Leveraging the Full Continuum of Care to Prevent Opioid Use Disorder.

Substance use disorder prevention programs are most effective when matched appropriately to the baseline risk of the population. Individuals who misuse opioids often have unique risk profiles different from those who use other substances such as alcohol or cannabis. However, most substance use prevention programs are geared toward universal audiences, neglecting key inflection points along the continuum of care. The HEAL Prevention Cooperative (HPC) is a unique cohort of research projects that represents a continuum of care, from community-level universal prevention to indicated prevention among older adolescents and young adults who are currently misusing opioids or other substances. This paper describes the theoretical basis for addressing opioid misuse and opioid use disorder across the prevention continuum, using examples from research projects in the HPC.

Accelerating Solutions for the Overdose Crisis: an Effectiveness-Implementation Hybrid Protocol for the HEAL Prevention Cooperative.

Given increasing opioid overdose mortality rates in the USA over the past 20 years, accelerating the implementation of prevention interventions found to be effective is critical. The Helping End Addiction Long-Term (HEAL) Prevention Cooperative (HPC) is a consortium of research projects funded to implement and test interventions designed to prevent the onset or escalation of opioid misuse among youth and young adults. The HPC offers a unique opportunity to synthesize and share lessons learned from participating research projects' varied implementation experiences, which can facilitate quicker integration of effective prevention interventions into practice. This protocol paper describes our hybrid approach to collecting and analyzing information about the implementation experiences of nine of the HPC research projects while they maintain their focus on assessing the effectiveness and cost-effectiveness of prevention interventions. To better understand implementation within this context, we will address five research questions: (1) What were the context and approach for implementing the prevention interventions, and how was the overall implementation experience? (2) How representative of the target population are the participants who were enrolled and retained in the research projects' effectiveness trials? (3) For what purposes and how were stakeholders engaged by the research projects? (4) What are the adaptable components of the prevention interventions? And finally, (5) how might implementation of the prevention interventions vary for non-trial implementation? This work will result in intervention-specific and general practical dissemination resources that can help potential adopters and deliverers of opioid misuse prevention make adoption decisions and prepare for successful implementation.

Skin manifestations and clinical features of drug reaction with eosinophilia and systemic symptoms: a retrospective multicentre study of 125 patients.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse drug reaction generally accompanied by skin manifestations as the first and most frequent symptoms. However, skin manifestations and associated clinical features of DRESS have not been fully explored and evaluated. OBJECTIVES: This study aimed to describe the skin manifestations of DRESS in detail and analyse their association with demographic characteristics and extra-cutaneous clinical features. METHODS: We conducted this retrospective study on patients with DRESS diagnosed between September 2009 and August 2021 at three medical institutes and validated using the RegiSCAR score. Data regarding demographics, skin manifestations and clinical characteristics were retrieved through thorough chart reviews. RESULTS: Among 182 potential cases of DRESS, the validated 125 cases were analysed. A widespread rash extending over more than 50% of the body surface area was observed in 122 patients (97.6%) and typical facial oedema was experienced by 67 patients (53.6%). Polymorphous maculopapules were the most common rash morphology (106, 84.8%): specifically, exfoliative (59, 47.2%), urticarial (57, 45.6%) and purpuric forms (39, 31.2%) were common. Mucosal involvement was observed in 41 patients (32.8%). Patients with carboxamide antiepileptics (carbamazepine and oxcarbazepine) experienced more oedema (P = 0.014) and typical facial oedema than those with allopurinol (P = 0.021). The RegiSCAR score was higher in patients with purpura (P < 0.01). CONCLUSIONS: Skin manifestations of DRESS exhibit a wide range of skin lesions and can vary according to the culprit drugs. Early suspicion and prompt intervention are needed to improve prognosis.

Histopathological predictor of the progression from actinic keratosis to squamous cell carcinoma: quantitative computer-aided image analysis.

BACKGROUND: The current histopathological classifications for actinic keratosis (AK) are subjective, and histopathological factors predicting the progression into invasive squamous cell carcinoma (SCC) remain unclear. OBJECTIVES: To quantitatively assess the histopathological findings of AK and to investigate the predisposing factors for malignant transformation of AK. METHODS: A total of 502 AK specimens were retrospectively reviewed. The AK lesions were divided into the atrophic, intermediate, hypertrophic and bowenoid types. Histopathological features were quantitatively analysed using computer-aided image analysis. RESULTS: The epidermal thickness excluding the horny layer increased with statistical significance (P < 0.001) in order of atrophic, intermediate, hypertrophic and bowenoid type. The proportion of keratinocytic atypia was not significantly different among subtypes, except for the bowenoid type. Five of 498 cases were confirmed to develop into SCC. Bowenoid type, epidermal thickening and higher proportion of keratinocytic atypia were significantly associated with progression to invasive SCC in univariate analysis (OR = 12.571, 95% CI: 1.392-113.57; OR = 1.004, 95% CI: 1.001-1.007; OR = 1.069, 95% CI: 1.011-1.130, respectively). In multivariate analysis, only the proportion of keratinocytic atypia was an independent predisposing factor for progression to invasive SCC (OR = 1.069; 95% CI: 1.011-1.130). CONCLUSIONS: Histopathological subtypes based on the essential change of the epidermis well correlated with the actual epidermal thickness excluding the horny layer. The overall severity of keratinocytic atypia might be an independent risk factor for malignant transformation of AK.

OsFKBP20-1b interacts with the splicing factor OsSR45 and participates in the environmental stress response at the post-transcriptional level in rice.

Sessile plants have evolved distinct mechanisms to respond and adapt to adverse environmental conditions through diverse mechanisms including RNA processing. While the role of RNA processing in the stress response is well understood for Arabidopsis thaliana, limited information is available for rice (Oryza sativa). Here, we show that OsFKBP20-1b, belonging to the immunophilin family, interacts with the splicing factor OsSR45 in both nuclear speckles and cytoplasmic foci, and plays an essential role in post-transcriptional regulation of abiotic stress response. The expression of OsFKBP20-1b was highly upregulated under various abiotic stresses. Moreover genetic analysis revealed that OsFKBP20-1b positively affected transcription and pre-mRNA splicing of stress-responsive genes under abiotic stress conditions. In osfkbp20-1b loss-of-function mutants, the expression of stress-responsive genes was downregulated, while that of their splicing variants was increased. Conversely, in plants overexpressing OsFKBP20-1b, the expression of the same stress-responsive genes was strikingly upregulated under abiotic stress. In vivo experiments demonstrated that OsFKBP20-1b directly maintains protein stability of OsSR45 splicing factor. Furthermore, we found that the plant-specific OsFKBP20-1b gene has uniquely evolved as a paralogue only in some Poaceae species. Together, our findings suggest that OsFKBP20-1b-mediated RNA processing contributes to stress adaptation in rice.

Dermatologist-level classification of malignant lip diseases using a deep convolutional neural network.

BACKGROUND: Deep convolutional neural networks (DCNNs) can classify skin diseases at a level equivalent to a dermatologist, but their performance in specific areas requires further research. OBJECTIVE: To evaluate the performance of a trained DCNN-based algorithm in classifying benign and malignant lip diseases. METHODS: A training set of 1629 images (743 malignant, 886 benign) was used with Inception-Resnet-V2. Performance was evaluated using another set of 344 images and 281 images from other hospitals. Classifications by 44 participants (six board-certified dermatologists, 12 dermatology residents, nine medical doctors not specialized in dermatology and 17 medical students) were used for comparison. RESULTS: The outcomes based on the area under curve, sensitivity and specificity were 0·827 [95% confidence interval (CI) 0·782-0·873], 0·755 (95% CI 0·673-0·827) and 0·803 (95% CI 0·752-0·855), respectively, for the set of 344 images; and 0·774 (95% CI 0·699-0·849), 0·702 (95% CI 0·579-0·808) and 0·759 (95% CI 0·701-0·813), respectively, for the set of 281 images. The DCNN was equivalent to the dermatologists and superior to the nondermatologists in classifying malignancy. After referencing the DCNN result, the mean ± SD Youden index increased significantly for nondermatologists, from 0·201 ± 0·156 to 0·322 ± 0·141 (P < 0·001). CONCLUSIONS: DCNNs can classify lip diseases at a level similar to dermatologists. This will help unskilled physicians discriminate between benign and malignant lip diseases. What's already known about this topic? Deep convolutional neural networks (DCNNs) can classify malignant and benign skin diseases at a level equivalent to dermatologists. The lips are a unique feature in terms of histology and morphology. Previous studies of DCNNs have not investigated tumours on specific locations. What does this study add? This study shows that DCNNs can distinguish rare malignant and benign lip disorders at the same rate as dermatologists. DCNNs can help nondermatologists to distinguish malignant lip diseases. What are the clinical implications of this work? DCNNs can distinguish malignant and benign skin diseases even at specific locations such as the lips, as well as board-certified dermatologists. Malignant lip diseases are rare and difficult for less trained doctors to differentiate them from benign lesions. This study shows that in dermatology, DCNN can help improve decision-making processes for rare skin diseases in specific areas of the body.

Basic symptoms in young people at ultra-high risk of psychosis: Association with clinical characteristics and outcomes.

There has been limited research into the predictive value of basic symptoms and their relationship with other psychopathology in patients identified using the 'ultra high risk' (UHR) for psychosis approach. The current study investigated whether basic symptoms, specifically cognitive disturbances (COGDIS), were associated with a greater risk of transition to psychotic disorder and persistent attenuated psychotic symptoms (APS) at medium term follow-up (mean = 3.4 years) in UHR patients, as well as with general psychopathology at baseline. The sample included 304 UHR participants (mean age = 19.12 years) involved in an international multicenter trial of omega-3 fatty acids. UHR individuals who also met the COGDIS criteria (basic symptoms risk criteria) did not have a greater risk of transition than those who met the UHR criteria alone. However, meeting COGDIS risk criteria was associated with a greater likelihood of meeting the UHR attenuated psychotic symptoms risk group (i.e., having persistent attenuated psychotic symptoms) at 12-month follow-up (odds ratio = 1.85; 95% CI = 1.03, 3.32). Greater severity of cognitive basic symptoms was also independently associated with more severe general psychopathology at study entry. The findings do not support the notion that combined risk identification approaches (UHR and basic symptoms) aid in the identification of individuals at greatest risk of psychosis, although this interpretation is limited by the modest transition to psychosis rate (13%) and the time of follow up. However, the findings indicate that basic symptoms may be a clinically useful marker of more severe general psychopathology in UHR groups and risk for persistent attenuated psychotic symptoms.

The relationship between clinical characteristics including presence of exposed lesions and health-related quality of life (HRQoL) in patients with psoriasis: analysis from the nationwide epidemiologic study for psoriasis in Korea (EPI-PSODE study).

BACKGROUND: Psychological aspect and quality of life should be considered in treating patients with psoriasis. OBJECTIVE: We sought to ascertain which clinical characteristics including presence of exposed lesions are associated with impairment of health-related quality of life (HRQoL) in patients with psoriasis. METHODS: The EPI-PSODE study was a nationwide, multicenter, cross-sectional study conducted in Korea that included 1260 adult patients with psoriasis. In addition to clinical characteristics including presence of exposed lesions, data were collected using the Psoriatic Arthritis (PsA) Screening and Evaluation (PASE), Dermatology Life Quality Index (DLQI), MOS 36-Item Short-Form Health Survey (SF-36), Work Productivity and Activity Impairment Questionnaire Psoriasis (WPAI: PSO) and Medication Satisfaction Questionnaire (MSQ). RESULTS: Patients with a DLQI score > 5 (n = 990) were younger, had an earlier onset of psoriasis, scored higher on the Psoriasis Area and Severity Index (PASI), had higher body surface area (BSA) and had higher PASE scores than patients with DLQI ≤ 5 (n = 266). The group of patients with exposed lesions (n = 871) were younger and male predominance, earlier onset of psoriasis, longer disease duration, higher PASI/BSA score and a higher proportion with drinking and smoking history each than the group of patients without exposed lesions (n = 389). Presence of exposed lesions negatively influenced DLQI, 36-Item Short-Form Health Survey (SF-36) (mental component), presenteeism, total work productivity impairment and total activity impairment in the WPAI: PSO. In multiple regression model, PASI score was the only variable which was significantly associated with all HRQoL measures. Presence of exposed lesions was a significant factor affecting DLQI and SF-36 (mental). CONCLUSION: The presence of exposed lesions has a negative impact on quality of life, mental health and work productivity. Therefore, effective treatments are particularly needed for psoriasis patients with exposed lesions.

Application of loop-mediated isothermal amplification with propidium monoazide treatment to detect live Salmonella in chicken carcasses.

Raw chicken products are major causes of human foodborne salmonellosis worldwide. In particular, there is a significant risk of human exposure to Salmonella originating from the chicken slaughtering process. Controlling the contamination of chicken carcasses by Salmonella has been a considerable challenge in chicken-slaughtering facilities and involves routine microbiological monitoring using reliable detection methods. Simple and rapid detection methods, particularly those capable of determining cell viability, will significantly facilitate routine monitoring of Salmonella Here, we report an invA-based loop-mediated isothermal amplification method coupled with a simple propidium monoazide treatment (PMA-LAMP) for simple and rapid detection and quantification of viable Salmonella in rinse water of chicken carcasses. In this study, PMA-LAMP consistently gave negative results for isopropanol-killed Salmonella with concentrations up to 8.0 × 106 CFU/reaction. The detection limit of PMA-LAMP was 8.0 × 101 CFU/reaction with viable Salmonella in both pure culture and rinse water of chicken carcasses, and 10-fold lower than a conventional polymerase chain reaction coupled with PMA (PMA-PCR) targeting invA There was a high correlation (R2 = 0.99 to 0.976) between LAMP time threshold (TT) values and viable Salmonella with a quantification range of 1.0 × 103 to 1.0 × 108 CFU/mL in pure culture and rinse water of chicken carcasses. The PMA-LAMP assay took less than 2 h to detect Salmonella contaminated in test samples. Therefore, this simple and rapid method will be a very useful tool to detect live Salmonella contamination of chicken carcasses without pre-enrichment at the slaughterhouse where sanitizing treatments are commonly used.

Optimal maintenance treatment with calcipotriol/betamethasone dipropionate gel in Korean patients with psoriasis vulgaris: a multicentre randomized, controlled clinical trial.

BACKGROUND: There is a lack of response data for topical treatments for psoriasis vulgaris in Asian patients. OBJECTIVES: To determine the optimal maintenance regimen for topical treatment with calcipotriol monohydrate/betamethasone dipropionate gel in Korean patients with psoriasis vulgaris, by comparing the efficacy of three 8-week maintenance regimens. METHODS: This was a multicentre, prospective, randomized, controlled, parallel-group, open-label, phase 4 clinical trial, conducted in South Korea. Patients with psoriasis vulgaris on the limbs/trunk received once-daily treatment with calcipotriol monohydrate (50 µg/g)/betamethasone dipropionate (500 µg/g) gel for 8 weeks (induction phase). Responders (defined as an Investigator's Global Assessment of Disease Severity (IGA) grade of 'clear' or 'almost clear') were then randomized to receive 8 weeks' maintenance treatment with Xamiol® gel once daily as needed [pro re nata (PRN Group)], once daily every day (Continuous group), or twice weekly - on Saturday and Sunday (Weekend group). The primary endpoint was the percentage of IGA responders at week 16. RESULTS: At the end of the induction phase, 62.18% of patients were IGA responders. At the end of the maintenance phase (week 16), the responder rate was 63.89% for the PRN group, 67.5% for the Continuous group and 31.43% for the Weekend group. The PRN and Continuous groups were statistically superior to the Weekend group (P = 0.0109 and P = 0.0015), but the PRN and Continuous groups did not differ statistically. The incidence of adverse events did not differ significantly between the groups. CONCLUSION: Among Korean patients with psoriasis vulgaris, maintenance treatment with calcipotriol monohydrate/betamethasone dipropionate using a continuous daily regimen or an 'as needed' daily regimen provided similar efficacy, whereas a twice-weekly regimen was significantly less efficacious than either of these regimens.

Increased efficacy of inactivated vaccine candidates prepared with Salmonella enterica serovar Typhimurium strains of predominant genotypes in ducks.

Salmonella enterica serovar Typhimurium has been a major causative agent of food-borne human disease, mainly due to consumption of contaminated food animal products. In particular, ducks serve as a reservoir of serovar Typhimurium, and are one of the common sources of human infection. To prevent infection of ducks, and therefore minimize human infection, it is critical to control the persistent epidemic strains in ducks. Here, we analyzed the genetic diversity and virulence of serovar Typhimurium isolates from ducks in Korea to identify the predominant strains that might be used as efficient vaccine candidates for ducks. Among the isolates, 2 representative isolates (ST26 and ST76) of predominant genotypes were selected as vaccine strains on the basis of genotypic analysis by pulsed-field gel electrophoresis and DNA microarrays. Two-week-old ducks were then injected intramuscularly with inactivated vaccine candidates prepared using ST26 or ST76 (10(8) cfu/0.5 mL/duck or 10(9) cfu/0.5 mL/duck), and oral challenge with a highly virulent serovar Typhimurium strain (10(9) cfu/0.5 mL/duck) was carried out 2 wk later. Shedding of the challenge strain was significantly decreased in group 2 after vaccination. The antibody levels by enzyme-linked immunosorbent assay in all vaccinated groups were enhanced significantly (P < 0.05) compared to the unvaccinated control group. Overall, vaccination with ST26 or ST76 reduced bacterial shedding and colonization in internal organs, and induced elevated antibody response. In particular, serovar Typhimurium ST26 (10(8) cfu/0.5 mL/duck) was the most effective vaccine candidate, which can provide efficient protection against serovar Typhimurium in ducks with higher effectiveness compared to a commercial vaccine currently used worldwide.

First norovirus outbreaks associated with consumption of green seaweed (Enteromorpha spp.) in South Korea.

In February 2012, an outbreak of gastroenteritis was reported in school A; a successive outbreak was reported at school B. A retrospective cohort study conducted in school A showed that seasoned green seaweed with radishes (relative risk 7·9, 95% confidence interval 1·1-56·2) was significantly associated with illness. Similarly, a case-control study of students at school B showed that cases were 5·1 (95% confidence interval 1·1-24·8) times more likely to have eaten seasoned green seaweed with pears. Multiple norovirus genotypes were detected in samples from students in schools A and B. Norovirus GII.6 isolated from schools A and B were phylogenetically indistinguishable. Green seaweed was supplied by company X, and norovirus GII.4 was isolated from samples of green seaweed. Green seaweed was assumed to be linked to these outbreaks. To our knowledge, this is the first reported norovirus outbreak associated with green seaweed.

Characterization of the AWARE 10 two-gigapixel wide-field-of-view visible imager.

System requirements for many military electro-optic and IR camera systems reflect the need for both wide-field-of-view situational awareness as well as high-resolution imaging for target identification. In this work we present a new imaging system architecture designed to perform both functions simultaneously and the AWARE 10 camera as an example at visible wavelengths. We first describe the basic system architecture and user interface followed by a laboratory characterization of the system optical performance. We then describe a field experiment in which the camera was used to identify several maritime targets at varying range. The experimental results indicate that users of the system are able to correctly identify ~10 m targets at between 4 and 6 km with 70% accuracy.

Comparative virulence of reproductive diseases caused by type 1 (European-like) and type 2 (North American-like) porcine reproductive and respiratory syndrome virus in experimentally infected pregnant gilts.

The aim of this study was to compare the virulence of type 1 and type 2 porcine reproductive and respiratory syndrome virus (PRRSV) as assessed by the level of viral replication, viral distribution and apoptosis in stillborn fetuses and live-born piglets from infected pregnant gilts. Type 1 or type 2 PRRSV was given intranasally to pregnant gilts at 3 weeks before the expected date of parturition. Regardless of virus genotype, PRRSV-infected gilts farrowed between 102 and 109 days of gestation, while control uninfected gilts carried the pregnancy to term and farrowed at 114-115 days of gestation. There were no significant differences in the mean number of virus-infected cells per unit area of tissue when type 1 and type 2 virus infections were compared between stillborn fetuses and live-born piglets. Stillborn fetuses from the type 1 PRRSV-infected pregnant gilts had a significantly higher mean number of apoptotic cells per unit area of thymus (P = 0.013) than those from type 2 PRRSV-infected pregnant gilts. Significant differences in virulence were not observed between types 1 and 2 PRRSV in terms of female reproductive failure, although thymic apoptosis differed in stillborn fetuses from type 1 and type 2 PRRSV-infected pregnant gilts.

Outbreak of enterotoxigenic Escherichia coli O169 enteritis in schoolchildren associated with consumption of kimchi, Republic of Korea, 2012.

Enterotoxigenic Escherichia coli (ETEC) is now recognized as a common cause of foodborne outbreaks. This study aimed to describe the first ETEC O169 outbreak identified in Korea. In this outbreak, we identified 1642 cases from seven schools. Retrospective cohort studies were performed in two schools; and case-control studies were conducted in five schools. In two schools, radish kimchi was associated with illness; and in five other schools, radish or cabbage kimchi was found to have a higher risk among food items. Adjusted relative risk of kimchi was 5·87-7·21 in schools that underwent cohort studies; and adjusted odds ratio was 4·52-12·37 in schools that underwent case-control studies. ETEC O169 was isolated from 230 affected students, and was indistinguishable from the isolates detected from the kimchi product distributed by company X, a food company that produced and distributed kimchi to all seven schools. In this outbreak, we found that the risk of a kimchi-borne outbreak of ETEC O169 infection is present in Korea. We recommend continued monitoring regarding food safety in Korea, and strengthening surveillance regarding ETEC O169 infection through implementation of active laboratory surveillance to confirm its infection.