Brain sex differences are established developmentally and generate enduring changes in circuitry and behavior. Steroid-mediated masculinization of the rat amygdala during perinatal development ...produces higher levels of juvenile rough-and-tumble play by males. This sex difference in social play is highly conserved across mammals, yet the mechanisms by which it is established are unknown. Here, we report that androgen-induced increases in endocannabinoid tone promote microglia phagocytosis during a critical period of amygdala development. Phagocytic microglia engulf more viable newborn cells in males; in females, less phagocytosis allows more astrocytes to survive to the juvenile age. Blocking complement-dependent phagocytosis in males increases astrocyte survival and prevents masculinization of play. Moreover, increased astrocyte density in the juvenile amygdala reduces neuronal excitation during play. These findings highlight novel mechanisms of brain development whereby endocannabinoids induce microglia phagocytosis to regulate newborn astrocyte number and shape the sexual differentiation of social circuitry and behavior.
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•Microglia are more phagocytic in the male amygdala during neonatal development•Androgen-induced endocannabinoids increase phagocytosis in males•Microglia engulf viable newborn astrocytes in a complement-dependent manner•Developmental phagocytosis produces a sex difference in juvenile social play
VanRyzin et al. demonstrate that microglia in the developing amygdala engulf and kill otherwise viable newborn astrocytes, establishing sex differences in social circuits. This process, which depends on gonadal hormones and endocannabinoid signaling, promotes juvenile play by males.
Overnight consolidation processes are thought to operate in a selective manner, such that important (i.e. future-relevant) memories are strengthened ahead of irrelevant information. Using an online ...protocol, we sought to replicate the seminal finding that the memory benefits of sleep are enhanced when people expect a future test Wilhelm et al., 2011. Participants memorised verbal paired associates to a criterion of 60 percent (Experiment 1) or 40 percent correct (Experiment 2) before a 12-hour delay containing overnight sleep (sleep group) or daytime wakefulness (wake group). Critically, half of the participants were informed that they would be tested again the following day, whereas the other half were told that they would carry out a different set of tasks. We observed a robust memory benefit of overnight consolidation, with the sleep group outperforming the wake group in both experiments. However, knowledge of an upcoming test had no impact on sleep-associated consolidation in either experiment, suggesting that overnight memory processes were not enhanced for future-relevant information. These findings, together with other failed replication attempts, show that sleep does not provide selective support to memories that are deemed relevant for the future.
Objectives
Middle ear surgery increasingly employs endoscopes as an adjunct to or replacement for the operative microscope. We provide a systematic review of endoscope applications in middle ear ...surgery with an emphasis on outcomes, including the need for conversion to microscope, audiometric findings, length of follow‐up, as well as disease‐specific outcomes.
Data Sources
PubMed, Embase, and Cochrane CENTRAL database.
Methods
A literature review was performed using the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis recommendations. Articles were categorized based on study design, indication, and use of an endoscope either as an adjunct to or as a replacement for a microscope. Qualitative and descriptive analyses of studies and outcomes data were performed.
Results
One‐hundred three articles met inclusion and exclusion criteria. Of the identified articles, 38 provided outcomes data. The majority of these studies were moderate quality, retrospective, case‐series reports. The indications for use of the endoscope were broad, with the most common being resection of cholesteatoma. In cholesteatoma surgery, endoscope approaches routinely identified residual cholesteatoma in primary and second‐look cases. Other outcomes, including robust audiometric data, operating room times, wound healing, and quality of life surveys were not well described.
Conclusions
Endoscopes have consistently been used as an adjunct to the microscope to improve visualization of the tympanic cavity. Recent reports utilize the endoscope exclusively during surgical dissection; however, data comparing patient outcomes following the use of an endoscope to a microscope are lacking. Areas in need of additional research are highlighted.
Level of Evidence
NA Laryngoscope, 125:1205–1214, 2015
Background
Although meta-analyses of randomized controlled trials (RCTs) of salt reduction report a reduction in the level of blood pressure (BP), the effect of reduced dietary salt on cardiovascular ...disease (CVD) events remains unclear.
Methods
We searched for RCTs with follow-up of at least 6 months that compared dietary salt reduction (restricted salt dietary intervention or advice to reduce salt intake) to control/no intervention in adults, and reported mortality or CVD morbidity data. Outcomes were pooled at end of trial or longest follow-up point.
Results
Seven studies were identified: three in normotensives, two in hypertensives, one in a mixed population of normo- and hypertensives and one in heart failure. Salt reduction was associated with reductions in urinary salt excretion of between 27 and 39mmol/24h and reductions in systolic BP between 1 and 4mmHg. Relative risks (RRs) for all-cause mortality in normotensives (longest follow-up-RR: 0.90, 95% confidence interval (CI): 0.58-1.40, 79 deaths) and hypertensives (longest follow-up RR 0.96, 0.83-1.11, 565 deaths) showed no strong evidence of any effect of salt reduction CVD morbidity in people with normal BP (longest follow-up: RR 0.71, 0.42-1.20, 200 events) and raised BP at baseline (end of trial: RR 0.84, 0.57-1.23, 93 events) also showed no strong evidence of benefit. Salt restriction increased the risk of all-cause mortality in those with heart failure (end of trial RR 2.59, 1.04-6.44, 21 deaths).We found no information on participant's health-related quality of life.
Conclusions
Despite collating more event data than previous systematic reviews of RCTs (665 deaths in some 6,250 participants) there is still insufficient power to exclude clinically important effects of reduced dietary salt on mortality or CVD morbidity. Our estimates of benefits from dietary salt restriction are consistent with the predicted small effects on clinical events attributable to the small BP reduction achieved.
A more detailed review has been published and will be updated in the Cochrane Database of Systematic Reviews Taylor RS, Ashton KE, Moxham T, Hooper L, Ebrahim S. Reduced dietary salt for the prevention of cardiovascular disease. Cochrane Database of Systematic Reviews (CDSR) 2011, Issue 7 (see www.thecochranelibrary.com for information). This is a version of a Cochrane review, which is available in The Cochrane Library. Cochrane systematic reviews are regularly updated to include new research, and in response to feedback from readers. The results of a Cochrane review can be interpreted differently, depending on people's perspectives and circumstances. Please consider the conclusions presented carefully. They are the opinions of review authors, and are not necessarily shared by The Cochrane Collaboration.
American Journal of Hypertension, advance online publication 6 July 2011; doi:10.1038/ajh.2011.115
Background
There are various approaches to the psychological management of chronic pain and it is difficult to know which components of psychological therapies are necessary or desirable for the ...effective management of chronic pain.
Methods
We conducted a Delphi study to develop a consensus on the necessary and desirable psychological intervention strategies for chronic pain management. First, we identified 49 components of treatments that had been used in a treatment evaluated in a randomized controlled trial (RCT) through a systematic review. In the first round of the Delphi process, 23 (32% of 72) authors who had completed RCTs in chronic pain took part. In round 2, these experts plus clinicians working at pain management programs around Australia were invited to take part, and 44 experts completed the study.
Results
The panel agreed that it was necessary to include psycho‐education, particularly about pain mechanisms and the role of thoughts in maintaining pain. Cognitive approaches were deemed necessary, although the panel did not specify one particular strategy. Finally, approaches to increase activity were deemed necessary, including the strategies of pacing, goal setting and graded exposure. Relaxation training and relapse prevention were also deemed necessary.
Conclusions
There was a consensus that there were many desirable strategies to include in psychological chronic pain management approaches, but that treatments should include psycho‐education, approaches to increase activity and cognitive approaches as a first line of intervention. Where patients fail to benefit from these approaches, experts identified other desirable strategies that could be utilized.
Significance
The expert consensus indicated that psycho‐education, strategies to increase activity and cognitive therapy strategies were necessary for effective psychological treatment of patients with chronic pain. While other strategies were deemed desirable, psychological treatments should include at least those three components.
First-generation EGFR tyrosine kinase inhibitors (EGFR TKI) provide significant clinical benefit in patients with advanced EGFR-mutant (EGFRm(+)) non-small cell lung cancer (NSCLC). Patients ...ultimately develop disease progression, often driven by acquisition of a second T790M EGFR TKI resistance mutation. AZD9291 is a novel oral, potent, and selective third-generation irreversible inhibitor of both EGFRm(+) sensitizing and T790M resistance mutants that spares wild-type EGFR. This mono-anilino-pyrimidine compound is structurally distinct from other third-generation EGFR TKIs and offers a pharmacologically differentiated profile from earlier generation EGFR TKIs. Preclinically, the drug potently inhibits signaling pathways and cellular growth in both EGFRm(+) and EGFRm(+)/T790M(+) mutant cell lines in vitro, with lower activity against wild-type EGFR lines, translating into profound and sustained tumor regression in EGFR-mutant tumor xenograft and transgenic models. The treatment of 2 patients with advanced EGFRm(+) T790M(+) NSCLC is described as proof of principle.
We report the development of a novel structurally distinct third-generation EGFR TKI, AZD9291, that irreversibly and selectively targets both sensitizing and resistant T790M(+) mutant EGFR while harboring less activity toward wild-type EGFR. AZD9291 is showing promising responses in a phase I trial even at the first-dose level, with first published clinical proof-of-principle validation being presented.
This research provides the first support for a possible psychological universal: Human beings around the world derive emotional benefits from using their financial resources to help others (prosocial ...spending). In Study 1, survey data from 136 countries were examined and showed that prosocial spending is associated with greater happiness around the world, in poor and rich countries alike. To test for causality, in Studies 2a and 2b, we used experimental methodology, demonstrating that recalling a past instance of prosocial spending has a causal impact on happiness across countries that differ greatly in terms of wealth (Canada, Uganda, and India). Finally, in Study 3, participants in Canada and South Africa randomly assigned to buy items for charity reported higher levels of positive affect than participants assigned to buy the same items for themselves, even when this prosocial spending did not provide an opportunity to build or strengthen social ties. Our findings suggest that the reward experienced from helping others may be deeply ingrained in human nature, emerging in diverse cultural and economic contexts.
Despite coronavirus disease 2019 (COVID-19) primarily being identified as a respiratory illness, some patients who seemingly recovered from initial infection, developed chronic multi-system ...complications such as cardiovascular (CV), pulmonary and neurological issues leading to multiple organ injuries. However, to date, there is a dearth of understanding of the acute and chronic implications of a COVID-19 infection on the CV system in adults. A systematic review of the literature was conducted according to PRISMA guidelines and prospectively registered via Prospero (ID: CRD42022360444). The MEDLINE Ovid, Cochrane Library and PubMed databases were searched from inception to August 2022. The search strategy keywords and MeSH terms used included: 1) COVID; 2) coronavirus; 3) long COVID; 4) cardiovascular; and 5) cardiovascular disease. Reference lists of all relevant systematic reviews identified were searched for additional studies. A total of 11,332 records were retrieved from database searches, of which 310 records were duplicates. A further 9887 were eliminated following screening of titles and abstracts. After full-text screening of 1135 articles, 9 manuscripts were included for review. The evidence of CV implications post-COVID-19 infection is clear, and this must be addressed with appropriate management strategies that recognise the acute and chronic nature of cardiac injury in COVID-19 patients. Efficacious management strategies will be needed to address long standing issues and morbidity.
Our ability to recall memories is improved when sleep follows learning, suggesting that sleep facilitates memory consolidation. A number of factors are thought to influence the impact of sleep on ...newly learned information, such as whether or not we rehearse that information (e.g. via restudy or retrieval practice), or the extent to which the information is consistent with our pre-existing schematic knowledge. In this pre-registered, online study, we examined the effects of both rehearsal and schematic congruency on overnight consolidation. Participants learned noun-colour pairings (e.g. elephant-red) and rated each pairing as plausible or implausible before completing a baseline memory assessment. Afterwards, participants engaged in a period of restudy or retrieval practice for the pairings, and then entered a 12 h retention interval of overnight sleep or daytime wakefulness. Follow-up assessments were completed immediately after sleep or wake, and again 24 h after learning. Our data indicated that overnight consolidation was amplified for restudied relative to retested noun-colour pairings, but only when sleep occurred soon after learning. Furthermore, whereas plausible (i.e. schematically congruent) pairings were generally better remembered than implausible (i.e. schematically incongruent) pairings, the benefits of sleep were stronger for implausible relative to plausible memories. These findings challenge the notion that schema-conformant memories are preferentially strengthened during post-learning sleep.
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