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Abstract Inactivating mutations in SMARCB1 confer an oncogenic dependency on EZH2 in atypical teratoid rhabdoid tumors (ATRTs), but the underlying mechanism has not been fully elucidated. We found that the sensitivity of ATRTs to EZH2 inhibition (EZH2i) is associated with the viral mimicry response. Unlike other epigenetic therapies targeting transcriptional repressors, EZH2i-induced viral mimicry is not triggered by cryptic transcription of endogenous retroelements, but rather mediated by increased expression of genes enriched for intronic inverted-repeat Alu (IR-Alu) elements. Interestingly, interferon-stimulated genes (ISGs) are highly enriched for dsRNA-forming intronic IR-Alu elements, suggesting a feedforward loop whereby these activated ISGs may reinforce dsRNA formation and viral mimicry. EZH2i also upregulates the expression of full-length LINE-1s, leading to genomic instability and cGAS/STING signaling in a process dependent on reverse transcriptase activity. Co-depletion of dsRNA sensing and cytoplasmic DNA sensing completely rescues the viral mimicry response to EZH2i in SMARCB1-deficient tumors.

Advanced myoelectric prostheses feature multiple degrees of freedom (DoFs) and sophisticated control algorithms that interpret user motor intentions as commands. While enhancing their capability to assist users in a wide range of daily activities, these control solutions still pose challenges. Among them, the need for extensive learning periods and users’ limited control proficiency. To investigate the relationship between these challenges and the limited alignment of such methods with human motor control strategies, we examine motor learning processes in two different control maps testing a synergistic myoelectric system. In particular, this work employs a DoF-wise synergies control algorithm tested in both intuitive and non-intuitive control mappings. Intuitive mapping aligns body movements with control actions to replicate natural limb control, whereas non-intuitive mapping (or non-biomimetic) lacks a direct correlation between aspects, allowing one body movement to influence multiple DoFs. The latter offers increased design flexibility through redundancy, which can be especially advantageous for individuals with motor disabilities. The study evaluates the effectiveness and learning process of both control mappings with 10 able-bodied participants. The results revealed distinct patterns observed while testing the two maps. Furthermore, muscle synergies exhibited greater stability and distinction by the end of the experiment, indicative of varied learning processes.

After decades of effort by shareholders, including government agencies, patient advocacy groups, and professional organizations, the U.S. Food and Drug Administration (FDA) established a new medical device category for over-the-counter (OTC) hearing aids on October 17, 2022. This FDA regulation allows adults aged 18 years or older with perceived mild-to-moderate hearing loss to purchase OTC hearing aids without a prescription or even a hearing test. The goal is to increase hearing aid accessibility, potentially leading to improved hearing and a better quality of life. In our analysis of the FDA Establishment Registration & Device Listing database, we found that the current OTC hearing aid market is still dominated by traditional hearing aid manufacturers, with limited disruptor from major consumer electronics and startup companies. Our technological analyses showed that the relatively high-level output specification without gain limitation allows sufficient amplification even for people with severe-to-profound hearing loss. Additionally, borrowing from the cochlear implant mapping strategy, we propose novel amplification algorithms for fitting OTC hearing aids without an audiogram. We argue that smartphones and true-wireless-stereo earbuds can functionally serve as OTC hearing aids, further increasing accessibility and affordability while reducing the stigma associated with hearing aids, especially in low- and mid-income countries. By treating more people at a younger age with less hearing loss than traditional prescription hearing aids, OTC hearing aids can potentially have a significant impact beyond hearing care, such as delaying or preventing cognitive decline in the elderly.

We have conducted a study that focuses on designing a quasi-1D ultrathin and long ferromagnetic nanowires array with excellent linearity. The purpose of this design is to test the presence of Majorana zero modes in pairs over a long distance and the influence of the lateral interaction. Specifically, we investigate the magnetic properties of a one-unit cell thick MoSX nanowire array, where dopant X (H, C, N, O, and F. etc) is utilized, to assess its suitability for our intended purposes. Our findings reveal that the edge magnetization of the optimized MoSX nanowires is comparable to that of 3d transition metals with the Curie transition temperature surpassing room temperature. Our study indicates that the ferromagnetism of the optimized MoSX nanowires is unlikely to be eliminated when placed on an s-wave superconductor due to lattice mismatch. By conducting comparative case studies of various dopants, we establish a connection between the source of magnetism in the nanowires and internal electric fields, charge perturbation, spin-orbital coupling and p-d hybridization. The strong exchange interaction, robust spin-orbital coupling and large local magnetic moment exhibited by long and ultrathin room-temperature ferromagnetic nanowires open up avenues for diverse topological applications.

Abstract Continuous, objective monitoring of motor signs and symptoms may help improve tracking of disease progression and treatment response in Parkinson’s disease (PD). This study assessed the analytical and clinical validity of multi-sensor smartwatch measurements in hospitalized and home-based settings (96 patients with PD; mean wear time 19 h/day) using a twice-daily virtual motor examination (VME) at times representing medication OFF/ON states. Digital measurement performance was better during inpatient clinical assessments for composite V-scores than single-sensor–derived features for bradykinesia (Spearman |r|= 0.63, reliability = 0.72), tremor (|r|= 0.41, reliability = 0.65), and overall motor features (|r|= 0.70, reliability = 0.67). Composite levodopa effect sizes during hospitalization were 0.51–1.44 for clinical assessments and 0.56–1.37 for VMEs. Reliability of digital measurements during home-based VMEs was 0.62–0.80 for scores derived from weekly averages and 0.24–0.66 for daily measurements. These results show that unsupervised digital measurements of motor features with wrist-worn sensors are sensitive to medication state and are reliable in naturalistic settings. Trial Registration: Japan Pharmaceutical Information Center Clinical Trials Information (JAPIC-CTI): JapicCTI-194825; Registered June 25, 2019.

Abstract Plasmodium knowlesi infections in Malaysia are a new threat to public health and to the national efforts on malaria elimination. In the Kapit division of Sarawak, Malaysian Borneo, two divergent P. knowlesi subpopulations (termed Cluster 1 and Cluster 2) infect humans and are associated with long-tailed macaque and pig-tailed macaque hosts, respectively. It has been suggested that forest-associated activities and environmental modifications trigger the increasing number of knowlesi malaria cases. Since there is a steady increase of P. knowlesi infections over the past decades in Sarawak, particularly in the Kapit division, we aimed to identify hotspots of knowlesi malaria cases and their association with forest activities at a geographical scale using the Geographic Information System (GIS) tool. A total of 1064 P. knowlesi infections from 2014 to 2019 in the Kapit and Song districts of the Kapit division were studied. Overall demographic data showed that males and those aged between 18 and 64 years old were the most frequently infected (64%), and 35% of infections involved farming activities. Thirty-nine percent of Cluster 1 infections were mainly related to farming surrounding residential areas while 40% of Cluster 2 infections were associated with activities in the deep forest. Average Nearest Neighbour (ANN) analysis showed that humans infected with both P. knowlesi subpopulations exhibited a clustering distribution pattern of infection. The Kernel Density Analysis (KDA) indicated that the hotspot of infections surrounding Kapit and Song towns were classified as high-risk areas for zoonotic malaria transmission. This study provides useful information for staff of the Sarawak State Vector-Borne Disease Control Programme in their efforts to control and prevent zoonotic malaria.

Objectives Direct comparisons between COVID-19 and influenza A in the critical care setting are limited. The objective of this study was to compare their outcomes and identify risk factors for hospital mortality.Design and setting This was a territory-wide, retrospective study on all adult (≥18 years old) patients admitted to public hospital intensive care units in Hong Kong. We compared COVID-19 patients admitted between 27 January 2020 and 26 January 2021 with a propensity-matched historical cohort of influenza A patients admitted between 27 January 2015 and 26 January 2020. We reported outcomes of hospital mortality and time to death or discharge. Multivariate analysis using Poisson regression and relative risk (RR) was used to identify risk factors for hospital mortality.Results After propensity matching, 373 COVID-19 and 373 influenza A patients were evenly matched for baseline characteristics. COVID-19 patients had higher unadjusted hospital mortality than influenza A patients (17.5% vs 7.5%, p

Abstract Sensor-based remote monitoring could help better track Parkinson’s disease (PD) progression, and measure patients’ response to putative disease-modifying therapeutic interventions. To be useful, the remotely-collected measurements should be valid, reliable, and sensitive to change, and people with PD must engage with the technology. We developed a smartwatch-based active assessment that enables unsupervised measurement of motor signs of PD. Participants with early-stage PD (N = 388, 64% men, average age 63) wore a smartwatch for a median of 390 days. Participants performed unsupervised motor tasks both in-clinic (once) and remotely (twice weekly for one year). Dropout rate was 5.4%. Median wear-time was 21.1 h/day, and 59% of per-protocol remote assessments were completed. Analytical validation was established for in-clinic measurements, which showed moderate-to-strong correlations with consensus MDS-UPDRS Part III ratings for rest tremor (⍴ = 0.70), bradykinesia (⍴ = −0.62), and gait (⍴ = −0.46). Test-retest reliability of remote measurements, aggregated monthly, was good-to-excellent (ICC = 0.75–0.96). Remote measurements were sensitive to the known effects of dopaminergic medication (on vs off Cohen’s d = 0.19–0.54). Of note, in-clinic assessments often did not reflect the patients’ typical status at home. This demonstrates the feasibility of smartwatch-based unsupervised active tests, and establishes the analytical validity of associated digital measurements. Weekly measurements provide a real-life distribution of disease severity, as it fluctuates longitudinally. Sensitivity to medication-induced change and improved reliability imply that these methods could help reduce sample sizes needed to demonstrate a response to therapeutic interventions or disease progression.

Abstract Plasmodium knowlesi, a simian malaria parasite responsible for all recent indigenous cases of malaria in Malaysia, infects humans throughout Southeast Asia. There are two genetically distinct subpopulations of Plasmodium knowlesi in Malaysian Borneo, one associated with long-tailed macaques (termed cluster 1) and the other with pig-tailed macaques (cluster 2). A prospective study was conducted to determine whether there were any between-subpopulation differences in clinical and laboratory features, as well as in epidemiological characteristics. Over 2 years, 420 adults admitted to Kapit Hospital, Malaysian Borneo with knowlesi malaria were studied. Infections with each subpopulation resulted in mostly uncomplicated malaria. Severe disease was observed in 35/298 (11.7%) of single cluster 1 and 8/115 (7.0%) of single cluster 2 infections (p = 0.208). There was no clinically significant difference in outcome between the two subpopulations. Cluster 1 infections were more likely to be associated with peri-domestic activities while cluster 2 were associated with interior forest activities consistent with the preferred habitats of the respective macaque hosts. Infections with both P. knowlesi subpopulations cause a wide spectrum of disease including potentially life-threatening complications, with no implications for differential patient management.

Abstract Background Globally, mortality rates of patients admitted to the intensive care unit (ICU) have decreased over the last two decades. However, evaluations of the temporal trends in the characteristics and outcomes of ICU patients in Asia are limited. The objective of this study was to describe the characteristics and risk adjusted outcomes of all patients admitted to publicly funded ICUs in Hong Kong over a 11-year period. The secondary objective was to validate the predictive performance of Acute Physiology And Chronic Health Evaluation (APACHE) IV for ICU patients in Hong Kong. Methods This was an 11-year population-based retrospective study of all patients admitted to adult general (mixed medical-surgical) intensive care units in Hong Kong public hospitals. ICU patients were identified from a population electronic health record database. Prospectively collected APACHE IV data and clinical outcomes were analysed. Results From 1 April 2008 to 31 March 2019, there were a total of 133,858 adult ICU admissions in Hong Kong public hospitals. During this time, annual ICU admissions increased from 11,267 to 14,068, whilst hospital mortality decreased from 19.7 to 14.3%. The APACHE IV standard mortality ratio (SMR) decreased from 0.81 to 0.65 during the same period. Linear regression demonstrated that APACHE IV SMR changed by − 0.15 (95% CI − 0.18 to − 0.11) per year (Pearson’s R = − 0.951, p < 0.001). Observed median ICU length of stay was shorter than that predicted by APACHE IV (1.98 vs. 4.77, p < 0.001). C-statistic for APACHE IV to predict hospital mortality was 0.889 (95% CI 0.887 to 0.891) whilst calibration was limited (Hosmer–Lemeshow test p < 0.001). Conclusions Despite relatively modest per capita health expenditure, and a small number of ICU beds per population, Hong Kong consistently provides a high-quality and efficient ICU service. Number of adult ICU admissions has increased, whilst adjusted mortality has decreased over the last decade. Although APACHE IV had good discrimination for hospital mortality, it overestimated hospital mortality of critically ill patients in Hong Kong.

Abstract Background Haemoptysis is an uncommon presenting symptom in children and is usually caused by acute lower respiratory tract infection or foreign body aspiration. We report a rare case of right unilateral pulmonary vein atresia (PVA) as the underlying aetiology of recurrent haemoptysis in a child. Case presentation A 4 years old girl presented with history of recurrent haemoptysis. Bronchoscopic evaluation excluded a foreign body aspiration but revealed right bronchial mucosal hyperaemia and varices. Diagnosis of right unilateral PVA was suspected on transthoracic echocardiography which demonstrated hypoplastic right pulmonary artery and non-visualization of right pulmonary veins. Final diagnosis was confirmed on cardiac CT angiography. A conservative treatment approach was opted with consideration for pneumonectomy in future when she is older. Conclusion Rarer causes should be considered when investigating for recurrent haemoptysis in children. Bronchoscopy and cardiac imaging are useful tools to establish the diagnosis of unilateral PVA in our case.

To monitor the incidence of Plasmodium knowlesi infections and determine whether other simian malaria parasites are being transmitted to humans, we examined 1,047 blood samples from patients with malaria at Kapit Hospital in Kapit, Malaysia, during June 24, 2013–December 31, 2017. Using nested PCR assays, we found 845 (80.6%) patients had either P. knowlesi monoinfection (n = 815) or co-infection with other Plasmodium species (n = 30). We noted the annual number of these zoonotic infections increased greatly in 2017 (n = 284). We identified 6 patients, 17–65 years of age, with P. cynomolgi and P. knowlesi co-infections, confirmed by phylogenetic analyses of the Plasmodium cytochrome c oxidase subunit 1 gene sequences. P. knowlesi continues to be a public health concern in the Kapit Division of Sarawak, Malaysian Borneo. In addition, another simian malaria parasite, P. cynomolgi, also is an emerging cause of malaria in humans.

Introduction: Several studies have reaffirmed the use of regular pentoxifylline therapy in increasing the penile brachial pressure index in men affected by erectile dysfunction when compared to placebo. Aim: The aim of this study was to evaluate the efficacy of pentoxifylline as an adjunctive treatment for patients with erectile dysfunction. Methods: This study was a single center, prospective, randomized, double-blind, placebo-controlled trial. Subjects were recruited between April 2014 and November 2016 from the National University Hospital, Singapore. The combination therapy group was given pentoxifylline 400 mg thrice daily orally and the monotherapy group was given placebo capsules thrice daily orally. Both groups continued their on-demand 100 mg sildenafil. The treatment duration was 8 weeks. Efficacy was measured via the International Index of Erectile Function (IIEF-5) questionnaire at the eighth week. Differences in mean IIEF-5 score and the domains of the IIEF at 8 weeks between the 2 treatment groups were compared using independent sample t-test. Main Outcome Measure: Baseline IIEF-5 and the IIEF-15 score vs post-therapy IIEF-5 and the IIEF-15 score. Results: 50 patients were randomized into 2 groups. Patients in the 2 groups were comparable in terms of the demographic and clinical characteristics, comorbidities, and baseline IIEF-5 scores. The mean IIEF-5 score post-therapy of the combination therapy group vs the monotherapy group was 14.11 and 14.87, respectively. There was no significant difference between the outcomes of these 2 groups (unadjusted mean difference -0.76; 95% CI -4.01 to 2.49; P = .641) and the outcomes are the same even after adjusting for baseline IIEF-5 scores. There was a significant improvement in the “overall satisfaction” portion of the IIEF score for the combination therapy group as compared to the monotherapy group (unadjusted mean difference 0.12; 95% CI -1.49 to 1.25) and even after adjustment for baseline scores (adjusted mean difference 1.11; 95% CI 0.10 to 2.12; P = .032) the improvement is significant. Conclusion: Our trial suggests that the use of combination therapy does not improve the management of patients compared to monotherapy.Law YXT, Tai BC, Tan YQ et al. A Small Group Randomized Double-Blind Placebo-Controlled Study to Evaluate the Efficacy of Daily Pentoxifylline in the Management of Patients With Erectile Dysfunction with Suboptimal Treatment Response to Sildenafil. Sex Med 2019;8:14–20. Key Words: Pentoxifylline, Erectile Dysfunction, Placebo-Controlled Trial, Phosphodiesterase-5 Inhibitor

In myo-control, for computational and setup constraints, the measurement of a high number of muscles is not always possible: the choice of the muscle set to use in a myo-control strategy depends on the desired application scope and a search for a reduced muscle set, tailored to the application, has never been performed. The identification of such set would involve finding the minimum set of muscles whose difference in terms of intention detection performance is not statistically significant when compared to the original set. Also, given the intrinsic sensitivity of muscle synergies to variations of EMG signals matrix, the reduced set should not alter synergies that come from the initial input, since they provide physiological information on motor coordination. The advantages of such reduced set, in a rehabilitation context, would be the reduction of the inputs processing time, the reduction of the setup bulk and a higher sensitivity to synergy changes after training, which can eventually lead to modifications of the ongoing therapy. In this work, the existence of a minimum muscle set, called optimal set, for an upper-limb myoelectric application, that preserves performance of motor activity prediction and the physiological meaning of synergies, has been investigated. Analyzing isometric contractions during planar reaching tasks, two types of optimal muscle sets were examined: a subject-specific one and a global one. The former relies on the subject-specific movement strategy, the latter is composed by the most recurrent muscles among subjects specific optimal sets and shared by all the subjects. Results confirmed that the muscle set can be reduced to achieve comparable hand force estimation performances. Moreover, two types of muscle synergies namely “Pose-Shared” (extracted from a single multi-arm-poses dataset) and “Pose-Related” (clustering pose-specific synergies), extracted from the global optimal muscle set, have shown a significant similarity with full-set related ones meaning a high consistency of the motor primitives. Pearson correlation coefficients assessed the similarity of each synergy. The discovering of dominant muscles by means of the optimization of both muscle set size and force estimation error may reveal a clue on the link between synergistic patterns and the force task.

Quantifiable erectile dysfunction (ED) diagnosis involves the monitoring of rigidity and tumescence of the penile shaft during nocturnal penile tumescence (NPT). In this work, we introduce Erectile Dysfunction SENsor (EDSEN), a home-based wearable device for quantitative penile health monitoring based on stretchable microtubular sensing technology. Two types of sensors, the T- and R-sensors, are developed to effectively measure penile tumescence and rigidity, respectively. Conical models mimicking penile shaft were fabricated with polydimethylsiloxane (PDMS) material, using different base to curing agent ratios to replicate the different hardness properties of a penile shaft. A theoretical buckling force chart for the different penile models is generated to determine sufficiency criteria for sexual intercourse. An average erect penile length and circumference requires at least a Young’s modulus of 179 kPa for optimal buckling force required for satisfactory sexual intercourse. The conical penile models were evaluated using EDSEN. Our results verified that the circumference of a penile shaft can be accurately measured by T-sensor and rigidity using the R-sensor. EDSEN provides a private and quantitative method to detect ED within the comfortable confines of the user’s home.

A audição é um dos sentidos mais significativos para a comunicação humana, de tal maneira que a sua ausência acarreta efeitos negativos no bem-estar e na qualidade de vida da população envolvida. Diante desse contexto, esse estudo teve como objetivo relatar a experiência das atividades de pesquisa e de extensão desenvolvidas no Programa Saúde Auditiva do Escolar (PSAE), voltadas à educação em saúde auditiva. Foram realizados testes auditivos em uma comunidade escolar e verificadas as alterações auditivas mais prevalentes nessa população. Os principais achados foram obstrução de orelhas por cerume e relato do uso frequente de fones de ouvido. Os resultados encontrados contribuíram para a realização da ação de extensão “Ouvir por toda a vida: Dia Mundial da Audição 2020”, durante a qual foram realizadas quatro atividades por meio de recursos didáticos e lúdicos com essa população, sendo elas (1) “higienização das orelhas”, (2) “mapa do barulho”, (3) avaliação da intensidade do fone de ouvido com o auxílio da “Cocleannny”, (4) roda de conversa com os escolares com o auxílio da “Alexa” (personagem virtual) e (5) roda de conversa com os professores, sobre os problemas mais frequentes detectados. Todas as atividades apresentaram bons resultados, além de engajamento por parte da comunidade escolar, contribuindo para que os escolares possam tomar decisões mais adequadas quanto aos hábitos deletérios antes praticados: excessiva utilização do fone de ouvido e ruído durante as aulas. Palavras-chave: Transtornos da Audição; Estudantes; Educação em Saúde; Prevenção Primária School Auditory Health Program: an integration between research and extension Abstract: Hearing is one of the most significant meanings for human communication, so that its absence has adverse effects on the well-being and quality of life of the population involved. Given this context, this study aimed to report the experience of research and extension activities developed in the School Auditory Health Program (SAHP), focused on hearing health education. Hearing tests were carried out in a school community, and the most prevalent hearing disorders in this population were verified. The main findings were ear obstruction by cerumen and self-report of the frequent use of headphones. The results found contributed to the implementation of the extension action “Listening for life: World Hearing Day 2020”, during which four interactive activities were carried out through didactic and ludic resources with this population, which are (1) “ear cleaning,” (2) “noise map,” (3) earphone intensity assessment with the help of “Cocleanny,” (4) conversation with students with the help of the virtual character “Alexa” and (5) conversation with the teachers, all aiming to reduce the most frequent problems detected. All activities showed promising results and engagement by the school community, helping the students make more appropriate decisions regarding the harmful habits previously practiced, e. g. excessive use of the headset and noise during classes. Keywords: Hearing Disorders; Students; Health Education; Primary Prevention

OBJECTIVE: To determine the prevalence and incidence of tuberculosis in one of Uganda's poor peri-urban areas. METHODS: Multi-stage sampling was used to select a sample of households whose members were evaluated for presence of signs and/or symptoms of active tuberculosis; history of tuberculosis treatment; and relevant demographic, socioeconomic, and household environment characteristics. Patients with suspected tuberculosis underwent standardized evaluation for active disease. FINDINGS: A sample of 263 households with 1142 individuals was evaluated. Nineteen people were classified as having had tuberculosis during the one-year reference period (May 2001-April 2002): nine (47%) cases already had been diagnosed through the health care system, while 10 cases (53%) were diagnosed through the survey. The prevalences for all forms of tuberculosis and for sputum smear-positive tuberculosis were 14.0 (95% confidence interval (CI) 7.8-20.3) and 4.4 (CI = 0.83-7.89) per thousand, respectively. The incidences for all forms of tuberculosis and for sputum smear-positive tuberculosis were 9.2 (CI = 3.97-14.4) and 3.7 (CI = 0.39-6.95) per thousand per year, respectively. CONCLUSION: The rate of tuberculosis in this peri-urban community was exceptionally high and may be underestimated by current surveillance systems. The need for interventions aimed at reducing tuberculosis transmission in this, and other similar communities with high case rates, is urgent.

Filarial worms are parasitic nematodes that cause devastating diseases such as lymphatic filariasis (LF) and onchocerciasis. Filariae are nematodes with complex anatomy including fully developed digestive tracts and reproductive organs. To better understand the basic biology of filarial parasites and to provide insights into drug targets and vaccine design, we conducted a proteomic analysis of different anatomic fractions of Brugia malayi, a causative agent of LF. Approximately 500 adult female B. malayi worms were dissected, and three anatomical fractions (body wall, digestive tract, and reproductive tract) were obtained. Proteins from each anatomical fraction were extracted, desalted, trypsinized, and analyzed by microcapillary reverse-phase liquid chromatography-tandem-mass spectrometry. In total, we identified 4,785 B. malayi proteins. While 1,894 were identified in all three anatomic fractions, 396 were positively identified only within the digestive tract, 114 only within the body wall, and 1,011 only within the reproductive tract. Gene set enrichment analysis revealed a bias for transporters to be present within the digestive tract, suggesting that the intestine of adult filariae is functional and important for nutrient uptake or waste removal. As expected, the body wall exhibited increased frequencies of cytoskeletal proteins, and the reproductive tract had increased frequencies of proteins involved in nuclear regulation and transcription. In assessing for possible vaccine candidates, we focused on proteins sequestered within the digestive tract, as these could possibly represent "hidden antigens" with low risk of prior allergic sensitization. We identified 106 proteins that are enriched in the digestive tract and are predicted to localize to the surface of cells in the the digestive tract. It is possible that some of these proteins are on the luminal surface and may be accessible by antibodies ingested by the worm. A subset of 27 of these proteins appear especially promising vaccine candidates as they contain significant non-cytoplasmic domains, only 1-2 transmembrane domains, and a high degree of homology to W. bancrofti and/or O. volvulus.

A major advance in our understanding of the natural history of Schistosoma haematobium-related morbidity has come through the introduction of the portable ultrasound machines for non-invasive examination of the kidneys and bladder. With the use of generators or battery packs to supply power in non-clinical field settings, and with the use of instant photography or miniaturized thermal printers to record permanent images, it is possible to examine scores of individuals in endemic communities every day. Broad-based ultrasound screening has allowed better definition of age-specific disease risks in urinary schistosomiasis. Results indicate that urinary tract abnormalities are common (18% overall prevalence) in S. haematobium transmission areas, with a 2-4% risk of either severe bladder abnormality or advanced ureteral obstruction. In longitudinal surveys, ultrasound studies have shown that praziquantel and metrifonate therapy are rapidly effective in reversing urinary tract abnormalities among children. The benefits of treating adults are less well known, but research in progress should help to define this issue. Similarly, the prognosis of specific ultrasound findings needs to be clarified, and the ease of sonographic examination will make such long-term follow-up studies feasible. In summary, the painless, quick, and reproducible ultrasound examination has become an essential tool in the study of urinary schistosomiasis.

Prostate cancer patients often have increased levels of psychological stress or anxiety, but the molecular mechanisms underlying the interaction between psychological stress and prostate cancer as well as therapy resistance have been rarely studied and remain poorly understood. Recent reports show that stress inhibits apoptosis in prostate cancer cells via epinephrine/beta2 adrenergic receptor/PKA/BAD pathway. In this study, we used experimental data on the signaling pathways that control BAD phosphorylation to build a dynamic network model of apoptosis regulation in prostate cancer cells. We then compared the predictive power of two different models with or without the role of Mcl-1, which justified the role of Mcl-1 stabilization in anti-apoptotic effects of emotional stress. Based on the selected model, we examined and quantitatively evaluated the induction of apoptosis by drug combination therapies. We predicted that the combination of PI3K inhibitor LY294002 and inhibition of BAD phosphorylation at S112 would produce the best synergistic effect among 8 interventions examined. Experimental validation confirmed the effectiveness of our predictive model. Moreover, we found that epinephrine signaling changes the synergism pattern and decreases efficacy of combination therapy. The molecular mechanisms responsible for therapeutic resistance and the switch in synergism were explored by analyzing a network model of signaling pathways affected by psychological stress. These results provide insights into the mechanisms of psychological stress signaling in therapy-resistant cancer, and indicate the potential benefit of reducing psychological stress in designing more effective therapies for prostate cancer patients.