Cytidine deamination-induced perpetual immunity to SAR-CoV-2 infection is a potential new therapeutic target.

As the world is racing to develop perpetual immunity to the SARS-CoV-2 virus. The emergence of new viral strains, together with vaccination and reinfections, are all contributing to a long-term immunity against the deadly virus that has taken over the world since its introduction to humans in late December 2019. The discovery that more than 95 percent of people who recovered from COVID-19 had long-lasting immunity and that asymptomatic people have a different immune response to SARS-CoV-2 than symptomatic people has shifted attention to how our immune system initiates such diverse responses. These findings have provided reason to believe that SARS-CoV-2 days are numbered. Hundreds of research papers have been published on the causes of long-lasting immune responses and variations in the numbers of different immune cell types in COVID 19 survivors, but the main reason of these differences has still not been adequately identified. In this article, we focus on the activation-induced cytidine deaminase (AID), which initiates molecular processes that allow our immune system to generate antibodies against SARS-CoV-2. To establish lasting immunity to SARS-CoV-2, we suggest that AID could be the key to unlocking it.

SAR-CoV-2 infection, emerging new variants and the role of activation induced cytidine deaminase (AID) in lasting immunity.

As the world faces a fourth COVID-19 spike, scientists are learning a lot more about the new SARS-CoV-2 strains that were previously unknown. Currently, the Delta versions of SARS-CoV-2 have become the prevalent strains in much of the world since it first appeared in India in late 2020. Researchers believe they have discovered why Delta has been so successful: those infected with it create significantly more virus than those infected with the original strain of SARS-CoV-2, making it extremely contagious. This has redirected the focus to how our immune system defends us from these various pathogens and initiates such varied responses. Hundreds of research papers have been published on the origins of long-lasting immune responses and disparities in the numbers of different immune cell types in COVID 19 survivors, but the primary architect of these discrepancies has yet to be discovered. In this essay, we will concentrate on the primary architect protein, activation induced cytidine deaminase (AID), which triggers molecular processes that allow our immune system to produce powerful antibodies and SARS-CoV-2 specific B cells, allowing us to outwit the virus. We believe that if we ever achieve permanent immunity to SARS-CoV-2 infection, AID will be the key to releasing it.

Paediatric injuries due to falls from windows and balconies: an 8-year prospective and retrospective review.

BACKGROUND: Unintentional falls from windows and balconies pose a serious health risk to children. Limited Canadian data describing such falls currently exist. This study aimed to describe the frequency, demographic characteristics, injury patterns, and risk factors associated with paediatric falls from windows and balconies. METHODS: This study employed both prospective data collection and retrospective medical record review. Prospectively, consenting families were enrolled from February 2015 to February 2017; retrospectively, charts from January 2009 to December 2014 were reviewed. Children 0 to 16 years of age, who presented to the Stollery Children's Hospital (Edmonton, Alberta) emergency department due to a fall from a window or balcony, were included. RESULTS: A total of 102 children were included; thirty were enrolled prospectively and 72 retrospectively. Median age was 4.5 years (interquartile range 2.83 to 6.83) with 63.7% (65 of 102) males. About 87.2% (89 of 102) of falls were from windows and 12.8% (13 of 102) from balconies. The median estimated height of fall was 4.1 m (interquartile range 3.04 to 4.73). About 58.4% (59 of 101) had at least one major injury (i.e., concussion, fractured skull, internal injury, fractured limb, severe laceration), 36.6% had minor injuries only (i.e., abrasions, contusions, sprains), and 5.0% had no documented injuries. There were no fatalities. About 30.4% (31 of 102) were admitted, with 48.4% of these children (15 of 31) requiring surgery. CONCLUSION: Most falls from windows and balconies occurred in children under the age of 5 years and were associated with serious morbidity, high admission rates, and need for surgery. Child supervision as well as installation of key safety features in windows may help minimize paediatric fall-related injuries.

Experiences of pediatric emergency physicians in providing alcohol-related care to adolescents in the emergency department.

OBJECTIVE: The emergency department (ED) is a key clinical care setting for identifying and managing patients with alcohol-related presentations. We explored the experiences of emergency physicians in providing alcohol-related care to adolescents. METHODS: Purposeful sampling was used to identify pediatric emergency physicians with at least 1 year of experience (n = 12) from pediatric EDs across Canada. Data were collected via telephone using a semistructured interview guide. Hermeneutic phenomenology was used to identify common and unique experiences among respondents, using Moustakas' immersion/crystallization procedures. RESULTS: Physicians expressed frustration with patient behaviors accompanying intoxication and described providing care as a struggle; developing an effective therapeutic alliance was challenging. Physicians believed intoxicated adolescent patients required more clinical time and resources than they could offer. Although physicians described the ED as unsuitable for ensuring continuity of care and addressing the broader social issues that accompany alcohol use, they did view the ED as a place to medically stabilize the patient and initiate a discussion on alcohol use and its harmful effects. CONCLUSIONS: Pediatric ED physicians struggled during the caring experience and were skeptical that broader, more chronic social issues that are often associated with adolescent alcohol misuse can be effectively managed in a clinical setting where they feel primarily responsible for providing medical stabilization. Physicians did believe the ED was an appropriate place to ensure medical stability of a patient and then initiate a conversation regarding alcohol use and its harmful effects.

Brief emergency department interventions for youth who use alcohol and other drugs: a systematic review.

OBJECTIVE: Brief intervention (BI) is recommended for use with youth who use alcohol and other drugs. Emergency departments (EDs) can provide BIs at a time directly linked to harmful and hazardous use. The objective of this systematic review was to determine the effectiveness of ED-based BIs. METHODS: We searched 14 electronic databases, a clinical trial registry, conference proceedings, and study references. We included randomized controlled trials with youth 21 years or younger. Two reviewers independently selected studies and assessed methodological quality. One reviewer extracted and a second verified data. We summarized findings qualitatively. RESULTS: Two trials with low risk of bias, 2 trials with unclear risk of bias, and 5 trials with high risk of bias were included. Trials evaluated targeted BIs for alcohol-positive (n = 3) and alcohol/other drug-positive youth (n = 1) and universal BIs for youth reporting recent alcohol (n = 4) or cannabis use (n = 1). Few differences were found in favor of ED-based BIs, and variation in outcome measurement and poor study quality precluded firm conclusions for many comparisons. Universal and targeted BIs did not significantly reduce alcohol use more than other care. In one targeted BI trial with high risk of bias, motivational interviewing (MI) that involved parents reduced drinking quantity per occasion and high-volume alcohol use compared with MI that was delivered to youth only. Another trial with high risk of bias reported an increase in abstinence and reduction in physical altercations when youth received peer-delivered universal MI for cannabis use. In 2 trials with unclear risk of bias, MI reduced drinking and driving and alcohol-related injuries after the ED visit. Computer-based MI delivered universally in 1 trial with low risk of bias reduced alcohol-related consequences 6 months after the ED visit. CONCLUSIONS: Clear benefits of using ED-based BI to reduce alcohol and other drug use and associated injuries or high-risk behaviours remain inconclusive because of variation in assessing outcomes and poor study quality.

The impact of pediatric traumatic brain injury (TBI) on family functioning: a systematic review.

PURPOSE: To explore the impact moderate to severe traumatic brain injury (TBI) in a child has on family functioning. METHODS: The search was conducted using 9 bibliographic databases for articles published between 1980 and 2013. Two reviewers independently screened for inclusion and assessed study quality. Two reviewers extracted study data and a third checked for completeness and accuracy. Findings are presented by three domains: injury-related burden and stress, family adaptability, and family cohesion. RESULTS: Nine observational studies were included. Across the studies, differences between study groups for family functioning varied, but there was a trend for more dysfunction in families whose child had a severe TBI as compared to families whose child had a moderate TBI or orthopedic injury. In three studies, injury-associated burden was persistent post-injury and was highest in families whose child had a severe TBI followed by families with a child who had a moderate TBI. One study found fathers reported more family dysfunction caused by their child's injury compared to mothers. Two studies found that mothers' adaptability depended on social support and stress levels while fathers' adaptability was independent of these factors and injury severity. CONCLUSION: Moderate to severe TBI has a significant, long-standing impact on family functioning. Factors associated with family adaptability vary by parental role.

Instruments to detect alcohol and other drug misuse in the emergency department: a systematic review.

CONTEXT: Alcohol and other drug (AOD) misuse by youth is a significant public health concern. Unanticipated treatment for AOD-related morbidities is often sought in hospital emergency departments (EDs). Screening instruments that rapidly identify patients who require further diagnostic evaluation and/or brief intervention are critically important. OBJECTIVE: To summarize evidence on screening instruments that can assist emergency care clinicians in identifying AOD misuse in pediatric patients. METHODS: Fourteen electronic databases (including Medline, Embase, and PsycINFO) and reference screening were used. Psychometric and prospective diagnostic studies were selected if the instrument focused on detecting AOD misuse in patients aged 21 years or younger in the ED. Two reviewers independently assessed quality and extracted data. Validity and reliability data were collected for psychometric studies. Instrument performance was assessed by using sensitivity, specificity, and positive (LR(+)) and negative (LR(-)) likelihood ratios. Meta-analysis was not possible because of clinical and measurement heterogeneity. RESULTS: Of the 1545 references initially identified, 6 studies met inclusion criteria; these studies evaluated 11 instruments for universal or targeted screening of alcohol misuse. Instruments based on diagnostic criteria for AOD disorders were effective in detecting alcohol abuse and dependence (sensitivity: 0.88; specificity: 0.90; LR(+): 8.80) and cannabis use disorder (sensitivity: 0.96; specificity: 0.86; LR(+): 6.83). CONCLUSIONS: On the basis of the current evidence, we recommend that emergency care clinicians use a 2-question instrument for detecting youth alcohol misuse and a 1-question instrument for detecting cannabis misuse. Additional research is required to definitively answer whether these tools should be used as targeted or universal screening approaches in the ED.