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Fumonisins are naturally occurring mycotoxins that contaminate food for human and animal consumption. They have neurotoxic effects, but the mechanisms by which these toxins affect the nervous system are not fully known. In the present study, male Wistar rats were fed between 21 and 63 days of age with diets that contained fumonisins B

Objective To describe how a fixed regimen of intravitreal injections (IVI) was helpful to continue activity during the COVID-19 outbreak and lockdown and to address basic conditions to resume activity. Methods A fixed regimen of IVI was conceived to significantly reduce the number of visits while keeping a number of injections related to the best outcomes. We retrospectively collected data of surgeries performed in 2019 and in the first seven months of 2020 and from OCTs in the first semester of 2020. Results IVI per month, from January to July 2020, were 304, 291, 256, 204, 276, 297 and 322, respectively. Phacoemulsification surgeries in the same period were 397, 408, 171, 0, 304, 391 and 389. Posterior vitrectomies were 23, 21, 17, 10, 21, 28 and 25. Laser sessions were 44, 26, 33, 17, 23 and 33, respectively. OCTs dropped from a mean of 25.7 per day in the first half of March 2020 to 5.8 per day in the second half of March. A mean of 6.5 OCTs per day was made in April, rising to 19.1 in May and 39.5 in June. Conclusion It was possible to keep the ophthalmological activity during the pandemic outbreak due to the existence of a pre-scheduled fixed regimen for IVI and to the availability of personal protective equipment. The air-borne nature of the peril we are facing addresses the need to evaluate the physical conditions of health facilities, including ventilation, size of waiting and consult rooms and the need to avoid elevators.

Amyloidosis is a rare complication of non-Hodgkin lymphoma, almost exclusively of AL-type, AA-type amyloidosis secondary to non-Hodgkin lymphoma is extremely rare. We report a case of a 55-year-old woman diagnosed with follicular lymphoma that developed nephrotic proteinuria; further investigation confirmed the diagnosis of AA-type amyloidosis, and other long-term inflammatory disorders were excluded. Despite initiation of combined chemotherapy, there was no hematological response and kidney function and clinical condition continued to deteriorate. This case describes an unexpected association, AA-type amyloidosis secondary to non-Hodgkin lymphoma, a condition with poor renal prognosis where treating the underlying disease is paramount.

A displasia cemento ossea florida (DCOF) faz parte de um grupo de lesoes benignas, no qual mostra predilecao por mulheres negras de meia idade. Presente na maioria das vezes no apice dos incisivos ânteroinferiores bilateralmente em mandibula, e normalmente sao diagnosticadas em radiografias de rotina. O objetivo do presente trabalho trata-se do relato de caso de uma paciente com displasia ossea florida, suas caracteristicas clinicas e radiograficas, acompanhados por um periodo de 1 ano. Relata-se o caso de uma paciente do genero feminino, melanoderma, 52 anos, que procurou atendimento para consulta de rotina, e entao diagnosticada com DCOF nos exames complementares, no entanto como a paciente era assintomatica, optou-se pelo acompanhamento clinico e radiografico da lesao. Diante do exposto, o conhecimento sobre a classificacao das displasias e relevante, evitando dessa forma diagnosticos erroneos e, por conseguinte, tratamentos invasivos desnecessarios.

BackgroundThe SARS-CoV-2 Delta variant (B.1.617.2), initially identified in India, has become predominant in several countries, including Portugal. Few studies have compared the effectiveness of mRNA vaccines against Delta versus Alpha variant of concern (VOC) and estimated variant-specific viral loads in vaccine infection breakthroughs cases. In the context of Delta dominance, this information is critical to inform decision-makers regarding the planning of restrictions and vaccination roll-out.MethodsWe developed a case-case study to compare mRNA vaccines’ effectiveness against Delta (B.1.617.2) versus Alpha (B.1.1.7) variants. We used RT-PCR positive cases notified to the National Surveillance System between 17th of May and 4th of July 2021 (week 20 to 26) and information about demographics and vaccination status through the electronic vaccination register. Whole-genome sequencing (WGS) or spike (S) gene target failure (SGTF) data were used to classify SARS-CoV-2 variants. The odds of vaccinated individuals to become infected (odds of vaccine infection breakthrough) in Delta cases compared to Alpha SARS-CoV-2 cases was estimated by conditional logistic regression adjusted for age group, sex, and matched by the week of diagnosis. As a surrogate of viral load, mean RT-PCR Ct values were stratified and compared between vaccine status and VOC.ResultsOf the 2 097 SARS-CoV-2 RT-PCR positive cases included in the analysis, 966 (46.1%) were classified with WGS and 1131 (53.9%) with SGTF. Individuals infected with the Delta variant were more frequently vaccinated 162 (12%) than individuals infected with the Alpha variant 38 (5%). We report a statistically significant higher odds of vaccine infection breakthrough for partial (OR=1.70; CI95% 1.18 to 2.47) and complete vaccination (OR=1.96; CI95% 1.22 to 3.14) in the Delta cases when compared to the Alpha cases, suggesting lower mRNA vaccine effectiveness against Delta cases. On our secondary analysis, we observed lower mean Ct values for the Delta VOC cases versus Alpha, regardless the vaccination status. Additionally, the Delta variant cases revealed a Ct-value mean increase of 2.24 (CI95% 0.85 to 3.64) between unvaccinated and fully vaccinated breakthrough cases contrasting with 4.49 (CI95% 2.07 to 6.91) in the Alpha VOC, suggesting a lower impact of vaccine on viral load of Delta cases.ConclusionsWe found significantly higher odds of vaccine infection breakthrough in Delta cases when compared to Alpha cases, suggesting lower effectiveness of the mRNA vaccines in preventing infection with the Delta variant. Additionally, the vaccine breakthrough cases are estimated to be of higher mean Ct values, suggesting higher infectiousness with the Delta variant infection. These findings can help decision-makers weigh on the application or lifting of control measures and adjusting vaccine roll-out depending on the predominance of the Delta variant and the coverage of partial and complete mRNA vaccination.

Aging is associated with cognitive decline. Herein, we studied a large cohort of old age and young adult male rats and confirmed that, as a group, old rats display poorer spatial learning and behavioral flexibility than younger adults. Surprisingly, when animals were clustered as good and bad performers, our data revealed that while in younger animals better cognitive performance was associated with longer dendritic trees and increased levels of synaptic markers in the hippocampus and prefrontal cortex, the opposite was found in the older group, in which better performance was associated with shorter dendrites and lower levels of synaptic markers. Additionally, in old, but not young individuals, worse performance correlated with increased levels of BDNF and the autophagy substrate p62, but decreased levels of the autophagy complex protein LC3. In summary, while for younger individuals "bigger is better", "smaller is better" is a more appropriate aphorism for older subjects., Portuguese Foundation for Science and Technology (FCT) with fellowships granted to: Cristina Mota (SFRH/BD/81881/2011), Susana Monteiro (SFRH/BD/69311/2010), Sofia Pereira das Neves and Sara Monteiro-Martins (PIC/IC/83213/2007); and by the European Commission within the 7th framework program, under the grant agreement: Health-F2-2010-259772 (Switchbox). In addition, this work was co-funded by the Northern Portugal Regional Operational Programme (ON.2 SR&TD Integrated Program – NORTE-07-0124-FEDER-000021), through the European Regional Development Fund (FEDER) and by national funds granted by FCT (PEst-C/SAU/LA0026/2013), and FEDER through the COMPETE (FCOMP-01-0124-FEDER-037298).

Tuberculosis is considered a serious public health problem. Therefore, this work aimed to analyze the spatial distribution of tuberculosis and its relationship with primary health care public policies in the Para’s northeastern mesoregion, on the period from 2015 to 2019. This is an ecological, descriptive and cross-sectional study that used data available on digital platforms. Choropletics maps were made to visualize the distribution of the disease in the region, where geoprocessing techniques were used. The statistical significance analyzes were performed with the chi-square test: expected equal proportions. The most affected epidemiological profile was male individuals, between 20 and 59 years old, brown in color and with schooling up to elementary school. A non-homogeneous spatial distribution of the disease was observed among the 49 municipalities belonging to the region, which were being related to the number of Basic Health Units (BHU). As for vaccination coverage, it was observed that most of the municipalities belonging to this region were below the national goal of immunization by BCG. Furthermore, such data provide a better comprehension of the spatial distribution of tuberculosis in the region, being important for the construction of epidemiological scenarios and public health policies in this particular area. Keywords: Tuberculosis. Epidemiology. Geoprocessing.

Highlights • Sensitivity heterogeneity among SARS-CoV-2 serological tests. • Maximum sensitivity achieved 21 days since symptoms onset. • COVID-19 clinical outcome is associated with different Igs levels., Background Commercial availability of serological tests to evaluate immunoglobulins (Ig) towards severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has grown exponentially since the onset of disease outbreak. Their thorough validation is of extreme importance before using them as epidemiological tools to infer seroprevalence in specific populations, and as complementary diagnostic tools to molecular approaches (e.g. RT- qPCR). Methods Commercial serological tests from 11 suppliers were assayed side-by-side using 126 samples from SARS-CoV-2-infected inpatients, and 36 healthy and HIV-infected individuals. Results Most of the tests assayed have >95% specificity. For sensitivity calculation, samples were stratified by days since symptoms onset; sensitivity peaks at 16-21 days for IgM and IgA (maximum: 91.2%; Euroimmun); and, varying with the test, at 16-21 or at >21 days for IgG (maximum: 94.1%; Snibe). Data from semiquantitative tests show that patients with severe clinical outcome, in comparison with patients with a non-severe presentation, reveal lower levels of Ig against SARS-CoV-2 at 21 days. Conclusions This study highlights the sensitivity heterogeneity accompanied by an almost general high specificity of most tests and sets the basis for the usefulness of these tests as a complement for diagnosis and population seroprevalence studies.

Analysis of refractive outcomes, using biometry data collected with a new biometer (Pentacam-AXL, OCULUS, Germany) and a reference biometer (Lenstar LS 900, HAAG-STREIT AG, Switzerland), in order to assess differences in the predicted and actual refraction using different formulas. Prospective, institutional study, in which intraocular lens (IOL) calculation was performed using the Haigis, SRK/T and Hoffer Q formulas with the two systems in patients undergoing cataract surgery between November 2016 and August 2017. Four to 6 weeks after surgery, the spherical equivalent (SE) was derived from objective refraction. Mean prediction error (PE), mean absolute error (MAE) and the median absolute error (MedAE) were calculated. The percentage of eyes within ± 0.25, ± 0.50, ± 1.00, and ± 2.00 D of MAE was determined. 104 eyes from 76 patients, 35 males (46.1%), underwent uneventful phacoemulsification with IOL implantation. Mean SE after surgery was − 0.29 ± 0.46 D. Mean prediction error (PE) using the SRK/T, Haigis and Hoffer Q formulas with the Lenstar was significantly different (p > 0.0001) from PE calculated with the Pentacam in all three formulas. Percentage of eyes within ± 0.25 D MAE were larger with the Lenstar device, using all three formulas. The difference between the actual refractive error and the predicted refractive error is consistently lower when using Lenstar. The Pentacam-AXL user should be alert to the critical necessity of constant optimization in order to obtain optimal refractive results.

Background Deoxynivalenol (DON), a mycotoxin produced by Fusarium spp., is commonly found in cereals ingested by humans and animals. Its ingestion is correlated with hepatic, hematologic, renal, splenic, cardiac, gastrointestinal, and neural damages, according to dose, duration of exposure and species. In this work, the effects of the ingestion of DON-contaminated diet at concentrations considered tolerable for human and animal intake were assessed. Methods Male Wistar rats aging 21 days were allotted to five groups that were given, for 42 days, diets contaminated with different concentrations of DON (0, 0.2, 0.75, 1.75, and 2 mg kg-1 of chow). Food ingestion, bodyweight, oxidative status and morphometric analyses of gliocytes, and neurons of jejunal myenteric ganglia were recorded. Key results At these concentrations, there was no food rejection, decrease in bodyweight gain, changes in oxidative status, or loss of either neurons or gliocytes. However, DON decreased gliocyte area, general neuronal population, nitrergic, cholinergic and NADH-diaphorase positive subpopulations and, as a result, ganglion area. Conclusions & inferences It was concluded that, even in the absence of visible effect, DON exposure reduces cell body area of gliocytes and neurons of the myenteric plexus of the rat jejunum.

Purpose: Comparison of biometric measurements and calculation of intraocular lens with a new biometer (Pentacam®-AXL, Oculus, Germany) and a reference biometer (Lenstar LS 900®, Haag-Streit AG, Switzerland), in order to assess the agreement between these two devices. Setting: Centro Hospitalar de Leiria, Portugal Materials and methods: Prospective, institutional study, in which measurements of axial length, anterior chamber depth from the corneal epithelium and endothelium to the anterior surface of the lens (anterior chamber depth ext and anterior chamber depth int), central corneal thickness and keratometry readings of the flattest and steepest meridians (K1 and K2) were obtained with the two systems. Intraocular lens calculation was also performed, using the Haigis, SRK/T and HofferQ formulas. Results: The study sample included 136 eyes of 79 patients. Of these, 42 were women and 37 were men. Statistically significant differences were found (p Conclusion: Axial length measurements obtained with the Pentacam® and Lenstar® appear to be interchangeable, while measurements of anterior chamber depth, K1 and K2, and central corneal thickness do not appear to be interchangeable between different devices. Statistically significant differences were found in the calculation of intraocular lenses in all formulas used.

Anemia and inflammation are common clinical conditions in emergency departments. This study explored a cohort of patients admitted to the emergency department with a particular interest in determining the frequency of anemia and inflammation and the association between hemoglobin (Hb) and C-reactive protein (CRP) concentrations. The study included 125 patients categorized according to their demographic (gender and age) and clinical condition (Hb and CRP concentrations, pathological background, and diagnostic). We found that anemia and inflammation were simultaneously present in 36.0% of the cohort, reaching 67.0% in patients that were subsequently hospitalized. The Hb level was significantly lower in patients with elevated concentration of CRP when compared to individuals with normal CRP levels (11.58 ± 2.23 vs. 13.25 ± 1.80, p = 0.001), furthermore, we found a significantly negative correlation between Hb concentration and the CRP level (rs = −0.42, p &lt, 0.001). The linear regression model applied to the cohort showed that CRP levels explain 15% of Hb variations. The sensitivity of the CRP/Hb ratio (cut-off = 1.32) as a predictor of hospitalization was 80.0%, with a specificity of 68.4% for all patients. These findings confirmed the prevalence of anemia and inflammation and identified a moderate but significant association between Hb and serum CRP in a heterogeneous group of patients admitted to the emergency department.

Background Better knowledge of the efficacy and safety of single-dose 40 mg/kg oral praziquantel in preschool-age children is required, should preventive chemotherapy programs for schistosomiasis be expanded to include this age group. Methodology We analyzed individual participant-level data from 16 studies (13 single-arm or cohort studies and three randomized trials), amounting to 683 preschool-age children (aged, Author summary Schistosomiasis is a diseases caused by helminths (parasitic worms) which affects the intestinal and urogenital systems. In areas where schistosomiasis is endemic, the disease is controlled by the large scale distributing of praziquantel, primarily targeting school-age children. Younger children (preschool-age) too might be affected by schistosomiasis, but are currently not receiving praziquantel within treatment campaigns. Instead, preschool-age children are treated on a case-by-case basis because the current praziquantel formulation is not adapted to young children. Questions have also been raised as to whether the standard dose of 40 mg/kg given once is effective in preschool-age children. To answer this question, we collected individual-participant data from a series of studies in which 40 mg/kg of praziquantel had been given to children with intestinal or urinary schistosomiasis, and compared its efficacy and tolerability across age-groups. Since few direct comparisons had been made, we used statistical tools to make these comparisons. We found no evidence that treatment is less efficacious in preschool- than in school-age children and conclude that 40 mg/kg praziquantel may be given to preschool-age children in large-scale programs. When this happens, efficacy and tolerability will have to be closely monitored.

Objetivo: Relatar o caso de clínico de mucosa mordiscada associada a hábitos parafuncionais e possível transtorno de ansiedade, apresentando suas características clínicas, diagnóstico diferencial e manejo proposto. Detalhamento do caso: Paciente do gênero masculino, 15 anos, buscou atendimento após ser encaminhado por seu médico, com lesões nas regiões de mucosa jugal bilateral, lábio inferior e borda lateral direita de língua. Após anamnese e exame físico, foi observado que o paciente não possuía sinais e sintomas da disfunção temporomandibular, apresentando apenas as lesões nas regiões citadas, causada pelo hábito parafuncional. A terapia indicada para o paciente foi a orientação de cessar os hábitos parafuncionais para regressão da lesão, prescrição de pomada para aplicação tópica e encaminhamento para a clínica de psicologia. Discussão: A mucosa mordiscada é descrita como irritações físicas e crônicas, que também pode lesionar regiões circunvizinhas da mucosa jugal, como os lábios e a língua. Predominantemente a mucosa mordiscada é vista em pessoas com altos níveis de estresse ou debilitadas psicologicamente. Considerações finais: Torna-se importante o correto diagnóstico dessas lesões orais, tal como a correlação com a história médica através de uma anamnese precisa, a fim de orientar a correção de hábitos parafuncionais e acompanhamento multidisciplinar quando necessário.

Case: We present a rare case of cervical spinal epidural abscess due to Mycobacterium tuberculosis without osseous involvement that was treated with decompression and arthrodesis in a 2-stage procedure. Conclusion: Spinal epidural abscess due to Mycobacterium tuberculosis is the least common of the various forms of spinal tuberculosis. This abscess represents a severe infection of the epidural space that can compromise neural elements and can require urgent surgical intervention to avoid permanent neurological deficits. Early diagnosis and early decompression remain the 2 most important predictors of a successful neurological outcome.

This article brings the choroid plexus into the context of health and disease. It is remarkable that the choroid plexus, composed by a monolayer of epithelial cells that lie in a highly vascularized stroma, floating within the brain ventricles, gets so little attention in major physiology and medicine text books and in the scientific literature in general. Consider that it is responsible for producing most of the about 150 mL of cerebrospinal fluid that fills the brain ventricles and the subarachnoid space and surrounds the spinal cord in the adult human central nervous system, which is renewed approximately 2-3 times daily. As such, its activity influences brain metabolism and function, which will be addressed. Reflect that it contains an impressive number of receptors and transporters, both in the apical and basolateral sides of the epithelial cells, and as such is a key structure for the communication between the brain and the periphery. This will be highlighted in the context of neonatal jaundice, multiple sclerosis and Alzheimer's disease. Realize that the capillaries that irrigate the choroid plexus stroma do not possess tight junctions and that the blood flow to the choroid plexus is five times higher than that in the brain parenchyma, allowing for a rapid sensing system and delivery of molecules such as nutrients and metals as will be revised. Recognize that certain drugs reach the brain parenchyma solely through the choroid plexus epithelia, which has potential to be manipulated in diseases such as neonatal jaundice and Alzheimer's disease as will be discussed. Without further notice, it must be now clear that understanding the choroid plexus is necessary for comprehending the brain and how the brain is modulated and modulates all other systems, in health and in disease. This review article intends to address current knowledge on the choroid plexus, and to motivate the scientific community to consider it when studying normal brain physiology and diseases of the central nervous system. It will guide the reader through several aspects of the choroid plexus in normal physiology, in diseases characteristic of various periods of life (newborns-kernicterus, young adults-multiple sclerosis and the elder Alzheimer's disease), and how sex-differences may relate to disease susceptibility., The work at ICVS/3B's has the support of Portuguese North Regional Operational Program (ON.2 – O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER). JCS, FM and JAP have the support of a fellowship from Bial Foundation through Grant 217/12. Fernanda Marques is a recipient of a FCT Investigator award (IF/ 00231/2013) of the Fundação para a Ciência e Tecnologia (FCT, Portugal). The work by JP has been financed by the following grants: Deutsche Forschungsgemeinschaft DFG PA930/9, DFG PA930/12; VIAA Latvia NFI/ R/2014/023; Leibniz Society SAW-2015-IPB-2; HelseSØ No: 2016062; Norsk forskningsrådet: NFR251290, NFR246392, NFR248772, JPND NeuroGEM NFR247179, JPND PROP-AD NFR260786. The work by CS has been supported by the Portuguese Foundation for Science and Technology (FCT, Portugal – hrrp://www.fct.pt) project grants (PTDC/SAU-NEU/114800/2009); and by FEDER funds through the POCI - COMPETE 2020 - Operational Programme Competitiveness and Internationalisation in Axis I - Strengthening research, technological development and innovation (Project No. 007491) and National Funds by FCT - Foundation for Science and Technology (Project UID/ Multi/00709). The work by AB at Faculty of Pharmacy, Universidade de Lisboa, was funded, in part, by iMed.ULisboa (UID/DTP/04138/2013) from Fundação para a Ciência e a Tecnologia (FCT), Portugal., info:eu-repo/semantics/publishedVersion

Objective. To characterize the vaginal microbiome and the rate of sexually transmitted infections (STIs) in the women of Príncipe (São Tomé and Príncipe). Methods. Cross-sectional study of 100 consecutive women, invited for a free appointment and cervical cancer screening. A vaginal slide (wet mount microscopy) and a cervical sample (ThinPrep®) (Pap test, high risk human papillomavirus [HR-HPV], N. gonorrhea [NG], T. vaginalis [TV], and C. trachomatis [CT]) were obtained. Results. TV, NG, CT, and HIV were found in 8.0%, 2.0%, 3.0%, and 2.0%, respectively, and were more prevalent in younger women. HR-HPV was positive in 36.7%; 2 were positive for HPV18, but none for HPV16. Coinfection of HPV with other STIs was 8.3%. Prevalence of abnormal vaginal flora (AVF) was 82.5%, mostly bacterial vaginosis (BV) 54.6%, and moderate/severe aerobic vaginitis (msAV) 25.8%. HR-HPV was not related to BV (p=0.67). The association of abnormal Pap test with msAV was not significant (p=0.08). Conclusion. The prevalence of NG, CT, TV, and HR-HPV was according to expected, while that of HR-AVF was higher. The surprisingly low prevalence of HPV16 and HPV18 must be considered in the design of programs for prevention and vaccination; this setting can be useful as a model for postvaccination scenarios.

BACKGROUND A sensitive and reliable rapid diagnostic test (RDT) which should have comparable diagnostic performance against reference host serological methods is urgently needed for use in point-of-care (POC) diagnosis of intestinal schistosomiasis in pre school-aged children. METHODS The diagnostic accuracy of a RDT incorporating Schistosoma mansoni cercarial transformation fluid (SmCTF) for anti-schistosome antibody detection was evaluated with serum samples from a cohort of children from Uganda: 42 children aged under the age of 3 years and 40 children aged between 3 and 5 years. The infection status of these children had been previously determined by inspection of quadruplicate Kato-Katz faecal smears, a single urine circulating cathodic antigen (CCA) dipstick and antibody titres to S. mansoni soluble egg antigen (SmSEA) with a commercially available ELISA. RESULTS Upon comparison with quadruplicate Kato-Katz the sensitivity and specificity of the RDT were 75.7% and 31.1%, respectively. When using the SmSEA-ELISA as an alternate reference test, the RDT achieved 81.3% sensitivity and 61.1% specificity. Sensitivity and specificity compared to the urine-CCA test was 74.5% and 32.3% respectively. Sensitivity differed significantly according to age group. CONCLUSIONS The performance of the RDT within this study appeared favourable when compared with the currently-available SmSEA-ELISA. Looking to the future a serological POC test would be particularly promising for use in disease mapping in younger children especially in guiding administration of praziquantel treatment in selective treatment settings.

Preventive chemotherapy campaigns against schistosomiasis have progressively scaled-up during the last decade, administering single standard dose praziquantel (40 mg/kg) treatments to millions of African children. Steps taken in securing international advocacy and national level implementation are traced to highlight an international treatment platform set for further expansion, including surveillance of schistosomiasis, school-level targeting with better on-site drug administration and annual reporting of programmatic indicators (i.e., treatment coverage), potentially in real-time. Several shortcomings in need of resolution are identified and efficacy of praziquantel is assessed by a systematic review. If WHO predictions in reduction of schistosomiasis are to be realized, careful international harmonization and tailoring of national resources are required. Maintaining an effective drug distribution system and regularly checking drug efficacy are paramount.

The occurrence of schistosomiasis within African infants and preschool children has been much better documented in recent years, revealing an important burden of disease previously overlooked. Despite mounting evidence showing that treatment with praziquantel is safe, beneficial, and could be delivered within ongoing public health interventions, young children still do not have satisfactory access to this drug, and a significant treatment gap exists. Progress towards resolution of this unfortunate health inequity is highlighted, including the development of an appropriate paediatric praziquantel formulation, and present blocks are identified on securing this issue within the international health agenda.

Each year, millions of African children receive praziquantel (PZQ) by mass drug administration (MDA) to treat schistosomiasis at a standard single dose of 40 mg/kg of body weight, a direct extrapolation from studies of adults. A higher dose of 60 mg/kg is also acceptable for refractory cases. We conducted the first PZQ pharmacokinetic (PK) and pharmacodynamic (PD) study in young children comparing dosing. Sixty Ugandan children aged 3 to 8 years old with egg patent Schistosoma mansoni received PZQ at either 40 mg/kg or 60 mg/kg. PK parameters of PZQ racemate and enantiomers (R and S) were quantified. PD outcomes were assessed by standard fecal egg counts and novel schistosome-specific serum (circulating anodic antigen [CAA]) and urine (circulating cathodic antigen [CCA]) antigen assays. Population PK and PD analyses were performed to estimate drug exposure in individual children, and the relationship between drug exposure and parasitological cure was estimated using logistic regression. Monte Carlo simulations were performed to identify better, future dosing regimens. There was marked PK variability between children, but the area under the concentration-time curve (AUC) of PZQ was strongly predictive of the parasitological cure rate (CR). Although no child achieved antigenic cure, which is suggestive of an important residual adult worm burden, higher AUC was associated with greater CAA antigenic decline at 24 days. To optimize the performance of PZQ, analysis of our simulations suggest that higher doses (>60 mg/kg) are needed, particularly in smaller children., IMPORTANCE Schistosomiasis is a neglected tropical disease, typically associated with chronic morbidity, and its control is a global health priority. Praziquantel (PZQ) is the only available antiparasitic drug and is often given out, as a single oral dose (40 mg/kg), to school-aged children by mass drug administration (MDA) schemes operating within preventive chemotherapy campaigns as endorsed by the World Health Organization (WHO). This current strategy has several limitations. (i) It excludes preschool children who can be patently infected. (ii) It delivers PZQ at a dose directly extrapolated from adult pharmacological studies. To address these problems, we conducted the first pharmacokinetic and pharmacodynamic study of young children within an area of Uganda where Schistosoma mansoni is hyperendemic. Our results demonstrate that a higher dose (>60 mg/kg) is required, especially in smaller children, and draw attention to the need for further optimization of PZQ treatment based on schistosome antigenic assays, which are more sensitive to pharmacodynamic markers.

It is estimated that more than 2.5 million individuals worldwide have multiple sclerosis (MS). MS is an autoimmune neurodegenerative disease resulting from the destruction of the myelin sheath that enwraps axons driven by an immune cell attack to the central nervous system. Current therapeutic programs for MS focus in immunosuppression and more recently in the use of immunomodulatory molecules. These therapeutic approaches provide significant improvements in the management of the disease, but are frequently associated with an increased susceptibility of opportunistic infection. In this commentary, we highlight the application of nano and micro-technologies as emerging and innovative solutions for MS therapy with the potential to restore immune homeostasis via antigen-specific interactions. Furthermore, we propose and discuss the usage of a minimally invasive approach, namely microneedle patches, as a new therapeutic route. Microneedle patches for the delivery of specific antigens to restore immunotolerance in the context of multiple sclerosis.

There is a need for field-applicable markers to assess morbidity associated with intestinal schistosomiasis, especially in the context of preventive chemotherapy in young children. We investigated whether fecal occult blood (FOB) point-of-care tests could be used to assess intestinal pathology over a 12-month period in a cohort of 382 children (< 5 years of age). We found a strong association between egg-patent schistosomiasis and FOB at baseline (odds ratio [OR] = 3.1, P < 0.0001), 6 months (OR = 3.4, P < 0.0001), and 12 months (OR = 3.5, P < 0.0001), despite repeated chemotherapy. There were tendencies for prevalence of FOB to decrease in children who became egg negative and increase in those who became egg positive. Our results demonstrate overt disease in children less than five years of age. We therefore propose that FOB is useful for assessing dynamics of intestinal morbidity in young children at the community level and monitoring changes in morbidity after mass chemotherapy.

Urine-dipstick diagnostic tests that detect schistosome circulating cathodic antigen (CCA) have the potential to provide more sensitive and rapid testing for intestinal schistosomiasis in field-based surveys; this is especially so when examining preschool children, from whom it may be difficult to obtain consecutive stool samples. To assess the performance of urine dipsticks, 569 preschool children from four villages along the shore of Lake Albert, Uganda, were screened for Schistosoma mansoni by Kato-Katz (K-K) examination of a single stool sample and CCA urine dipsticks. The prevalence of infection was 32.2% by K-K and 40.0% by CCA tests. Sensitivity and specificity were influenced by whether 'trace' results from the CCA test were characterised as positive or negative for infection with S. mansoni; ambiguities around this issue need to be resolved. Nevertheless, the CCA test showed particular promise for routine epidemiological screening in this setting.

Summary To facilitate administration of praziquantel (PZQ) to African infants and preschool-aged children using a dose pole, the performance of two downwardly extended versions (the first created in 2010 using biometric data from Uganda alone and the second version created here using data from 36 countries) was assessed against height/weight data from a total of 166 210 preschool-aged children (≤6 year olds) from 36 African countries. New and optimized thresholds for PZQ tablet administration at one tablet (600 mg), ¾ and ½ tablet divisions are suggested here. Both dose poles investigated estimated an acceptable PZQ dosage (30–60 mg/Kg) for more than 95% of children. Extension and optimization of the current PZQ dose pole, followed by theoretical validation using biometric data from preschool-aged children (0–6 years of age, 60–110 cm in height) from 36 African countries will help future mass drug administration campaigns incorporate younger children. This newly optimized dose pole with single 600 mg (height: 99–110 cm), ¾ (height: 83–99 cm) and ½ (height: 66–83 cm) tablet divisions, also reduces drug waste and facilitates inclusion of preschool-aged children. Our findings also have bearings on the use of other dose poles for treatment of young children.

The purpose of this study was to understand the effects of the July 2006 heat wave through the use of the heat index, in mortality (all causes) and morbidity (all causes, respiratory and circulatory diseases) in general, and in people over 74 years and by gender, in Porto. In this paper, the Poisson generalized additive regression model was used to estimate the impact of apparent temperature (heat index) and daily mortality and morbidity during the July 2006 heat wave. Daily mortality, morbidity and heat index were correlated with lags of apparent temperature up to 7 days using Pearson correlation. For a 1°C increase in mean apparent temperature we observed a 2.7 % (95 % CI: 1.7–3.6 %) increase in mortality (all cause), a 1.7 % (95 % CI: 0.6–2.9 %) increase in respiratory morbidity, a 2.2 % (95 % CI: 0.4–4.1 %) increase in respiratory morbidity in women, a 5.4 % (95%CI: 1.1–6.6 %) increase in chronic obstructive pulmonary morbidity, and a 7.5 % (95 % CI: 1.3–14.1 %) increase in chronic obstructive pulmonary morbidity in women, for the entire population. For people ≥ 75 years, our results showed a 3.3 % increase (95 % CI: 1.7–5.0 %) in respiratory morbidity, a 2.7 % (95 % CI: 0.4–5.1 %) increase in respiratory morbidity in men, a 3.9 % (95 %CI: 1.6–6.3 %) increase in respiratory morbidity in women, a 7.0 % (95 % CI: 1.1–13.2 %) in chronic obstructive pulmonary disease, and a 9.0 % (95 % CI: 0.3–18.5 %) in chronic obstructive pulmonary disease in women. The use of heat index in a Mediterranean tempered climate enabled the identification of the effects of the July 2006 heat wave in mortality due to all causes and in respiratory morbidity of the general population, as well as in respiratory morbidity of individuals with more than 74 years of age.

SUMMARYAnaemia is a severe public health issue among African preschool-aged children, yet little effective progress has been made towards its amelioration, in part due to difficulties in unravelling its complex, multifactorial aetiology. To determine the current anaemia situation and assess the relative contribution of malaria, intestinal schistosomiasis and infection with soil-transmitted helminths, two separate cross-sectional epidemiological surveys were carried out in Uganda including 573 and 455 preschool-aged children (⩽6 years) living along the shores of Lake Albert and on the islands in Lake Victoria, respectively. Anaemia was found to be a severe public health problem in Lake Albert, affecting 68·9% of children (ninety-five percent confidence intervals (95% CI) 64·9–72·7%), a statistically significant higher prevalence relative to the 27·3% detected in Lake Victoria (95% CI: 23·3–31·7%). After multivariate analysis (controlling for sex and age of the child), the only factor found to be significantly associated with increased odds of anaemia in both lake systems was malaria (Lake Albert, odds ratio (OR)=2·1, 95% CI: 1·4–3·2; Lake Victoria, OR=1·9, 95% CI: 1·2–2·9). Thus intervention strategies primarily focusing on very young children and combating malaria appear to represent the most appropriate use of human and financial resources for the prevention of anaemia in this age group and area. Looking to the future, these activities could be further emphasised within the National Child Health DaysPLUSagenda.

To control intestinal schistosomiasis at a national level in sub-Saharan Africa, there is a need for field-applicable markers to measure morbidity associated with this disease. The purpose of this study was to determine whether fecal calprotectin or fecal occult blood assays could be used as morbidity indicators for intestinal schistosomiasis. The study was carried out in Uganda with a cohort of young children (n = 1,327) and their mothers (n = 726). The prevalence of egg-patent schistosomiasis was 27.2% in children and 47.6% in mothers. No association was found between schistosomiasis infection and fecal calprotectin in children (n = 83, odds ratio [OR] = 1.08, P = 0.881), although an inverse relationship (n = 58, OR = 0.17, P = 0.043) was found in mothers. Fecal occult blood was strongly associated with Schistosoma mansoni infection in children (n = 814, OR = 2.30, P < 0.0001) and mothers (n = 448, OR = 1.95, P = 0.004). Fecal occult blood appears to be useful for measuring morbidity associated with intestinal schistosomiasis and could be used in assessing the impact of control programs upon disease.

Increased levels of neuropeptide Y have been reported in transthyretin-null mice. This effect might be related to transthyretin ligands (retinol and thyroxine) since, through binding to nuclear receptors, they modulate the expression of genes that control cellular metabolism. The retinoic X receptors form obligatory heterodimers with peroxisome proliferator-activated receptors and liver X receptors - potent regulators of fat, glucose and cholesterol homeostasis. We used transthyretin-null mice to investigate whether the absence of transthyretin influences metabolism. Transthyretin-null mice do not differ from controls in body weight and white adipose tissue morphology, nor in basal or fast-induced circulating levels of glucose, lipids, and leptin. Glucose tolerance tests show that transthyretin-null mice have normal capacity to remove and metabolize energy substrates. Expression of genes encoding lipid transporters and nuclear receptors are also similar in transthyretin-null and control mice. Therefore, the absence of transthyretin does not seem to influence the regulation of lipid and glucose metabolism., POCTI / NSE / 37315 / 2001 and POCI/SAU-NEU/56618/2004, FEDER from Fundação para a Ciência e Tecnologia (Portugal)

Early-life stress (ELS) induces long-lasting changes in gene expression conferring an increased risk for the development of stress-related mental disorders. Glucocorticoid receptors (GR) mediate the negative feedback actions of glucocorticoids (GC) in the paraventricular nucleus (PVN) of the hypothalamus and anterior pituitary and therefore play a key role in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and the endocrine response to stress. We here show that ELS programs the expression of the GR gene (Nr3c1) by site-specific hypermethylation at the CpG island (CGI) shore in hypothalamic neurons that produce corticotropin-releasing hormone (Crh), thus preventing Crh upregulation under conditions of chronic stress. CpGs mapping to the Nr3c1 CGI shore region are dynamically regulated by ELS and underpin methylation-sensitive control of this region's insulation-like function via Ying Yang 1 (YY1) binding. Our results provide new insight into how a genomic element integrates experience-dependent epigenetic programming of the composite proximal Nr3c1 promoter, and assigns an insulating role to the CGI shore., European Union Directorate General for Research & Innovation through the CRESCENDO Consortium (O.F.X.A. and D.S) and the NINA Initial Training Program (D.S. and O.F.X.A)

Transthyretin (TTR), the major transporter of thyroid hormones and vitamin A in cerebrospinal fluid (CSF), binds the Alzheimer β-peptide and thus might confer protection against neurodegeneration. In addition, altered TTR levels have been described in the CSF of patients with psychiatric disorders, yet its function in the CNS is far from understood. To determine the role of TTR in behaviour we evaluated the performance of TTR-null mice in standardized tasks described to assess depression, exploratory activity and anxiety. We show that the absence of TTR is associated with increased exploratory activity and reduced signs of depressive-like behaviour. In order to investigate the mechanism underlying these alterations, we measured the levels of cathecolamines. We found that the levels of noradrenaline were significantly increased in the limbic forebrain of TTR-null mice. This report represents the first clear indication that TTR plays a role in behaviour, probably by modulation of the noradrenergic system.

Transthyretin is the major thyroxine-binding protein in the plasma of rodents, and the main thyroxine-binding protein in the cerebrospinal fluid of both rodents and humans. The choroid plexus synthesizes transthyretin and secretes it to the cerebrospinal fluid. Although it was suggested that transthyretin might play an important role in mediating thyroxine transfer from the blood into the brain across the choroid plexus–cerebrospinal fluid barrier, newer findings question this hypothesis. Because thyroid hormone passage across brain barriers is a precondition for its action in the CNS, and because brain is an important target of thyroid hormone action, we investigated the role of transthyretin in mediating thyroid hormone access to and distribution within the brain in a transthyretin-null mouse model system. In this report we describe the results derived from use of film autoradiography, a technique that yields definitive morphological results. Film autoradiograms were prepared at 3 and 19 h after intravenous injection of either high specific activity [125I]thyroxine or [125I]triiodothyronine. Image analyses were designed to demonstrate regional changes in hormone distribution, and to highlight alterations in iodothyronine delivery from ventricles to brain parenchyma. We find no qualitative or quantitative differences in these parameters between the transthyretin-null and the wild-type mouse brain after either [125I]thyroxine or [125I]triiodothyronine administration. The data presented here now provide definitive evidence that, under standard laboratory conditions, transthyretin is not required for thyroid hormone access to or distribution within the mouse brain. This study also provides the first map of iodothyronine distribution in the brain of the mouse.

Purpose: To assess the sociodemographic profiles, teratogen exposures, and ocular congenital abnormalities in Brazilian patients with Möbius sequence. Method: Forty-four patients were recruited from the Brazilian Möbius Sequence Society. This cross-section comprised 41 patients (age, mean ± standard deviation, 9.0 ± 5.5 years) who fulfilled the inclusion criteria. The parent or caregiver answered a questionnaire regarding sociodemographic data and pregnancy history. Patients underwent ophthalmological assessments. They were subdivided into groups according to misoprostol exposure during pregnancy, and the two groups were compared. Results: Mothers/caregivers reported unplanned pregnancies in 36 (88%) cases. Of these, 19 (53%) used misoprostol during their first trimesters. A stable marital status tended to be more frequent in the unexposed group (P=0.051). Incomplete elementary school education was reported by two (11%) mothers in the exposed group and by three (14%) mothers in the unexposed group (P=0.538). The mothers' gestational exposures to cocaine, marijuana, alcohol, and cigarettes were similar in both groups (P=0.297, P=0.297, P=0.428, and P=0.444, respectively). One (5%) case of Rubella infection during pregnancy was found in the unexposed group. The main malformations in the exposed and unexposed groups were the following: strabismus (72% and 77%, respectively), lack of emotional tearing (47% and 36%, respectively), and lagophthalmos (32% and 41%, respectively). Conclusion: Stable marital statuses tended to be more frequent among mothers that did not take misoprostol during pregnancy. Exposures to other teratogens and the main ocular abnormalities were similar in both groups. Objetivo: Descrever o perfil sóciodemográfico, exposição à teratógenos e anormalidades oculares congênitas em pacientes brasileiros portadores da sequência de Möbius Método: Quarenta e quatro pacientes recrutados da Sociedade Brasileira de Sequência de Möbius foram examinados. Este estudo transversal incluiu 41 pacientes que preencheram os critérios de inclusão do estudo (média das idades: 9,0 ± 5,5 anos). Mãe/responsável dos pacientes responderam a um questionário sobre perfil sóciodemográfico e história gestacional. Foi realizado exame oftalmológico de todos os pacientes. Eles foram agrupados em dois grupos de acordo com a exposição ao misoprostol durante a gestação e seus dados foram comparados. Resultados: Mães/responsáveis referiram gravidez indesejada em 36 (88%) dos casos. Destas, 19 (53%) fizeram uso de misoprostol no primeiro trimestre de gestação. Houve uma tendência do grupo de mães não expostas ao misoprostol de terem um estado civil estável (P=0,051). Duas (11%) mães do grupo de expostas ao misoprostol relataram primeiro grau incompleto e três (14%) do grupo de não expostas (P=0,538). A exposição das mães à cocaína, maconha, álcool e cigarro foi similar em ambos os grupos (P=0,297, P=0,297, P=0,428, P=0,444, respectivamente). Houve um caso (5%) de Rubéola no grupo de mães não expostas. As principais malformações associadas nos pacientes expostos e não expostos foram, respectivamente: estrabismo (72% e 77%), e diminuição da lágrima emocional (47% e 36%) e lagoftalmia (32% and 41%). Conclusão: Estado civil estável foi mais frequente em mães que não fizeram uso de misoprostol durante a gestação. Exposição à outros teratógenos e malformações oculares tiveram distribuição semelhante em ambos os grupos.

HIV/AIDS and schistosomiasis both cause a substantial disease burden in sub-Saharan Africa and the two diseases often overlap in their epidemiological characteristics. Although disease-specific control interventions are continuing, potential synergies in the control efforts for these two diseases have not been investigated. With a focus on children with schistosomiasis, we assess the risk for increased HIV transmission, HIV progression, and impaired response to drugs when given alongside HIV interventions. A new research agenda tailored to children is needed to better understand the interactions of these two diseases and the potential for combined responses.

SUMMARYIt is generally recommended to perform multiple stool examinations in order to improve the diagnostic accuracy when assessing the impact of mass drug administration programmes to control human intestinal worm infections and determining efficacy of the drugs administered. However, the collection and diagnostic work-up of multiple stool samples increases costs and workload. It has been hypothesized that these increased efforts provide more accurate results when infection and drug efficacy are summarized by prevalence (proportion of subjects infected) and cure rate (CR, proportion of infected subjects that become egg-negative after drug administration), respectively, but not when these indicators are expressed in terms of infection intensity and egg reduction rate (ERR). We performed a meta-analysis of six drug efficacy trials and one epidemiological survey. We compared prevalence and intensity of infection, CR and ERR based on collection of one or two stool samples that were processed with single or duplicate Kato-Katz thick smears. We found that the accuracy of prevalence estimates and CR was lowest with the minimal sampling effort, but that this was not the case for estimating infection intensity and ERR. Hence, a single Kato-Katz thick smear is sufficient for reporting infection intensity and ERR following drug treatment.

Fumonisins are mycotoxins that naturally occur as contaminants in grains that are destined for animal and human consumption. These mycotoxins cause hepatotoxic, nephrotoxic, carcinogenic, teratogenic, immunotoxic, and neurotoxic effects in different intensities based on dose, time of exposure, and animal species. In the present study, male Wistar rats were fed between postnatal days 21 and 63 with diets that contained fumonisins B1+B2 at concentrations of 1 and 3mg/kg. The objective of the present study was to evaluate the effects of fumonisins on food intake, growth, weight gain, serum activity of the alanine aminotransferase and aspartate aminotransferase enzymes, and quantitative and morphometric parameters of myenteric neurons in the jejunum that are immunoreactive to HuC/D protein and neuronal nitric oxide synthase enzyme (nNOS). Diets that contained fumonisins did not significantly alter food intake or body and blood parameters. We did not observe significant differences in the neuronal density and proportion of nitrergic neurons but found a significant reduction of cell body areas in both neuronal populations. This study is the first to report the effects of fumonisins in the enteric nervous system. The possible mechanisms by which fumonisins impair neuronal development and the use of the enteric nervous system as a tool for the study of the neurotoxic effects of fumonisins are discussed. In conclusion, fumonisin-containing food negatively affected the growth of myenteric neurons.

In large-scale interventions for control of schistosomiasis, use of the WHO dose pole is favoured for mass drug administration of praziquantel. Application of this simple tool has enabled pragmatic tablet dosing using patient height as a proxy for bodyweight, allowing control programmes to expand into resource-poor settings. Here we briefly summarize the inception and development of the existing WHO dose pole and discuss a proposed update which now permits dosing of infants and preschool children (height

To present the results of a retrospective comparative unicentric institutional study of the incidence of postcataract surgery endophthalmitis before and after the introduction of the European Society of Cataract and Refractive Surgeons (ESCRS) protocol in 2007 in our department.This study included 15,689 eyes of patients undergoing cataract surgery between 2005 and 2011. Surgeries were performed by 9 different surgeons. After June 2007, the ESCRS protocol was introduced, and all patients underwent intracameral injection of 1 mg of cefuroxime (10 mg/mL) at the end of cataract surgery. Cefuroxime was prepared prior to surgery in the operating room. All patients were observed between 6 weeks and 3 months after surgery.Between January 2005 and June 2007, before the introduction of the ESCRS protocol in our department, 2299 patients underwent cataract surgery and there were 6 cases of postoperative endophthalmitis (0.26%). After the introduction of the protocol, 13,390 surgeries were performed and there were no cases of endophthalmitis.Postoperative endophthalmitis is one of the most devastating cataract surgery complications. Our results provide strong evidence of the utility of cefuroxime as prophylaxis of endophthalmitis after cataract surgery.

Similarly to schistosomiasis, a single dose of PZQ eliminates the vast majority of Hymenolepis egg excretion [10–12]. However, it is likely that a PZQ gap exists in many communities being targeted by MDA in that the geographical location of Hymenolepis infections may not necessarily overlap with that of schistosomiasis. Guiding PZQ delivery solely on the basis of the distribution of schistosomiasis may miss communities endemic to Hymenolepis infection also in need of PZQ. This means that the populations at risk of hymenolepiasis may need to also be identified so that PZQ delivery can be extended to those areas. In order to test our proposition, we have analysed data from a parasitic disease survey of 2,168 children aged #15 years, including 1,098 girls and 1,070 boys in the Dande municipality in Northern Angola. Previous analysis of this dataset revealed that children were at significantly increased risk of H. nana infection (prevalence of 6.2% [95% CI: 4.9–7.8%] in preschool children and 7.3% [95% CI: 5.8–9.0%] in school-age children) compared to adults (prevalence of 1.9% [95% CI: 1.1–3.1%]) [13]. Using these data, we aimed to describe the epidemiology of H. nana infection by quantifying the role of individual and household factors and the physical environment (land surface temperature, distance to irrigation canals and rivers) in H. nana infection; quantify the role of H. nana infection on morbidity outcomes such as anaemia, diarrhoea, abdominal pain, and growth; quantify the geographical variation in H. nana infection prevalence in children aged #15 years; generate the first high-resolution H. nana infection map; and compare this map with a preexisting S. haematobium

Background Calprotectin is a calcium-binding cytoplasmic protein found in neutrophils and increasingly used as a marker of bowel inflammation. Fecal occult blood (FOB) is also a dependable indicator of bowel morbidity. The objective of our study was to determine the applicability of these tests as surrogate markers of Schistosoma mansoni intestinal morbidity before and after treatment with praziquantel (PZQ). Methods 216 children (ages 3–9 years old) from Buliisa District in Lake Albert, Uganda were examined and treated with PZQ at baseline in October 2012 with 211 of them re-examined 24 days later for S. mansoni and other soil transmitted helminths (STH). POC calprotectin and FOB assays were performed at both time points on a subset of children. Associations between the test results and infection were analysed by logistic regression. Results Fecal calprotectin concentrations of 150–300 µg/g were associated with S. mansoni egg patent infection both at baseline and follow up (OR: 12.5 P = 0.05; OR: 6.8 P = 0.02). FOB had a very strong association with baseline anemia (OR: 9.2 P = 0.03) and medium and high egg intensity schistosomiasis at follow up (OR: 6.6 P = 0.03; OR: 51.3 P = 0.003). Both tests were strongly associated with heavy intensity S. mansoni infections. There was a significant decrease in FOB and calprotectin test positivity after PZQ treatment in those children who had egg patent schistosomiasis at baseline. Conclusions Both FOB and calprotectin rapid assays were found to correlate positively and strongly with egg patent S. mansoni infection with a positive ameloriation response after PZQ treatment indicative of short term reversion of morbidity. Both tests were appropriate for use in the field with excellent operational performance and reliability. Due to its lower-cost which makes its scale-up of use affordable, FOB could be immediately adopted as a monitoring tool for PC campaigns for efficacy evaluation before and after treatment., Author Summary The severity of intestinal schistosomiasis, a disease caused by Schistosoma mansoni infection, is likely under-reported in part due to the scarcity of field-appropriate morbidity markers. Downstream potential complications of this disease include anemia, failure to thrive, and chronic multi-organ damage. Point-of-care (POC) tools to monitor intestinal schistosomiasis in low resource settings are urgently needed to better quantify the burden of disease in endemic countries and to gauge the clinical impact of scale-up of preventive PC. For the present study in rural Uganda, fecal occult blood and fecal calprotectin were identified as potential surrogate markers of intestinal morbidity. We tested both POC tests and found that they were both associated with active schistosomiasis as detected by eggs in stool with significant decrease in test positivity after PZQ treatment demonstrating short term morbidity reversion. Calprotectin was a strong indicator of intestinal inflammation, however, owing to its high per-test price makes it difficult to scale-up accordingly. Conversely, fecal occult blood was technically feasible, low-cost and had optimal performance as a morbidity marker, hence we strongly advocate for its immediate inclusion as a monitoring tool for PC programs.

The establishment of a national control programme (NCP) in Uganda has led to routine treatment of intestinal schistosomiasis with praziquantel in the communities along Lake Albert. However, because regular water contact remains a way of life for these populations, re-infection continues to mitigate the sustainability of the chemotherapy-based programme. A six-month longitudinal study was conducted in one Lake Albert community with the aim of characterizing water contact exposure and infection among mothers and their young preschool-aged children as the latter are not yet formally included within the NCP. At baseline the cohort of 37 mothers, 36 preschool-aged children had infection prevalences of 62% and 67%, respectively, which diminished to 20% and 29%, respectively, at the 6-month post-treatment follow-up. The subjects wore global positioning system (GPS) datalogging devices over a 3-day period shortly after baseline, allowing for the estimation of time spent at the lakeshore as an exposure metric, which was found to be associated with prevalence at follow-up (OR = 2.1, P = 0.01 for both mothers and young children and odds ratio (OR) = 4.4, P = 0.01 for young children alone). A social network of interpersonal interactions was also derived from the GPS data, and the exposures were positively associated both with the number and duration of peer interaction, suggesting the importance of socio-cultural factors associated with water contact behaviour. The findings illustrate reduction in both prevalence and intensity of infection in this community after treatment as well as remarkably high rates of water contact exposure and re-infection, particularly among younger children. We believe that this should now be formally considered within NCP, which may benefit from more in-depth ethnographic exploration of factors related to water contact as this should provide new opportunities for sustaining control.

Objective: To evaluate the results from subcutaneous anterior transposition of the cubital nerve for treating cubital tunnel syndrome (CTS) and the influence of prognostic factors such as preoperative McGowan stage, age and duration of symptoms. Methods: 36 patients with CTS who underwent subcutaneous anterior transposition of the cubital nerve between 2006 and 2009 were evaluated after an average follow-up of 28 months. Their mean age was 41.6 years. Nine patients were in McGowan stage I, 18 in stage II and nine in stage III. Results: There was a statistically significant improvement in sensory and motor deficits. 78% of the patients with severe neuropathy improved after surgery. According to the modified Bishop score, 21 patients (58.3%) had excellent results, seven (19.4%) good, six (16.7%) satisfactory and two (5.55%) poor. The satisfaction rate was 86% and 72% of the patients recovered their daily activities without limitations. Conclusion: The severity of neuropathy and preoperative duration of symptoms, but not age, had a negative influence on the outcome. The subcutaneous anterior transposition of the cubital nerve is safe and effective for treating CTS of different degrees of severity. Given the major prognostic factors identified, surgical treatment should be advised as soon as axonal loss has become clinically evident.

OBJETIVO: Avaliar os resultados da transposição anterior subcutânea do nervo cubital no tratamento da síndrome do túnel cubital (STC) e a influência de fatores de prognóstico, tais como o estádio de McGowan pré-operatório, a idade e a duração dos sintomas. MÉTODOS: Foram avaliados 36 doentes com STC submetidos à transposição anterior subcutânea do nervo cubital entre 2006 e 2009, com um tempo médio de follow-up de 28 meses. A idade média foi de 41,6 anos. Nove doentes foram incluídos no estádio I de McGowan, 18 no estádio II e nove no estádio III. RESULTADOS: Obteve-se melhoria estatisticamente significativa dos défices motores e sensitivos. 78% dos doentes com neuropatia severa melhoraram após a cirurgia. Segundo a escala de Bishop modificada, obtiveram-se 21 (58,3%) resultados excelentes, sete (19,4%) bons, seis (16,7%) satisfatórios e dois maus (5.55%). A taxa de satisfação foi de 86% e 72% dos doentes recuperaram as atividades diárias sem limitações. CONCLUSÕES: A gravidade da neuropatia e a duração pré-operatória dos sintomas, mas não a idade, tiveram uma influência negativa no outcome. A transposição anterior subcutânea do nervo cubital é segura e eficaz no tratamento da STC com diversos graus de gravidade. Tendo em conta os principais fatores de prognóstico identificados, o tratamento cirúrgico deve ser aconselhado logo que a perda axonal se torne clinicamente evidente. OBJECTIVE: To evaluate the results from subcutaneous anterior transposition of the cubital nerve for treating cubital tunnel syndrome (CTS) and the influence of prognostic factors such as preoperative McGowan stage, age and duration of symptoms. METHODS: 36 patients with CTS who underwent subcutaneous anterior transposition of the cubital nerve between 2006 and 2009 were evaluated after an average follow-up of 28 months. Their mean age was 41.6 years. Nine patients were in McGowan stage I, 18 in stage II and nine in stage III. RESULTS: There was a statistically significant improvement in sensory and motor deficits. 78% of the patients with severe neuropathy improved after surgery. According to the modified Bishop score, 21 patients (58.3%) had excellent results, seven (19.4%) good, six (16.7%) satisfactory and two (5.55%) poor. The satisfaction rate was 86% and 72% of the patients recovered their daily activities without limitations. CONCLUSIONS: The severity of neuropathy and preoperative duration of symptoms, but not age, had a negative influence on the outcome. The subcutaneous anterior transposition of the cubital nerve is safe and effective for treating CTS of different degrees of severity. Given the major prognostic factors identified, surgical treatment should be advised as soon as axonal loss has become clinically evident.

SUMMARYWhere very young children come into contact with water containing schistosome cercariae, infections occur and schistosomiasis can be found. In high transmission environments, where mothers daily bathe their children with environmentally drawn water, many infants and preschool-aged children have schistosomiasis. This ‘new’ burden, inclusive of co-infections with Schistosoma haematobium and Schistosoma mansoni, is being formally explored as infected children are not presently targeted to receive praziquantel (PZQ) within current preventive chemotherapy campaigns. Thus an important PZQ treatment gap exists whereby infected children might wait up to 4–5 years before receiving first treatment in school. International treatment guidelines, set within national treatment platforms, are presently being modified to provide earlier access to medication(s). Although detailed pharmacokinetic studies are needed, to facilitate pragmatic dosing in the field, an extended ‘dose pole’ has been devised and epidemiological monitoring has shown that administration of PZQ (40 mg/kg), in either crushed tablet or liquid suspension, is both safe and effective in this younger age-class; drug efficacy, however, against S. mansoni appears to diminish after repeated rounds of treatment. Thus use of PZQ should be combined with appropriate health education/water hygiene improvements for both child and mother to bring forth a more enduring solution.

Preschool children (aged ≤5 years) have so far been overlooked by mass treatment campaigns targeting schistosomiasis, even though praziquantel (PZQ) has been shown to be well tolerated and effective within this age group. The WHO provided the Ugandan Ministry of Health with a syrup formulation of PZQ with the aim of assessing its safety and efficacy in comparison with crushed PZQ tablets for the treatment of intestinal schistosomiasis in preschool children. This study included 1144 preschool children randomly assigned to two treatment arms (PZQ syrup or crushed PZQ tablet) regardless of infection status for direct comparison. Diagnosis of intestinal schistosomiasis was assessed using single stool sample, double Kato-Katz smear examinations. Parasitological cure was assessed 3 weeks after treatment. The observed cure rate was 80.9% for the PZQ syrup arm and 81.7% for the crushed PZQ tablet arm, with egg reduction rates of 86.1% and 89.0%, respectively. Pre-treatment infection intensity was observed to influence cure rates significantly, with cure rates of 88.6% for light infections, 74.5% for moderate infections and 67.4% for heavy infections. No significant difference was found in non-compliance between the PZQ syrup (11.1%) and crushed PZQ tablet (14.7%) arms. PZQ syrup and crushed PZQ tablets have very similar efficacies in the treatment of intestinal schistosomiasis in preschool children.