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Background Many individuals hospitalised with severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) infection experience post-acute sequelae of SARS-CoV-2 infection (PASC), sometimes referred to as "long COVID". Our objective was to conduct a systematic literature review and meta-analysis to identify PASC-associated symptoms in previously hospitalised patients and determine the frequency and temporal nature of PASC. Methods Searches of MEDLINE, Embase, Cochrane Library (2019-2021), World Health Organization International Clinical Trials Registry Platform and reference lists were performed from November to December 2021. Articles were assessed by two reviewers against eligibility criteria and a risk of bias tool. Symptom data were synthesised by random effects meta-analyses. Results Of 6942 records, 52 studies with at least 100 patients were analysed; ~70% were Europe-based studies. Most data were from the first wave of the pandemic. PASC symptoms were analysed from 28 days after hospital discharge. At 1-4 months post-acute SARS-CoV-2 infection, the most frequent individual symptoms were fatigue (29.3% (95% CI 20.1-40.6%)) and dyspnoea (19.6% (95% CI 12.8-28.7%)). Many patients experienced at least one symptom at 4-8 months (73.1% (95% CI 44.2-90.3%)) and 8--12 months (75.0% (95% CI 56.4-87.4%)). Conclusions A wide spectrum of persistent PASC-associated symptoms were reported over the 1-year follow-up period in a significant proportion of participants. Further research is needed to better define PASC duration and determine whether factors such as disease severity, vaccination and treatments have an impact on PASC. [ABSTRACT FROM AUTHOR]

Observation of paraesophageal hernias (PEHs) may lead to emergent surgery for hernia-related complications. This study evaluated urgent or emergent repair outcomes to quantify the possible sequelae of failed conservative PEH management. The impact of operative status (elective vs urgent or emergent) on perioperative mortality or major morbidity for patients who underwent hiatal hernia repair for a PEH diagnosis from 2012 to 2021 in the Society of Thoracic Surgery General Thoracic Surgery Database was evaluated with multivariable logistic regression models. Overall, 2082 (10.9%) of 19,122 patients with PEHs underwent urgent or emergent repair. Patients undergoing nonelective surgery were significantly older than patients undergoing elective surgery (median age, 73 years [interquartile range, 63-82 years] vs 66 years [interquartile range, 58-74 years]) and had a lower preoperative performance score (P <.001). Nonelective surgical procedures were more likely to be performed through the chest or by laparotomy rather than by laparoscopy (20% vs 11.4%; P <.001), and they were associated with longer hospitalizations (4 days vs 2 days; P <.001), higher operative mortality (4.5% vs 0.6%; P <.001), and higher major morbidity (27% vs 5.5%; P <.001). Nonelective surgery was a significant independent predictor of major morbidity in multivariable analysis (odds ratio, 2.06; P <.001). Patients more than the age of 80 years had higher operative mortality (4.3% vs 0.6%; P < 0.001) and major morbidity (19% vs 6.1%; P <.001) than younger patients overall, and these older patients more often had nonelective surgery (26% vs 8.6%; P <.001) The operative morbidity of PEH repair is significantly increased when surgery is nonelective, particularly for older patients. These results can inform the potential consequences of choosing watchful waiting vs elective PEH repair. [Display omitted] [ABSTRACT FROM AUTHOR]

Traumatic events that affect physiology and behavior in the current generation may also impact future generations. We demonstrate that an ecologically realistic degree of predation risk prior to conception causes lasting changes in the first filial (F1) and second filial (F2) generations. We exposed male and female mice to a live rat (predator stress) or control (non-predator) condition for 5 min. Ten days later, stressed males and females were bred together as were control males and females. Adult F1 offspring from preconception-stressed parents responded to a mild stressor with more anxiety-like behavior and hyperarousal than offspring from control parents. Exposing these F1 offspring to the mild stressor increased neuronal activity (cFOS) in the hippocampus and altered glucocorticoid system function peripherally (plasma corticosterone levels). Even without the mild stressor, F1 offspring from preconception-stressed parents still exhibited more anxiety-like behaviors than controls. Cross-fostering studies confirmed that preconception stress, not maternal social environment, determined offspring behavioral phenotype. The effects of preconception parental stress were also unexpectedly persistent and produced similar behavioral phenotypes in the F2 offspring. Our data illustrate that a surprisingly small amount of preconception predator stress alters the brain, physiology, and behavior of future generations. A better understanding of the 'long shadow' cast by fearful events is critical for understanding the adaptive costs and benefits of transgenerational plasticity. It also suggests the intriguing possibility that similar risk-induced changes are the rule rather than the exception in free-living organisms, and that such multigenerational impacts are as ubiquitous as they are cryptic. [ABSTRACT FROM AUTHOR]

Trace amine-associated receptor 1 (TAAR1) is an established neuroregulatory G protein-coupled receptor with recent studies suggesting additional functions related to immunomodulation. Our lab has previously investigated TAAR1 expression within cells of the innate immune system and herein we aim to further elucidate TAAR1 function in both peripherally-derived and CNS-resident macrophages. The selective TAAR1 agonist RO5256390 was used in combination with common damage associated molecular patterns (ATP and ADP) to observe the effect of TAAR1 agonism on modulating cytokine secretion and metabolic profiles. In mouse bone-marrow derived macrophages, TAAR1 agonism inhibited TNF secretion following ATP stimulation, which appeared to be downstream of an associated pro-inflammatory shift in metabolic profile and transcriptional regulation of TNF synthesis. In contrast, TAAR1 agonism had no effect on ADP-induced TNF and IL-6 secretion in mouse microglia in either the presence or absence of astrocytes. In summary, we report a novel interaction between TAAR1 and purinergic signaling in peripherally-derived, but not CNS-resident, macrophages. These findings provide the first evidence of trace aminergic and purinergic crosstalk, and support the potential for TAAR1 as a novel therapeutic target in inflammatory disorders. [ABSTRACT FROM AUTHOR]