA sequencing and proteomics, we identify that decreased IR in nuclear transcripts is associated with enhanced nonsense mediated decay and increased cytoplasmic expression of transcripts and proteins regulating reactive transformation. These findings are consistent with a molecular model for reactive transformation in astrocytes whereby poised nuclear reactivity-related IR transcripts are spliced, undergo nuclear-to-cytoplasmic translocation and translation. Our study therefore provides new insights into the molecular regulation of reactive transformation in astrocytes.A protective role for vitamin K in cardiovascular disease (CVD), a leading cause of morbidity and mortality, has been proposed because vitamin K-dependent proteins, such as matrix Gla (γ-carboxyglutamic acid) protein (MGP), are present in vascular tissue. MGP functions as a vascular calcification inhibitor-but only when it is carboxylated, which requires vitamin K. There is more than one naturally occurring form of vitamin K. Phylloquinone (vitamin K1) is found in plant-based foods, whereas menaquinones (vitamin K2) are a class of vitamin K compounds found in animal-based and fermented foods. Phylloquinone and menaquinones are capable of carboxylating MGP and other vitamin K-dependent proteins. In rodent models, high intakes of either phylloquinone or menaquinone reduced vascular calcification. Evidence of the relative importance of phylloquinone and menaquinone to CVD in humans is limited and controversial. In some observational studies, higher dietary menaquinone intake, but not phylloquinone intake, was associated with less coronary artery calcification (a subclinical manifestation of CVD) and a lower risk for clinical CVD events. These findings have led to claims that menaquinones have unique cardiovascular health benefits compared with phylloquinone. However, this claim is not supported by the results of the limited number of intervention trials conducted to date. The purpose of this review is to evaluate the strengths and limitations of the available evidence regarding the role of vitamin K in vascular calcification, CVD, and mortality.Mutations in the Plasmodium falciparum genes Pfdhfr and Pfdhps, particularly the sextuple mutant haplotype threatens the antimalarial effectiveness of sulfadoxine-pyrimethamine as intermittent preventive treatment during pregnancy (IPTp). To explore the impact of sextuple mutant haplotype infections on outcome measures after provision of IPTp-SP, we monitored birth outcomes in women followed from prior to conception or from the first trimester until delivery. Women infected with sextuple haplotypes in early 2 nd trimester specifically, delivered newborns with a lower birth weight (-267g, 95% CI -454; -59, p=0·01) compared to women who did not have malaria during pregnancy and women infected with less SP resistant haplotypes (-461g, 95% CI -877; -44, p=0·03). Thus, sextuple haplotype infections seems to impact the effectiveness of SP for IPTp and directly impact birth outcome by lowering birth weight. Close monitoring and targeted malaria control during early pregnancy is therefore crucial to improve birth outcomes.

International medical electives (IMEs) are entry points to global health opportunities. IME uptake at German universities is unclear. We analyse 14 y of IME.

Student registry data were collected. Univariate linear regression examined relationships between enrolment year and IMEs.

The median (IQR) number of IMEs of all enrolment years was 54 (32-80) and 51 (38-67)% of all students took an IME. Enrolment year significantly predicted IME frequency and the proportion of students taking IMEs.

Student interest in IMEs is increasing. Universities should invest more broadly in IME opportunities for student, faculty and university enrichment.

Student interest in IMEs is increasing. Universities should invest more broadly in IME opportunities for student, faculty and university enrichment.

Team-based care offers potential improvements in communication, care coordination, efficiency, value and satisfaction levels of both patients and providers. However, the question of how to balance the need for information in team-based care without disregarding patient preferences remains unanswered. This study aims to determine patients’ perceptions of information sharing via electronic health records (EHRs) in team-based care.

This qualitative study used a focus group approach. Participants were primary care patients and representative members from minority groups (ethnic, racial or social). Audio recordings of the sessions were transcribed and coded consistent with thematic analyses.

The analysis revealed that the participants in the focus groups had diverging levels of understanding and personal beliefs around five major themes including (i) patient’s understanding of the care team, (ii) perceptions of electronic health records, (iii) defining basic health care information, (iv) sharing information ormation but disagreed about what information should be considered to be basic. Moreover, based on their trust and comfort level, many participants want to control what information is recorded and shared in the electronic health record.

Rapid multi-viral respiratory microbiological point-of-care tests (POCTs) have not been evaluated in UK primary care. The aim of this study was to evaluate the use of a multi-viral microbiological POCT for suspected respiratory tract infections (RTIs).

In this observational, mixed-methods feasibility study practices were provided with a POCT machine for any patient aged ≥3 months with suspected RTI. Dual throat/nose swabs tested for 17 respiratory viruses and three atypical bacteria, 65 minutes per sample.

Twenty clinicians recruited 93 patients (estimated 13 of all RTI cases). Patient’s median age was 29, 57% female, and 44% with co-morbidities. Pre-test diagnoses upper RTI (48%); lower RTI (30%); viral/influenza-like illness (18%); other (4%). Median set-up time was 2.72 minutes, with 72% swabs processed <4 hours, 90% <24 hours. Tests detected ≥1 virus in 58%, no pathogen 37% and atypical bacteria 2% (3% inconclusive). Antibiotics were prescribed pre-test to 35% of patients with no pathogen detected and 25% with a virus. Post-test diagnoses changed in 20%, and diagnostic certainty increased (P = 0.02), more so when the test was positive rather than negative (P < 0.001). Clinicians predicted decreased antibiotic benefit post-test (P = 0.02). Interviews revealed the POCT has clear potential, was easy to use and well-liked, but limited by time-to-result and the absence of testing for typical respiratory bacteria.

This POCT was acceptable and appeared to influence clinical reasoning. Clinicians wanted faster time-to-results and more information about bacteria. Randomized trials are needed to understand the safety, efficacy and patient perceptions of these POCTs.

This POCT was acceptable and appeared to influence clinical reasoning. Clinicians wanted faster time-to-results and more information about bacteria. Randomized trials are needed to understand the safety, efficacy and patient perceptions of these POCTs.

Automated text messaging programs have been studied as a treatment tool, but have not been studied as an outreach tool to increase the reach of smoking cessation treatment.

Two distinct text messaging programs were developed. One was aimed at connecting smokers to quitline phone counseling via text message (Text4Coach (T4C)) and the other was aimed at connecting smokers to a smoking cessation text messaging program (Text&Quit (T&Q)). Adult daily smokers with Medicaid insurance (N=80) were recruited from the Emergency Department at an urban hospital and randomized to T4C or T&Q. The primary outcome was program reach.

Outreach text messages were found to have moderately high uptake, with the majority of participants (63.8%) opting into their assigned tobacco treatment program and younger and female participants more likely to opt in (p<.01). Receipt of the treatment portion of the program differed among the programs with 67.5% of T&Q receiving the treatment program and 27.5 % of T4C receiving the program (p<.001). Most participants across both groups replied to at least 1 message (71.3%) and very few unsubscribed from the service over the 3 week trial. The majority of participants reported overall satisfaction with their program (63.8%), found it helpful for quitting smoking (60.0%) and would recommend the program to a friend (62.5%). Overall, 11 (13.8 %) participants reported being abstinent from smoking for the past 7 days at follow-up, with no differences between groups.

Outreach text messages were found to have moderately high reach among Medicaid smokers. Larger trials are needed to evaluate the impact of such programs on helping low-income smokers quit.

Outreach text messages were found to have moderately high reach among Medicaid smokers. Larger trials are needed to evaluate the impact of such programs on helping low-income smokers quit.

Age and disease prevalence are the two biggest risk factors for COVID-19 symptom severity and death. We therefore hypothesized that increased biological age, beyond chronological age, may be driving disease-related trends in COVID-19 severity.

Using the UK Biobank England data, we tested whether a biological age estimate (PhenoAge) measured more than a decade prior to the COVID-19 pandemic was predictive of two COVID-19 severity outcomes (inpatient test positivity and COVID-19 related mortality with inpatient test-confirmed COVID-19). Logistic regression models were used with adjustment for age at the pandemic, sex, ethnicity, baseline assessment centers, and pre-existing diseases/conditions.

613 participants tested positive at inpatient settings between March 16 and April 27, 2020, 154 of whom succumbed to COVID-19. PhenoAge was associated with increased risks of inpatient test positivity and COVID-19 related mortality (ORMortality=1.63 per 5 years, 95% CI 1.43-1.86, p=4.7×10 -13) adjusting for demograthe accumulation of age-related comorbid conditions.

We sought to determine the prevalence and factors associated with the use of skilled assistance during delivery in Papua New Guinea.

We analysed nationally representative data from 5210 women in Papua New Guinea using the 2016-2018 Demographic and Health survey. Both bivariate and multivariable analyses were performed. Statistical significance was set at p<0.05.

The prevalence of skilled assistance during delivery was 57.6%. The richest women (adjusted OR [AOR]=3.503, 95% CI 2.477 to 4.954), working women (AOR=1.221, 95% CI 1.037 to 1.439), women with primary (AOR=1.342, 95% CI 1.099 to 1.639), secondary or higher education (AOR=2.030, 95% CI 1.529 to 2.695), women whose partners had a secondary or higher level of education (AOR=1.712, 95% CI 1.343 to 2.181], women who indicated distance was not a big problem in terms of healthcare (AOR=1.424, 95% CI 1.181 to 1.718), women who had ≥4 antenatal care (ANC) visits (AOR=10.63, 95% CI 8.608 to 13.140), women from the Islands region (AOR=1.305, 95% CI 1.04 of residence, influence the utilisation of skilled delivery services.

Coronavirus disease 2019 (COVID-19) test performance depends on predictive values in settings of increasing disease prevalence. Geospatially distributed diagnostics with minimal uncertainty facilitate efficient point-of-need strategies.

To use original mathematics to interpret COVID-19 test metrics; assess US Food and Drug Administration Emergency Use Authorizations and Health Canada targets; compare predictive values for multiplex, antigen, polymerase chain reaction kit, point-of-care antibody, and home tests; enhance test performance; and improve decision-making.

PubMed/newsprint-generated articles documenting prevalence. Mathematica and open access software helped perform recursive calculations, graph multivariate relationships, and visualize performance by comparing predictive value geometric mean-squared patterns.

Tiered sensitivity/specificity comprised T1, 90%, 95%; T2, 95%, 97.5%; and T3, 100%, ≥99%. Tier 1 false negatives exceeded true negatives at >90.5% prevalence; false positives exceed year.

The overriding principle is to select the best combined performance and reliability pattern for the prevalence bracket. Some public health professionals recommend repetitive testing to compensate for low sensitivity. More logically, improved COVID-19 assays with less uncertainty conserve resources. Multiplex differentiation of COVID-19 from influenza A/B-respiratory syncytial virus represents an effective strategy if seasonal flu surges next year.

Anesthetics aim to prevent memory of unpleasant experiences. The amygdala and dorsal anterior cingulate cortex participate in forging emotional and valence-driven memory formation. It was hypothesized that this circuitry maintains its role under sedation.

Two nonhuman primates underwent aversive tone-odor conditioning under sedative states induced by ketamine or midazolam (1 to 8 and 0.1 to 0.8 mg/kg, respectively). The primary outcome was behavioral and neural evidence suggesting memory formation. This study simultaneously measured conditioned inspiratory changes and changes in firing rate of single neurons in the amygdala and the dorsal anterior cingulate cortex in response to an expected aversive olfactory stimulus appearing during acquisition and tested their retention after recovery.

Aversive memory formation occurred in 26 of 59 sessions under anesthetics (16 of 29 and 10 of 30, 5 of 30 and 21 of 29 for midazolam and ketamine at low and high doses, respectively). Single-neuron responses in the amyole in acquisition and maintenance of aversive memories in nonhuman primates under sedation with ketamine and midazolam and that the stimulus valence is sufficient to drive memory formation.

Leaf senescence is important for crop yield as delaying it can increase the average yield. In this study, population genetics and transcriptomic profiling were combined to dissect its genetic basis in maize. To do this, the progenies of an elite maize hybrid Jidan27 and its parental lines Si-287 (early senescence) and Si-144 (stay-green), as well as 173 maize inbred lines were used. We identified two novel loci and their candidate genes, Stg3 (ZmATG18b) and Stg7 (ZmGH3.8), which are predicted to be members of autophagy and auxin pathways, respectively. Genomic variations in the promoter regions of these two genes were detected, and four allelic combinations existed in the examined maize inbred lines. The Stg3Si-144/Stg7Si-144 allelic combination with lower ZmATG18b expression and higher ZmGH3.8 expression could distinctively delay leaf senescence, increase ear weight and the improved hybrid of NIL-Stg3Si-144/Stg7Si-144 × Si-144 significantly reduced ear weight loss under drought stress, while opposite effects were observed in the Stg3Si-287/Stg7Si-287 combination with a higher ZmATG18b expression and lower ZmGH3.8 expression. Thus, we identify a potential interaction between autophagy and auxin which could modulate the timing of maize leaf senescence.A meta-analysis of prospective studies was conducted to examine the association of total, supplemental, and dietary magnesium intakes with risk of all-cause, cancer, and cardiovascular disease (CVD) mortality and identify the dose-response relations involved in these association. We performed a systematic search of PubMed, Scopus, Google Scholar, and ISI Web of Knowledge up to April 2020. Prospective cohort studies that reported risk estimates for the association between total, supplemental, and dietary magnesium intakes and risk of mortality were included. Random effects models were used. Nineteen publication with a total of 1,168,756 participants were included in the current meta-analysis. In total, 52,378 deaths from all causes, 23,478 from CVD, and 11,408 from cancer were identified during the follow-up period of 3.5 to 32 years. Dietary magnesium intake was associated with a lower risk of all-cause [pooled effect size (ES) 0.87; 95% CI 0.79, 0.97; P = 0.009; I2 = 70.7%; P less then 0.001] and cancer mortality (pooled ES 0.80; 95% CI 0.67, 0.97; P = 0.023; I2 = 55.7%; P = 0.027), but not with CVD mortality (pooled ES 0.93; 95% CI 0.82, 1.07; P = 0.313; I2 = 72.3%; P less then 0.001). For supplemental and total magnesium intakes, we did not find any significant associations with risks of all-cause, CVD, and cancer mortality. However, linear dose-response meta-analysis indicated that each additional intake of 100 mg/d of dietary magnesium was associated with a 6% and 5% reduced risk of all-cause and cancer mortality, respectively. In conclusion, higher intake of dietary magnesium was associated with a reduced risk of all-cause and cancer mortality, but not CVD mortality. Supplemental and total magnesium intakes were not associated with the risk of all-cause, CVD, and cancer mortality. These findings indicate that consumption of magnesium from dietary sources may be beneficial in reducing all-cause and cancer mortality and thus have practical importance for public health.The elongation step of translation is a key contributor to the abundance, folding and quality of proteins and to the stability of mRNA. However, control over translation elongation has not been thoroughly investigated. In this study, a Renilla-firefly luciferase fusion reporter system was further developed to investigate the in vitro elongation rate and processivity of ribosomes independent of the initiation and termination steps. The reporter mRNA was constructed to contain a single ORF encoding in-frame Renilla luciferase, a specific domain moiety and firefly luciferase. Such a reporter structure enables the quantitative and individual evaluation of the synthesis of a specific domain. As a proof of principle, the synthesis of three protein domains of different lengths and structures was analyzed. Using a cell-free translation assay, both the elongation rate and processivity of ribosomes were shown to vary depending on the domain synthesized. Additionally, a stalling sequence consisting of ten rare arginine codons notably reduced the elongation rate and the processivity of the ribosomes. All these results are consistent with the previously known dynamics of elongation in vivo. Overall, the methodology presented in this report provides a framework for studying aspects that contribute to the elongation step of translation.Urocleidus sayani n. sp. is described from the gills of pirate perch (Aphredoderus sayanus) in the Wisconsin backwaters of the upper Mississippi River and was found in samples from the Southeastern United States. Urocleidus sayani n. sp. is the second monogenean described from the pirate perch and the first for this host within Dactylogyridae. The description includes a partial 18S rRNA gene sequence (623 bp), filling a void in sequence data from North American monogeneans.Peroxisome-proliferator activator receptor γ (PPARγ) has an anti-inflammatory role that inhibits the nuclear factor-κB (NF-κB) pathway and regulates the expressions of pro-inflammatory proteins, whereas its role in parasitic meningoencephalitis remains unknown. In this study we investigated the role of PPARγ and related mechanisms in eosinophilic meningoencephalitis caused by the rat lungworm Angiostrongylus cantonensis. We observed increased protein NF-κB expression in mouse brain tissue using GW9662, which is the specific antagonist of PPARγ, in a mouse model of angiostrongyliasis. Then we investigated NF-κB-related downstream proteins, such as COX-2, NOSs, and IL-1β, with Western blot or enzyme-linked immunosorbent assay and found that the protein expression was upregulated. The results of gelatin zymography also showed that the MMP-9 activities were upregulated. Treatment with GW9662 increased the permeability of the blood-brain barrier and the number of eosinophils in cerebrospinal fluid. These results suggested that in angiostrongyliasis, PPARγ may play an anti-inflammation role in many inflammatory mediators, including NOS-related oxidative stress, cytokines, and matrix metalloproteinase cascade by decreasing the NF-κB action.

The most commonly cited argument for imposing or lifting various restrictions in the context of the coronavirus disease 2019 (COVID-19) pandemic is an assumed impact on the reproductive ratio of the pathogen. It has furthermore been suggested that less-developed countries are particularly affected by this pandemic. Empirical evidence for this is lacking.

Based on a dataset covering 170 countries, patterns of empirical 7-d reproductive ratios during the first months of the COVID-19 pandemic were analysed. Time trends and associations with socio-economic development indicators, such as gross domestic product per capita, physicians per population, extreme poverty prevalence and maternal mortality ratio, were analysed in mixed linear regression models using log-transformed reproductive ratios as the dependent variable.

Reproductive ratios during the early phase of a pandemic exhibited high fluctuations and overall strong declines. Stable estimates were observed only several weeks into the pandemic, with a mports the first quantitative empirical evidence that COVID-19 net transmissibility remains less controlled in socio-economically disadvantaged countries, even months into the pandemic. This needs to be addressed by the global scientific community as well as international politics.Nutritional epidemiological studies have frequently reported associations between higher (poly)phenol intake and a decrease in the risk or incidence of noncommunicable diseases. However, the assessment methods that have been used to quantify the intakes of these compounds in large-population samples are highly variable. This systematic review aims to characterize the methods used to assess dietary (poly)phenol intake in observational studies, report the validation status of the methods, and give recommendations on method selection and data reporting. Three databases were searched for publications that have used dietary assessment methods to measure (poly)phenol intake and 549 eligible full texts were identified. Food-frequency questionnaires were found to be the most commonly used tool to assess dietary (poly)phenol intake (73%). Published data from peer-reviewed journals were the major source of (poly)phenol content data (25%). An increasing number of studies used open-access databases such as Phenol-Explorer and USDA databases on flavonoid content since their inception, which accounted for 11% and 23% of the data sources, respectively. Only 16% of the studies reported a method that had been validated for measuring the target (poly)phenols. For future research we recommend 1) selecting a validated dietary assessment tool according to the target compounds and target period of measurement; 2) applying and combining comprehensive (poly)phenol content databases such as USDA and Phenol-Explorer; 3) detailing the methods used to assess (poly)phenol intake, including dietary assessment method, (poly)phenol content data source; 4) follow the Strengthening the Reporting of Observational Studies in Epidemiology-Nutritional Epidemiology (STROBE-nut) framework; and 5) complementing dietary intake assessment based on questionnaires with measurement of (poly)phenols in biofluids using appropriate and validated analytical methods.Dietary diversity has long been recognized as a key component of diet quality and many dietary diversity indicators (DDIs) have been developed. This systematic scoping review aimed to present a comprehensive inventory of DDIs and summarize evidence linking DDIs and dietary adequacy or health outcomes in adolescents and adults. Two search strategies were developed to identify peer-reviewed articles published in English up until June 2018 and were applied to Medline, Web of Science, and Scopus. A 2-stage screening process was used to select the studies to be reviewed. Four types of DDIs were identified among 161 articles, the majority of them belonging to the food group-based indicator type (n = 106 articles). Fifty studies indicated that DDIs were proxies of nutrient adequacy, but there was a lack of evidence about their relation with nutrients to limit. Associations between DDIs and health outcomes were largely inconsistent among 137 studies, especially when the outcomes studied were body weight (n = 60) and noncommunicable diseases (n = 41). We conclude that the ability of DDIs to reflect diet quality was found to be principally limited to micronutrient adequacy and that DDIs do not readily relate to health outcomes. These findings have implications for studies in low- and lower-middle-income economies where DDIs are often used to assess dietary patterns and overall diet quality.The state-resolved photodissociation of the CO(1Σ+) + S(1S0) photoproduct channel, formed by vacuum ultraviolet photoexcitation of OCS to a progression of the symmetric stretching vibration (ν1′) in the E and F states, has been investigated by using the time-sliced velocity map ion imaging technique. The total kinetic energy release spectra and the vibrational state specific anisotropy parameters (β) were obtained based on the raw images of S(1S0) photoproducts detected in the wavelength ranges of 134.40-140.98 nm, respectively. Except for vibrational band origins, the CO(1Σ+) photoproducts are found to have more significant populations at highly vibrationally excited states as the symmetric stretching vibrational excitation of the E and F states increases. Furthermore, the vibrational-state specific β values for the CO(1Σ+) + S(1S0) channel via the E and F states both show a sudden change from negative to positive in the vicinity of moderately vibronic levels of the E and F states. This anomalous phenomenon suggests that multiple excited states with different symmetries are involved in the photoexcitation process at relatively short photolysis wavelengths due to the strong vibronic couplings existing in the higher vibronic levels of the E and F states, and the formation of CO(1Σ+) + S(1S0) photoproducts may proceed by different nonadiabatic interactions from the prepared excited states to the lower dissociative state 1Σ+, with strong dependence of the initially symmetric stretching excitation in the Rydberg-type transitions.