Improving Skin Condition Classification with a Visual Symptom Checker Trained using Reinforcement Learning

We present a visual symptom checker that combines a pre-trained Convolutional Neural Network (CNN) with a Reinforcement Learning (RL) agent as a Question Answering (QA) model. This method increases the classification confidence and accuracy of the visual symptom checker, and decreases the average number of questions asked to narrow down the differential diagnosis. A Deep Q-Network (DQN)-based RL agent learns how to ask the patient about the presence of symptoms in order to maximize the probability of correctly identifying the underlying condition. The RL agent uses the visual information provided by CNN in addition to the answers to the asked questions to guide the QA system. We demonstrate that the RL-based approach increases the accuracy more than 20% compared to the CNN-only approach, which only uses the visual information to predict the condition. Moreover, the increased accuracy is up to 10% compared to the approach that uses the visual information provided by CNN along with a conventional decision tree-based QA system. We finally show that the RL-based approach not only outperforms the decision tree-based approach, but also narrows down the diagnosis faster in terms of the average number of asked questions.Comment: Accepted for the Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) 201

DNA unzipped under a constant force exhibits multiple metastable intermediates

Single molecule studies, at constant force, of the separation of double-stranded DNA into two separated single strands may provide information relevant to the dynamics of DNA replication. At constant applied force, theory predicts that the unzipped length as a function of time is characterized by jumps during which the strands separate rapidly, followed by long pauses where the number of separated base pairs remains constant. Here, we report previously uncharacterized observations of this striking behavior carried out on a number of identical single molecules simultaneously. When several single lphage molecules are subject to the same applied force, the pause positions are reproducible in each. This reproducibility shows that the positions and durations of the pauses in unzipping provide a sequence-dependent molecular fingerprint. For small forces, the DNA remains in a partially unzipped state for at least several hours. For larger forces, the separation is still characterized by jumps and pauses, but the double-stranded DNA will completely unzip in less than 30 min

Child labor and childhood behavioral and mental health problems in Ethiopia

Background: According to ILO estimates, at least 180 million children aged 5 to 14 years are currently engaged in fulltime work in the developing countries. However, very little information exists about childhood behavioral and mental disorders in Ethiopia. Objective: The objectives of this study are to estimate the prevalence and describe the nature of behavioral and mental health problems, as well as child abuse, nutritional problems, gross physical illness and injury among child laborers aged 8 to 15 years in Ethiopia. However, only the behavioral and mental health problems of the study population are examined here. Methods: A cross-sectional survey of children aged 8 to 15 years, and who were engaged in fulltime work in different formal and informal sectors non-laborers, was conducted in four major towns of Ethiopia. The screening instrument known as Reported Questionnaire on Children (RQC) and a diagnostic instrument known as the Diagnostic Interview for Children and Adolescents ( DICA) were used to detect symptoms and signs of behavioral and mental problems in the children. br> Results: A total of 2000 child laborers and 400 non-laborers were interviewed using RQC to screen for probable cases of behavioral and mental problems. Of these, 50% of the laborers and 42% of the non-laborers were males. The mean age of the laborers was 13.8 ±1.8 years while that of the non-laborers was 12.2 ±2.1 years. More females (76.8%) were found to have been engaged in domestic labor than males. The RQC interview screened 9.4% (n=226) of the children as probable cases of mental/ behavioral disorders, (14.0% non-laborers and 8.5% laborers). The second stage DICA interview gave an overall prevalence of 5.5% (4.9% in laborers and 8.8% in non-laborers). Conclusion: The prevalence of childhood behavioral and mental disorders in this study is within the range reported in previews studies conducted on children of the same age group. However, the lower prevalence of childhood disorders in the child laborers compared to that of the non-laborers found in the current study is probably due to selection bias or healthy workers effect. Thus, further study is recommended to explain this unexpected finding. The Ethiopian Journal of Health Development Vol. 20 (2) 2006: 119-12

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Perspective on Employment Opportunities of People with Disabilities in San Gabriel, La Union

For PWDs, employment is not only a way to gain income; it also gives a chance to showcase untapped skills, provide opportunities and allow social inclusion. However, PWDs still experience common patterns of discrimination and suffer high unemployment rates. In spite of several promotions worldwide, the employment rate is considerably lower for PWDs than for people without disabilities. This study sought to know the status of inclusion of PWDs in employment in San Gabriel, La Union, the opportunities present, and the interventions to address them. The descriptive qualitative design was utilized in this study. A semi-structured interview was conducted with the PWDs. Thematization was used to analyze the responses. Results revealed that the respondents face difficulties in finding a job before the pandemic because of the limited number of jobs available and became even more challenging during the pandemic due to imposed restrictions. Although they find it difficult because of limitations, results showed that they are not discriminated against in the workplace. Moreover, the available employment opportunities for PWDs are classified under blue-collar jobs. Additionally, respondents recommend giving attention to PWDs in order to address the employment opportunities through interventions. The researchers concluded that the status of inclusion of PWDs in employment is considerably low because of the limited jobs available. Similarly, work opportunities are also insufficient. Interventions to address the employment opportunities include facilitating programs and skills training for PWDs and opening simple job positions in the municipality or barangays

A distinct first replication cycle of DNA introduced in mammalian cells

Many mutation events in microsatellite DNA sequences were traced to the first embryonic divisions. It was not known what makes the first replication cycles of embryonic DNA different from subsequent replication cycles. Here we demonstrate that an unusual replication mode is involved in the first cycle of replication of DNA introduced in mammalian cells. This alternative replication starts at random positions, and occurs before the chromatin is fully assembled. It is detected in various cell lines and primary cells. The presence of single-stranded regions increases the efficiency of this alternative replication mode. The alternative replication cannot progress through the A/T-rich FRA16B fragile site, while the regular replication mode is not affected by it. A/T-rich microsatellites are associated with the majority of chromosomal breakpoints in cancer. We suggest that the alternative replication mode may be initiated at the regions with immature chromatin structure in embryonic and cancer cells resulting in increased genomic instability. This work demonstrates, for the first time, differences in the replication progression during the first and subsequent replication cycles in mammalian cells

Cholesterol redistribution triggered by CYP46A1 gene therapy improves major hallmarks of Niemann-Pick type C disease but is not sufficient to halt neurodegeneration

Funding Information: This work was funded by FEDER and by National Funds through Fundação para a Ciência e a Tecnologia (FCT) under project PTDC/MED-NEU/29455/2017 , Bolsa de Investigação da Sociedade Portuguesa de Doenças Metabólicas (SPDM), and BrainVectis Technologies . Publisher Copyright: © 2023 The AuthorsCholesterol 24-hydroxylase (CYP46A1) is an exclusively neuronal cytochrome P450 enzyme responsible for converting cholesterol into 24S-hydroxycholesterol, which serves as the primary pathway for eliminating cholesterol in the brain. We and others have shown that increased activity of CYP46A1 leads to reduced levels of cholesterol and has a positive effect on cognition. Therefore, we hypothesized that CYP46A1 could be a potential therapeutic target in Niemann-Pick type C (NPC) disease, a rare and fatal neurodegenerative disorder, characterized by cholesterol accumulation in endolysosomal compartments. Herein, we show that CYP46A1 ectopic expression, in cellular models of NPC and in Npc1tm(I1061T) mice by adeno-associated virus-mediated gene therapy improved NPC disease phenotype. Amelioration in functional, biochemical, molecular and neuropathological hallmarks of NPC disease were characterized. In vivo, CYP46A1 expression partially prevented weight loss and hepatomegaly, corrected the expression levels of genes involved in cholesterol homeostasis, and promoted a redistribution of brain cholesterol accumulated in late endosomes/lysosomes. Moreover, concomitant with the amelioration of cholesterol metabolism dysregulation, CYP46A1 attenuated microgliosis and lysosomal dysfunction in mouse cerebellum, favoring a pro-resolving phenotype. In vivo CYP46A1 ectopic expression improves important features of NPC disease and may represent a valid therapeutic approach to be used concomitantly with other drugs. However, promoting cholesterol redistribution does not appear to be enough to prevent Purkinje neuronal death in the cerebellum. This indicates that cholesterol buildup in neurons might not be the main cause of neurodegeneration in this human lipidosis.publishersversionpublishe

Prevalence of pulmonary TB and spoligotype pattern of Mycobacterium tuberculosis among TB suspects in a rural community in Southwest Ethiopia

<p>Abstract</p> <p>Background</p> <p>In Ethiopia where there is no strong surveillance system and state of the art diagnostic facilities are limited, the real burden of tuberculosis (TB) is not well known. We conducted a community based survey to estimate the prevalence of pulmonary TB and spoligotype pattern of the <it>Mycobacterium tuberculosis </it>isolates in Southwest Ethiopia.</p> <p>Methods</p> <p>A total of 30040 adults in 10882 households were screened for pulmonary TB in Gilgel Gibe field research centre in Southwest Ethiopia. A total of 482 TB suspects were identified and smear microscopy and culture was done for 428 TB suspects. Counseling and testing for HIV/AIDS was done for all TB suspects. Spoligotyping was done to characterize the <it>Mycobacterium tuberculosis </it>isolates.</p> <p>Results</p> <p>Majority of the TB suspects were females (60.7%) and non-literates (83.6%). Using smear microscopy, a total of 5 new and 4 old cases of pulmonary TB cases were identified making the prevalence of TB 30 per 100,000. However, using the culture method, we identified 17 new cases with a prevalence of 76.1 per 100,000. There were 4.3 undiagnosed pulmonary TB cases for every TB case who was diagnosed through the passive case detection mechanism in the health facility. Eleven isolates (64.7%) belonged to the six previously known spoligotypes: T, Haarlem and Central-Asian (CAS). Six new spoligotype patterns of <it>Mycobacterium tuberculosis</it>, not present in the international database (SpolDB4) were identified. None of the rural residents was HIV infected and only 5 (5.5%) of the urban TB suspects were positive for HIV.</p> <p>Conclusion</p> <p>The prevalence of TB in the rural community of Southwest Ethiopia is low. There are large numbers of undiagnosed TB cases in the community. However, the number of sputum smear-positive cases was very low and therefore the risk of transmitting the infection to others may be limited. Active case finding through health extension workers in the community can improve the low case detection rate in Ethiopia. A large scale study on the genotyping of <it>Mycobacterium tuberculosis </it>in Ethiopia is crucial to understand transmission dynamics, identification of drug resistant strains and design preventive strategies.</p

Prejudice and misconceptions about tuberculosis and HIV in rural and urban communities in Ethiopia: a challenge for the TB/HIV control program

<p>Abstract</p> <p>Background</p> <p>In Ethiopia, where HIV and tuberculosis (TB) are very common, little is known about the prejudice and misconceptions of rural communities towards People living with HIV/AIDS (PLHA) and TB.</p> <p>Methods</p> <p>We conducted a cross sectional study in Gilgel Gibe Field Research area (GGFRA) in southwest Ethiopia to assess the prejudice and misconceptions of rural and urban communities towards PLHA and TB. The study population consisted of 862 randomly selected adults in GGFRA. Data were collected by trained personnel using a pretested structured questionnaire. To triangulate the findings, 8 focus group discussions among women and men were done.</p> <p>Results</p> <p>Of the 862 selected study participants, 750(87%) accepted to be interviewed. The mean age of the respondents was 31.2 (SD ± 11.0). Of the total interviewed individuals, 58% of them were females. More than half of the respondents did not know the possibility of transmission of HIV from a mother to a child or by breast feeding. For fear of contagion of HIV, most people do not want to eat, drink, and share utensils or clothes with a person living with HIV/AIDS. A higher proportion of females [OR = 1.5, (95% CI: 1.0, 2.2)], non-literate individuals [OR = 2.3, (95%CI: 1.4, 3.6)], rural residents [OR = 3.8, (95%CI: 2.2, 6.6)], and individuals who had poor knowledge of HIV/AIDS [OR = 2.8, (95%CI: 1.8, 2.2)] were more likely to have high prejudice towards PLHA than respectively males, literates, urban residents and individuals with good knowledge. Exposure to cold air was implicated as a major cause of TB. Literates had a much better knowledge about the cause and methods of transmission and prevention of TB than non-literates. More than half of the individuals (56%) had high prejudice towards a patient with TB. A larger proportion of females [OR = 1.3, (95% CI: 1.0, 1.9)] and non-literate individuals [OR = 1.4, (95% CI: 1.1, 2.0)] had high prejudice towards patients with TB than males and literate individuals.</p> <p>Conclusion</p> <p>TB/HIV control programs in collaboration with other partners should invest more in social mobilization and education of the communities to rectify the widespread prejudice and misconceptions.</p