In humans, neuroligin-3 mutations are associated with autism, whereas in mice, the corresponding mutations produce robust synaptic and behavioral changes. However, different neuroligin-3 mutations ...cause largely distinct phenotypes in mice, and no causal relationship links a specific synaptic dysfunction to a behavioral change. Using rotarod motor learning as a proxy for acquired repetitive behaviors in mice, we found that different neuroligin-3 mutations uniformly enhanced formation of repetitive motor routines. Surprisingly, neuroligin-3 mutations caused this phenotype not via changes in the cerebellum or dorsal striatum but via a selective synaptic impairment in the nucleus accumbens/ventral striatum. Here, neuroligin-3 mutations increased rotarod learning by specifically impeding synaptic inhibition onto D1-dopamine receptor-expressing but not D2-dopamine receptor-expressing medium spiny neurons. Our data thus suggest that different autism-associated neuroligin-3 mutations cause a common increase in acquired repetitive behaviors by impairing a specific striatal synapse and thereby provide a plausible circuit substrate for autism pathophysiology.
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•Neuroligin-3 mutations commonly enhance repetitive motor routines in mice•Repetitive behavior requires neuroligin-3 function in the nucleus accumbens•Neuroligin-3 is selectively essential in D1-dopamine receptor-containing neurons•Neuroligin-3 deletion impairs synaptic inhibition on striatal medium spiny neurons
Different neuroligin-3 mutations cause a common enhancement of repetitive behaviors by a selective effect in one particular type of medium spiny neuron in one particular brain region, the nucleus accumbens of the ventral striatum, in mice.
Radio Frequency Identification (RFID) has been identified as a crucial technology for the modern 21st century knowledge-based economy. Some businesses have realised benefits of RFID adoption through ...improvements in operational efficiency, additional cost savings, and opportunities for higher revenues. RFID research in warehousing operations has been less prominent than in other application domains. To investigate how RFID technology has had an impact in warehousing, a comprehensive analysis of research findings available from articles through leading scientific article databases has been conducted. Articles from years 1995 to 2010 have been reviewed and analysed with respect to warehouse operations, RFID application domains, benefits achieved and obstacles encountered. Four discussion topics are presented covering RFID in warehousing focusing on its applications, perceived benefits, obstacles to its adoption and future trends. This is aimed at elucidating the current state of RFID in the warehouse and providing insights for researchers to establish new research agendas and for practitioners to consider and assess the adoption of RFID in warehousing functions.
Rapid demographic, epidemiological, and nutritional transitons have brought a pressing need to track progress in adolescent health. Here, we present country-level estimates of 12 headline indicators ...from the Lancet Commission on adolescent health and wellbeing, from 1990 to 2016.
Indicators included those of health outcomes (disability-adjusted life-years DALYs due to communicable, maternal, and nutritional diseases; injuries; and non-communicable diseases); health risks (tobacco smoking, binge drinking, overweight, and anaemia); and social determinants of health (adolescent fertility; completion of secondary education; not in education, employment, or training NEET; child marriage; and demand for contraception satisfied with modern methods). We drew data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016, International Labour Organisation, household surveys, and the Barro-Lee education dataset.
From 1990 to 2016, remarkable shifts in adolescent health occurred. A decrease in disease burden in many countries has been offset by population growth in countries with the poorest adolescent health profiles. Compared with 1990, an additional 250 million adolescents were living in multi-burden countries in 2016, where they face a heavy and complex burden of disease. The rapidity of nutritional transition is evident from the 324·1 million (18%) of 1·8 billion adolescents globally who were overweight or obese in 2016, an increase of 176·9 million compared with 1990, and the 430·7 million (24%) who had anaemia in 2016, an increase of 74·2 million compared with 1990. Child marriage remains common, with an estimated 66 million women aged 20–24 years married before age 18 years. Although gender-parity in secondary school completion exists globally, prevalence of NEET remains high for young women in multi-burden countries, suggesting few opportunities to enter the workforce in these settings.
Although disease burden has fallen in many settings, demographic shifts have heightened global inequalities. Global disease burden has changed little since 1990 and the prevalence of many adolescent health risks have increased. Health, education, and legal systems have not kept pace with shifting adolescent needs and demographic changes. Gender inequity remains a powerful driver of poor adolescent health in many countries.
Australian National Health and Medical Research Council, and the Bill & Melinda Gates Foundation.
In a test-negative case–control study involving 1482 vaccinated health care workers and 3449 controls, the BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines were 88.8% and 96.3% effective, respectively, at ...preventing symptomatic Covid-19. Efficacy was similar in subgroups according to age (<50 or ≥50 years), racial and ethnic groups, underlying conditions, and various levels of patient contact.
Objective: To assess the prevalence of metabolic syndrome and its association with sociodemographic, clinical and lifestyle variables among Australian patients with a variety of psychiatric ...disorders.
Design and setting: Cross‐sectional study of patients attending a public mental health service in Western Australia between July 2005 and September 2006.
Participants: Patients who were aged 18–65 years; diagnosed with schizophrenia, schizoaffective disorder, bipolar disorder, major depressive disorder with psychotic symptoms, drug‐induced psychosis or borderline personality disorder; and currently taking at least one antipsychotic drug for a minimum of 2 weeks.
Main outcome measures: Prevalence of metabolic syndrome diagnosed with International Diabetes Federation criteria; fasting blood glucose and lipid levels; sociodemographic and lifestyle characteristics.
Results: Of 219 patients invited to participate, 203 agreed and had complete data. Prevalence of metabolic syndrome was 54% overall, and highest among patients with bipolar disorder or schizoaffective disorder (both 67%), followed by schizophrenia (51%). Sociodemographic variables, including age and ethnic background, were not significantly associated with metabolic syndrome, but a strong association was seen with mean body mass index. Other cardiovascular risk factors, such as smoking and substance misuse, were common among participants.
Conclusions: Prevalence of metabolic syndrome in this population was almost double that in the general Australian population, and patients with schizophrenia had a prevalence among the highest in the developed world. Prevalence was also high in patients with a variety of other psychiatric disorders.
Complete metastatic ablation of oligometastatic prostate cancer may provide an alternative to early initiation of androgen deprivation therapy (ADT).
To determine if stereotactic ablative ...radiotherapy (SABR) improves oncologic outcomes in men with oligometastatic prostate cancer.
The Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer (ORIOLE) phase 2 randomized study accrued participants from 3 US radiation treatment facilities affiliated with a university hospital from May 2016 to March 2018 with a data cutoff date of May 20, 2019, for analysis. Of 80 men screened, 54 men with recurrent hormone-sensitive prostate cancer and 1 to 3 metastases detectable by conventional imaging who had not received ADT within 6 months of enrollment or 3 or more years total were randomized.
Patients were randomized in a 2:1 ratio to receive SABR or observation.
The primary outcome was progression at 6 months by prostate-specific antigen level increase, progression detected by conventional imaging, symptomatic progression, ADT initiation for any reason, or death. Predefined secondary outcomes were toxic effects of SABR, local control at 6 months with SABR, progression-free survival, Brief Pain Inventory (Short Form)-measured quality of life, and concordance between conventional imaging and prostate-specific membrane antigen (PSMA)-targeted positron emission tomography in the identification of metastatic disease.
In the 54 men randomized, the median (range) age was 68 (61-70) years for patients allocated to SABR and 68 (64-76) years for those allocated to observation. Progression at 6 months occurred in 7 of 36 patients (19%) receiving SABR and 11 of 18 patients (61%) undergoing observation (P = .005). Treatment with SABR improved median progression-free survival (not reached vs 5.8 months; hazard ratio, 0.30; 95% CI, 0.11-0.81; P = .002). Total consolidation of PSMA radiotracer-avid disease decreased the risk of new lesions at 6 months (16% vs 63%; P = .006). No toxic effects of grade 3 or greater were observed. T-cell receptor sequencing identified significant increased clonotypic expansion following SABR and correlation between baseline clonality and progression with SABR only (0.082085 vs 0.026051; P = .03).
Treatment with SABR for oligometastatic prostate cancer improved outcomes and was enhanced by total consolidation of disease identified by PSMA-targeted positron emission tomography. SABR induced a systemic immune response, and baseline immune phenotype and tumor mutation status may predict the benefit from SABR. These results underline the importance of prospective randomized investigation of the oligometastatic state with integrated imaging and biological correlates.
ClinicalTrials.gov Identifier: NCT02680587.
Facemask use is associated with reduced transmission of SARS-CoV-2. Most surveys assessing perceptions and practices of mask use miss the most vulnerable racial, ethnic, and socio-economic ...populations. These same populations have suffered disproportionate impacts from the pandemic. The purpose of this study was to assess beliefs, access, and practices of mask wearing across 15 urban emergency department (ED) populations.
This was a secondary analysis of a cross-sectional study of ED patients from December 2020 to March 2021 at 15 geographically diverse, safety net EDs across the US. The primary outcome was frequency of mask use outside the home and around others. Other outcome measures included having enough masks and difficulty obtaining them.
Of 2,575 patients approached, 2,301 (89%) agreed to participate; nine had missing data pertaining to the primary outcome, leaving 2,292 included in the final analysis. A total of 79% of respondents reported wearing masks "all of the time" and 96% reported wearing masks over half the time. Subjects with PCPs were more likely to report wearing masks over half the time compared to those without PCPs (97% vs 92%). Individuals experiencing homelessness were less likely to wear a mask over half the time compared to those who were housed (81% vs 96%).
Study participants reported high rates of facemask use. Respondents who did not have PCPs and those who were homeless were less likely to report wearing a mask over half the time and more likely to report barriers in obtaining masks. The ED may serve a critical role in education regarding, and provision of, masks for vulnerable populations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose: Nasopharyngeal cancer (NPC) is a common cancer in Hong Kong, and relapse can occur frequently. Using protein chip profiling
analysis, we aimed to identify serum biomarkers that were useful ...in the diagnosis of relapse in NPC.
Experimental Design: Profiling analysis was performed on 704 sera collected from 42 NPC patients, 39 lung cancer patients, 30 patients with the
benign metabolic disorder thyrotoxicosis (TX), and 35 normal individuals (NM). Protein profile in each NPC patient during
clinical follow up was correlated with the relapse status.
Results: Profiling analysis identified two biomarkers with molecular masses of 11.6 and 11.8 kDa, which were significantly elevated
in 22 of 31 (71%) and 21 of 31 (68%) NPC patients, respectively, at the time of relapse (RP) as compared with 11 patients
in complete remission (CR; RP versus CR, P = 0.009), 30 TX (RP versus TX, P < 0.001), or 35 NM (RP versus NM, P < 0.001). The markers were also elevated in 16 of 39 (41%) lung cancer patients at initial diagnosis. By tryptic digestion,
followed by tandem mass spectrometry fragmentation, the markers were identified as two isoforms of serum amyloid A (SAA) protein.
Monitoring the patients longitudinally for SAA level both by protein chip and immunoassay showed a dramatic SAA increase,
which correlated with relapse and a drastic fall correlated with response to salvage chemotherapy. Serum SAA findings were
compared with those of serum Epstein-Barr virus DNA in three relapsed patients showing a similar correlation with relapse
and chemo-response.
Conclusions: SAA could be a useful biomarker to monitor relapse of NPC.
Article Note: The members of the Project COVERED Emergency Department Network are provided in the appendix. CDC disclaimer: The findings and conclusions in this article are those of the authors and ...do not necessarily represent the views of the Centers for Disease Control and Prevention. Supervising Editor: John H. Burton, MD. Funding information This project was funded by a cooperative agreement from the Centers for Disease Control and Prevention (U01CK000480) and was supported by the Institute for Clinical and Translational Science at the University of Iowa through a grant from the National Center for Advancing Translational Sciences at the National Institutes of Health (UL1TR002537). Byline: Walter A. Schrading, Stacy A. Trent, James H. Paxton, Robert M. Rodriguez, Morgan B. Swanson, Nicholas M. Mohr, David A. Talan,, Monica Bahamon, Jestin N Carlson, Makini Chisolm-Straker, Brian Driver, Brett Faine, James Galbraith, Philip A Giordano, John P Haran, Amanda Higgins, Jeremiah Hinson, Stacey House, Ahamed H Idris, Efrat Kean, Elizabeth Krebs, Michael C. Kurz, Lilly Lee, Stephen Y Liang, Stephen C Lim, Gregory Moran, Utsav Nandi, Kavitha Pathmarajah, Yesenia Perez, Richard Rothman, Jessica Shuck, Patricia Slev, Howard A. Smithline, Kimberly Souffront, Mark Steele, Michelle St. Romain, Amy Stubbs, Josh Tiao, Jesus R Torres, Lisandra Uribe, Arvind Venkat, Gregory Volturo, Kelli Wallace, Kurt D Weber
To evaluate risk factors for GI adverse events (AEs) within a phase III trial of bevacizumab in first-line ovarian cancer therapy.
Women with previously untreated advanced disease after surgery were ...randomly allocated to six cycles of platinum-taxane chemotherapy plus placebo cycles (C)2 to C22 (R1); chemotherapy plus bevacizumab C2 to C6 plus placebo C7 to C22 (R2); or chemotherapy plus bevacizumab C2 to C22 (R3). Patients were evaluated for history or on-study development of potential risk factors for GI AEs defined as grade ≥ 2 perforation, fistula, necrosis, or hemorrhage.
Of 1,873 patients enrolled, 1,759 (94%) were evaluable, and 2.8% (50 of 1,759) experienced a GI AE: 10 of 587 (1.7%, R1), 20 of 587 (3.4%, R2), and 20 of 585 (3.4%, R3). Univariable analyses indicated that previous treatment of inflammatory bowel disease (IBD; P = .005) and small bowel resection (SBR; P = .032) or large bowel resection (LBR; P = .012) at primary surgery were significantly associated with a GI AE. The multivariable estimated relative odds of a GI AE were 13.4 (95% CI, 3.44 to 52.3; P < .001) for IBD; 2.05 (95% CI, 1.09 to 3.88; P = .026) for LBR; 1.95 (95% CI, 0.894 to 4.25; P = .093) for SBR; and 2.15 for bevacizumab exposure (aggregated 95% CI, 1.05 to 4.40; P = .036).
History of treatment for IBD, and bowel resection at primary surgery, increase the odds of GI AEs in patients receiving first-line platinum-taxane chemotherapy for advanced ovarian cancer. After accounting for these risk factors, concurrent bevacizumab doubles the odds of a GI AE, but is not appreciably increased by continuation beyond chemotherapy.
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