Background: Due to the increasing amount of published data suggesting that endometrial carcinoma is a heterogenic entity with possible different treatment sequences and post-treatment follow-up, the Polish Society of Gynecological Oncology (PSGO) has developed new guidelines. Aim: to summarize the current evidence for diagnosis, treatment, and follow-up of endometrial carcinoma and to provide evidence-based recommendations for clinical practice. Methods: The guidelines have been developed according to standards set by the guideline evaluation tool AGREE II . The strength of scientific evidence has been defined in agreement with The Agency for Health Technology Assessment and Tariff System (AOTMiT) guidelines for scientific evidence classification. The grades of recommendation have been based on the strength of evidence and the level of consensus of the PSGO development group. Conclusion: Based on current evidence, both the implementation of the molecular classification of endometrial cancer patients at the beginning of the treatment sequence and the extension of the final postoperative pathological report of additional biomarkers are needed to optimize and improve treatment results as well as to pave the route for future clinical trials on targeted therapies. The Polish Society of Gynecological Oncology (PSGO) has developed the following recommendations for diagnosis, preoperative assessment for surgical treatment, radiotherapy, systemic treatment, treatment of recurrent disease and post-treatment surveillance of patients with endometrial carcinoma according to standards set by a guideline evaluation tool Appraisal of Guidelines for Research and Evaluation (AGREE) II .Recommendations apply to women over the age of 18 who suffer from endometrial carcinoma .The recommendations are intended for gynaecologists, gynaecological oncologists, surgeons, pathologists, geneticists, radiotherapists, clinical oncologists, general practitioners, palliative care specialists and allied health care professionals.Nomination of a multidisciplinary development group .Identification of scientific evidence.Formulation of guidelines.Assessment of coherence with ESGO/NCCN guidelines.Evaluation of guidelines by external reviewers.Integration of external reviewers’ comments with the original content of the guidelines.The PSGO guidelines were developed using a six-step process:The strength of scientific evidence was defined in agreement with The Agency for Health Technology Assessment and Tariff System (AOTMiT) guidelines for scientific evidence classification  Table 1Table 1.The grades of recommendation were based on the strength of evidence and level of consensus of the PTGO development group as described in Any clinician intending to apply PSGO guidelines is expected to perform a careful medical evaluation of individual clinical circumstances to determine the best course of patient care and/or treatment.For the first time, recommendations were developed according to standards set by the guideline tool Appraisal of Guidelines for Research and Evaluation (AGREE) II in gynaecologic oncology.The strengths of the guidelines are they are comprehensive and up-to-date.The limitation is the uncertainty of how many of the authors using guideline AGREE II were methodological experts.Recommendations indicate an urgent need for changes in the system of financing health services in Poland.The 2005 WHO classification (5th edition) identifies 10 histological subtypes of endometrial cancer  3,4,5,66,7,8 (sttype I—endometrioid carcinoma (adenocarcinoma) .type II—non-endometrioid carcinoma, which includes serous carcinoma, clear cell adenocarcinoma, undifferentiated and dedifferentiated carcinoma, mixed carcinoma of the endometrium and carcinosarcoma   is recommended for(1)Women with postmenopausal bleeding whose endometrial thickness is > 3 mm  (strengt(2)Women with adult granulosa cell tumour undergoing fertility-sparing treatment (with preservation of the uterus)  (strengt(3)Women with bleeding during tamoxifen treatment lasting up to 5 years    .The endometrial thickness cut-off at which biopsy in asymptomatic women in the general population  and in those with increased risk of endometrial cancer  *, which would have acceptable sensitivity and specificity, has not been established. Thus, an individual approach is recommended (expert opinion) (strength of evidence V) (grade of recommendation 2B). * Note: The management of endometrial hyperplasia (a precancerous condition) is a separate subject not covered by this recommendation.The sensitivity of endometrial biopsy  is 89% and the false-negative rate is 10%  .The report should specify the histological type, and for endometroid carcinoma, its differentiation grade assessed in two categories: low-grade (G1/G2) and high-grade G3) [ 3,4,5,6,65,6,7,8The existing scientific evidence indicates(1)The advantage of the new molecular classification over the former based solely on the type of endometrial cancer and grading in making therapeutic decisions at the beginning of treatment ,21,22 (s(2)A significantly higher concordance between pre- and postoperative results for the new molecular classification based on the ProMisE classifier and/or sequencing compared to previously considered features (type and grading) ,26,27,28(3)High sensitivity and specificity of the ProMisE classifier ,30 . A similar requirement applies to high-risk patients with comorbidities who do not qualify for surgical treatment (grade of recommendation 2A).A detailed description of the ProMisE classifier and comprehensive endometrial carcinoma diagnosis algorithm NGS+IHC is included in The centres where the diagnostic minimum (ProMisE molecular classification) cannot be performed may, in the transitional period, use existing criteria: type and grading (does not apply to the decision on fertility-sparing treatment and management of nonoperable cases) (grade of recommendation 3).The report should include a verified histological type, and for endometroid carcinoma, verified grading assessed in two categories: low-grade (G1/G2) and high-grade G3) [ 3,4,5,6,65,6,7,8If molecular classification was not performed at the time of the biopsy, it must be performed for the final report (at least a basic variant of ProMisE) (grade of recommendation 2B).LVSI invasion is a very important predictive factor indicating individual risk of recurrence and a decisive factor in the choice of adjuvant therapy   and does not include LVSI within the tumour and in the immediate vicinity of the tumour margin   is magnetic resonance imaging (MRI) with contrast ,36 .In justified cases, expert ultrasound can replace magnetic resonance imaging in the assessment of changes in the pelvis (grade of recommendation 2B).FIGO staging for endometrial carcinoma is shown in Standard surgery is a simple total hysterectomy with bilateral salpingo-oophorectomy (BSO) **; peritoneal fluid sampling for cytological examination is not recommended ,38  and total robotic hysterectomy (TRH)) does not compromise the prognosis and has a significant advantage in perioperative and postoperative outcomes over open surgery ,40  increases the number of complications and does not improve results  (strengt(1)Sparing treatment in women who want to preserve fertility and who have met the criteria * and achieved complete clinicopathological remission after hormone therapy  (strengt(2)No oophorectomy in women < 45 years old who have met the criteria ** ,43,44  and exclusion of metastatic disease (CT of the abdomen and chest); bioptate G1 TP53wt or every G when POLE  strengt.HNPCC) (Lynch syndrome).** Criteria: age < 45; FIGO I/II—necessary exclusion of FIGO IIIC by systematic lymphadenectomy or sentinel lymph node procedure in the group at high risk of metastases in radiologically negative lymph nodes (see indications for lymphadenectomy); and high risk of ovarian cancer excluded such as for BRCA1/2 mutation carriers or hereditary nonpolyposis colorectal cancer , does not affect overall survival and the time-to-recurrence; it is, however, associated with a significant number of complications   risk of metastases in radiologically negative lymph nodes (grade of recommendation 1).The goal of lymphadenectomy is to rule out the highly probable FIGO IIIC in this group of patients. The potential up-stage change is of prognostic significance  ;Non-endometroid carcinoma (high risk);TP53abn, every histological type (high risk);High-grade endometroid carcinoma excluding POLEmut (high risk) ,21,22  are as follows:Furthermore, in the group of patients at high risk of metastasis, lymphadenectomy should include the removal of radiologically negative pelvic and para-aortic lymph nodes up to the left renal vein because it increases overall survival  (strengtThe sentinel lymph node procedure can be considered to assess the status of the nodes (pN) ,55  is recommended ,62  and external beam radiation therapy (EBRT) are recommended (strength of evidence V) (grade of recommendation 1).There is a lack of randomised studies comparing different methods of radiotherapy (EBRT/BT) in the radical treatment of inoperable FIGO stage I/II endometrial cancer.Retrospective cohort studies have shown that the use of BT HDR in the radical treatment of inoperable endometrial cancer improves overall survival (OS) and progression-free survival (PFS) time  .Low-grade endometroid carcinoma with myometrial invasion > 50% excluding POLEmut (high-intermediate risk).Non-endometroid carcinoma (high risk).TP53abn, every histological type (high risk).High-grade endometroid carcinoma excluding POLEmut (high risk) ,21,22  with significant risk factors for metastasis to the lymph nodes, the following are recommended:In other cases, only BT should be used (expert opinion) (strength of evidence V) (grade of recommendation 2B).It is recommended that the intensity-modulated radiation therapy (IMRT)/VMAT technique or conformal radiotherapy be used in the area of the reproductive organs and lymph nodes. HDR brachytherapy should be planned based on CT or MRI performed after the insertion of the applicator (expert opinion) (strength of evidence V) (grade of recommendation 2B).Simple TLH/TRH/TAH with BSO is recommended; peritoneal fluid sampling for cytological examination and systematic lymphadenectomy is not recommended   is allowed only when the patient’s general condition is good  and when the operator can perform complete cytoreduction   , the recommended method of surgical treatment is en-block cancer resection with reconstruction of the gastrointestinal tract or * radical hysterectomy (expert opinion) (strength of evidence V) (grade of recommendation 2B).Systematic lymphadenectomy, in these cases, is not recommended ,50  (strength of evidence V) (grade of recommendation 2B).CAUTION: This applies to preoperative apparent FIGO I/II cases in which FIGO IIIA or IIIC was diagnosed postoperatively as a result of surgical staging and successfully resected cases of operable FIGO IIIB.Radiochemotherapy is a method of choice  ,69  (grade of recommendation 2B). In POLE and MMRd endometrial cancer subtypes, EBRT alone is recommended because the addition of chemotherapy (CHT) before and during irradiation is of no benefit in this group of patients   who are not eligible for surgery , the method of choice is EBRT including uterus and lesions in the pelvis depending on their location  and/or metastatic para-aortic lymph nodes combined with BT (uterus) (expert opinion) (strength of evidence V) (grade of recommendation 2B).It is recommended that the IMRT/VMAT technique or conformal radiotherapy be used in the area of reproductive organs and pelvic lymph nodes. HDR BT should be planned based on CT or MRI performed after the insertion of the applicator. In cases where radical treatment is not feasible, the method of choice is systemic treatment with or without palliative radiotherapy (expert opinion) (strength of evidence V) (grade of recommendation 2B).In patients with incomplete resection  or disseminated cancer, i.e., cases with unresectable metastases to the lungs or liver with a multifocal spread in the abdominal cavity (FIGO IVB) or with unresectable recurrence, the method of choice is systemic treatment (+/− radiotherapy) ,74,75,76The type of therapy should be selected individually considering the histological type, receptor status and/or molecular profile.For patients with low-grade endometroid carcinoma, it is recommended to determine the expression of E/P receptors (receptor status) because hormone therapy is a preferred option in this group (the percentage of objective responses (ORR) is 21.6%: ER + 26.5% and PR + 35.5%) (does not apply to cases with rapid progression of the disease)   after the use of aromatase inhibitors is low (7%), but due to the high (44%) clinical benefit (stabilisation and response)  , a carboplatin and paclitaxel regimen is recommended   [p = 0.046) [In the arm of patients receiving trastuzumab, a significantly longer median PFS was achieved, reaching 12.6 vs. 8.0 months   (strengt= 0.046)  (strengtp = 0.013) [p = 0.041) [A particular benefit of trastuzumab was observed in the first line of treatment with PFS of 17.9 vs. 9.3 months   (strengt= 0.041)   is the most favourable (recommended) therapeutic option in the group of HER2-positive patients (grade of recommendation 1).The standards for determining the status of the HER2 receptor are included in Based on the results of a randomised phase III trial   may only take place in clinically justified situations or when there are limitations in the availability of immunotherapy (grade of recommendation 3).When choosing chemotherapy, the patient should be informed of a significantly worse prognosis (expert opinion) (grade of recommendation 2B).In the entire population of patients with recurrent or advanced endometrial cancer, regardless of MMR/MSI status, the use of a combination of a PD-1 inhibitor (pembrolizumab) with a multiply tyrosine kinase inhibitor against VEGFR1, VEGFR2 and VEGFR3 (lenvatinib) was superior to chemotherapy (reduction in the risk of recurrence by 46% (HR of 0.54) and the risk of death by 38% (HR of 0.62)). The objective response rate (ORR) was 32%. The rate of serious adverse events was 89%, and 33% of patients discontinued therapy  (strengtIn a single-arm study  (strengtThe objective response rate (ORR) was 44% for dostarlimab     or disseminated cancer (FIGO IVB) or with unresectable recurrence who progressed after platinum-based chemotherapy (at least one cycle), the treatment of choice is immunotherapy ,74,75 (sMMRd)/MSI-H cancers may be treated with PD-1 inhibitors (dostarlimab or pebrolizumab) or with a combination of PD-1 inhibitor (pembrolizumab) and lenvatinib (grade of recommendation 1). Due to the high percentage of treatment discontinuation observed in the combo therapy of pembrolizumab and lenvatinib, monotherapy with PD-1 inhibitors is the preferred option in this group of patients (expert opinion—strength of evidence V) (grade of recommendation 2B).In the group of patients with a mismatch repair proficiency (MMRp), the treatment of choice is a combination of a PD-1 inhibitor (pembrolizumab) with lenvatinib (strength of evidence IIA) (grade of recommendation 1).There is no evidence that any post-treatment surveillance regimen for endometrial cancer improves patient survival time.The randomised TOTEM study assessed the role of intensive (INT) vs. minimalist (MIN) surveillance after the treatment of patients with endometroid carcinoma of the endometrium   (strength of evidence V) (grade of recommendation 2B).Extrapolating the results of the TOTEM study  and expeHNPCC) (Lynch syndrome).Hereditary nonpolyposis colorectal cancer    proteins [EPCAM deletions (EPCAM-MSH2) and thus has Lynch syndrome [In this group, every 8th woman  has a germinal mutation in the proteins   are detected in 3% of Lynch syndrome cases [me cases   and MSH2 (33%) and the lowest for mutations in MSH6 (26%) and PMS2 (10–12%) [The lifetime risk of developing colorectal cancer in the female population is 4.7%  (strengt(10–12%) ,87 (streMSH2 (51%) and MSH6 (49%) and the lowest for the mutations in MLH1 (34%) and PMS2 (12–24%) [The lifetime risk of developing endometrial cancer in the general population is 2.9%  (strengt(12–24%) ,86,87,88MSH2 mutation are affected the earliest (mean age 47) and MSH6 mutation carriers the latest (mean age 53) [Hereditary endometrial cancer is diagnosed in the fourth and fifth decades of life. Carriers of the  age 53)     verified pathologically;One is a first-degree relative of the other two;At least two successive generations affected;At least one relative is diagnosed before the age of 50;Familial adenomatous polyposis has been ruled out;Tumours should be verified by pathologic examination   are as follows:Other rare hereditary syndromes predisposing to endometrial cancer are described below.PTEN germline mutations (<1%) increase the risk of developing endometrial cancer by 25%   and susceptibility to treatment with platinum compounds and PARP inhibitors. In contrast, biallelic inactivation of  is rare   (Lynch syndrome) in BRCA1/2 (HBss/HBOC/HOC) and in PTEN (Cowden’s syndrome) should result in genetic testing among relatives to identify carriers of the germline mutation.Confirmation of mutations in In the case of Lynch syndrome, each family member with a confirmed mutation (regardless of gender) should undergo colonoscopy screening according to the Polish Society of Oncological Surgery (PSOS) recommendations (expert opinion) (strength of evidence V) (grade of recommendation 2B).Women (Lynch syndrome and Cowden syndrome) should be encouraged to have children early and be offered prophylactic hysterectomy after the completion of reproductive plans ,87,92  (strength of evidence V) (grade of recommendation 2B).BRCA1/2 (HOC/HBOC/HOC) [Prophylactic oophorectomy and salpingectomy are recommended in Lynch syndrome ,87 (streBOC/HOC)  (strengtPTEN (Cowden syndrome) germinal mutation, a prophylactic oophorectomy and salpingectomy are not recommended [In the case of ommended  (strengtBRCA1/2 germline mutation (HOC/HBOC/HOC), prophylactic hysterectomy is not recommended [In the case of the ommended  (strengt


Cognitive training has the potential to help older adults maintain or improve their cognitive abilities, but there has been debate regarding how susceptible cognitive outcomes in these studies are to placebo effects. Some previous research has found that expectations can shape performance on study outcomes, although this is not always a consistent finding. The degree to which perceived intervention efficacy can lead to changes in the performance of objective outcome measures typically assessed in these studies is unclear. The aim of the current study is to explore the effects of perceived effectiveness of cognitive training on actual improvements in a large sample of older adults. The current study utilized data from the Intervention Comparative Effectiveness for Adult Cognitive Training  Trial. Two hundred and thirty older adults (Mean age = 72) were randomized into one of four training conditions: (1) a web-based brain game suite, Brain HQ, (2) a strategy video game, Rise of Nations, (3) Instrumental Activities of Daily Living (IADL) training, or (4) an active control condition of puzzle solving. Reasoning, memory, processing speed, and IADL performance were measured before and after the intervention. Perceived efficacy of training in those outcome domains were also measured. Bayesian ANOVA analysis showed strong evidence of group differences in perceived efficacy within all outcome domains across the training conditions whereas Bayesian regression showed moderate to strong evidence against influences of perceived efficacy on changes in performance. Discussion will focus on implications of those results on behavioral and cognitive intervention designs.


A mental health promotion programme called ‘Healthy Me’, was a collaboration between Action Mental Health (AMH) MensSana, Child and Adolescent Mental Health Services (CAMHS) in the Southern Health and Social Care Trust and the Royal College of Psychiatry (RCPsych) in Northern Ireland in 2014. Adapting ‘Healthy Me’ for delivery in special schools was recommended in evaluation of this pilot programme. A co-produced pilot adapted ‘healthy me’ programme, for young people with ID was taken forward by Action Mental Health (AMH) MensSana and Intellectual Disability Child and Adolescent Mental Health Service (ID CAMHS) in the Southern Health and Social Care Trust (SHSCT). To determine the feasibility of adaptation and delivery of the programme for the needs of the ID population. To inform changes to be made before wider roll-out. To promote children's social and emotional well-being and emotional literacy through the teaching of problem-solving, coping skills, conflict management and managing feelings. To evaluate the effectiveness of this intervention with children being able to retain learning, information and ideas.Pre programme quiz July 2021 (young people)Post session 1–5 quizzes (young people)Post programme quiz October 2021 (young people)Simple visual blob tree (young people)Outcome MeasuresPre programme initial outcome measure (parent) The Mood, Interest and Pleasure Questionnaire-short form (MIPQ-S) July 2021Pre programme initial outcome measure (parent) non standardised, based on the strength and difficulties questionnaire (SDQ) and the Child and Youth Resilience Measure-Revised Person Most Knowledgeable version (PMK-CYRM-R) July 2021Post programme repeated outcome measure (parent) MIPQ-S October 2021Post programme repeated outcome measure (parent) Based on SDQ & PMK-CYRM-R October 2021EvaluationSix participants identified at outset and four attended and engaged consistently, young people aged between 14 and 17 years. Participants were supported 1:1 to fill in a simple evaluation forms after sessions rating their enjoyment and what they had learnt. Repeating the MIPQ-S with parents highlighted some improved scores indicating positive affect and elevated interest and pleasure.The programme will be offered to in the next stage of the pilot to Special Schools in NI. It is hoped to show that similar positive gains can be made in the school settings for children and young people with intellectual disability in terms of promoting positive mental health and social and emotional well-being.


Dear Editor et al. "The Prevalence of HPV Genotypes in Iranian Population: An Update", which pathologically mostly lead to Squamous intraepithelial lesions (9). Our findings suggested which Pap smear report is most associated with each serotype of HPV; however, the "No Inflammation" state is the most common among all serotypes (39.4%). Detailed HPV PCR test and Pap smear cross-tabulation results are shown in . We recommend cytologists report the presence of Anucleated squamous or Keratinized cells and exudates in the positive smears in order to prevent HPV-related Cancers in the population.Thus Type 16 is the most serotype involving in HPV infections among the average Iranian population , 6, 7, 8


ABSTRACT IMPACT: This project will use human neuron models and bioinformatics techniques to elucidate mechanisms of cocaine neurotoxicity, which will allow treatments to be developed for minimizing or preventing neurological damage caused by cocaine abuse and overdose. OBJECTIVES/GOALS: The goals of this project are to identify genes and gene networks altered by cocaine exposure in neurons (short term), and to use these pathways to understand mechanisms of cocaine neurotoxicity for the establishment of therapeutic targets (long term). METHODS/STUDY POPULATION: To study the molecular effects of cocaine, we generated preliminary proteomics and next-generation RNA sequencing (RNAseq) data from human postmortem prefrontal cortex (Broadmann area 9 or BA9) of 12 cocaine overdose subjects and 17 controls. Future directions for this project include RNAseq analysis of neuronal nuclei sorted from human postmortem BA9 and a human induced pluripotent stem cell-derived neuron (hiPSN) model of cocaine exposure from the same postmortem subjects from whom we have brain samples. RESULTS/ANTICIPATED RESULTS: We found alterations in neuronal synaptic protein levels and gene expression, including the serotonin transporter SLC6A4, and synaptic proteins SNAP25, SYN2, SYNGR3. Pathway analysis of our results revealed alterations in specific pathways involved with neuronal function including voltage-gated calcium channels, and GABA receptor signaling. In the future, we expect to see an enhancement in neuron-specific gene expression signatures in our sorted neuronal nuclei and our hiPSN model of cocaine exposure. The hiPSN model will help elucidate which effects are due to acute versus chronic exposure of cocaine. DISCUSSION/SIGNIFICANCE OF FINDINGS: Transcriptomic signatures found with this analysis can help us understand mechanisms of cocaine neurotoxicity in human neurons. With this work and future proposed studies, we can discover targetable molecular pathways to develop drugs that can reduce or reverse cocaine-related impairment.


Whereas previous studies have investigated life regrets, little attention has been paid to the important accomplishments older adults include in their autobiographic life narratives. Phenomenon such as the memory positivity effect suggest that accomplishments should be observed. We used a Health and Retirement Study 2017 Life History Mail Survey  to examine the characteristics of participants over age 65 who reported accomplishments (max = 3), what was reported, and whether early-life decisions about balancing family and work are associated with the reports. Women, whites, and people with at least high school education and normal cognitive status were more likely to report accomplishments (67%). We categorized reports as family-related (39%), personal (19%), combined family/personal (25%) or other (16%). Multinominal logistic regression models revealed that participants who themselves favored family over work in early life or whose spouse decided for family, were more likely to report family-related accomplishments.


Solanum (9), Ribes (8), Berberis (7), Hypochaeris (7) and Oxalis (6). Perennial herbs are the predominant life form (40%), followed by shrubs (35%), trees (14%), and annual and biannual herbs (11%). Fruits (35.8%), roots (21.5%) and leaves (20.0%) are the parts of plants consumed the most. Nine different food preparation categories were identified, with ‘raw’ forming the largest group (43%), followed by ‘beverages’ (27%), ‘savoury preparations’ (27%), and ‘sweet’ (13%). Almost all native Chilean WEPs have reported traditional food uses, while only a few of them have contemporary uses, with food products mainly sold in local and specialised markets. Species’ richness, taxonomic diversity and family representation have similar patterns to those observed for the world flora and other countries where surveys have been carried out. Some Chilean native WEPs have the potential to become new crops and important sources of nutritious and healthy products in the food industry. However, there are still many gaps in knowledge about their nutritional, anti-nutritional and biochemical characteristics; future research is recommended to unveil their properties and potential uses in agriculture and the food industry.Wild Edible Plants (WEPs) still play a vital role in the subsistence of many traditional communities, while they are receiving increasing recognition in tackling food security and nutrition at the international level. This paper reviews the use patterns of native WEPs in Chile and discusses their role as future crops and sources of food products. We conducted an extensive literature review by assessing their taxonomic diversity, life forms, consumption and preparation methods, types of use , and nutritional properties. We found that 330 native species were documented as food plants, which represent 7.8% of the total flora of Chile. These species belong to 196 genera and 84 families. The most diverse families are Asteraceae (34), Cactaceae (21), Fabaceae (21), Solanaceae (20) and Apiaceae (19), and the richest genera in terms of number of species are  The benefits derived from biodiversity are also at the heart of the Convention on Biological Diversity , with 109 WEPs (33.5%), followed by Rosids (Fabids (49 spp.) + Malvids (37) + Vitales (0)), with 86 WEPs (26.5%). Monocots contain 48 WEPs (14.8%), while gymnosperms and Monilophytes  have only 3 WEP species each . The perAccording to our revision, the main consumed parts of Chilean native WEPs are fruits and infructescences (35.8%), roots (21.5%), leaves (20.0%), seeds (9.1%), and stems (7.0%) . InfloreThe most frequent form of consumption was raw (43% of species) among the nine different categories , followeThe relation between the organs consumed and the preparation forms  showed tJubaea chilensis (Molina) Baill., an endemic Chilean palm tree; fruits and seeds are eaten fresh and used in sweet dishes; the sap is boiled to produce syrup , [binomial name + edible], [binomial name + beverages] and so on. All queries were made both in Spanish and English.Initial data were obtained from the database on the uses of Chilean native flora ) by Rodríguez et al., (2018) [http://www.plantsoftheworldonline.org/ (accessed on 12 February 2022)). The nomenclature follows the International Plant Name Index [The taxonomy of the species was updated based on the catalogue of the flora of Chile   and by rme Index  and the me Index , with whme Index , rgdal vme Index , dplyr vme Index  and doByme Index .Life forms and origins of Chilean native plants were obtained from the catalogue of the flora of Chile . To infeWe considered all species naturally occurring in Chilean territory and used as food and beverages as native wild edible plants (WEPs). According to the Economic Botany Data Collection standard (EBDCS) , plant uThe flora of Chile has a high number of native WEPs, some of which were domesticated by the original peoples of south-western South America before the Spanish conquest . In contrast, others were transformed or are the progenitors of important main crops that are part of the world food base, such as potatoes, quinoa, and Chilean strawberries. However, many more WEPs have the potential to become new crops and sources of new industrial food products in the future.Innovation based on Chilean WEPs requires strengthening both the biochemical studies to characterise the nutritional content of species in detail and agriculture research for the domestication of species and the development of breeding programmes enabling the creation of new crops.However, in the face of future social, cultural, economic, environmental and climatic change scenarios, the food development of native Chilean WEPs must be responsibly supported by sustainable consumption and food innovation, which require access to plant genetic material and the cultivation of these plants in line with international access and benefit-sharing agreements and the creation of sustainable value chains.


During October 2019, the West Virginia Bureau for Public Health (WVBPH) noted that an increasing number of persons who inject drugs (PWID) in Kanawha County received a diagnosis of HIV. The number of HIV diagnoses among PWID increased from less than five annually during 2016–2018 to 11 during January–October 2019 . KanawhaAfter suspension of the KCHD syringe services program (SSP) in March 2018 and a community-based SSP in April 2021 (because of concerns about program administration), a state lawAn HIV outbreak case was defined as a confirmed HIV diagnosis on or after January 1, 2019 in a PWID living in Kanawha County at the time of diagnosis. Investigators conducted qualitative interviews with 26 PWID and 45 community partners (including service providers),***As of October 27, 2021, 85 persons met the HIV outbreak case definition; 54 (52%) patients were male, 67 (79%) were aged 20–39 years at diagnosis, and 77 (91%) were non-Hispanic White. Forty patients (47%) had experienced unstable housing during the past year, and 73 (86%) had previous or current hepatitis C infection. Among 80 living persons, 20 (25%) had an HIV care visit during the preceding 90 days,Interview and medical record data indicated that methamphetamines and heroin were the most frequently injected drugs, and polysubstance use was common (57 [88%] of 65 patients). PWID reported reusing or sharing syringes, mainly because of limited access to sterile syringes after SSP closures. PWID expressed medical mistrust because of experiences of stigma and discrimination in health care settings. Medical record abstraction revealed that HIV screening tests were performed at fewer than one third of health care encounters before diagnosis, and none of the patients had been prescribed preexposure prophylaxis (PrEP). Prescriptions of naloxone for overdose prevention and medications for opioid use disorder were documented at fewer than a quarter of opioid-related health care encounters.Recommendations based on investigation findings and HIV surveillance data are guiding response activities.


Scientific Reports 10.1038/s41598-021-82092-9, published online 19 February 2021Correction to: The original version of this Article contained errors. Legends for Table 1 and Table 2 were reversed.Table 1 legend "List of all strains examined in this study with their GenBank accession numbers (BOLD ID). Geographic position and description of sample sites indicated."Hantzschia from studied material with similar taxa."now reads: “Comparison of species and strains of Hantzschia from studied material with similar taxa."Table 2 legend "Comparison of species and strains of now reads: "List of all strains examined in this study with their GenBank accession numbers (BOLD ID). Geographic position and description of sample sites indicated."These errors have now been corrected in the PDF and HTML versions of the Article.


This systematic review assesses variation in international and national guidelines on respiratory protection for health care professionals during the COVID-19 pandemic. We assessed variation in international and national guidelines on respiratory protection for HCPs in hospital settings during the first year of the COVID-19 pandemic.Conflicting evidence surrounding SARS-CoV-2 transmission, particularly airborne transmission, may have contributed to heterogeneous recommendations for respiratory protection across countries and organizations.PRISMA) reporting guideline. Infection prevention and control guidelines on respiratory protection for HCPs published from January 1 to December 31, 2020, by leading organizations in 4 countries and 2 international organizations were collected through a monthly consultation of their official websites  were excluded  and 59 guidelines (51.8%) were included. In January 2020, all initial guidelines recommended respirators  for HCPs in direct contact with patients with suspected or confirmed COVID-19 infection . After F3 The most recent assessment of the clinical evidence for the risk of transmission of acute respiratory infections to HCPs caring for patients undergoing AGPs dates back to a 2012 systematic review of a limited volume of studies .4 More evidence is still needed to clearly define what AGPs are and the level of risk associated with different procedures.5In this systematic review, we observed 4 strategies regarding the use of respirators: (1) systematic: recommended for care of COVID-19 patients, as in German guidelines; (2) flexible: recommended with use of MFs in the absence of available respirators, as in US and ECDC guidelines; (3) unit based, as in UK guidelines; and (4) recommended exclusively during AGPs, as in French and WHO guidelines. These discrepancies may reflect controversies related to SARS-CoV-2 transmission routes.6 Some guideline updates may have been dated incorrectly, representing the main study limitation.Initial uncertainties surrounding asymptomatic transmission of SARS-CoV-2 and the initial global shortage of MFs may explain some of the early delays in universal face-masking recommendations. The growing recognition of the role played by asymptomatic HCPs and the publication of a major positioning paper may have triggered the extension of face masking.Over the course of the COVID-19 pandemic, contextual factors  may have generated variability in recommendations owing to a lack of scientific evidence. Inconsistencies in respiratory protection guidelines between neighboring countries created confusion over optimal measures. Strong collaborations between national and international organizations are critical in such circumstances.


Ebolavirus cause severe and often lethal disease in humans: Sudan ebolavirus (SUDV), Bundibugyo ebolavirus (BDBV), Taï Forest ebolavirus (TAFV), and Zaire ebolavirus (EBOV) .,25.24,25While substantial progress has been made in the development of EBOV vaccines, multiple questions remain unanswered including the following: (1) what is the durability and the immediacy of immune responses generated by different vaccines; (2) what are the specific correlates and thresholds of protection; (3) do any interactions or interferences exist between vaccines and potential therapeutics; (4) what is the safety of these vaccines in special populations, particularly pregnant women and the immunocompromised; and (5) can vaccines be formulated to be stable for long-term storage at 2 to 8°C, which would be useful in endemic areas [Another major hurdle is mitigating the economic risks for manufacturers and distributors of EBOV vaccines since the demand may not be high enough to warrant stockpiling. Outbreaks also tend to occur in resource-poor countries leaving little financial incentive for commercial development. In January 2021, the International Coordinating Group (ICG) comprised of public and private benefactors established an Ebola vaccine stockpile in Sweden with the goal of manufacturing 500,000 doses. Stockpiling is an important step toward controlling EBOV outbreaks as it is critical for ensuring timely access to vaccines for at-risk populations .Ebolavirus: EBOV. Although multivalent vaccines  have and are being developed, no studies have specifically evaluated immune responses or efficacy against other Ebolavirus species . Future work should focus on the development of vaccines that confer protection across all medically relevant species of the genus Ebolavirus, bearing in mind that intraspecies mutations may also arise that impact vaccine effectiveness.Lastly, the most advanced vaccines are solely indicated for protection against one species of


ABSTRACT IMPACT: The pathophysiologic features of a metabolomic endotype that predicts patient outcomes due to sepsis have the potential to direct new therapies that target immune dysregulation and bioenergetic insufficiency. OBJECTIVES/GOALS: Acute respiratory failure (ARF) requiring mechanical ventilation is a frequent complication of sepsis and other disorders. It is associated with high morbidity and mortality. Despite its severity and prevalence, little is known about metabolic and bioenergetic changes that accompanying ARF. METHODS/STUDY POPULATION: In this study, semiquantitative and quantitative ultrahigh performance liquid chromatography mass spectrometry (UHPLC MS) analysis was performed on patient serum collected from the Trial with Acute Respiratory failure patients: evaluation of Global Exercise Therapies (TARGET). Serum from survivors (n=15) and nonsurvivors (n=15) was collected at day 1 and day 3 after admission to the medical intensive care unit as well as at discharge in survivors. Pathway analysis of the biochemical changes was performed to determine whether the disruption in specific metabolic pathways can identify the bioenergetic and metabolomic profile of these patients. RESULTS/ANTICIPATED RESULTS: Significant metabolomic differences were related to biosynthetic intermediates of redox cofactors nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP), increased acyl-carnitines, and decreased acyl-glycerophosphocholines in nonsurvivors compared to survivors. The metabolites associated with poor outcomes are substrates of enzymatic processes dependent on NAD(P), while the abundance of NAD cofactors rely on the bioavailability of dietary vitamins B1, B2 and B6. Changes in the efficiency of the nicotinamide-derived cofactors’ biosynthetic pathways also associate with an alteration of the glutathione-dependent drug metabolism as characterized by the substantial differences observed in the acetaminophen metabolome. DISCUSSION/SIGNIFICANCE OF FINDINGS: This metabolomic endotype represents a previously unappreciated association between severity of outcomes and micronutrient deficiency, thus pointing to new pharmacologic targets and highlighting the need for nutritional remediation upon hospitalization to improve patient outcomes due to ARF.


Senior adults’ reliance on the visual frame of reference for spatial orientation is a manifestation of an age-related shift in cognitive style from field independence to field dependence. We implemented a virtual reality rod and frame test (VR-RFT) to assess visual field dependence (VFD) in n=39 young adults (20-30 years old) and n=43 seniors (60 years old and above). The subjects were asked to determine subjective visual vertical (SVV) for 19 angles of frame tilt (running from -45 degrees to 45 degrees in steps of 5 degrees). The strong VFD of seniors was manifested not only by the increased error in the determination of SVV (SVVE) but also in its distribution. For small and large frame tilt angles, seniors’ SVVE skewness and kurtosis were greater than those of young adults. The SVVE median dependence on frame tilt may be accounted for with a phenomenological model whose two parameters describe the strengths of primary (P) and secondary (S) visual attractors which subjects use to infer SVV: the edges of the frame and its imaginary diagonals. For young adults, these parameters were: PY=14.91 and SY=12.51. For seniors, we observed an over 50% increase in the strength of the primary attractor PS=26.31 while the strength of the secondary one was only weakly affected by aging: SS=13.74. We demonstrate that the asymmetry between the strength of attractors significantly contributes to SVVE made by seniors at large frame tilts. We hypothesize that a variant VR-RFT may be used in rehabilitation to reduce excessive VFD.


Given the growing prevalence of Alzheimer’s Disease and related dementias, and the intensity of this population’s care needs, it is imperative that health plans (HPs) increase their dementia-capability. The Dementia Cal MediConnect (Dementia CMC) project proposes an innovative model of health care advocacy that can create dementia-capable systems change. The Dementia CMC project was a partnership (2013 – 2018) between local Alzheimer’s organizations and ten managed care HPs in California. It used the following model of health care advocacy: 1) Identify dementia-capable best practices to set as systems change indicators; 2) Identify and leverage public policies in support of systems change indicators; 3) Identify and engage champions; 4) Develop and advocate for a value and business case to improve dementia care; 5) Identify gaps in dementia-capable practices; 6) Provide technical assistance, tools, and staff training to address the gaps in dementia-capable practices; and 7) Track systems change. Systems change data was collected through participant observation with HPs and interviews with key informants. HPs reported making systems changes toward more dementia-capable practices such as: better pathways for identification and diagnosis; better identification, assessment, support, and engagement of caregivers; and improved systems of referral to Alzheimer’s organizations. Some indicators of systems change were inconclusive as a result of variability in HP practices and the lack of common record systems between HPs and providers. The application of this advocacy model has led to systems changes that can be replicated to improve care for people living with dementia and their caregivers.


Adequate sleep in hospitalised children is important for a variety of physiological and psychological processes associated with growth, development, and recovery from illness and injury. Hospitalisation often prioritises clinical care activities at the expense of age-appropriate sleep. Nurses and the wider healthcare team contribute to this paradox. However, through conscious practice and partnering with mothers, nurses are able to enact change and promote sleep.To adopt, adapt or contextualise existing guidelines to develop an evidence-based practice guideline to promote sleep-friendly ward environments and routines facilitated by nurses, and in partnership with mothers.A six-step methodology for guideline adaptation was followed, as recommended by the South African Guidelines Excellence project: (1) existing guidelines and protocols were identified and (2) appraised using the AGREE II instrument; (3) an evidence base was developed; (4) recommendations were modified, (5) assigned levels of evidence and grades of recommendation; and (6) end user guidance was developed. Expert consultation was sought throughout.Existing relevant guidance comprised 61 adult-centric recommendations. Modification of the evidence base led to six composited recommendations that facilitate sleep in hospitalised children: (1) prioritising patient safety; (2) collaborating with the mother or caregiver to promote sleep; (3) coordinating ward routine and (4) environment to improve sleep; (5) work with clinical and non-clinical staff; and (6) performing basic sleep assessments. Practice recommendations were aligned to the South African regulatory framework for nursing.Hospitalisation is a time of physiological and psychological dysregulation for children, which is amplified by poor sleep in a hospital. Nurses have the opportunity to promote sleep during hospitalisation by implementing this African-centric guideline in partnership with mothers. Sleep is crucial to the developmental processes of children Beebe , and is In critically ill adults, length of stay is adversely affected by in-hospital sleep disruption  was created. A guideline is a rigorously developed document that informs healthcare decisions through actionable recommendations  existing guidelines and protocols were identified and (2) appraised using the AGREE II instrument; (3) an evidence base was developed; (4) recommendations were modified and (5) assigned levels of evidence and grades of recommendation after which (6) end user guidance was developed. Expert consultation was sought throughout the process, particularly during the fourth and sixth stages of development. This methodology for guideline modification follows the recommendations made by the South African Guidelines Excellence (SAGE) project  approach  and staff. Involving mothers was crucial to the continuity of sleep for the child as sleep practices are known to vary by culture  and the website of the National Institute for Clinical Excellence (NICE United Kingdom [UK]), were performed to identify relevant guidance or policy documents. Keywords and MeSH terms included sleep, controlled environment, care, quiet (time), hospital, sleep and guideline or protocol. The search strategy was constructed using the P-C-C approach to aid definition of search terms and inclusion and exclusion criteria as summarised in Step 2: Appraisal of the existing guidelines: Identified sources were then screened for scope and purpose, and rigour of development using Domains one and three from the AGREE II instrument , contextualisation  and finally adaptation   resulted in the identification of 88 sources, whilst other methods identified 2345 sources (mostly grey literature). After de-duplication, a total of 2433 sources were screened by title and abstract or executive summary using the criteria described in The authors of the above sources were contacted and provided additional information that led to the identification of Elliott  and the AGREE II  safety and other special considerations, (2) collaboration with the bedside carer to promote individualised sleep, (3) coordination of the ward routine and (4) ward environment to improve sleep, (5) collaborating and communicating with staff and other persons to protect sleep and finally (6) performing a basic sleep assessment.The majority of modifications to the recommendations involved contextualisation, mainly for differences in resources and target population. As an example, original recommendations about a visitor policy were contextualised to accommodate the expected presence of a mother or other bedside carer. A sleep assessment tool for children was identified .A flowchart summary of recommendations is presented in The flowchart was incorporated into a poster summary together with an aide memoir: (1) safety first, (2) then a mother’s love; (3) next comes time; (4) low noise, dim light and calm. Pack the phone away, (5) collaborate with us; (6) then make sure sleep was enough.Sleep is disrupted during paediatric hospitalisation  Safety, (2) collaboration with the bedside carer to promote individualised sleep, coordination of the (3) ward routine and (4) ward environment to improve sleep, (5) involvement of the wider ward team and (6) sleep assessment. These recommendations and the supporting evidence-base are well-described in The second recommendation, concerning collaboration with the bedside carer, was adapted from original recommendations that encouraged family members and visitors to rest at home , we noted that children’s sleep needs differ in quantity by age, generally decreasing from infancy towards puberty  sleep during hospitalisation. However, nurses are ideally positioned to capitalise on time spent in hospital to aid children’s sleep through engagement and partnering with families, to promote health and enact their role as patient advocates. The guideline described throughout this article seeks to guide nurses to actively engage in sleep promotion for the hospitalised child. This evidence-based African-centric approach of partnering with families during hospitalisation exemplifies collaborative healthcare and holds the promise of benefits that extend beyond discharge home in resource-constrained contexts.


The dynamic interplay between dementia and psychological trauma can exert powerful effects on nursing home residents’ behavioral symptoms and quality of life. Our objectives in this exploratory study were to assess care aides’ perceptions of how often they worked with residents with past psychological trauma, the types of trauma encountered, and reasons for these beliefs. We conducted semi-structured cognitive interviews (n = 10) with care aides in June 2019 to inform the development of a trauma needs assessment (4 questions) that we included in a large survey of nursing staff (2019 - 2020). Care aides (n = 3761) were sampled from 91 randomly selected urban nursing homes stratified by health region, owner operator model, and size. We completed basic statistics and content analyses. Care aides identified residents they believed to have psychological trauma histories and provided reasons for their beliefs. Approximately 12% of the reported traumatic events were disclosed to staff. The most common, broad categories of trauma to emerge during analysis were abuse (40%) and war exposure (30%). Each had sub-categories. The most common categories of signs of trauma were re-experiencing symptoms such as flashbacks and nightmares (28%), and avoidance of specific triggers, such as water or intimate care (24%). The majority of the reported signs of trauma were persistent and distressing for staff and residents. Some behaviours assumed to be responsive behaviours of dementia may relate to traumatic stress symptomatology. Implementing trauma-informed supports for residents and care aides is essential to person-centred care and optimal quality of life.


The authors wish to make the following correction to their paper . In the All ingredients were assessed by Weender analysis. Dry matter (DM), crude ash (CA), crude protein (CP) and ether extract (EE) were analyzed in all feedstuff. Crude fiber (CF), neutral detergent fiber (NDF) and acid detergent fiber (ADF) were analyzed in the solid feed. In concentrate feed and TMR starch was analyzed and in concentrate feed additionally sugar was analyzed.


Although mindfulness therapies have demonstrated benefits for reducing stress and improving psychological symptoms in family dementia caregivers, the mechanisms underlying these salutary effects are unknown. We report a causal mediation pathway to improvement of stress symptoms in family dementia caregivers with Mentalizing Imagery Therapy (MIT), which employs mindfulness and guided imagery tools to reduce stress and improve understanding of self and others. In a randomized controlled trial of short-term 4-week MIT (N=24) versus a psychosocial support group (N=22), MIT demonstrated superior benefit for reducing perceived stress (p=.006). Increased trait mindfulness was a causal mediator of this effect (p=.02). Neuroimaging pre and post intervention found that increased mindfulness was associated with strengthened connectivity of the dorsolateral prefrontal cortex with an emotion regulation network (p<.001). The results are discussed in light of theories of cognitive control and may inform the design of future studies aimed at reducing family caregiver stress.


Structural isolation such as living alone poses a mental health risk in diverse groups of older adults, including older immigrants. Given that those living with others might also be disengaged, the present investigation included eating alone as another source of isolation and examined the impact of the combination of living and eating alone. The proposes of the study were to examine (1) how living and/or eating alone would impact mental distress, (2) whether the impact would be mediated by feelings of loneliness, and (3) if there would be gender differences in the mediation effect. The data were drawn from the Study of Older Korean Americans (SOKA), which surveyed older Korean immigrants in five states during 2017−2018. The living/eating arrangement was classified into four-groups: living/eating with others (57%), living with others/eating alone (12.4%), living alone/eating with others (7.3%), and living/eating alone (23.1%). Using the PROCESS macro, we tested the mediation effect of loneliness and the moderation effect of gender in the relationship between the typology and mental distress controlling for background/health characteristics and social capital related variables. Two groups  had sociodemographic, health, and social capital disadvantages. Analyses demonstrated that mental distress was linked with living with others/eating alone and living/eating alone, of which relationships were mediated by loneliness only among women. Findings suggest that not only structural isolation  but also disengagement with others  need to be considered to understand emotional well-being in older immigrant population and gender difference.


QuickDASH for use in assessment of limb function in patients with upper extremity lymphedema using modern psychometric techniques.This study aimed to evaluate and improve the accuracy and efficiency of the QuickDASH, and then fit the data to Samejima’s graded response model (GRM) and assessed the assumption of local independence of items and calibrated the item responses for CAT simulation.We conducted confirmative factor analysis (CFA) and Mokken analysis to examine the assumption of unidimensionality for IRT model on data from 285 patients who completed the QuickDash (r = 0.98). Items 2 (doing heavy chores) and 8 (limiting work or daily activities) were the most frequently used. The correlation among factor scores derived from the QuickDASH version with 11 items and the Ultra-QuickDASH version with items 2 and 8 was as high as 0.91.Initial CFA and Mokken analyses demonstrated good scalability of items and unidimensionality. However, the local independence of items assumption was violated between items 9 (severity of pain) and 11 (sleeping difficulty due to pain) (Yen’s Q3 = 0.46) and disordered thresholds were evident for item 5 (cutting food). After addressing these breaches of assumptions, the re-analyzed GRM with the remaining 10 items achieved an improved fit. Simulation of CAT administration demonstrated a high correlation between scores on the CAT and the QuickDash items we can obtain estimates that are very similar to those obtained from the full-length QuickDash without the need for CAT technology.By administering just these two best performing The online version contains supplementary material available at 10.1007/s11136-021-02979-y. The disabilities of the arm, shoulder, and hand (DASH) outcome measure is a widely used patient-reported outcome measure (PROM) assessing different disorders of the upper limb as well as the extent of impairments .QuickDASH (Online Appendix A), was developed in 2005 and comprises 11 items from the original 30-item DASH while still maintaining a strong correlation with the original DASH scores , whQuickDASH substantially, we found that a more efficient and precise estimation of disability level and symptom severity for American lymphedema patients can be achieved. In the meanwhile, the Concerto, as an emerging open-source CAT delivery platform, makes this CAT QuickDASH application in a real clinic setting possible [Ultra-QuickDASH mainly consisting of two best performing items and maintaining efficient and accurate estimations could be used as a CAT technology-free version of QuickDASH. Its application and promotion can break the obstacles of complex technology on health care professionals and providers on the use of CAT QuickDASH, making this super shortened instrument more convenient to apply into routine clinic practices.By utilizing CAT simulation based on the IRT framework to shorten the possible . All theQuickDASH Questionnaire (PDF 676 kb)Supplementary file1 Supplementary file2 (PDF 690 kb)QuickDASH Questionnaire (PDF 213 kb)Supplementary file3 Revised Below is the link to the electronic supplementary material.


The International Federation of Gynecology and Obstetrics (FIGO) stage remains the standard staging system for the assessment of endometrial cancer (EC) prognosis. Thus, we aim to identify the significant genes or biomarkers associated with the stage of endometrial cancer, which may also help reveal the mechanism of EC progression and assess the prognosis of patients with EC.We compared the mRNA expression levels of EC patients with stages I and II as well as stages III and IV in the Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) of EC patients at different stages were selected by volcano plot and Venn analysis. Gene Ontology (GO) and Pathways were applied to analyze the identified genes. Protein protein interaction (PPI) network was employed to identify the correlation. The survival analyses based on TCGA database were conducted for further screening. The Human Protein Atlas, quantitative PCR and immunohistochemistry were utilized to confirm the differences in expression of DEGs in endometrial cancer samples at different FIGO stages.CKMT1A was identified as a candidate gene. Through survival analyses, we found that CKMT1A may be a poor prognostic factor in the overall survival of endometrial cancer patients. GO and Pathways revealed that CKMT1A is closely associated with the metabolic process. More importantly, Human Protein Atlas and quantitative PCR confirmed the differences in expression of CKMT1A in endometrial cancer samples at different FIGO stages.CKMT1A is a newly identified essential tumor progression regulator of endometrial cancer, which may give rise to novel therapeutic strategies in the management of endometrial cancer patients to prolong its prognosis and prevent tumor progression.In summary, this study shows that  Endometrial cancer (EC) is one of the most common malignant tumors in the female reproductive tract . AccordiSOX11) hypomethylation is an independent poor prognostic marker in EC  and poor histological differentiation . In a multivariate analysis, histological differentiation  and FIGO stage  were found to be the independent predictors of tumor progression among the patients with endometrial cancer  and the difference of stage  were independent prognostic factors for the OS of patients with endometrial cancer Click here for additional data file.S2 TableLogFC: FoldChange.(DOC)Click here for additional data file.S3 TableLogFC: FoldChange.(DOC)Click here for additional data file.S4 TableBP: Biological Process; MF: Molecular Function; CC: Cellular Component; FDR: false discovery rate.(DOC)Click here for additional data file.S5 TableFDR: false discovery rate.(DOC)Click here for additional data file.S6 Table(DOC)Click here for additional data file.S7 Table(DOC)Click here for additional data file.


However, very few studies addressed its role in amyotrophic lateral sclerosis (ALS). Dominguez et al.3 recently brought some negative findings on this topic: (i) the genetic inactivation of receptor-interacting protein kinase (RIPK)1 did not protect against motor neuron degeneration in the superoxide dismutase (SOD)1 model of ALS and (ii) phosphorylated (p)-RIPK1 did not accumulate in the spinal cords of ALS compared to non-ALS patients. These findings raise doubts about the implication of necroptosis in the pathophysiology of ALS. In contrast, other studies detected robust activation of RIPK1, RIPK3, and mixed lineage kinases domain-like (MLKL) proteins in preclinical as well as clinical studies of ALS7. The discrepancies between these studies5 and others8 might be explained by (i) the use of western blotting in whole-tissue extracts8 versus in situ immunolabelling targeting motor neurons7, (ii) the removal of circulating blood cells—a rich source of necroptotic markers9—in some studies but not in others, (iii) the various time frame of tissue sampling, which matches or not the transient expression of necroptotic markers10, or (iv) technical limitations in the availability and specificity of in vivo tools of detection of necroptotic markers8.Interest in potential implications of necroptosis Fig. —i.e., a 7, including in situ experiments focusing selectively on the cells of upmost interest, i.e. motor neurons of the anterior horn of the spinal cord7. In contrast, the studies showing the absence of activation of necroptosis assessed only one molecular step of the cascade (p-RIPK1 or unphosphorylated RIPK1)5 were often untargeted on specific neural cells, and not always targeting the phosphorylation of key necroptotic markers, which are fundamental to demonstrate the execution process of necroptosis -α14.Altogether, the final conclusion about the role of necroptosis in ALS and the interplay between the various molecular mediators and cell subtypes involved would deserve further descriptive clinical findings on larger cohorts of ALS patients, as well as preclinical studies. Such research should combine pharmacological or genetic modulations of necroptotic signaling in ALS models to uncover the pathophysiological mechanisms potentially at play in the occurrence of ALS and define the key check points of putative intervention


In recent years several new drugs have been approved for treatment of heart failure and type 2 diabetes. Despite their life-prolonging benefits, uptake of new drugs is often slow among older patients with frailty due to under-representation of frail older adults in pivotal clinical trials and concerns for adverse events. To optimize pharmacotherapy, timely evaluation of the drug benefits and risks is urgently needed. We propose a novel drug monitoring framework that prospectively evaluates the effectiveness and safety of newly marketed drugs for frail and non-frail patients in real-world databases. This framework utilizes a validated claims-based frailty index (CFI)  to find early signals for effectiveness and safety of new drugs by updating the analysis at regular intervals as new data become available. In this symposium, we present early results of this prospective monitoring framework for 2 new drug classes using Medicare claims data from the approval date until the end of 2017: 1) angiotensin receptor-neprilysin inhibitor (ARNI) (approved in July 2015) for heart failure with reduced ejection fraction (HFrEF) and 2) sodium-glucose cotransporter-2 inhibitors (SGLT2i) (approved in March 2013) for type 2 diabetes. We first show the uptake of ARNI and SGLT2i over time among the eligible Medicare beneficiaries by clinical characteristics, including frailty. Subsequently we present the results of sequential cohort analysis for the effectiveness and safety results of ARNI and SGLT2i. After these presentations, the panel will discuss the strengths, limitations, and challenges of implementing our monitoring framework in real-world databases.


GamePlan4Care (GP4C) is a web-based adaptation of the Resources for Enhancing Alzheimer’s Caregiver Health II (REACH II) caregiver intervention, redesigned and reformatted for online delivery. The goal of GP4C is to create an online family caregiver support platform that facilitates self-directed exposure to evidence-based skills-training and support for dementia caregivers. This approach of utilizing technology enhanced with live support has the potential for scalability and sustainability. In preparation for an ongoing randomized clinical trial, the GP4C platform underwent industry standard user interface/user experience (UI/UX) testing with dementia caregivers as part of an iterative design process. Testing of caregiver’s reaction to technical and content-related aspects of the system was conducted with 31 caregivers. The thematic analysis revealed three themes for technical aspects  and two themes for content aspects (satisfaction and engagement). We will discuss technical and content modifications resulting from UI/UX.


Maine has a growing number of age-friendly community initiatives (AFCIs); 116 communities are actively working to adapt the social, service, and built environments for aging and 71 have formally joined the AARP Network of Age-Friendly States and Communities. During COVID, rural municipalities were faced with dynamic changes that limited older resident’s access to services and social engagement. To overcome these limitations, it is critical for emergent AFCIs to have tools and strategies to maintain and further enhance healthy environments and resilient communities. This study uses group interviews with 6 leaders of established AFCIs and 6 leaders of emergent AFCIs to explore how the Lifelong Fellows Program, a peer mentoring model that matches experienced leaders with newly formed initiatives, was able to spur development of new strategies to build community resilience. Prominent themes were (1) engaging new local and regional partners; (2) intergenerational volunteerism; (3) fun and flexibility; and (4) relationship-building.


A 14-year-old male adolescent, with no notable medical history presented to a medical consultation with pain and swelling in the left testicle of 5 months duration. Physical examination revealed scrotal varicosities, with small testicular volume. Doppler ultrasound (US) of the left pampiniform plexus and the renal vessels confirmed varicocele grade 3,  and revealed an associated nutcracker phenomenon . Computed tomography (CT) scan with contrast showed also the compression of the left renal vein (RV) between the superior mesenteric artery (SMA), and the abdominal aorta (AO) confirming the nutcracker phenomenon (NCS) (1) . Our patient was treated by inguinal varicocelectomy and had a partial resolution of symptoms after. He was then referred to a nutritionist to increase BMI in order to treat the NCS, before proceeding to invasive methods. Doppler ultrasound of the renal vessels must be performed in case of left varicocele to assess for an associated NCS (2).


We report 4 cases of COVID-19 in kidney transplant recipients (KTRs) 2 of them after 2 doses of Covishield vaccine and another 2 after a single dose. The study is approved by the Institutional Ethics committee. We also abided by the Declaration of Helsinki and Declaration of Istanbul principles. None of them reported any minor or major side effects postvaccination. The probable exposure was community acquired in all the 4 cases. Three patients were on triple immunosuppression. Three cases required critical care admission and received steroids, remdesivir, anticoagulation, and investigational therapies  as anti-COVID-19 therapy during the stay. Patient 1 died and patients 2 and 3 are on mechanical ventilation with a poor prognosis  has been reporting global peaks in India in April 2021. The enormous task of vaccinating such a bulk population has become more difficult in the state where health resources for managing coronavirus disease 2019 (COVID-19) are rapidly emptying amid the COVID-19 surge. Indian advisories have approved 2 vaccines: Oxford–AstraZeneca COVID-19 (Covishield) and BBV152 (Covaxin) as of April 2021. The efficacy of these vaccines has been reported lesser compared with the mRNA vaccines in general population.The authors express our sincere gratitude to all the resident doctors and healthcare staffs who are tirelessly doing a mammoth job of managing the COVID-19 cases in India, despite facing resource crisis.


In this study, the gamma radiation properties of four types of surgical-grade stainless steel  were investigated. The effective atomic number Z Technological development in various fields has increased the quality of life of patients by improving health services. In some circumstances, medical interventions require the use of metal materials with biocompatible compositions and properties, such as stainless steel. Stainless-steel materials are used as biocompatible mineral components for rebuilding teeth, manufacturing medical devices used in surgeries and other applications ,2. StainFour different samples of stainless steel were studied in this work. The chemical compositions and densities of the stainless steel used in this study are shown in The main parameter of photon penetration in samples is the mass attenuation coefficient Equation  23]:(1):(1)μm, wi relative to the total number of atoms of all elements in the alloy, and ith element in the alloy.Equation  shows thEquation  23]: (3: (3Δ(μm)Equation  [23]:(4)The effective atomic number Equation .(5)ZeffThe half-value layer  24,25],25Zeff),I and The linear and mass attenuation coefficients were evaluated by using an X-ray fluorescent (XRF) system. The XRF energies produced from pure metal plates were irradiated to the annular source of radioactive The mass attenuation coefficients of surgical stainless-steel samples obtained in the photon energy range of 17.50–25.29 keV using XRF beams from Mo, Pd, Ag and Sn are listed in HVL is an important parameter in the design of radiation protection and refers to the thickness of the sample required to absorb half the value of the radiation falling on it. The results of theoretically and experimentally calculated HVL values are presented in An experimental XRF system and the WinXCOM program were used to evaluate the mass attenuation coefficient (


A large number of common cold outbreaks in Hong Kong schools and childcare centers during October–November 2020 led to territorywide school dismissals. Increased susceptibility to rhinoviruses during prolonged school closures and dismissals for coronavirus disease and varying effectiveness of nonpharmaceutical interventions may have heightened transmission of cold-causing viruses after school attendance resumed.  Many countries implemented school closures and dismissals in 2020 as a public health measure to reduce spread of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In Hong Kong, schools were dismissed after the Lunar New Year holiday in late January 2020 and remained dismissed until late May; during early July–late September, schools were dismissed again in response to a surge in cases of COVID-19 , panel A>3 students in the same class each developing >2 symptoms of respiratory tract infection within 4 days  occurred in Hong Kong schools despite a wide range of infection control measures being in place. Staff and students wore face masks at all times; lunch hours were cancelled, desks were spaced out, and group activities were limited (


Scalds are the most common mechanism of burn in children, and a significant proportion of these injuries are associated with bathing. Burns sustained while bathing present a unique opportunity for injury prevention; previous studies have examined lowering water heater temperatures, however reputable infant bathing educational resources do not explicitly recommend avoiding running water and the risks that it could pose. In an effort to inform prevention programs, this study seeks to determine the incidence and circumstances of running water in bathing scald burns at our institution.A retrospective review was performed of records from an American Burn Association verified center over a ten year period (1/1/2010 to 12/31/2019). This center treats both children and adults and is affiliated with an academic hospital in a major urban center. The burn database was queried for scald injuries in children less than three years involving bathing. The Child Advocacy and Protective Services team provides inpatient consultation for all children less than three years old with burn injuries allowing us to analyze the specific events surrounding the bathing scald burns in this cohort.A total of 123 patients met inclusion criteria. Three bathing safety risk factors were specifically noted in the chart review: (1) running water, (2) lack of caregiver presence for duration of bathing, and (3) failure of caregiver to check water temperature before bathing. Of the cases identified, 107 (87%) had clear documentation of running water as part of the history of injury, 66 (54%) cases involved failure of caregiver to check the water temperature before bathing and 53 (43%) cases did not have a caretaker present for the duration of the bath. In cases with only one risk factor, running water was identified in 34 (94%) out of 36 cases, and in cases with one or two risk factors, running water remained the primary risk factor with 38 (90%) out of 42 cases. When looking at the combination of risk factors, only three (2%) cases had no risk factors while 77 (63%) involved two or more risk factors.The vast majority of bathing burn injuries in this series involved running water. In addition, a significant number of scald burns occurred from running water alone, even without the other identified risk factors. Conversely, only 2% of scald burns associated with bathing featured none of these three risk factors, suggesting that these injuries could be greatly impacted by safe bathing education.


Genetic networks that regulate meristem transitions were recurrent targets of selection during crop domestication and allow fine-tuning of plant architecture for improved crop productivity. Solanum lycopersicum) and that were recurrent targets of selection during crop domestication and breeding. Fine-tuning the activity of conserved regulators of meristem transitions allows re-balancing vegetative to reproductive growth to customize plant architecture for improved crop productivity.Flowering plants display enormous architectural diversity that mainly results from differences in the position and organization of branches within vegetative and reproductive shoot systems. Where and when branches develop are tightly linked to the onset of flowering, which triggers the release of lateral buds from apical dominance and the outgrowth of additional branches. The transition to flowering depends on the activity of apical meristems, which are small groups of stem cells located at the growing tips of shoots. During vegetative growth, apical meristems produce vegetative organs including leaves and stem until endogenous and environmental signals prompt the transition to reproductive development, which often culminates in the production of an inflorescence, the flower-bearing shoot. It becomes clear that the rate at which meristems transition from the vegetative to the reproductive phase determines the number and pattern of branches in shoots and inflorescences . Not surConserved regulators of meristem transitions were recurrent targets of crop domestication and breeding.Changes in the activity of conserved meristem regulators result in quantitative variation in shoot and inflorescence architecture.Tuning the expression of conserved meristem regulators by genome editing allows engineering plant architecture for crop improvement.de novo domestication of wild species.Targeting conserved meristem regulators by genome editing facilitates the rapid improvement of underutilized crops and Meristem maturation and plant architecture are omnigenic traits and dependent on genotypic context and environmental conditions.vegetativeness that changes gradually during plant development  and pepper (Capsicum annuum)) and multiflowered inflorescences (e.g. tomato and related wild species). The evolution of Solanaceae inflorescence diversity involved changes in the rate of meristem maturation, which are driven by an increased transcriptional divergence of conserved regulatory genes during a critical developmental window that marks the transition to reproductive development  that is released in the axil of the last leaf. This process of floral termination and sympodial meristem release is reiterated indeterminately and results in the production of modular structures  that consist of a shoot with a terminal flower, resulting in a compound shoot that is characteristic for sympodial plants. In tomato, sympodial growth is recapitulated in inflorescences where each inflorescence meristem releases a sympodial inflorescence meristem at its flank before terminating in a flower, which results in the zig-zag arrangement of flowers on the tomato inflorescence.self-pruning (sp) mutation, which transformed indeterminate tomato vines into determinate bushes with concentrated fruit set that allows mechanical harvesting in large-scale field production  and belongs to the CETS  gene family (SP encodes an antiflorigen that acts as a repressor of flowering and antagonizes the activity of SINGLE FLOWER TRUSS (SFT), another CETS gene and homolog of Arabidopsis FLOWERING LOCUS T (FT). SFT encodes the universal flowering hormone florigen and triggers the transition of meristems to reproductive growth , the ortholog of Arabidopsis LEAFY , a flowering repressor that belongs to the CETS gene family  and other closely related wild species rapidly transition to flowering  is associated with higher SFT expression and accelerated flowering in short days  and antiflorigen (TFL1) takes place through competition for bZIP transcription factors that are bound to cis-regulatory elements of floral identity genes -engineered sp null mutants  to obtain highly compact and early yielding varieties that are optimized for indoor cultivation  by genome editing transforms sympodial meristems into inflorescence meristems that terminate in single flowers  and MACROCALYX (MC) are mutated  mutants carry mutations in the homeobox transcription factor gene S/SlWOX9, a homolog of Arabidopsis WUSCHEL-RELATED HOMEOBOX9, WOX9 , which is a homolog of Arabidopsis UNUSUAL FLORAL ORGANS and encodes an F-box protein that interacts with the transcription factor FA to form a floral specification complex and trigger floral differentiation  develop highly branched inflorescences with dozens of flowers but have been largely avoided by breeders due to low fruit set . These nX9, WOX9 . Naturaled genes . This derescence . Completntiation . S/SlWOXntiation . Loss ofAN depends on the activity of TERMINATING FLOWER (TMF), which encodes an ALOG (Arabidopsis LSH1 and Oryza G1) transcriptional regulator that directly represses AN expression  genes and the quadruple tmf tfam123 mutant was shown to develop single-flowered inflorescences on all shoot systems  transcriptional regulators (BOP1–3), which are co-expressed with TMF during vegetative meristem stages and decline toward floral identity  mutation induces strong inflorescence branching and reduced fruit set in specific genetic backgrounds (j2 mutation is caused by a Rider transposon insertion in a SEPALLATA (SEP) class MADS -box transcription factor gene and induces inflorescence branching in genetic backgrounds that carry a secondary mutation in the homologous gene ENHANCER OF JOINTLESS2 (EJ2)  results in flowers with elongated sepals while complete loss of EJ2 activity from CRISPR null mutations lead to leaf-like sepals. Importantly, j2 and ej2 single mutants develop unbranched inflorescences, but epistasis between the homologous genes causes excessive inflorescence branching and low fertility in j2 ej2 double mutants. Expression analyses of j2 ej2 double mutants uncovered misexpression of meristem stage-enriched marker genes at transition and floral stages of meristem maturation suggesting that j2 ej2 branching results from delays in meristem maturation (LONG INFLORESCENCE (LIN) also affect inflorescence architecture and lead to inflorescences with additional flowers and longer internodes that weakly branch. Triple j2 ej2 lin mutants give rise to inflorescence meristems that fail to achieve floral identity and produce cauliflower-like inflorescence tissue similar to the an mutant, demonstrating that J2, EJ2, and LIN genes synergistically regulate inflorescence complexity. Interestingly, the Arabidopsis genome encodes four SEP gene homologs, which redundantly regulate floral organ differentiation , breeders reported that the causative kgrounds . The j2 S2 (EJ2) . The secanscript . The natturation . Mutationtiation . Hence, j2 andW ej2 mutations by selecting additional genetic loci that suppress inflorescence branching /SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1)-class MADS-box transcription factor gene (SISTER OF TM3 (STM3) leads to lower STM3 expression and suppression of branching. Both EJ2 and STM3 copy number variants were present as cryptic variants in the domesticated tomato germplasm before j2 andW ej2 collided during modern breeding, illustrating how standing genetic variation contributes to breeding. Complete loss of STM3 activity in CRISPR-induced stm3 null mutants leads to late flowering indicating that STM3 promotes meristem maturation toward the transition to flowering  branching in a gene dosage-dependent manner , determinate shoot growth from a mutation in CsTFL1 is modulated in a day-length sensitive manner by the homologous gene CsTFL1d (The genetic networks that regulate meristem transitions are highly plastic and tightly linked to environmental changes . Howevernditions . The del equator . However CsTFL1d . In toma CsTFL1d . The und CsTFL1d .de novo domestication has been tested in wild relative species of tomato and rice (cis-regulatory regions allows the generation of quantitative phenotypic variation, for example, allelic series of domestication genes that can be used to fine-tune agricultural traits (Understanding the genetic changes that were selected by humans for adapting plants to new climatic regions can outline strategies for the development of novel genotypes for agriculture during climate change. Pan-genomes of crops and their wild ancestors allow the identification of genes and networks that were altered during domestication and breeding to modulate architectural plasticity. The standing genetic variation that is preserved in crop germplasms already presents a rich resource for adapting crops to new growth conditions. However, introducing genetic variation to new genotypic backgrounds can be challenging due to genetic linkage with deleterious alleles and often leads to unexpected phenotypic outcomes due to genetic interactions . Genome and rice . By targand rice . Genome and rice . Finallyl traits . TogetheHow are the effects of conserved meristem regulators modified in different genetic backgrounds, and what is the identity of the interacting genes?How do we uncouple the gene networks that regulate successive stages of meristem maturation to independently exploit shoot and inflorescence architecture for crop improvement?Is architectural diversity in crop populations mainly established by quantitative variation in a small number of conserved regulators or rather by variation in a large and diverse set of genes?What is the genetic architecture of plasticity in meristem development that relays environmental change to plant architecture?What is the impact of domestication and breeding on plasticity in meristem maturation?


This Correction follows an Expression of Concern relating to this article previously published by Portland Press.Biosci Rep (2018) 38(6): BSR20181414; DOI: 10.1042/BSR20181414) would like to correct The Authors of the original article “Antioxidative and antiphotoaging activities of neferine upon UV-A irradiation in human dermal fibroblasts” (The Authors state that this error had occurred during the figure making process, and confirm that it does not affect the conclusions of their study. The correct version of


Little is known about the disparities in patient experience of home health (HH) care related to social vulnerability. This study examined the relationships of patient Medicare-Medicaid dual eligible status and race and ethnicity with patient experience of HH care. We analyzed national data from the Home Health Care Consumer Assessment of Healthcare Providers and Systems (HHCAHPS), Outcome and Assessment Information Set, Medicare claims and Area Health Resources File for 11,137 Medicare-certified HH agencies (HHA) that provided care for Medicare beneficiaries in 2017. Patient-reported experience of care star ratings (1-5) in HHCAHPS included 3 domains  with each dichotomized into high (4-5) and low (1-3) experience of care. The proportion of patients with dual eligibility and the proportion of racial/ethnic minorities were summarized at the HHA level. HHA with higher proportion of dual eligible patients were less likely to have high experience of care rating in professional care delivery , effective communication , and specific direct care issues . HHA with higher proportion of racial/ethnic minorities were also less likely to have high patient experience of care rating across all three domains . Disparities in patient experience of HH care exist and they are associated with low income and racial/ethnic minority status, indicating substantial unmet needs among these socially vulnerable patients.


OBJECTIVES/GOALS: This study’s goal is to examine the feasibility and acceptability of using VRM to impact the APP of adults in the inpatient setting. Aims include examining the: 1) feasibility of VRM for APP management; 2) acceptability of using VRM for APP management; and 3) experience of VRM for APP management. METHODS/STUDY POPULATION: To comprehensively examine participants’ experience of using VRM for APP, this study will employ a convergent mixed-methods design in which living kidney donors (N = 45) will be recruited to serially use VRM during their hospital stay. Feasibility and acceptability will be evaluated using descriptive and inferential statistics evaluating patient-reported outcome (PRO) measures taken pre-, post- and 1-hour post-VRM, PRO measures extracted from the participant’s electronic health record and data on VRM use. Semi-structured interviews will allow formulation of inferences based on participants’ experience of VRM for APP management and their insights on content, deployment, and clinical use of VRM. RESULTS/ANTICIPATED RESULTS: This in-process study expects: 1) an adequate sample of participants undergoing living kidney donor surgery who agree to enroll with retention of >90% of participants (Aim 1); 2) participants to report VRM as an acceptable and suitable treatment, feel “present” and interested in the VR environment, and feel comfortable using VRM in the hospital (Aim 2); and 3) to provide insight into participants’ experience of VRM for APP, understanding of extended VRM use for APP analgesia, examination of key variables affecting participants’ experience of VRM for APP and feedback about VRM procedures and protocol to inform future VRM use for APP management (Aim 3). DISCUSSION/SIGNIFICANCE OF IMPACT: Results of the proposed study will inform future clinical testing and deployment of VRM, guide future use of VRM as an adjunct for inpatient APP management, and provide insight into inpatients’ experience of VRM for APP analgesia.


We examined cross-sectional and prospective associations of sleep duration and insomnia symptoms with measures of cognitive function among older adults aged 45-75 y from the Boston Puerto Rican Health Study, a longitudinal cohort of 1500 participants of Puerto Rican ancestry. We found, statistically significant cross-sectional associations of sleep duration (hours) and an executive function domain before  and after  controlling for covariates ; between sleep duration and global cognition before  and a trend after controlling for covariates . In longitudinal associations, sleep duration (time2) was significantly associated with global condition at time3  after controlling for time2 global cognition. In conclusion, we found hours of sleep and insomnia symptoms significantly associated with various cognitive factors. A public health focus on sleep hygiene may improve cognitive health outcomes in older Puerto Rican adults.


ABSTRACT IMPACT: Better understanding how clinicians make decisions about pain management, particularly since our prior research has demonstrated that opioids prescribed at discharge is the strongest predictor of opioids taken, is critical to decrease high-risk medication prescribing while preserving high-quality care. OBJECTIVES/GOALS: (1) Identify major biological, psychological, and social determinants of medical and surgical residents’ pain management decisions; (2) Determine salient themes regarding the experience of residents in the management of acute and chronic pain METHODS/STUDY POPULATION: Focus groups of internal medicine and general surgery residents at an academic, tertiary care training hospital located in an urban setting were conducted. Due to the COVID-19 pandemic, all focus groups were conducted virtually and occurred during required didactic sessions to facilitate participation. All interviews were recorded and transcribed. Two reviewers independently reviewed and coded the data following the principles of constructivist grounded theory. RESULTS/ANTICIPATED RESULTS: 42 residents participated in ten focus groups ranging in size from two to five individuals. Six themes emerged demonstrating salient BPS factors in pain management decisions: (1) patient and clinician expectations determine what is considered normal/acceptable; (2) inability of pain scales to reliably capture patient pain; (3) desire for more objective methods of pain assessment, while simultaneously recognizing that pain is an inherently subjective experience; (4) difficulty in determine when pain is 'real’ or 'legitimate'; (5) lack of education and protocols regarding pain management; (6) the importance of engaging other services such as acute pain service or nurse educators in complicated situations. Junior residents often expressed doubt in the appropriateness of their approaches and decisions. DISCUSSION/SIGNIFICANCE OF FINDINGS: Surgical and medical trainees routinely treat pain and may struggle, particularly in the early phases of training, to determine if pain levels are appropriate. There is also a lack of education and/or best practices for assessing and managing pain. These areas represent high-value, clinician-focused targets for future interventions to improve care.


Psychosocial care for residents with serious mental illness (SMI) requires understanding of co-morbidities and careful attention to needs, rights, and preferences. Analyses of social services directors (SSDs) responses (n=924) to the National Nursing Home Social Service Director Survey considered perceived roles and competence to provide care stratified by the percentage of NH residents with SMI. Depression screenings and biopsychosocial assessments were common roles regardless of the percentage of residents with SMI. About one-quarter lacked confidence to train colleagues in recognizing distinctions between depression, delirium and depression (23.4% unable) or to develop care plans for residents with SMI (26% unable). A bachelor’s degree  or less  was associated with less perceived competence in care planning compared to those with a master’s degree. SSDs reported less involvement in referrals or interventions for resident aggression in homes with a high proportion of residents with SMI.


With the development of real-time and visualized neuroimaging techniques, the studies on the central mechanism of acupuncture analgesia gain increasing attention. The experimental pain models have been widely used in acupuncture-analgesia neuroimaging studies with quantitative and controlled advantages. This review aimed to analyze the study design and main findings of acupuncture neuroimaging studies to provide reference for future study. The original studies were collected and screened in English databases  and Chinese databases . As a result, a total of 27 articles were included. Heat stimulation and electroacupuncture were the mostly used pain modeling method and acupuncture modality, respectively. The neuroimaging scanning process can be divided into two models and five subtypes. The anterior cingulate cortex and insula were the most commonly reported brain regions involved in acupuncture analgesia with experimental pain models. Acupuncture has been used for alleviating pain in China and other oriental countries for thousands of years. It has been accepted as an alternative or complementary therapy for pain in western countries. Nearly half of the 64 recommended indications of acupuncture by WHO , Chinese Biomedical Literature Database (CBM), the Chongqing VIP Database (VIP), and the Wanfang Database (WF). The literature search was conducted from database inception 11th Nov 2020. Details of search terms were modified for each database and depicted in The article was included if (1) it was an original article, (2) experimental pain stimulation was conducted on participants, (3) participants received acupuncture as intervention, and (4) the study was performed with neuroimaging techniques . ArticleThe process of the data selection is described in Information including the year of publication, the corresponding author , the trial place, the method of modeling, the acupuncture intervention , the pain assessment, the neuroimaging techniques, and the results of brain regions involved in acupuncture analgesia were extracted.A total of 27 neuroimaging studies with experimental pain models performing on healthy participants were included in this review.The first study was published in 1980 in Chinese. Sixteen of these 27 studies were conducted in China, and 9 studies in the United States. There were 13 corresponding affiliations mentioned; the top two were Massachusetts General Hospital (6 studies) and Peking University (4 studies).The pain modeling methods included heat stimulation (11 studies), electrical stimulation (4 studies), pressure stimulation (3 studies), injections of hypertonic saline (2 studies), potassium iontophoresis stimulation (2 studies), cold pain stimulation (1 study), video stimulation (1 study), tactile stimulation (1 study), stabbing stimulation (1 study), and capsaicin allodynia stimulation (1 study) on healthy participants .Thirteen studies chose manual acupuncture (MA), and 12 studies chose electroacupuncture (EA) as the intervention method. Besides, the transcutaneous electrical nerve (TENS) and transcutaneous electric acupoint stimulation (TEAS) were applied in one study, respectively .Hegu (LI 4) (9 studies), Zusanli (ST 36) (8 studies), and Sanyinjiao (SP 6) (4 studies) were the most frequently used acupoints in these studies .Fifteen studies assessed the pain with the Visual Analogical Scale (VAS), and three studies applied the Gracely Sensory and Affective Scales (GSAS). Other pain assessment scales are shown in Twenty-one studies applied fMRI, two studies used event-related potentials (ERP), two studies used electroencephalogram (EEG), one study used arterial spin labeling (ASL), and one study used both fMRI and PET as neuroimaging techniques .Similar scanning processes were sorted together regardless of the scanning time and repetition times. Scanning processes can be divided into model 1 and model 2 based on whether the pain stimulation was a part of task scanning. Subsequently, according to the sequence of pain stimulation, model 1 was divided into three subtypes [model 1-A .The reported deactivated/activated brain regions are shown in This review mainly described the current status of the central mechanism research of acupuncture analgesia based on the experimental pain model and neuroimaging techniques.Since early 1980, researchers have applied the electrical experimental pain model to investigate the central mechanism of acupuncture analgesia based on the ERP technique  (Hegu (LI 4) (9 studies)  were theThis review showed that VAS is the preferred scale for assessing pain. Using VAS was previously recommended in both research and clinical practice with the advantages of its simplicity and adaptability  was the most used technique of these 27 studies. fMRI indirectly measures brain activity by detecting associated changes in blood flow (hemodynamic response) , affective , and cognitive factors   The selection of the types of experimental pain could be broadened but not limited to the neuropathic pain on the skin. (2) Researchers can evaluate the pain from multimodal dimensions and using more objective assessment methods to guarantee the objective results and profoundly shape the experience of pain. (3) Researchers can use the neuroimaging technologies to compare the central mechanisms of EA and MA at different acupoints, different stimulations, and different intensities, to give the reference for the selection of the clinical treatment.ZF and LS designed the study. MP, CS, and QY participated in screening studies. YT and XK extracted the data from the included studies. HZ and CS performed the analysis plan. MP, SR, and YT drafted the article. ZF revised the draft. All authors have read and approved the publication of the final article.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.