Nylon Suture Loop for Tagging Lymphatic Channels during Lymphaticovenular Anastomosis.

Background Lymphaticovenular anastomosis (LVA) requires special supermicrosurgery techniques designed for vessels less than 0.8 mm in size. While preparing the field for LVA, it is often difficult to handle the lymphatic vessel directly without injuring it or fracturing it entirely. Method We propose a novel technique, which is used in LVA for tagging of lymphatic vessels, with the use of a nylon 6-0 suture and micro-ligaclip. Results We have successfully performed 78 LVAs in 26 cases with this method. The average lymphatic vessel size was 0.3 mm (0.15-0.8 mm). Conclusion This novel technique to implement the use of a nylon suture with a micro-ligaclip to use as a vessel loop for lymphatics has not been previously described in the literature. It is a useful technique that we find beneficial to lymphatic identification through tagging of the lymphatic channels, contributing to greater success in each anastomosis.

Pediatric Tracheostomy.

This Patient Page describes the use of tracheostomy in the pediatric population.

Neuropsychological profiles of adolescents sentenced to detention in Western Australia with and without prenatal alcohol exposure.

BACKGROUND/AIMS: Youth with prenatal alcohol exposure (PAE) are under-recognised in the justice system, warranting improved identification. This study aimed to compare neuropsychological profiles of adolescents, with and without PAE and identify neuropsychological tasks predictive of PAE-group membership. It was hypothesised that participants with PAE would score significantly lower on neuropsychological tests. METHODS: Participants included 85 young people sentenced to detention (mean 15.7 years, 78 males), 46 with PAE. A one-way-multivariate analysis of variance tested differences in neuropsychological functioning between PAE/No-PAE groups, while logistic regression determined tests predictive of PAE. RESULTS: No statistically significant difference in test scores emerged between groups, and regression was not indicative of any models predictive of PAE-group membership. Neuropsychological profiles were characterised by both strengths and weaknesses, with lower verbal and mathematical skills. CONCLUSION(S): While no statistically significant differences were found between the groups, the results provided a unique insight into the neurocognitive profile of Australian youth in detention. Routine screening assessments were recommended for young people sentenced to detention.

Commercial milk formula marketing following increased restrictions in Singapore: A qualitative study.

The promotion of commercial milk formula (CMF) negatively impacts breastfeeding outcomes. In 2019, Singapore updated its 1979 Code of Ethics of the Sale of Infant Foods Ethics Committee Singapore (SIFECS) to increase marketing restrictions on CMF for infants 0-12 months. However, little is known about industry tactics to undermine these restrictions. This qualitative study explores health workers' and mothers' experiences with CMF marketing in Singapore following the 2019 restrictions. We conducted a qualitative study, using semistructured interviews with 14 mothers of infants aged less than 5 months and 20 health workers with expertise in antenatal, maternity, or paediatric care. We analysed data thematically using inductive coding. Five themes were identified. Mothers and health workers reported digital marketing, product line extensions with toddlers' milk and milk for mothers, and CMF sponsorships in the healthcare setting. Expert endorsement, competitive price, nutritional claims, and brand reputation influenced mothers' infant formula choices, yet both mothers and health workers appeared to be unaware of the impact of CMF marketing tactics on their own perceptions. The restriction of CMF marketing and infant feeding practices varied widely between hospitals, with private hospitals and practices having less strict controls on CMF marketing. Despite the updated SIFECS restrictions, CMF companies continue to target mothers and health workers in Singapore. SIFECS restrictions should be tightened to align with international guidelines, by increasing their scope to include toddlers' milk and prohibiting cross-promotion, digital marketing, and any sponsorships of events targeting health workers that may create a conflict of interest.

Core clock gene BMAL1 and RNA-binding protein MEX3A collaboratively regulate Lgr5 expression in intestinal crypt cells.

The intestinal epithelium is highly regenerative. Rapidly proliferating LGR5+ crypt base columnar (CBC) cells are responsible for epithelial turnover needed to maintain intestinal homeostasis. Upon tissue damage, loss of LGR5+ CBCs can be compensated by activation of quiescent +4 intestinal stem cells (ISCs) or early progenitor cells to restore intestinal regeneration. LGR5+ CBC self-renewal and ISC conversion to LGR5+ cells are regulated by external signals originating from the ISC niche. In contrast, little is known about intrinsic regulatory mechanisms critical for maintenance of LGR5+ CBC homeostasis. We found that LGR5 expression in intestinal crypt cells is controlled by the circadian core clock gene BMAL1 and the BMAL1-regulated RNA-binding protein MEX3A. BMAL1 directly activated transcription of Mex3a. MEX3A in turn bound to and stabilized Lgr5 mRNA. Bmal1 depletion reduced Mex3a and Lgr5 expression and led to increased ferroptosis, which consequently decreased LGR5+ CBC numbers and increased the number of crypt cells expressing +4 ISC marker BMI1. Together, these findings reveal a BMAL1-centered intrinsic regulatory pathway that maintains LGR5 expression in the crypt cells and suggest a potential mechanism contributing to ISC homeostasis.

Dynamic Reconstruction of Anal Sphincter with Camera Shutter Style Double-Opposing Gracilis Flaps.

Fournier's gangrene is a life-threatening infection which requires prompt recognition, early surgical debridement of unhealthy tissue, and initiation of broad-spectrum antibiotics. Relook debridement are usually performed until all the devitalized tissue has been removed. Involvement of the anal sphincter may result in significant morbidity such as permanent incontinence. Dynamic reconstruction of the anal sphincter has always been one of the holy grails in the field of pelvic reconstruction. We demonstrate a new method of camera shutter style double-opposing gracilis muscle flaps that allows dynamic sphincteric function without the need for electrostimulation. The bilateral gracilis muscles are inset in a fashion that allows orthograde contraction of the muscle to narrow and collapse the neoanal opening. With biofeedback training, the patient is able to regain dynamic continence and return to function without a stoma. There was also no need for neurotization or microsurgery techniques to restore sphincteric function to the anus. The patient was able to reverse his stoma 14 months after the initial insult and reconstruction with biofeedback training without the use of electrostimulation.

Exploring offending characteristics of young people with foetal alcohol spectrum disorder in Western Australia.

Neurodevelopmental impairments resulting from Foetal Alcohol Spectrum Disorder (FASD) can increase the likelihood of justice system involvement. This study compared offence characteristics in young people with FASD to demographically matched controls (n = 500) in Western Australia. A novel approach (i.e. association rule mining) was adopted to uncover relationships between personal attributes and offence characteristics. For FASD participants (n = 100), file records were reviewed retrospectively. Mean age of the total sample was 15.60 years (range = 10-24), with 82% males and 88% Australian Aboriginal. After controlling for demographic factors, regression analyses showed FASD participants were more likely than controls to be charged with reckless driving (odds ratio, OR = 4.20), breach of bail/community orders (OR = 3.19), property damage (OR = 1.84), and disorderly behaviour (OR = 1.54). Overall, our findings suggest justice-involved individuals with FASD have unique offending profiles. These results have implications for sentencing, diversionary/crime prevention programs and interventions.

Second-hand smoke and fine particulate matter exposures among multi-unit housing residents in Singapore: A pilot study.

Globally, approximately 1.2 million deaths among non-smokers are attributed to second-hand smoke (SHS) per year. Multi-unit housing is becoming the common type of residential dwelling in developed cities and the issue of neighbour SHS is of rising concern especially as 'Work From Home' became the norm during and post COVID-19 pandemic. The objective of this pilot study is to measure and compare the air quality of households that are exposed to SHS and unexposed households among smoking and non-smoking households in Singapore. A total of 27 households were recruited from April to August 2021. Households were categorized into smoking households with neighbour SHS, smoking households without neighbour SHS, non-smoking households with neighbour SHS, and non-smoking household without neighbour SHS. Air quality of the households was measured using calibrated particulate matter (PM2.5) sensors for 7-16 days. Socio-demographic information and self-reported respiratory health were collected. Regression models were used to identify predictors associated with household PM2.5 concentrations and respiratory health. Mean PM2.5 concentration was significantly higher among non-smoking households with neighbour SHS (n = 5, mean = 22.2, IQR = 12.7) than in non-smoking household without neighbour SHS (n = 2, mean = 4.1, IQR = 5.8). Smoking activity at enclosed areas in homes had the lowest PM2.5 concentration (n = 7 mean = 15.9, IQR = 11.0) among the three smoking locations. Exposure to higher household PM2.5 concentration was found to be associated with poorer respiratory health. A 'smoke-free residential building' policy is recommended to tackle the issue of rising neighbour SHS complaints and health concerns in densely populated multi-unit housing in Singapore. Public education campaigns should encourage smokers to smoke away from the home to minimize SHS exposure in household members.

Post-Treatment Neutrophil and Lymphocyte Counts Predict Progression-Free Survival Following First-Line Chemotherapy in Hodgkin's Lymphoma.

Hodgkin's lymphoma carries an excellent prognosis with modern chemotherapy, but a significant proportion of patients remain refractory to or relapse after first-line treatment. Immunological changes post-treatment, such as chemotherapy-induced neutropenia (CIN) or lymphopenia, have shown prognostic significance in multiple tumor types. Our study aims to investigate the prognostic value of immunologic changes in Hodgkin's lymphoma by examining the post-treatment lymphocyte count (pALC), neutrophil count (pANC) and the neutrophil-lymphocyte ratio (pNLR). Patients treated for classical Hodgkin's lymphoma at the National Cancer Centre Singapore using ABVD-based regimens were retrospectively analyzed. An optimal cut-off value for high pANC, low pALC and high pNLR in predicting progression-free survival was determined by receiver operating curve analysis. Survival analysis was performed using the Kaplan-Meier method and multivariable Cox proportional models. Overall OS and PFS were excellent, with a 5-year OS of 99.2% and a 5-year PFS of 88.2%. Poorer PFS was associated with high pANC (HR 2.99, p = 0.0392), low pALC (HR 3.95, p = 0.0038) and high pNLR (p = 0.0078). In conclusion, high pANC, low pALC and high pNLR confer a poorer prognosis for Hodgkin's lymphoma. Future studies should evaluate the potential of improving treatment outcomes by the adjustment of chemotherapy dose intensity based on post-treatment blood counts.

Influx of podoplanin-expressing inflammatory macrophages into the genital tract following Chlamydia infection.

Genital Chlamydia trachomatis infection remains a major health issue as it causes severe complications including pelvic inflammatory disease, ectopic pregnancy and infertility in females as a result of infection-associated chronic inflammation. Podoplanin, a transmembrane receptor, has been previously reported on inflammatory macrophages. Thus, strategies that specifically target podoplanin might be able to reduce local inflammation. This study investigated the expression level and function of podoplanin in a C. trachomatis infection model. C57BL/6 mice infected with the mouse pathogen Chlamydia muridarum were examined intermittently from days 1 to 60 using flow cytometry analysis. Percentages of conventional macrophages (CD11b+ CD11c- F4/80+ ) versus inflammatory macrophages (CD11b+ CD11c+ F4/80+ ), and the expression of podoplanin in these cells were investigated. Subsequently, a podoplanin-knockout RAW264.7 cell was used to evaluate the function of podoplanin in C. trachomatis infection. Our findings demonstrated an increased CD11b+ cell volume in the spleen at day 9 after the infection, with augmented podoplanin expression, especially among the inflammatory macrophages. A large number of podoplanin-expressing macrophages were detected in the genital tract of C. muridarum-infected mice. Furthermore, analysis of the C. trachomatis-infected patients demonstrated a higher percentage of podoplanin-expressing monocytes than that in the noninfected controls. Using an in vitro infection in a transwell migration assay, we identified that macrophages deficient in podoplanin displayed defective migratory function toward C. trachomatis-infected HeLa 229 cells. Lastly, using immunoprecipitation-mass spectrometry method, we identified two potential podoplanin interacting proteins, namely, Cofilin 1 and Talin 1 actin-binding proteins. The present study reports a role of podoplanin in directing macrophage migration to the chlamydial infection site. Our results suggest a potential for reducing inflammation in individuals with chronic chlamydial infections by targeting podoplanin.

Expanding the genetic causes of small-fiber neuropathy: SCN genes and beyond.

Small-fiber neuropathy (SFN) is a disorder that exclusively affects the small nerve fibers, sparing the large nerve fibers. Thinly myelinated Aδ-fibers and unmyelinated C-fibers are damaged, leading to development of neuropathic pain, thermal dysfunction, sensory symptoms, and autonomic disturbances. Although many SFNs are secondary and due to immunological causes or metabolic disturbances, the etiology is unknown in up to half of the patients. Over the years, this proportion of "idiopathic SFN" has decreased, as familial and genetic causes have been discovered, thus shifting a proportion of once "idiopathic" cases to the genetic category. After the discovery of SCN9A-gene variants in 2012, SCN10A and SCN11A variants have been found to be pathogenic in SFN. With improved accessibility of SFN diagnostic tools and genetic tests, many non-SCN variants and genetically inherited systemic diseases involving the small nerve fibers have also been described, but only scattered throughout the literature. There are 80 SCN variants described as causing SFN, 8 genes causing hereditary sensory autonomic neuropathies (HSAN) described with pure SFN, and at least 7 genes involved in genetically inherited systemic diseases associated with SFN. This systematic review aims to consolidate and provide an updated overview on the genetic variants of SFN to date---SCN genes and beyond. Awareness of these genetic causes of SFN is imperative for providing treatment directions, prognostication, and management of expectations for patients and their health-care providers.

MEX3A Mediates p53 Degradation to Suppress Ferroptosis and Facilitate Ovarian Cancer Tumorigenesis.

Epithelial ovarian cancer is a highly heterogeneous and malignant female cancer with an overall low survival rate. Mutations in p53 are prevalent in the major ovarian cancer histotype, high-grade serous ovarian carcinoma (HGSOC), while p53 mutations are much less frequent in other ovarian cancer subtypes, particularly in ovarian clear cell carcinoma (OCCC). Advanced stage OCCC with wild-type (WT) p53 has a worse prognosis and increased drug resistance, metastasis, and recurrence than HGSOC. The mechanisms responsible for driving the aggressiveness of WT p53-expressing ovarian cancer remain poorly understood. Here, we found that upregulation of MEX3A, a dual-function protein containing a RING finger domain and an RNA-binding domain, was critical for tumorigenesis in WT p53-expressing ovarian cancer. MEX3A overexpression enhanced the growth and clonogenicity of OCCC cell lines. In contrast, depletion of MEX3A in OCCC cells, as well as ovarian teratocarcinoma cells, reduced cell survival and proliferative ability. MEX3A depletion also inhibited tumor growth and prolonged survival in orthotopic xenograft models. MEX3A depletion did not alter p53 mRNA level but did increase p53 protein stability. MEX3A-mediated p53 protein degradation was crucial to suppress ferroptosis and enhance tumorigenesis. Consistently, p53 knockdown reversed the effects of MEX3A depletion. Together, our observations identified MEX3A as an important oncogenic factor promoting tumorigenesis in ovarian cancer cells expressing WT p53. SIGNIFICANCE: Degradation of p53 mediated by MEX3A drives ovarian cancer growth by circumventing p53 tumor suppressive functions, suggesting targeting MEX3A as a potential strategy for treating of ovarian cancer expressing WT p53.

Tobacco industry's 'behind the scenes' tactics in Singapore.

BACKGROUND: Tobacco companies have maintained a profitable business in Singapore, despite its strong anti-tobacco climate and commitment to protect public health policymaking from tobacco industry interference in line with Framework Convention on Tobacco Control Article 5.3. This study describes how tobacco companies influence policymaking in a highly regulated environment such as Singapore's, where there is a strong government commitment to Article 5.3. METHODS: Analysis of internal tobacco industry documents detailing the industry's lobbying activities in Singapore, retrieved via snowball searches in the Truth Tobacco Industry Documents Library. Subsequently, we conducted one-on-one interviews with key informants from sectors mentioned in the documents (academia, arts, government, public health, media, trade, education) to fill gaps in information and provide context to events described in the documents. RESULTS: In the 1980s and 1990s, tobacco companies observed that, to influence policy within Singapore's 'hostile' environment, they needed to use 'behind the scenes' tactics, targeting influential individuals at social functions or industry-sponsored events. Tobacco companies used arts and education sponsorships primarily for political purposes, to gain visibility with policymakers. Tobacco companies cultivated relationships with academic researchers and the media to avoid smoke-free legislation in the 1990s and, in the 2010s, appear to have used similar tactics to challenge Singapore's e-cigarette ban. CONCLUSIONS: Countries with a strong commitment to Article 5.3 should consider the tobacco industry's potential interference in policymaking beyond relationships in the government sector, particularly in academia, arts, education and the media, and the more subtle or indirect manners in which these relationships are built.

Tobacco industry strategies for flavour capsule cigarettes: analysis of patents and internal industry documents.

BACKGROUND: The global market for flavour capsule variants (FCVs), cigarettes with a crushable flavour capsule, has grown exponentially. To inform further regulatory efforts, it is important to understand tobacco industry strategies for FCVs. METHODS: Analysis of data from 65 patents and 179 internal tobacco industry documents, retrieved via snowball searches in Patsnap and the Truth Tobacco Industry Documents Library, describing tobacco industry developments related to FCVs. We used an inductive coding method to identify themes relating to FCV features or developments. RESULTS: Tobacco companies were developing FCVs since the 1960s, with little market success until the 2000s following the launch of Camel Crush, a brand which targeted millennials (in their teens or early 20s at the time). Tobacco companies have patented, but not yet marketed, FCVs with microcapsule surface coatings, adjustable or heat-triggered flavour release systems, airflow manipulation features, transparent filters to visualise flavour release, and various flavours and additives for capsules including nicotine/tobacco extracts for an on-demand nicotine hit. Tobacco companies developed FCVs purported to be reduced harm, although their own tests showed that FCVs have higher toxicant concentrations. They have also developed loose flavour capsule units designed to fit into cigarettes, packs, or recessed filters to enable users to customise cigarettes and circumvent tobacco flavour bans. CONCLUSIONS: To prevent tobacco companies from targeting young people and exploiting regulatory loopholes, regulations on tobacco products should ban flavours and consider the broad variety of FCV designs, additives and loose products designed to impart flavour into tobacco products.

Randomized Controlled Trial Investigating Perioperative Immunonutrition for Patients Undergoing Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

BACKGROUND: Immunonutrition has been shown to reduce hospital stay and postoperative morbidity in patients undergoing gastrointestinal, and head and neck surgery. However, its use has not been demonstrated in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). This study aims to determine the effectiveness of perioperative immunonutrition on patients undergoing CRS-HIPEC in reducing length of hospitalization and postoperative complications. PATIENTS AND METHODS: From April 2017 to December 2018, patients undergoing CRS-HIPEC for peritoneal metastases in a single center were enrolled in a randomized controlled trial. Patients with evidence of intestinal obstruction or with diabetes mellitus were excluded. Patients were randomly assigned in a 1:1 fashion to receive perioperative oral immunonutrition or standard nutritional feeds. Length of hospital stay and rates of wound infection and complications were recorded and compared between the two groups in an intention-to-treat manner. RESULTS: A total of 62 patients were recruited and randomized into two groups. Compliance to nutritional feeds in the preoperative period was significantly higher in the standard nutrition group (95.2% versus 75.4%, p = 0.004). There was no difference in postoperative compliance rates. Length of hospital stay and rates of wound infection and postoperative complications were higher in the standard nutrition group when compared with patients on immunonutrition (15.5 versus 11.1 days, p = 0.186; 19% versus 9.7%, p = 0.473; 16% versus 9.7%, p = 0.653; respectively). CONCLUSIONS: Patients undergoing CRS-HIPEC who received perioperative immunonutrition had shorter hospitalization and less wound infections and postoperative complications, although the differences with the standard nutrition group were not statistically significant. Potential benefits of perioperative immunonutrition need to be further evaluated in larger studies.

Automated lung ultrasound image assessment using artificial intelligence to identify fluid overload in dialysis patients.

BACKGROUND: Fluid assessment is challenging, and fluid overload poses a significant problem among dialysis patients, with pulmonary oedema being the most serious consequence. Our study aims to develop a simple objective fluid assessment strategy using lung ultrasound (LUS) and artificial intelligence (AI) to assess the fluid status of dialysis patients. METHODS: This was a single-centre study of 76 hemodialysis and peritoneal dialysis patients carried out between July 2020 to May 2022. The fluid status of dialysis patients was assessed via a simplified 8-point LUS method using a portable handheld ultrasound device (HHUSD), clinical examination and bioimpedance analysis (BIA). The primary outcome was the performance of 8-point LUS using a portable HHUSD in diagnosing fluid overload compared to physical examination and BIA. The secondary outcome was to develop and validate a novel AI software program to quantify B-line count and assess the fluid status of dialysis patients. RESULTS: Our study showed a moderate correlation between LUS B-line count and fluid overload assessed by clinical examination (r = 0.475, p < 0.001) and BIA (r = 0.356. p < 0.001). The use of AI to detect B-lines on LUS in our study for dialysis patients was shown to have good agreement with LUS B lines observed by physicians; (r = 0.825, p < 0.001) for the training dataset and (r = 0.844, p < 0.001) for the validation dataset. CONCLUSION: Our study confirms that 8-point LUS using HHUSD, with AI-based detection of B lines, can provide clinically useful information on the assessment of hydration status and diagnosis of fluid overload for dialysis patients in a user-friendly and time-efficient way.

Helicobacter pylori Infection Elicits Type I Interferon Response in Human Monocytes via Toll-Like Receptor 8 Signaling.

Helicobacter pylori colonization and persistence could precede gastric adenocarcinoma. Elucidating immune recognition strategies of H. pylori is therefore imperative to curb chronic persistence in the human host. Toll-like receptor 7 (TLR7) and TLR8 are widely known as viral single-stranded RNA (ssRNA) sensors yet less studied in the bacteria context. Here, we investigated the involvement of these receptors in the immunity to H. pylori. Human THP-1 monocytic cells were infected with H. pylori, and the expression levels of human Toll-like receptors (TLRs) were examined. The roles of TLR7 and TLR8 in response to H. pylori infection were further investigated using receptor antagonists. Among all TLR transcripts examined, TLR8 exhibited the most prominent upregulation, followed by TLR7 in the THP-1 cells infected with H. pylori J99 or SS1 strains. H. pylori infection-mediated IFN-α and IFN-ß transactivation was significantly abrogated by the TLR7/8 (but not TLR7) antagonist. Additionally, TLR7/8 antagonist treatment reduced H. pylori infection-mediated phosphorylation of interferon regulatory factor 7 (IRF7). Our study suggests a novel role of TLR8 signaling in host immunity against H. pylori through sensing live bacteria to elicit the production of type I interferon.

Adverse childhood experiences, associated stressors and comorbidities in children and youth with fetal alcohol spectrum disorder across the justice and child protection settings in Western Australia.

BACKGROUND: Individuals with Fetal Alcohol Spectrum Disorder (FASD) are at risk of having adverse childhood experiences (ACEs), especially those with child protection and/or justice system involvement. The complex relationship between FASD and psychosocial vulnerabilities in the affected individual is an important clinical risk factor for comorbidity. This study (1) explored the ACEs and associated stressors in individuals with FASD; (2) investigated the association between ACEs and negative outcomes, i.e., justice/child protection system involvement; and (3) examined the relationship between ACEs and comorbid conditions such as mood and neurodevelopmental disorders. METHODS: Data were collected retrospectively via file review from diagnostic clinics in Western Australia. Life adversity was coded using a standardised ACEs questionnaire. A total of 211 participants (72% males) with FASD with a mean age of 11 years (range = 2-21) were included in the final sample. 70% of the total sample had been involved with the child protection system and 40% had trouble with the law. RESULTS: Exposure to drinking/substance misuse at home (70%) and domestic violence (52%) were the two most common ACEs across the total sample. In the entire cohort, 39% had four or more ACEs, indicating higher risks of poor health outcomes. Additional stressors recorded were disengagement from school (43%), transiency (19%), victims of bullying (12%), traumatic brain injury (9%) and homelessness (5%). ACEs such as drinking/substance misuse at home, emotional neglect and physical neglect were positively associated with child protection system involvement. Additionally, exposure to domestic violence was positively correlated with justice system involvement. Higher rates of life adversity in this clinical population were associated with an increased number of comorbidities. Specifically, those with FASD who had comorbidities such as attachment disorder, substance use disorder, and PTSD also reported higher ACEs scores. CONCLUSION: ACEs were common in this clinical population. Increased ACEs in this sample were associated with increased comorbidities and involvement with the child protection and/or justice system. This highlights that prevention, intervention and early diagnosis of FASD are important for at risk children to reduce the negative effects of ACEs.