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Tripterygium wilfordii Hook F (TwHF)-based therapy is among the most efficient and crucial therapeutics for the treatment of rheumatoid arthritis (RA), which indicates that TwHF is a potential source of novel anti-RA drugs. However, accumulating studies have observed that TwHF-based therapy induces multi-organ toxicity, which prevents the wide use of this herb in clinical practice, although several recent studies have attempted to reduce the toxicity of TwHF. Notably, our research group developed a "Clinical Practice Guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in the Treatment of Rheumatoid Arthritis" (No. T/CACM 1337-2020) approved by the China Association of Chinese Medicine to standardize the clinical application of TwHF-based therapy and thus avoid adverse effects. Although great strides have been made toward the characterization of TwHF-based therapy and revealing its underlying pharmacological and toxicological mechanisms, several crucial gaps in knowledge remain as potential barriers to enhance its therapeutic effects on the premise of safety assurance. This review offers a global view of TwHF, ranging from its chemical constituents, quality control, clinical observations, and underlying pharmacological mechanisms to toxic manifestations and mechanisms. We focus on the important and emerging aspects of this field and highlight the major challenges and strategies for using novel techniques and approaches to gain new insights into unresolved questions. BAY 2402234 price We hope that this review will improve the understanding of TwHF application and draw increasing interdisciplinary attention from clinicians that practice both Chinese and Western medicine, basic researchers, and computer scientists.How do children develop associations among number symbols? For Grade 1 children (n = 66, M = 78 months), sequence knowledge (i.e., identify missing numbers) and number comparison (i.e., choose larger number) predicted addition, both concurrently and indirectly at the end of Grade 1. Number ordering (i.e., touch numbers in order) did not predict addition but was predicted by number comparison, suggesting that magnitude associations underlie ordering performance. In contrast, for Grade 2 children (n = 80, M = 90 months), number ordering predicted addition concurrently and at the end of Grade 2; number ordering was predicted by number comparison, sequencing, and inhibitory processing. Development of symbolic number competence involves the hierarchical integration of sequence, magnitude, order, and arithmetic associations.

Determine if antibiotic prescribing patterns differ for in-person versus virtual clinic visits for acute rhinosinusitis (ARS).

Cross sectional study.

All adult virtual clinical encounters from March to May 2020 with a principal diagnosis of ARS were reviewed for demographic data and the presence or absence of an antibiotic prescription during the coronavirus shut down in Massachusetts. In-person clinical encounters from March to May 2019 were similarly examined as a control. The rate of antibiotic prescription was compared between virtual (2020) and in-person (2019) visits for ARS diagnoses.

There were 2,075 patients in March to May 2020 and 3,654 patients March to May 2019 who received an ARS principal diagnosis at their virtual and in-person outpatient visits, respectively. There was a statistically significant lower rate of antibiotic prescriptions for ARS in 2020 (72.1%) versus 2019 (76.7%).The odds ratio for an antibiotic prescription for ARS was 0.783 (95% confidence interval, 0.693-0.86; P < .001) for patients seen in the 2020 cohort versus the 2019 cohort. The compared rates for antibiotic prescribing for 2020 versus 2019 were not different in individual month-to-month comparisons. When stratified by otolaryngology providers there was no statistically significant difference of antibiotic prescriptions between the 2019 and 2020 cohort (P = .781).

During the massive transition to virtual visits for March to May 2020 due to the coronavirus pandemic shut down in Massachusetts, the total rate of outpatient antibiotic prescribing for ARS was lower in the virtual visit environment compared to the traditional in-person visit. In this scenario, telemedicine did not result in an increase in antibiotic prescribing despite the lack of an in-person physical exam.

IV Laryngoscope, 2020.

IV Laryngoscope, 2020.

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm infants. Survivors may suffer both short- and long-term morbidities. Current evidence suggests that the incidence of NEC can be reduced by standardizing the care delivery in addressing key risk factors including an altered gut microbiome, use of formula milk, hyperosmolar feeds, and unrestricted use of high-risk medications METHODS Since 2014, the department has a workgroup who analyzed all cases of NEC within a month of diagnosis to identify preventable risk factors. Existing evidence-based quality improvement strategies were revised and new ones were implemented sequentially over the next 4 years. These strategies include (1) a standardized feeding protocol, (2) early initiation of enteral feeding using human milk, (3) optimization of the osmolality of preterm milk feeds using standardized dilution guidelines for additives, and (4) promotion of healthy microbiome by use of probiotics, early oral care with colostrum anrth-weight (VLBW) infants dropped from 7% in 2014 to 0% (P less then .001) in 2018. The duration of parenteral nutrition, use of central line, and days to full feeds were also reduced significantly (P less then .05) CONCLUSION Adopting evidence-based best practices resulted in a significant decrease in the incidence of NEC and improved the nutrition outcomes in VLBW infants.

The zona incerta (ZI) and ventral tegmental area (VTA) are brain areas that are both implicated in feeding behaviour. The ZI projects to the VTA, although it has not yet been investigated whether this projection regulates feeding. We experimentally (in)activated the ZI to VTA projection by using dual viral vector technology, and studied the effects on feeding microstructure, the willingness to work for food, general activity and body temperature. Activity of the ZI to VTA projection promotes feeding by facilitating action initiation towards food, as reflected in meal frequency and the willingness to work for food reward, without affecting general activity or directly modulating body temperature. We show for the first time that activity of the ZI to VTA projection promotes feeding, which improves the understanding of the neurobiology of feeding behaviour and body weight regulation.

Both the zona incerta (ZI) and the ventral tegmental area (VTA) have been implicated in feeding behaviour. The ZI provides pro projecting to the VTA, we used a combination of canine adenovirus-2 in the VTA, as well as Cre-dependent designer receptors exclusively activated by designer drugs (DREADD) or tetanus toxin (TetTox) light chain in the ZI. TetTox-mediated inactivation of ZI to VTA projection neurons reduced food-motivated behaviour and feeding by reducing meal frequency. Conversely, DREADD-mediated chemogenetic activation of ZI to VTA projection neurons promoted food-motivated behaviour and feeding. (In)activation of ZI to VTA projection neurons did not affect locomotor activity or directly regulate core body temperature. Taken together, ZI neurons projecting to the VTA exert bidirectional control overfeeding behaviour. More specifically, activity of ZI to VTA projection neurons facilitate action initiation towards feeding, as reflected in both food-motivated behaviour and meal initiation, without affecting general activity.Threat-related information strongly competes for attentional selection, and can subsequently be more strongly represented within visual working memory. This is particularly the case for individuals reporting high trait anxious personality. The present study examined the role of anxiety in both attention and memory-related interactions with threat. We employed a hybrid working memory/visual search task, with participants preselected for low and high anxious personality traits. They selected and memorized an emotional face (angry or happy) appearing together with a neutral face in encode displays. Following a delay period, they matched the identity of the memorized face to a probe display item. Event-related markers of attentional selection (N2pc components) and memory maintenance during the delay period (i.e., CDA) were measured. Selection biases toward angry faces were observed within both encode and probe displays, evidenced by earlier and larger N2pcs. A similar threat-related bias was also found during working memory maintenance, with larger CDA components when angry faces were stored. High anxious individuals showed large selection biases for angry faces at encoding. For low anxious individuals, this bias was smaller but still significant. In contrast, only high anxious individuals showed larger CDA components for angry faces. These results suggest that threat biases in attentional selection are modulated by trait anxiety, and that threat biases within working memory may only be present for high anxious individuals. These findings highlight the key role of individual differences in trait anxiety on threat-related biases in visual processing, especially at the level of working memory maintenance.

Limited data are available on the real-world effectiveness and safety of systemic therapies for advanced (surgically unresectable and/or metastatic) epithelioid sarcoma (ES).

A retrospective medical records review was conducted in patients with advanced ES who were initiating first-line or ≥2 lines of systemic therapy (2000-2017) at 5 US cancer centers. The real-world overall response rate (rwORR), the duration of response (rwDOR), the disease control rate (rwDCR) (defined as stable disease for ≥32 weeks or any duration of response), and progression-free survival (rwPFS) were assessed by radiology reports. Overall survival (OS), rwDOR, and rwPFS were estimated from the time therapy was initiated using the Kaplan-Meier method. Serious adverse events were assessed.

Of 74 patients (median age at diagnosis, 33 years; range, 10.6-76.3 years), 72% were male, and 85% had metastatic disease. The median number of lines of therapy was 2 (range, 1-7 lines of therapy), and 46 patients (62%) received ≥2 lines of systemic therapy. First-line regimens were usually anthracycline-based (54%) or gemcitabine-based (24%). For patients receiving first-line systemic therapy, the rwORR was 15%, the rwDCR was 20%, the median rwDOR was 3.3 months (95% CI, 2.1-5.2 months), the median rwPFS was 2.5 months (95% CI, 1.7, 6.9 months), and the median OS was 15.2 months (95% CI, 11.4-21.7 months). For those who received ≥2 lines of systemic therapy, the rwORR was 9%, the rwDCR was 20%, the median rwDOR was 4.5 months (95% CI, 0.7-5.6 months), and the median rwPFS was 6.0 months (95% CI, 3.2-7.4 months). Over one-half of patients (51.4%) experienced an adverse event, most frequently febrile neutropenia (14%), pain (10%), anemia, dyspnea, fever, thrombocytopenia, or transaminitis (5% each).

Systemic therapies demonstrate limited efficacy in patients with advanced ES and have associated toxicities.

Systemic therapies demonstrate limited efficacy in patients with advanced ES and have associated toxicities.

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