Multi-Omics Profiling Approach to Asthma: An Evolving Paradigm

Asthma is a complex multifactorial and heterogeneous respiratory disease. Although genetics is a strong risk factor of asthma, external and internal exposures and their interactions with genetic factors also play important roles in the pathophysiology of asthma. Over the past decades, the application of high-throughput omics approaches has emerged and been applied to the field of asthma research for screening biomarkers such as genes, transcript, proteins, and metabolites in an unbiased fashion. Leveraging large-scale studies representative of diverse population-based omics data and integrating with clinical data has led to better profiling of asthma risk. Yet, to date, no omic-driven endotypes have been translated into clinical practice and management of asthma. In this article, we provide an overview of the current status of omics studies of asthma, namely, genomics, transcriptomics, epigenomics, proteomics, exposomics, and metabolomics. The current development of the multi-omics integrations of asthma is also briefly discussed. Biomarker discovery following multi-omics profiling could be challenging but useful for better disease phenotyping and endotyping that can translate into advances in asthma management and clinical care, ultimately leading to successful precision medicine approaches.

Like mother, like child? Sex differences in the maternal transmission of offending among a Scottish cohort of pre-adolescent children

That parental offending acts as a strong risk factor for offending in children is well-established within criminology. Yet, research on maternal offending is relatively limited, even though many women take on a significantly higher share of childcare responsibilities, and as such, might reasonably be expected to exert an especially strong influence on their children. In part, this lacuna might be attributed to a male-centric lens within criminology, which has tended to overlook female offending. Aimed in part at redressing this imbalance, this article investigates the maternal transmission of offending among a cohort of 12-year-olds, using self-report data from the longitudinal Growing Up in Scotland study. The analysis shows that intragenerational maternal offending acts as a significant predictor of offending among daughters, but that intergenerational offending does not. We found no significant relationship between mothers’ offending and sons’, who appear more vulnerable to a range of wider risk factors.

Postoperative hypothermia following non-cardiac high-risk surgery: A prospective study of temporal patterns and risk factors

Background and objectives Hypothermia occurs commonly during surgery and can cause postoperative complications. We aimed to describe the characteristics and outcomes of hypothermia in patients undergoing major surgeries. Methods This prospective, observational, multicenter study of a nationally representative sample included all patients over 18 years of age admitted to an intensive care unit (ICU). Thirty ICUs were selected randomly at national level. The main outcome measure was the proportion of patients who developed postoperative hypothermia in the first 24 hours of ICU admission. Patients were divided into three groups based on temperature: <35°C, <36°C, and ≥36°C (no hypothermia). Patients’ characteristics, postoperative complications, and risk factors were evaluated in all groups. To verify whether hypothermia was a strong risk factor for postoperative complications, a Kaplan–Meier curve was generated and adjusted using a Cox regression model. Results In total, 738 patients had their temperatures measured. The percentage of patients with temperature <35°C (median [Q1-Q3], 34.7°C [34.3–34.9°C]) was 19.1% (95% confidence interval [CI] = 16.1–22.5) and that of patients with temperature <36°C (median [Q1-Q3], 35.4°C [35.0–35.8°C]) was 64% (95% CI = 58.3–70.0). The percentage of surgical complications was 38.9%. Patients with hypothermia were older, had undergone abdominal surgeries, had undergone procedures of longer duration, and had more comorbidities. A postoperative temperature ≤35°C was an independent risk for composite postoperative complications (hazard ratio = 1.523, 95% CI = 1.15–2.0), especially coagulation and infection. Conclusions Inadvertent hypothermia was frequent among patients admitted to the ICU and occurred more likely after abdominal surgery, after a long procedure, in elderly patients, and in patients with a higher number of comorbidities. Low postoperative temperature was associated with postoperative complications.

Effects of Sex, Age, and Apolipoprotein E Genotype on Brain Ceramides and Sphingosine-1-Phosphate in Alzheimer’s Disease and Control Mice

Apolipoprotein ε4 (APOE)4 is a strong risk factor for the development of Alzheimer’s disease (AD) and aberrant sphingolipid levels have been implicated in AD. We tested the hypothesis that the APOE4 genotype affects brain sphingolipid levels in AD. Seven ceramides and sphingosine-1-phosphate (S1P) were quantified by LC-MSMS in hippocampus, cortex, cerebellum, and plasma of &lt;3 months and &gt;5 months old human APOE3 and APOE4-targeted replacement mice with or without the familial AD (FAD) background of both sexes (145 animals). APOE4 mice had higher Cer(d18:1/24:0) levels in the cortex (1.7-fold, p = 0.002) than APOE3 mice. Mice with AD background showed higher levels of Cer(d18:1/24:1) in the cortex than mice without (1.4-fold, p = 0.003). S1P levels were higher in all three brain regions of older mice than of young mice (1.7-1.8-fold, all p ≤ 0.001). In female mice, S1P levels in hippocampus (r = −0.54 [−0.70, −0.35], p &lt; 0.001) and in cortex correlated with those in plasma (r = −0.53 [−0.71, −0.32], p &lt; 0.001). Ceramide levels were lower in the hippocampus (3.7–10.7-fold, all p &lt; 0.001), but higher in the cortex (2.3–12.8-fold, p &lt; 0.001) of female than male mice. In cerebellum and plasma, sex effects on individual ceramides depended on acyl chain length (9.5-fold lower to 11.5-fold higher, p ≤ 0.001). In conclusion, sex is a stronger determinant of brain ceramide levels in mice than APOE genotype, AD background, or age. Whether these differences impact AD neuropathology in men and women remains to be investigated.

The Depletion of Carbohydrate Metabolic Genes in the Gut Microbiome Contributes to the Transition From Central Obesity to Type 2 Diabetes

Obesity, especially central obesity, is a strong risk factor for developing type 2 diabetes (T2D). However, the mechanism underlying the progression from central obesity to T2D remains unknown. Therefore, we analyzed the gut microbial profiles of central obese individuals with or without T2D from a Chinese population. Here we reported both the microbial compositional and gene functional alterations during the progression from central obesity to T2D. Several opportunistic pathogens were enriched in obese T2D patients. We also characterized thousands of genes involved in sugar and amino acid metabolism whose abundance were significantly depleted in obese T2D group. Moreover, the abundance of those genes was negatively associated with plasma glycemia level and percentage of individuals with impaired plasma glucose status. Therefore, our study indicates that the abundance of those depleted genes can be used as a potential biomarker to identify central obese individuals with high risks of developing T2D.

Post-operative hypocalcemia in patients undergoing thyroid surgeries in tertiary care hospital: an observational study

<p><strong>Background: </strong>Post-operative hypocalcaemia is one of the most common complications of thyroid and parathyroid surgery. Temporary hypocalcaemia has been reported to occur in 1.6-50% of the patients undergoing bilateral thyroid resection. Permanent hypoparathyroidism results in 0-13% of patients after bilateral thyroid surgery.</p><p><strong>Method: </strong>We have analyzed the data of 34 patients undergoing total thyroid surgery (with or without neck dissection) and completion thyroidectomy at the department of ENT and HNS, SMHS hospital over a period of 1.5 years between May 2019 to November 2020.</p><p><strong>Results:</strong> Hypocalcemia was found in a total of 15 patients out of 34 patients in the post-op period. Among the total patients who developed hypocalcemia 5 (14.7%) were males and 10 (29.4%) were females. Among the patients who developed post-op hypocalcemia 14 patients developed transient hypocalcemia (p&gt;0.01) which is not statistically significant and 1 patient developed permanent hypocalcemia (p&gt;0.01) which also has no statistical significance.</p><p><strong>Conclusions: </strong>The study suggests that female gender is a strong risk factor for developing post-operative hypocalcemia, other factors that play a role include difference in serum calcium levels in the perioperative period and type of surgery.</p>

Risk Factors of Sectio Caesarea Delivery at Djafar Harun Hospital

The number of mothers giving birth with sectio caesarae delivery at BLUD R.S H.M Djafar Harun North Kolaka in 2015 was 254 people, then increased in 2016 to 521 people. The purpose of this study was to analyze the risk factors for the incidence of Sectio Caesarea delivery at H.M Djafar Harun Hospital, North Kolaka. This type of research is an analytic observational study with a case-control study approach. The study population was 68 with a sample of 136 people using the Accidental Sampling Technique. Data analysis using the Odds Ratio test. The results of the risk analysis based on narrow pelvic factors showed the value of OR= 9,681; LL= 2,728; UL= 34,355, and then placenta previa factor showed the value of OR= 6,484; LL= 0,759; UL= 55,385. In conclusion, narrow pelvis is a strong risk factor and placenta previa is not a strong risk factor for Sectio Caesarea delivery. It is hoped that the hospital will seek to identify high-risk pregnancies, complications or pregnancy abnormalities so that they can be detected early so that they are able to more optimally handle complications during childbirth.

Thrombophilia Testing After Ischemic Stroke

Thrombophilia testing is frequently performed after an ischemic stroke, particularly when cryptogenic. However, there is minimal evidence supporting a significant association between most conditions assessed through thrombophilia testing and ischemic stroke, and the rationale for thrombophilia testing in many clinical situations remains uncertain. In this topical review, we review and contextualize the existing data on the risks, predictors, and outcomes of thrombophilic conditions in patients with ischemic stroke. We report that inherited thrombophilias have an uncertain relationship with ischemic stroke. Conversely, antiphospholipid syndrome, an acquired immune-mediated thrombophilia, seems to be a strong risk factor for arterial thromboembolic events, including ischemic stroke, and especially among young patients. Our findings suggest that certain circumstances may warrant targeted thrombophilia testing, such as stroke in the young, cryptogenic stroke, and high estrogen states. Future prospective studies should investigate the utility and cost effectiveness of thrombophilia testing in various stroke settings, including among patients with patent foramen ovale; as well as the optimal secondary stroke prevention regimen in patients with confirmed thrombophilia, particularly if no other potential stroke mechanism is identified.

Definition of acute kidney injury impacts prevalence and prognosis in ACS patients undergoing coronary angiography

Background Development of acute kidney injury (AKI) in invasively managed patients with acute coronary syndrome (ACS) is associated with a markedly increased mortality risk. Different definitions of AKI are in use, leading to varying prevalence and outcome measurements. The aim of the present study is to analyze an ACS population undergoing coronary angiography for differences in AKI prevalence and outcome using four established AKI definitions. Methods 944 patients (30% female) were enrolled in a prospective registry between 2003 and 2005 with 6-month all-cause mortality as outcome measure. Four established AKI definitions were used: an increase in serum creatinine (sCR) ≥ 1.5 fold, ≥ 0.3 mg/dl, and ≥ 0.5 mg/dl and a decrease in eGFR > 25% from baseline (AKIN 1, AKIN 2, CIN, and RIFLE definition groups, respectively). Results AKI rates varied widely between the different groups. Using the CIN definition, AKI frequency was lowest (4.4%), whereas it was highest if the RIFLE definition was applied (13.2%). AKIN 2 displayed a twofold higher AKI prevalence compared with AKIN 1 (10.2% vs. 5.3% (p < 0.001)). AKI was a strong risk factor for mid-term mortality, with distinctive variability between the definitions. The lowest mortality risk was found in the RIFLE group (HR 6.0; 95% CI 3.7–10.0; p < 0.001), whereas CIN revealed the highest risk (HR 16.7; 95% CI 9.9–28.1; p < 0.001). Conclusion Prevalence and outcome in ACS patients varied considerably depending on the AKI definition applied. To define patients with highest renal function-associated mortality risk, use of the CIN definition seems to have the highest prognostic relevance.