Volatile organic compounds produced during postmortem processes can be linked via chromatographic profiles to individual postmortem bacterial 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.

Distinct changes in serum metabolites and lipid species in the onset and progression of NAFLD in Obese Chinese.

Introduction: Metabolic disturbances are major contributors to the onset and progression of non-alcoholic fatty liver disease (NAFLD), which includes a histological spectrum ranging from single steatosis (SS) to non-alcoholic steatohepatitis (NASH). This study aimed to identify serum metabolites and lipids enriched in different histological stages of NAFLD and to explore metabolites/lipids as non-invasive biomarkers in risk prediction of NAFLD and NASH in obese Chinese. Methods: Serum samples and liver biopsies were obtained from 250 NAFLD subjects. Untargeted metabolomic and lipidomic profiling were performed using Liquid Chromatography-Mass Spectrometry. Significantly altered metabolites and lipids were identified by MaAsLin2. Pathway enrichment was conducted with MetaboAnalyst and LIPEA. WGCNA was implemented to construct the co-expression network. Logistic regression models were developed to classify different histological stages of NAFLD. Results: A total of 263 metabolites and 550 lipid species were detected in serum samples. Differential analysis and pathway enrichment analysis revealed the progressive patterns in metabolic mechanisms during the transition from normal liver to SS and to NASH, including N-palmitoyltaurine, tridecylic acid, and branched-chain amino acid signaling pathways. The co-expression network showed a distinct correlation between different triglyceride and phosphatidylcholine species with disease severity. Multiple models classifying NAFLD versus normal liver and NASH versus SS identified important metabolic features associated with significant improvement in disease prediction compared to conventional clinical parameters. Conclusion: Different histological stages of NAFLD are enriched with distinct sets of metabolites, lipids, and metabolic pathways. Integrated algorithms highlight the important metabolic and lipidomic features for diagnosis and staging of NAFLD in obese individuals.

Ten metabolites-based algorithm predicts the future development of type 2 diabetes in Chinese.

INTRODUCTION: Type 2 diabetes (T2D) is a heterogeneous metabolic disease with large variations in the relative contributions of insulin resistance and ß-cell dysfunction across different glucose tolerance subgroups and ethnicities. A more precise yet feasible approach to categorize risk preceding T2D onset is urgently needed. This study aimed to identify potential metabolic biomarkers that could contribute to the development of T2D and investigate whether their impact on T2D is mediated through insulin resistance and ß-cell dysfunction. METHODS: A non-targeted metabolomic analysis was performed in plasma samples of 196 incident T2D cases and 196 age- and sex-matched non-T2D controls recruited from a long-term prospective Chinese community-based cohort with a follow-up period of âˆ¼ 16 years. RESULTS: Metabolic profiles revealed profound perturbation of metabolomes before T2D onset. Overall metabolic shifts were strongly associated with insulin resistance rather than ß-cell dysfunction. In addition, 188 out of the 578 annotated metabolites were associated with insulin resistance. Bi-directional mediation analysis revealed putative causal relationships among the metabolites, insulin resistance and T2D risk. We built a machine-learning based prediction model, integrating the conventional clinical risk factors (age, BMI, TyG index and 2hG) and 10 metabolites (acetyl-tryptophan, kynurenine, γ-glutamyl-phenylalanine, DG(18:2/22:6), DG(38:7), LPI(18:2), LPC(P-16:0), LPC(P-18:1), LPC(P-20:0) and LPE(P-20:0)) (AUROC = 0.894, 5.6% improvement comparing to the conventional clinical risk model), that successfully predicts the development of T2D. CONCLUSIONS: Our findings support the notion that the metabolic changes resulting from insulin resistance, rather than ß-cell dysfunction, are the primary drivers of T2D in Chinese adults. Metabolomes as a valuable phenotype hold potential clinical utility in the prediction of T2D.

Belun Ring (Belun Sleep System BLS-100): Deep learning-facilitated wearable enables obstructive sleep apnea detection, apnea severity categorization, and sleep stage classification in patients suspected of obstructive sleep apnea.

GOAL AND AIMS: Our objective was to evaluate the performance of Belun Ring with second-generation deep learning algorithms in obstructive sleep apnea (OSA) detection, OSA severity categorization, and sleep stage classification. FOCUS TECHNOLOGY: Belun Ring with second-generation deep learning algorithms REFERENCE TECHNOLOGY: In-lab polysomnography (PSG) SAMPLE: Eighty-four subjects (M: F = 1:1) referred for an overnight sleep study were eligible. Of these, 26% had PSG-AHI<5; 24% had PSG-AHI 5-15; 23% had PSG-AHI 15-30; 27% had PSG-AHI ≥ 30. DESIGN: Rigorous performance evaluation by comparing Belun Ring to concurrent in-lab PSG using the 4% rule. CORE ANALYTICS: Pearson's correlation coefficient, Student's paired t-test, diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, Cohen's kappa coefficient (kappa), Bland-Altman plots with bias and limits of agreement, receiver operating characteristics curves with area under the curve, and confusion matrix. CORE OUTCOMES: The accuracy, sensitivity, specificity, and kappa in categorizing AHI ≥ 5 were 0.85, 0.92, 0.64, and 0.58, respectively. The accuracy, sensitivity, specificity, and Kappa in categorizing AHI ≥ 15 were 0.89, 0.91, 0.88, and 0.79, respectively. The accuracy, sensitivity, specificity, and Kappa in categorizing AHI ≥ 30 were 0.91, 0.83, 0.93, and 0.76, respectively. BSP2 also achieved an accuracy of 0.88 in detecting wake, 0.82 in detecting NREM, and 0.90 in detecting REM sleep. CORE CONCLUSION: Belun Ring with second-generation algorithms detected OSA with good accuracy and demonstrated a moderate-to-substantial agreement in categorizing OSA severity and classifying sleep stages.

Prevalence and Characteristics of Peripapillary Gamma Zone in Children With Different Refractive Status: The Hong Kong Children Eye Study.

Purpose: This study aimed to assess the prevalence and characteristics of the peripapillary gamma zone in myopic, emmetropic, and hyperopic eyes of Chinese children. Methods: Overall, 1274 children aged 6 to 8 years from the Hong Kong Children Eye Study underwent ocular examinations, including measurements of cycloplegic auto-refraction and axial length (AL). The optic disc was imaged using a Spectralis optical coherence tomography (OCT) unit and a protocol involving 24 equally spaced radial B-scans. The Bruch's membrane opening (BMO) was identified in over 48 meridians in each eye. The peripapillary gamma zone was defined as the region between the BMO and the border of the optic disc, identified by the OCT. Results: The prevalence of the peripapillary gamma zone was higher in myopic eyes (36.3%) than in emmetropic (16.1%) and hyperopic eyes (11.5%, P < 0.001). AL (per 1 mm; odds ratio [OR]) = 1.861, P < 0.001) and a more oval disc shape (OR = 3.144, P < 0.001) were associated with the presence of a peripapillary gamma zone after adjusting for demographic, systemic, and ocular variables. In the subgroup analysis, a longer AL was associated with the presence of a peripapillary gamma zone in myopic eyes (OR = 1.874, P < 0.001), but not in emmetropic (OR = 1.033, P = 0.913) or hyperopic eyes (OR = 1.044, P = 0.883). A peripapillary zone was not observed in the region nasal to the optic nerve in myopic eyes, in contrast to its presence in the same region in 1.9% of emmetropic eyes and 9.3% of hyperopic eyes; these intergroup differences were statistically significant (P < 0.001). Conclusions: Although peripapillary gamma zones were observed in the eyes of both myopic and non-myopic children, their characteristics and distribution patterns were substantially different.

Laparotomy for Abdominal Stab Wound With Combined Omental and Organ Evisceration: 10-Year Experience From a Major Trauma Centre in South Africa.

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.

Fisher ratio feature selection by manual peak area calculations on comprehensive two-dimensional gas chromatography data using standard mixtures with variable composition, storage, and interferences.

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.

Specific triacylglycerol, diacylglycerol, and lyso-phosphatidylcholine species for the prediction of type 2 diabetes: a ~ 16-year prospective study in Chinese.

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.

Adipocyte-derived lactate is a signalling metabolite that potentiates adipose macrophage inflammation via targeting PHD2.

Adipose tissue macrophage (ATM) inflammation is involved with meta-inflammation and pathology of metabolic complications. Here we report that in adipocytes, elevated lactate production, previously regarded as the waste product of glycolysis, serves as a danger signal to promote ATM polarization to an inflammatory state in the context of obesity. Adipocyte-selective deletion of lactate dehydrogenase A (Ldha), the enzyme converting pyruvate to lactate, protects mice from obesity-associated glucose intolerance and insulin resistance, accompanied by a lower percentage of inflammatory ATM and reduced production of pro-inflammatory cytokines such as interleukin 1ß (IL-1ß). Mechanistically, lactate, at its physiological concentration, fosters the activation of inflammatory macrophages by directly binding to the catalytic domain of prolyl hydroxylase domain-containing 2 (PHD2) in a competitive manner with α-ketoglutarate and stabilizes hypoxia inducible factor (HIF-1α). Lactate-induced IL-1ß was abolished in PHD2-deficient macrophages. Human adipose lactate level is positively linked with local inflammatory features and insulin resistance index independent of the body mass index (BMI). Our study shows a critical function of adipocyte-derived lactate in promoting the pro-inflammatory microenvironment in adipose and identifies PHD2 as a direct sensor of lactate, which functions to connect chronic inflammation and energy metabolism.

Serum Thrombospondin-2 Levels Are Closely Associated With the Severity of Metabolic Syndrome and Metabolic Associated Fatty Liver Disease.

CONTEXT: Metabolic associated fatty liver disease (MAFLD) is the hepatic manifestation of obesity-related metabolic syndrome (MetS). Noninvasive biomarkers for monitoring the progression and severity of these metabolic comorbidities are needed. OBJECTIVES: To investigate the associations of serum thrombospondin-2 (TSP2) with MetS and MAFLD severity, and the potential diagnostic value of serum TSP2 for identifying at-risk metabolic associated steatohepatitis (MASH). METHODS: Blood samples, clinical data, and liver biopsies were collected from consecutively recruited 252 individuals with morbid obesity receiving bariatric surgery. Histopathology samples of liver biopsies were examined in a blinded fashion by 3 independent pathologists. Serum TSP2 levels were measured by enzyme-linked immunosorbent assay. RESULTS: Serum TSP2 levels were significantly elevated in MetS (1.58 [1.07-2.20] ng/mL) compared with non-MetS (1.28 [0.84-1.73] ng/mL; P = .006) in obese patients and positively correlated with increasing number of the MetS components, fasting glucose, glycated hemoglobin, fasting insulin, C-peptide, and homeostatic model assessment of insulin resistance after adjustment of conventional confounders. Serum TSP2 levels differentiated MASH (1.74 [1.32-3.09] ng/mL) from the other non-MASH less severe groups: normal liver (1.41 [1.04-1.63] ng/mL), simple steatosis (1.45 [0.89-1.92] ng/mL), and borderline MASH (1.30 [0.99-2.17] ng/mL) (P < .05). Elevated serum TSP2 was positively associated with the severity of hepatic steatosis, inflammation, fibrosis, and abnormal liver function independent of age, sex and adiposity. Furthermore, high serum TSP2 identified at-risk MASH with area under the operating curve of 0.84 (95% CI 0.70-0.98). CONCLUSION: Serum TSP2 is closely associated with severity and progression of MetS and MAFLD, and is a promising noninvasive biomarker for differentiating MASH from benign steatosis and identifying at-risk MASH patients among individuals with obesity.

Investigating volatiles as the secondary metabolome of Piper methysticum from root powder and water extracts using comprehensive two-dimensional gas chromatography.

ETHNOPHARMACOLOGICAL RELEVANCE: 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. AIM OF THE STUDY: 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. MATERIALS AND METHODS: 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. RESULTS: Dry root powder samples contained high levels of ß-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. CONCLUSIONS: 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.

Foley Catheter Balloon Tamponade for Actively Bleeding Wounds Following Penetrating Neck Injury is an Effective Technique for Controlling Non-Compressible Junctional External Haemorrhage.

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.

Trends in the Management of Abdominal Gunshot Wounds Over the Last Decade: A South African Experience.

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.

Laparotomy for penetrating gastric trauma - A South African experience.

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.

The Management of Penetrating Neck Injury With Retained Knife: 15-Year Experience From a Major Trauma Center in South Africa.

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.

Extracellular Matrix in Synthetic Hydrogel-Based Prostate Cancer Organoids Regulate Therapeutic Response to EZH2 and DRD2 Inhibitors.

Following treatment with androgen receptor (AR) pathway inhibitors, ≈20% of prostate cancer patients progress by shedding their AR-dependence. These tumors undergo epigenetic reprogramming turning castration-resistant prostate cancer adenocarcinoma (CRPC-Adeno) into neuroendocrine prostate cancer (CRPC-NEPC). No targeted therapies are available for CRPC-NEPCs, and there are minimal organoid models to discover new therapeutic targets against these aggressive tumors. Here, using a combination of patient tumor proteomics, RNA sequencing, spatial-omics, and a synthetic hydrogel-based organoid, putative extracellular matrix (ECM) cues that regulate the phenotypic, transcriptomic, and epigenetic underpinnings of CRPC-NEPCs are defined. Short-term culture in tumor-expressed ECM differentially regulated DNA methylation and mobilized genes in CRPC-NEPCs. The ECM type distinctly regulates the response to small-molecule inhibitors of epigenetic targets and Dopamine Receptor D2 (DRD2), the latter being an understudied target in neuroendocrine tumors. In vivo patient-derived xenograft in immunocompromised mice showed strong anti-tumor response when treated with a DRD2 inhibitor. Finally, we demonstrate that therapeutic response in CRPC-NEPCs under drug-resistant ECM conditions can be overcome by first cellular reprogramming with epigenetic inhibitors, followed by DRD2 treatment. The synthetic organoids suggest the regulatory role of ECM in therapeutic response to targeted therapies in CRPC-NEPCs and enable the discovery of therapies to overcome resistance.

Trauma to the gallbladder is associated with concurrent injuries to the extra hepatic biliary system: A South African experience.

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.

Factors associated with high compliance behaviour against COVID-19 in the early phase of pandemic: a cross-sectional study in 12 Asian countries.

INTRODUCTION: Regardless of having effective vaccines against COVID-19, containment measures such as enhanced physical distancing and good practice of personal hygiene remain the mainstay of controlling the COVID-19 pandemic. Countries across Asia have imposed these containment measures to varying extents. However, residents in different countries would have a differing degree of compliance to these containment measures potentially due to differences in the level of awareness and motivation in the early phase of pandemic. OBJECTIVES: In our study, we aimed to describe and correlate the level of knowledge and attitude with the level of compliance with personal hygiene and physical distancing practices among Asian countries in the early phase of pandemic. METHODS: A multinational cross-sectional study was carried out using electronic surveys between May and June 2020 across 14 geographical areas. Subjects aged 21 years and above were invited to participate through social media, word of mouth and electronic mail. RESULTS: Among the 2574 responses obtained, 762 (29.6%) participants were from East Asia and 1812 (70.4%) were from Southeast Asia (SEA). A greater proportion of participants from SEA will practise physical distancing as long as it takes (72.8% vs 60.6%). Having safe distancing practices such as standing more than 1 or 2 m apart (AdjOR 5.09 95% CI (1.08 to 24.01)) or more than 3 or 4 m apart (AdjOR 7.05 95% CI (1.32 to 37.67)), wearing a mask when they had influenza-like symptoms before the COVID-19 pandemic, preferring online news channels such as online news websites/applications (AdjOR 1.73 95% CI (1.21 to 2.49)) and social media (AdjOR 1.68 95% CI (1.13 to 2.50) as sources of obtaining information about COVID-19 and high psychological well-being (AdjOR 1.39 95% CI (1.04 to 1.87)) were independent factors associated with high compliance. CONCLUSIONS: We found factors associated with high compliance behaviour against COVID-19 in the early phase of pandemic and it will be useful to consider them in risk assessment, communication and pandemic preparedness.

Pilot Study on Exhaled Breath Analysis for a Healthy Adult Population in Hawaii.

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.

Association between well-being and compliance with COVID-19 preventive measures by healthcare professionals: A cross-sectional study.

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.