Selective visuoconstructional impairment following mild COVID-19 with inflammatory and neuroimaging correlation findings.

People recovered from COVID-19 may still present complications including respiratory and neurological sequelae. In other viral infections, cognitive impairment occurs due to brain damage or dysfunction caused by vascular lesions and inflammatory processes. Persistent cognitive impairment compromises daily activities and psychosocial adaptation. Some level of neurological and psychiatric consequences were expected and described in severe cases of COVID-19. However, it is debatable whether neuropsychiatric complications are related to COVID-19 or to unfoldings from a severe infection. Nevertheless, the majority of cases recorded worldwide were mild to moderate self-limited illness in non-hospitalized people. Thus, it is important to understand what are the implications of mild COVID-19, which is the largest and understudied pool of COVID-19 cases. We aimed to investigate adults at least four months after recovering from mild COVID-19, which were assessed by neuropsychological, ocular and neurological tests, immune markers assay, and by structural MRI and 18FDG-PET neuroimaging to shed light on putative brain changes and clinical correlations. In approximately one-quarter of mild-COVID-19 individuals, we detected a specific visuoconstructive deficit, which was associated with changes in molecular and structural brain imaging, and correlated with upregulation of peripheral immune markers. Our findings provide evidence of neuroinflammatory burden causing cognitive deficit, in an already large and growing fraction of the world population. While living with a multitude of mild COVID-19 cases, action is required for a more comprehensive assessment and follow-up of the cognitive impairment, allowing to better understand symptom persistence and the necessity of rehabilitation of the affected individuals.

Effects of yoga on impulsivity in patients with and without mental disorders: a systematic review.

BACKGROUND: Yoga can be used as a complementary intervention to conventional treatments, whether pharmacological or non-pharmacological. Sustained practice of yoga can generate a series of benefits for individuals' quality of life and improve their physical fitness. OBJECTIVE: To investigate the potential effects of yoga as an adjunct intervention in conditions involving impulse control issues, such as attention deficit hyperactivity disorder (ADHD), borderline personality disorder, bipolar affective disorder, and substance use disorders. METHODS: We performed a systematic review of placebo-controlled, randomized trials of yoga in patients with impulsivity. PubMed, Web of Science, and Science Direct databases were searched for trials published up to January, 2023. Data were extracted from published reports and quality assessment was performed per Cochrane recommendations. RESULTS: Out of 277 database results, 6 RCT were included in this systematic review. To assess the level of attention and impulsiveness, the following scales were analyzed: Barratt Impulsiveness, UPPS-P Impulsive Behavior scale, Conners' Continuous Performance Test IIª and Conners' Parent Rating Scale-Revised: Long. CONCLUSIONS: Yoga didn't have a significant improvement in impulsivity when compared to placebo. There are many tools to assess impulsivity, but they mean different concepts and domains consisting in a weakness on comparison of yoga effects. PROSPERO REGISTRATION: CRD42023389088.

What has been done to improve learning for intellectual disability? An umbrella review of published meta-analyses and systematic reviews.

BACKGROUND: Intellectual disability (ID) affects 1%-3% of the paediatric population. Currently, there is no consensus as to the most effective strategies for improving the learning skills of children and adolescents with ID. This review aims to systematically gather information regarding interventions to promote and improve learning skills in children/adolescents with ID from previously published systematic reviews and meta-analyses. METHODS: Systematic search strategies, including appropriate descriptors, were employed on Medline, Cochrane, Scopus, Web of Science, Lilacs, SciELO, ERIC, and PsycINFO databases. Quality assessment was conducted via the AMSTAR-2. RESULTS: Fifty-nine studies were selected, subdivided by outcome domains and by the type of intervention. Interventions were related to caregiving, education, pharmaco-dietary, physical, and technology approaches. The overall low quality of the studies limited our recommendations.

Comparison of the First and Second Waves of the Coronavirus Disease 2019 Pandemic in Children and Adolescents in a Middle-Income Country: Clinical Impact Associated with Severe Acute Respiratory Syndrome Coronavirus 2 Gamma Lineage.

OBJECTIVE: To evaluate the severity and clinical outcomes of the SARS-CoV-2 gamma variant in children and adolescents hospitalized with COVID-19 in Brazil. STUDY DESIGN: In this observational retrospective cohort study, we performed an analysis of all 21 591 hospitalized patients aged <20 years with confirmed SARS-CoV-2 infection registered in a national database in Brazil. The cohort was divided into 2 groups according to the predominance of SARS-CoV-2 lineages (WAVE1, n = 11 574; WAVE2, n = 10 017). The characteristics of interest were age, sex, geographic region, ethnicity, clinical presentation, and comorbidities. The primary outcome was time to death, which was evaluated by competing-risks analysis, using cumulative incidence functions. A predictive Fine and Gray competing-risks model was developed based on the WAVE1 cohort with temporal validation in the WAVE2 cohort. RESULTS: Compared with children and adolescents admitted during the first wave, those admitted during the second wave had significantly more hypoxemia (52.5% vs 41.1%; P < .0001) and intensive care unit admissions (28.3% vs 24.9%; P < .0001) and needed more noninvasive ventilatory support (37.3% vs 31.6%; P < .0001). In-hospital deaths and death rates were 896 (7.7%) in the first wave and 765 (7.6%) in the second wave (P = .07). The prediction model of death included age, ethnicity, region, respiratory symptoms, and comorbidities. In the validation set (WAVE2), the C statistic was 0.750 (95% CI, 0.741-0.758; P < .0001). CONCLUSIONS: This large national study found a more severe spectrum of risk for pediatric patients with COVID-19 caused by the gamma variant. However, there was no difference regarding the probability of death between the waves.

Parental experiences of homeschooling during the COVID-19 pandemic: differences between seven European countries and between children with and without mental health conditions.

The aim of the present study was to examine parental experiences of homeschooling during the COVID-19 pandemic in families with or without a child with a mental health condition across Europe. The study included 6720 parents recruited through schools, patient organizations and social media platforms (2002 parents with a child with a mental health condition and 4718 without) from seven European countries: the UK (n = 508), Sweden (n = 1436), Spain (n = 1491), Belgium (n = 508), the Netherlands (n = 324), Germany (n = 1662) and Italy (n = 794). Many parents reported negative effects of homeschooling for themselves and their child, and many found homeschooling to be of poor quality, with insufficient support from schools. In most countries, contact with teachers was limited, leaving parents with primary responsibility for managing homeschooling. Parents also reported increased levels of stress, worry, social isolation, and domestic conflict. A small number of parents reported increased parental alcohol/drug use. Some differences were found between countries and some negative experiences were more common in families with a child with a mental health condition. However, differences between countries and between families with and without a mental health condition were generally small, indicating that many parents across countries reported negative experiences. Some parents also reported positive experiences of homeschooling. The adverse effects of homeschooling will likely have a long-term impact and contribute to increased inequalities. Given that school closures may be less effective than other interventions, policymakers need to carefully consider the negative consequences of homeschooling during additional waves of the COVID-19 pandemic and future pandemics.

Cognitive impairment in the HTLV-1 infection: a comparative study associated with functional performance.

Human T cell leukemia virus type-I (HTLV-1) infection courses with a myelopathy, the tropical spastic paraparesis (HAM/TSP). In a case-control study, we compared the neuropsychological profile and functional characteristics in two case HTLV-1-infected groups (asymptomatic and with HAM/TSP) with a control group negative for HTLV-1. Subjects were paired for age, sex, and educational features. The case group differed from control group in neuropsychological measures such as in episodic memory recall, executive functions, and fine motor dexterity measure. Individuals with HAM/TSP have more depressive symptoms and worst performance in activities of daily living (ADL) presenting a less functionality. In multivariate models, the fine motor performance, the executive functioning, the recognition memory, and the depressive symptoms explained part of the variance in functionality. Those findings may contribute to understand of everyday life impairments and limitations of HTLV-1-infected population and to organize the rehabilitation. Once more, based in neuropsychological and functional data, we can reaffirm that HTLV-1 is never a benign condition, but sometimes it is only in a stage coursing with less symptoms.

Attention deficit and hyperactivity disorder and nocturnal enuresis co-occurrence in the pediatric population: a systematic review and meta-analysis.

BACKGROUND: Attention deficit and hyperactivity/impulsivity disorder (ADHD) and enuresis are common behavioral disorders in childhood, impacting adolescence and adult life. Enuresis (NE) is an incontinence disorder frequently observed in children with ADHD. The relationship between ADHD and NE has been a matter of debate. OBJECTIVES: We aimed to verify the relationship between ADHD and enuresis and how these conditions can modify each other during development. Using PRISMA guidelines, under the PROSPERO registration number CRD42020208299, we systematically searched the literature and conducted a meta-analysis to answer the following question: how frequent is ADHD and enuresis comorbidity? Twenty-five studies were fully read, and data from seven less heterogeneous case-control studies were pooled to estimate enuresis prevalence comparing ADHD and control samples, whereas six studies were combined to evaluate ADHD frequencies in children with and without enuresis. RESULTS: We found the ADHD rates in children with enuresis are similar to the enuresis rates in the group of children with ADHD. The presence of ADHD and enuresis comorbidity does not seem to play a role in gender distribution and the presence of other comorbidities in comparison to controls. However, enuresis seems to persist for more time in children with ADHD. LIMITATIONS: The selected papers differed in study type, research question, samples, and controls utilized. CONCLUSIONS: Our systematic review with meta-analysis supports the reciprocal association between enuresis and ADHD. Further studies are necessary to build more robust evidence.

Molecular epidemiology and prevalence of babesial infections in dogs in two hyperendemic foci in Brazil.

Babesial parasites are some of the most ubiquitous blood pathogens and consequently have considerable worldwide veterinary impact. Dogs living in the tropics are highly exposed to babesial parasites, particularly to Babesia vogeli. Limited data on the seroprevalence and molecular prevalence of Babesia spp. in dogs are available in Latin America. We conducted a cross-sectional study combining serological and molecular tests to estimate the seroprevalence and molecular epidemiology of Babesia spp. infections in dogs in two hyperendemic foci in Brazil. A total of 630 privately owned dogs (417 from Goiana municipality, Pernambuco state, north-eastern Brazil, and 213 from São Joaquim de Bicas municipality, Minas Gerais state, south-eastern Brazil) were sampled and molecularly and serologically tested for Babesia spp. Overall, 519 dogs (82.4%) presented detectable IgG antibodies against Babesia spp., and seropositivity was significantly higher in dogs older than 1 year. Molecularly, 34 dogs (5.4%) were positive for a ~ 200 bp fragment of the 18S rRNA gene of Babesia spp. and 88 (14.0%) for a longer fragment (~ 450 bp) of the same gene of Babesia spp. and other protozoa. The 18S rRNA gene sequences generated herein corresponded to B. vogeli (n = 52) or Hepatozoon canis (n = 20). This study confirms a high level of exposure to B. vogeli in two areas of Brazil and highlights that most of the dogs living in these areas are infected during the course of their life, reflected by increased seroprevalence in older dogs. Increased awareness and prevention of tick-borne protozoa infections in dogs from Brazil and Latin America are urgently needed.

Partner responsiveness moderates the relation between COVID-19-related stressors and changes in mood during the pandemic.

The COVID-19 pandemic has created an unusually stressful situation for many people around the world. Due to the restrictions, many have been isolated in their homes, and having a responsive partner may have become even more important. The present study aimed to investigate (1) whether there were any differences in social and work-related stressors and changes in negative mood during the COVID-19 pandemic as a function of marital status, and (2) whether perceived partner responsiveness can attenuate the associations between COVID-19-related stressors and changes in negative mood. The participants were 2,400 Brazilian adults recruited via the Internet, using a virtual sampling strategy. They were assigned to three distinct groups based on their relationship status. The results showed that a relatively large proportion of the sample reported increased levels of negative mood, and that married/cohabitating couples reported low levels of negative change in mood compared to single participants. We also found that partner responsiveness attenuated the association between stress and mental health, but only for people who were dating. Our study contributes new insights by showing that effects on mental health during the COVID-19 pandemic are dependent on relationship type and perceived partner responsiveness.

Optogenetic Stimulation of the M2 Cortex Reverts Motor Dysfunction in a Mouse Model of Parkinson's Disease.

Neuromodulation of deep brain structures (deep brain stimulation) is the current surgical procedure for treatment of Parkinson's disease (PD). Less studied is the stimulation of cortical motor areas to treat PD symptoms, although also known to alleviate motor disturbances in PD. We were able to show that optogenetic activation of secondary (M2) motor cortex improves motor functions in dopamine-depleted male mice. The stimulated M2 cortex harbors glutamatergic pyramidal neurons that project to subcortical structures, critically involved in motor control, and makes synaptic contacts with dopaminergic neurons. Strikingly, optogenetic activation of M2 neurons or axons into the dorsomedial striatum increases striatal levels of dopamine and evokes locomotor activity. We found that dopamine neurotransmission sensitizes the locomotor behavior elicited by activation of M2 neurons. Furthermore, combination of intranigral infusion of glutamatergic antagonists and circuit specific optogenetic stimulation revealed that behavioral response depended on the activity of M2 neurons projecting to SNc. Interestingly, repeated M2 stimulation combined with l-DOPA treatment produced an unanticipated improvement in working memory performance, which was absent in control mice under l-DOPA treatment only. Therefore, the M2-basal ganglia circuit is critical for the assembly of the motor and cognitive function, and this study demonstrates a therapeutic mechanism for cortical stimulation in PD that involves recruitment of long-range glutamatergic projection neurons.SIGNIFICANCE STATEMENT Some patients with Parkinson's disease are offered treatment through surgery, which consists of delivering electrical current to regions deep within the brain. This study shows that stimulation of an area located on the brain surface, known as the secondary motor cortex, can also reverse movement disorders in mice. Authors have used a brain stimulation technique called optogenetics, which allowed targeting a specific type of surface neuron that communicates with the deep part of the brain involved in movement control. The study also shows that a combination of this stimulation with drug treatment might be useful to treat memory impairment, a kind of cognitive problem in Parkinson's disease.

Motor learning and COMT Val158met polymorphism: Analyses of oculomotor behavior and corticocortical communication.

Differences in motor learning can be partially explained by differences in genotype. The catechol-O-methyltransferase (COMT) Val158Met polymorphism regulates the dopamine (DA) availability in the prefrontal cortex modulating motor learning and performance. Given the differences in tonic and phasic DA transmission, this study aimed to investigate whether the greater cognitive flexibility associated with the Val allele would favor the learning of movement parametrization, while the greater cognitive stability associated with the Met allele favors the acquisition of the movement pattern. Furthermore, we investigated if the genotypic characteristics impact visual scanning of information related to parametrization and to the movement pattern, and the level of cortical connectivity associated with motor planning and control. Performance and learning of a sequential motor task were compared among three genotypes (Val/Val, Val/Met, and Met/Met), as well as their oculomotor behavior and level of cortical coherence. The findings show that the cognitive flexibility promoted by the Val allele is associated with a better parametrization. The search for information through visual scanning was specific to each genotype. Also, a greater cortical connectivity associated with the Val allele was found. The combined study of behavioral, electrophysiological and molecular levels of analysis showed that the cognitive stability and flexibility associated with the COMT alleles, influence specific aspects of motor learning.

Ocular alterations, molecular findings, and three novel pathological mutations in a series of NF2 patients.

PURPOSE: To evaluate ophthalmological and molecular findings in eight patients with a clinical diagnosis of neurofibromatosis type 2 (NF2). New pathological mutations are described and variability in the ophthalmic phenotype and NF2 allelic heterogeneity are discussed. METHODS: Eye examination was performed in eight NF2 patients, and it included the measurement of the visual acuity, biomicroscopy, dilated fundus examination, color fundus photography, infrared photography, and spectral domain optical coherence tomography (SD-OCT). Molecular analysis was performed with whole-exome sequencing using DNA derived from peripheral blood mononuclear cells from each individual. RESULTS: Ophthalmological features were present in all patients, ranging from subtle retinal alterations identified only using SD-OCT to severe ocular damage present at birth. Six mutations were observed: two patients with stop codon mutation as shown on table 1 and result section, three patients with frameshift mutation as shown on table 1 and result section. Three novel mutations were found among them. CONCLUSIONS: It is a descriptive study of a rare disease, with poor previous literature. Clinical and genetic data are shown, reviving the need to further studies to clarify the genotype-phenotype correlations in NF2.

HTLV-1 proviral load in cerebrospinal fluid may not be a good marker to differentiate asymptomatic carriers with high proviral load in blood from HAM/TSP patients.

An elevated human T cell leukemia virus type 1 (HTLV-1) proviral load (PVL) is an important risk factor for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), although there is a considerable frequency of asymptomatic carriers (AC) with high PVL in blood. Our objective was to evaluate whether PVL quantified in cerebrospinal fluid (CSF) is helpful to distinguish AC from HAM when AC have high PVL in blood (ACH). ACH (n = 7) were characterized to have high PVL in blood by quantification of samples collected over time (mean 7 years). HAM patients (n = 14) also had analyzed blood samples collected at different times (mean 9 years). Comparing paired CSF and blood samples of each individual, CSF PVL mean was 4.7-fold higher than blood PVL in the ACH group and 10.8-fold in the HAM group. CSF PVL was significantly greater than blood PVL in the HAM group (p = 0.004), but not in the ACH group. Important to highlight, CSF PVL was not significantly different between the ACH and the HAM groups. These results suggested that significantly higher PVL in CSF than in blood is a hallmark of HAM/TSP patients, but this is also true for asymptomatic carriers with high PVL in blood, thus reducing its usefulness as a marker for HAM/TSP. A greater number of ACH should be analyzed, but whether they will eventually develop HAM/TSP or why they have not developed the disease are still questions to be clarified. Longitudinal studies are necessary to answer these questions.

Autoimmune Hepatitis and Autoimmune Hepatitis Overlap With Sclerosing Cholangitis: Immunophenotype Markers in Children and Adolescents.

OBJECTIVE: The pathophysiology of autoimmune hepatitis (AIH) may involve the activation of immune cells and changes in the expression of cellular markers. The aim of the present study was to characterize the immunophenotype markers of lymphocytes and monocytes in the peripheral blood of children and adolescents with type 1 AIH and AIH overlap with sclerosing cholangitis (overlap syndrome [OS]). METHODS: This is a cross-sectional study of 20 children and adolescents diagnosed with type 1 AIH and 19 with OS. Fifteen healthy subjects were included as controls. Flow cytometric analysis was used to identify markers of inflammation and autoimmunity. RESULTS: The total number of CD4 T cells was higher in the AIH patients compared with the controls. The number of CD4 T cells expressing CCR3 and CD28 was higher in the AIH group than in the control group. CD45RO was more highly expressed in the AIH group, whereas CD45RA was more highly expressed in the OS group. In regard to CD8 T lymphocytes, the CCR3 expression was higher in both groups of patients. Patients with OS had the highest expression of CD45RA and CD25. In monocytes, human leukocyte antigen DR (HLA-DR) was less expressed in both groups of patients. CONCLUSIONS: Complex phenotype features may be involved in the pathophysiology of AIH, accounting for changes in immune system regulation mechanisms. In conclusion, even after good response to treatment, patients still have immune activity signals at the cellular level.

Spectrum of germline mutations in smokers and non-smokers in Brazilian non-small-cell lung cancer (NSCLC) patients.

Lung cancer (LC) is a leading cause of cancer-related mortality. Although smoking is the major risk factor, ~15% of all cases occur in never-smokers, suggesting that genetic factors play a role in LC predisposition. Indeed, germline mutations in the TP53 gene predispose to multiple cancer types, including LC. To date, few studies compared the somatic and germline mutational profiles of LC cases by smoking status, and none was reported in Brazilians. Whole-exome sequencing (WES) was performed on two pools (seven smokers and six non-smokers) of tumor-derived DNA using the Illumina HiSeq2000 platform. Files from pools were analyzed separately using Ingenuity®Variant AnalysisTM and Mendel,MD. Validation of all candidate variants was performed by Sanger sequencing. Subsequently, validated mutations were analyzed in germline DNA from the same patients and in ethnically matched controls. In addition, a single recurring Brazilian TP53 germline mutation (R337H) was genotyped in 45 non-small-cell lung cancer patients.Four novel germline variants in the ATAD2, AURKA, PTPRD and THBS1 genes were identified exclusively in smoker patients, and four germline missense variants in PLCD1, RAD52, CP and CDC6 genes were identified solely in non-smokers. There were 4/45 (8.9%) germline carriers of the R337H TP53 mutation. In conclusion, the recurring Brazilian TP53 mutation should be genotyped in all non-small-cell lung cancer in Brazil, regardless of smoking status. Distinct pathogenic mutations and novel sequence variants are detected in Brazilian non-small-cell lung cancer patients, by smoking status. The contribution of these sequence variants to LC pathogenesis remains to be further explored.

Possible involvement of ACSS2 gene in alcoholism.

Alcoholism is a psychiatric disorder that composes one of the principal causes of health disabilities in the world population. Furthermore, the available pharmacotherapy is limited. Therefore, this research was carried out to better understand the basis of the underlying neurobiological processes of this disorder and to discover potential therapeutic targets. Real-time PCR analysis was performed in the amygdala nuclei region of the brain of mice exposed to a chronic three-bottle free-choice model (water, 5 and 10% v/v ethanol). Based on individual ethanol intake, the mice were classified into three groups: "compulsive-like" (i.e., ethanol intake not affected by quinine adulteration), "ethanol-preferring" and "ethanol non-preferring". A fourth group had access only to tap water (control group). The candidate gene ACSS2 was genotyped in human alcoholics by real-time polymerase chain reaction using the markers rs6088638 and rs7266550. Seven genes were picked out (Acss2, Acss3, Acat1, Acsl1, Acaa2, Hadh, and Hadhb) and the mRNA level of the Acss2 gene was increased only in the "compulsive-like" group (p = 0.004). The allele frequency of rs6088638 for the gene ACSS2 was higher in the Alcoholic human group (p = 0.03), although sample size was very small. The gene ACSS2 is associated with alcoholism, suggesting that biochemical pathways where it participates may have a role in the biological mechanisms susceptible to the ethanol effects.

Posterior urethral valve in fetuses: evidence for the role of inflammatory molecules.

BACKGROUND: The aim of this cross-sectional study was to investigate inflammatory biomarkers in urine samples of 24 fetuses with posterior urethral valve (PUV) collected at 22 ± 4 weeks of gestation and to compare the findings with measurements in urine samples of 22 male healthy preterm neonates at 23 ± 4 weeks (control group). METHODS: Inflammatory biomarkers in urine were measured using a cytometric bead array [interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ, soluable tumor necrosis factor receptor (TNFR) 1, sTNFR2, monocyte chemoattractant protein-1/chemokine ligand 2 (MCP-1/CCL2), eotaxin/CCL11 and interferon gamma-induced protein/10/C-X-C motif chemokine 10 (IP-10/CXCL10)] and ELISA assays [TNF, IL-8/CXCL8 and transforming growth factor-beta (TGF-ß)]. The Mann-Whitney test was used to compare medians. Markers of glomerular (creatinine) and tubular [beta 2 (ß2)-microglobulin, uromodulin, osmolality] functions were correlated with inflammatory biomarkers (Spearman test). RESULTS: An intense inflammatory profile was identified, with significantly increased concentrations of urinary IL-2, IL-4, IL-6, TNF, sTNFRI, sTNFRII, IFN-γ, MCP-1/CCL2, eotaxin/CCL11 and IL-8/CXCL8 in the PUV group compared to the controls. The same was observed for the anti-inflammatory cytokine IL-10 and for the fibrogenic mediator TGF-ß. In the correlation analysis, ß2-microglobulin positively correlated with the presence of MCP-1/CCL2, sTNFRI and eotaxin/CCL11 and negatively correlated with the presence of creatinine. CONCLUSIONS: This study shows that inflammatory molecules are already increased in fetuses with PUV at the mean gestational age of 22 weeks, suggesting a physiopathological role for inflammation just after the embryological formation of the urethral membrane.

Urinary Levels of IL-1ß and GDNF in Preterm Neonates as Potential Biomarkers of Motor Development: A Prospective Study.

Objectives. To evaluate the association between inflammatory biomarkers, neurotrophic factors, birth conditions, and the presence of motor development abnormalities in preterm neonates. Methods. Plasma and urinary levels of cytokines (IL-1ß, IL-6, IL-10, TNF, and IL-12p70), chemokines (CXCL8/IL-8, CCL2/MCP-1, CCL5/RANTES, CXCL10/IP-10, and CXCL9/MIG), and neurotrophic factors (BDNF and GDNF) were evaluated in 40 preterm neonates born between 28 and 32 incomplete weeks of gestation, at four distinct time points: at birth (umbilical cord blood) (T0), at 48 (T1), at 72 hours (T2), and at 3 weeks after birth (T3). Biomarkers levels were compared between different time points and then associated with Test of Infant Motor Performance (TIMP) percentiles. Results. Maternal age, plasma, and urinary concentrations of inflammatory molecules and neurotrophic factors were significantly different between groups with normal versus lower than expected motor development. Higher levels of GDNF were found in the group with lower than expected motor development, while IL-1ß and CXCL8/IL-8 values were higher in the group with typical motor development. Conclusion. Measurements of cytokines and neurotrophic factors in spot urine may be useful in the follow-up of motor development in preterm neonates.

Fake anti-malarials: start with the facts.

This meeting report presents the key findings and discussion points of a 1-day meeting entitled 'Fake anti-malarials: start with the facts' held on 28th May 2015, in Geneva, Switzerland, to disseminate the findings of the artemisinin combination therapy consortium's drug quality programme. The teams purchased over 10,000 samples, using representative sampling approaches, from six malaria endemic countries: Equatorial Guinea (Bioko Island), Cambodia, Ghana, Nigeria, Rwanda and Tanzania. Laboratory analyses of these samples showed that falsified anti-malarials (<8 %) were found in just two of the countries, whilst substandard artemisinin-based combinations were present in all six countries and, artemisinin-based monotherapy tablets are still available in some places despite the fact that the WHO has urged regulatory authorities in malaria-endemic countries to take measures to halt the production and marketing of these oral monotherapies since 2007. This report summarizes the presentations that reviewed the public health impact of falsified and substandard drugs, sampling strategies, techniques for drug quality analysis, approaches to strengthen health systems capacity for the surveillance of drug quality, and the ensuing discussion points from the dissemination meeting.