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Comprehensive two-dimensional gas chromatography (GC×GC) is becoming increasingly more common for non-targeted characterization of complex volatile mixtures. The information gained with higher peak capacity and sensitivity provides additional sample composition information when one-dimensional GC is not adequate. GC×GC generates complex multivariate data sets when using non-targeted analysis to discover analytes. Fisher ratio (FR) analysis is applied to discern class markers, limiting complex GC×GC profiles to the most discriminating compounds between classes. While many approaches for feature selection using FR analysis exist, FR can be calculated relatively easily directly on peak areas after any native software has performed peak detection. This study evaluated the success rates of manual FR calculation and comparison to a critical F-value for samples analyzed by GC×GC with defined concentration differences. Long-term storage of samples and other spiked interferences were also investigated to examine their impact on analyzing mixtures using this FR feature selection strategy. Success rates were generally high with mostly 90–100% success rates and some instances of percentages between 80 and 90%. There were rare cases of false positives present and a low occurrence of false negatives. When errors were made in the selection of a compound, it was typically due to chromatographic artifacts present in chromatograms and not from the FR approach itself. This work provides foundational experimental data on the use of manual FR calculations for feature selection from GC×GC data. [ABSTRACT FROM AUTHOR]

Introduction: Combined omental and organ evisceration following anterior abdominal stab wound (SW) is uncommon and there is a paucity of literature describing the management and spectrum of injuries encountered at laparotomy. Methods: A retrospective study was undertaken on all patients who presented with anterior abdominal SW involving combined omental and organ evisceration who underwent laparotomy over a 10-year period from January 2008 to January 2018 at a major trauma centre in South Africa. Results: A total of 61 patients were eligible for inclusion and all underwent laparotomy: 87% male, mean age: 29 years. Ninety-two percent (56/61) had a positive laparotomy whilst 8% (5/61) underwent a negative procedure. Of the 56 positive laparotomies, 91% (51/56) were considered therapeutic and 9% (5/56) were non-therapeutic. In addition to omental evisceration, 59% (36/61) had eviscerated small bowel, 28% (17/61) had eviscerated colon and 13% (8/61) had eviscerated stomach. A total of 92 organ injuries were identified. The most commonly injured organs were small bowel, large bowel and stomach. The overall complication rate was 11%. Twelve percent (7/61) required intensive care unit admission. The mean length of hospital stay was 9 days. The overall mortality rate for all 61 patients was 2%. Conclusions: The presence of combined omental and organ evisceration following abdominal SW mandates laparotomy. The small bowel, large bowel and stomach were the most commonly injured organs in this setting. [ABSTRACT FROM AUTHOR]

Background: This study reviews our cumulative experience with the management of patients presenting with a retained knife following a penetrating neck injury (PNI).Methods: A retrospective cohort study was conducted at a major trauma center in South Africa over a 15-year period from July 2006 to December 2020. All patients who presented with a retained knife in the neck following a stab wound (SW) were included.Results: Twenty-two cases were included: 20 males (91%), mean age: 29 years. 77% (17/22) were retained knives and 23% (5/22) were retained blades. Eighteen (82%) were in the anterior neck, and the remaining 4 cases were in the posterior neck. Plain radiography was performed in 95% (21/22) of cases, and computed tomography (CT) was performed in 91% (20/22). Ninety-five percent (21/22) had the knife or blade extracted in the operating room (OR). Formal neck exploration (FNE) was undertaken in 45% (10/22) of cases, and the remaining 55% (12/22) underwent simple extraction (SE) only. Formal neck exploration was more commonly performed for anterior neck retained knives than the posterior neck, although not statistically significant [56% (10/18) vs 0% (0/18), P = .096]. There were no significant differences in the need for intensive care admission, length of hospital stay, morbidities, or mortalities between anterior and posterior neck retained knives.Discussion: Uncontrolled extraction of a retained knife in the neck outside of the operating room may be dangerous. Retained knives in the anterior neck commonly required formal neck exploration but not for posterior neck retained knives. [ABSTRACT FROM AUTHOR]

Background: Tube thoracostomy (TT) insertion is a commonly performed procedure in trauma that is standardised, but the optimal removal technique based on the timing in relation to the respiratory cycle remains controversial. Methods: A prospective study was undertaken at a major trauma centre in South Africa over a 4‐year period from January 2010 to December 2013, and included all patients with pneumothorax secondary to thoracic stab wounds. TTs were removed by either end of inspiration technique (EIT) or end of expiration (EET) technique and the rate of recurrent pneumothorax (RPTX) following removal was compared. We hypothesized that there is no difference in the rate of RPTX between the end inspiratory (EI) and end expiratory (EE) removal technique. Results: A total 347 patients were included. Of the 184 TTs removed by EIT, there were 17 (9%) RPTXs. Of the 163 with EET, there were 11 RPTXs (7%), (9% versus 7%, chi‐squared, P = 0.395). Of the total 28 (9%) patients with RPTXs following removal of chest tubes, two (7%) required reinsertion of chest tube (0.5% (1/184) in EIT and 0.6% (1/163) in EET, P = 0.747). Conclusions: Timing of TT removal in relation to the respiratory cycle does not appear to influence the incidence of RPTX in patients with thoracic stab wounds. Technique of removal may well be a more important consideration and more attention must be focused on refining the optimal technique. [ABSTRACT FROM AUTHOR]

Information about genetic engineering (GE) for vector control in the United States is disseminated primarily in English, though non-English speakers are equally, and in some geographic regions even more affected by such technologies. Non-English-speaking publics should have equal access to such information, which is especially critical when the technology in question may impact whole communities. We convened an interdisciplinary workgroup to translate previously developed narrated slideshows on gene drive mosquitoes from English into Spanish, reviewing each iteration for scientific accuracy and accessibility to laypeople. Using the finalised stimuli, we conducted five online, chat-based focus groups with Spanish-speaking adults from California. Overall, participants expressed interest in the topic and were able to summarise the information presented in their own words. Importantly, participants asked for clarification and expressed scepticism about the information presented, indicating critical engagement with the material. Through collaboration with Spanish-speaking scientists engaged in the development of GE methods of vector control, we translated highly technical scientific information into Spanish that successfully engaged Spanish-speaking participants in conversations about this topic. In this manuscript, we document the feasibility of consulting Spanish-speaking publics about a complex emerging technology by drawing on the linguistic diversity of the scientific teams developing the technology. [ABSTRACT FROM AUTHOR]

Introduction: Pneumoperitoneum on chest radiograph (CXR) following abdominal stab wounds (SW) is generally considered as surrogate evidence of viscus perforation and an absolute indication for laparotomy. The exact yield of this radiographic finding is unknown.Materials and Methods: A retrospective study was conducted on all patients who presented with abdominal SW with no peritoneal signs but had pneumoperitoneum alone who underwent mandatory laparotomy from December 2012 to October 2020 at a major trauma centre in South Africa.Results: During the 8-year study period, 55 patients were included (91% male, mean age: 24 years). Laparotomy was positive in 67% (37/55). Of the 37 positive laparotomies, 28 (76%) were considered therapeutic and the remaining 9 (24%) were nontherapeutic. The negative laparotomy rate was 33%. A total of 52 organ injuries were identified at laparotomy in the 37 positive laparotomies. Twenty-five per cent (14/55) of patients experienced complications. The complication rate of the subgroup of 18 patients who had a negative laparotomy was 33% (6/18). Two per cent (1/55) of all 55 patients required intensive care admission. The mean length of hospital stay was 6 days. There were no mortalities in this cohort.Conclusions: Pneumoperitoneum alone in patients with no peritoneal signs on initial assessment following abdominal SW cannot be considered an absolute indication for operative exploration. Up to one third of patients have no intra-abdominal injuries. This specific subgroup of patients can potentially be managed by a selective non-operative management approach. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: The availability of whole genome sequencing (WGS) is increasing in clinical care, and WGS is a promising tool in diagnostic odyssey cases. Physicians' ability to effectively communicate genomic information with patients, however, is unclear. In this multiperspective study, we assessed physicians' communication of patient genome sequencing information in a diagnostic odyssey case series. METHODS: We evaluated physician communication of genome sequencing results in the context of an ongoing study of the utility of WGS for the diagnosis of rare and idiopathic diseases. A modified version of the Medical Communication Competence Scale was used to compare patients' ratings of their physicians' communication of general medical information to communication of genome sequencing information. Physician self-ratings were also compared with patient ratings. RESULTS: A total of 47 patients, parents, and physicians across 11 diagnostic odyssey cases participated. In 6 of 11 cases (54%), the patient respondent rated the physician's communication of genome sequencing information as worse than that of general medical information. In 9 of 11 cases (82%), physician self-ratings of communication of genome sequencing information were worse than the patient respondent's rating. Identification of a diagnosis via WGS was positively associated with physician self-ratings (P = .021) but was not associated with patient respondent ratings (P = .959). CONCLUSIONS: These findings reveal that even in diagnostic odyssey cases, in which genome sequencing may be clinically beneficial, physicians may not be well-equipped to communicate genomic information to patients. Future studies may benefit from multiperspective approaches to assessing and understanding physician-patient communication of genome-sequencing information. [ABSTRACT FROM AUTHOR]

B Introduction: b Ketamine, an NMDA receptor antagonist and mu/kappa opioid agonist, may be used for its anesthetic and analgesic properties as an alternative for sedation and analgesia in mechanically ventilated patients. B Results: b A total of 107 patients met criteria for inclusion, of which 54 received ketamine and 53 received non-ketamine-based sedation. [Extracted from the article]

Introduction: Advances in health technology such as genome sequencing and wearable sensors now allow for the collection of highly granular personal health data from individuals. It is unclear how people think about privacy in the context of these emerging health technologies. An open question is whether early adopters of these advances conceptualize privacy in different ways than non-early adopters. Purpose: This study sought to understand privacy attitudes of early adopters of emerging health technologies. Methods: Transcripts from in-depth, semi-structured interviews with early adopters of genome sequencing and health devices and apps were analyzed with a focus on participant attitudes and perceptions of privacy. Themes were extracted using inductive content analysis. Results: Although interviewees were willing to share personal data to support scientific advancements, they still expressed concerns, as well as uncertainty about who has access to their data, and for what purpose. In short, they were not dismissive of privacy risks. Key privacy-related findings are organized into four themes as follows: first, personal data privacy; second, control over personal information; third, concerns about discrimination; and fourth, contributing personal data to science. Conclusion: Early adopters of emerging health technologies appear to have more complex and nuanced conceptions of privacy than might be expected based on their adoption of personal health technologies and participation in open science. Early adopters also voiced uncertainty about the privacy implications of their decisions to use new technologies and share their data for research. Though not representative of the general public, studies of early adopters can provide important insights into evolving attitudes toward privacy in the context of emerging health technologies and personal health data research. [ABSTRACT FROM AUTHOR]

Kava (Piper methysticum G. Forst) is a plant grown in the Pacific that is used in traditional medicines. The roots are macerated and powdered for consumption as a beverage in social settings as well as in ceremonies. Other types of preparations can also be used as traditional medicines. There has been an increase in demand for kava as there is continued traditional use and as it is becoming utilized more both socially and medicinally outside of Oceania. Currently, most research of this plant has focused on bioactive kavalactones and flavokawains, and there are few studies focusing on the other compounds that kava contains, such as volatile and semivolatile components. This study investigated the kava volatile organic compound (VOC) profile from nine different commercially available samples of dried, powdered kava root sourced across the Pacific region. The headspace above the kava samples was analyzed, both from the root powder as originally purchased and by performing a scaled-down extraction into water mimicking traditional preparation of the beverage. The headspace of each sample was extracted using solid-phase microextraction arrow (SPME Arrow), followed by analysis using comprehensive two-dimensional gas chromatography – quadrupole mass spectrometry/flame ionization detection (GC×GC-qMS/FID). The superior peak capacity of GC×GC was invaluable in effectively separating the complex mixture of compounds found in all samples, which enabled improved monitoring of minor differences between batches. Dry root powder samples contained high levels of β-caryophyllene while water extracted samples showed high levels of camphene. Many alcohols, aldehydes, ketones, terpenes, terpenoids, and aromatics were also characterized from both types of samples. All water extracted samples from the different brands followed similar trends in terms of compounds being detected or not. Additional major compounds found in water extracts included benzaldehyde, hexanal, methoxyphenyloxime, camphor, limonene, 1-hexanol, endoborneol, and copaene. While some samples could be differentiated based on brand, samples did not group by purported geographic origin. This study provides foundational data about a different subset of compounds within kava than previous research has studied, and also informs the community of the compounds that transfer into the consumed beverage during the traditional means of preparing kava. [Display omitted] • This study presents the volatile organic compound profile of kava. • Dry kava powder contained high levels of β-caryophyllene. • Water extracted kava contained high levels of camphene. • One third of the chemical profile consisted of terpenes and terpenoids. • Review of terpene pharmacological benefits to explore kava's therapeutic effects. [ABSTRACT FROM AUTHOR]

Prostaglandin biosynthesis is catalyzed by two spatially and functionally distinct active sites in cyctooxygenase (COX) enzymes. Despite the crucial role of COXs in biology, molecular details regarding the function and regulation of these enzymes are incompletely defined. Reactive nitrogen species, formed during oxidative stress, produce modifications that alter COX functionalities and prostaglandin biosynthesis. We previously established that COX-1 undergoes selective nitration on Tyr385 via a mechanism that requires the presence of bound heme cofactor. As this is a critical residue for COX-1 catalysis, nitration at this site results in enzyme inactivation. We now show that occupancy of the COX-1 active site with substrate protects against Tyr385 nitration and redirects nitration to alternative Tyr residues on COX-1, preserving catalytic activity. This study reveals a novel role for the substrate in protecting COX-1 from inactivation by nitration in pathophysiological settings. [ABSTRACT FROM AUTHOR]

Fast diagnostic results using breath analysis are an anticipated possibility for disease diagnosis or general health screenings. Tests that do not require sending specimens to medical laboratories possess capabilities to speed patient diagnosis and protect both patient and healthcare staff from unnecessary prolonged exposure. The objective of this work was to develop testing procedures on an initial healthy subject cohort in Hawaii to act as a range-finding pilot study for characterizing the baseline of exhaled breath prior to further research. Using comprehensive two-dimensional gas chromatography (GC×GC), this study analyzed exhaled breath from a healthy adult population in Hawaii to profile the range of different volatile organic compounds (VOCs) and survey Hawaii-specific differences. The most consistently reported compounds in the breath profile of individuals were acetic acid, dimethoxymethane, benzoic acid methyl ester, and n-hexane. In comparison to other breathprinting studies, the list of compounds discovered was representative of control cohorts. This must be considered when implementing proposed breath diagnostics in new locations with increased interpersonal variation due to diversity. Further studies on larger numbers of subjects over longer periods of time will provide additional foundational data on baseline breath VOC profiles of control populations for comparison to disease-positive cohorts. [ABSTRACT FROM AUTHOR]

Introduction: Penetrating gastric injury (PGI) is common and although primary repair is sufficient for most injuries, several areas surrounding the peri-operative management remain contentious. This study reviews our experience in the management of PGI and review the clinical outcome at a major trauma centre in South Africa.Materials and Methods: A retrospective study was conducted from January 2012 to April 2020 at a major trauma centre in South Africa.Results: 210 cases were included (184 male, median age: 30 years). Mechanism of injury was 59% stab wounds (SWs) and 41% gunshot wounds (GSWs). The AAST grade was predominantly (92%) grade 2 for all cases. 20% (41/210) were isolated gastric injuries. All cases underwent primary repair and there were no cases of suture line failure. Eleven cases (5%) had one or more injuries not identified at the index laparotomy: 7 were unidentified gastric injuries and the remaining 4 were unidentified non gastric injuries. There was no association between unidentified injuries and mechanism of injury or outcome. Fifty-seven (27%) cases experienced one or more complications. Eighty-two cases (39%) required intensive care unit admission. The overall median length of hospital stay was 7 (IQR 4-11) days. The overall mortality was 14%. GSW injuries were more likely to have additional organ injury, higher ISS and PATI scores, longer length of hospitalization, higher likelihood of ICU stay, greater morbidity and mortality than SW injuries. There was a slight increase in the wound sepsis rate as number of associated extra gastric injuries increased but this was not statistically significant. There was no difference in wound overall sepsis rate between SW and GSW injuries (2% vs 8%, p=0.121).Conclusions: Primary repair alone is sufficient for most PGI, but laparotomy is associated with high incidence of unidentified injury and surgeons must to be cognisant of the likelihood of these occult injuries. [ABSTRACT FROM AUTHOR]

Background: The foley catheter balloon tamponade (FCBT) has been widely employed in the management of trauma. This study reviews our cumulative experience with the use of FCBT in the management of patients presenting with a penetrating neck injury (PNI). Methods: A retrospective study was conducted at a major trauma centre in South Africa over a 9-year period from January 2012 to December 2020. All patients who presented with a PNI who had FCBT were included. Results: A total of 1581 patients with a PNI were managed by our trauma centre, and 44 (3%) patients had an FCBT. Of the 44 cases of FCBT, stab wounds accounted for 93% (41/44) and the remaining 7% were for gunshot wounds. Seventy-five per cent of all FCBT (33/44) were inserted at a rural hospital prior to transfer to our trauma centre; the remaining 25% (11/44) were inserted in our resuscitation room. The success rate of FCBT was 80% (35/44), allowing further CT with angiography (CTA) to be performed. CTA findings were: 10/35 (29%) positive, 18/35 (51%) negative, and 7/35 (20%) equivocal. Fifteen patients required additional intervention (open surgery or endovascular intervention). The overall morbidity was 14% (6/44). Eighteen per cent required intensive care unit admission. The median length of stay was 1 day. The overall mortality rate was 11% (5/44). Conclusion: FCBT is a simple and effective technique as an adjunct in the management of major haemorrhage from a PNI. In highly selective patients, it may also be used as definitive management. [ABSTRACT FROM AUTHOR]

Background: This study aimed to review our decade-long experience with the management of abdominal gunshot wounds (GSWs), to document trends in our approach and to develop an evidence base for our contemporary management algorithms in a major trauma in South Africa. Materials and methods: This was a retrospective study that included all adult patients with abdominal GSWs between January 2013 and October 2020 managed at a major trauma centre in South Africa. Result: Five hundred and ninety-six cases were included (87% male, mean age: 32 years). The median Injury Severity Score (ISS) was 12. 52% (309/596) of cases had indications of immediate laparotomy and proceeded directly to the operating room without any CT imaging. Of this cohort, the laparotomy was positive in 292 and in the remainder (5%) was negative. Of the remaining 287 cases, 209 underwent a CT scan (35%). 78 were managed without any CT imaging. Of the 78 who did not undergo CT scan, all were managed without any operation and discharged home well. Of the 209 who underwent CT scan, 99 were observed and only one case in this group subsequently required a laparotomy. The remaining 110 cases underwent a laparotomy, which was negative in 7. There were correlations with increasing use of CT, as well as a decrease in those proceeding directly to laparotomy. The overall morbidity rate was 8% (47/596). 32% (190/596) require intensive care unit (ICU) admission. The overall mortality rate was 8% (67/596). Conclusions: The management of abdominal GSWs has continued to evolve. There is now a well-defined role for selective non-operative management in this group of patients and relies on accurate CT assessment. CT scan is now an important component in the management of abdominal GSW even in our resource-constrained environment. [ABSTRACT FROM AUTHOR]

Background: We previously published that altered expression of gastric TRPV1, BDNF, and peripheral cytokines was present in patients with functional dyspepsia. We herein examine whether genetic predisposition in altered biomarkers influences dyspeptic, sleep, and mood symptoms in patients with FD without previous infection. Methods: Consecutive adult FD patients (Rome III) with no recent history of gastroenteritis and asymptomatic age‐ and sex‐matched healthy controls were recruited for upper endoscopy. Subjects with GERD and IBS as predominant symptoms, diabetes mellitus, current or previous H pylori infection, psychiatric illness, and recent use of NSAID or PPI were excluded. The genetic associations with dyspeptic symptoms, sleep quality, and mood symptoms were evaluated. Genetic polymorphisms in TRPV1, TGFB1, TNF, COMT, BDNF, IL6, IL8, IL10, and IL12 were analyzed. Key results: Twenty‐nine male FD patients and 104 female FD patients were age matched (±3 years) with 81 healthy subjects. All had postprandial distress syndrome (PDS) as predominant subtype (PDS: 130, EPS: 3). SNPs in TGFB1 showed significant associations in dyspeptic patients after age and sex adjustment [for RS4803455: in the codominant model (C/A, OR = 0.34 (0.18‐0.65), P = .004); in the dominant model (genotype C/C vs C/A‐A/A, OR = 0.42 (0.23‐0.77), P = .004); and in the overdominant model (genotype C/C‐A/A vs C/A, OR = 0.38 (0.21‐0.70), P < .001)] [for RS1800469: in dominant model (genotype A/A vs A/G‐G/G, OR = 0.52 (0.27‐0.99), P = .043)]. A allele in RS4803455 was associated with higher HADS depression score (P = .05) and epigastric burning sensation(P = .01). Conclusions and inferences: Our data showed that dyspeptic patients predispose genetic difference in TGFB1 which may influence the severity of dyspepsia. [ABSTRACT FROM AUTHOR]

Introduction: Gallbladder trauma is a rare injury. This study aimed to describe the significance of these injuries and the appropriate management strategies.Methods: A retrospective study was undertaken at a major trauma centre in South Africa and included all patients diagnosed with a gallbladder injury between January 2012 and October 2020.Results: A total of 51 cases were included (88% male, mean age: 38 years), with 44 (86%) penetrating trauma cases [28 stab wounds (SW), 16 sustained gunshot wounds (GSW)]. Of the 7 (13%) blunt trauma cases, five were involved in a motor vehicle crash, and two were injured via assault. All patients underwent laparotomy. Full-thickness gallbladder laceration or perforation was the most common type of injury (84%) and all patients with a gallbladder perforation or laceration had a cholecystectomy at index operation. Two out of 5 patients with a gallbladder contusion were managed conservatively without a cholecystectomy and the remaining three had evidence of gallbladder necrosis which were managed with cholecystectomy. Associated extrahepatic bile duct injuries occurred in 4% of cases, and 18 cases (35%) required intensive care unit (ICU) admission. The overall mortality was 8%.Conclusion: Gallbladder injury is rare but when encountered implies a significant degree of trauma. Although cholecystectomy is usually definitive, there is an association with other occult extra-hepatic biliary tract injuries. The severity of the associated injuries usually determines patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Over the last 50 years, the gold standard for paediatric trauma management has grown to be non‐operative management. This study reviews a South African experience with paediatric splenic trauma in order to benchmark this against the international standard and to identify discrepancies in access to care and in surgical outcomes. Methods: This was a retrospective study conducted at a major trauma centre in South Africa. All children less than 18 years of age who were admitted to our trauma centre following trauma between December 2012 and October 2020 were identified and all those who sustained splenic trauma were reviewed. Results: Of the 66 patients reviewed, 48 (72%) were male, and the median age was 12 years (0–18 years). Thirty‐three (51%) were of rural origin and 61 (93%) sustained blunt trauma. Only eight (12%) had an isolated splenic injury, while the remaining 58 (88%) had other associated injuries. Forty‐five patients (68%) were managed non‐operatively whilst the remainder were subjected to laparotomy. Five (7%) required a splenectomy and one required angio‐embolisation. Twenty‐six patients (39%) required intensive care unit (ICU) admission: 15 (37%) in the non‐operative cohort required ICU admission and eight (40%) in the laparotomy group required ICU admission. Twenty‐eight (42%) patients required ventilatory support. Median length of stay was 5.5 days. Four (6%) patients died. Conclusions: Although non‐operative management of paediatric splenic trauma can be undertaken successfully by adult trauma surgeons in a middle‐income country such as South Africa, there remains room for improvement. To achieve splenic salvage rates comparable to those in dedicated paediatric trauma centres in high‐income countries will require systematic quality improvement programmes. [ABSTRACT FROM AUTHOR]

Background/Aims The relationship between animal exposure and irritable bowel syndrome (IBS) is debated. Epidemiological studies have shown that atopy is more prevalent in IBS patients and vice versa. We set out to examine the association between animal danders sensitization and IBS-like symptoms in atopic patients. Methods We recruited 69 consecutive atopic patients from the allergy clinic of a tertiary hospital. Subjects completed validated bowel questionnaires, underwent skin prick test, blood was collected for serum total immunoglobulin E, and ImmunoCAP immune solidphase allergen chip (ISAC) IgE multiplex assay. Results Twenty-eight (41.0%) atopic patients fulfilled the Rome III IBS criteria (atopy-IBS). There were no differences in gender, age, pet ownership, total serum IgE, or food allergen sensitization between atopy-IBS group and atopy-non-IBS group. We found that atopy- IBS group had significantly higher number of positive skin prick test for cat dander (64.3% vs 24.4%, P < 0.001), dog dander (64.3% vs 41.5%, P = 0.015) and weed pollens (32.1% vs 14.6%, P = 0.050) compared to atopy-non-IBS group. Out of 112 components from 51 allergen sources (both aeroallergen and food allergens), only Fel d1 (a major cat dander antigen) IgE is significantly higher in atopy-IBS group than atopy-non-IBS group (21.4% vs 2.4%, P = 0.029). Majority of atopy-IBS patients had mixed-type IBS. Conclusions We demonstrated an association between animal danders sensitization, in particular cat dander sensitization, and IBS-like symptoms in atopic patients. Future studies are needed to explore the relationship between aeroallergen and functional gastrointestinal disorders. Sensitization may be related to the pathophysiology of IBS or it could be that we are missing aeroallergen-induced gut allergy. [ABSTRACT FROM AUTHOR]

Background: Bioactive lipids play an important role in insulin secretion and sensitivity, contributing to the pathophysiology of type 2 diabetes (T2D). This study aimed to identify novel lipid species associated with incident T2D in a nested case–control study within a long-term prospective Chinese community-based cohort with a median follow-up of ~ 16 years. Methods: Plasma samples from 196 incident T2D cases and 196 age- and sex-matched non-T2D controls recruited from the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS) were first analyzed using untargeted lipidomics. Potential predictive lipid species selected by the Boruta analysis were then verified by targeted lipidomics. The associations between these lipid species and incident T2D were assessed. Effects of novel lipid species on insulin secretion in mouse islets were investigated. Results: Boruta analysis identified 16 potential lipid species. After adjustment for body mass index (BMI), triacylglycerol/high-density lipoprotein (TG/HDL) ratio and the presence of prediabetes, triacylglycerol (TG) 12:0_18:2_22:6, TG 16:0_11:1_18:2, TG 49:0, TG 51:1 and diacylglycerol (DG) 18:2_22:6 were independently associated with increased T2D risk, whereas lyso-phosphatidylcholine (LPC) O-16:0, LPC P-16:0, LPC O-18:0 and LPC 18:1 were independently associated with decreased T2D risk. Addition of the identified lipid species to the clinical prediction model, comprised of BMI, TG/HDL ratio and the presence of prediabetes, achieved a 3.8% improvement in the area under the receiver operating characteristics curve (AUROC) (p = 0.0026). Further functional study revealed that, LPC O-16:0 and LPC O-18:0 significantly potentiated glucose induced insulin secretion (GSIS) in a dose-dependent manner, whereas neither DG 18:2_22:6 nor TG 12:0_18:2_22:6 had any effect on GSIS. Conclusions: Addition of the lipid species substantially improved the prediction of T2D beyond the model based on clinical risk factors. Decreased levels of LPC O-16:0 and LPC O-18:0 may contribute to the development of T2D via reduced insulin secretion. [ABSTRACT FROM AUTHOR]

• Volatiles from postmortem bacteria were profiled using GC×GC-qMS/FID. • Five species were monitored each over a five-day period on standard nutrient agar. • No volatile was found to be present from all five species. • Principal coordinate analysis gave similar results to principal component analysis. • Comparison showed a clear differentiation of volatile profiles between each species. Decomposition odor is produced during postmortem mammalian tissue breakdown by bacteria, insects, and intrinsic chemical processes. Past research has not thoroughly investigated which volatile organic compounds (VOCs) can be linked directly to individual bacterial species on decomposing remains. The purpose of this study was to profile the VOCs produced over time by individual species of bacteria using comprehensive two-dimensional gas chromatography (GC×GC) to expand our foundational knowledge of what each bacterial species contributes to decomposition odor. Five different species of bacteria (Bacillus subtilis, Ignatzschineria indica, Ignatzschineria ureiclastica, Curtobacterium luteum, and Vagococcus lutrae) were cultured on standard nutrient agar individually and monitored daily using solid phase microextraction arrow (SPME Arrow) and GC×GC in combination with quadrupole mass spectrometry (qMS) and flame ionization detection (FID). The GC×GC-qMS/FID approach was used to generate rich VOC profiles that represented the bacterial species' metabolic VOC production longitudinally. The data obtained from the chromatographic output was used to compare with a prior study using one-dimensional GC-qMS, and also between each of the five species to investigate the extent of overlap between species. No single VOC could be found in all five bacterial species investigated, and there was little overlap in the profile between species. To further visualize these differences, chromatographic peak data was investigated using two different ordination strategies, principal component analysis (PCA) and principal coordinate analysis (PCoA). The two ordination strategies were compared with each other using a Procrustes analysis. This was performed to understand differences in ordination strategies between the separation science community and chemical ecological community. Overall, ordination strategies were found to produce similar results, as evidenced by the correlation of PCA and PCoA in the Procrustes analysis. All analysis strategies yielded distinct VOC profiles for each species. Further study of additional species will support understanding of the holistic view of decomposition odor from a chemical ecology perspective, and further support our understanding of the production of decomposition odor that culminates from such a complex environment. [ABSTRACT FROM AUTHOR]

Protein 3-nitrotyrosine (3-NT) formation is frequently regarded as a simple biomarker of disease, an irreversible posttranslational modification that can disrupt protein structure and function. Nevertheless, evidence that protein 3-NT modifications may be site selective and reversible, thus allowing for physiological regulation of protein activity, has begun to emerge. We have previously reported that cyclooxygenase (COX)-1 undergoes heme-dependent nitration of Tyr385, an internal and catalytically essential residue. In the present study, we demonstrate that nitrated COX-1 undergoes a rapid reversal of nitration by substrateselective and biologically regulated denitrase activity. Using nitrated COX-1 as a substrate, denitrase activity was validated and quantified by analytic HPLC with electrochemical detection and determined to be constitutively active in murine and human endothelial cells, macrophages, and a variety of tissue samples. Smooth muscle cells, however, contained little denitrase activity. Further characterizing this denitrase activity, we found that it was inhibited by free 3-NT and may be enhanced by endogenous nitric oxide and exogenously administered carbon monoxide. Finally, we describe a purification protocol that results in significant enrichment of a discrete denitrasecontaining fraction, which maintains activity throughout the purification process. These findings reveal that nitrated COX-1 is a substrate for a denitrase in cells and tissues, implying that the reciprocal processes of nitration and denitration may modulate bioactive lipid synthesis in the setting of inflammation. In addition, our data reveal that denitration is a controlled process that may have broad importance for regulating cell signaling events in nitric oxide-generating systems during oxidative/nitrosative stress. [ABSTRACT FROM AUTHOR]

Background and Aim: Gastrointestinal manifestations of the coronavirus disease 2019 (COVID‐19) pandemic may mimic irritable bowel syndrome (IBS), and social distancing measures may affect IBS patients negatively. We aimed to study the impact of COVID‐19 on respondents with self‐reported IBS. Methods: We conducted an anonymized survey from May to June 2020 in 33 countries. Knowledge, attitudes, and practices on personal hygiene and social distancing as well as psychological impact of COVID‐19 were assessed. Statistical analysis was performed to determine differences in well‐being and compliance to social distancing measures between respondents with and without self‐reported IBS. Factors associated with improvement or worsening of IBS symptoms were evaluated. Results: Out of 2704 respondents, 2024 (74.9%) did not have IBS, 305 (11.3%) had self‐reported IBS, and 374 (13.8%) did not know what IBS was. Self‐reported IBS respondents reported significantly worse emotional, social, and psychological well‐being compared with non‐IBS respondents and were less compliant to social distancing measures (28.2% vs 35.3%, P = 0.029); 61.6% reported no change, 26.6% reported improvement, and 11.8% reported worsening IBS symptoms. Higher proportion of respondents with no change in IBS symptoms were willing to practice social distancing indefinitely versus those who deteriorated (74.9% vs 51.4%, P = 0.016). In multivariate analysis, willingness to continue social distancing for another 2–3 weeks (vs longer period) was significantly associated with higher odds of worsening IBS. Conclusion: Our study showed that self‐reported IBS respondents had worse well‐being and compliance to social distancing measures than non‐IBS respondents. Future research will focus on occupational stress and dietary changes during COVID‐19 that may influence IBS. [ABSTRACT FROM AUTHOR]

Importance: Knowledge and attitude influence compliance and individuals' practices. The risk and protective factors associated with high compliance to these preventive measures are critical to enhancing pandemic preparedness. Objective: This survey aims to assess differences in mental health, knowledge, attitudes, and practices (KAP) of preventive measures for COVID-19 amongst healthcare professionals (HCP) and non-healthcare professionals. Design: Multi-national cross-sectional study was carried out using electronic surveys between May-June 2020. Setting: Multi-national survey was distributed across 36 countries through social media, word-of-mouth, and electronic mail. Participants: Participants ≥21 years working in healthcare and non-healthcare related professions. Main outcome: Risk factors determining the difference in KAP towards personal hygiene and social distancing measures during COVID-19 amongst HCP and non-HCP. Results: HCP were significantly more knowledgeable on personal hygiene (AdjOR 1.45, 95% CI -1.14 to 1.83) and social distancing (AdjOR 1.31, 95% CI -1.06 to 1.61) compared to non-HCP. They were more likely to have a positive attitude towards personal hygiene and 1.5 times more willing to participate in the contact tracing app. There was high compliance towards personal hygiene and social distancing measures amongst HCP. HCP with high compliance were 1.8 times more likely to flourish and more likely to have a high sense of emotional (AdjOR 1.94, 95% CI (1.44 to 2.61), social (AdjOR 2.07, 95% CI -1.55 to 2.78), and psychological (AdjOR 2.13, 95% CI (1.59–2.85) well-being. Conclusion and relevance: While healthcare professionals were more knowledgeable, had more positive attitudes, their higher sense of total well-being was seen to be more critical to enhance compliance. Therefore, focusing on the well-being of the general population would help to enhance their compliance towards the preventive measures for COVID-19. [ABSTRACT FROM AUTHOR]

Background and Aim: A well‐validated, comprehensive checklist of functional gastrointestinal (FGI) disorder (FGID) symptom severity for tracking symptom profile changes over time is lacking. We aim to develop and validate a comprehensive symptom severity checklist for FGID. Methods: A 20‐item scale, including both upper and lower gastrointestinal symptoms, was generated to measure the symptom severity commonly found in FGID. Patients who experienced at least monthly symptoms of FGID with negative endoscopy findings were invited to complete the FGI‐Checklist, Patient Health Questionaire‐9 for assessing depressive symptoms, and Patient Health Questionnaire‐15 for assessing somatic symptoms at baseline. A subset of patients who met Rome III diagnostic criteria of gastroesophageal reflux disease, functional dyspepsia, and irritable bowel syndrome received medication treatment for 8–12 weeks and completed the FGI‐Checklist again at a follow‐up visit. Exploratory factor analysis was performed for subscales formation and psychometric properties were measured. Results: Six hundred and forty‐one patients were recruited for current study and 108 (16.8%) of them completed the FGI‐Checklist again at follow‐up. Exploratory factor analysis identified a five‐factor solution accounting for 66.8% of the total variance. The five factors are named esophageal syndrome, reflux syndrome, functional dyspepsia syndrome, nausea and vomiting syndrome, and abdominal and bowel syndrome. The FGI‐Checklist total score correlated with Patient Health Questionaire‐9 and Patient Health Questionnaire‐15 (all P < 0.001), which demonstrated good construct validity. Good item‐internal consistency was found (Cronbach's alphas: 0.69–0.87). Responsiveness for reflux syndrome subscale, functional dyspepsia syndrome subscale, and abdominal and bowel syndrome subscale after medication treatment was significant (paired‐t‐test: all P < 0.01). Conclusion: The instrument, Checklist, is valid and reliable. [ABSTRACT FROM AUTHOR]

A goal of the Precision Medicine Initiative All of Us Research Program (AoURP) is recruitment of participants who reflect the diversity of the US. Recruitment from among blood bank donors, which may better reflect the demographic makeup of local communities, is one proposed strategy. We evaluated this strategy by analyzing the results of a survey of San Diego Blood Bank donors conducted in November 2015. Whites were more likely than nonwhites to respond to the survey (7.1 percent versus 3.9 percent). However, race was not a significant predictor of interest in participating in precision medicine research. Using census data linked to donors' ZIP codes, we also found that people who indicated interest in research participation were more likely to come from regions with higher educational attainment. Although blood banks represent a viable recruitment strategy for AoURP, our findings indicate that bias toward inclusion of whites and more highly educated people persists. [ABSTRACT FROM AUTHOR]

Summary The transition from castration-resistant prostate adenocarcinoma (CRPC) to neuroendocrine prostate cancer (NEPC) has emerged as an important mechanism of treatment resistance. NEPC is associated with overexpression and gene amplification of MYCN (encoding N-Myc). N-Myc is an established oncogene in several rare pediatric tumors, but its role in prostate cancer progression is not well established. Integrating a genetically engineered mouse model and human prostate cancer transcriptome data, we show that N-Myc overexpression leads to the development of poorly differentiated, invasive prostate cancer that is molecularly similar to human NEPC. This includes an abrogation of androgen receptor signaling and induction of Polycomb Repressive Complex 2 signaling. Altogether, our data establishes N-Myc as an oncogenic driver of NEPC. [ABSTRACT FROM AUTHOR]

B Introduction: b Previous studies have shown that inhaled pulmonary vasodilators can improve oxygenation in patients with acute respiratory distress syndrome (ARDS). It is unclear whether inhaled nitric oxide (iNO) or aerosolized epoprostenol (aEPO) is superior in patients with ARDS from Coronavirus Disease-2019 (COVID-19). B Results: b A total of 68 patients were included for analysis; 10 patients in the iNO group and 58 patients in the aEPO group. [Extracted from the article]

Cyclooxygenase (COX)-derived prostaglandins (PGs) and nitric oxide (NO) play physiological and pathological roles in many processes e.g. vasodilation/vasoconstriction. In fact, PG and NO synthetic pathways converge to regulate PG production essential to vascular function. Recently, we showed that differential nitration and aggregation of COX-1 by peroxynitrite (ONOO-) occurs. We found that nitration at tyrosine 385 (essential to catalysis) is heme-driven and leads to COX deactivation. The following study assesses ONOO-modifications to COX-1 and its activity in physiological bicarbonate levels, in the presence and absence of heme, arachidonic acid, aspirin and the hydroperoxide scavenger glutathione peroxidase. When heme in COX-1 was substituted with CoIII-protoporphyrinIX, ONOO--treatment caused minimal nitration and aggregation, confirming the role of the Fe center in deactivation processes. Physiological bicarbonate levels markedly increased nitration levels in apoCOX-1 and holoCOX-1 compared to other buffers, without altering apoCOX-1 function. This result supports specific and heme-decisive tyrosine nitration that leads to COX-1 inactivation. Results also indicate that while arachidonic acid protects against nitration by ONOO-, aggregation is driven by arachidonic acid-hydroperoxides suggesting that ONOO--induced COX-1 modifications are regulated by arachidonic acid. [ABSTRACT FROM AUTHOR]

Diet and exercise are conventional methods for controlling body weight and are linked to alterations in gut microbiota. However, the associations of diet, exercise, and gut microbiota in the control of obesity remain largely unknown. In the present study, using 16S rRNA amplicon sequencing and fecal microbiota transplantation (FMT), normal fat diet (NFD), exercise and their combination resulted in improved metabolic profiles in comparison to sedentary lifestyle with high fat diet (HFD). Moreover, diet exerted more influence than exercise in shaping the gut microbiota. HFD-fed mice receiving FMT from NFD-exercised donors not only showed remarkably reduced food efficacy, but also mitigated metabolic profiles (p < 0.05). The transmissible beneficial effects of FMT were associated with bacterial genera Helicobacter, Odoribacter and AF12 and overrepresentation of oxidative phosphorylation and glycolysis genes. Our findings demonstrate that the beneficial effects of diet and exercise are transmissible via FMT, suggesting a potential therapeutic treatment for obesity. [ABSTRACT FROM AUTHOR]