Antibodies to Helminth Defense Molecule-1 are associated with inflammation, organomegaly, and decreased nutritional status in schistosomiasis japonica.

Immunomodulation enhances parasite fitness by reducing inflammation-induced morbidity in the mammalian host, as well as by attenuating parasite-targeting immune responses. Using a whole proteome differential screening method, we identified Schistosoma japonicum Helminth Defense Molecule (SjHDM-1) as a target of antibodies expressed by S. japonicum resistant, but not susceptible, individuals. In a longitudinal cohort study (N=644) conducted in a S. japonicum endemic region of the Philippines, antibody levels to SjHDM-1 did not predict resistance to reinfection but were associated with increased measures of inflammation. Individuals with high levels of anti-SjHDM-1 IgG had higher levels of C-reactive protein compared to individuals with low anti-SjHDM-1. High anti-SjHDM-1 IgG responses were also associated with reduced biomarkers of nutritional status (albumin), as well as decreased anthropometric measures of nutritional status (WAZ and HAZ) and increased measures of hepatomegaly. Our results suggest that anti-SjHDM-1 responses inhibit the immunomodulatory function of SjHDM-1, resulting in increased morbidity.

T follicular helper cell profiles differ by malaria antigen and for children compared to adults.

Background: Circulating T-follicular helper (cT FH ) cells have the potential to provide an additional correlate of protection against Plasmodium falciparum ( Pf) as they are essential to promote B cell production of long-lasting antibodies. Assessing the specificity of cT FH subsets to individual malaria antigens is vital to understanding the variation observed in antibody responses and identifying promising malaria vaccine candidates. Methods: Using spectral flow cytometry and unbiased clustering analysis we assessed antigen-specific cT FH cell recall responses in vitro to malaria vaccine candidates Pf SEA-1A and Pf GARP within a cross-section of children and adults living in a malaria holoendemic region of western Kenya. Findings: In children, a broad array of cT FH subsets (defined by cytokine and transcription factor expression) were reactive to both malaria antigens, Pf SEA-1A and Pf GARP, while adults had a narrow profile centering on cT FH 17- and cT FH 1/17-like subsets following stimulation with Pf GARP only. Interpretation: Because T FH 17 cells are involved in the maintenance of memory antibody responses within the context of parasitic infections, our results suggest that Pf GARP might generate longer lived antibody responses compared to Pf SEA-1A. These findings have intriguing implications for evaluating malaria vaccine candidates as they highlight the importance of including cT FH profiles when assessing interdependent correlates of protective immunity.

Evaluation of sensitivity and specificity of Kato-Katz and circulating cathodic antigen in terms of Schistosoma japonicum using latent class analysis.

Schistosoma japonicum is endemic in the Philippines. The Kato-Katz (KK) method was used to diagnose S. japonicum. This is impractical, particularly when the sample size is limited. Knowledge on point-of-care circulating cathodic antigen (CCA) test performance for S. japonicum is limited. Determining the sensitivity and specificity of new diagnostics is difficult when the gold standard test is less effective or absent. Latent class analysis (LCA) can address some limitations. A total of 484 children and 572 adults from the Philippines were screened for S. japonicum. We performed Bayesian LCA to estimate the infection prevalence, sensitivity and specificity of each test by stratifying them into two age groups. Observed prevalence assessed by KK was 50.2% and 31.8%, and by CCA was 89.9% and 66.8%, respectively. Using Bayesian LCA, among children, the sensitivity and specificity of CCA were 94.8% (88.7-99.4) and 21.5% (10.5-36.1) while those of KK were 66.0% (54.2-83.3) and 78.1% (61.1-91.3). Among adults, the sensitivity and specificity of CCA were 86.4% (76.6-96.9) and 62.8% (49.1-81.1) while those of KK were 43.6% (35.1-53.9) and 85.5% (75.8-94.6). Overall, CCA was more sensitive than KK, regardless of the age group at diagnosis, as KK was more specific. KK and CCA have different diagnostic performance, which should inform their use in the planning and implementation of S. japonicum control programs.

Relationships Between Schistosoma mansoni Infection Intensity and Nutritional Status and Anemia Among Preschool-aged Children in Uganda.

In a cross-sectional analysis of 354 Ugandan children (age 12-48 months) infected with Schistosoma mansoni, we assessed relationships between infection intensity and nutritional morbidities. Higher intensity was associated with an increased risk for anemia (RR = 1.05, 95% confidence interval [CI] 1.01-1.10) yet not associated with risk for underweight, stunting, or wasting.

Weight stigma from romantic partners: Its relations with maladaptive and adaptive coping and depressive symptoms.

Social devaluation of being overweight is common in daily life, but little is known about the weight stigma in romantic relationships. The present study investigated the roles of maladaptive and adaptive coping strategies in the relation between the experience of weight stigma in romantic relationships and depressive symptoms in men and women, respectively. Analyses of gender differences and structural equation modeling yielded several findings. First, while men and women experienced similar levels of weight stigma from their romantic partners, women were more likely to use exercise avoidance, disengagement coping, and reappraisal coping strategies, and to exhibit more depressive symptoms than men. Second, men who experienced weight stigma tended to cope with it through exercise avoidance and disengagement coping, which were related to greater depressive symptoms. Men also coped with weight stigma adaptively via reappraisal coping, which was additionally associated with more positive affect. Third, the relation between the experience of weight stigma and depressive symptoms in women was only explained by using disengagement coping. These findings extend the understanding of weight stigma to a specific context and provide some insight that future interventions to reduce the impacts of weight stigma should be tailored accordingly for men and women.

Immunohistochemical Characterization of a Large Cohort of Triple Negative Breast Cancer.

Introduction. Triple negative breast carcinomas are characterized by a lack of hormone receptor and HER2 expression and inconsistent expression of breast-specific immunohistochemical markers. The expression of many site-specific markers in these tumors is largely unknown. The objective of the study was to examine the expression of widely used immunohistochemical markers on a large cohort of triple negative breast cancer. Methods. Sections from tissue microarrays were stained with 47 markers using routine protocols. Most markers were scored using a modified Allred method. ATRX, BAP1, SMAD4, e-cadherin, and beta-catenin were scored as retained or lost. Mammaglobin was considered positive if there was at least moderate intensity staining in any tumor cells. P16 was scored as overexpressed or not overexpressed; p53 was scored as wildtype, overexpressed, null, or cytoplasmic. Results. The cohort consisted of 639 tumors including 601 primary and 32 metastases. Overall, 96% expressed GATA3, mammaglobin, and/or SOX10 while 97% of no special type tumors expressed this panel. Carcinoma of apocrine differentiation demonstrated an AR positive, SOX10 negative, K5 negative/focal immunophenotype. PAX8 (SP348), WT1, Napsin A, and TTF1 (8G7G3/1) were never or rarely expressed while CA9, CDX2, NKX3.1, SATB2 (SATBA410), synaptophysin, and vimentin were variably expressed. Conclusions. Almost all TNBC express at least 1 of the 3 IHC markers: GATA3, mammaglobin, and/or SOX10. Carcinoma of apocrine differentiation is characterized by an AR positive, SOX10 negative, K5 negative or focal immunophenotype. Cautious interpretation of so-called site-specific markers, with knowledge of antibody clones, is required in excluding the diagnosis of triple negative breast cancer.

Baseline Liver Ultrasound Findings in Preschool Children From the Praziquantel in Preschoolers Trial in Lake Albert, Uganda.

BACKGROUND: Periportal fibrosis is a late-stage manifestation of chronic infection with Schistosoma mansoni . Praziquantel (PZQ), the only drug available for the treatment of schistosomiasis, has limited effect in treating established morbidity. Preschool-age children (PSAC) are not considered to be an at-risk population for severe morbidity. However, the prevalence of periportal fibrosis in PSAC in S. mansoni endemic settings is unknown. METHODS: As part of a phase II clinical trial comparing different dosing regimens of PZQ in children age 12-47 months infected with S. mansoni in Uganda ("praziquantel in preschoolers" trial), we present baseline results assessing liver ultrasound (US) findings as per the WHO Niamey Protocol. RESULTS: A total of 7/347 (2%) PSAC had Image Pattern C with pipe stems and echogenic rings suggestive of periportal fibrosis, 29/347 (8%) had Image Pattern B and 58 (17%) had evidence of periportal thickening There were higher adjusted odds of periportal thickening with older age [odds ratio (OR): 1.04; 95% confidence interval (CI): 1.00-1.07], primary maternal education (OR: 1.04; 95% CI: 1.00-1.07) and being taken to the lake weekly (OR: 3.02; 95% CI: 1.19-7.63). A further 44/347 children (13%) had a rounded caudal liver edge which was associated with high S. mansoni infection intensity (adjusted OR: 3.31; 95% CI: 1.46-7.51). CONCLUSIONS: Incipient schistosomiasis-related liver morbidity was detected in young children enrolled in the praziquantel in preschoolers trial. Adequate age-adjusted reference measurements for liver ultrasound findings in very small children are lacking but urgently needed. Schistosomiasis-related fibrosis may be delayed or averted with early and repeated PZQ treatment.

You are how you speak: The roles of vocal pitch and semantic cues in shaping social perceptions.

Social perceptions of speakers are influenced by their voice information, including vocal characteristics and semantic content. Our study investigated how individuals' warmth- and competence-related perceptions of speakers were affected by vocal pitch levels (i.e., high/low) and three kinds of semantic cues (i.e., prosocial, antisocial, and neutral) simultaneously. We have three key findings. First, antisocial cues negatively affected social perceptions, regardless of speakers' gender. However, prosocial cues did not have positive impacts on evaluations of speakers because ratings were similar between prosocial cues and neutral cues. Second, female vocal pitch mattered for warmth-related perceptions but not for competence-related perceptions. The role of semantic cues should be additionally considered when investigating the impact of male vocal pitch on these perceptions. For example, higher-pitched men in prosocial contexts were perceived as warmer, while low-pitched men in antisocial contexts were judged as more competent. Third, the connection between vocal pitch and two kinds of perceptions showed an opposite trend, in which high pitch was related to more warmth but less competence, while the low pitch was associated with less warmth but more competence. These findings extend the understanding of the role of vocal pitch in the formation of stereotypes of strangers in different semantic contexts.

Characteristics of a COVID-19 Cohort With Large Vessel Occlusion: A Multicenter International Study.

BACKGROUND: The mechanisms and outcomes in coronavirus disease (COVID-19)-associated stroke are unique from those of non-COVID-19 stroke. OBJECTIVE: To describe the efficacy and outcomes of acute revascularization of large vessel occlusion (LVO) in the setting of COVID-19 in an international cohort. METHODS: We conducted an international multicenter retrospective study of consecutively admitted patients with COVID-19 with concomitant acute LVO across 50 comprehensive stroke centers. Our control group constituted historical controls of patients presenting with LVO and receiving a mechanical thrombectomy between January 2018 and December 2020. RESULTS: The total cohort was 575 patients with acute LVO; 194 patients had COVID-19 while 381 patients did not. Patients in the COVID-19 group were younger (62.5 vs 71.2; P < .001) and lacked vascular risk factors (49, 25.3% vs 54, 14.2%; P = .001). Modified thrombolysis in cerebral infarction 3 revascularization was less common in the COVID-19 group (74, 39.2% vs 252, 67.2%; P < .001). Poor functional outcome at discharge (defined as modified Ranklin Scale 3-6) was more common in the COVID-19 group (150, 79.8% vs 132, 66.7%; P = .004). COVID-19 was independently associated with a lower likelihood of achieving modified thrombolysis in cerebral infarction 3 (odds ratio [OR]: 0.4, 95% CI: 0.2-0.7; P < .001) and unfavorable outcomes (OR: 2.5, 95% CI: 1.4-4.5; P = .002). CONCLUSION: COVID-19 was an independent predictor of incomplete revascularization and poor outcomes in patients with stroke due to LVO. Patients with COVID-19 with LVO were younger, had fewer cerebrovascular risk factors, and suffered from higher morbidity/mortality rates.

Acute ischaemic stroke associated with SARS-CoV-2 infection in North America.

BACKGROUND: To analyse the clinical characteristics of COVID-19 with acute ischaemic stroke (AIS) and identify factors predicting functional outcome. METHODS: Multicentre retrospective cohort study of COVID-19 patients with AIS who presented to 30 stroke centres in the USA and Canada between 14 March and 30 August 2020. The primary endpoint was poor functional outcome, defined as a modified Rankin Scale (mRS) of 5 or 6 at discharge. Secondary endpoints include favourable outcome (mRS ≤2) and mortality at discharge, ordinal mRS (shift analysis), symptomatic intracranial haemorrhage (sICH) and occurrence of in-hospital complications. RESULTS: A total of 216 COVID-19 patients with AIS were included. 68.1% (147/216) were older than 60 years, while 31.9% (69/216) were younger. Median [IQR] National Institutes of Health Stroke Scale (NIHSS) at presentation was 12.5 (15.8), and 44.2% (87/197) presented with large vessel occlusion (LVO). Approximately 51.3% (98/191) of the patients had poor outcomes with an observed mortality rate of 39.1% (81/207). Age >60 years (aOR: 5.11, 95% CI 2.08 to 12.56, p<0.001), diabetes mellitus (aOR: 2.66, 95% CI 1.16 to 6.09, p=0.021), higher NIHSS at admission (aOR: 1.08, 95% CI 1.02 to 1.14, p=0.006), LVO (aOR: 2.45, 95% CI 1.04 to 5.78, p=0.042), and higher NLR level (aOR: 1.06, 95% CI 1.01 to 1.11, p=0.028) were significantly associated with poor functional outcome. CONCLUSION: There is relationship between COVID-19-associated AIS and severe disability or death. We identified several factors which predict worse outcomes, and these outcomes were more frequent compared to global averages. We found that elevated neutrophil-to-lymphocyte ratio, rather than D-Dimer, predicted both morbidity and mortality.

Comparison of self-reported and observed water contact measures in Schistosoma japonicum-endemic villages in Leyte, The Philippines.

BACKGROUND: We compared individuals' self-reported water contact from a questionnaire to direct observation of water contact. Questionnaires that accurately capture water contact are necessary to risk-stratify individuals and communities at high risk for schistosomiasis. METHODS: Individuals (N=677) ages 7-30 y were included from three Schistosoma japonicum-endemic villages in Leyte, The Philippines. Each individual was observed for 12 d over the course of the 18-month study and the questionnaire was administered six times. A questionnaire index was derived that captured the number of self-reported contacts with water bodies for any purpose. An exposure index was created based on the sum of contacts that was weighted by the percentage of body surface area (BSA) exposed and exposure duration. RESULTS: Of 16 water contact activities, only bathing and washing clothes exhibited a significant, positive correlation between self-reported contacts and the observed exposure index related to those contacts. CONCLUSIONS: We found that only the reported frequencies of bathing and washing clothes were significantly related to an individual's overall observed exposure index, while use of all reported contacts was not related to the observed exposure. This study further supports the need for questionnaires to be augmented by some measure of how much BSA is exposed and/or time is spent in the water on average for a specific activity.

In vitro antibacterial activity of nimbolide against Helicobacter pylori.

ETHNOPHARMACOLOGICAL RELEVANCE: Nimbolide is one of hundreds of phytochemicals that have been identified within the neem tree (Azadirachta indica A. Juss). As an evergreen tree native to the Indian subcontinent, components of the neem tree have been used for millennia in traditional medicine to treat dental, gastrointestinal, urinary tract, and blood-related ailments, ulcers, headaches, heartburn, and diabetes. In modern times, natural oils and extracts from the neem tree have been found to have activities against a variety of microorganisms, including human pathogens. AIM OF THE STUDY: Helicobacter pylori, a prevalent gastric pathogen, shows increasing levels of antibiotic resistance. Thus, there is an increasing demand for novel therapeutics to treat chronic infections. The in vitro activity of neem oil extract against H. pylori was previously characterized and found to be bactericidal. Given the numerous phytochemicals found in neem oil extract, the present study was designed to define and characterize specific compounds showing bactericidal activity against H. pylori. MATERIALS AND METHODS: Azadirachtin, gedunin, and nimbolide, which are all common in neem extracts, were tested for antimicrobial activity; the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined for nine strains of H. pylori. The specific properties of nimbolide were further characterized against H. pylori strain G27. Bactericidal kinetics, reversibility, effectiveness at low pH, and activity under bacteriostatic conditions were examined. The hemolytic activity of nimbolide was also measured. Finally, neem oil extract and nimbolide effectiveness against H. pylori biofilms were examined in comparison to common antibiotics used to treat H. pylori infection. RESULTS: Nimbolide, but not azadirachtin or gedunin, was effective against H. pylori; MICs and MBCs against the nine tested strains ranged between 1.25-5 µg/mL and 2.5-10 µg/mL, respectively. Additionally, neem oil extract and nimbolide were both effective against H. pylori biofilms. Nimbolide exhibited no significant hemolytic activity at biologically relevant concentrations. The bactericidal activity of nimbolide was time- and dose-dependent, independent of active H. pylori growth, and synergistic with low pH. Furthermore, nimbolide-mediated H. pylori cell death was irreversible after exposure to high nimbolide concentrations (80 µg/mL, after 2 h of exposure time and 40 µg/mL after 8 h of exposure). CONCLUSIONS: Nimbolide has significant bactericidal activity against H. pylori, killing both free living bacterial cells as well as cells within a biofilm. Furthermore, the lack of hemolytic activity, synergistic activity at low pH and bactericidal properties even against bacteria in a state of growth arrest are all ideal pharmacological and biologically relevant properties for a potential new agent. This study underscores the potential of neem oil extract or nimbolide to be used as a future treatment for H. pylori infection.

The praziquantel in preschoolers (PIP) trial: study protocol for a phase II PK/PD-driven randomised controlled trial of praziquantel in children under 4 years of age.

BACKGROUND: Over 200 million individuals worldwide are infected with Schistosoma species, with over half of infections occurring in children. Many children experience first infections early in life and this impacts their growth and development; however praziquantel (PZQ), the drug used worldwide for the treatment of schistosomiasis, only has regulatory approval among adults and children over the age of four, although it is frequently used "off label" in endemic settings. Furthermore, pharmacokinetic/pharmacodynamics (PK/PD) evidence suggests the standard PZQ dose of 40 mg/kg is insufficient in preschool-aged children (PSAC). Our goal is to understand the best approaches to optimising the treatment of PSAC with intestinal schistosomiasis. METHODS: We will conduct a randomised, controlled phase II trial in a Schistosoma mansoni endemic region of Uganda and a Schistosoma japonicum endemic region of the Philippines. Six hundred children, 300 in each setting, aged 12-47 months with Schistosoma infection will be randomised in a 1:1:1:1 ratio to receive either (1) 40 mg/kg PZQ at baseline and placebo at 6 months, (2) 40 mg/kg PZQ at baseline and 40 mg/kg PZQ at 6 months, (3) 80 mg/kg PZQ at baseline and placebo at 6 months, or (4) 80 mg/kg PZQ at baseline and 80 mg/kg PZQ at 6 months. Following baseline treatment, children will be followed up for 12 months. The co-primary outcomes will be cure rate and egg reduction rate at 4 weeks. Secondary outcomes include drug efficacy assessed by novel antigenic endpoints at 4 weeks, actively collected adverse events and toxicity for 12 h post-treatment, morbidity and nutritional outcomes at 6 and 12 months, biomarkers of inflammation and environmental enteropathy and PZQ PK/PD parameters. DISCUSSION: The trial will provide valuable information on the safety and efficacy of the 80 mg/kg PZQ dose in PSAC, and on the impact of six-monthly versus annual treatment, in this vulnerable age group. TRIAL REGISTRATION: ClinicalTrials.gov NCT03640377 . Registered on 21 Aug 2018.

High prevalence of Schistosoma japonicum by perfusion in naturally exposed water buffalo in a region of the Philippines endemic for human schistosomiasis.

In the past decade, ecological surveys emphasized rats and dogs as the most significant animal reservoirs for Schistosoma japonicum (S.j) in the Philippines. However, recent studies demonstrated 51-91% prevalence of schistosomiasis among water buffalo using qPCR in the Sj endemic regions in the Philippines. In order to resolve the inconsistency of reported surveys regarding Sj endemicity among carabao, a domestic water buffalo that is the most important draught animal, we introduced 42 schistosome negative water buffalo to Macanip, Jaro municipality, Leyte, the Philippines, a subsistence rice-farming village that has been the focus of schistosomiasis japonica studies of our group for the past 20 years. We conducted perfusion to the remaining 34 buffalo that survived 10 months of nature exposure and Typhoon Haiyan. Thirty-three water buffalo were found to be positive with at least 1 pair of worms from the mesenteric vein. The infection rate is 97%, with the worm burden of 94 (95% confidence interval, 49-138 worms) worms. To our knowledge, this is the first report about S. japonicum worm burden in naturally infected water buffalo in the Philippines. The fact that with less than one-year of exposure, in this human schistosomiasis endemic area, only 1 out of 34 water buffalo was uninfected is striking. Urgent attention is needed for a cost-effective technique for monitoring Sj infection in animals and humans. Meanwhile, intervention implementation, including water buffalo treatment and vaccination, should be taken into consideration.

Age and Acute Ischemic Stroke Outcome in North American Patients With COVID-19.

Background Acute ischemic stroke (AIS) in the context of COVID-19 has received considerable attention for its propensity to affect patients of all ages. We aimed to evaluate the effect of age on functional outcome and mortality following an acute ischemic event. Methods and Results A prospectively maintained database from comprehensive stroke centers in Canada and the United States was analyzed for patients with AIS from March 14 to September 30, 2020 who tested positive for SARS-CoV-2. The primary outcome was Modified Rankin Scale score at discharge, and the secondary outcome was mortality. Baseline characteristics, laboratory values, imaging, and thrombectomy workflow process times were assessed. Among all 126 patients with COVID-19 who were diagnosed with AIS, the median age was 63 years (range, 27-94). There were 35 (27.8%) patients with AIS in the aged ≤55 years group, 47 (37.3%) in the aged 56 to 70 group, and 44 (34.9%) in the aged >70 group. Intravenous tissue plasminogen activator and thrombectomy rates were comparable across these groups, (P=0.331 and 0.212, respectively). There was a significantly lower rate of mortality between each group favoring younger age (21.9% versus 45.0% versus 48.8%, P=0.047). After multivariable adjustment for possible confounders, a 1-year increase in age was significantly associated with fewer instances of a favorable outcome of Modified Rankin Scale 0 to 2 (odds ratio [OR], 0.95; 95 CI%, 0.90-0.99; P=0.048) and higher mortality (OR, 1.06; 95 CI%, 1.02-1.10; P=0.007). Conclusions AIS in the context of COVID-19 affects young patients at much greater rates than pre-pandemic controls. Nevertheless, instances of poor functional outcome and mortality are closely tied to increasing age.

Effect of maternal praziquantel treatment for Schistosoma japonicum infection on the offspring susceptibility and immunologic response to infection at age six, a cohort study.

In areas endemic to schistosomiasis, fetal exposure to schistosome antigens prime the offspring before potential natural infection. Praziquantel (PZQ) treatment for Schistosoma japonicum infection in pregnant women has been demonstrated to be safe and effective. Our objectives were to evaluate whether maternal PZQ treatment modifies the process of in utero sensitization to schistosome antigens potentially impacting later risk of infection, as well as immune response to S. japonicum. We enrolled 295 children at age six, born to mothers with S. japonicum infection who participated in a randomized control trial of PZQ versus placebo given at 12-16 weeks gestation in Leyte, The Philippines. At enrollment, we assessed and treated current S. japonicum infection and measured serum cytokines. During a follow-up visit four weeks later, we assessed peripheral blood mononuclear cell (PBMC) cytokine production in response to soluble worm antigen preparation (SWAP) or soluble egg antigen (SEA). Associations between maternal treatment group and the child's S. japonicum infection status and immunologic responses were determined using multivariate linear regression analysis. PZQ treatment during pregnancy did not impact the prevalence (P = 0.12) or intensity (P = 0.59) of natural S. japonicum infection among children at age six. Among children with infection at enrollment (12.5%) there were no significant serum cytokine concentration differences between maternal treatment groups. Among children with infection at enrollment, IL-1 production by PBMCs stimulated with SEA was higher (P = 0.03) in the maternal PZQ group compared to placebo. Among children without infection, PBMCs stimulated with SEA produced greater IL-12 (P = 0.03) and with SWAP produced less IL-4 (P = 0.01) in the maternal PZQ group compared to placebo. Several cytokines produced by PBMCs in response to SWAP and SEA were significantly higher in children with S. japonicum infection irrespective of maternal treatment: IL-4, IL-5, IL-10, and IL-13. We report that maternal PZQ treatment for S. japonicum shifted the PBMC immune response to a more inflammatory signature but had no impact on their offspring's likelihood of infection or serum cytokines at age six, further supporting the safe use of PZQ in pregnant women. Trial Registration: ClinicalTrials.gov NCT00486863.

Whole-Proteome Differential Screening Identifies Novel Vaccine Candidates for Schistosomiasis japonica.

Schistosomiasis remains a leading cause of chronic morbidity in endemic regions despite decades of widespread mass chemotherapy with praziquantel. Using our whole proteome differential screening approach, and plasma and epidemiologic data from a longitudinal cohort of individuals living in a Schistosoma japonicum-endemic region of the Philippines, we interrogated the parasite proteome to identify novel vaccine candidates for Schistosoma japonicum. We identified 16 parasite genes which encoded proteins that were recognized by immunoglobulin G or immunoglobulin E antibodies in the plasma of individuals who had developed resistance to reinfection, but were not recognized by antibodies in the plasma of individuals who remained susceptible to reinfection. Antibody levels to Sj6-8 and Sj4-1 measured in the entire cohort (N = 505) 1 month after praziquantel treatment were associated with significantly decreased risk of reinfection and lower intensity of reinfection over 18 months of follow-up.

Body weight contingent self-worth predicts depression in adolescent girls: The roles of self-esteem instability and interpersonal sexual objectification.

This 3-year longitudinal study examined the extent to which body weight contingent self-worth (CSW) predicted depressive symptoms in 439 adolescent girls and the roles of unstable self-esteem and interpersonal sexual objectification in this association. Half-longitudinal mediation showed that the indirect effect of body weight CSW on depression via instability of self-esteem was significant. Prior levels of body weight CSW predicted increases in unstable self-esteem, which predicted increments in depressive symptoms over time. However, earlier levels of depression did not significantly predict increases in self-esteem instability. Moderation analyses indicated that the indirect effect was conditional upon individuals' experience of interpersonal sexual objectification. The positive link between body weight CSW and unstable self-esteem was stronger in girls who experienced more interpersonal sexual objectification. The direct effect of body weight CSW on depression was also moderated by interpersonal sexual objectification. Taken together, basing self-worth on body weight appears to be a risk factor for depression through its association with unstable self-esteem in adolescent girls and sexually objectifying experiences serve to exacerbate the connection between body weight CSW and adverse outcomes.

FAM46C/TENT5C functions as a tumor suppressor through inhibition of Plk4 activity.

Polo like kinase 4 (Plk4) is a tightly regulated serine threonine kinase that governs centriole duplication. Increased Plk4 expression, which is a feature of many common human cancers, causes centriole overduplication, mitotic irregularities, and chromosomal instability. Plk4 can also promote cancer invasion and metastasis through regulation of the actin cytoskeleton. Herein we demonstrate physical interaction of Plk4 with FAM46C/TENT5C, a conserved protein of unknown function until recently. FAM46C localizes to centrioles, inhibits Plk4 kinase activity, and suppresses Plk4-induced centriole duplication. Interference with Plk4 function by FAM46C was independent of the latter's nucleotidyl transferase activity. In addition, FAM46C restrained cancer cell invasion and suppressed MDA MB-435 cancer growth in a xenograft model, opposing the effect of Plk4. We demonstrate loss of FAM46C in patient-derived colorectal cancer tumor tissue that becomes more profound with advanced clinical stage. These results implicate FAM46C as a tumor suppressor that acts by inhibiting Plk4 activity.