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PurposePeriodontitis is the sixth most prevalent disease worldwide and periodontal bone loss (PBL) detection is crucial for its early recognition and establishment of the correct diagnosis and prognosis. Current radiographic assessment by clinicians exhibits substantial interobserver variation. Computer-assisted radiographic assessment can calculate bone loss objectively and aid in early bone loss detection. Understanding the rate of disease progression can guide the choice of treatment and lead to early initiation of periodontal therapy.MethodologyWe propose an end-to-end system that includes a deep neural network with hourglass architecture to predict dental landmarks in single, double and triple rooted teeth using periapical radiographs. We then estimate the PBL and disease severity stage using the predicted landmarks. We also introduce a novel adaptation of MixUp data augmentation that improves the landmark localisation.ResultsWe evaluate the proposed system using cross-validation on 340 radiographs from 63 patient cases containing 463, 115 and 56 single, double and triple rooted teeth. The landmark localisation achieved Percentage Correct Keypoints (PCK) of 88.9%, 73.9% and 74.4%, respectively, and a combined PCK of 83.3% across all root morphologies, outperforming the next best architecture by 1.7%. When compared to clinicians’ visual evaluations of full radiographs, the average PBL error was 10.69%, with a severity stage accuracy of 58%. This simulates current interobserver variation, implying that diverse data could improve accuracy.ConclusionsThe system showed a promising capability to localise landmarks and estimate periodontal bone loss on periapical radiographs. An agreement was found with other literature that non-CEJ (Cemento-Enamel Junction) landmarks are the hardest to localise. Honing the system’s clinical pipeline will allow for its use in intervention applications.

Background Vaccine is supposed to be the most effective means to prevent COVID-19 as it may not only save lives but also reduce productivity loss due to resuming pre-pandemic activities. Providing the results of economic evaluation for mass vaccination is paramount important for all stakeholders worldwide. Methods We developed a Markov decision tree for the economic evaluation of mass vaccination against COVID-19. The effectiveness of reducing outcomes after the administration of three COVID-19 vaccines (BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and AZD1222 (Oxford-AstraZeneca)) were modelled with empirical parameters obtained from literatures. The direct cost of vaccine and COVID-19 related medical cost, the indirect cost of productivity loss due to vaccine jabs and hospitalization, and the productivity loss were accumulated given different vaccination scenarios. We reported the incremental cost-utility ratio and benefit/cost (B/C) ratio of three vaccines compared to no vaccination with a probabilistic approach. Results Moderna and Pfizer vaccines won the greatest effectiveness among the three vaccines under consideration. After taking both direct and indirect costs into account, all of the three vaccines dominated no vaccination strategy. The results of B/C ratio show that one dollar invested in vaccine would have USD $13, USD $23, and USD $28 in return for Moderna, Pfizer, and AstraZeneca, respectively when health and education loss are considered. The corresponding figures taking value of the statistical life into account were USD $176, USD $300, and USD $443. Conclusion Mass vaccination against COVID-19 with three current available vaccines is cost-saving for gaining more lives and less cost incurred.

We evaluated the impact of the coronavirus disease (COVID-19) on the sex work industry and assessed how it has impacted the health and social conditions of sex workers in Singapore. We conducted a sequential exploratory mixed methods study amidst the COVID-19 pandemic from April to October 2020, including in-depth interviews with 24 stakeholders from the sex work industry and surveyor-administered structured surveys with 171 sex workers. COVID-19 had a substantial impact on sex workers' income. The illegality of sex work, stigma, and the lack of work documentation were cited as exclusionary factors for access to alternative jobs or government relief. Sex workers had experienced an increase in food insecurity (57.3%), housing insecurity (32.8%), and sexual compromise (8.2%), as well as a decrease in access to medical services (16.4%). Being transgender female was positively associated with increased food insecurity (aPR = 1.23, 95% CI [1.08, 1.41]), housing insecurity (aPR = 1.28, 95% CI [1.03, 1.60]), and decreased access to medical services (aPR = 1.74, 95% CI [1.23, 2.46]); being a venue-based sex worker was positively associated with increased food insecurity (aPR = 1.46, 95% CI [1.00, 2.13]), and being a non-Singaporean citizen or permanent resident was positively associated with increased housing insecurity (aPR = 2.59, 95% CI [1.73, 3.85]). Our findings suggest that COVID-19 has led to a loss of income for sex workers, greater food and housing insecurity, increased sexual compromise, and reduced access to medical services for sex workers. A lack of access to government relief among sex workers exacerbated such conditions. Efforts to address such population health inequities should be implemented. Supplementary Information The online version contains supplementary material available at 10.1007/s10508-021-01951-8.

Background Gay, bisexual and queer (GBQ) men are frequently subjected to minority stressors that have negative impacts on their health. Milestones that include the acceptance and disclosure of sexual identity amongst GBQ men are hence key instruments in understanding the prevalence of internalised homophobia and predicting health outcomes. As such, this work takes a novel approach to deduce the correlates of delayed acceptance of sexual orientation in young GBQ men as a measure of internalised homophobia through retrospective self-reporting and age-based analysis. Methods Participants were recruited as part of a cohort study exploring the syndemic risks associated with HIV acquisition among young GBQ men in Singapore. We examined their levels of internalised, perceived, experienced homophobia, as well as their health behaviours and suicidal tendencies. Two separate variables were also self-reported by the participants – the age of questioning of sexual orientation and the age of acceptance of sexual orientation. We subsequently recoded a new variable, delayed acceptance of sexual orientation, by taking the difference between these two variables, regressing it as an independent and dependent variable to deduce its psychosocial correlates, as well as its association with other measured instruments of health. Results As a dependent variable, delayed acceptance of sexual orientation is positively associated with an increase of age and internalised homophobia, while being negatively associated with reporting as being gay, compared to being bisexual or queer. As an independent variable, delayed acceptance of sexual orientation was associated with a delayed age of coming out to siblings and parents, suicide ideation, historical use of substances including smoking tobacco cigarettes and consuming marijuana, as well as reporting higher levels of experienced, internalised and perceived homophobia. Conclusion Greater levels of early intervention and efforts are required to reduce the heightened experience of minority stress resulting from communal and institutional hostilities. Areas of improvement may include community-based counselling and psychological support for GBQ men, while not forsaking greater education of the social and healthcare sectors. Most importantly, disrupting the stigma narrative of a GBQ ‘lifestyle’ is paramount in establishing an accepting social environment that reduces the health disparity faced by GBQ men.

This article considers merits and drawbacks of "undetectable = untransmissible" (U = U) messaging in the global HIV response. First, viral suppression might be achieved with effective treatment, but not everyone living with HIV has access to such intervention and care. Second, although U = U can help individuals living with HIV, this messaging might stigmatize those for whom interventions have not achieved viral suppression. Third, although biomedical advances have attempted to address infectiousness, syndemic drivers that predispose individuals to HIV acquisition are not well accounted for by U = U messaging.

Objectives We considered how decision making around human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) among gay, bisexual, and other men who have sex with men (GBMSM) is made in the context of one’s perceived risk of HIV acquisition and the availability of condoms. Methods We recruited 648 GBMSM aged 18 years old and residing in Singapore through Grindr. Participants were given information on PrEP and participated in a discrete choice experiment requiring them to choose between 2 baskets of PrEP attributes and compare the chosen “PrEP only” option to default options of “condoms only” or “PrEP with condoms.” Generalized multinomial logit model was used to examine the scaling effect and preference heterogeneity. Latent class analysis was conducted to examine preference heterogeneity in the sample. Results Latent class analysis revealed 3 classes of GBMSM: PrEP conservatives (53.9%), moderates (31.1%), and liberals (14.9%). PrEP conservatives were more likely to report greater utility when using condoms only compared with PrEP only, as well as PrEP with condoms, compared with PrEP only, and more likely to report the lowest utility for PrEP as perceived HIV risk increased. PrEP liberals were more likely to report greatest utilities for PrEP only compared with condoms only, as well as PrEP only compared with PrEP with condoms. The utility for PrEP was not affected by perceived risk of HIV or sexually transmitted infections when risks were low. Conclusion This study provides some evidence for risk compensation among a class of GBMSM who already perceived themselves to be good candidates for PrEP before the discrete choice experiment.

Objective: To explore the effects of Huoxue Huayu detoxification method on the levels of GSK-3β and β-catenin in OSF patients and its mechanism. Methods: A total of 120 patients with oral submucosal fibrosis (OSF) treated in our hospital from May 2018 to December 2019 were selected and divided into routine treatment group and Huoxue Huayu detoxification group of 60 cases according to the lottery method. The routine treatment group was treated with triamcinolone acetonide injection, and the Huoxue Huayu detoxification group was treated with Huoxue Huayu detoxification. The lesion area, mouth opening degree, SFRP1 level in gingival crevicular fluid and saliva, TCM symptom score, TGF-β1, IL-6, GSK-3β, β-catenin expression and clinical effect were observed in the two groups. Results: After treatment, the lesion area of oral mucosa in the Huoxue Huayu detoxification group was smaller than that in the routine treatment group (P

Lavender ( Lavandula angustifolia ) is an important medicinal and aromatic plant. However, the application of lavender essential oil (LEO) is limited by its instability, low solubility and high volatility. Therefore, to improve the stabilities and antioxidant activities of LEO and thereby expand the applications, LEO was microencapsulated by metal-organic frameworks based on β-cyclodextrin and potassium cation (K-βCD-MOFs) with different mass core/wall ratios. The results showed that the best inclusion rate was 96.67% with the ratio of 1:10. Then, the optimum inclusion product was characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). The thermal and pH stabilities and the intracellular antioxidant activities were also studied. The results showed that the stabilities of the oil with K-βCD-MOFs inclusions and their abilities to resist acid and alkali were significantly stronger than those of LEO itself. In addition, the intracellular antioxidant activities of LEO were also enhanced by the K-βCD-MOFs inclusion. These results suggested the potential of K-βCD-MOFs as carriers for essential oils in food industry applications.

The Singapore Health Services cluster (SingHealth) radiology film archives are a valuable repository of local radiological cases dating back to the 1950s. Some of the cases in the archives are of historical medical interest, i.e. cerebral angiography in the workup of patients with hemiplegia. Other cases are of historical social interest, being conditions seen during earlier stages of Singapore’s development, i.e. bound feet. The archives form a unique portal into the development of local radiology as well as the national development of Singapore. A selection from the archives is published in commemoration of the International Day of Radiology in 2020, as well as the 200th anniversary of the Singapore General Hospital in 2021. This pictorial essay comprises gastroenterology, musculoskeletal and obstetrics and gynaecology cases from the archives.

Purpose We aimed to identify the anterolateral ligament (ALL) tears in anterior cruciate ligament (ACL)-deficient knees using standard 1.5-Tesla magnetic resonance imaging (MRI). Methods We included all patients who underwent primary ACL reconstruction at our center between 2012 and 2015. Exclusion criteria included patients with multiple ligament injuries, lateral collateral ligament, posterolateral corner, and infections, and patients who underwent MRI more than 2 months after their injury. All patients (n = 148) had ACL tears that were subsequently arthroscopically reconstructed. The magnetic resonance (MR) images of the injured knees performed within 2 months of injury were reviewed by a musculoskeletal radiologist and an orthopedic surgeon. The patients were divided into two groups. The first group of patients had MRI performed within 1 month of injury. The second group of patients had MRI performed 1–2 months after the index injury. Both assessors were blinded and the MR mages were read separately to assess the presence of ALL, presence of a tear and the location of the tear. Based on their readings, interobserver agreement (kappa statistic (K)), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were compared. Results The ALL was identified in 100% of the patients. However, there was a discrepancy of up to 15% in the identification of tear of the ALL. In the first group in which MRI scans were performed within 1 month of injury, the ALL tear was identified by the radiologist in 92% of patients and by the surgeon in 90% of patients (Κ = 0.86). In the second group in which MRI scans were performed within 1–2 months of the injury, the ALL tear was identified by the radiologist in 78% of patients and by the surgeon in 93% of patients (K = 0.62). Conclusion The ALL can be accurately identified on MRI, but the presence and location of ALL tear and its location cannot be reliably identified on MRI. The accuracy in identification and characterization of a tear was affected by the interval between the time of injury and the time when the MRI was performed. Level of evidence Diagnostic, level IIIb, retrospective.

Although hepatectomy is the mainstay of curative therapy for hepatocellular carcinoma (HCC), post-operative complications remain high. Presently there is conflicting data on the impact of morbidity on oncologic outcomes. We sought to identify predictors for the occurrence of post-hepatectomy complications, as well as to analyse the impact on overall survival (OS) and recurrence-free survival (RFS).We performed a retrospective review of 888 patients who underwent resection for HCC from 2001 to 2016 in our institution.A total of 237 patients (26.7%) developed 254 complications of Clavien-Dindo Grade ≥2. Hepatitis B (p = 0.0397), elevated ASA score (p = 0.0002), higher platelet counts (p = 0.0277), raised pre-operative APRI scores (p = 0.0105) and bloodloss (p 0.0001) were independently associated with the development of complications. After propensity-score matching, 458 patients were compared in a 1:1 ratio (229 with complications versus 229 without). Patients with complications had significantly longer median length of stay (9 days [IQR 7-15] versus 6 days [IQR 5-8], p 0.0001), higher 90-day mortality rates as well as inferior OS (p = 0.0139), but there was no difference in RFS (p = 0.4577). Age (p = 0.0006), elevated Child Pugh points (p 0.0001), microvascular invasion (p = 0.0002), multifocal tumours (p = 0.0002), R1 resection (p = 0.0443) and development of complications (p = 0.0091) were independent predictors of inferior OS.Post-operative morbidity affected both short-term and OS outcomes after hepatectomy for HCC. Hepatitis B, higher ASA scores, elevated preoperative APRI and increased blood loss were found to predict a higher likelihood of developing complications. This may potentially be mitigated by careful patient selection and adopting strict measures to minimise intraoperative bleeding.

Objectives Ultrasound measured optic nerve sheath diameter is a noninvasive, nonirradiating tool for estimating intracranial hypertension. The objective of this systematic review and meta-analysis is summarization of the current evidence for accuracy of ultrasound measured optic nerve sheath diameter in detecting intracranial hypertension in pediatric patients. Data sources Medical subject heading terms were used to search MEDLINE, Embase, Google Scholar, Web of Science, and the Cochrane Library for relevant citations. Publications from January 1, 2000, to June 30, 2019, were included in the search strategy. Study selection Studies were included if they involved patients less than 18 years, where ultrasound measured optic nerve sheath diameter was compared to conventional, nonophthalmic tests for intracranial hypertension. Studies were excluded if there was insufficient data to compute a sensitivity/specificity table. Case reports, case series, and manuscripts not published in English were also excluded. Data extraction The initial search returned 573 citations. Of these, 57 were selected for review. Data synthesis Eleven citations were included in the final meta-analysis. A bivariate random-effects meta-analysis was performed, which revealed a pooled sensitivity for ultrasound measured optic nerve sheath diameter of 93% (95% CI, 74-99%), a specificity of 74% (95% CI, 52-88%), and a diagnostic odds ratio of 39.00 (95% CI, 4.16-365.32). The area under the curve of the hierarchical summary receiver operating characteristic curve was 0.90 (95% CI, 0.87-0.93). Subgroup analyses of the test's performance evaluating new-onset intracranial hypertension and in comparison to invasively measured intracranial pressure were performed. The test performance in these instances was similar to findings in the primary analysis. Conclusions We are unable to identify a threshold value in ultrasound measured optic nerve sheath diameter for the determination of intracranial hypertension in children. Even though the ultrasound measured optic nerve sheath diameter measurement is highly sensitive to the presence of increased intracranial pressure, the test has only moderate specificity. Therefore, other confirmatory methods and further investigation is necessary in the clinical care of children. The technique is likely not sufficiently precise for clinical use in the absence of other confirmatory methods, and further investigation is necessary to determine clinical protocols for its use in children.

Background Traditional chemical methods were mainly used to evaluate the total antioxidant activity of essential oils. How to determine the bioactivity of each compound in mixtures is an interesting research topic. Nowadays, an ultra-fast gas chromatography electronic nose (E-nose) has been gradually used in the detection of volatile compounds, but the screening of the active components of essential oils has not been reported. E-nose coupled with chemical methodology was established using the essential oil from rosemary (EOR) as a specific application example. The proposed method can both identify the chemical constituents of EOR and quickly screen the antioxidant by comparing the change of chromatographic peak area of every component in EOR before and after reaction with free radicals. Results Among all chemical constituents in EOR, verbenone, eucalyptol and o-cymene showed the strongest scavenging abilities in 1,1'-diphenyl-2-picrylhydrazine (DPPH·), 2,2'-azino-bis(3-ethyl-benzothiazoline-6-sulphonate) (ABTS·+ ) and hydroxyl (·OH) radicals, respectively, with scavenging rates of 67.9%, 39.5%, and 69.9%. The reliability and feasibility of using E-nose to identify chemical constituents of EOR were verified by gas chromatography-tandem mass spectrometry (GC-MS/MS). The GC-MS/MS results showed that the main components of EOR were α-pinene (422.2 μg g-1 ), p-cymene (208.4 μg g-1 ), camphor (203.5 μg g-1 ), verbenone (160.2 μg g-1 ), and eucalyptol (129.1 μg g-1 ). Conclusions The E-nose methods can be used as a complementary method to traditional spectrophotometric techniques. Furthermore, this study will be of great significance for the rapid screening of antioxidant active components in essential oils from natural products. © 2020 Society of Chemical Industry.

Background Rehospitalizations are common in healthcare. They are costly for hospitals and patients and a substantial percentage are preventable, partly because hospital-to-community transitions are often unmanaged or poorly managed. In this study, we conducted a pragmatic randomized, controlled trial to evaluate the effectiveness of a new nurse–practitioner-led transitional care program called CareHub, piloted in Singapore’s National University Hospital. Methods Study population included all eligible cardiac patients admitted between July 2016 and November 2016. Patients were followed for six months post-discharge. Primary outcomes other than emergency department visits were all cardiac-related: number of readmissions, specialist visits, emergency department visits, and total days readmitted. Secondary outcomes: variables related to quality of life and transitional care. Regression analyses were used to estimate the intent-to-treat effect of CareHub and explore treatment heterogeneity. Results CareHub reduced the mean number of unplanned readmissions by 0.23 (a 39% reduction relative to control mean of 0.60 unplanned readmissions, p Conclusion A carefully designed protocolized cardiac hospital-to-home transition program can reduce resource utilization while improving quality of life.

Gay, bisexual, and other men who have sex with men (GBMSM) are a key population that is disproportionately affected by HIV. However, few studies have explored how and why disclosure of HIV status occurs in this population. To understand disclosure in the context of other socioecological factors, we conducted a qualitative study among 24 self-identified HIV-positive GBMSM, aged 21 and above, and who were Singaporean residents. Analysis of participants' interviews revealed that disclosure of HIV status was not a binary event; rather, each type of disclosure held varying degrees of positive and negative ramifications. Disclosure and self-acknowledgement of HIV status at each time point also had different consequences for participants' quality of life. Suggested potential interventions include increasing training for medical professionals and public awareness surrounding issues relating to HIV. Findings from this study provide a framework to describe the complexities that accompany serostatus disclosure in a setting where there are prevalent "shame-based", negative attitudes towards HIV. As such, this framework can also be utilized in the future planning and organization of services for this target population in similar contexts.

Gay, bisexual, and other men who have sex with men (GBMSM) are disproportionately affected by HIV and other sexually transmitted infections (STI). While levels of self-perceived risk of HIV or other STI acquisition has been well-established as a factor that is positively associated with HIV or other STI testing, less effort has been made to identify the processes through which GBMSM assess their perceived risk of HIV or other STI acquisition. We conducted a qualitative study exploring the factors influencing self-perceived risk of HIV or other STI among GBMSM. Semi-structured interviews were conducted with 35 self-identified GBMSM in Singapore from October 2017 to June 2018, and the data were analyzed through inductive thematic analysis. Participants reported drawing on individual factors including their own sexual health knowledge and past experiences of risk, interpersonal factors including their sexual partners' attributes or characteristics and perceived trust and familiarity with their sexual partners, and situational factors including the venue and familiarity with such venues where sexual activity took place, in determining their self-perceived risk of HIV or other STI acquisition. The results of this study have implications for HIV and other STI risk education.

Purpose: Thalassemia (HbH) is a chronic condition that may have potential complications of liver cirrhosis secondary to iron overload or hepatitis. Iron deposition in the liver can mask the classic imaging findings of hepatocellular carcinoma. We report an interesting case with similar nature with diagnostic dilemma, where multiple imaging modalities were unable to delineate the nature of the liver nature, and the patient was eventually diagnosed with hepatocellular carcinoma, after percutaneous biopsy was performed. Method: A 61-year-old male, with background history of HbH disease and transfusion dependent, presented with an incidental finding of 2 liver nodules on an ultrasound scan after complaints of right hypochondrium pain. A computed tomography (CT) scan diagnosed one nodule as a flash-filling haemangioma but was inconclusive about the other larger nodule. A magnetic resonance imaging (MRI) scan was also inconclusive but gave the differentials of extramedullary haematopoiesis. A sulphur colloid scan did not show uptake, making extramedullary haematopoiesis less likely. Results: A percutaneous biopsy of the indeterminate liver nodule was performed, and the histology showed hepatocellular carcinoma. The patient underwent wedge resection of the hepatocellular carcinoma and recovered well post-operatively. Conclusion: In the event of inconclusive imaging in patients with significant risk factors for hepatocellular carcinoma, a percutaneous biopsy should be performed for definitive diagnosis.

The current research tried to explore the effect of Qiweibaizhu powder (QWBZP) on the bacterial diversity and community structure of the intestinal mucosa of dysbiosis diarrhea mice and provide a scientific basis for the efficacy of QWBZP on antibiotic-induced diarrhea. A dysbiosis diarrhea mouse model was constructed with broad-spectrum antibiotics through a mixture of cephradine capsules and gentamicin sulfate (23.33 mL·kg-1·d-1). Intestinal mucosa was collected, and DNA was extracted from each group. The bacterial characteristics in intestinal mucosa were analyzed by MiSeq sequencing based on the 16S rRNA sequencing platform. There were no significant differences in alpha diversity indices among the three groups. The sample distributions in both the normal and QWBZP groups were relatively concentrated, and the distance among individuals was close. However, an opposite result was obtained in the model group. Furthermore, the composition and abundance of species were similar between the normal group and the QWBZP group at both the phylum and genus levels. After treatment with QWBZP, the abundance of Lactobacillus increased, and Proteobacteria decreased, and the Firmicutes/Bacteroidetes ratio decreased to a normal level. Our results indicate that QWBZP can help repair mucosal bacterial structure and recover mucosal microbiota. Specifically, QWBZP increased the abundance of Lactobacillus and Bacteroidales S24-7 group norank.

A 74-year-old woman receiving long-term anticoagulation with warfarin for chronic atrial fibrillation presented with severe acute abdominal pain, diarrhoea and vomiting. Initial laboratory workup revealed a deranged coagulation profile. Computed tomography of the abdomen and pelvis demonstrated spontaneous distal jejunal intramural haematoma with associated reactive ileus. No overt pneumatosis intestinalis, intraperitoneal free gas or haemoperitoneum was seen. Based on clinical and imaging findings, a diagnosis of over-anticoagulation complicated by small bowel intramural haematoma was made. The patient was managed non-operatively with analgesia, cessation of warfarin and reversal therapy with vitamin K. Warfarin therapy was recommenced upon resolution of symptoms and optimisation of coagulation status. The clinical presentation, radiological features and overall management of anticoagulation-induced bleeding are further discussed in this article.

Introduction Desmoid tumor is a locally-invasive neoplasm that causes significant morbidity. There is recent interest in cryotherapy for treatment of extra-abdominal desmoid tumors. This systematic review assesses evidence on safety and efficacy of cryotherapy in the treatment of extra-abdominal desmoid tumors. Materials and methods The systematic review was conducted with reference to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Literature search was performed using MEDLINE and the Cochrane Central Register of Controlled Trials. 9 full text papers were reviewed and meta-analysis was performed for measures of safety, efficacy and symptom relief. Results The estimated pooled proportion of major and minor complications was 4.2% (95% CI, 1.8–9.6; I 2 = 0%) and 10.2% (95% CI, 5.7–17.8; I 2 = 0%) respectively. The estimated pooled proportion of non-progressive disease rate of all studies was 85.8% (95% CI, 73.4–93.0; I 2 = 32.9%). The estimated progression free survival rate at 1 year was 84.5% (95% CI:74.6–95.8) and 78.0% at 3 years (95% CI: 63.8–95.3). As for pain control, the estimated pooled proportion of patients with decrease in visual analogue scale (VAS) > = 3 for those with VAS > = 3 before treatment for 2 studies was 87.5% (95% CI, 0.06–100; I 2 = 71.5%) while 37.5% to 96.9% of patients were reported to have experienced partial or complete symptom relief in the other studies. Conclusion Cryotherapy is a safe and effective treatment modality for extra-abdominal desmoid tumors with efficacy similar to those treated with traditional strategies in the short to medium term.

Although hemorrhagic sepsis caused by Aeromonas hydrophila infection is the dominant disease in the aquaculture of Chinese soft-shelled turtle, information on its molecular pathology is seriously limited. In this study, ninety turtles intraperitoneally injected with A. hydrophila exhibited two different phenotypes based on the pathological symptoms, referred to as active and inactive turtles. Comparative transcriptomes of liver and spleen from these two groups at 6, 24, and 72 h post-injection (hpi) were further analyzed. The results showed that cytokine–cytokine receptor interaction, PRRs mediated signaling pathway, apoptosis, and phagocytosis enriched in active and inactive turtles were significantly different. Pro-inflammatory cytokines, the TLR signaling pathway, NLR signaling pathway, and RLR signaling pathway mediating cytokine expression, and apoptosis-related genes, were significantly up-regulated in inactive turtles at the early stage (6 hpi). The significant up-regulation of phagocytosis-related genes occurred at 24 hpi in inactive turtles and relatively lagged behind those in active turtles. The anti-inflammatory cytokine, IL10, was significantly up-regulated during the tested periods (6, 24, and 72 hpi) in active turtles. These findings offer valuable information for the understanding of molecular immunopathogenesis after A. hydrophila infection, and facilitate further investigations on strategies against hemorrhagic sepsis in Chinese soft-shelled turtle T. sinensis.

Extracellular vesicle (EV), critical mediators of cell-cell communication, allow cells to exchange proteins, lipids, and genetic material and therefore profoundly affect the general homeostasis. A hypoxic environment can affect the biogenesis and secrete of EVs, and the cargoes carried can participate in a variety of physiological and pathological processes. In hypoxia-induced inflammation, microRNA(miRNA) in EV participates in transcriptional regulation through various pathways to promote or reduce the inflammatory response. Meanwhile, as an important factor of immune response, the polarization of macrophages is closely linked to miRNAs, which will eventually affect the inflammatory state. In this review, we outline the possible molecular mechanism of EV changes under hypoxia, focusing on the signaling pathways of several microRNAs involved in inflammation regulation and describing the process and mechanism of EV-miRNAs regulating macrophage polarization in hypoxic diseases., EV-miRNAs regulate the polarization phenotype of macrophages and promote the release of inflammation-related cytokines through a variety of signaling pathways under hypoxia, ultimately affect the development of inflammation.

ObjectivePrevious studies have identified that sleep-disordered breathing is associated with the increased risk of cardiovascular disease. However, CPAP, the preferred treatment of sleep apnea, does not appear to reduce the risk of adverse cardiovascular events and deaths in ischemic heart disease. Our aim was to determine whether OSA can be a prognostic factor for cardiovascular adverse events and deaths in patients with ischemia heart disease.MethodsWe searched Medline via PubMed, Embase, and the Cochrane Library database for clinical studies reporting the major adverse cardiac outcomes of SDB in patients with myocardial ischemia. Sleep apnea tests is mainly performed with cardiorespiratory polygraphy or portable diagnostic device. Summary hazard ratio(HR) and 95% CIs were conducted using random-effects meta-analysis.ResultsEighteen literatures were included, with total participants of 9,138. Sixteen studies reported MACCEs, there was significant association of SDB with MACCES (HR, 1.66[95% CI, 1.41 to 1.94]; P< 0.0001), all-cause mortality (HR, 1.39[95% CI 1.12 to 1.73], P=0.0027) and cardiovascular mortality (HR, 2.12[95% CI 1.23 to 3.65], P=0.007). Subgroup analysis showed that one study was the cause of heterogeneity, while no correlation between SDB and outcomes for sleep apnea severity, follow-up time or whether surgery was performed.ConclusionSDB is associated with adverse cardiac outcomes in patients with ischemic heart disease, suggesting that sleep apnea can be screened for patients with ischemic heart disease, which can be used as a clinically relevant strategy of secondary prevention to reduce the risk of adverse outcomes.

Objective: Arteriovenous fistulas are a principal mainstay of long-term dialysis access for patients with end stage renal failure. However, the patency of arteriovenous fistulas is limited, often requiring percutaneous transluminal angioplasty as a salvage procedure. We report a case of percutaneous method of arteriovenous fistula salvage. Methods: A gentleman with brachiocephalic arteriovenous fistula created in 2015 was admitted under us for dialysis access issue. His fistula history was notable for recurrent and refractory venous outflow stenosis of the cephalic vein and the cephalic arch with multiple previous interventions. Ultrasound showed cephalic arch occlusion with high venous pressures. He underwent left brachicephalic fistula percutaneous bypass. We describe the percutaneous creation of a brachial–subclavian arteriovenous fistula via a bypass graft from a worsening brachial-cephalic fistula with cephalic arch occlusion that is not amendable to angioplasty. Results: Final angiogram showed smooth flow to central vein. He is 2 years post procedure, and his fistula remained patent with no interventions required. Conclusion: Percutaneously created jump bypass grafts can reliably produce sustained long-term patency.

IntroductionCirculating tumor cells (CTCs) and cell-free tumor DNA (ctDNA) are tumor components present in circulation. Due to the limited access to both CTC enrichment platforms and ctDNA sequencing in most laboratories, they are rarely analyzed together.MethodsConcurrent isolation of ctDNA and single CTCs were isolated from lung cancer and breast cancer patients using the combination of size-based and CD45-negative selection method via DropCell platform. We performed targeted amplicon sequencing to evaluate the genomic heterogeneity of CTCs and ctDNA in lung cancer and breast cancer patients.ResultsHigher degrees of genomic heterogeneity were observed in CTCs as compared to ctDNA. Several shared alterations present in CTCs and ctDNA were undetected in the primary tumor, highlighting the intra-tumoral heterogeneity of tumor components that were shed into systemic circulation. Accordingly, CTCs and ctDNA displayed higher degree of concordance with the metastatic tumor than the primary tumor. The alterations detected in circulation correlated with worse survival outcome for both lung and breast cancer patients emphasizing the impact of the metastatic phenotype. Notably, evolving genetic signatures were detected in the CTCs and ctDNA samples during the course of treatment and disease progression.ConclusionsA standardized sample processing and data analysis workflow for concurrent analysis of CTCs and ctDNA successfully dissected the heterogeneity of metastatic tumor in circulation as well as the progressive genomic changes that may potentially guide the selection of appropriate therapy against evolving tumor clonality.

Background We evaluated the impact of the Coronavirus Disease (COVID-19) on the sex work industry, and assessed how it has impacted the health and social conditions of sex workers in Singapore. Methods We conducted a sequential exploratory mixed methods study amidst the COVID-19 pandemic from April to October 2020, including in-depth interviews with 24 stakeholders from the sex work industry and surveyor-administered structured surveys in the field with 171 sex workers. The in-depth interviews allowed the team to qualitatively explore and generate themes around how COVID-19 had impacted sex workers in Singapore, and informed the design of the quantitative surveyor-administered survey questionnaire. Qualitative data were analyzed through framework analysis while survey data were analyzed through descriptive statistics, and multivariable Poisson regression models. Results COVID-19 had a substantial impact on sex workers’ income, while the illegality of sex work, stigma, and the lack of work documentation were cited as exclusionary factors for access to alternative jobs or government relief. Sex workers had experienced an increase in food insecurity (57.3%), housing insecurity (32.8%), and sexual violence and compromise (8.2%), as well as a decrease in access to medical services (16.4%). Being transgender female was positively associated with increased food insecurity (aPR=1.23, 95%CI [1.08, 1.41]), housing insecurity (aPR=1.28, 95%CI [1.03, 1.60]) and decreased access to medical services (aPR=1.74, 95%CI [1.23, 2.46]), being a venue-based sex worker was positively associated with increased food insecurity (aPR=1.46, 95%CI [1.00, 2.13]), and being a non-Singaporean citizen or permanent resident was positively associated with increased housing insecurity (aPR=2.59, 95%CI [1.73, 3.85]). Conclusions Our findings suggest that COVID-19 has led to a loss of income for sex workers, leading to a worsening of social and health conditions for sex workers. A lack of access to government relief among sex workers exacerbated such conditions.

Background This study draws on qualitative insights on the barriers and facilitators to HIV testing, as well as perceptions of HIV self-testing (HIVST), to propose a framework to understand the benefits, but also potential knock-on implications of introducing HIVST in the context of other STI testing. Methods We conducted semi-structured, in-depth interviews with 30 gay, bisexual and other men who have sex with men (GBMSM) aged 18 and 39 years old in Singapore. Interview topics included barriers and facilitators to HIV and other STI testing, as well as perceptions of HIVST. Interviews were audio-recorded, transcribed, coded, and analysed using thematic analysis. Results For HIV testing, participants cited the perceived risk of acquiring, susceptibility to, and symptoms of HIV as internal motivators, while social influence and accessibility of HIV testing services were external motivators. For STI testing, perceived symptoms and partner notification of STI were reported as an internal and external motivator, respectively. Availability of bundle tests, starting a new relationship, and instances of mandatory testing motivated both simultaneous HIV and other STI testing. The fear of a positive diagnosis and lack of confidentiality were cited as internal and external barriers to HIV testing, respectively, while low perceived severity of other STI and the cost of STI tests were cited as internal and external barriers to other STI testing, respectively. We identified pathways to HIV and other STI testing and discussed how the introduction of HIVST may reduce opportunities for other STI testing. Conclusions The findings of this study suggest that introducing HIVST might weaken linkages to other STI testing if alternative strategies of promoting other STI testing are not simultaneously implemented. We recommend that future interventions address both the risks of HIV and other STI simultaneously, and that structural interventions promoting HIV and other STI prevention be balanced accordingly.

Background Shelter-in-place and related COVID-19 physical distancing measures may influence the risk of intimate partner violence (IPV). The current study aims to (1) describe perceived changes in IPV experienced during and prior to the COVID-19 outbreak, (2) identify social correlates of IPV. Methods The International Sexual Health and REproductive Health (I-SHARE) study collected data on sexual and reproductive health during the COVID-19 pandemic (10,717 respondents in 16 countries between July 26thand December 1st 2020). The sample comprises participants in 7 HICs, 5 UMICs, 2 LMICs, and 2 LICs: 6,643 (62.3%) participants identified as women, 3,650 (34.2%) as men, and 178 (1.7%) as another gender. The median age was 30 (IQR 24; 39). Adults (≥18yrs) were recruited online (social media, panel, or population-representative). IPV was a primary outcome measured using an adapted six-item version of the WHO IPV scale. Mixed effects modelling was used to assess participants’ experience of IPV in the three months prior to, and during, the COVID-19 physical distancing measures; participants were also asked about informal and formal reporting of IPV. Results Preliminary analysis indicated that 1,864 (17.4%) of the 10,717 participants reported experiencing at least one form of IPV before the introduction of COVID-19 control measures; 1,346 (12.6%) participants reported IPV during COVID-19 physical distancing measures. Among participants experiencing IPV when physical distancing measures were in place, 691 (37.1%) told either a friend, the police, social services or other organization. Participants with a reduction in household income during the COVID-19 measures (aOR 1.48, 95% CI 1.29–1.69) and increased consumption of alcohol during COVID-19 (aOR 1.51, 95% CI 1.26–1.81) had higher odds of experiencing IPV. Conclusion IPV may have decreased during COVID-19 measures, but remained common overall. Structural interventions are necessary to mitigate the impact of IPV.

Ethnopharmacological Relevance: Pepper essential oils have potential immunomodulatory, anti-tumor, and anti-cancer activities. Pepper exhibits the potential to prevent or attenuate carcinogenesis as therapeutic tools. However, the related mechanism remains unelucidated.Aim of the Study: The present study aims to provide reasonable information for the explanation of the dissimilarity of the essential oils from white (WPEO) and black pepper (BPEO).Materials and Methods: WPEO, BPEO, and their single active component, as well as synthetic antioxidants, were compared by the cell model methods and chemical methods, including intracellular antioxidant activity (CAA), total antioxidant activities (TAA), superoxide radical (SR), hydroxyl radical (HR), DPPH radical (DR) scavenging activities and inhibition ability of lipoprotein lipid peroxidation (ILLP).Results: The median effective concentration (EC50) values (mg/mL) of the WPEO and BPEO of SR, HR, DR, and ILLP were 0.437 and 0.327, 0.486 and 0.204, 7.332 and 6.348, 0.688, and 0.624 mg/mL, respectively. The CAA units of WPEO and BPEO were 50.644 and 54.806, respectively. CAA, DR, and TAA of BPEO were significantly higher than those of WPEO (p < 0.05). The BPEO and WPEO can be differentiated as the former have higher correlations with 3-carene, α-pinene, β-pinene, and limonene while the latter has a higher caryophyllene correlation. The WPEO and BPEO show a good intracellular scavenging ability of reactive oxygen species in HeLa cells.Conclusion: Generally, pepper oil has stronger activities than single components, indicating that pepper is a broad-spectrum natural antioxidant.

Oral submacosal fibrosis (OSF) has been recognized as one of the oral potentially malignant disorders. Areca nut chewing is implicated in this pathological fibrosis. The current treatments for OSF have failed to achieve the desired curative effect. Here, we propose that curcumin has excellent therapeutic effect on OSF and explore its specific mechanism. Transwell assay was performed to detected cell migration. Flow cytometry was used to measured apoptosis. And MTT assay was performed to test cell viability. Gene and protein levels were detected by quantitative real-time polymerase chain reaction (qPCR) and western blotting. Our results displayed that curcumin treatment reduced fibrosis-related molecules (collagen type I alpha 1, collagen type III alpha 1, tissue inhibitor of metalloprotease 2) in arecoline-treated oral mucosal fibroblasts and elevated matrix metalloproteinase 2 expression. Additionally, curcumin could suppress cell proliferation and migration, and enhance the apoptosis of arecoline-treated normal oral mucosal fibroblasts. Most importantly, the hypoxia-inducible factor-1α (HIF-1α), transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF) expressions in arecoline-treated normal oral mucosal fibroblasts were reduced after exposure to curcumin, whereas the activation of HIF-1α/TGF-β/CTGF axis reversed curcumin’s effect on improving fibrosis of arecoline-treated normal oral mucosal fibroblasts. Therefore, curcumin alleviated oral submucosal fibrosis via inhibiting HIF-1α/TGF-β/CTGF axis. In summary, curcumin effectively inhibited the migration and proliferation and promoted apoptosis in arecoline-induced normal oral mucosal fibroblasts by inactivating HIF-1α/TGF-β/CTGF pathway. And curcumin might be a potential therapeutic drug for OSF treatment.

The lifelong and complex nature of autism necessitates an array of services and supports spanning across different sectors and providers at different life stages of an autistic individual. However, research has shown that autistic individuals and their families often experience barriers accessing the autism-related services and supports that they need. This is the first qualitative study to explore the provision and coordination of autism services and supports in Singapore from the perspectives of service providers, autistic adults and caregivers. Semi-structured interviews with 21 participants revealed three main themes: (1) improving access to autism-specific services, (2) creating flexible supports in an inclusive environment and (3) addressing stigma and changing societal attitudes. Our findings suggest that Singapore may have achieved rapid growth in autism services, but broader social structures may be slower to change. To better support autistic individuals in society, autistic voices need to be amplified and a collective effort is needed to achieve a paradigm shift from impairment to capability. Lay abstract Because autism is a lifelong and complex condition, autistic people may need a range of supports cutting across different sectors (e.g. health, education and social care) at different stages of their lives. Studies in some countries have shown that autistic people and their families face difficulties accessing the services they need, but no research has been done on this topic in Singapore. To start addressing this gap, we interviewed 21 service providers, autistic adults and caregivers/parents of autistic children to find out their perceptions and experiences of autism services and supports in Singapore. Our participants told us that beyond improving access to autism-specific services, they also hoped to see more flexible supports in an inclusive environment and a broader change in societal attitudes. This study highlights that autism service provision should be informed by autistic voices and not only focus on impairment but also recognise the strengths of autistic people alongside their very real needs. The whole of society – including policymakers, professionals, employers, educators, families and autistic people themselves – needs to work together to fight autism stigma and discrimination.

Autophagy is a critical cytoprotective mechanism that takes a hand in innate or adaptive immune responses. Hypoxia is a common pathophysiological mechanism that can lead to systemic pathological reactions. In recent years, the impact of hypoxia on the central nervous system has attracted more attention. In the past, autophagy was thought to be directly involved in the apoptosis of nerve cells under hypoxia. An increasing amount of evidence shows that the neuroinflammatory response plays an indispensable role in the neural damage caused by hypoxia. There are many mechanisms related to the neuroinflammatory response induced by hypoxia, among which autophagy is an important aspect, but the role of autophagy is still unclear. This article focuses on how autophagy flux of central immune cells is modified under hypoxic conditions, and how this autophagy affects neuroinflammatory response.

Background Global burden of COVID-19 has not been well studied, disability-adjusted life years(DALYs) and value of statistical life(VSL) metrics were therefore proposed to quantify its impacts on health and economic loss globally. Methods The life expectancy, cases, and death numbers of COVID-19 until 30th April 2021 were retrieved from open data to derive the epidemiological profiles and DALYs (including years of life lost (YLL) and years loss due to disability (YLD)) by four periods. The VSL estimates were estimated by using hedonic wage method(HWM) and contingent valuation method(CVM). The estimate of willingness to pay using CVM was based on the meta-regression mixed model. Machine learning method was used for classification. Results Globally, DALYs (in thousands) due to COVID-19 was tallied as 31,930 from Period I to IV. YLL dominated over YLD. The estimates of VSL were US$591 billion and US$5,135 billion based on HWM and CVM, respectively. The estimate of VSL increased from US$579 billion in Period I to US$2160 billion in Period IV using CVM. The higher the human development index(HDI), the higher the value of DALYs and VSL. However, there exits the disparity even at the same level of HDI. Machine learning analysis categorized eight patterns of global burden of COVID-19 with a large variation from US$0.001 billion to US$691.4 billion. Conclusions Global burden of COVID-19 pandemic resulted in substantial health and value of life loss particularly in developed economies. Classifications of such health and economic loss is informative to early preparation of adequate resource to reduce impacts.

We report the first case of Tintelnotia destructans associated keratitis in a contact lens wearer in Australia. Corneal scrape showed fungal elements on direct microscopy leading to a prompt diagnosis of fungal keratitis and early topical and systemic antifungal therapy. The isolate was eventually identified by ITS gene sequencing. This case highlights the importance of accurate identification and antifungal susceptibility testing for the management of fungal keratitis. Keywords: Fungal keratitis, Tintelnotia, Voriconazole

A 48-year-old man presented with chest pain and ischemic manifestations according to an electrocardiogram due to coronary artery compression from a cardiac mass and was admitted to the emergency room and underwent extensive debulking followed by right atrium and ventricular three-dimensional reconstruction with concomitant tricuspid valve remodeling. He recovered a normal sinus rhythm and was discharged from the hospital a week later with a diagnosis of cardiac malignant angiosarcoma according to the pathological examination. He survived and had a normal cardiac structure and function performance, but vertebral metastasis was suspected after more than 4 months of follow-up after the procedure.

We report a case of a competitive athlete who complained of chronic pain over the first metatarsal head in the absence of preceding trauma that was exacerbated with forced plantar flexion of the big toe. Initial radiographic findings suggested a tripartite appearance of the medial hallux sesamoid, and the patient was treated as for sesamoiditis. However, persistent symptoms over a period of 12 months necessitated further imaging with magnetic resonance, which confirmed a fracture of the bipartite medial hallux sesamoid. Considering that it is clinically important to differentiate between a tripartite/multipartite hallux sesamoid variant and a fracture of a bipartite hallux sesamoid, an expedient diagnosis is vital to avoiding complications of stress fractures. This can be a diagnostic challenge for the radiologist, emergency physician, and orthopedic surgeon, requiring a high index of suspicion. Accurate and timely diagnosis can be achieved with a clear history, detailed physical examination, and appropriate radiological evaluation.

Although factors associated with HIV/sexually transmitted infection (STI) testing among gay, bisexual, and queer (GBQ) men are well-established in the literature, few studies have attempted to delineate the processes underlying different patterns of testing. We conducted a qualitative study involving 35 semistructured interviews with a purposive sample of GBQ men in Singapore from October 2017 to July 2018. Topics explored included formative sexual experiences, relationships, and experiences of HIV/STI testing. Interviews were audio-recorded, transcribed, coded, and analyzed through inductive thematic analysis. A typology comprising four distinct HIV/STI testing patterns was identified from the data, categorized based on the regularity of testing, relative to internal or external factors that motivate testing behaviors. These include triggered episodic testing, influenced episodic testing, institutionalized regular testing, and value-based regular testing. The typology highlights the preconditions that underlie different testing patterns and provides a framework for developing interventions that promote HIV/STI testing among GBQ men.

Comparative clinical trials of domestic dogs with spontaneously-occurring cancers are increasingly common. Canine cancers are likely more representative of human cancers than induced murine tumors. These trials could bridge murine models and human trials and better prioritize drug candidates. Such investigations also benefit veterinary patients. We aimed to evaluate the design and reporting practices of clinical trials containing ≥2 arms and involving tumor-bearing dogs. 163 trials containing 8552 animals were systematically retrieved from PubMed (searched 1/18/18). Data extracted included sample sizes, response criteria, study design, and outcome reporting. Low sample sizes were prevalent (median n = 33). The median detectable hazard ratio was 0.3 for overall survival and 0.06 for disease progression. Progressive disease thresholds for studies that did not adopt VCOG-RECIST guidelines varied in stringency. Additionally, there was significant underreporting across all Cochrane risk of bias categories. The proportion of studies with unclear reporting ranged from 44% (randomization) to 94% (selective reporting). 72% of studies also failed to define a primary outcome. The present study confirms previous findings that clinical trials in dogs need to be improved, particularly regarding low statistical power and underreporting of design and outcomes.